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Sample records for allergen challenge cac

  1. Challenges of CAC in Heterogeneous Wireless Cognitive Networks

    NASA Astrophysics Data System (ADS)

    Wang, Jiazheng; Fu, Xiuhua

    Call admission control (CAC) is known as an effective functionality in ensuring the QoS of wireless networks. The vision of next generation wireless networks has led to the development of new call admission control (CAC) algorithms specifically designed for heterogeneous wireless Cognitive networks. However, there will be a number of challenges created by dynamic spectrum access and scheduling techniques associated with the cognitive systems. In this paper for the first time, we recommend that the CAC policies should be distinguished between primary users and secondary users. The classification of different methods of cac policies in cognitive networks contexts is proposed. Although there have been some researches within the umbrella of Joint CAC and cross-layer optimization for wireless networks, the advent of the cognitive networks adds some additional problems. We present the conceptual models for joint CAC and cross-layer optimization respectively. Also, the benefit of Cognition can only be realized fully if application requirements and traffic flow contexts are determined or inferred in order to know what modes of operation and spectrum bands to use at each point in time. The process model of Cognition involved per-flow-based CAC is presented. Because there may be a number of parameters on different levels affecting a CAC decision and the conditions for accepting or rejecting a call must be computed quickly and frequently, simplicity and practicability are particularly important for designing a feasible CAC algorithm. In a word, a more thorough understanding of CAC in heterogeneous wireless cognitive networks may help one to design better CAC algorithms.

  2. Nasal allergen challenge and mediators release.

    PubMed

    Carlos, A G; Carlos, M L; Ferreira, M B; Santos, A S; Santos, M C; Pedro, E

    1997-11-01

    Nasal allergen challenges, despite not reproducing exactly natural allergen exposure, are a very useful method to understand the complex cellular kinetics and cellular interactions that occur in allergic rhinitis. Cell-specific soluble mediator measurements can give useful diagnostic information. In this paper we present data concerning eosinophil cationic protein (ECP) and tryptase measurements after nasal allergen challenge.

  3. Anterior rhinomanometry in nasal allergen challenges.

    PubMed

    Ferreira, M B; Carlos, A G

    1998-11-01

    Even simple and relatively safe provocation procedures like nasal allergen challenges, should aim to allow detection of positivity with the less possible discomfort to the patient. The objective of this work was to evaluate if the use of rhinomanometric measurements during nasal provocation procedures could allow a decrease in the total administered allergen dose, causing less symptoms to the patients but without increasing the number of false-negatives, comparatively to clinical scores or nasal peak-flow measurements. Our results showed that performing rhinomanometric measurements during nasal HDM challenge procedures can lead in many patients to a reduction in the total dose of allergen administered during the challenge, without loss of sensitivity or specificity. This allergen dose reduction translates in less time consumed during the provocation and less patients' discomfort.

  4. Challenging the nature of low-energy plasmon excitations in CaC6 using electron energy-loss spectroscopy

    NASA Astrophysics Data System (ADS)

    Roth, Friedrich; König, Andreas; Kramberger, Christian; Pichler, Thomas; Büchner, Bernd; Knupfer, Martin

    2013-04-01

    The nature of low-energy plasmon excitations plays an important role in understanding the low-energy electronic properties and coupling mechanism of different superconducting compounds such as CaC6. Recent ab initio studies predict a charge carrier intraband plasmon in keeping with a low-energy acoustic plasmon. Here, we have studied the low-energy electronic excitations of CaC6 using high-resolution electron energy-loss spectroscopy in transmission at low temperatures. The analysis of the core level excitations leads to the conclusion that hybridization between graphite and calcium states plays an essential role in this graphite-intercalated compound. Regarding the low-energy plasmon excitation, we observe the formation of an intraband (charge carrier) plasmon with a negative dispersion at about 3.5 eV in sound agreement with the theory. Finally, a weak excitation around 1.2 eV with an almost linear dispersion relation can be observed as predicted for an acoustic plasmon that may mediate the superconducting coupling in CaC6. However its optical limit at ~1 eV challenges the theoretical predictions and safely rules out an electronic superconducting coupling mechanism in CaC6

  5. Nasal mucosal blood flow after intranasal allergen challenge

    SciTech Connect

    Holmberg, K.; Bake, B.; Pipkorn, U.

    1988-03-01

    The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the /sup 133/Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated.

  6. 364 Zero Itch in Eyes Treated With Olopatadine Hydrochloride Ophthalmic Solution, 0.2% in Bilateral Conjunctival Allergen Challenge Studies

    PubMed Central

    Blaiss, Michael S.; Tort, Maria

    2012-01-01

    Purpose To further assess the prevention of ocular itching with olopatadine hydrochloride ophthalmic solution, 0.2% (OLO) in patients with allergic conjunctivitis. Methods This was a post-hoc analysis of 85 patients participating in 2 prospective, randomized, double-masked bilateral conjunctival allergen challenge (CAC) studies. Patients received OLO in one eye and placebo (vehicle) in the contralateral eye. Ocular itching was self-assessed by patients and rated on a scale of 0 (none) to 4 (severe). To assess onset of action, eligible patients were challenged with antigen 27 minutes after dosing. To assess duration of action, patients were challenged with allergen 16 hours after dosing. The percentage of eyes with zero itching in both studies was assessed at 3 minutes post allergen challenge. Results The percentage of eyes with zero itch at the 3 minutes timepoint after the onset of action allergen challenge was 60.0% for OLO-treated eyes compared with 5.9% for vehicle-treated eyes (P < .0001, OLO vs vehicle). The percentage of eyes with zero itch at 3 minutes post allergen challenge following the 16-hour dosing was 59.8% for OLO-treated eyes compared with 22.0% for vehicle-treated eyes (P < .0001, OLO vs vehicle). Conclusions In bilateral CAC studies, ocular itching was prevented in a higher percentage (P < .0001) of eyes treated with 0.2% olopatadine hydrochloride ophthalmic solution when compared with vehicle as early as 30 minutes and for at least 16 hours post dosing.

  7. Effect of Formaldehyde on Asthmatic Response to Inhaled Allergen Challenge

    PubMed Central

    Ezratty, Véronique; Bonay, Marcel; Neukirch, Catherine; Orset-Guillossou, Gaëlle; Dehoux, Monique; Koscielny, Serge; Cabanes, Pierre-André; Lambrozo, Jacques; Aubier, Michel

    2007-01-01

    Background Exposure to formaldehyde may lead to exacerbation of asthma. Objectives Our aim in this study was to investigate whether exposure to a low level (500 μg/m3) of formaldehyde enhances inhaled allergen responses. Methods Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge. Results The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD15FEV1) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before. Conclusion In this study, exposure to 500 μg/m3 formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect. PMID:17384766

  8. Evaluating the efficacy of epinastine ophthalmic solution using a conjunctivitis allergen challenge model in patients with birch pollen allergic conjunctivitis.

    PubMed

    Tagawa, Yoshiaki; Namba, Kenichi; Nakazono, Yumi; Iwata, Daiju; Ishida, Susumu

    2017-04-01

    The efficacy of epinastine 0.05% ophthalmic solution for pollen allergic conjunctivitis has already been shown in a conjunctival allergen challenge (CAC) test using cedar pollen as a challenge. The present study investigated the efficacy of this solution against birch pollen conjunctivitis in a CAC test. Ten adult subjects (eight males and two females) with asymptomatic birch pollen conjunctivitis were enrolled in this study. The average age of the subjects was 41.1 years. This study was conducted during a period without birch pollen dispersion. In each subject, the epinastine 0.05% ophthalmic solution was instilled in one eye, and an artificial tear fluid was instilled in the fellow eye in a double-blind manner. Five minutes or 4 h after the drug instillation, both eyes were challenged with an optimal concentration of birch pollen, and ocular itching and conjunctival hyperemia were then graded. Tears were collected before the drug instillation and 20 min after the pollen challenge, and the histamine level was measured. The ocular itching scores and palpebral conjunctival hyperemia scores of the epinastine-treated eyes were significantly lower than those of the contralateral control eyes when the eyes were pretreated with the drug 4 h before the CAC. There was a significant correlation between the tear histamine level and mean ocular itching score of three time points (3, 5 and 10 min) following the CAC in the control eyes but not the epinastine-treated eyes. Epinastine is effective in suppressing ocular itching and conjunctival hyperemia in birch pollen conjunctivitis. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  9. Effect of Mandarin Orange Yogurt on Allergic Conjunctivitis Induced by Conjunctival Allergen Challenge.

    PubMed

    Hara, Yuko; Shiraishi, Atsushi; Sakane, Yuri; Takezawa, Yuki; Kamao, Tomoyuki; Ohashi, Yuichi; Yasunaga, Sho; Sugahara, Takuya

    2017-06-01

    To evaluate the effects of mandarin orange yogurt containing nobiletin and β-lactoglobulin on the allergic conjunctivitis induced by a conjunctival allergen challenge (CAC). Experiment 1 was performed on 26 asymptomatic patients (age, 25.3 ± 5.3 years) with proven seasonal allergic conjunctivitis due to cedar pollen. We compared the degree of conjunctivitis induced by CAC before and after ingesting mandarin orange yogurt for 2 weeks. Experiment 2 was a double-blind, placebo-controlled trial performed on 31 patients (age, 32.5 ± 12.2 years). A diet containing mandarin orange yogurt was compared to a diet containing yogurt lacking the mandarin orange on the conjunctivitis induced by CAC. The temperature of the inferior bulbar conjunctiva was measured before and 20 minutes after the CAC with an ocular surface thermographer (OST). The degree of conjunctival injection and chemosis was graded by slit-lamp biomicroscopy. The changes in the symptoms were evaluated by a questionnaire. In experiment 1, the scores of redness (3.07 ± 3.03 vs. 1.05 ± 1.70), chemosis (2.84 ± 2.27 vs. 0.81 ± 1.11), itching (4.34 ± 3.05 vs. 1.39 ± 2.12), and temperature (0.73 ± 0.42°C vs. 0.45 ± 0.43°C) were significantly lower (P < 0.001) after a diet of mandarin orange yogurt for 2 weeks. In experiment 2, the scores of redness (1.03 ± 0.18 vs. 1.28 ± 0.52; P = 0.0156), itching (1.93 ± 1.92 vs. 2.82 ± 2.21; P = 0.0133), and surface temperature (0.54 ± 0.21°C vs. 0.31 ± 0.25°C; P < 0.001) were significantly lower in the mandarin orange yogurt group than in the control yogurt group. Mandarin orange yogurt can be an effective nutritional intervention for allergic conjunctivitis.

  10. Evaluation of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen challenge model.

    PubMed

    Spangler, D L; Bensch, G; Berdy, G J

    2001-08-01

    Olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochlofide 0.05% ophthalmic solution are 2 topical antiallergic agents indicated for the treatment of itching of the eye associated with allergic conjunctivitis. Olopatadine has recently received US Food and Drug Administration (FDA) approval for an expanded indication for the treatment of signs and symptoms of allergic conjunctivitis, including itching, tearing, eyelid swelling, redness, and chemosis. The purpose of this study was to compare the efficacy of olopatadine hydrochloride versus azelastine hydrochloride and placebo (artificial tears) in the conjunctival allergen challenge (CAC) model. This was a prospective, randomized, double-masked, contralaterally controlled, multicenter, allergen-challenge study. Itching was chosen as the primary efficacy variable since it is the only FDA-approved indication these 2 agents have in common. Subjects with a history of allergic conjunctivitis who responded to the CAC at screening visits 1 and 2 were randomized to 1 of 3 treatment groups: olopatadine in 1 eye and azelastine in the other eye; olopatadine in 1 eye and placebo in the other eye; or azelastine in 1 eye and placebo in the other eye. At the assessment visit (visit 3), subjects received masked study medication according to the randomization scheme. After 5 minutes, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at visits 1 and 2. Immediately after challenge, subjects gave itching assessments (scale, 0 = no itching to 4 = severe itching) every 30 seconds for a total period of 20 minutes. Mean itching scores for all eyes were compared by treatment. Mean itching scores at each time point were compared between treatments using 2 sample t tests. Of the 180 subjects screened, 111 responded to the CAC at visits 1 and 2 and completed the study; 65% (72/111) of patients were female, 87% (97/111) were white, and 49% (54

  11. The anti-allergic effects of a cromolyn sodium-chlorpheniramine combination compared to ketotifen in the conjunctival allergen challenge model.

    PubMed

    Leonardi, A; Busca, F; Tavolato, M; Secchi, A G

    2003-03-01

    To compare the inhibitory effects of a topical combination product, cromolyn sodium (DSCG) 4% with the antihistamine, chlorpheniramine, with those of topical ketotifen 0.05% on the clinical allergic reaction induced by the conjunctival allergen challenge (CAC). Ten allergic but non-active patients were challenged in both eyes with increasing doses of specific allergen to obtain a positive bilateral reaction (visit 1). They were then rechallenged after 1 week to confirm the allergic threshold dose response (visit 2). After 2 weeks, a third CAC was performed bilaterally 30 minutes after topical application of DSCG-chlorpheniramine in one eye and ketotifen in the contralateral eye in a double-masked fashion (visit 3). Clinical signs and symptoms were registered 5, 10, 15, and 20 minutes after challenge using the standard scoring system. Tear cytology was performed 30 minutes after challenge. Comparing the two drug effects at visit 3, DSCG-chlorpheniramine was shown to be superior to ketotifen at all time points for itching (p < 0.01) and at 5 minutes for redness (p < 0.01). For the total signs score, DSCG-chlorpheniramine was shown to be superior to ketotifen at all time points (p < 0.01), and at 10 and 15 minutes for the total symptoms score (p < 0.05). Compared to visit 2, DSCG-chlorpheniramine significantly lowered itching (p < 0.001) and redness (p < 0.05) at 5, 10, 15, and 20 minutes after challenge. Ketotifen significantly lowered itching at 5 and 10 minutes (p < 0.001) and redness at 5, 10, and 15 minutes (p < 0.05). Both drugs reduced the total number of cells evaluated by tear cytology during the early-phase reaction (p < 0.05). DSCG-chlorpheniramine was found to be more effective than ketotifen at preventing itching and redness in the CAC model.

  12. Animal models of protein allergenicity: potential benefits, pitfalls and challenges.

    PubMed

    Dearman, R J; Kimber, I

    2009-04-01

    Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross-react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end-points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge-induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.

  13. Allergen

    MedlinePlus

    Common allergens include: Animal proteins and animal dander Dust Drugs (such as antibiotics or medicines you put on your skin) Foods (such as egg, peanut, milk, nuts, soy, fish, animal meat, and wheat) Fungal spores ...

  14. Evaluation of comfort using olopatadine hydrochloride 0.1% ophthalmic solution in the treatment of allergic conjunctivitis in contact lens wearers compared to placebo using the conjunctival allergen-challenge model.

    PubMed

    Brodsky, Miguel; Berger, William E; Butrus, Salim; Epstein, Arthur B; Irkec, Murat

    2003-04-01

    Olopatadine hydrochloride 0.1% ophthalmic solution is a topical antiallergy agent indicated for treatment of the signs and symptoms of allergic conjunctivitis. The purpose of this study was to evaluate the comfort of olopatadine used for contact lens wearers in the conjunctival allergen-challenge (CAC) model. This was a single-center, randomized, double-masked, parallel-controlled CAC study. Contact lens-wearing subjects with a history of allergic conjunctivitis were randomized to receive olopatadine or placebo bilaterally. Fifteen minutes after study medication instillation, subjects inserted contact lenses. Allergen challenge was performed 10 minutes after contact lens insertion. Subjective evaluations of ocular comfort were obtained immediately and every minute after CAC, up to and including 10 minutes. Thereafter, comfort evaluations were made every 5 minutes up to and including 60 minutes. Subjects evaluated itching at 3, 7, and 10 minutes and redness was graded at 5, 10, and 20 minutes. All evaluations were graded on standardized scales. Subjects were given diaries in which to rate comfort at 2, 4, 6, 9, 12, and 13 hours and the time of contact lens removal. At post-study medication instillation, post-lens insertion, and at time points from 1 to 10 minutes post-allergen challenge, ocular comfort evaluations were statistically superior in subjects receiving olopatadine as compared with those receiving placebo (P < 0.05). The difference in time until contact lens removal was clinically significant, with subjects who were treated with olopatadine wearing lenses for an average of 2.1 hours longer than placebo group. As evidenced by significantly greater comfort and longer duration of lens wear, olopatadine provides superior comfort to contact lens wearers suffering from the signs and symptoms of seasonal allergic conjunctivitis, as induced by the CAC model.

  15. Airway responsiveness to mannitol 24 h after allergen challenge in atopic asthmatics.

    PubMed

    Davis, B E; Amakye, D O; Cockcroft, D W

    2015-06-01

    Airway responsiveness to indirect stimuli correlates positively with airway inflammation. In atopic asthmatics, allergen inhalation is associated with an influx of inflammatory cells and increased responsiveness to the direct-acting stimuli methacholine at 3 and 24 h after exposure. We have shown mannitol responsiveness decreases 3 h after allergen inhalation. The current investigation assessed mannitol responsiveness 24 h after allergen challenge. Eleven mild atopic asthmatics completed allergen challenges on two separate occasions. In random order, methacholine or mannitol challenges were performed 24 h pre- and post-allergen challenge. Levels of fractional exhaled nitric oxide were also measured. Allergen challenge increased airway responsiveness to methacholine 24 h postchallenge; the geometric mean (95% CI) methacholine PC20 decreased from 5.9 mg/ml (1.8-19.4) to 2.2 mg/ml (0.81-5.89); P = 0.01. This coincided with a significant increase (P = 0.02) in FeNO levels. Conversely, allergen challenge decreased airway responsiveness to mannitol; geometric mean (95% CI) dose-response ratio was significantly higher after allergen exposure (57 mg/% FEV1 fall [27-121] to 147 mg/% FEV1 fall [57-379]; P = 0.03), and FeNO levels were not significantly increased (P = 0.054). Allergen-induced changes in airway responsiveness to direct and indirect stimuli are markedly different. The loss in responsiveness to mannitol is likely not explainable by a refractory state. The effect(s) of allergen exposure on airway responsiveness to indirect-acting stimuli require further investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Influence of bronchial allergen challenge on histamine release by human basophils.

    PubMed

    Lie, W J; Van Der Veen, M J; Knol, E F; Mul, F P; Jansen, H M; Roos, D; Van Der Zee, J S

    2000-06-01

    Basophils can be primed by cytokines such as interleukin (IL) -3, IL-5 or granulocyte macrophage-colony stimulating factor (GM-CSF). It has been described that the concentrations of these cytokines are enhanced at sites of allergic inflammation as well as systemic in allergic asthma. To investigate the priming status of basophils as detected by thapsigargin-induced histamine release during bronchial allergen challenge. Ten subjects allergic to house dust mite were challenged via an aerosol delivery system. Spontaneous leucocyte histamine release as well as histamine release induced by various stimuli was measured in vitro at several time points. In addition, lung function parameters, serum IL-5 and blood eosinophil counts were evaluated. We found no effect of bronchial allergen challenge upon spontaneous leucocyte histamine release, nor upon histamine release induced by anti-immunoglobulin (Ig) E, house dust mite extract, C5a, fMLP, IL-3, PMA+ thapsigargin or IL-3+ thapsigargin. However, the priming status of basophils as measured by thapsigargin-induced histamine release was enhanced at 24 h after bronchial allergen challenge. Analysis of the individual data showed a heterogeneous initial response (30 min, 6 h) followed by a predominant increase at 24 h after allergen challenge. This increase in the thapsigargin-induced histamine release correlated with the increase in serum IL-5 levels at 24 h after allergen challenge. The priming status of human basophils as measured by thapsigargin-induced histamine release is enhanced 24 h after allergen challenge.

  17. Minimal tolerance to the bronchoprotective effect of inhaled salmeterol/fluticasone combination on allergene challenge.

    PubMed

    Paggiaro, P L; Giannini, D; Di Franco, A; Bacci, E; Dente, F L; Vagaggini, B; Tonelli, M; Zingoni, M

    2006-01-01

    In order to assess whether the administration of salmeterol/fluticasone propionate combination (50/250 mcg by Diskus) for 1 week induces tolerance to the bronchoprotective effect of salmeterol on allergen challenge, a single-blind, cross-over study was carried out. We studied nine subjects (eight men and one woman; mean age+/-SD: 31.3+/-11.0 yr) with mild intermittent allergic asthma, never treated with regular beta2-agonists or inhaled corticosteroids. In a previous allergen challenge all subjects had shown a positive early airway response (EAR) to allergen. They underwent allergen challenge after 1-week treatment with placebo and a single dose of placebo immediately before allergen challenge (T1), or 1-week treatment with placebo and a single dose of salmeterol/fluticasone immediately before allergen challenge (T2), or 1-week treatment with salmeterol/fluticasone combination bid and a single dose of salmeterol/fluticasone immediately before allergen challenge (T3). EAR was evaluated both as maximum decrease in FEV1 (MaxDeltaFEV1 %) after allergen challenge and as area under FEV1 -time curve. MaxDeltaFEV1 % during allergen challenge protected by placebo (T1) was significantly greater than MaxDeltaFEV1 % during allergen challenges protected by single dose of salmeterol/fluticasone (T2) and by salmeterol/fluticasone 1-week treatment (T3). No difference was found in MaxDeltaFEV1 % between T2 and T3. The same results were observed also after computing the area under the curve for each challenge. When individually considered, all subjects were protected against EAR (protection index > or = 80%) at T2, while at 3 seven out of nine subjects were still protected against EAR. In conclusion, the simultaneous administration of salmeterol and fluticasone in the same device prevents in almost 80% of examined subjects the development of tolerance to the protective effect of salmeterol on allergen challenge. This observation may contribute to explain the positive interaction

  18. Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge.

    PubMed

    Mah, Francis S; Rosenwasser, Lanny J; Townsend, William D; Greiner, Jack V; Bensch, George

    2007-06-01

    Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H(1) antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis. To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC). This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12 h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5 min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4. MAIN OUTCOME MEASURES; This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7 min and redness was assessed at 7, 15, and 20 min post-challenge. Drop comfort was assessed upon instillation, at 30s, and at 1, 2, and 5 min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 (p = 0.024) and 7 min (p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p < or = 0.013, conjunctival: p < or = 0.015, episcleral: p < or = 0.006). Olopatadine 0.2% was rated as significantly more comfortable than

  19. Workshop proceedings: challenges and opportunities in evaluating protein allergenicity across biotechnology industries.

    PubMed

    Stagg, Nicola J; Ghantous, Hanan N; Ladics, Gregory S; House, Robert V; Gendel, Steven M; Hastings, Kenneth L

    2013-01-01

    A workshop entitled "Challenges and Opportunities in Evaluating Protein Allergenicity across Biotechnology Industries" was held at the 51st Annual Meeting of the Society of Toxicology (SOT) in San Francisco, California. The workshop was sponsored by the Biotechnology Specialty Section of SOT and was designed to present the science-based approaches used in biotechnology industries to evaluate and regulate protein allergenicity. A panel of experts from industry and government highlighted the allergenicity testing requirements and research in the agricultural, pharmaceutical/biopharma, and vaccine biotechnology industries and addressed challenges and opportunities for advancing the science of protein allergenicity. The main learning from the workshop was that immunoglobulin E-mediated allergenicity of biotechnology-derived products is difficult to assess without human data. The approaches currently being used to evaluate potential for allergenicity across biotechnology industries are very different and range from bioinformatics, in vitro serology, in vivo animal testing, in vitro and in vivo functional assays, and "biosimilar" assessments (ie, biotherapeutic equivalents to innovator products). The challenge remains with regard to the different or lack of regulatory requirements for allergenicity testing across industries, but the novel approaches being used with bioinformatics and biosimilars may lead to opportunities in the future to collaborate across biotechnology industries.

  20. Oxidative stress and airway inflammation after allergen challenge evaluated by exhaled breath condensate analysis.

    PubMed

    Brussino, L; Badiu, I; Sciascia, S; Bugiani, M; Heffler, E; Guida, G; Malinovschi, A; Bucca, C; Rolla, G

    2010-11-01

    Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8-isoprostane. The aim of the study was to investigate oxidative stress induced by allergen challenge in mild asthmatics, by measuring 8-isoprostane in exhaled breath condensate (EBC), and to examine their relationship with mediators derived from arachidonic acid. Methods 8-isoprostane, cysteinyl leukotrienes (cys-LTs) and prostaglandin E2 (PGE(2) ) concentrations in EBC were measured at baseline and after allergen challenge in 12 patients with mild allergic asthma sensitized to cat allergen. At 24 h after allergen challenge, compared with baseline values, EBC 8-isoprostane increased [48.64 pg/mL (44.14-53.61) vs. 21.56 pg/mL (19.92, 23.35), P<0.001], cys-LTs increased [27.37 pg/mL (24.09-31.10) vs. 13.28 pg/mL (11.32, 15.57), P<0.001] and PGE(2) decreased [18.69 pg/mL (12.26, 28.50) vs. 39.95 pg/mL (34.37, 46.43), P<0.001]. The trend of increasing 8-isoprostane after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.85, P<0.001) whereas the trend of decreasing PGE(2) after allergen challenge was significantly correlated with the trend of increasing cys-LTs (R(2) =0.52, P=0.001). The increase in EBC 8-isoprostane observed after allergen challenge indicates that allergen exposure increases airway oxidative stress in allergic asthma. The strict correlation between cys-LTs and 8-isoprostane underlines the relationship between allergic inflammation and oxidative stress. A shift of arachidonic acid metabolism towards lipoxygenase pathway is induced by the allergen challenge. Airway oxidative stress occurs after allergen challenge even in patients with mild intermittent allergic asthma. © 2010 Blackwell Publishing Ltd.

  1. A comparison of the clinical efficacy of pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model.

    PubMed

    Greiner, Jack V; Udell, Ira J

    2005-05-01

    The signs and symptoms of allergic conjunctivitis include ocular redness and itching. Two treatment options currently indicated for acute ocular allergic reaction are pheniramine maleate 0.3%/naphazoline hydrochloride 0.025% ophthalmic solution, an over-the-counter antihistamine/vasoconstrictor combination; and olopatadine hydrochloride 0.1% ophthalmic solution, a prescription antihistamine/mast cell stabilizer. This study was designed to compare, at onset of action, the relative effectiveness of pheniramine/naphazoline and olopatadine, when administered before conjunctival allergen challenge (CAC), using the ocular allergy index (OAI) as the primary end point. This was a prospective, randomized, double-masked, contralateral, active- and placebo-controlled, single-center study of the CAC model. The first 2 study visits established and confirmed the subjects' ocular allergic reaction (no medication administered). At visit 3, the subjects were randomly assigned to 1 of 3 contralateral (right eye vs left eye) treatment combinations: pheniramine/naphazoline + olopatadine, pheniramine/naphazoline + placebo, or olopatadine + placebo. Medication was given 10 minutes before CAC. The subjects' erythema in the ciliary, conjunctival, and episcleral vessel beds; eyelid swelling; chemosis; and itching were evaluated at 7, 12, and 20 minutes after CAC. The OAI was calculated as a composite score of 6 signs and symptoms of allergic conjunctivitis to assess global severity. Between-treatment differences in OAI scores were used to evaluate efficacy. Subjects were asked their eye drop preference at the conclusion of visit 3. Subjects (n = 83) ranged in age from 20 to 70 years (mean, 42.5 years), 61.4% (n = 51) were female, and 94.0% (n = 78) were white. Both pheniramine/naphazoline and olopatadine were associated with significantly lower OAI scores than placebo at all 3 time points (all, P < 0.001). OAI scores were significantly lower with pheniramine/naphazoline than with

  2. Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes.

    PubMed

    Scadding, Guy W; Calderon, Moises A; Bellido, Virginia; Koed, Gitte Konsgaard; Nielsen, Niels-Christian; Lund, Kaare; Togias, Alkis; Phippard, Deborah; Turka, Laurence A; Hansel, Trevor T; Durham, Stephen R; Wurtzen, Peter Adler

    2012-10-31

    Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge.

  3. Eosinophil recruitment to nasal nerves after allergen challenge in allergic rhinitis.

    PubMed

    Thornton, Margaret A; Akasheh, Nadim; Walsh, Marie-Therese; Moloney, Michael; Sheahan, Patrick O; Smyth, Claire M; Walsh, Rory McConn; Morgan, Ross M; Curran, David R; Walsh, Michael T; Gleich, Gerald J; Costello, Richard W

    2013-04-01

    In allergen challenged animal models, eosinophils localize to airway nerves leading to vagally-mediated hyperreactivity. We hypothesized that in allergic rhinitis eosinophils recruited to nasal nerves resulted in neural hyperreactivity. Patients with persistent allergic rhinitis (n=12), seasonal allergic rhinitis (n=7) and controls (n=10) were studied. Inferior nasal turbinate biopsies were obtained before, 8 and 48h after allergen challenge. Eight hours after allergen challenge eosinophils localized to nerves in both rhinitis groups; this was sustained through 48h. Bradykinin challenge, with secretion collection on the contralateral side, was performed to demonstrate nasal nerve reflexes. Twenty fourhours after allergen challenge, bradykinin induced a significant increase in secretions, indicating nasal hyperreactivity. Histological studies showed that nasal nerves expressed both vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 26 (CCL-26). Hence, after allergen challenge eosinophils are recruited and retained at nerves and so may be a mechanism for neural hyperreactivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Vagal afferents contribute to exacerbated airway responses following ozone and allergen challenge

    PubMed Central

    Schelegle, Edward S.; Walby, William F.

    2012-01-01

    Brown-Norway rats (n = 113) sensitized and challenged with nDer f 1 allergen were used to examine the contribution of lung sensory nerves to ozone (O3) exacerbation of asthma. Prior to their third challenge rats inhaled 1.0 ppm O3 for 8 hours. There were three groups: 1) control; 2) vagus perineural capsaicin treatment (PCT) with or without hexamethonium; and 3) vagotomy. O3 inhalation resulted in a significant increase in lung resistance (RL) and an exaggerated response to subsequent allergen challenge. PCT abolished the O3-induced increase in RL and significantly reduced the increase in RL induced by a subsequent allergen challenge, while hexamethonium treatment reestablished bronchoconstriction induced by allergen challenge. Vagotomy resulted in a significant increase in the bronchoconstriction induced by O3 inhalation and subsequent challenge with allergen. In this model of O3 exacerbation of asthma, vagal C-fibers initiate reflex bronchoconstriction, vagal myelinated fibers initiate reflex bronchodilation, and mediators released within the airway initiate bronchoconstriction. PMID:22525484

  5. Using magnetic resonance imaging to quantify the inflammatory response following allergen challenge in allergic rhinitis.

    PubMed

    Leaker, Brian R; Scadding, Glenis; Jones, C Richard; Barnes, Peter J

    2015-12-01

    Current rhinometric and flow assessments measure nasal patency and are often poorly correlated with rhinitis symptoms. To evaluate magnetic resonance imaging (MRI) as a new method to measure inflammatory changes in nasal and sinus mucosa following nasal allergen challenge. A pilot study (n = 6) determined the optimal technical settings for MRI to measure inflammatory change which were then adopted for the main study. This study was a single blind, placebo-controlled, three-way crossover trial in 14 subjects with seasonal allergic rhinitis. Effects of cetirizine, cetirizine and pseudoephedrine (Cet+PE), or placebo on total nasal symptom scores (TNSS), peak nasal inspiratory flow (PNIF), nasal nitric oxide (nNO), acoustic rhinometry, and MRI end points following nasal intranasal allergen challenge were measured. There were significant changes in all parameters after allergen challenge (P < 0.01), except for nNO. MRI end points were less variable and more consistent than PNIF and acoustic rhinometry in detecting changes after allergen challenge. Total nasal airspace volume was the most sensitive and reproducible MRI measurement, with a mean reduction from -5.37 cm(3) (95%CI -7.35, -3.38; P < 0.001), which was maximal 60 min after allergen challenge. A change of one in TNSS corresponded to a change in MRI volume of -0.57 cm(3). There was an improvement in all parameters (except nNO) in subjects taking Cet+PE compared with placebo, however this did not achieve significance probably because of the small study size (overall analysis P > 0.07; comparison of active versus placebo P > 0.09). MRI provides novel insights into the anatomical inflammatory changes post allergen challenge and provides a new method for assessment of nasal patency and objective measurement of inflammatory responses.

  6. Setting Occupational Exposure Limits for Chemical Allergens--Understanding the Challenges.

    PubMed

    Dotson, G S; Maier, A; Siegel, P D; Anderson, S E; Green, B J; Stefaniak, A B; Codispoti, C D; Kimber, I

    2015-01-01

    Chemical allergens represent a significant health burden in the workplace. Exposures to such chemicals can cause the onset of a diverse group of adverse health effects triggered by immune-mediated responses. Common responses associated with workplace exposures to low molecular weight (LMW) chemical allergens range from allergic contact dermatitis to life-threatening cases of asthma. Establishing occupational exposure limits (OELs) for chemical allergens presents numerous difficulties for occupational hygiene professionals. Few OELs have been developed for LMW allergens because of the unique biological mechanisms that govern the immune-mediated responses. The purpose of this article is to explore the primary challenges confronting the establishment of OELs for LMW allergens. Specific topics include: (1) understanding the biology of LMW chemical allergies as it applies to setting OELs; (2) selecting the appropriate immune-mediated response (i.e., sensitization versus elicitation); (3) characterizing the dose (concentration)-response relationship of immune-mediated responses; (4) determining the impact of temporal exposure patterns (i.e., cumulative versus acute exposures); and (5) understanding the role of individual susceptibility and exposure route. Additional information is presented on the importance of using alternative exposure recommendations and risk management practices, including medical surveillance, to aid in protecting workers from exposures to LMW allergens when OELs cannot be established.

  7. Allergic Non-Asthmatic Adults Have Regional Pulmonary Responses to Segmental Allergen Challenge

    PubMed Central

    Kelly, Vanessa J.; Winkler, Tilo; Venegas, Jose G.; Kone, Mamary; Hamilos, Daniel L.; Afshar, Roshi; Cho, Josalyn L.; Luster, Andrew D.; Medoff, Benjamin D.; Harris, R. Scott

    2015-01-01

    Background Allergic non-asthmatic (ANA) adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic disease is truly isolated to the upper airways. Methods In 6 ANA subjects, bronchoalveolar lavages (BAL) were performed at baseline and 24h after instillation of an allergen and a diluent in separate lung lobes. After instillation (10h), functional imaging was performed to quantify and compare regional perfusion, ventilation, fractional gas content (Fgas), and glucose uptake rate (Ki) between the baseline, diluent and allergen lobes. BAL cell counts were also compared. Results In ANA subjects, compared to the baseline and diluent lobes, perfusion and ventilation were significantly lower in the allergen lobe (median [inter-quartile range], baseline vs. diluent vs. allergen: Mean-normalized perfusion; 0.87 [0.85–0.97] vs. 0.90 [0.86–0.98] vs. 0.59 [0.55–0.67]; p<0.05. Mean-normalized ventilation 0.89 [0.88–0.98] vs. 0.95 [0.89–1.02] vs. 0.63 [0.52–0.67], p<0.05). In contrast, no significant differences were found in Fgas between baseline, diluent and allergen lobes or in Ki. Total cell counts, eosinophil and neutrophil cell counts (cells/ml BAL) were significantly greater in the allergen lobe compared to the baseline lobe (all P<0.05). Conclusions Despite having no clinical symptoms of a lower airway allergic response (cough and wheeze) allergic non-asthmatic subjects have a pulmonary response to allergen exposure which manifests as reduced ventilation and perfusion. PMID:26640951

  8. Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis.

    PubMed

    Maniscalco, M; Sofia, M; Carratù, L; Higenbottam, T

    2001-05-01

    Nitric oxide has been detected by chemiluminescence in the lumen of nasal airway, which is increased in nasal breathing in patients with seasonal rhinitis during a chronic exposure. The purpose of this study was to determinate the effect of a NO-synthase inhibitor NGL-arginine methyl ester (L-NAME) on nasal airway resistance (NAR) in patients with seasonal allergic rhinitis after an acute challenge to the allergen. Nitric oxide levels in the nose were measured by the chemiluminescence method in nine non-atopic volunteers and in seven patients with seasonal rhinitis at rest and after an acute challenge with the allergen. NAR were measured by active anterior rhinomanometry. Basal nasal NO concentration in allergic rhinitis was 496.5 +/- 151.4 parts per billion (ppb). (n = 7) and it was not significantly different from levels found in the control group: 458.4 +/- 105.9 ppb (n = 9). The topical administration of L-NAME in allergic rhinitis reduced the NO concentration (338.6 +/- 99.3 ppb, P < 0.001; n = 7). In the rhinitic patients the challenge with the allergen did not modify the nasal NO levels (504.5 +/- 138.5 ppb). The application of the allergen after the pretreatment with placebo caused a significant increase in NAR (from 0.32 +/- 0.11 Pa s cm-3 to 1.01 +/- 0.12 Pa s cm-3, P < 0.001; n = 7). Pre-treatment with L-NAME did not prevent the increase in NAR induced by allergen challenge (from 0.36 +/- 0.15 Pa s cm-3 to 1.06 +/- 0.26 Pa s cm-3). The results indicate that nasal administration of a NOS inhibitor L-NAME, at doses capable of decreasing nasal NO levels, has no effect on NAR and it does not prevent the NAR increase induced by an acute challenge with allergen in subjects with seasonal rhinitis.

  9. T helper 17 cells and related cytokines after allergen inhalation challenge in allergic asthmatics.

    PubMed

    Naji, Nizar; Smith, Steven G; Gauvreau, Gail M; O'Byrne, Paul M

    2014-01-01

    T helper (Th)17 cells may play a role in allergic asthma. This study assessed the effect of allergen inhalation challenge on circulating Th17 cells and related cytokines in allergic asthmatics. Peripheral blood mononuclear cells were collected from 16 atopic asthmatics before and 24 h after allergen challenge, as well as from 10 atopic nonasthmatics and 10 normal controls. Cells were stained for Th17 cytokines and their receptors (IL-17A, IL-17F, IL-21, IL-22, IL-17R, and IL-23R) using flow cytometry. Cytokine concentrations from cell culture supernatants were quantified using a multiplex assay for IL-17A, IL-17F, IL-21, IL-22, and IL-23. At baseline, asthmatics had a higher percentage of circulating Th17 cells (1.2 ± 0.5%) compared to normal controls (0.9 ± 0.66%, p < 0.001) but not compared to atopic nonasthmatics (1.13 ± 0.5%). There was a significant increase in Th17 cells in asthmatics after allergen challenge to 1.55 ± 0.4% (p < 0.05) and a trend toward significance in IL-17R expression from 3.4 ± 4.3 to 6.86 ± 6.84% after allergen challenge (p = 0.06). There was also a significant reduction in IL-21-positive cells following allergen challenge from 3.46 ± 1.85 to 2.33 ± 1.37% (p < 0.001). There were no significant differences in IL-17F, IL-22 and IL-23R expression. The concentration of IL-17A in culture supernatant was significantly higher in asthmatics compared to normal controls and IL-17A significantly increased 24 h after allergen challenge. The increase of Th17 cells and IL-17A in atopic asthma after allergen inhalation challenge suggests a possible role for Th17 in allergen-induced airway responses. © 2014 S. Karger AG, Basel.

  10. Exhaled nitric oxide in asthmatic children and adolescents after nasal allergen challenge.

    PubMed

    Pedroletti, Christophe; Lundahl, Joachim; Alving, Kjell; Hedlin, Gunilla

    2005-02-01

    Epidemiological data suggest a comorbidity link between nasal and bronchial allergic disease. Exhaled nitric oxide (FENO) is a sensitive marker of bronchial inflammation and increases after bronchial allergen provocation. We studied FENO in 19 children and adolescents with allergic asthma and 10 controls before and 2, 6 and 24 h after a single nasal allergen challenge. The correlation between FENO and other markers of allergic inflammation, such as eosinophils in blood and eosinophil cationic protein (ECP) in serum and nasal lavage was also assessed. FENO remained unchanged 24 h post-challenge in both steroid and steroid-naive patients. At 6 h post-challenge, FENO decreased in both asthmatics and controls. The asthmatic subjects showed a positive correlation between FENO and blood eosinophils before (r=0.71, p=0.001) and after the challenge, and between FENO and ECP in nasal lavage (r=0.62, p=0.02) 2 h after the challenge. Mean ECP in nasal lavage increased post-challenge but not significantly. We conclude that a single nasal allergen challenge does not augment bronchial inflammation although FENO, is related to blood eosinophil count and to the nasal inflammatory response. Our data do not support the theory of a direct transmission of the nasal inflammation to the lower airways.

  11. Evaluation of FCB, BDP, and DSCG in allergen inhalation challenge test.

    PubMed

    Wüthrich, B; Chen-Walden, H

    1982-12-01

    The protective effect of a new inhaled steroid, fluocortin butyl (FCB), was compared to that of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDP) in patients with extrinsic asthma by means of the allergen-inhalation challenge test. Three different groups of 12 patients each participated in the study. One group was treated with FCB and BDP, the two others with FCB and DSCG, all in a randomized crossover study plan. After an initial allergen challenge (FEV1 fall greater than 15%), the patients were allocated to either treatment for 7-10 days. A second challenge test was then carried out, followed by a washout period of 4 days. The treatments were then crossed-over, and a third allergen challenge was carried out at the end of the second treatment period. With BDP 5 of 12 patients were protected; with FCB, 6 of 12 in two groups and 8 of 12 patients in a third group. With DSCG 3 of 12 patients were protected in the group in which the last medication was given 12 h before challenge, and 8 of 12 patients in the second group in which medication was given 1-2 h before challenge. In the same groups on FCB no such time-dependent effect was observed. No statistically significant differences were found between either FCB and BDP, or FCB and DSCG in either group.

  12. Comparison of the clinical efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension in the conjunctival allergen challenge model.

    PubMed

    Berdy, Gregg J; Stoppel, Juan O; Epstein, Arthur B

    2002-06-01

    Olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension are topical antiallergic agents indicated for treatment of the signs and symptoms of allergic conjunctivitis and seasonal allergic conjunctivitis (SAC), respectively. The purpose of this study was to compare the efficacy and tolerability of olopatadine, loteprednol, and placebo in inhibiting the early-phase allergic reaction (within 30 minutes) after conjunctival allergen challenge (CAC). This was a single-center, randomized, double-masked, parallel-controlled CAC study. It consisted of 3 visits, with CAC performed at visit 1, confirmation and randomization at visit 2, and evaluation of the treatments at visit 3. Subjects with a history of allergic conjunctivitis were randomized to receive olopatadine, loteprednol, or placebo in a 2:2:1 ratio. Because loteprednol requires a loading period to achieve maximum efficacy, subjects assigned to this treatment received loteprednol QID bilaterally for a 14-day period; the olopatadine and placebo groups received placebo QID bilaterally during this period. At the evaluation visit, subjects received 1 drop of the assigned treatment in each eye. Fifteen minutes later, they were challenged with allergen. Subjects evaluated itching at 3, 5, and 10 minutes after challenge using a standardized 5-point scale; the investigator evaluated redness at 10, 15, and 20 minutes after challenge. Intraocular pressure (IOP) was measured at baseline and after the 14-day loading period. Nonparametric analyses were performed on the change from visit 2 to visit 3 in mean itching and redness scores for each time point, and on the change in mean IOP from visit 1 to visit 3. Fifty subjects (86% white; 42% male, 58% female; age range, 21-71 years) were enrolled and completed the study (20 olopatadine, 20 loteprednol, 10 placebo). The allergens to which subjects reacted were ragweed pollen (40%), cat hair or dander (30%), grass pollen (24%), and tree

  13. Assessing mucus and airway morphology in response to a segmental allergen challenge using OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Adams, David C.; Miller, Alyssa J.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    Asthma affects hundreds of millions of people worldwide, and the prevalence of the disease appears to be increasing. One of the most important aspects of asthma is the excessive bronchoconstriction that results in many of the symptoms experienced by asthma sufferers, but the relationship between bronchoconstriction and airway morphology is not clearly established. We present the imaging results of a study involving a segmental allergen challenge given to both allergic asthmatic (n = 12) and allergic non-asthmatic (n = 19) human volunteers. Using OCT, we have imaged and assessed baseline morphology in a right upper lobe (RUL) airway, serving as the control, and a right middle lobe (RML) airway, in which the allergen was to be administered. After a period of 24 hours had elapsed following the administration of the allergen, both airways were again imaged and the response morphology assessed. A number of airway parameters were measured and compared, including epithelial thickness, mucosal thickness and buckling, lumen area, and mucus content. We found that at baseline epithelial thickness, mucosal thickness, and mucosal buckling were greater in AAs than ANAs. We also observed statistically significant increases in these values 24 hours after the allergen had been administered for both the ANA and AA sets. In comparison, the control airway which received a diluent showed no statistically significant change.

  14. Identification of Genes Expressed by Human Airway Eosinophils after an In Vivo Allergen Challenge

    PubMed Central

    Esnault, Stephane; Kelly, Elizabeth A.; Schwantes, Elizabeth A.; Liu, Lin Ying; DeLain, Larissa P.; Hauer, Jami A.; Bochkov, Yury A.; Denlinger, Loren C.; Malter, James S.; Mathur, Sameer K.; Jarjour, Nizar N.

    2013-01-01

    Background The mechanism for the contribution of eosinophils (EOS) to asthma pathophysiology is not fully understood. Genome-wide expression analysis of airway EOS by microarrays has been limited by the ability to generate high quality RNA from sufficient numbers of airway EOS. Objective To identify, by genome-wide expression analyses, a compendium of expressed genes characteristic of airway EOS following an in vivo allergen challenge. Methods Atopic, mild asthmatic subjects were recruited for these studies. Induced sputum was obtained before and 48h after a whole lung allergen challenge (WLAC). Individuals also received a segmental bronchoprovocation with allergen (SBP-Ag) 1 month before and after administering a single dose of mepolizumab (anti-IL-5 monoclonal antibody) to reduce airway EOS. Bronchoalveolar lavage (BAL) was performed before and 48 h after SBP-Ag. Gene expression of sputum and BAL cells was analyzed by microarrays. The results were validated by qPCR in BAL cells and purified BAL EOS. Results A total of 299 transcripts were up-regulated by more than 2-fold in total BAL cells following SBP-Ag. Mepolizumab treatment resulted in a reduction of airway EOS by 54.5% and decreased expression of 99 of the 299 transcripts. 3 of 6 post-WLAC sputum samples showed increased expression of EOS-specific genes, along with the expression of 361 other genes. Finally, the intersection of the 3 groups of transcripts (increased in BAL post SBP-Ag (299), decreased after mepolizumab (99), and increased in sputum after WLAC (365)) was composed of 57 genes characterizing airway EOS gene expression. Conclusion We identified 57 genes that were highly expressed by BAL EOS compared to unseparated BAL cells after in vivo allergen challenge. 41 of these genes had not been previously described in EOS and are thus potential new candidates to elucidate EOS contribution to airway biology. PMID:23844029

  15. Endobronchial allergen challenge in asthma. Demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization.

    PubMed Central

    Broide, D H; Firestein, G S

    1991-01-01

    Airway inflammation is thought to play an important role in the pathogenesis of asthma. We have used in situ hybridization and an immunoassay to determine whether granulocyte macrophage colony-stimulating factor (GM-CSF) (a cytokine capable of eosinophil activation) is present in the airway of asthmatics (n = 6) who have 37.0 +/- 15.1% airway eosinophilia after endobronchial allergen challenge. Levels of immunoreactive GM-CSF (less than 4 pg/ml pre-allergen versus 180.5 +/- 46.9 pg/ml post-allergen) increased significantly 24 h after endobronchial allergen stimulation. The cellular source of bronchoalveolar lavage (BAL) GM-CSF, as determined by in situ hybridization and immunoperoxidase staining, was derived predominantly from UCHL-1 positive BAL lymphocytes, as well as from a smaller population of alveolar macrophages. Before local endobronchial allergen challenge, less than 1% of lymphocytes and alveolar macrophages recovered by BAL expressed GM-CSF mRNA, whereas after allergen stimulation 92.6 +/- 3.4% of lymphocytes and 17.5 +/- 22.7% of alveolar macrophages expressed GM-CSF mRNA. This study provides evidence that in an experimental model of allergen-induced asthma, activation of the immune and inflammatory response (BAL lymphocyte and alveolar macrophage production of GM-CSF) is temporally associated with an inflammatory cell influx of eosinophils into the airway. Images PMID:1885766

  16. [A multicenter, double-masked, randomized evaluation of olopatadine 0.2% using the conjunctival allergen challenge model in Japanese patients with allergic conjunctivitis].

    PubMed

    Ohno, Shigeaki

    2012-12-01

    Olopatadine hydrochloride ophthalmic solution, 0.2% (olopatadine 0.2%) is approved for allergic conjunctivitis when instilled twice-daily. The objective of this study was to evaluate the efficacy and safety of olopatadine 0.2% (instilled twice-daily) versus vehicle and olopatadine 0.1% (instilled 4-times daily) in Japanese patients with allergic conjunctivitis. A multicenter, parallel-group, double-masked, randomized, conjunctival allergen challenge (CAC) study. Patients > or = 18 years of age with histories of allergic conjunctivitis were treated with either olopatadine 0.2% or olopatadine 0.1% in a single eye and the vehicle in the contralateral eye at 1 visit. Overall, 267 patients were enrolled. Olopatadine 0.2% was superior to its vehicle for ocular itching (p < 0.0001 at the time of observation) and marginally superior for total redness (p = 0.0543 at the time of observation). Olopatadine 0.2% was similar to olopatadine 0.1% for ocular itching at the time of observation. No trends were identified through a review of safety parameters. Olopatadine 0.2% (instilled twice-daily) is safe, well tolerated, superior to the vehicle, and similar to olopatadine 0.1% in preventing ocular itching. Olopatadine 0.2%, which can be instilled less often than olopatadine 0.1%, is a useful new option for allergic conjunctivitis in Japanese patients that could potentially result in better treatment compliance.

  17. Expression of surface markers on the blood cells during the delayed asthmatic response to allergen challenge

    PubMed Central

    2014-01-01

    Patients with bronchial asthma develop various types of asthmatic response to bronchial challenge with allergen, such as immediate/early asthmatic response (IAR), late asthmatic response (LAR) or delayed asthmatic response (DYAR), because of different immunologic mechanisms. The DYAR, occurring between 24 and 56 hours after the bronchial allergen challenge (p < 0.01), differs from IAR and LAR in clinical as well as immunologic features. This study investigates the expression of CD molecules (markers) on the surface of particular cell populations in the peripheral blood and their changes during the DYAR. In 17 patients developing the DYAR (p < 0.01), the bronchial challenge with allergen was repeated 2–6 weeks later. The repeated DYAR (p < 0.001) was combined with recording of CD molecule expression on various types of blood cells by means of flow cytometry up to 72 hours after the challenge. The results were expressed in percent of the mean relative fluorescence intensity. The DYAR was accompanied by (a) increased expression of CD11b, CD11b/18, CD16,CD32, CD35, CD62E, CD62L, CD64, and CD66b on neutrophils; CD203C on basophils; CD25 and CD62L on eosinophils; CD14, CD16, CD64, and CD86 on monocytes; CD3, CD4, CD8, CD11a, CD18, and CD69 on lymphocytes; CD16, CD56, CD57, and CD94 on natural killer (NK) cells; and CD31, CD41, CD61, CD62P, and CD63 on thrombocytes and (b) decreased expression of CD18 and CD62L on eosinophils, CD15 on neutrophils, and CD40 on lymphocytes. These results suggest involvement of cell-mediated hypersensitivity mechanism, on participation of Th1- lymphocytes, neutrophils, monocytes, NK cells, and thrombocytes in the DYAR. PMID:24988283

  18. Screening and identification of putative allergens in berry fruits of the Rosaceae family: technical challenges.

    PubMed

    Marzban, Gorji; Maghuly, Fatemeh; Herndl, Anita; Katinger, Hermann; Laimer, Margit

    2008-01-01

    Cross-reactive proteins in small fruits of the Rosaceae family like strawberry, raspberry and blackberry revealed an unexpected complex IgE-reactivity pattern. Several copies of PR-10 and PR-14 proteins were detected by Southern blots in strawberry, raspberry and blackberry. In raspberry, the highest similarity at the DNA level for PR-10 and PR-14 (Rub i 1 and Rub i 3) was detected to strawberry sequences of Fra a 1 and Fra a 3. At the protein level, Rub i 1 and Rub i 3 showed more than 70% identity with homologous proteins of rosaceous fruits. Furthermore, raspberries contained additional putative allergens, e.g. class III acidic chitinases and cyclophilins. Blackberries were shown to share at least two well-known major fruit allergens with other rosaceous fruits, namely PR-10s and PR-14s homologous proteins. However the IgE-reactive proteins of small fruits are still not extensively investigated. The main challenges in studying small fruit allergens are the complexity of the fruit matrix, the diversity of physico-chemical properties of fruit proteins, the lack of appropriate protein extraction procedures and the missing information about the influence of processing treatments on food components.

  19. Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects

    PubMed Central

    Dente, F.; Bancalari, L.; Bacci, E.; Bartoli, M.; Carnevali, S.; Cianchetti, S.; Di, F; Giannini, D.; Vagaggini, B.; Testi, R.; Paggiaro, P.

    1999-01-01

    BACKGROUND—The long acting β2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property.
METHODS—The protective effect of a single dose of salmeterol (50 µg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation.
RESULTS—Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol.
CONCLUSIONS—A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.

 PMID:10377209

  20. Randomised, double blind, crossover challenge study of allergenicity of peanut oils in subjects allergic to peanuts.

    PubMed Central

    Hourihane, J. O.; Bedwani, S. J.; Dean, T. P.; Warner, J. O.

    1997-01-01

    OBJECTIVE: To determine the in vivo allergenicity of two grades of peanut oil for a large group of subjects with proved allergy to peanuts. DESIGN: Double blind, crossover food challenge with crude peanut oil and refined peanut oil. SETTING: Dedicated clinical investigation unit in a university hospital. SUBJECTS: 60 subjects allergic to peanuts; allergy was confirmed by challenge tests. OUTCOME MEASURES: Allergic reaction to the tested peanut oils. RESULTS: None of the 60 subjects reacted to the refined oil; six (10%) reacted to the crude oil. Supervised peanut challenge caused considerably less severe reactions than subjects had reported previously. CONCLUSIONS: Crude peanut oil caused allergic reactions in 10% of allergic subjects studied and should continue to be avoided. Refined peanut oil did not pose a risk to any of the subjects. It would be reasonable to recommend a change in labelling to distinguish refined from crude peanut oil. PMID:9133891

  1. DP2 (CRTh2) antagonism reduces ocular inflammation induced by allergen challenge and respiratory syncytial virus.

    PubMed

    Stebbins, Karin J; Broadhead, Alexander R; Musiyenko, Alla; Barik, Sailen; Scott, Jill M; Truong, Yen P; Stearns, Brian A; Hutchinson, John H; Prasit, Peppi; Evans, Jilly F; Lorrain, Daniel S

    2012-01-01

    Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D(2) (PGD(2)), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD(2), therefore, may be involved in both early and late phase reactions in response to allergen challenge. Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection. Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production. These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis. Copyright © 2011 S. Karger AG, Basel.

  2. Oral peanut challenge identifies an allergy but the peanut allergen threshold sensitivity is not reproducible.

    PubMed

    Glaumann, Susanne; Nopp, Anna; Johansson, S G O; Borres, Magnus P; Nilsson, Caroline

    2013-01-01

    Double-blind placebo-controlled food challenge, DBPCFC, the gold standard for diagnosing food allergy, is time-consuming and potentially dangerous. A basophil allergen threshold sensitivity test, CD-sens, has shown promising results as a diagnostic tool in food allergy. To evaluate the reproducibility of oral peanut challenge and compare the outcome to CD-sens in peanut-sensitized children. Twenty-seven children (4-19 years) underwent a DBPCFC followed by a single-blind oral food-challenge. The peanut challenges (1 mg to 5 g) were evaluated by severity scoring. Blood samples were drawn for CD-sens before the two first challenges. Thirteen children (48%) did not react at any of the challenges. Fourteen reacted at both peanut challenges but not to placebo. Only two of these children reacted at the same threshold dose and with the same severity score. All other children scored differently or reacted at different doses. For children with a positive challenge the geometric mean of the ratio of the doses was 1.834 (p = 0.307) and the arithmetic mean of the difference between the severity scores was 0.143 (p = 0.952). No association was obtained between the two peanut challenges regarding severity score (r(s) = 0.11, p = 0.71) or threshold dose (r(s) = 0.35, p = 0.22). Among the children positive in peanut challenge, 12 were positive in CD-sens. Two were low-responders and could not be evaluated. Geometric mean of the ratio of CD-sens values in children with a positive challenge was 1.035 (p = 0.505) but unlike for the severity score and the threshold dose the association between the two CD-sens values was strong (r(s) = 0.94, P<0.001). For a positive/negative test the reproducibility is 100% for both peanut challenge and CD-sens. However, a comparison of the degree of allergen threshold sensitivity between the two tests is not possible since the threshold dose and severity scoring is not reproducible.

  3. Failure of introduction of food allergens after negative oral food challenge tests in children.

    PubMed

    van der Valk, J P M; Gerth van Wijk, R; Vergouwe, Y; de Jong, N W

    2015-08-01

    One of the purposes to perform an oral food challenge (FC) test is to avoid unnecessary elimination of food allergens. In case of a negative FC test result, the food can be introduced. It is, however, unknown if patients act according to the outcome of the test. This study evaluates the rate of introduction of peanut, hazelnut, cow's milk or hen's egg allergens after a negative FC test. We investigated the introduction rate of children (0-18 years) with a negative FC test visiting the Department of Allergology, Erasmus Medical Centre Rotterdam from 2008 till 2013 and the factors that influence the rate of introduction. Patients were asked to complete a comprehensive questionnaire about their FC test. In total, 157 (38% girls, mean age during challenge 6.9 years) participated in the study. Of these FC tests, 104 (56%) were followed by a successful introduction, 30 (16%) by a partly introduction (traces or processed foods) and 52 (28%) by a failed introduction. Peanut and hazelnut showed a statistically significant lower successful introduction rate. Age, gender, symptoms during FC test, dietary advice and time period to introduction significantly influenced the rate of introduction. One fourth of the children with failure of introducing foods experienced symptoms during the introduction. More than one quarter of all children with a negative FC test result did not introduce the food. The FC test in its current form does not achieve its objective for this group of children.

  4. Mast cells present protrusions into blood vessels upon tracheal allergen challenge in mice.

    PubMed

    Bose, Oishee; Baluk, Peter; Looney, Mark R; Cheng, Laurence E; McDonald, Donald M; Caughey, George H; Krummel, Matthew F

    2015-01-01

    Mast cells (MC) and myeloid dendritic cells (DC) act proximally in detecting and processing antigens and immune insults. We sought to understand their comparative dynamic behavior with respect to the airway epithelium in the steady state and in response to an allergic stimulus in mouse trachea. We devised methods to label MC in living trachea and to demonstrate that MC and DC occupy distinct layers of the tracheal mucosa, with DC being closer to the lumen. DC numbers doubled after allergen challenge, but MC numbers remained stable. MC and DC migrated minimally in either steady state or allergen-challenge conditions, and their interactions with one another appeared to be stochastic and relatively infrequent. While DC, unlike MC, exhibited probing behaviors involving dendrites, these projections did not cross the epithelium into the airway lumen. MC typically were located too far from the epithelial surface to contact the tracheal lumen. However, MC had protrusions toward and into blood vessels, likely to load with IgE. Thus, DC and MC occupy distinct niches and engage in sessile surveillance in the mouse trachea. Little or no access of these cell types to the airway lumen suggests that trans-epithelial transport of proteins in the steady state would be required for them to access luminal antigens.

  5. Delayed Asthmatic Response to Allergen Challenge and Cytokines Released by Nonspecifically Stimulated Blood Cells

    PubMed Central

    Pelikan, Zdenek

    2013-01-01

    Background. Bronchial asthma patients can develop various asthmatic response types following bronchial allergen challenge, such as immediate (IAR), late (LAR), dual late (DLAR), or delayed (DYAR), due to different immunologic mechanisms. The DYAR, recorded in 24 patients, beginning between 26 and 32 hrs and lasting up to 56 hrs after the bronchial allergen challenge, differs from the IAR, LAR, and DLAR in clinical, diagnostic, and immunologic aspects. Objective. To investigate amounts of particular cytokines released by the blood cells after an additional nonspecific stimulation with Phorbol 12-myristate 13-acetate (PMA) during the DYAR. Methods. In 24 patients, the repeated DYAR was supplemented with determination of cytokines both in the nonstimulated plasma and in the supernatants of the blood cells stimulated with PMA before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results. No significant changes of the prechallenge cytokine concentrations in the non-stimulated serum were recorded in the DYAR patients as compared with the healthy subjects. The DYAR was accompanied by significantly increased postchallenge concentrations (P < 0.05) of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, G-CSF, TNF-α, and TGF-β, while decreased concentration of IL-7 (P < 0.05) in the nonstimulated plasma. The significantly increased postchallenge concentrations of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, TNF-α, and TGF-β were released by peripheral blood cells after stimulation with PMA, as compared with both their prechallenge concentrations and with the PBS control values. Conclusions. These results would support evidence for an important role of the Th1 cells, neutrophils, monocytes, and probably also NK cells in the immunologic mechanism(s) leading to the development of the clinical DYAR. Nevertheless, an additional role of macrophages, endothelial and epithelial cells in these mechanisms cannot be even excluded. PMID:24049660

  6. Phase 3 Randomized Double-Masked Study of Efficacy and Safety of Once-Daily 0.77% Olopatadine Hydrochloride Ophthalmic Solution in Subjects With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge Model.

    PubMed

    McLaurin, Eugene; Narvekar, Abhijit; Gomes, Paul; Adewale, Adeniyi; Torkildsen, Gail

    2015-10-01

    To assess the efficacy and safety of a novel once-daily 0.77% olopatadine hydrochloride ophthalmic solution in subjects with allergic conjunctivitis (AC) using the conjunctival allergen challenge (CAC) model. In this 5-week, multicenter, double-masked, phase 3, randomized trial, subjects aged ≥18 years with a history of AC and a confirmed positive bilateral CAC response were randomized 2:2:2:1 to receive olopatadine 0.77%, olopatadine 0.2%, olopatadine 0.1%, or vehicle, respectively, following a single topical dose in each eye. The primary objective was superiority of olopatadine 0.77% over all comparators on ocular itching according to a 0 to 4 scale (0 = none and 4 = incapacitating itch) at 24-hour duration of action and over vehicle only at the onset of action (3, 5, and 7 minutes after CAC for both). In total, 345 subjects were randomized. Olopatadine 0.77% was superior to the vehicle at alleviating ocular itching at all post-CAC time points at the onset of action and at 24 hours (difference in means: -0.9 to -1.5; P < 0.0001). Superiority in relieving ocular itching was also demonstrated for olopatadine 0.77% versus olopatadine 0.2% and 0.1% at 24 hours (difference in means: -0.3 to -0.5; P < 0.05). Additionally, olopatadine 0.77% significantly improved conjunctival redness and total redness compared with all comparators at the onset of action (differences in means: -0.3 to -0.6 and -0.8 to -2.0, respectively; both P < 0.05). No safety concerns for olopatadine 0.77% were identified. Olopatadine 0.77% demonstrated a rapid onset and prolonged duration of action. It was superior to all comparators in alleviating AC-associated ocular itching with a favorable safety profile.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01743027.

  7. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    PubMed

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.

  8. Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide

    PubMed Central

    Kelly, MM; King, EM; Rider, CF; Gwozd, C; Holden, NS; Eddleston, J; Zuraw, B; Leigh, R; O'Byrne, PM; Newton, R

    2012-01-01

    BACKGROUND AND PURPOSE Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma. EXPERIMENTAL APPROACH Bronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis. KEY RESULTS Compared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects. CONCLUSIONS AND IMPLICATIONS Expression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy

  9. Dermatophagoides farinae house dust mite allergen challenges reduce stratum corneum ceramides in an experimental dog model of acute atopic dermatitis.

    PubMed

    Stahl, Jessica; Paps, Judy; Bäumer, Wolfgang; Olivry, Thierry

    2012-12-01

    Ceramides are essential stratum corneum (SC) lipids and they play a pivotal role in maintaining effective cutaneous barrier function. The present study aimed at determining the effect of a Dermatophagoides farinae house dust mite (Df-HDM) allergen challenge on SC ceramides of atopic dogs experimentally sensitized to these allergens. Six Df-HDM-sensitized atopic Maltese-beagle dogs were used. Prechallenge SC was obtained by cyanoacrylate stripping. One week later, the dogs were challenged topically with Df-HDM allergens, which resulted in mild to moderate inflammation 24 h later. Two weeks after challenge, SC of lesional and nonlesional skin was obtained. Finally, SC was collected from challenge sites 2 months after lesion resolution. The different SC lipids were quantified blindly by thin-layer chromatography. Significantly lower amounts of ceramides [AH], [AP], [AS], [NP], [EOP], [NS] and [EOS] were observed in lesional SC compared with prechallenge samples, while no significant effect was found on the amount of other lipids, including cholesterol and free fatty acids. The ceramide profile of nonlesional skin generally showed the same postchallenge reduction pattern. Ceramide amounts returned to normal within 2 months after lesion remission. These findings suggest that the allergic reactions caused by Df-HDM allergens lead to a selective reduction of SC ceramides, not only at sites of inflammation but also at sites away from those of allergen application. There is normalization of ceramide amounts after inflammation subsides. These observations suggest that the deficiency of ceramides observed in canine atopic skin occurs, at least in part, secondary to inflammation. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

  10. Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

    DOE PAGES

    Kelada, Samir N. P.

    2016-07-22

    Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design inmore » which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics.« less

  11. Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

    SciTech Connect

    Kelada, Samir N. P.

    2016-07-22

    Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design in which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics.

  12. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    PubMed

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  13. Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge

    PubMed Central

    Jahnsen, F; Moloney, E; Hogan, T; Upham, J; Burke, C; Holt, P

    2001-01-01

    BACKGROUND—Airway dendritic cells (DC) play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been difficult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen.
METHODS—Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC.
RESULTS—A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm2). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood.
CONCLUSION—We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy.

 PMID:11641504

  14. Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation.

    PubMed

    Wang, H; Mobini, R; Fang, Y; Barrenäs, F; Zhang, H; Xiang, Z; Benson, M

    2010-08-01

    Previously, expression profiling has been used to analyse allergen-challenged T-helper type 2 cells, nasal biopsies and nasal fluid cells from patients with seasonal allergic rhinitis (SAR). Allergen-challenged peripheral blood mononuclear cells (PBMCs) provide a human in vitro model of how antigen-presenting cells, CD4+ T cells and effector cells such as basophils interact in allergic inflammation. To identify novel genes and pathways in allergen-challenged PBMCs from patients with SAR using gene expression profiling and functional studies. PBMCs from 11 patients with SAR and 23 healthy controls were analysed with gene expression profiling. mRNA expression of IL17RB in basophils was evaluated using quantitative real-time PCR. Membrane protein expression and apoptosis of basophils were examined by flow cytometry. Degranulation of basophils was assessed by measuring beta-hexosaminidase release. Cytokine release was measured using ELISA. Gene expression microarray analysis of allergen-challenged PBMCs showed that 209 out of 44000 genes were differentially expressed in patients compared with controls. IL17RB was the gene whose expression increased most in patients (P<0.0001). FACS analysis of PBMCs showed, for the first time, that basophils express IL-17RB. Following allergen challenge, IL-17RB protein increased significantly on basophils from patients compared with controls (P<0.05). IL-3 significantly increased both mRNA and protein expressions of IL17RB. Activation of IL-17RB by its ligand, IL-25, inhibited apoptosis of basophils. Moreover, IgE-mediated degranulation was enhanced by IL-25. Increased expression of IL-17RB on allergen-challenged basophil is regulated by IL-3, inhibits apoptosis and promotes IgE-mediated degranulation of basophils.

  15. Allergen nomenclature*

    PubMed Central

    1994-01-01

    The revised nomenclature for allergens is presented together with proposed nomenclatures for (a) allergen genes, mRNAs and cDNAs, and (b) recombinant and synthetic peptides of allergenic interest. PMID:7955031

  16. The effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDA) on the delayed nasal mucosa response to allergen challenge.

    PubMed

    Pelikan, Z

    1984-02-01

    The protective effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDA) on the "delayed nasal response" to allergen challenge (DNR) were investigated in 37 patients with allergic rhinitis. These thirty-seven patients, from a group of 268, developed 43 "delayed nasal responses" (DNR), 16 cases of "isolated delayed responses" (IDNR) and 27 cases of "dual delayed responses" (DDNR), where the delayed response (DLDNR) was preceded by an immediate response (INR). BDA demonstrated significant protective effects on the DNR in both its modifications; however, to a higher degree in the case of the IDNR. DSCG significantly decreased only the INR, being a part of the DDNR, while in the case of the DNR in both its modifications, DSCG was completely ineffective. It is suggested that BDA should be the drug of first choice in allergic rhinitis patients demonstrating the DNR. When immediate responses to the same or other allergens are also present, DSCG should be added at the beginning of the treatment for a temporary period of a few months.

  17. Up-Regulation of Interleukin-9 and the Interleukin-9-Associated Calcium-Activated Chloride Channel hCLCA1 in Nasal Mucosa Following In Vivo Allergen Challenge

    PubMed Central

    2007-01-01

    Interleukin (IL)-9 is a pleiotropic T helper 2-type cytokine that has been shown to be up-regulated in allergic airway disease, including asthma. IL-9 has been demonstrated to be a potent stimulus for the production and secretion of mucus from airway epithelial cells via induction of a calcium-activated chloride channel, hCLCA1. The objective of this study was to investigate the expression of IL-9 and hCLCA1 following allergen challenge in the nasal mucosa of allergic rhinitis patients. Nasal biopsies were obtained from allergic rhinitis patients out of allergen season both before (baseline) and after local antigen challenge with either ragweed or diluent (control). Immunohistochemistry and in situ hybridization were used to assess IL-9 protein and hCLCA1 messenger ribonucleic acid. Eosinophils and T cells were detected using immunohistochemistry. IL-9 and hCLCA1 were very low at baseline, and expression was significantly up-regulated following ragweed challenge. Whereas the number of eosinophils increased after allergen challenge, T-cell counts did not change significantly. The results of this study demonstrate the relationship between specific allergen challenge and expression of both IL-9 and hCLCA1, suggesting a possible mechanism for the increased production of mucus from airway epithelial cells in allergic rhinitis. PMID:20525149

  18. Expression of neuronal protein Kidins220/ARMS in the spleen and peripheral blood of mice following airway allergen challenge.

    PubMed

    Li, Ning; Dong, Xu; Yang, Chang; Liu, Yuli; Ni, Xiuqin

    2013-12-01

    Nerve growth factor (NGF), combined with the high-affinity tyrosine kinase receptor A (TrkA), has been reported to be involved in the pathogenesis of asthma. Ankyrin-rich membrane spanning/transmembrane substrate of protein kinase D (ARMS/Kidins220), a TrkA‑binding protein, modulates the NGF signaling pathway. The aim of the present study was to investigate the expression of Kidins220/ARMS and the effect NGF has on the protein in the spleen and peripheral blood, following airway allergen challenge in mice. BALB/c mice were sensitized and challenged with ovalbumin. The effects of NGF on Kidins220/ARMS in the spleen and peripheral blood of mice were assessed by administering anti-NGF antibody. Expression of ARMS, interleukin (IL)-1β and IL-4 in the spleen and peripheral blood was observed by reverse transcription-polymerase chain reaction, western blot analysis and immunohistochemistry. Pathological changes in the bronchi and lung tissues were examined by hematoxylin and eosin staining. Results showed that Kidins220/ARMS, IL-1β and IL-4 were overexpressed in the spleen and peripheral blood following allergen challenge, compared with the control mice. Moreover, following treatment with anti-NGF, the levels of Kidins220/ARMS, IL-1β and IL-4 in the mice were downregulated. Therefore, the results of the present study showed that Kidins220/ARMS is expressed in the spleen and peripheral blood of normal BALB/c mice and may participate in the immuno-inflammation of asthma through the NGF-mediated signaling pathway.

  19. Allergic contact dermatitis caused by sodium metabisulfite: a challenging allergen: a case series and literature review.

    PubMed

    García-Gavín, Juan; Parente, Joana; Goossens, An

    2012-11-01

    Sulfites, preservatives and antioxidants used in the cosmetic, pharmaceutical and food industry are contact allergens whose relevance seems to be difficult to establish. To perform a retrospective study on patients patch tested with a sulfite. Materials and methods. Between 1990 and 2010, 2763 patients were patch tested with sodium metabisulfite. The reactions were considered to be relevant if there was a clear relationship between the dermatitis and sulfite exposure. One hundred and twenty-four (4.5%) of 2763 patients patch tested positively to sodium metabisulfite. The most frequent localizations of the lesions were the face (40.3%) and the hands (24.2%). Six patients also reported systemic symptoms. Thirteen cases (10.5%) were occupational, 10 of them presenting with hand eczema. Sodium metabisulfite was the single allergen found in 76 cases (61.3%). The reactions were considered to be relevant in 80 cases (64.5%), of which 11 were occupational. Allergic contact dermatitis caused by sulfites is frequent and often relevant. One should be aware of possible relevant sources of exposure, particularly in occupational settings such as hairdressing and the food industry, and in pharmaceutical and cosmetic products. Patch testing with sodium metabisulfite, which seems to be the best indicator for sulfite contact allergy, is also useful in cases of immediate reactions to sulfite-containing products. © 2012 John Wiley & Sons A/S.

  20. Allergen nomenclature.

    PubMed Central

    Marsh, D. G.; Goodfriend, L.; King, T. P.; Lowenstein, H.; Platts-Mills, T. A.

    1986-01-01

    This article presents a nomenclature system for allergens which has been officially recommended by the International Union of Immunological Societies (IUIS). The nomenclature is based on proposals of the IUIS Sub-Committee for Allergen Nomenclature and is applicable to highly purified, well-characterized allergens and to non-purified or partially purified allergenic extracts. PMID:3492310

  1. Low-dose gamma irradiation of food protein increases its allergenicity in a chronic oral challenge.

    PubMed

    Vaz, A F M; Souza, M P; Medeiros, P L; Melo, A M M A; Silva-Lucca, R A; Santana, L A; Oliva, M L V; Perez, K R; Cuccovia, I M; Correia, M T S

    2013-01-01

    Few chronic food protein models have described the relationship between allergenicity and the molecular structure of food protein after physical processing. The effect of γ-radiation on the structure of food protein was measured by fluorescence, circular dichroism and microcalorimetry. BALB/c mice were intraperitoneally sensitized and then given non-irradiated and irradiated Con-A by daily gavage for 28days. The tendency to form insoluble amorphous aggregates and partially unfolded species was observed after irradiation. The administration of non-irradiated and irradiated samples at low-dose significantly increased weight loss as well as plasma levels of eotaxin in animals repeatedly exposed to Con-A. Significant lymphocytic infiltrate filling completely the stroma of microvilli and tubular glands was observed in the small intestinal of the group given Con-A irradiated at a low dose. This phenotype was not observed in animals treated with Con-A irradiated at a high dose.

  2. MIG (CXCL9), IP-10 (CXCL10) and I-TAC (CXCL11) concentrations after nasal allergen challenge in patients with allergic rhinitis.

    PubMed

    Tworek, Damian; Kuna, Piotr; Młynarski, Wojciech; Górski, Paweł; Pietras, Tadeusz; Antczak, Adam

    2013-10-31

    The role of monokine induced by interferon-γ (IFN-γ, MIG/CXCL9), IFN-γ-inducible protein (IP-10/CXCL10), and IFN-inducible T cell α chemoattractant (I-TAC/CXCL11) in allergic inflammation has not been explored in detail in vivo. The aim of the study was to examine the changes in concentrations of MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 in nasal lavages collected from healthy and allergic subjects during nasal allergen challenge. Subjects allergic to grass pollen and healthy controls were included. Nasal allergen challenge preceded by placebo administration was performed outside the pollen season. Nasal lavages were collected before and 30 min after application of the placebo and 30 min after allergen administration. Concentrations of chemokines were determined using ELISA. We observed significantly higher concentrations of IP-10/CXCL10 in allergic patients compared to the healthy subjects before (354.49 ±329.24 vs. 164.62 ±175.94 pg/ml; p = 0.036), 30 min after placebo (420.3 ±421.28 vs. 246.88 ±353.24 pg/ml; p = 0.021) and 30 min after allergen administration (403.28 ±359.29 vs. 162.68 ±148.69 pg/ml; p = 0.025). IP-10/CXCL10 levels did not change 30 min after allergen provocation. In contrast, MIG/CXCL9 levels were similar in both groups before and after placebo. However, a significant rise in MIG/CXCL9 concentration was noted in allergic patients 30 min after the allergen (138.88 ±109.59 vs. 395.8 ±301.2 pg/ml; p = 0.00026). I-TAC/CXCL11 concentrations increased after placebo as well as the allergen in both groups. IP-10/CXCL10 concentrations are elevated in nasal lavages from allergic patients and this chemokine may play a role in chronic allergic inflammation. MIG/CXCL9 levels increase rapidly after allergen application, which may suggest its role in the early allergic response. Results on I-TAC/CXCL11 concentrations remain inconclusive.

  3. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    PubMed Central

    Herbert, Cristan; Siegle, Jessica S.; Shadie, Alexander M.; Nikolaysen, Stina; Garthwaite, Linda; Hansbro, Nicole G.; Foster, Paul S.; Kumar, Rakesh K.

    2013-01-01

    SUMMARY Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC). We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice

  4. An Effective Community Advisory Committee (CAC). Revised.

    ERIC Educational Resources Information Center

    Duganne-Glicksman, Mary Ann; Dutton, Donna H.

    This document presents one module in a set of training resources for trainers to use with parents and/or professionals serving children with disabilities; focus is on effective community advisory committees (CACs). The modules stress content and activities that build skills and offer resources to promote parent-professional collaboration. Each…

  5. A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study

    PubMed Central

    Benichou, Annie-Claude; Armanet, Marion; Bussière, Anthony; Chevreau, Nathalie; Cardot, Jean-Michel; Tétard, Jan

    2014-01-01

    Occasional rhinitis symptoms caused by exposure to pollution or allergens is a growing concern. Based first on empirical observation of a lesser occurrence of allergies in quail farmers and then scientific works on ovomucoids properties, we developed a dietary supplement for the relief of such occasional rhinitis symptoms. The objective of the study was to determine whether one acute oral dose of the study product attenuates nasal provocation and other allergy-related symptoms after exposure to a standardized allergenic challenge as compared to placebo. Healthy subjects were recruited to participate in a randomized, double-blind, two-arm crossover, placebo-controlled, clinical trial. One acute dose of either the active study product (proprietary blend of quail egg) or placebo was given concomitantly to the standardized allergenic challenge. The primary endpoint was peak nasal inspiratory flow (PNIF) measurement and the secondary endpoints were subjects' perceived feelings of well-being based on Visual Analog Scale (VAS) scores for allergy-related symptoms, as well as immunoglobulin E count. Forty-three healthy subjects were enrolled and evaluable in a per protocol analysis. A gradual increase in PNIF from nadir up to Time 120 reflected the normal, gradual recovery from nasal obstruction induced by allergenic challenge for both the active and the placebo groups. At all postchallenge time points, the active group had higher PNIF values compared to the placebo group, indicating that the active product was associated with fewer symptoms and reduced intensity of these symptoms. The active product resulted also in statistically significant improvements of most of the subjects' perceived feelings of well-being based on VAS scores. No adverse events occurred during the study. In conclusion, the dietary supplement consisting of proprietary blend made of quail eggs provides fast and efficient relief of allergic rhinitis symptoms caused by the most common outdoor and indoor

  6. A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study.

    PubMed

    Benichou, Annie-Claude; Armanet, Marion; Bussière, Anthony; Chevreau, Nathalie; Cardot, Jean-Michel; Tétard, Jan

    2014-11-01

    Occasional rhinitis symptoms caused by exposure to pollution or allergens is a growing concern. Based first on empirical observation of a lesser occurrence of allergies in quail farmers and then scientific works on ovomucoids properties, we developed a dietary supplement for the relief of such occasional rhinitis symptoms. The objective of the study was to determine whether one acute oral dose of the study product attenuates nasal provocation and other allergy-related symptoms after exposure to a standardized allergenic challenge as compared to placebo. Healthy subjects were recruited to participate in a randomized, double-blind, two-arm crossover, placebo-controlled, clinical trial. One acute dose of either the active study product (proprietary blend of quail egg) or placebo was given concomitantly to the standardized allergenic challenge. The primary endpoint was peak nasal inspiratory flow (PNIF) measurement and the secondary endpoints were subjects' perceived feelings of well-being based on Visual Analog Scale (VAS) scores for allergy-related symptoms, as well as immunoglobulin E count. Forty-three healthy subjects were enrolled and evaluable in a per protocol analysis. A gradual increase in PNIF from nadir up to Time 120 reflected the normal, gradual recovery from nasal obstruction induced by allergenic challenge for both the active and the placebo groups. At all postchallenge time points, the active group had higher PNIF values compared to the placebo group, indicating that the active product was associated with fewer symptoms and reduced intensity of these symptoms. The active product resulted also in statistically significant improvements of most of the subjects' perceived feelings of well-being based on VAS scores. No adverse events occurred during the study. In conclusion, the dietary supplement consisting of proprietary blend made of quail eggs provides fast and efficient relief of allergic rhinitis symptoms caused by the most common outdoor and indoor

  7. Allergen-induced asthma

    PubMed Central

    Cockcroft, Donald W

    2014-01-01

    It was only in the late 19th century that specific allergens, pollen, animal antigens and, later, house dust mite, were identified to cause upper and lower airway disease. Early allergen challenge studies, crudely monitored before measurement of forced expiratory volume in 1 s became widespread in the 1950s, focused on the immediate effects but noted in passing prolonged and/or recurrent asthma symptoms. The late asthmatic response, recurrent bronchoconstriction after spontaneous resolution of the early responses occurring 3 h to 8 h or more postchallenge, has been identified and well characterized over the past 50 years. The associated allergen-induced airway hyper-responsiveness (1977) and allergen-induced airway inflammation (1985) indicate that these late sequelae are important in the mechanism of allergen-induced asthma. Allergens are now recognized to be the most important cause of asthma. A standardized allergen inhalation challenge model has been developed and is proving to be a valuable research tool in the investigation of asthma pathophysiology and of potential new pharmacological agents for the treatment of asthma. PMID:24791256

  8. Other Allergens

    MedlinePlus

    ... Basics Facts and Statistics NIAID Resources Allergens Peanut Tree Nuts Milk Egg Wheat Soy Fish Shellfish Sesame ... Basics Facts and Statistics NIAID Resources Allergens Peanut Tree Nuts Milk Egg Wheat Soy Fish Shellfish Sesame ...

  9. New Insights into Cockroach Allergens.

    PubMed

    Pomés, Anna; Mueller, Geoffrey A; Randall, Thomas A; Chapman, Martin D; Arruda, L Karla

    2017-04-01

    This review addresses the most recent developments on cockroach allergen research in relation to allergic diseases, especially asthma. The number of allergens relevant to cockroach allergy has recently expanded considerably up to 12 groups. New X-ray crystal structures of allergens from groups 1, 2, and 5 revealed interesting features with implications for allergen standardization, sensitization, diagnosis, and therapy. Cockroach allergy is strongly associated with asthma particularly among children and young adults living in inner-city environments, posing challenges for disease control. Environmental interventions targeted at reducing cockroach allergen exposure have provided conflicting results. Immunotherapy may be a way to modify the natural history of cockroach allergy and decrease symptoms and asthma severity among sensitized and exposed individuals. The new information on cockroach allergens is important for the assessment of allergen markers of exposure and disease, and for the design of immunotherapy trials.

  10. [Nasal allergenic provocation test].

    PubMed

    Becerril Angeles, M H; Pérez López, A; Azuara Pliego, E

    2000-01-01

    This is a method to evaluate both specific sensitivity to allergens in the nasal mucosa, IgE-mediated hypersensitivity, and antiinflammatory and antiallergic drugs efficacy, whose objectives are for research in diagnosis and treatment. The method is based in allergen extracts delivery in the nasal mucosa and the post-challenge measurement of rhinitis symptoms, vasoactive mediators release quantification and nasal obstruction degree evaluated by rhinomanometry. Nasal allergen challenge is a procedure of diagnostic and therapeutic evaluation usefulness, that must be performed in selected patients, in adequate facilities, by experts physicians, with standardised allergen dosages, in an specific nasal area, with objective measurements (rhinomanometry, mediators and secretions of the allergic response) and symptoms scoring that allow get reliable results in patients with allergic rhinitis under study.

  11. Pressure-induced structural transformation of CaC2

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Huang, Xiaoli; Li, Da; Huang, Yanping; Bao, Kuo; Li, Fangfei; Wu, Gang; Liu, Bingbing; Cui, Tian

    2016-05-01

    The high pressure structural changes of calcium carbide CaC2 have been investigated with Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques in a diamond anvil cell at room temperature. At ambient conditions, two forms of CaC2 co-exist. Above 4.9 GPa, monoclinic CaC2-ii diminished indicating the structural phase transition from CaC2-ii to CaC2-i. At about 7.0 GPa, both XRD patterns and Raman spectra confirmed that CaC2-i transforms into a metallic Cmcm structure which contains polymeric carbon chains. Along with the phase transition, the isolated C2 dumbbells are polymerized into zigzag chains resulting in a large volume collapse with 22.4%. Above 30.0 GPa, the XRD patterns of CaC2 become featureless and remain featureless upon decompression, suggesting an irreversible amorphization of CaC2.

  12. Pressure-induced structural transformation of CaC2.

    PubMed

    Wang, Lu; Huang, Xiaoli; Li, Da; Huang, Yanping; Bao, Kuo; Li, Fangfei; Wu, Gang; Liu, Bingbing; Cui, Tian

    2016-05-21

    The high pressure structural changes of calcium carbide CaC2 have been investigated with Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques in a diamond anvil cell at room temperature. At ambient conditions, two forms of CaC2 co-exist. Above 4.9 GPa, monoclinic CaC2-ii diminished indicating the structural phase transition from CaC2-ii to CaC2-i. At about 7.0 GPa, both XRD patterns and Raman spectra confirmed that CaC2-i transforms into a metallic Cmcm structure which contains polymeric carbon chains. Along with the phase transition, the isolated C2 dumbbells are polymerized into zigzag chains resulting in a large volume collapse with 22.4%. Above 30.0 GPa, the XRD patterns of CaC2 become featureless and remain featureless upon decompression, suggesting an irreversible amorphization of CaC2.

  13. CAC - NUCLEAR THERMAL ROCKET CORE ANALYSIS CODE

    NASA Technical Reports Server (NTRS)

    Clark, J. S.

    1994-01-01

    One of the most important factors in the development of nuclear rocket engine designs is to be able to accurately predict temperatures and pressures throughout a fission nuclear reactor core with axial hydrogen flow through circular coolant passages. CAC is an analytical prediction program to study the heat transfer and fluid flow characteristics of a circular coolant passage. CAC predicts as a function of time axial and radial fluid conditions, passage wall temperatures, flow rates in each coolant passage, and approximate maximum material temperatures. CAC incorporates the hydrogen properties model STATE to provide fluid-state relations, thermodynamic properties, and transport properties of molecular hydrogen in any fixed ortho-para combination. The program requires the general core geometry, the core material properties as a function of temperature, the core power profile, and the core inlet conditions as function of time. Although CAC was originally developed in FORTRAN IV for use on an IBM 7094, this version is written in ANSI standard FORTRAN 77 and is designed to be machine independent. It has been successfully compiled on IBM PC series and compatible computers running MS-DOS with Lahey F77L, a Sun4 series computer running SunOS 4.1.1, and a VAX series computer running VMS 5.4-3. CAC requires 300K of RAM under MS-DOS, 422K of RAM under SunOS, and 220K of RAM under VMS. No sample executable is provided on the distribution medium. Sample input and output data are included. The standard distribution medium for this program is a 5.25 inch 360K MS-DOS format diskette. CAC was developed in 1966, and this machine independent version was released in 1992. IBM-PC and IBM are registered trademarks of International Business Machines. Lahey F77L is a registered trademark of Lahey Computer Systems, Inc. SunOS is a trademark of Sun Microsystems, Inc. VMS is a trademark of Digital Equipment Corporation. MS-DOS is a registered trademark of Microsoft Corporation.

  14. CAC - NUCLEAR THERMAL ROCKET CORE ANALYSIS CODE

    NASA Technical Reports Server (NTRS)

    Clark, J. S.

    1994-01-01

    One of the most important factors in the development of nuclear rocket engine designs is to be able to accurately predict temperatures and pressures throughout a fission nuclear reactor core with axial hydrogen flow through circular coolant passages. CAC is an analytical prediction program to study the heat transfer and fluid flow characteristics of a circular coolant passage. CAC predicts as a function of time axial and radial fluid conditions, passage wall temperatures, flow rates in each coolant passage, and approximate maximum material temperatures. CAC incorporates the hydrogen properties model STATE to provide fluid-state relations, thermodynamic properties, and transport properties of molecular hydrogen in any fixed ortho-para combination. The program requires the general core geometry, the core material properties as a function of temperature, the core power profile, and the core inlet conditions as function of time. Although CAC was originally developed in FORTRAN IV for use on an IBM 7094, this version is written in ANSI standard FORTRAN 77 and is designed to be machine independent. It has been successfully compiled on IBM PC series and compatible computers running MS-DOS with Lahey F77L, a Sun4 series computer running SunOS 4.1.1, and a VAX series computer running VMS 5.4-3. CAC requires 300K of RAM under MS-DOS, 422K of RAM under SunOS, and 220K of RAM under VMS. No sample executable is provided on the distribution medium. Sample input and output data are included. The standard distribution medium for this program is a 5.25 inch 360K MS-DOS format diskette. CAC was developed in 1966, and this machine independent version was released in 1992. IBM-PC and IBM are registered trademarks of International Business Machines. Lahey F77L is a registered trademark of Lahey Computer Systems, Inc. SunOS is a trademark of Sun Microsystems, Inc. VMS is a trademark of Digital Equipment Corporation. MS-DOS is a registered trademark of Microsoft Corporation.

  15. Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol

    PubMed Central

    2013-01-01

    Background The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals. Methods/Aims This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre. A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed. Conclusion The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population. PMID:24028324

  16. Recombinant allergens

    PubMed Central

    Jutel, Marek; Solarewicz-Madejek, Katarzyna; Smolinska, Sylwia

    2012-01-01

    Allergen specific immunotherapy (SIT) is the only known causative treatment of allergic diseases. Recombinant allergen-based vaccination strategies arose from a strong need to both to improve safety and enhance efficacy of SIT. In addition, new vaccines can be effective in allergies including food allergy or atopic dermatitis, which poorly respond to the current treatment with allergen extracts. A number of successful clinical studies with both wild-type and hypoallergenic derivatives of recombinant allergens vaccines have been reported for the last decade. They showed high efficacy and safety profile as well as very strong modulation of T and B cell responses to specific allergens. PMID:23095874

  17. Screening the allergenic repertoires of wheat and maize with sera from double-blind, placebo-controlled food challenge positive patients.

    PubMed

    Weichel, M; Vergoossen, N J; Bonomi, S; Scibilia, J; Ortolani, C; Ballmer-Weber, B K; Pastorello, E A; Crameri, R

    2006-01-01

    Food allergy to wheat and maize is an increasing factor of deterioration of life quality, especially childhood and can, in rare cases, even induce anaphylaxis. Although omega-5 gliadin from wheat and maize lipid transfer protein have been characterized as major cereal allergens on the molecular level, the list of food allergens is far to be complete. To identify the IgE-binding repertoires of wheat and maize we screened respective cDNA libraries displayed on phage surface with sera from patients with a confirmed food allergy. The study included six patients with a positive double-blind, placebo-controlled food challenge (DBPCFC) to wheat, nine patients with a positive DBPCFC to maize, and six patients with anaphylactic reactions after ingestion of wheat. The enriched sequences encoding IgE-binding proteins showed heterogeneous repertoires for both, wheat and maize. The selected wheat repertoire yielded 12, the maize repertoire 11 open reading frames. Among these we identified allergens belonging to already characterized allergens families, such as gliadin, profilin and beta-expansin. Besides, we found novel proteins with high cross-reactive potential, such as thioredoxins, as well as sequences that had so far not been related to cereal allergy at all. The IgE-binding capacity of some selected proteins was evaluated in vitro and cross-reactivity was demonstrated by competition ELISA. With regard to the heterogeneity of the characterized sequences as well as to the biochemical nature of the new allergens detected we conclude that wheat and maize-related food allergy is more complex than so far anticipated.

  18. Understanding allergic asthma from allergen inhalation tests

    PubMed Central

    Cockcroft, Donald W; Hargreave, Fredrick E; O’Byrne, Paul M; Boulet, Louis-Philippe

    2007-01-01

    The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors’ involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic) airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta2-agonist-induced increase in airway response to allergen (including eosinophilic inflammation), advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a muticentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma. PMID:17948142

  19. Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

    PubMed

    Proud, D; Togias, A; Naclerio, R M; Crush, S A; Norman, P S; Lichtenstein, L M

    1983-11-01

    Using a recently developed model of nasal challenge, we have obtained data that clearly demonstrate, for the first time, kinin generation during a local allergic reaction in vivo. Allergic individuals (n = 8) and matched nonallergic controls (n = 8) were challenged intranasally with the appropriate antigen and nasal washes were taken before and after challenge. Washes were assayed for kinin, histamine, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity. Increased kinin generation was found by radioimmunoassay (RIA) in the nasal washes of all the allergics (5,560 +/- 1,670 pg/ml) but in none of the controls (38 +/- 16 pg/ml). The presence of kinin was highly correlated with that of histamine and TAME-esterase activity and with the onset of clinical symptoms (P less than 0.001). Serial dilutions of nasal washes produced RIA displacement curves that paralleled the standard curve, and recovery of standard kinins that were added to nasal washes was 100 +/- 4% (n = 14). Kinin recovery was identical in both allergics and controls and did not vary significantly with antigen challenge. The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes. High performance liquid chromatography analysis of the immunoreactive kinin in nasal washes showed it to be a mixture of lysylbradykinin and bradykinin. We conclude that kinins are produced during local allergic reactions in the nose and may contribute to the symptomatology of the allergic response.

  20. Quality Control of Biomedicinal Allergen Products - Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses.

    PubMed

    Spiric, Jelena; Engin, Anna M; Karas, Michael; Reuter, Andreas

    2015-01-01

    Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied.

  1. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

    PubMed

    Dharajiya, Nilesh; Vaidya, Swapnil; Sinha, Mala; Luxon, Bruce; Boldogh, Istvan; Sur, Sanjiv

    2009-12-21

    According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation.

  2. Loss of sirtuin 1 (SIRT1) disrupts skin barrier integrity and sensitizes mice to epicutaneous allergen challenge.

    PubMed

    Ming, Mei; Zhao, Baozhong; Shea, Christopher R; Shah, Palak; Qiang, Lei; White, Steven R; Sims, Diane M; He, Yu-Ying

    2015-04-01

    Skin barrier integrity requires a highly coordinated molecular system involving the structural protein filaggrin (FLG). Mutational loss of the skin barrier protein FLG predisposes subjects to the development of atopic dermatitis (AD). We sought to determine the role of sirtuin 1 (SIRT1) in skin barrier function, FLG expression, and development of AD. Skin histology of mice with skin-specific SIRT1 deletion and wild-type control animals was examined by using hematoxylin and eosin staining. Protein and mRNA abundance was analyzed by means of immunoblotting, immunohistochemistry, immunofluorescence, and RT-PCR. Serum antibody levels were assessed by means of ELISA. Here we show that FLG is regulated by the protein deacetylase SIRT1 and that SIRT1 is critical for skin barrier integrity. Epidermis-specific SIRT1 ablation causes AD-like skin lesions in mice, and mice with epidermal SIRT1 deletion are sensitive to percutaneous challenge by the protein allergen ovalbumin. In normal human keratinocytes and mouse skin SIRT1 knockdown or genetic deletion downregulates FLG, and regulation of FLG expression by SIRT1 requires the deacetylase activity of SIRT1. SIRT1 also promotes activation of the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor ligand restores FLG expression in SIRT1-inhibited cells. Compared with normal human skin, SIRT1 is downregulated in both AD and non-AD lesions. Our findings demonstrate a critical role of SIRT1 in skin barrier maintenance, open up new opportunities to use SIRT1 as a pharmacologic target, and might facilitate the development of mechanism-based agents for AD prevention and therapy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Loss of sirtuin 1 (SIRT1) disrupts skin barrier integrity and sensitizes mice to epicutaneous allergen challenge

    PubMed Central

    Ming, Mei; Zhao, Baozhong; Shea, Christopher R.; Shah, Palak; Qiang, Lei; White, Steven R.; Sims, Diane M.; He, Yu-Ying

    2014-01-01

    Background Skin barrier integrity requires a highly coordinated molecular system involving the structural protein filaggrin. Mutational loss of the skin barrier protein filaggrin predisposes individuals to the development of atopic dermatitis (AD). Objective to determine the role of SIRT1 in skin barrier function, filaggrin expression, and the development of AD. Methods Skin histology of mice with skin-specific SIRT1 deletion and wild-type controls was examined by Hematoxyline and Eosin (H&E). Protein and mRNA abundance was analyzed by immunoblot, immunohistochemistry, immunofluorescence, and RT-PCR. Serum antibody levels were assessed by ELISA. Results Here we show that filaggrin is regulated by the protein deacetylase SIRT1, and that SIRT1 is critical for skin barrier integrity. Epidermis-specific SIRT1 ablation causes AD-like skin lesions in mice, and mice with epidermal SIRT1 deletion are sensitive to percutaneous challenge by the protein allergen ovalbumin. In normal human keratinocytes and mouse skin, SIRT1 knockdown or genetic deletion down-regulates filaggrin, and regulation of filaggrin expression by SIRT1 requires the deacetylase activity of SIRT1. SIRT1 also promotes the activation of the aryl hydrocarbon receptor (AhR), and the AhR ligand restores filaggrin expression in SIRT1-inhibited cells. As compared with normal human skin, SIRT1 is down-regulated in the lesions of atopic dermatitis as well as non-atopic dermatitis. Conclusion Our findings demonstrate a critical role of SIRT1 in skin barrier maintenance, open up new opportunities to use SIRT1 as a pharmacological target, and may facilitate the development of mechanism-based agents for AD prevention and therapy. PMID:25445829

  4. NF-kB Induction in Airway Epithelium Increases Lung Inflammation in Allergen Challenged Mice

    PubMed Central

    Sheller, James R.; Polosukhin, Vasiliy V.; Mitchell, Daphne; Cheng, D-S.; Peebles, R. Stokes; Blackwell, Timothy S.

    2012-01-01

    NF-kB is a critical transcription factor for the production of many inflammatory cytokines. It is activated in the airway epithelium of human asthmatics and in mice after allergic stimulation. To examine the role of NF-kB activation in allergic inflammation we generated transgenic mouse lines that allowed for the inducible stimulation of NF-kB in airway epithelial cells. After allergic sensitization with ovalbumin and alum, mice were challenged daily with ovalbumin aerosols and NF-kB was activated in airway epithelium by administration of doxycycline. Enhancement of airway epithelial NF-kB expression alone did not lead to increased airway responsiveness to methacholine. However induction of epithelial NF-kB during allergic inflammation caused airway hyperresponsiveness, increased airway neutrophilic and lymphocytic inflammation and goblet cell hyperplasia. Accompanying the exaggerated inflammation was an increase in the cytokines, G-CSF, IL-15, and KC. Interestingly, the counter regulatory interleukin, IL-10, was suppressed by NF-kB activation. The epithelial NF-kB dependent modulation of these cytokines provides a plausible explanation for the increased inflammation seen with overexpression of NF-kB. Modulation of airway epithelial NF-kB activation enhances the airway hyperresponsiveness and mucus secretion found in the mouse lung during allergic inflammation. NF-kB represents a potential target for pharmacologic intervention in human asthma. PMID:19995280

  5. Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors, lipid transfer proteins and low-molecular-weight glutenins. Allergenic molecules recognized by double-blind, placebo-controlled food challenge.

    PubMed

    Pastorello, Elide A; Farioli, Laura; Conti, Amedeo; Pravettoni, Valerio; Bonomi, Simona; Iametti, Stefania; Fortunato, Donatella; Scibilia, Joseph; Bindslev-Jensen, Carsten; Ballmer-Weber, Barbara; Robino, Anna M; Ortolani, Claudio

    2007-01-01

    Three main problems hamper the identification of wheat food allergens: (1) lack of a standardized procedure for extracting all of the wheat protein fractions; (2) absence of double-blind, placebo-controlled food challenge studies that compare the allergenic profile of Osborne's three protein fractions in subjects with real wheat allergy, and (3) lack of data on the differences in IgE-binding capacity between raw and cooked wheat. Sera of 16 wheat-challenge-positive patients and 6 patients with wheat anaphylaxis, recruited from Italy, Denmark and Switzerland, were used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting of the three Osborne's protein fractions (albumin/globulin, gliadins and glutenins) of raw and cooked wheat. Thermal sensitivity of wheat lipid transfer protein (LTP) was investigated by spectroscopic approaches. IgE cross-reactivity between wheat and grass pollen was studied by blot inhibition. The most important wheat allergens were the alpha-amylase/trypsin inhibitor subunits, which were present in all three protein fractions of raw and cooked wheat. Other important allergens were a 9-kDa LTP in the albumin/globulin fraction and several low-molecular-weight (LMW) glutenin subunits in the gluten fraction. All these allergens showed heat resistance and lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only in Italian patients. The alpha-amylase inhibitor was confirmed to be the most important wheat allergen in food allergy and to play a role in wheat-dependent exercise-induced anaphylaxis, too. Other important allergens were LTP and the LMW glutenin subunits.

  6. Does CAC testing alter downstream treatment patterns for cardiovascular disease?

    PubMed

    Chi, Wiinie Chia-hsuan; Sylwestrzak, Gosia; Barron, John; Kasravi, Barsam; Power, Thomas; Redberg, Rita

    2014-08-01

    To assess if coronary artery calcium (CAC) scans influence treatment patterns as reflected by subsequent rates of cardiac imaging and therapeutic interventions, and their effect on ischemic events downstream. Longitudinal observational study from January 1, 2005, through August 31, 2011, using a large managed-care medical and pharmacy claims database. Two cohorts were evaluated: CAC patients who received CAC testing, and Reference patients, subject to preauthorization, who were denied CAC scans. Patients were adults less than 65 years old. Index date was CAC scan date for CAC and pre-authorization request date for Reference. Patients were stratified into high-risk and non-high-risk categories; outcomes were analyzed only for non-high-risk where CAC scores could potentially modify risk classification. Cardiac imaging, coronary revascularizations, and pharmaceutical interventions were evaluated for 6 months post index and adverse ischemic events were assessed using all available follow-up time. The study included 2679 CAC and 1135 Reference patients. Among non-high-risk patients, similar proportions of both groups received an imaging test within 6 months (23.2% vs 23.8%, respectively; P = .5); revascularization rates and pharmaceutical utilization were similar. Adverse events were rare. Age-sex adjusted incidence rate ratio for adverse events was 1.1 (95% CI, 0.36-3.38) among CAC relative to Reference. High-risk patients, considered inappropriate for CAC testing, represented 20.2% and 23.5% of CAC and Reference, respectively (P <.05). Patients having CAC scans were not associated with fewer downstream ischemic events nor with reduced subsequent imaging and therapeutic interventions among non-high-risk patients. Results also indicated inappropriate testing of high-risk patients.

  7. Fungal allergens.

    PubMed Central

    Horner, W E; Helbling, A; Salvaggio, J E; Lehrer, S B

    1995-01-01

    Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immunotherapy of allergy to fungi require well-characterized or standardized extracts that contain the relevant allergen(s) of the appropriate fungus. Production of standardized extracts is difficult since fungal extracts are complex mixtures and a variety of fungi are allergenic. Thus, the currently available extracts are largely nonstandardized, even uncharacterized, crude extracts. Recent significant progress in isolating and characterizing relevant fungal allergens is summarized in the present review. Particularly, some allergens from the genera Alternaria, Aspergillus, and Cladosporium are now thoroughly characterized, and allergens from several other genera, including some basidiomycetes, have also been purified. The availability of these extracts will facilitate definitive studies of fungal allergy prevalence and immunotherapy efficacy as well as enhance both the diagnosis and therapy of fungal allergy. PMID:7621398

  8. The many phases of CaC2

    NASA Astrophysics Data System (ADS)

    Konar, Sumit; Nylén, Johanna; Svensson, Gunnar; Bernin, Diana; Edén, Mattias; Ruschewitz, Uwe; Häussermann, Ulrich

    2016-07-01

    Polymorphic CaC2 was prepared by reacting mixtures of CaH2 and graphite with molar ratios between 1:1.8 and 1:2.2 at temperatures between 700 and 1400 °C under dynamic vacuum. These conditions provided a well controlled, homogeneous, chemical environment and afforded products with high purity. The products, which were characterized by powder X-ray diffraction, solid state NMR and Raman spectroscopy, represented mixtures of the three known polymorphs, tetragonal CaC2-I and monoclinic CaC2-II and -III. Their proportion is dependent on the nominal C/CaH2 ratio of the reaction mixture and temperature. Reactions with excess carbon produced a mixture virtually free from CaC2-I, whereas high temperatures (above 1100 °C) and C-deficiency favored the formation of CaC2-I. From first principles calculations it is shown that CaC2-I is dynamically unstable within the harmonic approximation. This indicates that existing CaC2-I is structurally/dynamically disordered and may possibly even occur as slightly carbon-deficient phase CaC2-δ. It is proposed that monoclinic II is the ground state of CaC2 and polymorph III is stable at temperatures above 200 °C. Tetragonal I represents a metastable, heterogeneous, phase of CaC2. It is argued that a complete understanding of the occurrence of three room temperature modifications of CaC2 will require a detailed characterization of compositional and structural heterogeneities within the high temperature form CaC2-IV, which is stable above 450 °C. The effect of high pressure on the stability of the monoclinic forms of CaC2 was studied in a diamond anvil cell using Raman spectroscopy. CaC2-II and -III transform into tetragonal CaC2-I at about 4 and 1GPa, respectively.

  9. Outdoor allergens.

    PubMed Central

    Burge, H A; Rogers, C A

    2000-01-01

    Outdoor allergens are an important part of the exposures that lead to allergic disease. Understanding the role of outdoor allergens requires a knowledge of the nature of outdoor allergen-bearing particles, the distributions of their source, and the nature of the aerosols (particle types, sizes, dynamics of concentrations). Primary sources for outdoor allergens include vascular plants (pollen, fern spores, soy dust), and fungi (spores, hyphae). Nonvascular plants, algae, and arthropods contribute small numbers of allergen-bearing particles. Particles are released from sources into the air by wind, rain, mechanical disturbance, or active discharge mechanisms. Once airborne, they follow the physical laws that apply to all airborne particles. Although some outdoor allergens penetrate indoor spaces, exposure occurs mostly outdoors. Even short-term peak outdoor exposures can be important in eliciting acute symptoms. Monitoring of airborne biological particles is usually by particle impaction and microscopic examination. Centrally located monitoring stations give regional-scale measurements for aeroallergen levels. Evidence for the role of outdoor allergens in allergic rhinitis is strong and is rapidly increasing for a role in asthma. Pollen and fungal spore exposures have both been implicated in acute exacerbations of asthma, and sensitivity to some fungal spores predicts the existence of asthma. Synergism and/or antagonism probably occurs with other outdoor air particles and gases. Control involves avoidance of exposure (staying indoors, preventing entry of outdoor aerosols) as well as immunotherapy, which is effective for pollen but of limited effect for spores. Outdoor allergens have been the subject of only limited studies with respect to the epidemiology of asthma. Much remains to be studied with respect to prevalence patterns, exposure and disease relationships, and control. PMID:10931783

  10. Allergen databases and allergen semantics.

    PubMed

    Gendel, Steven M

    2009-08-01

    The efficacy of any specific bioinformatic analysis of the potential allergenicity of new food proteins depends directly on the nature and content of the databases that are used in the analysis. A number of different allergen-related databases have been developed, each designed to meet a different need. These databases differ in content, organization, and accessibility. These differences create barriers for users and prevent data sharing and integration. The development and application of appropriate semantic web technologies, (for example, a food allergen ontology) could help to overcome these barriers and promote the development of more advanced analytic capabilities.

  11. The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber.

    PubMed

    Horak, Friedrich; Zieglmayer, Petra; Zieglmayer, René; Lemell, Patrick

    2010-05-01

    This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis. Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2. Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

  12. Optimization of allergen standardization.

    PubMed

    Jeong, Kyoung Yong; Hong, Chein-Soo; Lee, Joo-Shil; Park, Jung-Won

    2011-05-01

    Preparation of high quality allergen extracts is essential for the diagnosis and immunotherapy of allergic disorders. Standardization of allergen extracts concerns determination of the allergen unit, development of reference material and measurement of the overall IgE binding capacity of an allergen extract. Recently, quantification of individual allergens has been the main focus of allergen standardization because the allergenicity of most allergen extracts is known to be mainly dependent on the content of a small number of allergen molecules. Therefore, characterization of major allergens will facilitate the standardization of allergens. In this article, we review the current state of allergen standardization. In addition, we briefly summarize the components of allergen extracts that should be under control for the optimization of allergen standardization, since its adjuvant-like activities could play an important role in allergic reactions even though the molecule itself does not bind to the IgE antibodies from subjects.

  13. SALT Spectroscopic classification of nuclear transient Gaia16cac

    NASA Astrophysics Data System (ADS)

    Hamanowicz, A.; Wyrzykowski, L.; Buckley, David; Whitelock, Patricia

    2016-12-01

    We report the spectroscopic classification of a nuclear transient Gaia16cac discovered by Gaia. The spectrum was obtained using the Robert Stobie Spectrograph (RSS) on the South African Large Telescope (SALT).

  14. Efficacy and safety of olopatadine hydrochloride 0.77% in patients with allergic conjunctivitis using a conjunctival allergen-challenge model

    PubMed Central

    Torkildsen, Gail; Narvekar, Abhijit; Bergmann, Mark

    2015-01-01

    Background Symptom relief for the duration of 24 hours after treatment would benefit patients with allergic conjunctivitis. Objective To compare the safety and efficacy of olopatadine 0.77% with vehicle or olopatadine 0.2% in patients with allergic conjunctivitis in a conjunctival allergen-challenge clinical study. Patients and methods In this Phase III, multicenter, double-masked, parallel-group, randomized trial, patients with allergic conjunctivitis received olopatadine 0.77%, its vehicle, or olopatadine 0.2%, administered once at visits 3A (day 0), 4A (day 14 ±2), and 5 (day 21 +3). Allergic conjunctivitis-associated sign and symptom assessments included ocular itching, conjunctival redness, total redness, chemosis, and tearing scores. Adverse events and ocular safety parameters were also assessed. Results A total of 202 qualifying patients were randomized. Olopatadine 0.77% was superior (P<0.001) to vehicle for treatment of ocular itching at 3, 5, and 7 minutes postchallenge at onset of action and 16- and 24-hour duration of action. Conjunctival redness mean scores were significantly lower for olopatadine 0.77% versus vehicle at all three post-conjunctival allergen-challenge time points: onset (−1.52 to −1.48; P<0.001), 16 hours (−1.50 to −1.38; P<0.01), and 24 hours (−1.58 to −1.38; P<0.05). At 24 hours, olopatadine 0.77% was superior to olopatadine 0.2% at all three postchallenge time points for ocular itching (P<0.05), conjunctival redness (P<0.05), and total redness (P<0.05). No clinically relevant differences in safety parameters or adverse events were observed between the treatment groups. Conclusion Olopatadine 0.77% is superior to both its vehicle and olopatadine 0.2% for the treatment of allergen-mediated ocular itching and conjunctival redness. Ocular itching symptom relief is maintained over 24 hours, supporting once-daily dosing and demonstrating a comparable safety profile to olopatadine 0.2%. PMID:26392751

  15. Efficacy and safety of olopatadine hydrochloride 0.77% in patients with allergic conjunctivitis using a conjunctival allergen-challenge model.

    PubMed

    Torkildsen, Gail; Narvekar, Abhijit; Bergmann, Mark

    2015-01-01

    Symptom relief for the duration of 24 hours after treatment would benefit patients with allergic conjunctivitis. To compare the safety and efficacy of olopatadine 0.77% with vehicle or olopatadine 0.2% in patients with allergic conjunctivitis in a conjunctival allergen-challenge clinical study. In this Phase III, multicenter, double-masked, parallel-group, randomized trial, patients with allergic conjunctivitis received olopatadine 0.77%, its vehicle, or olopatadine 0.2%, administered once at visits 3A (day 0), 4A (day 14 ±2), and 5 (day 21 +3). Allergic conjunctivitis-associated sign and symptom assessments included ocular itching, conjunctival redness, total redness, chemosis, and tearing scores. Adverse events and ocular safety parameters were also assessed. A total of 202 qualifying patients were randomized. Olopatadine 0.77% was superior (P<0.001) to vehicle for treatment of ocular itching at 3, 5, and 7 minutes postchallenge at onset of action and 16- and 24-hour duration of action. Conjunctival redness mean scores were significantly lower for olopatadine 0.77% versus vehicle at all three post-conjunctival allergen-challenge time points: onset (-1.52 to -1.48; P<0.001), 16 hours (-1.50 to -1.38; P<0.01), and 24 hours (-1.58 to -1.38; P<0.05). At 24 hours, olopatadine 0.77% was superior to olopatadine 0.2% at all three postchallenge time points for ocular itching (P<0.05), conjunctival redness (P<0.05), and total redness (P<0.05). No clinically relevant differences in safety parameters or adverse events were observed between the treatment groups. Olopatadine 0.77% is superior to both its vehicle and olopatadine 0.2% for the treatment of allergen-mediated ocular itching and conjunctival redness. Ocular itching symptom relief is maintained over 24 hours, supporting once-daily dosing and demonstrating a comparable safety profile to olopatadine 0.2%.

  16. Maize food allergy: lipid-transfer proteins, endochitinases, and alpha-zein precursor are relevant maize allergens in double-blind placebo-controlled maize-challenge-positive patients.

    PubMed

    Pastorello, Elide A; Farioli, Laura; Pravettoni, Valerio; Scibilia, Joseph; Conti, Amedeo; Fortunato, Donatella; Borgonovo, Linda; Bonomi, Simona; Primavesi, Laura; Ballmer-Weber, Barbara

    2009-09-01

    Italian patients with maize anaphylaxis have been shown to have IgE toward two major maize allergens: an alpha-amylase inhibitor and a 9-kDa LTP. A complete study on maize food allergens in patients with positive maize double-blind, placebo-controlled food challenge (DBPCFC) is lacking. The objective was to utilize the three maize protein fractions to identify and characterize the most relevant IgE-binding proteins recognized by the sera of Italian and Swiss patients with either a positive maize-DBPCFC or a history of maize-induced anaphylaxis. Osborne's protein fractions of maize were extracted to obtain water-soluble, total zein, and total protein fractions. Protein IgE-binding capacity was investigated by SDS-PAGE immunoblotting using the sera from DBPCFC-positive patients and from patients with maize-induced anaphylaxis. Purified maize LTP was used to inhibit the IgE immunoblotting of the three protein fractions. IgE immunoblotting demonstrated that the 9-kDa LTP was recognized by all the Italian patients and by none of the Swiss patients. Other allergens were: 14-kDa alpha-amylase inhibitor, 30-kDa endochitinases A and -B, 19 kDa zein-beta precursor, and 26 kDa zein-alpha precursor; a newly described allergen, the globulin-2 precursor, identified in the total protein fraction. It is noteworthy that maize LTP and endochitinase were cross-reactive with grape LTP and one grape endochitinase. LTP was found to be the only major allergen in Italian patients with either positive maize challenge or a history of maize-induced anaphylaxis. We have identified other maize allergens in subjects with maize food allergy, as grape cross-reactive endochitinase, however, the clinical significance of these proteins needs to be investigated in larger groups of patients with allergy to these food items.

  17. A multicenter evaluation of the efficacy and duration of action of alcaftadine 0.25% and olopatadine 0.2% in the conjunctival allergen challenge model

    PubMed Central

    Ackerman, Stacey; D’Ambrosio, Francis; Greiner, Jack V; Villanueva, Linda; Ciolino, Joseph B; Hollander, David A

    2013-01-01

    Background The purpose of this study was to evaluate the efficacy and duration of action of once-daily dosing with alcaftadine 0.25% ophthalmic solution and olopatadine 0.2% ophthalmic solution as compared with placebo in the prevention of ocular itching, and to directly compare the efficacy of alcaftadine 0.25% with olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis using the conjunctival allergen challenge model. Methods Subjects with allergic conjunctivitis (n = 127) were enrolled in a multicenter, double-masked, randomized, active-controlled and placebo-controlled clinical trial. Using the conjunctival allergen challenge model, this study was conducted over the course of approximately 5 weeks. Subjects were randomized into one of three treatment arms: alcaftadine 0.25% ophthalmic solution, olopatadine 0.2% ophthalmic solution, or placebo. Study medications were administered twice over the course of the trial. The primary efficacy measure for the study was ocular itching evaluated by the subject at 3, 5, and 7 minutes post challenge. Secondary endpoints, measured at 7, 15, and 20 minutes post challenge, included conjunctival, ciliary, and episcleral redness, lid swelling, chemosis, and tearing. Duration of action was measured at 16 and 24 hours post-instillation of the study medication at visits 3 and 4, respectively. Results For the primary measure of ocular itching, both actives, alcaftadine 0.25% and olopatadine 0.2%, were statistically superior to placebo at all three measured time points for both the 16-hour and 24-hour measures (P < 0.0001). Eyes treated with alcaftadine 0.25% had numerically lower mean ocular itching scores than eyes treated with olopatadine 0.2% at every time point, and this difference was statistically significant at the 3-minute time point 16 hours post instillation (P = 0.026). Eyes treated with alcaftadine 0.25% and with olopatadine 0.2% displayed significantly less lid swelling relative to

  18. Prevalence of sensitization to food allergens and challenge proven food allergy in patients visiting allergy centers in Rawalpindi and Islamabad, Pakistan.

    PubMed

    Inam, Muhammad; Shafique, Rubaba Hamid; Roohi, Nabila; Irfan, Muhammad; Abbas, Shahid; Ismail, Muhammad

    2016-01-01

    In this study, we estimated the prevalence of food allergy in the adult allergic patients of Rawalpindi and Islamabad , Pakistan, based on self-report, skin prick test (SPT) and oral food challenge test (OFC). SPT was used for the estimation of sensitization to wheat, egg, milk, beef, chicken, mutton, fish, corn, lentils, rice, soya, peanut and banana. Among 689 patients, 39.19 % showed sensitivity to one or more foods, where, sensitization to wheat (156; 22.6 %) was highest, followed by egg (148; 21.48 %) and milk (138; 20.03 %). Sensitization to various proteins ranged between 15.53-15.97 %, while lentils, corn, rice, soya and peanut sensitization was 15.4, 16, 12.5, 12 and 11.5 % respectively. Only 7.1 % patients were SPT positive for banana allergen. SPT was performed in patients with self-reported food allergy (341/689) and also with no self-reported history of food allergy (348/689). SPT results were positive in 69.8 % of the self-report group, whereas, in the patients with no self-reported food allergy 9.2 % were found sensitized to one or more tested food allergens. 101 patients were recruited for OFC, 61 % of these were confirmed of food allergy. The prevalence of food allergy in the study population was 9 %. Food specific OFC results show that wheat allergy is affecting 1.6 % (95 % CI 0.9-2.84 %) of the total allergy patients, followed by egg allergy 1.31 % (95 % CI 0.70-2.47 %). Furthermore, corn allergy, rice allergy and peanut allergy were 1.02, 0.87 and 0.73 %, respectively. In conclusion, wheat allergy is the most prevalent, followed by egg, chicken, beef and fish allergy, respectively.

  19. Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats.

    PubMed

    Mauser, Peter J; House, Aileen; Jones, Howard; Correll, Craig; Boyce, Christopher; Chapman, Richard W

    2013-12-01

    Late phase airflow obstruction and reduction in forced vital capacity are characteristic features of human asthma. Airway microvascular leakage and lung edema are also present in the inflammatory phase of asthma, but the impact of this vascular response on lung functions has not been precisely defined. This study was designed to evaluate the role of increased lung microvascular leakage and edema on the late phase changes in forced vital capacity (FVC) and peak expiratory flow (PEF) in allergen-challenged Brown Norway rats using pharmacological inhibitors of the allergic inflammatory response. Rats were sensitized and challenged with ovalbumin aerosol and forced expiratory lung functions (FVC, PEF) and wet and dry lung weights were measured 48 h after antigen challenge. Ovalbumin challenge reduced FVC (63% reduction) and PEF (33% reduction) and increased wet (65% increase) and dry (51% increase) lung weights. The antigen-induced reduction in FVC and PEF was completely inhibited by oral treatment with betamethasone and partially attenuated by inhibitors of arachidonic acid metabolism including indomethacin (cyclooxygenase inhibitor), 7-TM and MK-7246 (CRTH2 antagonists) and montelukast (CysLT1 receptor antagonist). Antagonists of histamine H1 receptors (mepyramine) and 5-HT receptors (methysergide) had no significant effects indicating that these pre-formed mast cell mediators were not involved. There was a highly significant (P < 0.005) correlation for the inhibition of FVC reduction and increase in wet and dry lung weights by these pharmacological agents. These results strongly support the hypothesis that lung microvascular leakage and the associated lung edema contribute to the reduction in forced expiratory lung functions in antigen-challenged Brown Norway rats and identify an important role for the cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in these responses.

  20. New contact allergens and allergen sources.

    PubMed

    Rudzki, E; Grzywa, Z; Krajewska, D; Kozłowska, A; Czerwińska-Dihm, I

    1978-01-01

    In the report new contact allergens and allergen sources detected in Warsaw in the period 1975-1977 are described. They are divided into 3 groups: industrial allergens, remaining occupational allergens and cosmetics. There are given some data concerning the substances present in industrial oils, hardeners and epoxy resin solvents, drugs sensitizing nurses, several new sources of chromium allergens, essential oils and synthetic flavours. Results obtained with various star anise oil samples are described. Essential oils and synthetic flavours. Results obtained with various star anise oil samples are described. Essential oils and synthetic flavours are discussed as the main allergens in cosmetics.

  1. The effect of cromolyn sodium and albuterol on early and late phase bronchoconstriction and airway leukocyte infiltration after allergen challenge of nonanesthetized guinea pigs.

    PubMed

    Hutson, P A; Holgate, S T; Church, M K

    1988-11-01

    We describe the effects of the antiallergic drug cromolyn sodium and the beta 2-selective adrenoceptor agonist albuterol against early and late phase changes in specific airways conductance (sGaw) and leukocyte infiltration into the airways after allergen challenge of nonanesthetized guinea pigs. Inhalation of ovalbumin by sensitized guinea pigs induced three phases of airways obstruction: an early asthmatic response (EAR) peaking at 2 h, a late response (LAR) peaking at 17 h, and a further late response (LLAR) being observed at 72 h. The LAR was accompanied by a 13-fold rise in neutrophils and a four-fold rise in eosinophils recovered by bronchoalveolar lavage (BAL) at 17 h. By 72 h, the BAL content of neutrophils had returned to near normal, whereas eosinophil numbers had risen to 6.7-fold above baseline. Inhalation of an aerosolized solution of cromolyn, 10 mg/ml, 15 min before challenge inhibited both the EAR and LAR and the influx of neutrophils into the airways at 17 h but had no effect on eosinophil accumulation. Inhalation of cromolyn at 6 h, i.e., after the completion of the EAR, inhibited the LAR, the LLAR, and the rise in eosinophils at 72 h but did not reduce the influx of neutrophils at 17 h. Administration of cromolyn at both 15 min before and 6 h after challenge inhibited all changes in sGaw and reduced the accumulation of neutrophils at 17 h and the influx of eosinophils at 72 h. In contrast, inhalation of albuterol, 0.1 mg/ml, 15 min before allergen provocation blocked the EAR and the rise in BAL neutrophils at 17 h but did not inhibit the LAR. Inhalation of albuterol at 6 h partially reversed the LAR but had no effect on either the LLAR or cellular changes. Given at both times, albuterol inhibited the EAR and neutrophil accumulation at 17 h and partially reversed the LAR but produced no other effects.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Peanut Allergen Threshold Study (PATS): Novel single-dose oral food challenge study to validate eliciting doses in children with peanut allergy.

    PubMed

    Hourihane, Jonathan O'B; Allen, Katrina J; Shreffler, Wayne G; Dunngalvin, Gillian; Nordlee, Julie A; Zurzolo, Giovanni A; Dunngalvin, Audrey; Gurrin, Lyle C; Baumert, Joseph L; Taylor, Steve L

    2017-05-01

    Eliciting doses (EDs) of allergenic foods can be defined by the distribution of threshold doses for subjects within a specific population. The ED05 is the dose that elicits a reaction in 5% of allergic subjects. The predicted ED05 for peanut is 1.5 mg of peanut protein (6 mg of whole peanut). We sought to validate the predicted peanut ED05 (1.5 mg) with a novel single-dose challenge. Consecutive eligible children with peanut allergy in 3 centers were prospectively invited to participate, irrespective of previous reaction severity. Predetermined criteria for objective reactions were used to identify ED05 single-dose reactors. Five hundred eighteen children (mean age, 6.8 years) were eligible. No significant demographic or clinical differences were identified between 381 (74%) participants and 137 (26%) nonparticipants or between subjects recruited at each center. Three hundred seventy-eight children (206 male) completed the study. Almost half the group reported ignoring precautionary allergen labeling. Two hundred forty-five (65%) children experienced no reaction to the single dose of peanut. Sixty-seven (18%) children reported a subjective reaction without objective findings. Fifty-eight (15%) children experienced signs of a mild and transient nature that did not meet the predetermined criteria. Only 8 (2.1%; 95% CI, 0.6%-3.4%) subjects met the predetermined criteria for an objective and likely related event. No child experienced more than a mild reaction, 4 of the 8 received oral antihistamines only, and none received epinephrine. Food allergy-related quality of life improved from baseline to 1 month after challenge regardless of outcome (η(2) = 0.2, P < .0001). Peanut skin prick test responses and peanut- and Ara h 2-specific IgE levels were not associated with objective reactivity to peanut ED05. A single administration of 1.5 mg of peanut protein elicited objective reactions in fewer than the predicted 5% of patients with peanut allergy. The novel

  3. Quantitative Rietveld analysis of CAC clinker phases using synchrotron radiation

    SciTech Connect

    Guirado, F. . E-mail: francesc.guirado@urv.cat; Gali, S.

    2006-11-15

    The quantitative Rietveld analyses of twenty samples of CAC from four different manufacturers over the world, one synthetic mixture and a NIST standard were performed using synchrotron radiation. As compared with conventional XRD, synchrotron powder diffraction permitted to find new minor phases, improve the characterization of solid solutions of iron rich CAC phases and reduce preferential orientation and microabsorption effects. Diffraction data were complemented with XRF and TG/DT analyses. Synchrotron results were used as a reference test to improve the performance of conventional powder diffraction, by an accurate selection of refinable profile and structural parameters, and permitted to extract several recommendations for conventional quantitative Rietveld procedures. It is shown that with these recommendations in mind, conventional XRD based Rietveld analyses are comparable to those obtained from synchrotron data. In summary, quantitative XRD Rietveld analysis is confirmed as an excellent tool for the CAC cement industry.

  4. CACS: Master Textbook List Helps Solve On-Going Problem.

    ERIC Educational Resources Information Center

    Anderson, Robert

    1979-01-01

    The use of a master textbook list developed by the Southern California Association of College Stores (CACS) is described. The three-part program is explained and the information assimilation process, format for revising lists, procedures for implementation, and general guidelines are among areas covered. (PHR)

  5. Grayscale optical correlator for CAD/CAC applications

    NASA Astrophysics Data System (ADS)

    Chao, Tien-Hsin; Lu, Thomas

    2008-03-01

    This paper describes JPL's recent work on high-performance automatic target recognition (ATR) processor consisting of a Grayscale Optical Correlator (GOC) and neural network for various Computer Aided Detection and Computer Aided Classification (CAD/CAC) applications. A simulation study for sonar mine and mine-like target detection and classification is presented. Applications to periscope video ATR is also presented.

  6. CACS: Master Textbook List Helps Solve On-Going Problem.

    ERIC Educational Resources Information Center

    Anderson, Robert

    1979-01-01

    The use of a master textbook list developed by the Southern California Association of College Stores (CACS) is described. The three-part program is explained and the information assimilation process, format for revising lists, procedures for implementation, and general guidelines are among areas covered. (PHR)

  7. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

    PubMed

    Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

    2015-03-15

    Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE.

  8. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus

    PubMed Central

    Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C.; Pasricha, Pankaj J.; Li, Xingde

    2015-01-01

    Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

  9. Quality Control of Biomedicinal Allergen Products – Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses

    PubMed Central

    Spiric, Jelena; Engin, Anna M.; Karas, Michael; Reuter, Andreas

    2015-01-01

    Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied. PMID:26561299

  10. Progression of CAC Score and Risk of Incident CVD.

    PubMed

    Radford, Nina B; DeFina, Laura F; Barlow, Carolyn E; Lakoski, Susan G; Leonard, David; Paixao, Andre R M; Khera, Amit; Levine, Benjamin D

    2016-12-01

    The authors sought to determine the relative contributions of baseline coronary artery calcification (CAC), follow-up CAC, and CAC progression on incident cardiovascular disease (CVD). Repeat CAC scanning has been proposed as a method to track progression of total atherosclerotic burden. However, whether CAC progression is a useful predictor of future CVD events remains unclear. This was a prospective observational study of 5,933 participants free of CVD who underwent 2 examinations, including CAC scores, and subsequent CVD event assessment. CAC progression was calculated using the square root method. The primary outcome was total CVD events (CVD death, nonfatal myocardial infarction, nonfatal atherosclerotic stroke, coronary artery bypass surgery, percutaneous coronary intervention). Secondary outcomes included hard CVD events, total coronary heart disease (CHD) events, and hard CHD events. CAC was detected at baseline in 2,870 individuals (48%). The average time between scans was 3.5 ± 2.0 years. After their second scan, 161 individuals experienced a total CVD event during a mean follow-up of 7.3 years. CAC progression was significantly associated with total CVD events (hazard ratio: 1.14, 95% confidence interval: 1.01 to 1.30 per interquartile range; p = 0.042) in the model including baseline CAC, but the contribution of CAC progression was small relative to baseline CAC (chi-square 4.16 vs. 65.92). Furthermore, CAC progression was not associated with total CVD events in the model including follow-up CAC instead of baseline CAC (hazard ratio: 1.05, 95% confidence interval: 0.92 to 1.21; p = 0.475). A model that included follow-up CAC alone performed as well as the model that included baseline CAC and CAC progression. Although CAC progression was independently, but modestly, associated with CVD outcomes, this relationship was no longer significant when including follow-up CAC in the model. These findings imply that if serial CAC scanning is performed

  11. Coronary artery calcification (CAC) classification with deep convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Liu, Xiuming; Wang, Shice; Deng, Yufeng; Chen, Kuan

    2017-03-01

    Coronary artery calcification (CAC) is a typical marker of the coronary artery disease, which is one of the biggest causes of mortality in the U.S. This study evaluates the feasibility of using a deep convolutional neural network (DCNN) to automatically detect CAC in X-ray images. 1768 posteroanterior (PA) view chest X-Ray images from Sichuan Province Peoples Hospital, China were collected retrospectively. Each image is associated with a corresponding diagnostic report written by a trained radiologist (907 normal, 861 diagnosed with CAC). Onequarter of the images were randomly selected as test samples; the rest were used as training samples. DCNN models consisting of 2,4,6 and 8 convolutional layers were designed using blocks of pre-designed CNN layers. Each block was implemented in Theano with Graphics Processing Units (GPU). Human-in-the-loop learning was also performed on a subset of 165 images with framed arteries by trained physicians. The results from the DCNN models were compared to the diagnostic reports. The average diagnostic accuracies for models with 2,4,6,8 layers were 0.85, 0.87, 0.88, and 0.89 respectively. The areas under the curve (AUC) were 0.92, 0.95, 0.95, and 0.96. As the model grows deeper, the AUC or diagnostic accuracies did not have statistically significant changes. The results of this study indicate that DCNN models have promising potential in the field of intelligent medical image diagnosis practice.

  12. Standardization and Regulation of Allergen Products in the European Union.

    PubMed

    Zimmer, Julia; Vieths, Stefan; Kaul, Susanne

    2016-03-01

    Product-specific standardization is of prime importance to ensure persistent quality, safety, and efficacy of allergen products. The regulatory framework in the EU has induced great advancements in the field in the last years although national implementation still remains heterogeneous. Scores of methods for quantification of individual allergen molecules are developed each year and also the challenging characterization of chemically modified allergen products is progressing. However, despite the unquestionable increase in knowledge and the subsequent improvements in control of quality parameters of allergen products, an important aim has not been reached yet, namely cross-product comparability. Still, comparison of allergen product potency, either based on total allergenic activity or individual allergen molecule content, is not possible due to a lack of standard reference preparations in conjunction with validated standard methods. This review aims at presenting the most recent developments in product-specific standardization as well as activities to facilitate cross-product comparability in the EU.

  13. The absence of mrp4 has no effect on the recruitment of neutrophils and eosinophils into the lung after LPS, cigarette smoke or allergen challenge.

    PubMed

    Schymeinsky, Jürgen; Mayer, Hannah; Tomsic, Christopher; Tilp, Cornelia; Schuetz, John D; Cui, Yunhai; Wollin, Lutz; Gantner, Florian; Erb, Klaus J

    2013-01-01

    The multidrug resistance protein 4 (Mrp4) is an ATP-binding cassette transporter that is capable of exporting the second messenger cAMP from cells, a process that might regulate cAMP-mediated anti-inflammatory processes. However, using LPS- or cigarette smoke (CS)-inflammation models, we found that neutrophil numbers in the bronchoalveolar lavage fluid (BALF) were similar in Mrp4(-/-) and Mrp4(+/+) mice treated with LPS or CS. Similarly, neutrophil numbers were not reduced in the BALF of LPS-challenged wt mice after treatment with 10 or 30 mg/kg of the Mrp1/4 inhibitor MK571. The absence of Mrp4 also had no impact on the influx of eosinophils or IL-4 and IL-5 levels in the BALF after OVA airway challenge in mice sensitized with OVA/alum. LPS-induced cytokine release in whole blood ex vivo was also not affected by the absence of Mrp4. These data clearly suggest that Mrp4 deficiency alone is not sufficient to reduce inflammatory processes in vivo. We hypothesized that in combination with PDE4 inhibitors, used at suboptimal concentrations, the anti-inflammatory effect would be more pronounced. However, LPS-induced neutrophil recruitment into the lung was no different between Mrp4(-/-) and Mrp4(+/+) mice treated with 3 mg/kg Roflumilast. Finally, the single and combined administration of 10 and 30 mg/kg MK571 and the specific breast cancer resistance protein (BCRP) inhibitor KO143 showed no reduction of LPS-induced TNFα release into the BALF compared to vehicle treated control animals. Similarly, LPS-induced TNFα release in murine whole blood of Mrp4(+/+) or Mrp4(-/-) mice was not reduced by KO143 (1, 10 µM). Thus, BCRP seems not to be able to compensate for the absence or inhibition of Mrp4 in the used models. Taken together, our data suggest that Mrp4 is not essential for the recruitment of neutrophils into the lung after LPS or CS exposure or of eosinophils after allergen exposure.

  14. New tree nut allergens

    USDA-ARS?s Scientific Manuscript database

    The 7S vicilin and 11S legumin seed storage globulins belong to the cupin protein superfamily and are major food allergens in many of the “big eight” food allergen groups. Korean pine vicilin and pecan vicilin are thus predicted to be food allergens. Recombinant vicilins were expressed in E. coli an...

  15. Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.

    PubMed

    Scadding, Guy W; Calderon, Moises A; Shamji, Mohamed H; Eifan, Aarif O; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M; Plough, Audrey G; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K; Togias, Alkis; Durham, Stephen R

    2017-02-14

    Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5

  16. Allergens in veterinary medicine.

    PubMed

    Mueller, R S; Janda, J; Jensen-Jarolim, E; Rhyner, C; Marti, E

    2016-01-01

    Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses.

  17. Pressure-induced superconductivity in CaC2

    PubMed Central

    Li, Yan-Ling; Luo, Wei; Zeng, Zhi; Lin, Hai-Qing; Mao, Ho-kwang; Ahuja, Rajeev

    2013-01-01

    Carbon can exist as isolated dumbbell, 1D chain, 2D plane, and 3D network in carbon solids or carbon-based compounds, which attributes to its rich chemical binding way, including sp-, sp2-, and sp3-hybridized bonds. sp2-hybridizing carbon always captures special attention due to its unique physical and chemical property. Here, using an evolutionary algorithm in conjunction with ab initio method, we found that, under compression, dumbbell carbon in CaC2 can be polymerized first into 1D chain and then into ribbon and further into 2D graphite sheet at higher pressure. The C2/m structure transforms into an orthorhombic Cmcm phase at 0.5 GPa, followed by another orthorhombic Immm phase, which is stabilized in a wide pressure range of 15.2–105.8 GPa and then forced into MgB2-type phase with wide range stability up to at least 1 TPa. Strong electron–phonon coupling λ in compressed CaC2 is found, in particular for Immm phase, which has the highest λ value (0.562–0.564) among them, leading to its high superconducting critical temperature Tc (7.9∼9.8 K), which is comparable with the 11.5 K value of CaC6. Our results show that calcium not only can stabilize carbon sp2 hybridization at a larger range of pressure but also can contribute in superconducting behavior, which would further ignite experimental and theoretical interest in alkaline–earth metal carbides to uncover their peculiar physical properties under extreme conditions. PMID:23690580

  18. Raman scattering from the CaC6 superconductor

    NASA Astrophysics Data System (ADS)

    Mialitsin, A.; Kim, J.; Kremer, R.; Blumberg, G.

    2008-03-01

    Phys. Rev. B Phys. Rev. Lett. Phys. Lett. A Phys. Rev. 2MgB2 -1cm-1,-1cm-1/T,2gE2g 1gA1g 2DS2δS^E 2δL^E 2DA2Â 02δ0 6CaC6 A polarized Raman scattering study has been performed on bulk 1st stage intercalated graphite CaC6 crystals at sub-Tc temperatures. We identify all three Raman active Eg bands expected for the Rm6 space group of CaC6 at 440, 1120 and 1508,-1 and find them to be in agreement with zone center modes predicted by first principles calculations of phonon dispersion.^1 In addition the equivalents of the graphite D and G bands are observed at respective frequencies. Inherent to the disorder induced double resonant scattering process^2 the D band shifts from 1308,-1 to 1332,-1 upon the change of the excitation laser wavelength from 647,m to 476 ,m. Assuming linear dependence of the D band peak position as a function of excitation energy this translates to the frequency shift of 35,-1/,V. By comparing the integrated intensity of the G band at 1582,-1 in 6 to the one in kish graphite the relative fraction of higher stage domains to the 1st stage intercalation is estimated to be less then 0.2%. Finally upon the superconducting phase transition we observe a 2δ peak with the frequency of 24,-1 at 5,K. With temperature increase this peak persists shortly up to the SC phase transition at 11.6,and shows temperature dependence consistent with the strong coupling regime. ^1M. Calandra and F. Mauri, PRL 95, 237002 (2005). ^2C. Thomson and S. Reich, PRL 85, 5214 (2000).

  19. 3-dimensional electronic structures of CaC6

    NASA Astrophysics Data System (ADS)

    Kyung, Wonshik; Kim, Yeongkwan; Han, Garam; Leem, Choonshik; Kim, Junsung; Kim, Yeongwook; Kim, Keunsu; Rotenberg, Eli; Kim, Changyoung; Postech Collaboration; Advanced Light Source Collaboration; Yonsei University Team

    2014-03-01

    There is still remaining issues on origin of superconductivity in graphite intercalation compounds, especially CaC6 because of its relatively high transition temperature than other GICs. There are two competing theories on where the superconductivity occurs in this material; intercalant metal or charge doped graphene layer. To elucidate this issue, it is necessary to confirm existence of intercalant driven band. Therefore, we performed 3 dimensional electronic structure studies with ARPES to find out 3d dispersive intercalant band. However, we could not observe it, instead observed 3d dispersive carbon band. This support the aspect of charge doped graphene superconductivity more than intercalant driving aspect.

  20. Photodissociation spectroscopy of Ca+(C2H4)

    NASA Astrophysics Data System (ADS)

    Holmes, J. H.; Kleiber, P. D.; Olsgaard, D. A.; Yang, K.-H.

    2000-04-01

    We have studied Ca+(C2H4) by photodissociation spectroscopy in a reflectron time-of-flight mass spectrometer over the spectral range 440-790 nm. Ca+ is the only photofragment observed. We find four absorption bands of the complex and assign them to metal-centered transitions correlating with excitation of Ca+(3d and 4p). Spectral assignment is supported by ab initio electronic structure calculations of the complex and isotope substitution experiments. Calculations find a weakly bound ground state equilibrium structure with C2V π-bonding geometry and a dissociation energy of De″=0.506 eV. Theoretical and experimental results show the 4pπ(2 2B2 & 2 2B1) excited states to be relatively weakly bound at long range. Spectral analysis gives vibrational constants for the Ca+--C2H4 intermolecular a1-stretch in the 1 2A1, 2 2B1, and 2 2B2 states, and for the CH2-CH2 a1-wag and the HCH a1-bend in 2 2B2. The results offer an interesting comparison with previous studies of similar weakly bound bimolecular complexes of light metal ions with alkene or alkane hydrocarbons.

  1. Allergen immunotherapy and allergic rhinitis: false beliefs

    PubMed Central

    2013-01-01

    Background Over the last 100 years, several persistent misconceptions or ‘false beliefs’ have built up around allergen immunotherapy and its use in allergic rhinitis. This is perhaps because enthusiastic physicians administered complex allergen extracts to a diverse population of patients suffering from heterogeneous atopic conditions. Here, we review evidence that counters seven of these ‘false beliefs.’ Discussion 1. The symptoms of allergic rhinitis can be more heterogeneous, more severe and more troublesome in everyday life than many physicians believe. Large-scale epidemiological surveys show that the majority of allergic rhinitis patients have at least one symptom severe enough to interfere with sleep quality, productivity and/or well-being. 2. Allergen immunotherapy is not necessarily suitable for all allergic rhinitis patients (notably those with mild symptoms). Recent evidence from double-blind, placebo-controlled, randomized clinical trials suggests that the more severe the disease, the greater the treatment effect. 3. Allergen immunotherapy is often accused of lack of efficacy (relative to pharmacotherapy, for example). However, there are now many meta-analyses, systematic reviews and high-quality clinical trials that find overwhelmingly in favor of the efficacy of allergen immunotherapy (including sublingual formulations) in allergic rhinitis induced by pollen and, increasingly, other allergens. 4. Natural-exposure and challenge-chamber trials have shown that symptom relief may become apparent within months or even weeks of the initiation of allergen immunotherapy. 5. In pollen-induced allergic rhinitis, several years of subcutaneous or sublingual allergen immunotherapy are associated with sustained clinical efficacy after subsequent treatment cessation – confirming the disease-modifying nature of this therapy. 6. Most patients seeking treatment for allergic rhinitis are polysensitized, and allergen immunotherapy has proven efficacy in large

  2. Common Aviation Command and Control System Increment 1 (CAC2S Inc 1)

    DTIC Science & Technology

    2016-03-01

    2016 Major Automated Information System Annual Report Common Aviation Command and Control System Increment 1 (CAC2S Inc 1) Defense Acquisition...usmc.mil Phone: 703-432-3093 Fax: DSN Phone: 378-3093 DSN Fax: Date Assigned: August 9, 2012 Program Information Program Name Common Aviation ...CAC2S Inc 1 2016 MAR UNCLASSIFIED 4 Program Description The Common Aviation Command and Control System (CAC2S) provides an integrated and coordinated

  3. Analysis of olive allergens.

    PubMed

    Esteve, C; Montealegre, C; Marina, M L; García, M C

    2012-04-15

    Olive pollen is one of the most important causes of seasonal respiratory allergy in Mediterranean countries, where this tree is intensely cultivated. Besides this, some cases of contact dermatitis and food allergy to the olive fruit and olive oil have been also described. Several scientific studies dealing with olive allergens has been reported, being the information available about them constantly increasing. Up to date, twelve allergens have been identified in olive pollen while just one allergen has been identified in olive fruit. This review article describes considerations about allergen extraction and production, also describing the different methodologies employed in the physicochemical and immunological characterization of olive allergens. Finally, a revision of the most relevant studies in the analysis of both olive pollen and olive fruit allergens is carried out.

  4. Molecular approaches to allergen standardization.

    PubMed

    Chapman, Martin D; Briza, Peter

    2012-10-01

    Molecular approaches to allergen standardization include the development of purified natural or recombinant allergen standards whose structural and allergenic properties have been validated, in tandem with certified immunoassays for allergen measurement. Purified allergens can be used individually or incorporated into multiple allergen standards. Multicenter international collaborative studies are required to validate candidate allergen standards and immunoassays, as a prelude to being approved by regulatory agencies. Mass spectrometry is a sophisticated and powerful proteomics tool that is being developed for allergen analysis. Recent results using pollen allergens show that mass spectrometry can identify and measure specific allergens in a complex mixture and can provide precise information of the variability of natural allergen extracts. In future, the combined use of immunoassays and mass spectrometry will provide complete standardization of allergenic products. Molecular standardization will form the basis of new allergy diagnostics and therapeutics, as well as assessment of environmental exposure, and will improve the quality of treatment options for allergic patients.

  5. Roles of 5-Lipoxygenase and Cysteinyl-Leukotriene Type 1 Receptors in the Hematological Response to Allergen Challenge and Its Prevention by Diethylcarbamazine in a Murine Model of Asthma

    PubMed Central

    Masid-de-Brito, Daniela; Queto, Túlio; Gaspar-Elsas, Maria Ignez C.

    2014-01-01

    Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC. PMID:25477712

  6. Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma.

    PubMed

    Masid-de-Brito, Daniela; Queto, Túlio; Gaspar-Elsas, Maria Ignez C; Xavier-Elsas, Pedro

    2014-01-01

    Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC.

  7. New Trends in Food Allergens Detection: Toward Biosensing Strategies.

    PubMed

    Alves, Rita C; Barroso, M Fátima; González-García, María Begoña; Oliveira, M Beatriz P P; Delerue-Matos, Cristina

    2016-10-25

    Food allergens are a real threat to sensitized individuals. Although food labeling is crucial to provide information to consumers with food allergies, accidental exposure to allergenic proteins may result from undeclared allergenic substances by means of food adulteration, fraud or uncontrolled cross-contamination. Allergens detection in foodstuffs can be a very hard task, due to their presence usually in trace amounts, together with the natural interference of the matrix. Methods for allergens analysis can be mainly divided in two large groups: the immunological assays and the DNA-based ones. Mass spectrometry has also been used as a confirmatory tool. Recently, biosensors appeared as innovative, sensitive, selective, environmentally friendly, cheaper and fast techniques (especially when automated and/or miniaturized), able to effectively replace the classical methodologies. In this review, we present the advances in the field of food allergens detection toward the biosensing strategies and discuss the challenges and future perspectives of this technology.

  8. Analyzing coronary artery disease in patients with low CAC scores by 64-slice MDCT.

    PubMed

    Lu, Nan-Han; Yeh, Lee-Ren; Chen, Tai-Been; Huang, Yung-Hui; Kuo, Chung-Ming; Ding, Hueisch-Jy

    2012-01-01

    Coronary artery calcification (CAC) scores are widely used to determine risk for Coronary Artery Disease (CAD). A CAC score does not have the diagnostic accuracy needed for CAD. This work uses a novel efficient approach to predict CAD in patients with low CAC scores. The study group comprised 86 subjects who underwent a screening health examination, including laboratory testing, CAC scanning, and cardiac angiography by 64-slice multidetector computed tomographic angiography. Eleven physiological variables and three personal parameters were investigated in proposed model. Logistic regression was applied to assess the sensitivity, specificity, and accuracy of when using individual variables and CAC score. Meta-analysis combined physiological and personal parameters by logistic regression. The diagnostic sensitivity of the CAC score was 14.3% when the CAC score was ≤30. Sensitivity increased to 57.13% using the proposed model. The statistically significant variables, based on beta values and P values, were family history, LDL-c, blood pressure, HDL-c, age, triglyceride, and cholesterol. The CAC score has low negative predictive value for CAD. This work applied a novel prediction method that uses patient information, including physiological and society parameters. The proposed method increases the accuracy of CAC score for predicting CAD.

  9. Food processing and allergenicity.

    PubMed

    Verhoeckx, Kitty C M; Vissers, Yvonne M; Baumert, Joseph L; Faludi, Roland; Feys, Marcel; Flanagan, Simon; Herouet-Guicheney, Corinne; Holzhauser, Thomas; Shimojo, Ryo; van der Bolt, Nieke; Wichers, Harry; Kimber, Ian

    2015-06-01

    Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat treatment) on the allergenic potential of proteins, and on the antigenic (IgG-binding) and allergenic (IgE-binding) properties of proteins has been considered. A variety of allergenic foods (peanuts, tree nuts, cows' milk, hens' eggs, soy, wheat and mustard) have been reviewed. The overall conclusion drawn is that processing does not completely abolish the allergenic potential of allergens. Currently, only fermentation and hydrolysis may have potential to reduce allergenicity to such an extent that symptoms will not be elicited, while other methods might be promising but need more data. Literature on the effect of processing on allergenic potential and the ability to induce sensitisation is scarce. This is an important issue since processing may impact on the ability of proteins to cause the acquisition of allergic sensitisation, and the subject should be a focus of future research. Also, there remains a need to develop robust and integrated methods for the risk assessment of food allergenicity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Criteria to determine food allergen priority.

    PubMed

    Yeung, J M; Applebaum, R S; Hildwine, R

    2000-07-01

    The emergent health issue of food allergens presents an important challenge to the food industry. More than 170 foods have been reported in the scientific literature as causing allergic reactions. Clearly, it would be impossible to deal with the presence of trace amounts of all these in the context of food labeling. If the decision to classify major allergens is based solely on the knowledge and experience of allergists and food scientists in the field, without scientifically defined criteria, it is likely to lead to a proliferation of lists. Such practices may lead to an unnecessary elimination of foods containing important nutrients. This paper defines food allergy, food intolerance, and food anaphylaxis and identifies criteria for classifying food allergens associated with frequent allergic reactions. A practical list of food allergens that may result in potentially life-threatening allergic reactions is provided. A mechanism-based (i.e., immunoglobulin E mediated), acute life-threatening anaphylaxis that is standardized and measurable and reflects the severity of health risk is proposed as the principal inclusion criterion for food allergen labeling. Where available, prevalence in the population and threshold levels of allergens should be used as an additional guide to identify possible future labeling needs.

  11. Hypersensitivity to latex and Ficus benjamina allergens.

    PubMed

    Delbourg, M F; Moneret-Vautrin, D A; Guilloux, L; Ville, G

    1995-12-01

    Association between allergy to Ficus benjamina and Hevea brasiliensis, two botanically unrelated plants, was suspected in consequence of two clinical observations. Symptoms were rhinitis and asthma. This study was undertaken to assess the in vivo and in vitro cross-reactivity between Ficus benjamina and Hevea brasiliensis allergens. The two patients were asked about use and contact with latex devices and relationship between symptoms and Ficus benjamina exposure. Skin prick tests were performed with Ficus benjamina, Hevea brasiliensis extracts and common allergens. Double-blind nasal and bronchial challenge tests were done using the rinse fluid from a brand of latex gloves. Total and specific IgE antibodies to Ficus benjamina and Hevea brasiliensis were determined. In vitro cross-reactivity was investigated by means of CAP RAST and immunodot inhibition experiments. We observed that for the first patient the primary phenomenon is probably allergy to latex followed by allergy to Ficus benjamina. For the second patient, allergy to Ficus benjamina was diagnosed (improvement related to the avoidance of exposure to Ficus benjamina allergens) and positivity to latex skin prick tests may be due to the cross-reacting allergens. In vitro assays showed specific IgE antibodies to both allergens and cross-reactivity was confirmed in the two cases by reciprocal inhibition of the two extracts. The increasing risk of sensitization to widely used latex devices and extensive exposure to Ficus species in households and offices indicates increased allergenic risk from this newly recognized cross-reactivity.

  12. Emerging pollen allergens.

    PubMed

    Rodríguez, Rosalía; Villalba, Mayte; Batanero, Eva; Palomares, Oscar; Salamanca, Guillermo

    2007-01-01

    Numerous pollen allergens have been reported over the last few years. Most of them belong to well-known families of proteins but some others constitute the first member of new allergenic families. Some of the factors that can contribute to the detection and identification of new pollen allergens are: a) advances in the technology tools for molecular analysis; and b) the deep knowledge of many allergenic sources. The combination of these factors has provided vast information on the olive pollen allergogram and the identification of minor allergens that become major ones for a significant population. The close taxonomical relationship between olive tree and ash -both Oleaceae- has permitted to identify Fra e 1 (the Ole e 1-like allergen) in ash pollen and to detect the presence of protein homologues of Ole e 3 and Ole e 6. In the other hand, extensive areas of south Europe are suffering an increasing desertification. As a consequence of this, new botanical species are spontaneously growing in these areas or being used in greening ground programs: Chenopodium album and Salsola kali are some examples recently recognized as allergenic woods. The identification of the complete panel of allergens from the hypersensitizing sources might help to develop more accurate diagnosis, and efficient and safer therapy tools for Type-I allergic diseases.

  13. [New aero-allergens].

    PubMed

    De Blay, F; Bessot, J C; Pauli, G

    1996-01-01

    As the number of proteins recognized as causing allergic respiratory diseases increases, new aero allergens have appeared in the animal and vegetable realms, both in home and professional environments. Lepidoglyphus destructor and Blomia tropicalis, two mites found in storage areas, are particularly important in agricultural areas and in homes. Over the last ten years, the frequency of reactions to cockroaches has also increased in several countries. The allergenicity of non-biting insects is a frequent cause of allergy in certain countries including Japan. Chironomides cause respiratory diseases in professional and outdoor environments. The important role of Alternaria, a mold, in producing severe asthma has also been demonstrated. The pathophysiology of pollen-induced asthma has been shown to result from pollen allergens carried by particles less than 5 microns in diameter. Cyprus and ash tree pollen also cause an increasing number of pollinoses and flowers can cause rhinitis and asthma. Respiratory allergy to Ficus benjamina inaugurated a new type of allergies caused airborne allergens from non-pollinating plants. Allergy to latex raises a particular problem for health care workers. The immunochemical structures of the major and minor airborne allergens are now better known and the homologous structures of different allergens largely explains certain cross-reactions. In the future, recombinant allergens will probably be used to better understand the role of allergens in inducing and maintaining the allergic reaction and should help in our approach to diagnosis and therapy.

  14. 32 CFR 156.6 - Common access card (CAC) investigation and adjudication.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Common access card (CAC) investigation and... SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM (PSP) § 156.6 Common access card (CAC... OPM Memorandum, “Final Credentialing Standards for Issuing Personal Identity Verification Cards under...

  15. Distribution and Burden of Newly Detected Coronary Artery Calcium (CAC): Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Alluri, Krishna; McEvoy, John W.; Dardari, Zeina A; Jones, Steven R.; Nasir, Khurram; Blankstein, Ron; Rivera, Juan J.; Agatston, Arthur A.; Kaufman, Joel D.; Budoff, Matthew J.; Blumenthal, Roger S.; Blaha, Michael J.

    2015-01-01

    Background The transition from no coronary artery calcium (CAC) to detectable CAC is important, as even mild CAC is associated with increased cardiovascular events. We sought to characterize the anatomical distribution and burden of newly detectable CAC over 10-years follow-up. Methods We evaluated 3112 participants (mean age 58, 64% female) with baseline CAC=0 from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants underwent repeat CAC testing at different time intervals (between 2–10 years after baseline) per MESA protocol. Among participants who developed CAC on a follow-up scan, we used logistic regression and marginal probability modeling to describe the coronary distribution and burden of new CAC by age, gender, and race/ethnicity after adjustment for cardiovascular risk factors and time-to-detection. Results A total of 1125 participants developed detectable CAC during follow-up with mean time-to-detection of 6.1 ± 3 years. New CAC was most commonly isolated to one vessel (72% of participants), with the left anterior descending (44% of total) most commonly affected followed by the right coronary (12%), left circumflex (10%) and left main (6%). These patterns were similar across age, gender, and race/ethnicity. In multivariable models, residual predictors of multi-vessel CAC (28% of total) included male gender, African-American or Hispanic race/ethnicity, hypertension, obesity, and diabetes. At the first detection of CAC>0, burden was usually low with median Agatston CAC score of 7.1, and <5% with CAC scores >100. Conclusion New onset CAC most commonly involves just one vessel, occurs in the left anterior descending artery, has low CAC burden. New CAC can be detected at an early stage when aggressive preventive strategies may provide benefit. PMID:26088381

  16. Hereditary and histologic characteristics of the CF1/b cac mouse cataract model.

    PubMed

    Kondo, Tomohiro; Nagai, Hiroaki; Kawashima, Takamune; Taniguchi, Yusuke; Koyabu, Nozomu; Takeshita, Ai; Kusakabe, Ken-Takeshi; Okada, Toshiya

    2014-10-01

    A substrain of mice originating from the CF1 strain (an outbred colony) reared at Osaka Prefecture University (CF1/b cac mice) develops cataracts beginning at 14 d old. Affected mice were fully viable and fertile and had developed cataracts by 22 d of age. The incidence of cataracts did not differ between male and female mice. Histologically, 14-wk-old CF1/b cac mice showed vacuolated lens epithelial cells, swollen lens fibers, many pyknotic nuclei, and vacuolation of the lens cortex. To elucidate the mode of inheritance, we analyzed heterozygous mutants hybrids generated from CF1/b cac and wildtype BALB/c mice and the offspring of the backcrossed heterozygous mutants. None of the heterozygous mutants was affected, but the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. The initial genomewide screen of 20 affected backcrossed offspring (CF1/b cac × [CF1/b cac × BALB/c]) indicated that the mutant gene resides on chromosome 16. For further mapping, we used affected progeny of CF1/b cac × (CF1/b cac × MSM/Ms) mice. We concluded that the cataracts in CF1/b cac mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 16 between D16Mit5 and D16Mit92 and between D16Mit92 and D16Mit201. The mapping of the mutant gene of the CF1/b cac mice to mouse chromosome 16 provides the positional information necessary to identify the candidate gene responsible for the CF1/b cac phenotype.

  17. Impact of Exercise on the Relationship Between CAC Scores and All-Cause Mortality.

    PubMed

    Arnson, Yoav; Rozanski, Alan; Gransar, Heidi; Hayes, Sean W; Friedman, John D; Thomson, Louise E J; Berman, Daniel S

    2017-05-11

    This study aims to assess the correlations among coronary artery calcium (CAC), self-reported exercise, and mortality in asymptomatic patients. The interaction between reported exercise habits and CAC scores for predicting clinical risk is not yet well known. We followed 10,690 asymptomatic patients who underwent CAC scanning. Patients were divided into 4 groups based on a single-item self-reported exercise. Mean follow-up was 8.9 ± 3.5 years for the occurrence of all-cause mortality (ACM). Annualized ACM progressively increased with increasing CAC score (p < 0.001) and decreasing exercise (p < 0.001). Among patients with CAC scores of 0, ACM was low regardless of the amount of exercise. Among patients with CAC scores from 1 to 399, there was a stepwise increase in ACM for each reported decrement in exercise, and this difference was markedly more pronounced among patients with CAC scores ≥400. Compared with highly active patients with a CAC score of 0, highly sedentary patients with CAC scores ≥400 had a 3.1-fold increase (95% confidence interval: 1.35 to 7.11) in adjusted ACM risk. Our single-item physical activity questionnaire was also predictive of risk factors and clinical and lipid profile measurements. In asymptomatic patients, self-reported exercise is a significant predictor of long-term outcomes. Prognostic value of the reported exercise is additive to the increasing degree of underlying atherosclerosis. Among patients with high CAC scores, exercise may play a protective role, whereas reported minimal or no exercise substantially increases clinical risk. Our results suggest there is clinical utility for the use of a simple single-item exercise questionnaire for such assessments. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Cockroach allergens: function, structure and allergenicity.

    PubMed

    Pomés, A; Wünschmann, S; Hindley, J; Vailes, L D; Chapman, M D

    2007-01-01

    Cockroach allergy is a widespread health problem in the world, associated with the development of asthma. The German and American cockroach species are important producers of a wide variety of allergens. Knowledge of their structure and function contributes to understand their role in allergy and to design tools for diagnosis and immunotherapy.

  19. Single recombinant and purified major allergens and peptides: How they are made and how they change allergy diagnosis and treatment.

    PubMed

    Curin, Mirela; Garib, Viktoriya; Valenta, Rudolf

    2017-09-01

    To review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides. PubMed, homepages relevant to the topic, and the National Institutes of Health clinical trial database were searched. The literature was screened for studies describing purified and recombinant allergens and allergen-derived peptides. Studies relevant to the topic were included in this review. Advantages and drawbacks of pure and defined recombinant allergens and peptides over allergen extracts in the context of allergy research, diagnosis, and allergen immunotherapy are discussed. We describe how these molecules are manufactured, which products are currently available on the market, and what the regulative issues are. We furthermore provide an overview of clinical studies with vaccines based on recombinant allergens and synthetic peptides. The possibility of prophylactic vaccination based on recombinant fusion proteins consisting of viral carrier proteins and allergen-derived peptides without allergenic activity are also discussed. During the last 25 years more than several hundred allergen sequences were determined, which led to a production of recombinant allergens that mimic biochemically and immunologically their natural counterparts. Especially in Europe, recombinant allergens are increasingly replacing allergen extracts in diagnosis of allergy. Despite many challenges, such as high cost of clinical trials and regulative issues, allergy vaccines based on recombinant allergens and peptides are being developed and will likely soon be available on the market. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. kz Dependent Electronic Structure Studies of CaC6 and Inter Layer State Driven Superconductivity

    NASA Astrophysics Data System (ADS)

    Kyung, Wonshik; Kim, Yeongkwan; Han, Garam; Leem, Choonshik; Kim, Chul; Koh, Yoonyoung; Kim, Beomyoung; Kim, Yeongwook; Kim, Junsung; Kim, Keunsu; Rotenberg, Eli; Denlinger, Jonathan; Kim, Changyoung; Yonsei University Team; Postech Collaboration; Advanced light source Collaboration

    2015-03-01

    We performed angle-resolved photoemission experiments on CaC6 and measured kz dependent electronic structures to investigate the interlayer states. The results reveal a spherical interlayer Fermi surface centered at the Γ point. We also find the graphene driven band possesses a weak kz dispersion. The overall electronic structure shows a peculiar single graphene layer periodicity in the kz direction although CaC6 unit cell is supposed to contain three graphene layers. This suggests that c-axis ordering of Ca has little effect on the electronic structure of CaC6. In addition to CaC6, we also studied the non-superconducting BaC6. For BaC6, the graphene band Dirac point energy is smaller than that of CaC6. Based on data from CaC6 and BaC6, we rule out Cxy phonon mode as the origin of the superconductivity in CaC6, which strongly suggests interlayer state driven supercondutivity.

  1. Identification and characterization of CAC1 as a novel CDK2-associated cullin.

    PubMed

    Kong, Ying; Nan, Kejun; Yin, Yuxin

    2009-11-01

    Cell cycle progression is tightly controlled by cyclins and cyclin-dependent kinases (CDKs). CDK2 plays a crucial role in regulating cell cycle progression, but how CDK2 is regulated is still incompletely understood. In this study, we report the identification and characterization of a novel gene CAC1 that regulates CDK2 activity. The open reading frame sequence of this gene encodes a protein of 369 amino acids which contains a Cullin domain, and this protein is physically associated with CDK2. As such, we have designated it Cdk-Associated Cullin1, or CAC1. CAC1 is highly expressed in cancer tissues and cancer cell lines. Interestingly, CAC1 is expressed in a cell cycle-dependent manner and its expression is high in late G(1) to S phase. Knockdown of CAC1 by RNAi inhibits cell proliferation and induces G(1)/S arrest. Since CAC1 interacts with CDK2 and promotes the kinase activity of CDK2 protein, we propose that CAC1 is a novel cell cycle associated protein capable of promoting cell proliferation. Our data provide insight into the mechanism by which CDK2 is regulated and the molecular basis of cell cycle progression in cancer.

  2. Allergens in the Lab.

    ERIC Educational Resources Information Center

    Fisher, Thomas M.

    1987-01-01

    Points out the health and legal implications related to laboratory substances that could cause allergic reactions. Presents a list of potential cosmetic allergens and irritants. Includes precautionary measures dealing with allergy situations. (ML)

  3. Allergens in the Lab.

    ERIC Educational Resources Information Center

    Fisher, Thomas M.

    1987-01-01

    Points out the health and legal implications related to laboratory substances that could cause allergic reactions. Presents a list of potential cosmetic allergens and irritants. Includes precautionary measures dealing with allergy situations. (ML)

  4. Allergens and thunderstorm asthma.

    PubMed

    Nasser, Shuaib M; Pulimood, Thomas B

    2009-09-01

    Thunderstorm-related asthma is increasingly recognized in many parts of the world. This review focuses on important advances in the understanding of the mechanism of the role of allergens, in particular fungal spores such as Alternaria, in asthma epidemics associated with thunderstorms. From our observations, we have proposed that the prerequisites for this phenomenon are as follows: 1) a sensitized, atopic, asthmatic individual; 2) prior airway hyperresponsiveness before a sudden, large allergen exposure; 3) a large-scale thunderstorm with cold outflow occurring at a time and location during an allergen season in which large numbers of asthmatics are outdoors; and 4) sudden release of large amounts of respirable allergenic fragments, particularly fungal spores such as Alternaria.

  5. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy.

    PubMed

    Jackson, H A; Jackson, M W; Coblentz, L; Hammerberg, B

    2003-08-01

    Fourteen dogs with known clinical hypersensitivity to soy and corn were maintained on a limited antigen duck and rice diet until cutaneous manifestations of pruritus were minimal (78 days). Sequential oral challenges with cornstarch, corn and soy were then performed. Subsequently, the dogs were fed a diet containing hydrolysed soy protein and cornstarch. Throughout the study period the dogs were examined for cutaneous manifestations of pruritus and, additionally, serum was collected for measurement of allergen-specific and total immunoglobulin (Ig)E concentrations. Intradermal testing with food antigens was performed prior to entry into the study and after 83 days. A statistically significant clinical improvement was measured between days 0 and 83. Significant pruritus was induced after oral challenge with cornstarch, corn and soy (P = 0.04, 0.002, 0.01, respectively) but not with the hydrolysed diet (P = 0.5). The positive predictive value of the skin test for soy and corn allergy was reduced after feeding a soy and corn free diet. Although increases in soy and corn-specific serum IgE concentrations were measured in individual dogs post challenge they were not statistically significant and could not be used to predict clinical hypersensitivity.

  6. Monitoring for airborne allergens

    SciTech Connect

    Burge, H.A. )

    1992-07-01

    Monitoring for allergens can provide some information on the kinds and levels of exposure experienced by local patient populations, providing volumetric methods are used for sample collection and analysis is accurate and consistent. Such data can also be used to develop standards for the specific environment and to begin to develop predictive models. Comparing outdoor allergen aerosols between different monitoring sites requires identical collection and analysis methods and some kind of rational standard, whether arbitrary, or based on recognized health effects.32 references.

  7. Allergens in corticosteroid vehicles.

    PubMed

    Coloe, Jacquelyn; Zirwas, Matthew J

    2008-01-01

    Whereas allergy to vehicle ingredients (ie, excipients and preservatives) in topical steroid vehicles is well recognized, there are no data regarding which vehicle ingredients are in common use or on which vehicles and active molecules are associated with which ingredients. To produce descriptive data on the use of allergenic vehicle ingredients in prescription topical corticosteroids. The package insert for every steroid in widespread use in the United States was obtained from the manufacturer and used to generate an ingredient list for the product. There are seven vehicle ingredients that are commonly used in topical corticosteroid vehicles that are well-known allergens: propylene glycol, sorbitan sesquioleate, formaldehyde-releasing preservatives, parabens, methylchloroisothiazolinone/methylisothiazolinone, lanolin, and fragrance. Of 166 topical corticosteroids, 128 (including all creams) had at least one of these vehicle ingredients. More generic products were free of allergens than were branded products. Solutions and ointments were the least allergenic vehicles. The most commonly present potential allergens were propylene glycol and sorbitan sesquioleate. Most prescription topical corticosteroids have the potential to cause allergic contact dermatitis owing to vehicle ingredients. Dermatologists should be aware of this possibility and should consider prescribing agents that do not contain potentially allergenic vehicle ingredients.

  8. [New aero-allergens. Interaction between allergens and the environment].

    PubMed

    Charpin, D; Vervloet, D

    1997-11-01

    There is a qualitative as well as a quantitative change in allergen exposure. From a qualitative viewpoint, the relevance of some allergens (domestic allergens i.e. cockroaches, outdoor allergens i.e. plane tree, chestnut and ash tree pollens) has been established. The role of some other allergens has been, strictly speaking, discovered: latex from Hevea and ficus, trichophyton mold, some occupational allergens and very recently transgenic allergens. From a quantitative viewpoint, the concentration and/or distribution of some allergens has increased. Plantation of numerous trees or fortuitous introduction of weeds has led to an increased specific sensitization. In like manner, introduction of new foods or food processing procedures has created new food allergens and allergy. Besides, the distribution of some well-known aero-allergens is better known since discovery of ELISA--technology allowing measurements of minute amounts of these allergens. A burning issue today is to know whether irritant factors could modify allergens. Few data, sometimes contradictory, are available in the field of interaction between air pollutants and allergens.

  9. Enhanced sensitization and elicitation responses caused by mixtures of common fragrance allergens.

    PubMed

    Bonefeld, Charlotte Menné; Nielsen, Morten Milek; Rubin, Ingrid Maria Cecilia; Vennegaard, Marie Torp; Dabelsteen, Sally; Gimenéz-Arnau, Elena; Lepoittevin, Jean-Pierre; Geisler, Carsten; Johansen, Jeanne Duus

    2011-12-01

    Perfumes are complex mixtures composed of many fragrance ingredients, many of which are known to be only weak allergens when tested individually. It is therefore surprising that fragrance contact allergy is one of the most common forms of contact allergy. To investigate whether mixing different fragrance allergens leads to increased sensitization potency, and to examine the difference in the challenge response to one chemical in mice sensitized either with the mixture of allergens or with only the relevant allergen. CBA mice were sensitized with three different concentrations of three fragrance allergens alone or as a mixture. The sensitization and elicitation responses were measured by ear thickness plus infiltration of B and T cells and T cell proliferation in the draining lymph nodes. We found a dose-dependent sensitization response for each of the allergens. An increased response was seen when the allergens were mixed. A stronger challenge response to cinnamal was seen in mice sensitized with the allergen mixture than in mice sensitized with cinnamal alone. Our findings suggest that mixtures of allergens increase the primary response that potentiates the generation of memory T cells in response to the specific allergen. Thus, allergen mixtures enhance both induction and elicitation of contact allergy. © 2011 John Wiley & Sons A/S.

  10. Low serum bilirubin concentration is associated with coronary artery calcification (CAC).

    PubMed

    Tanaka, Muhei; Fukui, Michiaki; Tomiyasu, Ki-ichiro; Akabame, Satoshi; Nakano, Koji; Hasegawa, Goji; Oda, Yohei; Nakamura, Naoto

    2009-09-01

    Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. The purpose of this study was to assess the correlation between serum bilirubin concentration and coronary artery calcification (CAC). This study consisted of 637 participants and we evaluated the relationship between CAC score determined by multislice computed tomography and serum bilirubin concentration. An inverse correlation was found between serum bilirubin concentration and log(CAC+1) (r=-0.361, P<0.0001). Multiple regression analysis also demonstrated that age (beta=0.261, P=0.0125), systolic blood pressure (beta=0.153, P=0.0237), uric acid (beta=0.126, P=0.0441), estimated glomerular filtration rate (beta=-0.139, P=0.0416) and serum bilirubin concentration (beta=-0.281, P<0.0001) were independent determinants of log(CAC+1). An increment of 1 micromol/L in serum bilirubin concentration was associated with 14% decrease in the odds for CAC score > or =400 after adjustment for several risk factors. Both age and SBP were also positively associated with CAC score > or =400, but the odds ratio for CAC score > or =400 was greater for every 1 micromol/L increment in serum bilirubin concentration than for every 1-year increment in age and 1-mmHg increment in SBP. Low serum bilirubin concentration is associated with coronary artery calcification. Serum bilirubin concentration can be measured easily in the clinical laboratory and applied in medical practice, and low serum bilirubin concentration would be useful as a provisional new risk factor of CAC.

  11. U-shaped relationship between insulin level and coronary artery calcification (CAC).

    PubMed

    Tanaka, Muhei; Fukui, Michiaki; Tomiyasu, Ki-ichiro; Akabame, Satoshi; Nakano, Koji; Hasegawa, Goji; Oda, Yohei; Nakamura, Naoto

    2010-10-27

    Recent studies have suggested that hyperinsulinemia is associated with high cardiovascular risk. The purpose of this study was to assess the relationship between the serum insulin level and coronary artery calcification (CAC). We performed a cross-sectional study of 582 consecutive and nondiabetic participants with clinical suspicion of coronary heart disease, and assessed the CAC score determined by multislice computed tomography. A standard 75-g oral glucose tolerance test was performed and venous blood was collected at 0, 30, 60 and 120 min for the measurement of plasma glucose and serum insulin. Statistical analyses were conducted for 4 subgroups according to fasting insulin and insulin area under the concentration time curve (InsAUC). Mean log (CAC+1) and InsAUC were 1.6 and 109.1 µIU/mL, respectively. Unadjusted analysis demonstrated that the fasting insulin quartiles (p=0.0256) and InsAUC quartiles (p<0.0001) were significantly associated with log (CAC+1), and the lowest fasting insulin quartiles (p<0.0001) and the lowest InsAUC quartile (p=0.0006) had lower glucose AUC. Analysis of covariance demonstrated that the lowest InsAUC quartile had the highest log (CAC+1), and the highest InsAUC quartile had a higher log (CAC+1) than the second and third InsAUC quartiles, adjusted for several coronary risk factors (p<0.0001). The lowest InsAUC quartile was related to CAC, although the lowest InsAUC quartile maintained glucose homeostasis, in this study population. Not only hyperinsulinemia but also a low insulin level are independently associated with CAC.

  12. Added value of CAC in risk stratification for cardiovascular events: a systematic review.

    PubMed

    Peters, Sanne A E; Bakker, Marina; den Ruijter, Hester M; Bots, Michiel L

    2012-01-01

    Identification of individuals at high risk for cardiovascular disease (CVD) is important to initiate adequate treatment and to prevent future events. Moreover, identification of low-risk individuals is important to refrain from unneeded therapy. Current risk prediction models do not accurately predict the risk of CVD in individuals, and new markers have been sought to improve the risk assessment in individuals. Coronary artery calcification (CAC) is a marker of atherosclerosis that might improve current risk assessment when added to traditional risk factors. We performed a systematic review on PubMed search (1 February 2011) on studies reporting on the added value of CAC in risk prediction in asymptomatic individuals. Of 39 publications on CAC and CVD, nine studies were carried out in asymptomatic individuals. All studies showed an increase in area under the curve ranging from 0.05 to 0.20 when CAC was added to the risk model. Four studies reported on improvements of individuals in low-, intermediate-, and high-risk categories. Addition of CAC to the risk model resulted in a net reclassification improvement ranging from 14% to 30%, meaning that CAC measurement reclassified a substantial proportion of individuals into correct risk categories. This improvement was most pronounced in those at intermediate Framingham risk. The available studies consistently showed that CAC scoring improves risk stratification in CVD risk categories when added to traditional risk factors only, especially among individuals at intermediate risk for CVD. Cost-effectiveness analyses together with a randomized controlled trial are needed before widespread introduction of CAC in clinical care. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Improving the CAC Score by Addition of Regional Measures of Calcium Distribution: Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Blaha, Michael J; Budoff, Matthew J; Tota-Maharaj, Rajesh; Dardari, Zeina A; Wong, Nathan D; Kronmal, Richard A; Eng, John; Post, Wendy S; Blumenthal, Roger S; Nasir, Khurram

    2016-12-01

    The aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events. Agatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque. We studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The "diffusivity index" was calculated as: 1 - (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score. Mean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p < 0.01). Addition of number of vessels with CAC significantly improved capacity to predict CHD and CVD events in survival analysis (hazard ratio: 1.9 to 3.5 for 4-vessel vs. 1-vessel CAC), area under the curve analysis (C-statistic improvement of 0.01 to 0.033), and net reclassification improvement analysis (category-less net reclassification improvement 0.10 to 0.45). Although a diffuse CAC pattern was associated with worse outcomes in participants with ≥2 vessels with CAC (hazard ratio: 1.33 to 1.41; p < 0.05), adding this variable to the Agatston CAC score and number of vessels with CAC did not further improve global risk prediction. The number of coronary

  14. Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

    PubMed

    Ryan, D; Gerth van Wijk, R; Angier, E; Kristiansen, M; Zaman, H; Sheikh, A; Cardona, V; Vidal, C; Warner, A; Agache, I; Arasi, S; Fernandez-Rivas, M; Halken, S; Jutel, M; Lau, S; Pajno, G; Pfaar, O; Roberts, G; Sturm, G; Varga, E M; Van Ree, R; Muraro, A

    2017-08-29

    The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. We undertook a mixed-methods, situational analysis. This involved a purposeful literature search, and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Positive reaction to allergen (image)

    MedlinePlus

    Allergic reaction is a sensitivity to a specific substance, called an allergen, that is contacted through the skin, inhaled into the lungs, swallowed or injected. The body's reaction to an allergen can be mild, such as ...

  16. Quantum magnetoresistance in the Ca-intercalated graphite superconductor CaC6

    NASA Astrophysics Data System (ADS)

    Mu, Gang; Ji, Qiucheng; Li, Wei; Xu, Xuguang; Hu, Tao; Jiang, Da; Wang, Zhi; Gao, Bo; Xie, Xiaoming; Jiang, Mianheng

    2014-12-01

    The search for exotic materials with a linear Dirac-like dispersion in the electronic structure is one of the most challenging tasks of the condensed matter community and materials science. Revealing the nature of the interplay between such a Dirac-like and superconducting states is a crucial issue for the study of fundamental physics. Here we report the experimental observations of a large linear magnetoresistance (MR) in the Ca-intercalated graphite superconductor CaC6. A large nonsaturating MR with a magnitude as high as 244% is observed at low temperature under a magnetic field of 9 T. The magnetic field (B ) dependence of MR shows a linear behavior above 3 T at low temperature, which deviates from the classical B2 behavior, pointing to the existence of an intrinsic linear Dirac-like state. The presence of such a low-energy Dirac-like dispersion in energy band structure is confirmed qualitatively by performing first-principles calculations. These findings may pave an avenue for potential applications in magnetoelectronic sensors and for further studying the interplay between the linear Dirac-like and superconducting states in exotic materials.

  17. Tree nut allergens.

    PubMed

    Roux, Kenneth H; Teuber, Suzanne S; Sathe, Shridhar K

    2003-08-01

    Allergic reactions to tree nuts can be serious and life threatening. Considerable research has been conducted in recent years in an attempt to characterize those allergens that are most responsible for allergy sensitization and triggering. Both native and recombinant nut allergens have been identified and characterized and, for some, the IgE-reactive epitopes described. Some allergens, such as lipid transfer proteins, profilins, and members of the Bet v 1-related family, represent minor constituents in tree nuts. These allergens are frequently cross-reactive with other food and pollen homologues, and are considered panallergens. Others, such as legumins, vicilins, and 2S albumins, represent major seed storage protein constituents of the nuts. The allergenic tree nuts discussed in this review include those most commonly responsible for allergic reactions such as hazelnut, walnut, cashew, and almond as well as those less frequently associated with allergies including pecan, chestnut, Brazil nut, pine nut, macadamia nut, pistachio, coconut, Nangai nut, and acorn. Copyright 2003 S. Karger AG, Basel

  18. Clinical and Laboratory Studies of the Fate of Intranasal Allergen

    PubMed Central

    Rimmer, Janet; Santos, Conceição; Yli-Panula, Eija; Noronha, Virginia; Viander, Markku

    2015-01-01

    Background The precise way in which allergen is handled by the nose is unknown. The objective of this study was to determine recovery of Der p 1 allergen following nasal administration and to determine whether Der p 1 can be detected in nasal biopsies after natural exposure and nasal challenge to allergen. Methods (1) 20 nonatopic non-rhinitics were challenged with Der p 1 and recovery was measured by ELISA in the nasal wash, nasal mucus and induced sputum up to 30 minutes. Particulate charcoal (<40 μm) served as control. (2) In 8 subjects (5 atopics), 30 to 60 minutes after challenge histological localisation of Der p 1 in the nasal mucosal epithelium, subepithelial mucous glands and lamina propria was performed. Co-localisation of Der p 1 with macrophages and IgE-positive cells was undertaken. Results (1) Less than 25% of total allergen was retrievable after aqueous or particulate challenge, most from the nasal mucus during 1-5 min after the challenge. The median of carbon particles recovered was 9%. (2) Prechallenge Der p 1 staining was associated with the epithelium and subepithelial mucous glands. After challenge there was a trend for greater Der p 1 deposition in atopics, but both atopics and nonatopics showed increases in the number of Der p 1 stained cells and stained tissue compartments. In atopics, increased eosinophils, macrophages and IgE positive cells co-localized with Der p 1 staining. Conclusions Der p 1 allergen is detected in nasal tissue independent of atopic status after natural exposure. After challenge the nose effectively retains allergen, which remains mucosally associated; in atopics there is greater Der p 1 deposition and inflammatory response than in nonatopics. These results support the hypothesis that nasal mucus and tissue act as a reservoir for the inhaled Der p 1 allergen leading to a persistent allergic inflammatory response in susceptible individuals. PMID:25969994

  19. Secretion of adrenocorticotropic hormone induced by allergen inhalation in patients with atopic asthma.

    PubMed

    Yokoyama, A; Kohno, N; Sakai, K; Kondo, K; Hamada, H; Hiwada, K

    2000-09-01

    Allergen inhalation in atopic patients results in cytokines production or release of preformed cytokines, some of which are known to induce adrenocorticotropic hormone (ACTH) secretion in experimental conditions. We examined whether allergen inhalation can induce ACTH secretion in vivo. A significant elevation of ACTH levels was observed in 2 and 24 hr after allergen inhalation challenge. However, methacholine challenge with the same degree of airflow limitation did not induce ACTH elevation, indicating that this may not be due to bronchoconstriction per se. Our results indicate that allergen inhalation can trigger ACTH secretion in patients with atopic asthma.

  20. Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens.

    PubMed

    Bonefeld, Charlotte M; Geisler, Carsten; Gimenéz-Arnau, Elena; Lepoittevin, Jean-Pierre; Uter, Wolfgang; Johansen, Jeanne D

    2017-09-01

    Allergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Cross-React: a new structural bioinformatics method for predicting allergen cross-reactivity.

    PubMed

    Negi, Surendra S; Braun, Werner

    2017-04-01

    The phenomenon of cross-reactivity between allergenic proteins plays an important role to understand how the immune system recognizes different antigen proteins. Allergen proteins are known to cross-react if their sequence comparison shows a high sequence identity which also implies that the proteins have a similar 3D fold. In such cases, linear sequence alignment methods are frequently used to predict cross-reactivity between allergenic proteins. However, the prediction of cross-reactivity between distantly related allergens continues to be a challenging task. To overcome this problem, we developed a new structure-based computational method, Cross-React, to predict cross-reactivity between allergenic proteins available in the Structural Database of Allergens (SDAP). Our method is based on the hypothesis that we can find surface patches on 3D structures of potential allergens with amino acid compositions similar to an epitope in a known allergen. We applied the Cross-React method to a diverse set of seven allergens, and successfully identified several cross-reactive allergens with high to moderate sequence identity which have also been experimentally shown to cross-react. Based on these findings, we suggest that Cross-React can be used as a predictive tool to assess protein allergenicity and cross-reactivity. : Cross-React is available at: http://curie.utmb.edu/Cross-React.html. ssnegi@utmb.edu.

  2. Redefining the major peanut allergens

    PubMed Central

    Zhuang, Yonghua

    2015-01-01

    Food allergy has become a major public health concern in westernized countries, and allergic reactions to peanuts are particularly common and severe. Allergens are defined as antigens that elicit an IgE response, and most allergenic materials (e.g., pollens, danders, and foods) contain multiple allergenic proteins. This has led to the concept that there are “major” allergens and allergens of less importance. “Major allergens” have been defined as allergens that bind a large amount of IgE from the majority of patients and have biologic activity. However, the ability of an allergen to cross-link complexes of IgE and its high-affinity receptor FcεRI (IgE/FcεRI), which we have termed its allergic effector activity, does not correlate well with assays of IgE binding. To identify the proteins that are the most active allergens in peanuts, we and others have employed in vitro model assays of allergen-mediated cross-linking of IgE/FcεRI complexes and have demonstrated that the most potent allergens are not necessarily those that bind the most IgE. The importance of a specific allergen can be determined by measuring the allergic effector activity of that allergen following purification under non-denaturing conditions and by specifically removing the allergen from a complex allergenic extract either by chromatography or by specific immunodepletion. In our studies of peanut allergens, our laboratory has found that two related allergens, Ara h 2 and Ara h 6, together account for the majority of the effector activity in a crude peanut extract. Furthermore, murine studies demonstrated that Ara h 2 and Ara h 6 are not only the major elicitors of anaphylaxis in this system, but also can effectively desensitize peanut-allergic mice. As a result of these observations, we propose that the definition of a major allergen should be based on the potency of that allergen in assays of allergic effector activity and demonstration that removal of that allergen from an extract

  3. Allergenic pollen and pollen allergy in Europe.

    PubMed

    D'Amato, G; Cecchi, L; Bonini, S; Nunes, C; Annesi-Maesano, I; Behrendt, H; Liccardi, G; Popov, T; van Cauwenberge, P

    2007-09-01

    The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas. Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers. Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases.

  4. Grass Pollen Allergens

    PubMed Central

    Augustin, Rosa

    1959-01-01

    Grass pollen allergens are shown to remain associated with protein material and a yellow pigment during paper chromatography and during dialyses and ultrafiltrations of various types. Dialysable* allergens comprise only a fraction of 1 per cent of the total activity and the amount of activity extractable by diethylene glycol (DEG) and similar solvents is of the same order. Besides the allergens, the DEG and aqueous extracts contain large amounts of inositol, glucose and fructose, also some yellow pigments and phosphates. Larger amounts of free and combined amino acids are found in the aqueous than in the DEG extracts, but the reverse is true for sucrose. In addition the DEG extracts contain a yellow glucoside different from the dactylen of the aqueous extracts, a glucosan and an arabinose-galactose-pigment complex, only the latter being associated with any activity. The spontaneous release of the crystalline dactylen from originally clear aqueous pollen extracts is found not to be caused by enzymes. The washed crystals are found to be chromatographically and electrophoretically homogeneous and devoid of allergenic activity. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:13640676

  5. Bleach Neutralizes Mold Allergens

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  6. Allergenicity of processed food.

    USDA-ARS?s Scientific Manuscript database

    Food allergies have become a major public health issue in many countries. In the U.S. it is estimated that approximately 150 individuals die each year from accidental ingestion of an allergic food. As a result, the federal government recently passed the food allergen labeling law which went into ef...

  7. Serum albumins - unusual allergens

    PubMed Central

    Chruszcz, Maksymilian; Mikolajczak, Katarzyna; Mank, Nicholas; Majorek, Karolina A.; Porebski, Przemyslaw J.; Minor, Wladek

    2015-01-01

    Background Albumins are multifunctional proteins present in the blood serum of animals. They can bind and transport a wide variety of ligands which they accommodate due to their conformational flexibility. Serum albumins are highly conserved both in amino acid sequence and three-dimensional structure. Several mammalian and avian serum albumins (SAs) are also allergens. Sensitization to one of the SAs coupled with the high degree of conservation between SAs may result in cross-reactive antibodies in allergic individuals. Sensitivity to SA generally begins with exposure to an aeroallergen, which can then lead to cross-sensitization to serum albumins present in food. Scope of Review This review focuses on the allergenicity of SAs presented in a structural context. Major Conclusions SA allergenicity is unusual taking into account the high sequence identity and similarity between SA from different species and human serum albumin. Cross-reactivity of human antibodies towards different SAs is one of the most important characteristics of these allergens. General Significance Establishing a relationship between sequence and structure of different SAs and their interactions with antibodies is crucial for understanding the mechanisms of cross-sensitization of atopic individuals. Structural information can also lead to better design and production of recombinant SAs to replace natural proteins in allergy testing and desensitization. Therefore, structural analyses are important for diagnostic and treatment purposes. PMID:23811341

  8. Bleach Neutralizes Mold Allergens

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  9. Prospective and randomized study to evaluate the clinical impact of cap assisted colonoscopy (CAC).

    PubMed

    Frieling, T; Neuhaus, F; Kuhlbusch-Zicklam, R; Heise, J; Kreysel, C; Hülsdonk, A; Blank, M; Czypull, M

    2013-12-01

    Although colonoscopy is the standard procedure in the diagnosis of colorectal neoplasia, a significant number of clinical relevant lesions may be missed even by experienced endoscopists using current technology. A transparent cap mounted at the tip of a colonoscope may be an easy way to extend the visual field during colonoscopy and may improve the detection rate of mucosal lesions. The significance of cap assisted (CAC) vs. conventional colonoscopy (CC) on polyp detection rate was evaluated in a prospective randomized controlled trial in 504 patients. CC and CAC detected polyps in 39.3 % and 31.8, not significantly different. There was also no significant difference between CAC and CC according to age, sex, indication for colonoscopy, diverticulosis, sedation, bowel cleansing, withdrawal time, time/number of attempts to intubate the cecal walve, number, localization, size or histology of polyps,. However, the time to reach the cecal floor and the overall time of colonoscopy were significantly lower for CAC (1 minute). CAC was without clinical impact on polyp detection rate or performance of colonoscopy. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Genetic engineering of plant food with reduced allergenicity.

    PubMed

    Scheurer, Stephan; Sonnewald, Sophia

    2009-01-01

    Food allergies are a major health concern in industrialized countries. Since a specific immunotherapy for food allergies is not available in clinical routine praxis till now, reduction of allergens in foods, either by food processing or genetic engineering are strategies to minimize the risk of adverse reactions for food allergic patients. This review summarizes biotechnological approaches, especially the RNA interference (RNAi) technology, for the reduction of selected allergens in plant foods. So far, only a limited number of reports showing proof-of-concept of this methodology are available. Using RNAi an impressive reduction of allergen accumulation was obtained which was stable in the next generations of plants. Since threshold doses for most food allergens are not known, the beneficial effect has to be evaluated by oral challenge tests in the future. The article critically addresses the potential and limitations of genetic engineering, as well as of alternative strategies to generate "low allergic" foods.

  11. Contact allergens for armpits--allergenic fragrances specified on deodorants.

    PubMed

    Klaschka, Ursula

    2012-11-01

    According to the so-called "26 allergens rule" 26 supposedly allergenic fragrances must be specified on the containers of cosmetic products if they are present above 0.001% in leave-on products and, 0.01% in rinse-off products. This declaration is meant to inform the consumers of potential risks of skin sensitizers in the products. As many consumers of deodorants suffer from allergic or irritant contact dermatitis in the axillae, the presence of allergens in deodorants deserves special attention. The objective of this study was to find answers to the following questions: Does compulsory labeling lead to omission of strong allergenic fragrances in deodorants? Is there a difference in the use patterns of strong and weak allergens? What is the quantitative exposure to fragrances by deodorants? Is the situation in Germany different from other European countries? Is there a difference between deodorants for men and for women? I tested the implementation of the "26 allergens rule" and compiled which allergenic fragrances are specified on the containers of deodorants. Three market studies were conducted in Germany in 2008, 2010 and 2011. The labels of a total number of 374 deodorants were analyzed as to whether any of the "26 allergens" were listed. The frequency of each allergen in the deodorants was compared with results from previous studies by other authors. It was found that up to 83% of the deodorants contain at least one of the "26 allergens" and that up to 30% of all products contain strong allergens above the threshold for labeling (0.001% in the product). The most frequently listed allergens are medium or weak allergens. In comparison with other authors, the frequency of the "26 allergens" in products is slightly smaller in these recent studies for the German market. There is no significant difference between deodorants for men and women, as far as the labeling of the "26 allergens" is concerned. The results show that the mandatory labeling procedure as designed

  12. Oral administration of allergen extracts from Dermatophagoides farinae desensitizes specific allergen-induced inflammation and airway hyperresponsiveness in rats.

    PubMed

    Xie, Qiang-min; Wu, Ximei; Wu, Hui-min; Deng, Yang-mei; Zhang, Shui-juan; Zhu, Jian-ping; Dong, Xin-wei

    2008-12-10

    Clinically sublingual immunotherapy (SLIT) by using allergen extracts effectively alleviates the symptoms of allergic rhinitis and asthma. Supposed that oral administration of high-dose of allergen extracts imitates SLIT and may prevent IgE-related responses in allergic diseases, we investigated the effects of oral administration of allergen extracts from Dermatophagoides farinae (Derf) on allergen-induced inflammation and airway hyperresponsiveness (AHR) in a model of asthmatic rat. After administration to the specific Derf-sensitized rats with Derfdrop solution containing Derf1 and Derf2 extracts derived from Derf, the effects of Derfdrop on AHR, inflammatory cell accumulation, cytokine production in the bronchoalveolar lavage fluid and lung tissue, as well as serum IgE and IgG levels were investigated. Results indicated that Derfdrop not only dose-dependently prevented the AHR in response to methacholine, but also significantly reduced the serum total and allergen-specific IgE levels, all the maximal effects were achieved at dose of 5 mg/kg/d, and were as comparable as those of dexamethasone at dose of 1.0 mg/kg/d. Furthermore, oral administration of Derfdrop not only dose-dependently elevated allergen-specific serum IgG levels and reduced total and allergen-specific IgE levels, but also normalized the imbalance between the Th1 cytokine, IFN-gamma and Th2 cytokine, IL-4. Finally, oral administration of Derfdrop significantly reduced Goblet cell hyperplasia and eosinophilia in the Derf-sensitized allergic rat model. These data suggest that Derfdrop effectively improves specific allergen-induced inflammation and AHR in Derf-sensitized and -challenged rats and provide with the rationale for clinical SLIT by using Derfdrop in a specific allergen-induced asthma.

  13. Inhalant Allergens in Portugal.

    PubMed

    Gomes Câmara Camacho, Irene

    2017-02-23

    This review aims to present in a simple manner the work performed in Portugal regarding the identification of the most prevalent aeroallergens in the country and the sensitization levels in Portuguese patients. Much of the data was summarized in tables and illustrated on maps, enabling the community of clinicians, researchers, and patient organizations to access the knowledge about the research performed. This study provides an overview about the distribution of aeroallergens in Portugal, signaling regions and critical periods of exposure of the sensitized population. The illustrated data can help the community of allergy specialists to view the temporal and spatial distribution of aeroallergens across the country. In addition, this information can guide clinicians to select the most appropriate allergens for allergy diagnostic testing, treatment, and allergen avoidance.

  14. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells.

    PubMed

    Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

    2015-12-15

    Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-β1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity.

  15. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen Induced Inflammation by Modulating Mesenchymal Stem Cells

    PubMed Central

    Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

    2015-01-01

    Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen treated AhR-deficient (AhR−/−) mice showed exacerbation of lung inflammation when compared to wild-type (WT) mice. In contrast, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen challenged AhR−/− mice as compared to WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes, cyp1a1 and cyp1b1. Furthermore, we tracked the migration of intravenously injected GFP+ MSCs and found that cockroach allergen-challenged AhR−/− mice displayed less migration of MSCs to the lungs compared to WT. The AhR mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium (ECM) prepared from CRE-challenged epithelial cells significantly induced MSC migrations, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGFβ1 neutralizing antibody. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity. PMID:26561548

  16. Eosinophils generate brominating oxidants in allergen-induced asthma

    PubMed Central

    Wu, Weijia; Samoszuk, Michael K.; Comhair, Suzy A.A.; Thomassen, Mary Jane; Farver, Carol F.; Dweik, Raed A.; Kavuru, Mani S.; Erzurum, Serpil C.; Hazen, Stanley L.

    2000-01-01

    Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific “molecular fingerprint” for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans. PMID:10811853

  17. Relationship between cardio-ankle vascular index (CAVI) and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus.

    PubMed

    Mineoka, Yusuke; Fukui, Michiaki; Tanaka, Muhei; Tomiyasu, Ki-ichiro; Akabame, Satoshi; Nakano, Koji; Yamazaki, Masahiro; Hasegawa, Goji; Oda, Yohei; Nakamura, Naoto

    2012-03-01

    Early detection of atherosclerosis is important for patients with type 2 diabetes mellitus because cardiovascular disease (CVD) is a main cause of death in these people. In this study, we investigated the relationship between an arterial stiffness parameter called cardio-ankle vascular index (CAVI) and coronary artery calcification (CAC). We performed a cross-sectional study in 371 type 2 diabetic patients with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAVI and CAC score determined by multislice computed tomography as well as major cardiovascular risk factors, including age, body mass index, hemoglobinA1c and the Framingham CHD risk score. CAVI was correlated with age (r = 0.301, p < 0.0001), uric acid (r = 0.236, p < 0.0001), estimated glomerular filtration rate (r = -0.145, p = 0.0166), CHD risk score (r = 0.327, p < 0.0001) and log (CAC + 1) (r = 0.303, p < 0.0001). The area under the receiver operating characteristic curve for CAVI was higher than that of CHD risk score in predicting CAC >0, CAC >100, CAC >400, or CAC >1000. CAVI is positively correlated with CAC, and is considered to be a useful method to detect CAC.

  18. Breaking with Precedent: Community-Based Development of a CAC Program.

    ERIC Educational Resources Information Center

    Gruba, Paul; Tapper, Joanna

    The Communication across the Curriculum (CAC) program at the University of Melbourne (Australia) was set up in a top-down manner, which was partly driven by outside pressures. Although informed by writing-across-the-curriculum theory and practice, the program reflects the university's original concern about the teaching of communication skills by…

  19. Formation of Nanofoam carbon and re-emergence of Superconductivity in compressed CaC6

    PubMed Central

    Li, Yan-Ling; Luo, Wei; Chen, Xiao-Jia; Zeng, Zhi; Lin, Hai-Qing; Ahuja, Rajeev

    2013-01-01

    Pressure can tune material's electronic properties and control its quantum state, making some systems present disconnected superconducting region as observed in iron chalcogenides and heavy fermion CeCu2Si2. For CaC6 superconductor (Tc of 11.5 K), applying pressure first Tc increases and then suppresses and the superconductivity of this compound is eventually disappeared at about 18 GPa. Here, we report a theoretical finding of the re-emergence of superconductivity in heavily compressed CaC6. The predicted phase III (space group Pmmn) with formation of carbon nanofoam is found to be stable at wide pressure range with a Tc up to 14.7 K at 78 GPa. Diamond-like carbon structure is adhered to the phase IV (Cmcm) for compressed CaC6 after 126 GPa, which has bad metallic behavior, indicating again departure from superconductivity. Re-emerged superconductivity in compressed CaC6 paves a new way to design new-type superconductor by inserting metal into nanoporous host lattice. PMID:24276612

  20. Practical Issues in Estimating Classification Accuracy and Consistency with R Package cacIRT

    ERIC Educational Resources Information Center

    Lathrop, Quinn N.

    2015-01-01

    There are two main lines of research in estimating classification accuracy (CA) and classification consistency (CC) under Item Response Theory (IRT). The R package cacIRT provides computer implementations of both approaches in an accessible and unified framework. Even with available implementations, there remains decisions a researcher faces when…

  1. Formation of Nanofoam carbon and re-emergence of Superconductivity in compressed CaC6.

    PubMed

    Li, Yan-Ling; Luo, Wei; Chen, Xiao-Jia; Zeng, Zhi; Lin, Hai-Qing; Ahuja, Rajeev

    2013-11-26

    Pressure can tune material's electronic properties and control its quantum state, making some systems present disconnected superconducting region as observed in iron chalcogenides and heavy fermion CeCu2Si2. For CaC6 superconductor (Tc of 11.5 K), applying pressure first Tc increases and then suppresses and the superconductivity of this compound is eventually disappeared at about 18 GPa. Here, we report a theoretical finding of the re-emergence of superconductivity in heavily compressed CaC6. The predicted phase III (space group Pmmn) with formation of carbon nanofoam is found to be stable at wide pressure range with a Tc up to 14.7 K at 78 GPa. Diamond-like carbon structure is adhered to the phase IV (Cmcm) for compressed CaC6 after 126 GPa, which has bad metallic behavior, indicating again departure from superconductivity. Re-emerged superconductivity in compressed CaC6 paves a new way to design new-type superconductor by inserting metal into nanoporous host lattice.

  2. Practical Issues in Estimating Classification Accuracy and Consistency with R Package cacIRT

    ERIC Educational Resources Information Center

    Lathrop, Quinn N.

    2015-01-01

    There are two main lines of research in estimating classification accuracy (CA) and classification consistency (CC) under Item Response Theory (IRT). The R package cacIRT provides computer implementations of both approaches in an accessible and unified framework. Even with available implementations, there remains decisions a researcher faces when…

  3. Formation of Nanofoam carbon and re-emergence of Superconductivity in compressed CaC6

    NASA Astrophysics Data System (ADS)

    Li, Yan-Ling; Luo, Wei; Chen, Xiao-Jia; Zeng, Zhi; Lin, Hai-Qing; Ahuja, Rajeev

    2013-11-01

    Pressure can tune material's electronic properties and control its quantum state, making some systems present disconnected superconducting region as observed in iron chalcogenides and heavy fermion CeCu2Si2. For CaC6 superconductor (Tc of 11.5 K), applying pressure first Tc increases and then suppresses and the superconductivity of this compound is eventually disappeared at about 18 GPa. Here, we report a theoretical finding of the re-emergence of superconductivity in heavily compressed CaC6. The predicted phase III (space group Pmmn) with formation of carbon nanofoam is found to be stable at wide pressure range with a Tc up to 14.7 K at 78 GPa. Diamond-like carbon structure is adhered to the phase IV (Cmcm) for compressed CaC6 after 126 GPa, which has bad metallic behavior, indicating again departure from superconductivity. Re-emerged superconductivity in compressed CaC6 paves a new way to design new-type superconductor by inserting metal into nanoporous host lattice.

  4. Pharmacological characterisation of the adenosine receptor mediating increased ion transport in the mouse isolated trachea and the effect of allergen challenge

    PubMed Central

    Kornerup, Kristin N; Page, Clive P; Moffatt, James D

    2005-01-01

    The effect of adenosine on transepithelial ion transport was investigated in isolated preparations of murine trachea mounted in Ussing chambers. The possible regulation of adenosine receptors in an established model of allergic airway inflammation was also investigated. Mucosally applied adenosine caused increases in short-circuit current (ISC) that corresponded to approximately 50% of the response to the most efficacious secretogogue, ATP (ΔISC 69.5±6.7 μA cm2). In contrast, submucosally applied adenosine caused only small (<20%) increases in ISC, which were not investigated further. The A1-selective (N6-cyclopentyladenosine, CPA, 1 nM–10 μM), A2A-selective (2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxoamido adenosine; CGS 21680; 0.1–100 μM) and A3-selective (1-deoxy-1-[6-[[(3-iodophenyl)-methyl]amino]-9H-purin-9-yl]-N-methyl-β-D-ribofuranuronamide; IB-MECA; 30 nM–100 μM) adenosine receptor agonists were either equipotent or less potent than adenosine, suggesting that these receptors do not mediate the response to adenosine. The A1 receptor selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 nM–1 μM) caused a rightward shift of the adenosine concentration–effect curve only at 1 μM. The mixed A2A/A2B receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) also caused rightward shift of the adenosine concentration–effect curve, again only at micromolar concentrations, suggestive of the involvement of A2B receptors. In preparations from animals sensitised to ovalbumin and challenged over 3 days with aerosol ovalbumin, a decrease in baseline ISC was observed and responses to ATP were diminished. Similarly, the amplitude of responses to adenosine were attenuated although there was no change in potency. These results suggest that the A2B receptor mediates the ISC response to adenosine in the mouse trachea. This receptor does not appear to be

  5. Pharmacological characterisation of the adenosine receptor mediating increased ion transport in the mouse isolated trachea and the effect of allergen challenge.

    PubMed

    Kornerup, Kristin N; Page, Clive P; Moffatt, James D

    2005-04-01

    The effect of adenosine on transepithelial ion transport was investigated in isolated preparations of murine trachea mounted in Ussing chambers. The possible regulation of adenosine receptors in an established model of allergic airway inflammation was also investigated. Mucosally applied adenosine caused increases in short-circuit current (I(SC)) that corresponded to approximately 50% of the response to the most efficacious secretogogue, ATP (delta I(SC) 69.5 +/- 6.7 microA cm2). In contrast, submucosally applied adenosine caused only small (<20%) increases in I(SC), which were not investigated further. The A1-selective (N6-cyclopentyladenosine, CPA, 1 nM-10 microM), A2A-selective (2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxoamido adenosine; CGS 21680; 0.1-100 microM) and A3-selective (1-deoxy-1-[6-[[(3-iodophenyl)-methyl]amino]-9H-purin-9-yl]-N-methyl-beta-D-ribofuranuronamide; IB-MECA; 30 nM-100 microM) adenosine receptor agonists were either equipotent or less potent than adenosine, suggesting that these receptors do not mediate the response to adenosine. The A1 receptor selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 nM-1 microM) caused a rightward shift of the adenosine concentration-effect curve only at 1 microM. The mixed A2A/A2B receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) also caused rightward shift of the adenosine concentration-effect curve, again only at micromolar concentrations, suggestive of the involvement of A2B receptors. In preparations from animals sensitised to ovalbumin and challenged over 3 days with aerosol ovalbumin, a decrease in baseline I(SC) was observed and responses to ATP were diminished. Similarly, the amplitude of responses to adenosine were attenuated although there was no change in potency. These results suggest that the A2B receptor mediates the I(SC) response to adenosine in the mouse trachea. This receptor does not appear to be

  6. An excess vessel in the posterior part of the human cerebral arterial circle (CAC): a case series.

    PubMed

    Vasović, Ljiljana; Trandafilović, Milena; Jovanović, Ivan; Antović, Aleksandra; Stojanović, Jovan; Zdravković, Miodrag; Milić, Miroslav

    2010-06-23

    As a continuation of the previous findings in human fetuses, accidental finding of an accessory vascular component in the posterior part of CAC of human adult cadavers inspired the authors to present and compare its posterior part configuration. Examination was carried out on brains of 48 human adult cadavers, routinely dissected at the Institute of Forensic Medicine. The aberrant vessel in the posterior part of four CACs was discovered.Vascular components of the posterior segment of CAC or of the whole CAC were described and photographed. A comparison between fetal and adult cases was also presented. Based on the fact that the age of the four presented cases ranged from 73 to 84 and based on the causes of their death, we concluded that the angioarchitecture of the posterior part of the CAC is a consequence of the embryonic or primitive arterial stabilization and interaction with normal adult vessels.

  7. Identification of gene expression changes from colitis to CRC in the mouse CAC model.

    PubMed

    Li, Xin; Gao, Yuyan; Yang, Ming; Zhao, Qi; Wang, Guangyu; Yang, Yan Mei; Yang, Yue; Liu, Hui; Zhang, Yanqiao

    2014-01-01

    A connection between colorectal carcinogenesis and inflammation is well known, but the underlying molecular mechanisms have not been elucidated. Chemically induced colitis-associated cancer (CAC) is an outstanding mouse model for studying the link between inflammation and cancer. Additionally, the CAC model is used for examining novel diagnostic, prognostic, and predictive markers for use in clinical practice. Here, a CAC model was established in less than 100 days using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice. We examined the mRNA expression profiles of three groups: control untreated mice (K), DSS-induced chronic colitis mice (D), and AOM/DSS-induced CAC (AD) mice. We identified 6301 differentially expressed genes (DEGs) among the three groups, including 93 persistently upregulated genes and 139 persistently downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the most persistent DEGs were significantly enriched in metabolic or inflammatory components in the tumor microenvironment. Furthermore, several associated DEGs were identified as potential DEGs by protein-protein interaction (PPI) network analysis. We selected 14 key genes from the DEGs and potential DEGs for further quantitative real-time PCR (qPCR) verification. Six persistently upregulated, 3 persistently downregulated DEGs, and the other 3 genes showed results consistent with the microarray data. We demonstrated the regulation of 12 key genes specifically involved in Wnt signaling, cytokine and cytokine receptor interactions, homeostasis, and tumor-associated metabolism during colitis-associated CRC. Our results suggest that a close relationship between metabolic and inflammatory mediators of the tumor microenvironment is present in CAC.

  8. Single-dose desloratadine and montelukast and allergen-induced late airway responses.

    PubMed

    Davis, B E; Illamperuma, C; Gauvreau, G M; Watson, R M; O'Byrne, P M; Deschesnes, F; Boulet, L P; Cockcroft, D W

    2009-06-01

    Montelukast and desloratadine synergistically inhibit the allergen-induced early asthmatic response. Montelukast also suppresses the allergen-induced late asthmatic response, but there are no reports on the effect of desloratadine or the combination on the allergen-induced late asthmatic response. Atopic asthmatics (n = 10) completed a multicentric randomised double-blind crossover study comparing single-dose placebo, 5 mg desloratadine, 10 mg montelukast and the combination administered 2 h prior to allergen inhalation challenge. Methacholine challenges were performed 24 h before and after allergen challenge. Exhaled nitric oxide measurements and sputum inflammatory cell counts were also carried out. All active treatments significantly decreased the late asthmatic response area under the curve. Combination therapy provided the greatest inhibition compared to desloratadine and montelukast. Montelukast was nonsignificantly better than desloratadine but not as effective as the combination. There was a trend towards a decrease in airway responsiveness following montelukast and combination. Montelukast, but not desloratadine or the combination, decreased exhaled NO levels 24 h after allergen. The allergen-induced increase in sputum eosinophil numbers was significantly suppressed at 7 h with desloratadine and combination therapy, and at 24 h with montelukast and combination therapy. Single-dose co-administration of desloratadine and montelukast 2 h prior to allergen inhalation clinically abolished the late asthmatic response and eosinophil recruitment.

  9. Air pollution and allergens.

    PubMed

    Bartra, J; Mullol, J; del Cuvillo, A; Dávila, I; Ferrer, M; Jáuregui, I; Montoro, J; Sastre, J; Valero, A

    2007-01-01

    It is well known that the prevalence of allergic diseases has increased in recent decades in the industrialized world. Exposure to environmental pollutants may partially account for this increased prevalence. In effect, air pollution is a growing public health problem. In Europe, the main source of air pollution due to particles in suspension is represented by motor vehicles--particularly those that use diesel fuel. Diesel exhaust particles (DEPs) are composed of a carbon core upon which high-molecular weight organic chemical components and heavy metals deposit. Over 80% of all DEPs are in the ultrafine particle range (< 0.1 pm in diameter). Air pollutants not only have a direct or indirect effect upon the individual, but also exert important actions upon aeroallergens. Pollen in heavily polluted zones can express a larger amount of proteins described as being allergenic. Through physical contact with the pollen particles, DEPs can disrupt the former, leading to the release of paucimicronic particles and transporting them by air--thus facilitating their penetration of the human airways. Climate change in part gives rise to variations in the temperature pattern characterizing the different seasons of the year. Thus, plants may vary their pollination calendar, advancing and prolonging their pollination period. In addition, in the presence of high CO2 concentrations and temperatures, plants increase their pollen output. Climate change may also lead to the extinction of species, and to the consolidation of non-native species--with the subsequent risk of allergic sensitization among the exposed human population. In conclusion, there is sufficient scientific evidence on the effect of air pollution upon allergens, increasing exposure to the latter, their concentration and/or biological allergenic activity.

  10. Structural aspects of fungal allergens.

    PubMed

    Crameri, Reto

    2015-03-01

    Despite the increasing number of solved crystal structures of allergens, the key question why some proteins are allergenic and the vast majority is not remains unanswered. The situation is not different for fungal allergens which cover a wide variety of proteins with different chemical properties and biological functions. They cover enzymes, cell wall, secreted, and intracellular proteins which, except cross-reactive allergens, does not show any evidence for structural similarities at least at the three-dimensional level. However, from a diagnostic point of view, pure allergens biotechnologically produced by recombinant technology can provide us, in contrast to fungal extracts which are hardly producible as standardized reagents, with highly pure perfectly standardized diagnostic reagents.

  11. Buckwheat anaphylaxis: an unusual allergen in Taiwan.

    PubMed

    Wang, Tsung-Chi; Shyur, Shyh-Dar; Wen, Da-Chin; Kao, Yu-Hsuan; Huang, Li-Hsin

    2006-01-01

    IgE-mediated hypersensitivity to buckwheat is common in Korea, Japan, and some other Asian countries. However, buckwheat is not a common allergen in Taiwan. We report a woman with asthma who had anaphylactic shock, generalized urticaria, and an acute exacerbation of asthma five minutes after ingesting buckwheat. The patient underwent skin prick and Pharmacia CAP testing (Uppsala, Sweden) for specific IgE to buckwheat, white sesame and soybean as well as other common allergens in Taiwan including Dermatophagoides pteronyssinus (Dp), D. farinae (Df), cat and dog dander, cockroach, egg white, cow milk and codfish. The patient had a strongly positive skin prick test response to buckwheat and positive reactions to Dp and latex. Specific IgE results were class 6 for buckwheat, class 4 for Dp and Df, and class 2 for dog dander, wheat, sesame and soybean. Results of an open food challenge with white sesame and soybean were negative. Although buckwheat is a rare allergen in Taiwan, it can cause extremely serious reactions and should be considered in patients presenting with anaphylaxis after exposure to buckwheat.

  12. Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific Immune Tolerance.

    PubMed

    Gebe, John A; Yadava, Koshika; Ruppert, Shannon M; Marshall, Payton; Hill, Paul; Falk, Ben A; Sweere, Johanna M; Han, Hongwei; Kaber, Gernot; Medina, Carlos; Mikecz, Katalin; Ziegler, Steven F; Balaji, Swathi; Keswani, Sundeep G; Perez, Vinicio A de Jesus; Butte, Manish J; Nadeau, Kari; Altemeier, William A; Fanger, Neil; Bollyky, Paul L

    2017-01-01

    The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-HA can be adapted to promote tolerance to airway allergens. HMW-HA was thiolated to prevent its catabolism and was tethered to allergens via thiol linkages. This platform, which we call "XHA," delivers antigenic payloads in the context of antiinflammatory costimulation. Allergen/XHA was administered intranasally to mice that had been sensitized previously to these allergens. XHA prevents allergic airway inflammation in mice sensitized previously to either ovalbumin or cockroach proteins. Allergen/XHA treatment reduced inflammatory cell counts, airway hyperresponsiveness, allergen-specific IgE, and T helper type 2 cell cytokine production in comparison with allergen alone. These effects were allergen specific and IL-10 dependent. They were durable for weeks after the last challenge, providing a substantial advantage over the current desensitization protocols. Mechanistically, XHA promoted CD44-dependent inhibition of nuclear factor-κB signaling, diminished dendritic cell maturation, and reduced the induction of allergen-specific CD4 T-helper responses. XHA and other potential strategies that target CD44 are promising alternatives for the treatment of asthma and allergic sinusitis.

  13. Large particulate allergens can elicit mast cell-mediated anaphylaxis without exit from blood vessels as efficiently as do small soluble allergens.

    PubMed

    LiHua, Li; Yoshikawa, Soichiro; Ohta, Takuya; Horiguchi, Kayo; Kawano, Yohei; Ohtsu, Hiroshi; Yamanishi, Yoshinori; Karasuyama, Hajime

    2015-11-06

    Anaphylaxis is a rapid-onset, life-threatening allergic reaction in that IgE, mast cells and histamine are commonly involved. It can be experimentally induced in IgE-sensitized animals by intravenous injection of corresponding allergens, and the sign of anaphylactic reaction can be detected within minutes after allergen challenge. However, it remains puzzling why the anaphylactic reaction can be initiated in vivo so quickly, considering that allergens are delivered into the blood circulation while mast cells reside within peripheral tissues but not in the blood circulation. To address this issue, we compared two different forms of the same allergen, small soluble and large particulate ones, in their ability to induce anaphylaxis in IgE-sensitized mice. In contrast to our expectation, particulate allergens could induce anaphylaxis as quickly and efficiently as did soluble allergens, even though they remained inside of blood vessels. In vivo imaging analysis suggested the direct interaction of intravascular particulate allergens and perivascular mast cells across the capillary wall. Taken together with previous report that perivascular mast cells can capture IgE in the blood circulation by extending cell processes across the vessel wall, our findings imply that blood-circulating allergens, regardless of their size, can stimulate mast cells without exit from blood vessels, by means of cross-linking IgE on mast cell processes inserted into the vessel lumen, and hence initiate anaphylactic reaction so quickly. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Grass Pollen Allergens

    PubMed Central

    Augustin, Rosa

    1959-01-01

    Heat and pH stability studies and experiments with organic solvents show that the A-antigens discussed in the preceding paper (Augustin, 1959c) are much more labile than the I- (`inner ring') antigens. Breakdown products and/or aggregates are produced which no longer precipitate with antisera to the original extracts, but act as inhibitors. Solutions of pollen allergens, on the other hand, are found to withstand even autoclaving for 15 min. at 20 atm. and vigorous boiling over the naked flame of a bunsen burner. None of the carbohydrates tested has a demonstrable effect on skin reactivity which is, however, destroyed by crystalline pepsin, crystalline trypsin, a crystalline mould protease and a tissue protease (a partially purified extract from rabbit spleen). It follows that the bulk of the allergens—if not all—are proteins. The relation of skin reactivity, immuno-electrophoretic patterns, carbohydrate and protein reactions to the selective destruction of the pollen antigens is investigated. Pollen components prove to have a somewhat wider range of electrophoretic mobilities than serum proteins and are probably as complicated a mixture. The most and least highly negatively charged components are without skin reactivity in allergic subjects. The skin reactive allergens appear to have the mobilities of α- and β-globulins. Not all the hay fever subjects react equally to all the components, and Cocksfoot and Timothy activity patterns vary in different subjects. ImagesFIG. 5 PMID:13795119

  15. [Allergenic pollens in Spain].

    PubMed

    Subiza Garrido-Lestache, J

    2004-01-01

    Allergenic pollens that cause rhinoconjuctivitis and/or asthma are those from trees or plants that pollinate through the air (anemophilic pollination) and not through insects (entomophilic pollination). Although pollen grains would seem to be too large to easily reach the intrapulmonary airways, the relationship between pollen counts and the presence of asthmatic symptoms is only too evident. This is probably because the allergens inducing seasonal asthma are not only found within pollen grains but also outside the grains in particles of less than 10 mm that are freely found in the atmosphere. The most important pollens producing pollinosis in Spain are those from cypress trees from January-March, birch trees in April (macizo galaico), Platanus hispanica (March-April), grasses and olive trees from April-June, Parietaria from April-July and Chenopodium and/or Salsola from July-September. By geographical areas, the main cause of pollinosis are grasses in the center and north of the peninsula, olive trees in the south (Jaén, Sevilla, Granada, Córdoba) and Parietaria in the Mediterranean coast (Barcelona, Murcia, Valencia).

  16. Taxonomy of Allergenic Fungi.

    PubMed

    Levetin, Estelle; Horner, W Elliott; Scott, James A

    2016-01-01

    The Kingdom Fungi contains diverse eukaryotic organisms including yeasts, molds, mushrooms, bracket fungi, plant rusts, smuts, and puffballs. Fungi have a complex metabolism that differs from animals and plants. They secrete enzymes into their surroundings and absorb the breakdown products of enzyme action. Some of these enzymes are well-known allergens. The phylogenetic relationships among fungi were unclear until recently because classification was based on the sexual state morphology. Fungi lacking an obvious sexual stage were assigned to the artificial, now-obsolete category, "Deuteromycetes" or "Fungi Imperfecti." During the last 20 years, DNA sequencing has resolved 8 fungal phyla, 3 of which contain most genera associated with important aeroallergens: Zygomycota, Ascomycota, and Basidiomycota. Advances in fungal classification have required name changes for some familiar taxa. Because of regulatory constraints, many fungal allergen extracts retain obsolete names. A major benefit from this reorganization is that specific immunoglobulin E (IgE) levels in individuals sensitized to fungi appear to closely match fungal phylogenetic relationships. This close relationship between molecular fungal systematics and IgE sensitization provides an opportunity to systematically look at cross-reactivity and permits representatives from each taxon to serve as a proxy for IgE to the group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Raman spectroscopy and x-ray diffraction of sp3CaC O3 at lower mantle pressures

    NASA Astrophysics Data System (ADS)

    Lobanov, Sergey S.; Dong, Xiao; Martirosyan, Naira S.; Samtsevich, Artem I.; Stevanovic, Vladan; Gavryushkin, Pavel N.; Litasov, Konstantin D.; Greenberg, Eran; Prakapenka, Vitali B.; Oganov, Artem R.; Goncharov, Alexander F.

    2017-09-01

    The exceptional ability of carbon to form sp2 and sp3 bonding states leads to a great structural and chemical diversity of carbon-bearing phases at nonambient conditions. Here we use laser-heated diamond-anvil cells combined with synchrotron x-ray diffraction, Raman spectroscopy, and first-principles calculations to explore phase transitions in CaC O3 at P >40 GPa . We find that postaragonite CaC O3 transforms to the previously predicted P 21/c CaC O3 with sp3-hybridized carbon at 105 GPa (˜30 GPa higher than the theoretically predicted crossover pressure). The lowest-enthalpy transition path to P 21/c CaC O3 includes reoccurring sp2 and sp3CaC O3 intermediate phases and transition states, as revealed by our variable-cell nudged-elastic-band simulation. Raman spectra of P 21/c CaC O3 show an intense band at 1025 c m-1 , which we assign to the symmetric C-O stretching vibration based on empirical and first-principles calculations. This Raman band has a frequency that is ˜20 % lower than the symmetric C-O stretching in sp2CaC O3 due to the C-O bond length increase across the sp2-sp3 transition and can be used as a fingerprint of tetrahedrally coordinated carbon in other carbonates.

  18. Interlayer-state-driven superconductivity in CaC6 studied by angle-resolved photoemission spectroscopy

    NASA Astrophysics Data System (ADS)

    Kyung, Wonshik; Kim, Yeongkwan; Han, Garam; Leem, Choonshik; Kim, Chul; Koh, Yoonyoung; Kim, Beomyoung; Kim, Youngwook; Kim, Jun Sung; Kim, Keun Su; Rotenberg, Eli; Denlinger, Jonathan D.; Kim, Changyoung

    2015-12-01

    We performed angle-resolved photoemission experiments on CaC6 and measured kz-dependent electronic structures to investigate the interlayer states. The results reveal a spherical interlayer Fermi surface centered at the Γ point. We also find that the graphene-driven band possesses a weak kz dispersion. The overall electronic structure shows a peculiar single-graphene-layer periodicity in the kz direction although the CaC6 unit cell is supposed to contain three graphene layers. This suggests that the c -axis ordering of Ca has little effect on the electronic structure of CaC6. In addition to CaC6, we also studied the a low-temperature superconductor BaC6. For BaC6, the graphene-band Dirac-point energy is smaller than that of CaC6. Based on data from CaC6 and BaC6, we rule out the Cx y phonon mode as the origin of the superconductivity in CaC6, which strongly suggests interlayer-state-driven superconductivity.

  19. ALLERGEN PROVOCATION AUGMENTS ENDOTOXIN-INDUCED NASAL INFLAMMATION IN ATOPIC ASTHMATICS

    EPA Science Inventory

    Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis.
    Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenges in subjects with atopi...

  20. Dietary assessment in children adhering to a food allergen avoidance diet for allergy prevention.

    PubMed

    Vlieg-Boerstra, B J; van der Heide, S; Bijleveld, C M A; Kukler, J; Duiverman, E J; Wolt-Plompen, S A A; Dubois, A E J

    2006-12-01

    The purpose of this investigation was to verify if avoidance of allergenic foods in children adhering to a food allergen avoidance diet from birth was complete and feasible, and whether dietary assessment can be used as a tool in predicting the outcome of double-blind, placebo-controlled food challenges (DBPCFCs). Children adhering to an allergen avoidance diet from birth underwent DBPCFCs. The investigator-dietician verified whether the elimination was complete, using food frequency questionnaires for common allergenic foods. University Medical Centre Groningen, the Netherlands. Thiry-eight children aged 1-13 years, who were consecutively referred to the University Medical Centre Groningen for DBPCFC between January 2002 and February 2004. Among the 38 children undergoing DBPCFCs, there were 15 challenges with egg, 15 with peanut, five with hazelnut and three with soy. Fifteen food challenges (39%) were positive. Small quantities of allergenic foods were inadvertently present in the diets of 13 patients (34%), were possibly present in the diets of 14 patients (37%) and could not be identified in the diets of 11 patients (29%). Seven patients (54%) who had inadvertently ingested small quantities of allergenic foods without sequelae had a positive DBPCFC. Dietary avoidance was incomplete and not feasible in most cases. Tolerance of small amounts of allergenic foods does not preclude positive challenge reactions. Dietary assessment does not seem a useful tool in predicting the outcome of DBPCFC in children adhering to an elimination diet. The Stichting Astma Bestrijding (Foundation for the Prevention of Asthma), The Netherlands.

  1. Incidence and progression of coronary artery calcium (CAC) in HIV-infected and HIV-uninfected men

    PubMed Central

    KINGSLEY, Lawrence A; DEAL, Jennifer; JACOBSON, Lisa; BUDOFF, Matthew; WITT, Mallory; PALELLA, Frank; CALHOUN, Bridget; POST, Wendy S.

    2015-01-01

    Objective To determine whether HIV-infected men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared to HIV-uninfected controls. Design Prospective observational study. Setting Multicenter study in four USA academic research centers; University of Pittsburgh, Johns Hopkins University, University of California Los Angeles and Northwestern University. Participants 825 men (541 HIV-infected and 284 HIV-uninfected) enrolled in the cardiovascular sub-study of the Multicenter AIDS Cohort Study who underwent serial cardiac CT imaging during a mean follow-up of 5 years (range, 2–8 years). Main Outcome Measures Incidence and progression of CAC assessed by cardiac computed tomography (CT). Results During follow-up, 21% of HIV-infected men developed incident CAC as compared to 16% of HIV-uninfected men. This association persisted after adjustment for traditional and HIV-associated risk factors: HR 1.64 [1.13–3.14]. However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy. Conclusions In this large study of HIV-infected and HIV-uninfected men who underwent serial cardiac CT scan imaging, HIV-infected men were at significantly higher risk for development of CAC: HR 1.64 [1.13–3.14]. In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV-infected men. PMID:26558542

  2. Enhanced approaches for identifying Amadori products: application to peanut allergens

    USDA-ARS?s Scientific Manuscript database

    The dry roasting of peanuts is suggested to influence allergenic sensitization due to formation of advanced glycation end products (AGE) on peanut proteins. Identifying AGEs is technically challenging. The AGE composition of peanut proteins was probed with nanoLC-ESI-MS and MS/MS analyses. Amadori ...

  3. Association analysis of food allergens.

    PubMed

    Kanagawa, Yoshiyuki; Matsumoto, Shinya; Koike, Soichi; Imamura, Tomoaki

    2009-06-01

    Food allergy patients are known to present with allergic reactions to multiple allergens, but extrapolating these associations is difficult. Data mining, a procedure that analyzes characteristic combinations among large amounts of information, is often used to analyze and predict consumer purchasing behaviour. We applied this technique to the extrapolation of food allergen associations in allergy patients. We sent 1510 families our 'Questionnaire survey for the prevention of food allergies'. Responses noting 6549 allergens came from 878 families with 1383 patients, including 402 with anaphylaxis. Some results of the survey have already been published and here we presented the results of our association analysis of combinations of food allergens. Egg, milk, wheat, peanuts, and buckwheat are the most common food allergens. The most common simultaneous combinations of these allergens were 'egg-milk', 'egg-wheat', and 'milk-wheat'. The occurrence probability of a combination (i.e. one person suffering from a certain allergen also suffers from another) is called 'confidence'. Confidence was higher for 'chicken-egg', 'abalone-salmon eggs', and 'matsutake mushroom-milk'. As well, the combinations of 'crab-shrimp', 'squid-shrimp', and 'squid-crab' also indicated higher values in a statistical examination of the occurrence probabilities of these allergen combinations (Z-score). From the results of the association analysis, we speculated that some food allergens, such as abalone, orange, salmon, chicken, pork, matsutake mushroom, peach and apple did not independently induce food allergies. We also found that combinations, such as 'crab-shrimp', 'squid-shrimp', 'squid-crab', 'chicken-beef', and 'salmon-mackerel' had strong associations.

  4. Corrosion of aluminium metal in OPC- and CAC-based cement matrices

    SciTech Connect

    Kinoshita, Hajime; Swift, Paul; Utton, Claire; Carro-Mateo, Beatriz; Collier, Nick; Milestone, Neil

    2013-08-15

    Corrosion of aluminium metal in ordinary Portland cement (OPC) based pastes produces hydrogen gas and expansive reaction products causing problems for the encapsulation of aluminium containing nuclear wastes. Although corrosion of aluminium in cements has been long known, the extent of aluminium corrosion in the cement matrices and effects of such reaction on the cement phases are not well established. The present study investigates the corrosion reaction of aluminium in OPC, OPC-blast furnace slag (BFS) and calcium aluminate cement (CAC) based systems. The total amount of aluminium able to corrode in an OPC and 4:1 BFS:OPC system was determined, and the correlation between the amount of calcium hydroxide in the system and the reaction of aluminium obtained. It was also shown that a CAC-based system could offer a potential matrix to incorporate aluminium metal with a further reduction of pH by introduction of phosphate, producing a calcium phosphate cement.

  5. [Hemothorax complicated with celiac artery compression syndrome (CACS); report of a case].

    PubMed

    Uga, Naoko; Adachi, Katsutoshi; Tarukawa, Tomohito; Okuda, Yasuyuki; Tanigawa, Kanji; Nakaya, Hitoshi; Sato, Tomoaki; Hioki, Iwao

    2014-05-01

    We report a case of hemothorax complicated with celiac artery compression syndrome (CACS). A 43-year-old man presented with a sudden onset left back pain. Computed tomography (CT) showed its hemothorax, esophageal artery aneurysm and severe stenosis of the celiac truncus with its anterior compression by median accurate ligament, and a diagnosis of CACS associated with rupture of the aneurysm was made. Emergent transcatheter arterial embolization of the aneurysm resulted in a technical failure, although the patient's condition was stable and performed esophageal artery ligation through video-assisted thoracoscopic surgery on day 5 after onset. After surgery, the patient recovered without significant incidents. A cause of this aneurysmal development was supposed to be a significantly increased esophageal arterial blood flow with its luminal dilation to compensate a decreased celiac blood flow. Segmental arterial mediolysis could not be excluded as another cause.

  6. Application of Fisher fusion techniques to improve the individual performance of sonar computer-aided detection/computer-aided classification (CAD/CAC) algorithms

    NASA Astrophysics Data System (ADS)

    Ciany, Charles M.; Zurawski, William C.

    2009-05-01

    Raytheon has extensively processed high-resolution sidescan sonar images with its CAD/CAC algorithms to provide classification of targets in a variety of shallow underwater environments. The Raytheon CAD/CAC algorithm is based on non-linear image segmentation into highlight, shadow, and background regions, followed by extraction, association, and scoring of features from candidate highlight and shadow regions of interest (ROIs). The targets are classified by thresholding an overall classification score, which is formed by summing the individual feature scores. The algorithm performance is measured in terms of probability of correct classification as a function of false alarm rate, and is determined by both the choice of classification features and the manner in which the classifier rates and combines these features to form its overall score. In general, the algorithm performs very reliably against targets that exhibit "strong" highlight and shadow regions in the sonar image- i.e., both the highlight echo and its associated shadow region from the target are distinct relative to the ambient background. However, many real-world undersea environments can produce sonar images in which a significant percentage of the targets exhibit either "weak" highlight or shadow regions in the sonar image. The challenge of achieving robust performance in these environments has traditionally been addressed by modifying the individual feature scoring algorithms to optimize the separation between the corresponding highlight or shadow feature scores of targets and non-targets. This study examines an alternate approach that employs principles of Fisher fusion to determine a set of optimal weighting coefficients that are applied to the individual feature scores before summing to form the overall classification score. The results demonstrate improved performance of the CAD/CAC algorithm on at-sea data sets.

  7. Sensitization to fungal allergens: Resolved and unresolved issues.

    PubMed

    Fukutomi, Yuma; Taniguchi, Masami

    2015-10-01

    Exposure and sensitization to fungal allergens can promote the development and worsening of allergic diseases. Although numerous species of fungi have been associated with allergic diseases in the literature, the significance of fungi from the genera Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia has been well documented. However, it should be emphasized that the contribution of different fungal allergens to allergic diseases is not identical, but species-specific. Alternaria and Cladosporium species are considered to be important outdoor allergens, and sensitization and exposure to species of these genera is related to the development of asthma and rhinitis, as well as epidemics of asthma exacerbation, including life-threatening asthma exacerbation. In contrast, xerophilic species of Penicillium and Aspergillus, excluding Aspergillus fumigatus, are implicated in allergic diseases as indoor allergens. A. fumigatus has a high capacity to colonize the bronchial tract of asthmatic patients, causing severe persistent asthma and low lung function, and sometimes leading to allergic bronchopulmonary aspergillosis. Malassezia are common commensals of healthy skin, although they are also associated with atopic dermatitis, especially on the head and neck, but not with respiratory allergies. Despite its importance in the management of allergic diseases, precise recognition of species-specific IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identification of specific and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufficient. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  8. Superconducting graphene sheets in CaC6 enabled by phonon-mediated interband interactions

    NASA Astrophysics Data System (ADS)

    Yang, Shuolong; Sobota, Jonathan; Howard, Chris; Pickard, Chris; Hashimoto, Makoto; Lu, Donghui; Mo, Sung-Kwan; Kirchmann, Patrick; Shen, Zhi-Xun

    2014-03-01

    The superconducting mechanism of graphite intercalation compounds has been under intense debate. To reveal this mechanism, we studied a prototypical compound CaC6 using angle-resolved photoelectron spectroscopy. Both the calcium-derived and graphene-derived bands were clearly resolved. We performed analysis on the superconducting gaps and electron-phonon coupling constants. We will also discuss the important implications in fabricating superconducting graphene devices.

  9. AllergenFP: allergenicity prediction by descriptor fingerprints.

    PubMed

    Dimitrov, Ivan; Naneva, Lyudmila; Doytchinova, Irini; Bangov, Ivan

    2014-03-15

    Allergenicity, like antigenicity and immunogenicity, is a property encoded linearly and non-linearly, and therefore the alignment-based approaches are not able to identify this property unambiguously. A novel alignment-free descriptor-based fingerprint approach is presented here and applied to identify allergens and non-allergens. The approach was implemented into a four step algorithm. Initially, the protein sequences are described by amino acid principal properties as hydrophobicity, size, relative abundance, helix and β-strand forming propensities. Then, the generated strings of different length are converted into vectors with equal length by auto- and cross-covariance (ACC). The vectors were transformed into binary fingerprints and compared in terms of Tanimoto coefficient. The approach was applied to a set of 2427 known allergens and 2427 non-allergens and identified correctly 88% of them with Matthews correlation coefficient of 0.759. The descriptor fingerprint approach presented here is universal. It could be applied for any classification problem in computational biology. The set of E-descriptors is able to capture the main structural and physicochemical properties of amino acids building the proteins. The ACC transformation overcomes the main problem in the alignment-based comparative studies arising from the different length of the aligned protein sequences. The conversion of protein ACC values into binary descriptor fingerprints allows similarity search and classification. The algorithm described in the present study was implemented in a specially designed Web site, named AllergenFP (FP stands for FingerPrint). AllergenFP is written in Python, with GIU in HTML. It is freely accessible at http://ddg-pharmfac.net/Allergen FP. idoytchinova@pharmfac.net or ivanbangov@shu-bg.net.

  10. Kinetic Study on Desulfurization of Hot Metal Using CaO and CaC2

    NASA Astrophysics Data System (ADS)

    Lindström, David; Sichen, Du

    2015-02-01

    The kinetics and reaction mechanisms of hot metal desulfurization using CaO and CaC2 were studied in a well-controlled atmosphere with a lab scale high temperature furnace. The growths of CaS around CaO and CaC2 were measured and compared at 1773 K (1500 °C). The parabolic rate constant was evaluated to be 5 × 10-7 (cm s-1) on CaO particles, and 2.4 × 10-7 (cm s-1) on CaC2. The bigger parabolic constant of CaO resulted in more efficient desulfurization. Agglomerates and big CaO particles led to 2CaO·SiO2 formation which hindered further utilization of CaO for desulfurization. The 2CaO·SiO2 formation was favoured by a high oxygen potential. Since the desulfurization reaction of CaO not only produced CaS but also oxygen, the local oxygen concentration around big CaO particles was higher than around small particles.

  11. Kinetic Study on Desulfurization of Hot Metal Using CaO and CaC2

    NASA Astrophysics Data System (ADS)

    Lindström, David; Sichen, Du

    2014-09-01

    The kinetics and reaction mechanisms of hot metal desulfurization using CaO and CaC2 were studied in a well-controlled atmosphere with a lab scale high temperature furnace. The growths of CaS around CaO and CaC2 were measured and compared at 1773 K (1500 °C). The parabolic rate constant was evaluated to be 5 × 10-7 (cm s-1) on CaO particles, and 2.4 × 10-7 (cm s-1) on CaC2. The bigger parabolic constant of CaO resulted in more efficient desulfurization. Agglomerates and big CaO particles led to 2CaO·SiO2 formation which hindered further utilization of CaO for desulfurization. The 2CaO·SiO2 formation was favoured by a high oxygen potential. Since the desulfurization reaction of CaO not only produced CaS but also oxygen, the local oxygen concentration around big CaO particles was higher than around small particles.

  12. Allergen Peptides, Recombinant Allergens and Hypoallergens for Allergen-Specific Immunotherapy.

    PubMed

    Marth, Katharina; Focke-Tejkl, Margarete; Lupinek, Christian; Valenta, Rudolf; Niederberger, Verena

    2014-01-01

    Allergic diseases are among the most common health issues worldwide. Specific immunotherapy has remained the only disease-modifying treatment, but it is not effective in all patients and may cause side effects. Over the last 25 years, allergen molecules from most prevalent allergen sources have been isolated and produced as recombinant proteins. Not only are these molecules useful in improved allergy diagnosis, but they also have the potential to revolutionize the treatment of allergic disease by means of immunotherapy. Panels of unmodified recombinant allergens have already been shown to effectively replace natural allergen extracts in therapy. Through genetic engineering, several molecules have been designed with modified immunological properties. Hypoallergens have been produced that have reduced IgE binding capacity but retained T cell reactivity and T cell peptides which stimulate allergen-specific T cells, and these have already been investigated in clinical trials. New vaccines have been recently created with both reduced IgE and T cell reactivity but retained ability to induce protective allergen-specific IgG antibodies. The latter approach works by fusing per se non-IgE reactive peptides derived from IgE binding sites of the allergens to a virus protein, which acts as a carrier and provides the T-cell help necessary for immune stimulation and protective antibody production. In this review, we will highlight the different novel approaches for immunotherapy and will report on prior and ongoing clinical studies.

  13. Gastrointestinal digestion of food allergens: effect on their allergenicity.

    PubMed

    Moreno, F Javier

    2007-01-01

    This paper reviews the in vitro digestion models developed to assess the stability digestion of food allergens, as well as the factors derived from the methodology and food structure that may affect the assay results. The adequacy of using the digestion stability of food allergens as a criterion for assessing potential allergenicity is also discussed. Data based on the traditional pepsin digestibility test in simulated gastric fluid are discussed in detail, with special attention to the influence of the pH and pepsin: allergen ratio in the pepsinolysis rate. This review points out the importance of using physiologically relevant in vitro digestion systems for evaluating digestibility of allergens. This would imply the sequential use of digestive enzymes in physiological concentrations, simulation of the stomach/small intestine environment (multi-phase models) with addition of surfactants such as phospholipids or bile salts, as well as the consideration of the gastrointestinal transit and the effect of the food matrices on the allergen digestion and subsequent absorption through the intestinal mucosa. In vitro gastrointestinal digestion protocols should be preferably combined with immunological assays in order to elucidate the role of large digestion-resistant fragments and the influence of the food matrix on the stimulation of the immune system.

  14. Grass Pollen Allergens

    PubMed Central

    Augustin, Rosa; Hayward, Barbara J.

    1962-01-01

    Cocksfoot and Timothy pollen extracts are each found to contain at least fifteen components antigenic in rabbits. Most of these can also be allergens for man, but only a few are regularly so. These `principal' allergens have now been isolated in highly purified form. Procedures are given for a simple method of preparing extracts for clinical purposes and for the partial separation, concentration and purification of the allergens by means of differential extractions of the pollens and by means of ultrafiltration, isoelectric precipitation and salt fractionations (at acid and neutral pH) of the extracts. Isoelectric precipitations gave highly pigmented acid complexes, two of which moved as single sharp peaks at pH 7.4 in free electrophoresis, but proved to be hardly active by skin tests. Acid NaCl fractionation of the remainder resulted for Cocksfoot and Timothy in the isolation of a nearly white powder (T21.111121112 = T21B) which was weight for weight 1000–10,000 times as active as the pollen from which it had been derived. The powders have retained their activity for 7 years. By gel diffusion tests, they were found to contain two antigens (one in each preparation) which were immunologically partially related, but the Timothy preparation contained in addition the `innermost' `twin' antigens specific for Timothy that we had discovered previously in the crude extracts by gel diffusion methods. Skin reactions could be elicited in hay-fever subjects by prick tests with concentrations of 10-9–10-8 g./ml., which is equivalent to intradermal injections of 10-11–10-10 mg. and represents a 300-fold purification with respect to the concentrates of crude pollen extracts prepared by ultrafiltration and dialysis. Fractionation on DEAE-cellulose of one of the highly purified Timothy preparations (T21.11112112 = T21A) and other, crude Timothy and Cocksfoot extracts resulted in considerable and reproducible separation of the various antigens, with no indication of the

  15. Pollen Allergens for Molecular Diagnosis.

    PubMed

    Pablos, Isabel; Wildner, Sabrina; Asam, Claudia; Wallner, Michael; Gadermaier, Gabriele

    2016-04-01

    Pollen allergens are one of the main causes of type I allergies affecting up to 30% of the population in industrialized countries. Climatic changes affect the duration and intensity of pollen seasons and may together with pollution contribute to increased incidences of respiratory allergy and asthma. Allergenic grasses, trees, and weeds often present similar habitats and flowering periods compromising clinical anamnesis. Molecule-based approaches enable distinction between genuine sensitization and clinically mostly irrelevant IgE cross-reactivity due to, e. g., panallergens or carbohydrate determinants. In addition, sensitivity as well as specificity can be improved and lead to identification of the primary sensitizing source which is particularly beneficial regarding polysensitized patients. This review gives an overview on relevant pollen allergens and their usefulness in daily practice. Appropriate allergy diagnosis is directly influencing decisions for therapeutic interventions, and thus, reliable biomarkers are pivotal when considering allergen immunotherapy in the context of precision medicine.

  16. Cap-assisted colonoscopy (CAC) significantly extends visualization in the right colon.

    PubMed

    Frieling, T; Neuhaus, F; Heise, J; Kreysel, C; Hülsdonk, A; Blank, M; Czypull, M

    2012-03-01

    Although colonoscopy is the standard procedure in the diagnosis of colorectal neoplasia, a significant number of clinically relevant lesions may be missed even by experienced endoscopists using current technology. Particular problems may occur with blind spots behind the semilunar folds and within the right colon. A transparent cap mounted at the tip of a colonoscope may be an easy way to extend the visual field during colonoscopy and may improve the detection rate of mucosal lesions. However, data in the literature are controversial and the quantity of the potential extension of visualization by a transparent cap has not been reported yet. The significance of cap-assisted colonoscopy (CAC) to increase visualization within different colonic segments (rectum, sigmoid colon, descending colon, transverse colon, ascending colon, cecum) was quantitatively analyzed by randomized back-to-back colonoscopies with and without cap. The investigations were performed in a colonic training model by 5 investigators. The inner colonic surface was stained by a raster of dots and the number of dots counted during colonoscopy served as a measure for the visible surface area of each segment. The time to advance the colonoscope to the respective colonic segments and the overall time to reach the cecum were not significantly different between conventional and CAC. In contrast, overall withdrawal time and withdrawal times for the cecum, ascending colon, descending colon and rectum were significantly longer for CAC, but not for the transverse and sigmoid colon. Visualization of the colonic surface was significantly increased during CAC. Overall, 59.76 ± 2.70 % of the maximal countable dots were visualized without cap and 85.36 ± 9.62 % with cap. The improvement of visualization was only significant for the right colon, but not for the rectum, sigmoid or descending colon. The finding of the present study suggests that the extension of visualization by CAC may be of particular

  17. A revisit to cockroach allergens.

    PubMed

    Sookrung, Nitat; Chaicumpa, Wanpen

    2010-01-01

    Among cockroaches (CR) that live in people's homes, two species, i.e., German CR (Blattella germanica) and American CR (Periplaneta americana) predominate in temperate and tropical areas, respectively. CR is an important source of inhalant indoor allergens that sensitize atopic subjects to (localized) type I hypersensitivity or atopy including allergic rhinitis and atopic asthma. In Thailand the predominant CR species is P. americana. CR allergens are found throughout CR infested houses; the number found in kitchens correlates with the degree of CR infestation while sensitization and reactivation of the allergic morbidity are likely to occur in the living room and bedroom. Levels of the CR allergens in homes of CR allergic Thais, measured by using locally made quantification test kits, revealed that the highest levels occur in dust samples collected from the wooden houses of urban slums and in the cool and dry season. CR allergens are proteins that may be derived from any anatomical part of the insect at any developmental stage. The allergens may be also from CR secretions, excretions, body washes or frass. The proteins may be the insect structural proteins, enzymes or hormones. They may exist as dimers/multimers and/or in different isoforms. Exposure to CR allergens in infancy leads to allergic morbidity later in life. Clinical symptoms of CR allergy are usually more severe and prolonged than those caused by other indoor allergens. The mechanisms of acute and chronic airway inflammation and airway hyper-responsiveness (AHR) have been addressed including specific IgE- and non-IgE-mediated mechanisms, i.e., role of protease-activated receptor-2 (PAR2). Participation of various allergen activated-CD4+ T cells of different sublineages, i.e., Th2, Th17, Th22, Th9, Th25, Tregs/Th3 as well as invariant NKT cells, in asthma pathogenesis have been mentioned. The diagnosis of CR allergy and the allergy intervention by CR population control are also discussed.

  18. Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

    NASA Technical Reports Server (NTRS)

    Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi; Parsons-Wingerter, Patricia; Oudit, Gavin Y.; Grant, Maria B.

    2016-01-01

    Purpose: In diabetes, the impaired vasoreparative function of Circulating Angiogenic Cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) ACE2 Angiotensin-(1-7) Mas plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy. Methods: Study subjects (n43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5M 96-well chemotaxis cell migration assay. Results: ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls. Conclusions: These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential

  19. Evaluation of the Compressed Air Challenge(R) Training Program (Executive Summary)

    SciTech Connect

    Not Available

    2004-03-01

    The final report of the evaluation of the Compressed Air Challenge (CAC) Training Program. The training program is designed to provide plant personnel and compressed air system vendors with knowledge and tools required to effect improvements to the energy efficiency and overall performance of plant compressed air systems. As of May 2001, 3,029 individuals had attended the CAC Fundamentals of Compressed Air Training Systems and 925 individuals had attended ''Advanced Management of Compressed Air Systems''. These individuals represented 1,400-1,500 separate business establishments. The evaluation is based on three main research tasks: analysis of the CAC registration database, interviews with 100 end-user personnel who attended the CAC training, and interviews with 100 compressed air system vendors and consulting engineers who attended the training sessions.

  20. Assessment of endogenous allergenicity of genetically modified plants exemplified by soybean - Where do we stand?

    PubMed

    Selb, R; Wal, J M; Moreno, F J; Lovik, M; Mills, C; Hoffmann-Sommergruber, K; Fernandez, A

    2017-03-01

    According to EU regulation, genetically modified (GM) plants considered to be allergenic have to be assessed concerning their endogenous allergens before placement on the EU market, in line with the international standards described in Codex Alimentarius. Under such premises, a quantitative relevant increase in allergens might occur in GM plants as an unintended effect compared with conventionally produced crops, which could pose a risk to consumers. Currently, data showing a connection between dose and allergic sensitisation are scarce since the pathophysiological mechanisms of sensitisation are insufficiently understood. In contrast, data on population dose-distribution relationships acquired by oral food challenge are available showing a connection between quantity of allergenic protein consumed and the population of allergic individuals experiencing reactions. Soybean is currently the only recognised allergenic GM food by law for which EFSA has received applications and was therefore taken as an example for defining an assessment strategy. Identification of potential allergens, methodology for quantification as well as risk assessment considerations, are discussed. A strategy is proposed for the identification, assessment and evaluation of potential hazards/risks concerning endogenous allergenicity in food derived from plants developed by biotechnology. This approach could be expanded to other allergenic foods in the future, whenever required.

  1. Magnitude of late asthmatic response to allergen in relation to baseline and allergen-induced sputum eosinophilia in mild asthmatic patients.

    PubMed

    Dente, Federico L; Bacci, Elena; Bartoli, Maria Laura; Cianchetti, Silvana; Di Franco, Antonella; Costa, Francesco; Vagaggini, Barbara; Paggiaro, Pier Luigi

    2008-05-01

    Late asthmatic response (LAR) to allergen challenge is a validated method for studying the pathogenesis of and new treatments for asthma in the laboratory. To evaluate the relationship between the magnitude of allergen-induced LAR and clinical and biological determinants, including sputum and blood eosinophil percentages and eosinophil cationic protein concentrations. Thirty-eight untreated mild asthmatic patients (mean age, 21.2 years) were selected for the presence of allergen-induced early asthmatic response (EAR) and LAR. Each patient measured methacholine responsiveness (provocation dose that caused a decrease in forced expiratory volume in 1 second of 20% [PD20FEV1]) at baseline, differential blood cell counts and eosinophil cationic protein levels in blood and induced sputum, and serum neutrophil chemotactic activity at baseline and 24 hours after allergen challenge. A correlation was found between LAR (as area under the curve [AUC]) and sputum eosinophil percentages at baseline (r = 0.51; P = .001) and 24 hours after allergen challenge (r = 0.44; P < .007). Furthermore, we found significant correlations between AUC LAR and AUC EAR, baseline methacholine PD20FEV1, baseline blood eosinophil percentages, and baseline serum neutrophil chemotactic activity. A stepwise multiple regression analysis showed that the stronger determinants of AUC LAR were baseline sputum eosinophilia and AUC EAR. Baseline sputum eosinophilia and functional findings are determinants of the magnitude of allergen-induced LAR.

  2. Application of DNA fingerprinting with digoxigenated oligonucleotide probe (CAC)5 to analysis of the genetic variation within Taenia taeniaeformis.

    PubMed

    Okamoto, M; Ueda, H; Hayashi, M; Oku, Y; Kurosawa, T; Kamiya, M

    1995-04-01

    DNA from T. taeniaeformis digested with the restriction endonuclease was hybridized with digoxigenated oligonucleotide probe (CAC)5. Metacestode and adult showed same clear multibanding patterns, which were characteristic of multilocus DNA fingerprinting. The fingerprinting patterns were quite different from those of the rodent hosts. Genetic variations in 4 laboratory-reared isolates of T. taeniaeformis, including 3 isolates which have been reported to be indistinguishable by infectivity, morphology and protein composition of metacestode, were investigated using this technique. Each of the 4 isolates exhibited isolate-specific fingerprinting patterns and were easily distinguished from one another, thus it was considered that (CAC)5 was a highly resolvable and informative probe for cestodes. However, it was also indicated that (CAC)5 was so sensitive that applying fingerprinting with (CAC)5 to taxonomical or phylogenetic analysis was limited where habitat of the host was restricted to the small area. In comparison to fingerprinting with 32P-labeled (CAC)5, fingerprinting with digoxigenated (CAC)5 represented more and sharper bands. It was considered that a digoxigenated probe was more useful for genetic analysis of cestodes.

  3. Factors influencing the prescription of allergen immunotherapy: the allergen immunotherapy decision analysis (AIDA) study.

    PubMed

    Frati, F; Incorvaia, C; Cadario, G; Fiocchi, A; Senna, G E; Rossi, O; Romano, A; Scala, E; Romano, C; Ingrassia, A; Zambito, M; Dell'albani, I; Scurati, S; Passalacqua, G; Canonica, G W

    2013-10-01

    The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy has been demonstrated by a number of meta-analyses. However, the daily practice of AIT is quite different from controlled trials, facing challenges in terms of selection of patients, practical performance, and, of particular importance, use of allergen extracts of inadequate quality. We here performed a survey, named the Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are used by specialists to choose a product for sublingual immunotherapy (SLIT) in patients with respiratory allergy. A questionnaire composed of 14 items to be ranked by each participant according to the importance attributed when choosing SLIT products was submitted to 444 Italian specialists. The responses of the 169 (38.1%) physicians, who answered all questions, were analysed. Most of the respondents were allergists (79%), followed by pulmonologists (10.8%), both allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of the respondents were males and 40.2% were females. The age distribution showed that 89.9% of the respondents were aged between 35 and 64 years. All respondents usually prescribed AIT products in their clinical practice: 31.4% used only SLIT, whereas 69.2% used both subcutaneous and sublingual administration. The rankings, expressed as means, attributed by physicians for each of the 14 items were as follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44), level of EBM validation of safety (4.30), standardization of the product (5.37), efficacy based on personal experience (5.82), defined content(s) of the major allergen(s) in micrograms (5.96), scientific evidence for each single allergen (6.17), safety based on personal experience (6.32), ease of administration protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose personalization (9.24), patient preference (9.25), ease of product storage (9.93), reimbursement

  4. Crystal structure of peanut (Arachis hypogaea) allergen Ara h 5

    USDA-ARS?s Scientific Manuscript database

    Profilins from numerous species are known to be allergens, including food allergens, such as peanut (Arachis hypogaea) allergen Ara h 5, and pollen allergens, such as birch allergen Bet v 2. Patients with pollen allergy can also cross-react to peanut. Structural characterization of allergens will al...

  5. Allergens in celery and zucchini.

    PubMed

    Vieths, Stefan; Lüttkopf, D; Reindl, J; Anliker, M D; Wüthrich, B; Ballmer-Weber, B K

    2002-01-01

    The aim of this study was to confirm allergy to celery tuber and to zucchini, for the first time, by DBPCFC, and to identify the allergens recognized by IgE from DBPCFC-positive patients. Therefore, raw vegetables were hidden in a broccoli drink, and a DBPCFC-procedure was developed that consisted of a spit and swallow protocol, making sure that the procedure was safe for the patients and that reactions strictly localized to the oral cavity as well as systemic reactions could be reproduced by DBPCFC. The allergens in celery and zucchini extract were identified by immunoblot inhibition using allergen extracts, recombinant allergens and purified N-glycans as inhibitors. Celery allergy was confirmed in 69% (22/32) of subjects with a positive case history. Four subjects with a history of allergic reactions to zucchini had a positive DBPCFC to this vegetable. During DBPCFC, systemic reactions were provoked in 50% (11/22) of the patients to celery, and in 3/4 of the zucchini-allergic patients. The Bet v 1-related major celery allergen was detected by IgE of 59% (13/22) of the patients. Cross-reactive carbohydrate epitopes (CCD) bound IgE of 55% (12/22) of the celery-allergic patients and in 2/4 of the subjects with zucchini allergy. Profilin was a food allergen in celery in 23% (5/22) and in zucchini in 2/4 of the cases. A zucchini-specific allergen was detected by IgE from one patient. We conclude that ubiquitous cross-reactive structures are important in allergy to both, celery and zucchini, and that a specific association to birch pollen allergy exists in allergy to celery (mediated by Api g 1), but not in zucchini allergy.

  6. [Allergenic activity of non-calcinated egg shell calcium].

    PubMed

    Ebisawa, Motohiro; Tachimoto, Hiroshi; Ikematsu, Kaori; Sugizaki, Chizuko; Masuda, Yasunobu; Kimura, Mamoru

    2005-05-01

    There is few data to prove the safety of egg shell calcium as allergen. Especially, non-calcinated egg shell calcium is not allowed to use without the description of origin of egg on food labels in Japan. We evaluated the possibly contaminated egg allergens in commercial non-calcinated egg shell calcium made from egg by in vitro methodologies (SDS-PAGE, western blotting, inhibition ELISA and sandwich ELISA) and by single-blind oral non-calcinated egg shell calcium challenge on 6 egg hypersensitivity patients. The allergenic activity of non-calcinated egg shell calcium was almost negligible compared to egg white by all in vitro methods. Furthermore, six patients with egg hypersensitivity were unresponsive to oral non-calcinated egg shell calcium challenge test. These results indicate that there is little contamination of egg white in non-calcinated egg shell calcium, and that the allergenic activity of non-calcinated egg shell calcium is equivalent to that of calcinated egg shell calcium.

  7. Categorisation of protein respiratory allergens: the case of Subtilisin.

    PubMed

    Kimber, Ian; Basketter, David A

    2014-04-01

    Characterisation of the relative sensitizing potency of protein and chemical allergens remains challenging, particularly for materials causing allergic sensitization of the respiratory tract. There nevertheless remains an appetite, for priority setting and risk management, to develop paradigms that distinguish between individual respiratory allergens according to perceptions of the hazards and risks posed to human health. One manifestation thereof is recent listing of certain respiratory allergens as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). Although priority setting is a laudable ambition, it is important the process is predicated on evidence-based criteria that are transparent, understood and owned. The danger is that in the absence of rigorous criteria unwanted precedents can be created, and confidence in the process is compromised. A default categorisation of sensitisers as SVHC requiring assessment under the authorisation process is not desirable. We therefore consider here the value and limitations of selective assignment of certain respiratory allergens as being SVHC. The difficulties of sustaining such designations in a sound and equitable way is discussed in the context of the challenges that exist with respect to assessment of potency, and information available regarding the effectiveness of exposure-based risk management.

  8. Navigating through the Jungle of Allergens: Features and Applications of Allergen Databases.

    PubMed

    Radauer, Christian

    2017-01-01

    The increasing number of available data on allergenic proteins demanded the establishment of structured, freely accessible allergen databases. In this review article, features and applications of 6 of the most widely used allergen databases are discussed. The WHO/IUIS Allergen Nomenclature Database is the official resource of allergen designations. Allergome is the most comprehensive collection of data on allergens and allergen sources. AllergenOnline is aimed at providing a peer-reviewed database of allergen sequences for prediction of allergenicity of proteins, such as those planned to be inserted into genetically modified crops. The Structural Database of Allergenic Proteins (SDAP) provides a database of allergen sequences, structures, and epitopes linked to bioinformatics tools for sequence analysis and comparison. The Immune Epitope Database (IEDB) is the largest repository of T-cell, B-cell, and major histocompatibility complex protein epitopes including epitopes of allergens. AllFam classifies allergens into families of evolutionarily related proteins using definitions from the Pfam protein family database. These databases contain mostly overlapping data, but also show differences in terms of their targeted users, the criteria for including allergens, data shown for each allergen, and the availability of bioinformatics tools. © 2017 S. Karger AG, Basel.

  9. Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK.

    PubMed

    Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H

    2014-10-01

    Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10). Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05). Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Analysis to support allergen risk management: Which way to go?

    PubMed

    Cucu, Tatiana; Jacxsens, Liesbeth; De Meulenaer, Bruno

    2013-06-19

    Food allergy represents an important food safety issue because of the potential lethal effects; the only effective treatment is the complete removal of the allergen involved from the diet. However, due to the growing complexity of food formulations and food processing, foods may be unintentionally contaminated via allergen-containing ingredients or cross-contamination. This affects not only consumers' well-being but also food producers and competent authorities involved in inspecting and auditing food companies. To address these issues, the food industry and control agencies rely on available analytical methods to quantify the amount of a particular allergic commodity in a food and thus to decide upon its safety. However, no "gold standard methods" exist for the quantitative detection of food allergens. Nowadays mostly receptor-based methods and in particular commercial kits are used in routine analysis. However, upon evaluation of their performances, commercial assays proved often to be unreliable in processed foods, attributed to the chemical changes in proteins that affect the molecular recognition with the receptor used. Unfortunately, the analytical outcome of other methods, among which are chromatographic combined with mass spectrometric techniques as well as DNA-based methods, seem to be affected in a comparable way by food processing. Several strategies can be employed to improve the quantitative analysis of allergens in foods. Nevertheless, issues related to extractability and matrix effects remain a permanent challenge. In view of the presented results, it is clear that the food industry needs to continue to make extra efforts to provide accurate labeling and to reduce the contamination with allergens to an acceptable level through the use of allergen risk management on a company level, which needs to be supported inevitably by a tailor-validated extraction and detection method.

  11. Household Arthropod Allergens in Korea

    PubMed Central

    Jeong, Kyoung Yong

    2009-01-01

    Arthropods are important in human health, which can transmit pathogens to humans, parasitize, or produce important allergens. Allergy prevalence becomes higher in Korea recently as well as other developed countries in contrast to a decrease of infectious diseases. Allergic diseases caused by household arthropods have increased dramatically during the last few decades since human beings spend more their time for indoor activities in modernized life style. Household arthropods are one of the most common causes of allergic diseases. Biological characterization of household arthropods and researches on their allergens will provide better understanding of the pathogenesis of allergic diseases and suggest new therapeutic ways. Therefore, studies on arthropods of allergenic importance can be considered one of the major research areas in medical arthropodology and parasitology. Here, the biology of several household arthropods, including house dust mites and cockroaches, the 2 most well known arthropods living indoor together with humans worldwide, and characteristics of their allergens, especially the research activities on these allergens performed in Korea, are summarized. PMID:19885330

  12. Recombinant allergens for specific immunotherapy.

    PubMed

    Cromwell, Oliver; Häfner, Dietrich; Nandy, Andreas

    2011-04-01

    Recombinant DNA technology provides the means for producing allergens that are equivalent to their natural counterparts and also genetically engineered variants with reduced IgE-binding activity. The proteins are produced as chemically defined molecules with consistent structural and immunologic properties. Several hundred allergens have been cloned and expressed as recombinant proteins, and these provide the means for making a very detailed diagnosis of a patient's sensitization profile. Clinical development programs are now in progress to assess the suitability of recombinant allergens for both subcutaneous and sublingual immunotherapy. Recombinant hypoallergenic variants, which are developed with the aim of increasing the doses that can be administered while at the same time reducing the risks for therapy-associated side effects, are also in clinical trials for subcutaneous immunotherapy. Grass and birch pollen preparations have been shown to be clinically effective, and studies with various other allergens are in progress. Personalized or patient-tailored immunotherapy is still a very distant prospect, but the first recombinant products based on single allergens or defined mixtures could reach the market within the next 5 years. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  13. Mystery of the disappearing allergen: published allergens rarely seen again.

    PubMed

    Zapolanski, Tamar; Maibach, Howard I

    2008-01-01

    Patch testing is an important tool in the diagnosis of allergic contact dermatitis. Although this technique can be accurate, occasionally the results may be inconclusive. A previously positive result to an allergen may become negative upon repeat testing, and this may complicate the process of achieving a definitive diagnosis. There are some potential explanations for such inconsistencies, including the Excited Skin Syndrome, irritant reactions, a need to repeat the diagnostic algorithm, "rogue" reactions, and "contact allergy." These explanations should be taken into account when interpreting these results. However, further knowledge is needed to solve the mystery of an allergen that subsequently disappears.

  14. Sputum RNA signature in allergic asthmatics following allergen bronchoprovocation test

    PubMed Central

    Zuiker, Rob G.J.A.; Tribouley, Catherine; Diamant, Zuzana; Boot, J. Diderik; Cohen, Adam F.; Van Dyck, K.; De Lepeleire, I.; Rivas, Veronica M.; Malkov, Vladislav A.; Burggraaf, Jacobus; Ruddy, Marcella K.

    2016-01-01

    Background Inhaled allergen challenge is a validated disease model of allergic asthma offering useful pharmacodynamic assessment of pharmacotherapeutic effects in a limited number of subjects. Objectives To evaluate whether an RNA signature can be identified from induced sputum following an inhaled allergen challenge, whether a RNA signature could be modulated by limited doses of inhaled fluticasone, and whether these gene expression profiles would correlate with the clinical endpoints measured in this study. Methods Thirteen non-smoking, allergic subjects with mild-to-moderate asthma participated in a randomised, placebo-controlled, 2-period cross-over study following a single-blind placebo run-in period. Each period consisted of three consecutive days, separated by a wash-out period of at least 3 weeks. Subjects randomly received inhaled fluticasone ((FP) MDI; 500 mcg BID×5 doses in total) or placebo. On day 2, house dust mite extract was inhaled and airway response was measured by FEV1 at predefined time points until 7 h post-allergen. Sputum was induced by NaCl 4.5%, processed and analysed at 24 h pre-allergen and 7 and 24 h post-allergen. RNA was isolated from eligible sputum cell pellets (<80% squamous of 500 cells), amplified according to NuGEN technology, and profiled on Affymetrix arrays. Gene expression changes from baseline and fluticasone treatment effects were evaluated using a mixed effects ANCOVA model at 7 and at 24 h post-allergen challenge. Results Inhaled allergen-induced statistically significant gene expression changes in sputum, which were effectively blunted by fluticasone (adjusted p<0.025). Forty-seven RNA signatures were selected from these responses for correlation analyses and further validation. This included Th2 mRNA levels for cytokines, chemokines, high-affinity IgE receptor FCER1A, histamine receptor HRH4, and enzymes and receptors in the arachidonic pathway. Individual messengers from the 47 RNA signatures correlated significantly

  15. Allergenic compounds on the inner and outer surfaces of natural latex gloves: MALDI mass spectrometry and imaging of proteinous allergens.

    PubMed

    Marchetti-Deschmann, Martina; Allmaier, Günter

    2009-01-01

    Natural latex gloves are the cause of a severe health problem to an increasing number of healthcare workers or patients due to the presence of protein allergens as Hevein or Rubber Elongation Factor (REF). One of the most challenging problems is the in situ localization of theses allergens in, e.g. gloves, to estimate the allergenic potential of the latex material. A sample preparation protocol applying a binary matrix-assisted laser desorption/ionization(MALDI) matrix containing alpha-cyano-4-hydroxy cinnamic acid (CHCA) and 2,5-dihydroxy benzoic acid (DHB) on trifluoro acetic acid (TFA) etched latex glove surfaces allowed the direct determination (exact molecular weight) of Hevein, REF and a truncated form of REF (tREF) within nine different brands of natural latex gloves by means of MALDI-TOF-MS in the linear mode. MALDI mass spectrometry demonstrated that Hevein, tREF and REF were present on the inner surfaces (in direct contact with the skin) of many, but not all, investigated gloves without any prior extraction procedure. Additionally, different isoforms of the allergen Hevein were detected (exhibiting ragged C-termini). tREF and REF could always be detected beside each other, but were not observed on every latex glove sample, which contained Hevein. It was also demonstrated that there is a significant difference in terms of proteins and polymers between inner and outer surfaces of gloves, which helps to explain the different allergenic potential of these.MALDI imaging allowed for the first time the unambiguous localization of all three allergens in parallel and showed that Hevein was present on 36% of the investigated area of a latex glove with a certain localization, whereupon, tREF and REF were only found on 25% of the investigated material.

  16. Removing peanut allergens by tannic acid

    USDA-ARS?s Scientific Manuscript database

    Tannic acid (TA) is known to bind and form insoluble complexes with proteins, including peanut allergens; however, whether such complexes would dissociate and release the allergens at pH 2 and 8 (i.e., gastric and intestinal pH) is not clear. Release of the allergens in the gut could lead to absorpt...

  17. Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice

    PubMed Central

    Rayapudi, Madhavi; Mavi, Parm; Zhu, Xiang; Pandey, Akhilesh K.; Abonia, J. Pablo; Rothenberg, Marc E.; Mishra, Anil

    2010-01-01

    EE is an emerging disease reported in children and adults of urbanized countries, where indoor insect allergens are major health risk factors. Review of our hospital patient database uncovered that a number of EE patients have hypersensitivity to indoor cat, dog, cockroach, and dust mite allergens. We tested the hypothesis whether inhaled indoor insect allergens are effective inducers of experimental EE. We delivered cat, dog, cockroach, and dust mite allergen extracts intranasally to wild-type and eotaxin-1/2-, CCR3-, and IL-5-deficient mice. Interestingly, wild-type mice exposed to cockroach or dust mite allergens develop a significant increase in the levels of esophageal eosinophils and mast cells compared with saline-challenged mice. The eosinophil numbers in the esophagus of cockroach- and dust mite-exposed mice were 18.3 ± 6.8/mm2 and 33.4 ± 11.1/mm2 compared with 2.3 ± 1.8/mm2 and 2.1 ± 1.2/mm2 in saline-challenged mice. Additionally, we observed an additive effect of these two allergens in inducing esophageal eosinophilia and mastocytosis. Histopathological analysis detected intraepithelial esophageal eosinophilia in mice exposed to both allergens. Furthermore, mice exposed to cockroach and/or dust mite had increased levels of total IgE and antigen-specific IgG1 in the blood and increased esophageal expression of eosinophil-active cytokines (IL-13) and chemokines (eotaxin-1). Notably, mice deficient in eotaxin-1/2, CCR3, and IL-5 showed ablated esophageal eosinophilia following cockroach or dust mite allergen exposure. These data indicate that indoor insect allergens are potent inducers of IL-5 and eotaxin-mediated esophageal eosinophilia. These experimental studies are in accordance with clinical data but may have some limitations inherent to animal models of human disease. PMID:20413729

  18. Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice.

    PubMed

    Rayapudi, Madhavi; Mavi, Parm; Zhu, Xiang; Pandey, Akhilesh K; Abonia, J Pablo; Rothenberg, Marc E; Mishra, Anil

    2010-08-01

    EE is an emerging disease reported in children and adults of urbanized countries, where indoor insect allergens are major health risk factors. Review of our hospital patient database uncovered that a number of EE patients have hypersensitivity to indoor cat, dog, cockroach, and dust mite allergens. We tested the hypothesis whether inhaled indoor insect allergens are effective inducers of experimental EE. We delivered cat, dog, cockroach, and dust mite allergen extracts intranasally to wild-type and eotaxin-1/2-, CCR3-, and IL-5-deficient mice. Interestingly, wild-type mice exposed to cockroach or dust mite allergens develop a significant increase in the levels of esophageal eosinophils and mast cells compared with saline-challenged mice. The eosinophil numbers in the esophagus of cockroach- and dust mite-exposed mice were 18.3+/-6.8/mm2 and 33.4+/-11.1/mm2 compared with 2.3+/-1.8/mm2 and 2.1+/-1.2/mm2 in saline-challenged mice. Additionally, we observed an additive effect of these two allergens in inducing esophageal eosinophilia and mastocytosis. Histopathological analysis detected intraepithelial esophageal eosinophilia in mice exposed to both allergens. Furthermore, mice exposed to cockroach and/or dust mite had increased levels of total IgE and antigen-specific IgG1 in the blood and increased esophageal expression of eosinophil-active cytokines (IL-13) and chemokines (eotaxin-1). Notably, mice deficient in eotaxin-1/2, CCR3, and IL-5 showed ablated esophageal eosinophilia following cockroach or dust mite allergen exposure. These data indicate that indoor insect allergens are potent inducers of IL-5 and eotaxin-mediated esophageal eosinophilia. These experimental studies are in accordance with clinical data but may have some limitations inherent to animal models of human disease.

  19. Challenger

    ERIC Educational Resources Information Center

    Allday, Jonathan

    2002-01-01

    The events that led to the spectacular destruction of the Space Shuttle "Challenger" in 1986 are detailed here. They show how NASA should have heeded engineers' worries over materials problems resulting from a launch in cold weather. Suggestions are made of how pupils could also learn from this tragedy. (Contains 4 figures and 2 footnotes.)

  20. Challenges

    ERIC Educational Resources Information Center

    Moore, Thomas R.

    1975-01-01

    Domestic and international challenges facing the National Society for the Prevention of Blindness are discussed; and U.S. and Russian programs in testing and correcting children's vision, developing eye safety programs in agriculture and industry, and disseminating information concerning the detection and treatment of cataracts are compared. (SB)

  1. Challenger

    ERIC Educational Resources Information Center

    Allday, Jonathan

    2002-01-01

    The events that led to the spectacular destruction of the Space Shuttle "Challenger" in 1986 are detailed here. They show how NASA should have heeded engineers' worries over materials problems resulting from a launch in cold weather. Suggestions are made of how pupils could also learn from this tragedy. (Contains 4 figures and 2 footnotes.)

  2. Fish Allergens at a Glance: Variable Allergenicity of Parvalbumins, the Major Fish Allergens

    PubMed Central

    Kuehn, Annette; Swoboda, Ines; Arumugam, Karthik; Hilger, Christiane; Hentges, François

    2014-01-01

    Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand, some individuals have IgE antibodies directed against unique, species-specific parvalbumin epitopes, and these patients show clinical symptoms only with certain fish species. Furthermore, different parvalbumin isoforms and isoallergens are present in the same fish and might display variable allergenicity. This was shown for salmon homologs, where only a single parvalbumin (beta-1) isoform was identified as allergen in specific patients. In addition to the parvalbumins, several other fish proteins, enolases, aldolases, and fish gelatin, seem to be important allergens. New clinical and molecular insights advanced the knowledge and understanding of fish allergy in the last years. These findings were useful for the advancement of the IgE-based diagnosis and also for the management of fish allergies consisting of advice and treatment of fish-allergic patients. PMID:24795722

  3. Fish allergens at a glance: variable allergenicity of parvalbumins, the major fish allergens.

    PubMed

    Kuehn, Annette; Swoboda, Ines; Arumugam, Karthik; Hilger, Christiane; Hentges, François

    2014-01-01

    Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand, some individuals have IgE antibodies directed against unique, species-specific parvalbumin epitopes, and these patients show clinical symptoms only with certain fish species. Furthermore, different parvalbumin isoforms and isoallergens are present in the same fish and might display variable allergenicity. This was shown for salmon homologs, where only a single parvalbumin (beta-1) isoform was identified as allergen in specific patients. In addition to the parvalbumins, several other fish proteins, enolases, aldolases, and fish gelatin, seem to be important allergens. New clinical and molecular insights advanced the knowledge and understanding of fish allergy in the last years. These findings were useful for the advancement of the IgE-based diagnosis and also for the management of fish allergies consisting of advice and treatment of fish-allergic patients.

  4. Shellfish allergens: tropomyosin and beyond.

    PubMed

    Faber, M A; Pascal, M; El Kharbouchi, O; Sabato, V; Hagendorens, M M; Decuyper, I I; Bridts, C H; Ebo, D G

    2016-12-27

    IgE-mediated shellfish allergy constitutes an important cause of food-related adverse reactions. Shellfish are classified into mollusks and crustaceans, the latter belonging to the class of arthropoda. Among crustaceans, shrimps are the most predominant cause of allergic reactions and thus more extensively studied. Several major and minor allergens have been identified and cloned. Among them, invertebrate tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, and hemocyanin are the most relevant. This review summarizes our current knowledge about these allergens.

  5. New and emerging cosmetic allergens.

    PubMed

    Davies, Rosie F; Johnston, Graham A

    2011-01-01

    Human skin is exposed to a large variety of cosmetic allergens. Most allergic contact dermatitis occurs after exposure to fragrance, preservatives, and hair dyes. Such reactions can often be occult. As a result, a high index of suspicion is needed in assessing the patient with facial or cosmetic dermatitis. This contribution looks at why such a large number of chemicals are in everyday usage, at how dermatologists monitor trends in allergy to cosmetics, and at a number of new and emerging allergens to consider in the assessment of suspected cosmetic allergy.

  6. Role of alkalis of aggregate origin in the deterioration of CAC concrete

    SciTech Connect

    Blanco-Varela, M.T.

    2005-09-01

    Both hexagonal and cubic calcium aluminate cement (CAC) hydrates react with atmospheric CO{sub 2}, bringing about mineralogical changes in concrete, which may, on occasion, lead to loss of mechanical strength. Alkaline hydrolysis or carbonation in the presence of alkalis is a highly destructive process. The purpose of the study was to determine what caused CAC concrete deterioration in a prestressed beam that had suffered intense external damage and showed signs of alkaline hydrolysis or a reaction between the aggregate and the cement. Samples of the internal (sound) and external (damaged) parts of the concrete were studied using XRF, XRD, FTIR, OM, SEM/EDX, and BSE techniques, and mechanical strength was measured on microspecimens extracted from both zones. The conclusion drawn from these analyses was that alkaline hydrolysis took place on or near the surface of the concrete. The white deposits observed around the alkali-containing aggregate were found to consist primarily of bayerite whose very loose consistency undermined the aggregate-matrix bond, greatly weakening the material.

  7. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation

    SciTech Connect

    Zhu, Houbao; Xu, Wangyang; Zhang, Hongxin; Liu, Jianbing; Xu, Haimin; Lu, Shunyuan; Dang, Suying; Kuang, Ying; Jin, Xiaolong; Wang, Zhugang

    2013-08-16

    Highlights: •Kif18A is up-regulated in CAC of mouse model. •Kif18a{sup −/−} mice are protected from CAC. •Tumor cells from Kif18a{sup −/−} mice undergo more apoptosis. •Kif18A deficiency induces poor Atk phosphorylation. -- Abstract: Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM–DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC.

  8. Phthalocyanine-dyed fibers adsorb allergenic proteins.

    PubMed

    Yano, H; Sugihara, Y; Shirai, H; Wagatsuma, Y; Kusada, O; Matsuda, T; Kuroda, S; Higaki, S

    2006-05-01

    Phthalocyanine (Pc)-dyed fiber is reported to reduce atopic symptoms in some patients when they use underwear made of the fiber. We investigated the adsorption of allergens on Pc-fiber. Pc-fiber trapped house dust/pollen/food allergens with varied molecular weight and pI. The adsorbed allergens were released in the presence of mild detergent. Pc-fiber did not change the molecular weight or disulfide bonding of the allergens. These observations imply that Pc-fiber is applicable as an "allergen trap" for a wide variety of products.

  9. Emergent and unusual allergens in cosmetics.

    PubMed

    Pascoe, David; Moreau, Linda; Sasseville, Denis

    2010-01-01

    Allergic contact dermatitis from cosmetics is a common problem that is occasionally caused by new or rare allergens. When a patient has a positive patch test to a cosmetic product but to none of the common or commercially available allergens, it is important to further patch-test this patient to the ingredients of the product. Thorough testing with the breakdown of ingredients, usually obtained through cooperation with the manufacturer, often allows identification of the culprit allergen in the cosmetic product. In this article, we discuss emerging or rare allergens discovered by this method, including nail lacquer and lipstick allergens, copolymers, shellac, alkyl glucosides, glycols, protein derivatives, idebenone, and octocrylene.

  10. Encapsulation of hydrophobic allergens into nanoparticles improves the in vitro immunological diagnosis of allergic contact dermatitis.

    PubMed

    Cortial, Angèle; Nosbaum, Audrey; Rozières, Aurore; Baeck, Marie; de Montjoye, Laurence; Grande, Sophie; Briançon, Stéphanie; Nicolas, Jean-François; Vocanson, Marc

    2015-05-01

    The diagnosis of allergic contact dermatitis (ACD) relies on in vivo patch testing. In vitro immunological assays based on the characterization of circulating allergen-specific memory T cells represent a promising alternative to patch testing. However, their development is hampered by the technical challenge of assessing hydrophobic allergens in serum-based assays. In this study, we show that the encapsulation of fragrance mix 1 (FMI, a mixture of 8 hydrophobic allergens) into poly-ε-caprolactone nanoparticle (NP) vectors: (1) dramatically increases the solubilization of allergens in conventional cell culture media and (2) allows for a robust in vitro reactivation of allergen-specific T cells in large numbers of fragrance allergic patients. Therefore, the encapsulation of hydrophobic allergens into NP vectors opens new avenues to improve the in vitro immunobiological diagnosis of ACD. Allergic Contact Dermatitis (ACD) is a delayed-type hypersensivity reaction prevalent in many individuals. Currently, skin patch testing has been the mainstay for diagnosis clinically. In this study, the authors described an improvement to in vitro immunological assays measuring circulating allergen-specific memory T cells, using nanoparticle vectors. The positive data might provide an exciting alternative to current practice of patch-testing. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Nomenclature and structural biology of allergens.

    PubMed

    Chapman, Martin D; Pomés, Anna; Breiteneder, Heimo; Ferreira, Fatima

    2007-02-01

    Purified allergens are named using the systematic nomenclature of the Allergen Nomenclature Sub-Committee of the World Health Organization and International Union of Immunological Societies. The system uses abbreviated Linnean genus and species names and an Arabic number to indicate the chronology of allergen purification. Most major allergens from mites, animal dander, pollens, insects, and foods have been cloned, and more than 40 three-dimensional allergen structures are in the Protein Database. Allergens are derived from proteins with a variety of biologic functions, including proteases, ligand-binding proteins, structural proteins, pathogenesis-related proteins, lipid transfer proteins, profilins, and calcium-binding proteins. Biologic function, such as the proteolytic enzyme allergens of dust mites, might directly influence the development of IgE responses and might initiate inflammatory responses in the lung that are associated with asthma. Intrinsic structural or biologic properties might also influence the extent to which allergens persist in indoor and outdoor environments or retain their allergenicity in the digestive tract. Analyses of the protein family database suggest that the universe of allergens comprises more than 120 distinct protein families. Structural biology and proteomics define recombinant allergen targets for diagnostic and therapeutic purposes and identify motifs, patterns, and structures of immunologic significance.

  12. Dermatophagoides farinae allergens diversity identification by proteomics.

    PubMed

    An, Su; Chen, Lingling; Long, Chengbo; Liu, Xiaoyu; Xu, Xuemei; Lu, Xingre; Rong, Mingqiang; Liu, Zhigang; Lai, Ren

    2013-07-01

    The most important indoor allergens for humans are house dust mites (HDM). Fourteen Dermatophagoides farinae allergens (Der f 1-3, 6, 7, 10, 11, 13-18, and 22) are reported although more than 30 allergens have been estimated in D. farinae. Seventeen allergens belonging to 12 different groups were identified by a procedure of proteomics combined with two-dimensional immunoblotting from D. farina extracts. Their sequences were determined by Edman degradation, mass spectrometry analysis, and cDNA cloning. Their allergenicities were assayed by enzyme-linked immunosorbent assay inhibition tests, immunoblots, basophil activation test, and skin prick tests. Eight of them are the first report as D. farinae allergens. The procedure of using a proteomic approach combined with a purely discovery approach using sera of patients with broad IgE reactivity profiles to mite allergens was an effective method to investigate a more complete repertoire of D. farinae allergens. The identification of eight new D. farinae allergens will be helpful for HDM allergy diagnosis and therapy, especially for patients without response for HDM major allergens. In addition, the current work significantly extendedthe repertoire of D. farinae allergens.

  13. New insights into ragweed pollen allergens.

    PubMed

    Bordas-Le Floch, Véronique; Groeme, Rachel; Chabre, Henri; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent; Moingeon, Philippe

    2015-11-01

    Pollen allergens from short ragweed (Ambrosia artemisiifolia) cause severe respiratory allergies in North America and Europe. To date, ten short ragweed pollen allergens belonging to eight protein families, including the recently discovered novel major allergen Amb a 11, have been recorded in the International Union of Immunological Societies (IUIS) allergen database. With evidence that other components may further contribute to short ragweed pollen allergenicity, a better understanding of the allergen repertoire is a requisite for the design of proper diagnostic tools and efficient immunotherapies. This review provides an update on both known as well as novel candidate allergens from short ragweed pollen, identified through a comprehensive characterization of the ragweed pollen transcriptome and proteome.

  14. Immunosuppression in early postnatal days induces persistent and allergen-specific immune tolerance to asthma in adult mice.

    PubMed

    Chen, Yan; Zhang, Jin; Lu, Yong; Wang, Libo

    2015-01-01

    Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma.

  15. Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences.

    PubMed

    Radauer, C; Nandy, A; Ferreira, F; Goodman, R E; Larsen, J N; Lidholm, J; Pomés, A; Raulf-Heimsoth, M; Rozynek, P; Thomas, W R; Breiteneder, H

    2014-04-01

    The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into allergen nomenclature, while keeping changes of established names to a minimum in the interest of continuity. Allergens for which names have been updated include respiratory allergens from birch and ragweed pollen, midge larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and cereal grain allergens. The IUIS Allergen Nomenclature Sub-Committee encourages researchers to use these updated allergen names in future publications.

  16. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation.

    PubMed

    Zhu, Houbao; Xu, Wangyang; Zhang, Hongxin; Liu, Jianbing; Xu, Haimin; Lu, Shunyuan; Dang, Suying; Kuang, Ying; Jin, Xiaolong; Wang, Zhugang

    2013-08-16

    Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM-DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Characteristic motifs for families of allergenic proteins

    PubMed Central

    Ivanciuc, Ovidiu; Garcia, Tzintzuni; Torres, Miguel; Schein, Catherine H.; Braun, Werner

    2008-01-01

    The identification of potential allergenic proteins is usually done by scanning a database of allergenic proteins and locating known allergens with a high sequence similarity. However, there is no universally accepted cut-off value for sequence similarity to indicate potential IgE cross-reactivity. Further, overall sequence similarity may be less important than discrete areas of similarity in proteins with homologous structure. To identify such areas, we first classified all allergens and their subdomains in the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to their closest protein families as defined in Pfam, and identified conserved physicochemical property motifs characteristic of each group of sequences. Allergens populate only a small subset of all known Pfam families, as all allergenic proteins in SDAP could be grouped to only 130 (of 9318 total) Pfams, and 31 families contain more than four allergens. Conserved physicochemical property motifs for the aligned sequences of the most populated Pfam families were identified with the PCPMer program suite and catalogued in the webserver Motif-Mate (http://born.utmb.edu/motifmate/summary.php). We also determined specific motifs for allergenic members of a family that could distinguish them from non-allergenic ones. These allergen specific motifs should be most useful in database searches for potential allergens. We found that sequence motifs unique to the allergens in three families (seed storage proteins, Bet v 1, and tropomyosin) overlap with known IgE epitopes, thus providing evidence that our motif based approach can be used to assess the potential allergenicity of novel proteins. PMID:18951633

  18. Allergen exposure induces adipose tissue inflammation and insulin resistance.

    PubMed

    Jung, Chien-Cheng; Tsai, Yau-Sheng; Chang, Chih-Ching; Cheng, Tsun-Jen; Chang, Ching-Wen; Liu, Ping-Yen; Chiu, Yi-Jen; Su, Huey-Jen

    2014-11-01

    This study investigates whether exposure to allergen elicits insulin resistance as a result of adipose tissue inflammation. Male C57BL/6 mice were challenged with ovalbumin (OVA) allergen for 12 weeks, and blood and adipose tissue samples were collected at 24h after the last challenge. Levels of adhesion molecules, fasting insulin, fasting glucose, and adipokines in the blood were analyzed, and fasting homeostasis model assessment was applied to determine insulin resistance (HOMA-IR). The expression of pro- and anti-inflammatory genes in dissected adipose tissues was analyzed by real-time RT-PCR. Our results showed that OVA exposure increased insulin resistance as well as resistin and E-selectin, but reduced adiponectin in the serum. Resistin level was significantly correlated with HOMA-IR. Moreover, in adipose tissues of OVA-challenged mice, the pro-inflammatory M1 genes were more abundant while the anti-inflammatory M2 genes were less than those of PBS-treated mice. The expressional changes of both M1 and M2 genes were significantly associated with serum levels of adiponectin, resistin, and E-selectin. Hematoxylin and eosin (HE) and immunohistochemistry (IHC) stain also showed that there was more obvious inflammation in OVA-challenged mice. In conclusion, the current study suggests the relationship between allergen-elicited adipose tissue inflammation and circulating inflammatory molecules, which are possible mediators for the development of insulin resistance. Therefore, we propose that allergen exposure might be one risk factor for insulin resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor I with chromatin.

    PubMed

    Jeffery, Daniel C B; Kakusho, Naoko; You, Zhiying; Gharib, Marlene; Wyse, Brandon; Drury, Erin; Weinreich, Michael; Thibault, Pierre; Verreault, Alain; Masai, Hisao; Yankulov, Krassimir

    2015-01-01

    Chromatin Assembly Factor I (CAF-I) plays a key role in the replication-coupled assembly of nucleosomes. It is expected that its function is linked to the regulation of the cell cycle, but little detail is available. Current models suggest that CAF-I is recruited to replication forks and to chromatin via an interaction between its Cac1p subunit and the replication sliding clamp, PCNA, and that this interaction is stimulated by the kinase CDC7. Here we show that another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S phase and regulates its association with chromatin, but not its association with PCNA. Mutations in the Cac1p-phosphorylation sites of CDC28 but not of CDC7 substantially reduce the in vivo phosphorylation of Cac1p. However, mutations in the putative CDC7 target sites on Cac1p reduce its stability. The association of CAF-I with chromatin is impaired in a cdc28-1 mutant and to a lesser extent in a cdc7-1 mutant. In addition, mutations in the Cac1p-phosphorylation sites by both CDC28 and CDC7 reduce gene silencing at the telomeres. We propose that this phosphorylation represents a regulatory step in the recruitment of CAF-I to chromatin in early S phase that is distinct from the association of CAF-I with PCNA. Hence, we implicate CDC28 in the regulation of chromatin reassembly during DNA replication. These findings provide novel mechanistic insights on the links between cell-cycle regulation, DNA replication and chromatin reassembly.

  20. CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor i with chromatin

    PubMed Central

    Jeffery, Daniel CB; Kakusho, Naoko; You, Zhiying; Gharib, Marlene; Wyse, Brandon; Drury, Erin; Weinreich, Michael; Thibault, Pierre; Verreault, Alain; Masai, Hisao; Yankulov, Krassimir

    2015-01-01

    Chromatin Assembly Factor I (CAF-I) plays a key role in the replication-coupled assembly of nucleosomes. It is expected that its function is linked to the regulation of the cell cycle, but little detail is available. Current models suggest that CAF-I is recruited to replication forks and to chromatin via an interaction between its Cac1p subunit and the replication sliding clamp, PCNA, and that this interaction is stimulated by the kinase CDC7. Here we show that another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S phase and regulates its association with chromatin, but not its association with PCNA. Mutations in the Cac1p-phosphorylation sites of CDC28 but not of CDC7 substantially reduce the in vivo phosphorylation of Cac1p. However, mutations in the putative CDC7 target sites on Cac1p reduce its stability. The association of CAF-I with chromatin is impaired in a cdc28–1 mutant and to a lesser extent in a cdc7–1 mutant. In addition, mutations in the Cac1p-phosphorylation sites by both CDC28 and CDC7 reduce gene silencing at the telomeres. We propose that this phosphorylation represents a regulatory step in the recruitment of CAF-I to chromatin in early S phase that is distinct from the association of CAF-I with PCNA. Hence, we implicate CDC28 in the regulation of chromatin reassembly during DNA replication. These findings provide novel mechanistic insights on the links between cell-cycle regulation, DNA replication and chromatin reassembly. PMID:25602519

  1. Intestinal Anastomosis by Use of a Memory-shaped Compression Anastomosis Clip (Hand CAC 30): Early Clinical Experience.

    PubMed

    Lee, Hak-Youn; Woo, Jin-Hee; Park, Si-Young; Kang, Nam-Wook; Park, Ki-Jae; Choi, Hong-Jo

    2012-04-01

    The safety and the efficacy of the compression anastomosis clip (Hand CAC 30) have been demonstrated by animal studies. This study was designed to evaluate the clinical validity of the Hand CAC 30 in enterocolic side-to-side anastomosis after colonic or enteric resections. A non-randomized prospective data collection was performed for patients undergoing a side-to-side anastomosis using the Hand CAC 30. Eligibility criteria for the use of the Hand CAC 30 were for anastomoses between the colon and the ileum or between two small bowels. The primary short-term endpoint was the rate of anastomotic leakage. Other clinical outcomes, including intra- and postoperative complications, length of operation time and hospital stay, and the clip elimination time were recorded. A total of 63 patients (male, 36) underwent an enteric or right-sided colonic resection followed by a side-to-side anastomosis using the Hand CAC 30. Laparoscopic surgery was performed in 36 patients, in whom one patient who underwent a laparoscopic right hemicolectomy was converted to an open procedure (1/32, 3.1%). One patient with ascending colon cancer showed postoperative anastomotic leakage and died of co-morbid ischemic heart disease. There were no other surgical mortalities. The exact date of expulsion of the clip could not be recorded because most patients were not aware of clip elimination. No patients manifested clinical symptoms of anastomotic stricture. Short-term evaluation of the Hand CAC 30 anastomosis in patients undergoing enterocolic surgery proved it to be a safe and efficacious alternative to the standard hand-sewn or stapling technique.

  2. Thresholds of allergenic proteins in foods

    SciTech Connect

    Hourihane, Jonathan O'B. . E-mail: J.Hourihane@soton.ac.uk; Knulst, Andre C.

    2005-09-01

    Threshold doses or Estimated Eliciting Doses (EEDs) represent an important new field of research in food allergy. Clinicians and regulators have embraced some toxicological concepts such as LOAEL and NOAEL and applied them to an area of significant clinical uncertainty and interest. The impact of intrinsic human factors (e.g., asthma and exercise) and extrinsic event factors (e.g., season, location and especially dose of allergen) on a future allergic reaction in the community needs to be considered carefully when interpreting results of clinical and research low-dose food challenges. The ongoing cooperation of food allergy research groups in medicine, food science and government will surely deliver results of the highest importance to the wider communities of allergology, food science and technology and the increasing number of allergic consumers.

  3. Shotcrete -- Understanding of the hydration process of mixes containing CAC and Portland cement and proposal for a simple rheological characterization

    SciTech Connect

    Bayoux, J.P.; Testud, M.; Guinot, D.; Willocq, J.; Capmas, A.

    1995-12-31

    In order to better understand the performances of CAC-slag cement and CAC--PC cement the hydration study of these mixes was undertaken. The hydrates which are responsible for the early stiffening/strengthening are identical in both mixes; it is only the time of appearance and amount which varies. Ettringite always forms first followed by the precipitation of C{sub 4}AH{sub 13}. They will both form faster then the temperature rises. As a complement, a simple laboratory equipment is proposed to characterize the stiffening behavior of the mixes straight after gauging.

  4. Allergy after ingestion or inhalation of cereals involves similar allergens in different ages.

    PubMed

    Armentia, A; Rodríguez, R; Callejo, A; Martín-Esteban, M; Martín-Santos, J-M; Salcedo, G; Pascual, C; Sánchez-Monge, R; Pardo, M

    2002-08-01

    Cereals are among the major foods that account for food hypersensitivity reactions. Salt-soluble proteins appear to be the most important allergens contributing to the asthmatic response. In contrast, very limited information is available regarding cereal allergens responsible for allergic reactions after ingestion of cereal proteins. The aim of this study was to evaluate the allergenic reactivity of ingested and inhaled cereal allergens in different ages, in order to investigate if the response to different allergens would depend on the sensitization route. We included 66 patients in three groups. Group 1: 40 children aged 3 to 6 months who suffered from diarrhoea, vomiting, eczema or weight loss after the introduction of cereal formula in their diet and in which a possibility of coeliac disease was discarded. Group 2: 18 adults with food allergy due to cereals tested by prick tests, specific IgE and food challenge. Group 3: eight patients previously diagnosed as having baker's asthma. Sera pool samples were collected from each group of patients and IgE immunoblotting was performed. We found an important sensitization to cereal in the 40 children. The most important allergens were wheat followed by barley and rye. Among the adults with cereal allergy, sensitization to other allergens was common, especially to Lolium perenne (rye grass) pollen. Immunoblotting showed similar allergenic detection in the three groups. Clinically significant reactivity to cereal may be observed in early life. Inhalation and ingestion routes causing cereal allergy seem to involve similar allergens. The diet control was more effective in children. The possibility of cereal allergy after the introduction of cereal formula during the lactation period should not be underestimated.

  5. [Allergenic activity of mites of the genus Dermatophagoides].

    PubMed

    Berzhets, V M; Petrova, N S; Sinitsyna, N E; Emel'ianova, O Iu; Kanchurin, A Kh

    1987-04-01

    The allergenic activities of the laboratory batches of D. farinae allergens have been studied by the methods of indirect mast-cell degranulation, neuroglial cytocrit, electrophoretic mobility changes. D. farinae allergens have been shown to possess specific activity. The method of changes in the electrophoretic mobility of sheep red blood cells has demonstrated that D. pteronyssimus and D. farinae allergens possess common allergenic properties.

  6. Vitamin E prevents NRF2 suppression by allergens in asthmatic alveolar macrophages in vivo.

    PubMed

    Dworski, Ryszard; Han, Wei; Blackwell, Timothy S; Hoskins, Aimee; Freeman, Michael L

    2011-07-15

    Asthma is a chronic inflammatory airway disease associated with increased generation of reactive oxidant species and disturbed antioxidant defenses. NRF2 is the master transcription factor that regulates the expression of Phase II antioxidant and detoxifying enzymes. Disruption of NRF2 augments oxidative stress and inflammation in a mouse model of asthma, suggesting a protective role for NRF2 in the lungs in vivo. Yet, little is known about the regulation and function of NRF2 in human asthmatics. Using segmental allergen challenge, a well-established experimental model of IgE-mediated asthma exacerbation in human atopic asthmatics, we investigated the effects of a specific allergen and the modulatory role of vitamin E on NRF2 and a NRF2-target gene, superoxide dismutase, in alveolar macrophages recovered from the airways at 24h after allergen instillation in vivo. Allergen-provoked airway inflammation in sensitive asthmatics caused a profound inhibition of macrophage NRF2 activity and superoxide dismutase, rendering them incapable of responding to the NRF2 inducers. Prolonged treatment with high doses of the antioxidant vitamin E lessened this allergen-induced drop in alveolar macrophage NRF2. These results are the first to demonstrate that NRF2 expression in human asthmatics is compromised upon allergen challenge but can be rescued by vitamin E in vivo.

  7. On the source of stochastic volatility: Evidence from CAC40 index options during the subprime crisis

    NASA Astrophysics Data System (ADS)

    Slim, Skander

    2016-12-01

    This paper investigates the performance of time-changed Lévy processes with distinct sources of return volatility variation for modeling cross-sectional option prices on the CAC40 index during the subprime crisis. Specifically, we propose a multi-factor stochastic volatility model: one factor captures the diffusion component dynamics and two factors capture positive and negative jump variations. In-sample and out-of-sample tests show that our full-fledged model significantly outperforms nested lower-dimensional specifications. We find that all three sources of return volatility variation, with different persistence, are needed to properly account for market pricing dynamics across moneyness, maturity and volatility level. Besides, the model estimation reveals negative risk premium for both diffusive volatility and downward jump intensity whereas a positive risk premium is found to be attributed to upward jump intensity.

  8. Charge density waves in the graphene sheets of the superconductor CaC(6).

    PubMed

    Rahnejat, K C; Howard, C A; Shuttleworth, N E; Schofield, S R; Iwaya, K; Hirjibehedin, C F; Renner, Ch; Aeppli, G; Ellerby, M

    2011-11-29

    Graphitic systems have an electronic structure that can be readily manipulated through electrostatic or chemical doping, resulting in a rich variety of electronic ground states. Here we report the first observation and characterization of electronic stripes in the highly electron-doped graphitic superconductor, CaC(6), by scanning tunnelling microscopy and spectroscopy. The stripes correspond to a charge density wave with a period three times that of the Ca superlattice. Although the positions of the Ca intercalants are modulated, no displacements of the carbon lattice are detected, indicating that the graphene sheets host the ideal charge density wave. This provides an exceptionally simple material-graphene-as a starting point for understanding the relation between stripes and superconductivity. Furthermore, our experiments suggest a strategy to search for superconductivity in graphene, namely in the vicinity of striped 'Wigner crystal' phases, where some of the electrons crystallize to form a superlattice.

  9. Isotropic and anisotropic description of superconducting state in CaC6 compound

    NASA Astrophysics Data System (ADS)

    Szczȩśniak, R.; Drzazga, E. A.; Szczȩśniak, D.

    2015-02-01

    The thermodynamic parameters of the superconducting state in CaC6 have been determined in the framework of the isotropic and anisotropic Eliashberg formalism. The obtained results determine the anisotropy effect on the values of the thermodynamic functions. In particular, it has been found that the anisotropy of the electron-phonon coupling constant and the Coulomb pseudopotential significantly affects the order parameter and the wave function renormalization factor, which determines the electron effective mass. These results mean that anisotropy should be also visible in the total normalized density of states. In the case of the thermodynamic critical field, anisotropy lowers its value in the low-temperature area. On the other hand, it does not affect the specific heat jump at the critical temperature.

  10. Food Allergens: Is There a Correlation between Stability to Digestion and Allergenicity?

    PubMed

    Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard

    2016-07-03

    Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. It has not yet been established what makes a dietary protein a food allergen. Several characteristics have been proposed to be shared by food allergens. One of these is resistance to digestion. This paper reviews data from digestibility studies on purified food allergens and evaluates the predictive value of digestibility tests on the allergenic potential. We point out that food allergens do not necessarily resist digestion. We discuss how the choice of in vitro digestibility assay condition and the method used for detection of residual intact protein as well as fragments hereof may greatly influence the outcome as well as the interpretation of results. The finding that digests from food allergens may retain allergenicity, stresses the importance of using immunological assays for evaluating the allergenic potential of food allergen digestion products. Studies assessing the allergenicity of digestion products, by either IgE-binding, elicitation or sensitizing capacity, shows that digestion may abolish, decrease, have no effect, or even increase the allergenicity of food allergens. Therefore, the predictive value of the pepsin resistance test for assessing the allergenic potential of novel proteins can be questioned.

  11. Production of recombinant allergens in plants

    PubMed Central

    2010-01-01

    A large percentage of allergenic proteins are of plant origin. Hence, plant-based expression systems are considered ideal for the recombinant production of certain allergens. First attempts to establish production of plant-derived allergens in plants focused on transient expression in Nicotiana benthamiana infected with recombinant viral vectors. Accordingly, allergens from birch and mugwort pollen, as well as from apple have been expressed in plants. Production of house dust mite allergens has been achieved by Agrobacterium-mediated transformation of tobacco plants. Beside the use of plants as production systems, other approaches have focused on the development of edible vaccines expressing allergens or epitopes thereof, which bypasses the need of allergen purification. The potential of this approach has been convincingly demonstrated for transgenic rice seeds expressing seven dominant human T cell epitopes derived from Japanese cedar pollen allergens. Parallel to efforts in developing recombinant-based diagnostic and therapeutic reagents, different gene-silencing approaches have been used to decrease the expression of allergenic proteins in allergen sources. In this way hypoallergenic ryegrass, soybean, rice, apple, and tomato were developed. PMID:21258627

  12. Indoor allergen exposure and asthma outcomes

    PubMed Central

    Sheehan, William J.; Phipatanakul, Wanda

    2016-01-01

    Purpose of review The aim of the present review is to discuss updates on research regarding the relationship between indoor allergen exposure and childhood asthma with a focus on clinical effects, locations of exposure, and novel treatments. Recent findings Recent data continue to demonstrate that early life sensitization to indoor allergens is a predictor of asthma development later in life. Furthermore, avoidance of exposure to these allergens continues to be important especially given that the vast majority of children with asthma are sensitized to at least one indoor allergen. New research suggests that mouse allergen, more so than cockroach allergen, may be the most relevant urban allergen. Recent evidence reminds us that children are exposed to clinically important levels of indoor allergens in locations away from their home, such as schools and daycare centers. Exposure to increased levels of indoor mold in childhood has been associated with asthma development and exacerbation of current asthma; however, emerging evidence suggests that early exposure to higher fungal diversity may actually be protective for asthma development. Novel treatments have been developed that target TH2 pathways thus decreasing asthmatic responses to allergens. These therapies show promise for the treatment of severe allergic asthma refractory to avoidance strategies and standard therapies. Summary Understanding the relationship between indoor allergens and asthma outcomes is a constantly evolving study of timing, location, and amount of exposure. PMID:27653703

  13. Impact of thermal processing on legume allergens.

    PubMed

    Verma, Alok Kumar; Kumar, Sandeep; Das, Mukul; Dwivedi, Premendra D

    2012-12-01

    Food induced allergic manifestations are reported from several parts of the world. Food proteins exert their allergenic potential by absorption through the gastrointestinal tract and can even induce life threatening anaphylaxis reactions. Among all food allergens, legume allergens play an important role in induction of allergy because legumes are a major source of protein for vegetarians. Most of the legumes are cooked either by boiling, roasting or frying before consumption, which can be considered a form of thermal treatment. Thermal processing may also include autoclaving, microwave heating, blanching, pasteurization, canning, or steaming. Thermal processing of legumes may reduce, eliminate or enhance the allergenic potential of a respective legume. In most of the cases, minimization of allergenic potential on thermal treatment has generally been reported. Thus, thermal processing can be considered an important tool by indirectly prevent allergenicity in susceptible individuals, thereby reducing treatment costs and reducing industry/office/school absence in case of working population/school going children. The present review attempts to explore various possibilities of reducing or eliminating allergenicity of leguminous food using different methods of thermal processing. Further, this review summarizes different methods of food processing, major legumes and their predominant allergenic proteins, thermal treatment and its relation with antigenicity, effect of thermal processing on legume allergens; also suggests a path that may be taken for future research to reduce the allergenicity using conventional/nonconventional methods.

  14. SVM-Based CAC System for B-Mode Kidney Ultrasound Images.

    PubMed

    Subramanya, M B; Kumar, Vinod; Mukherjee, Shaktidev; Saini, Manju

    2015-08-01

    The present study proposes a computer-aided classification (CAC) system for three kidney classes, viz. normal, medical renal disease (MRD) and cyst using B-mode ultrasound images. Thirty-five B-mode kidney ultrasound images consisting of 11 normal images, 8 MRD images and 16 cyst images have been used. Regions of interest (ROIs) have been marked by the radiologist from the parenchyma region of the kidney in case of normal and MRD cases and from regions inside lesions for cyst cases. To evaluate the contribution of texture features extracted from de-speckled images for the classification task, original images have been pre-processed by eight de-speckling methods. Six categories of texture features are extracted. One-against-one multi-class support vector machine (SVM) classifier has been used for the present work. Based on overall classification accuracy (OCA), features from ROIs of original images are concatenated with the features from ROIs of pre-processed images. On the basis of OCA, few feature sets are considered for feature selection. Differential evolution feature selection (DEFS) has been used to select optimal features for the classification task. DEFS process is repeated 30 times to obtain 30 subsets. Run-length matrix features from ROIs of images pre-processed by Lee's sigma concatenated with that of enhanced Lee method have resulted in an average accuracy (in %) and standard deviation of 86.3 ± 1.6. The results obtained in the study indicate that the performance of the proposed CAC system is promising, and it can be used by the radiologists in routine clinical practice for the classification of renal diseases.

  15. [Exposition and sensitisation to indoor allergens, house dust mite allergen and cat allergens].

    PubMed

    Jovanovic, S; Felder-Kennel, A; Gabrio, T; Kouros, B; Link, B; Maisner, V; Piechotowski, I; Schick, K-H; Schrimpf, M; Schwenk, M; Weidner, U; Zöllner, I

    2003-07-01

    The study examined the exposure to biological indoor air agents and their possible role for allergies and respiratory tract illnesses of children. It was conducted as a case control study (atopic vs non-atopic children) at the four surveillance public health departments in Baden-Württemberg in the winter season 1999/2000 and included 379 children of the fourth class. The concentrations of the house dust mite antigens Der F1, Der p1, and Der Gr2 as well as cat allergen Fel d1 were determined in the children's bedrooms on the ground and in the mattress. Specific IgE-antibodies against allergens from house dust, mites and cat were determined in the serum of the children. For mite allergens the following medians ( micro g/g) were estimated in floor dust: Der p1 = 0.6, Der f1 = 2.3, Gr2 = 0.1; in mattresses: Der p1 = 1.2, Der f1 = 3.4, Gr2 = 0.3. The median of Fel d1 in floor dust was 0.2 microg/g, in mattresses 0.1 microg/g. Sensitisation to dust mite allergen was found to be more prevalent than sensitisation to cat. The distribution of sensitisation among the cases and controls is different. Among the cases, more subjects were sensitised to dust mites (32.9 %) and cat (13.1 %). Among the controls, 17.1 % were sensitised to dust mites and 4.1 % to cat. The results showed no direct association between the prevalence of allergies or respiratory tract illnesses and the indoor concentrations of the allergens. Possible reasons for these findings are discussed.

  16. Orthologous Allergens and Diagnostic Utility of Major Allergen Alt a 1

    PubMed Central

    Moreno, Antonio; Alcover, Javier; Rodríguez, David; Palacios, Ricardo; Martínez-Naves, Eduardo

    2016-01-01

    Purpose Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi. The type of indoor fungi related to asthma/allergy varies according to geographic, climatic, and seasonal factors, making their study difficult. The aim of this study was to determine hypersensitivity to indoor fungi in a population from Cuenca, Spain. Methods Thirty-five patients with symptoms compatible with rhinitis or asthma who showed clear worsening of their symptoms in their homes or workplace were included. In vivo and in vitro tests were made with a battery of fungal allergens, including the species isolated in the home or workplace. Results Ulocladium botrytis (U. botrytis) and A. alternata were the most representative species as a source of home sensitization. These species showed very high concordance in skin tests, specific IgE, and histamine release. The allergen Alt a 1, which was recognized in all patients, was detected in A. alternata, U. botrytis, and Stemphylium botryosum (S. botryosum). Conclusions U. botrytis and A. alternata were the most representative species as a source of home sensitization. Alt a 1 was recognized in all patients and may be considered a non-species-specific allergen that could be used as a diagnostic source of sensitization to some species of the Pleosporaceae family. PMID:27334781

  17. Molecular Diagnosis of Shrimp Allergy: Efficiency of Several Allergens to Predict Clinical Reactivity.

    PubMed

    Pascal, Mariona; Grishina, Galina; Yang, Ariana C; Sánchez-García, Silvia; Lin, Jing; Towle, David; Ibañez, Maria Dolores; Sastre, Joaquín; Sampson, Hugh A; Ayuso, Rosalia

    2015-01-01

    The diagnosis of shellfish allergy remains a challenge for clinicians. Several shellfish allergens have been characterized and their IgE epitopes identified. However, the clinical relevance of this sensitization is still not clear. The objective of this study was to identify allergens and epitopes associated with clinical reactivity to shrimp. Shrimp-sensitized subjects were recruited and grouped based on the history of shrimp-allergic reactions and challenge outcome. IgE reactivity to recombinant crustacean allergens, and IgE and IgG4 reactivity to peptides were determined. Subjects sensitized to dust mites and/or cockroach without shrimp sensitization or reported allergic reactions, as well as nonatopic individuals, were used as controls. A total of 86 subjects were recruited with a skin prick test to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16 were tolerant. All subjects without a history of reactions had negative challenges. The individuals with a positive challenge more frequently recognized tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test is very likely to result in a positive challenge, though the frequency of recognition is low. Subjects with dust mite and/or cockroach allergy not sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes of these allergens may be important in predicting clinical reactivity. Tropomyosin and sarcoplasmic-calcium-binding-protein sensitization is associated with clinical reactivity to shrimp. Myosin light chain testing may help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin appear to be cross-reacting allergens between shrimp and arthropods. Detection of IgE to these allergens and some of their epitopes may be better diagnostic tools in the routine workup

  18. Allergenicity and allergens of amphipods found in nori (dried laver).

    PubMed

    Motoyama, Kanna; Hamada, Yuki; Nagashima, Yuji; Shiomi, Kazuo

    2007-09-01

    Gammaridean and caprellid amphipods, crustaceans of the order Amphipoda, inhabit laver culture platforms and, hence, are occasionally found in nori (dried laver) sheets. Amphipods mixed in nori may cause allergic reactions in sensitized patients, as is the case with other crustaceans, such as shrimp and crab, members of the order Decapoda. In this study, dried samples of amphipods (unidentified) found in nori and fresh samples of gammaridean amphipod (Gammarus sp., not accurately identified) and caprellid amphipod (Caprella equilibra) were examined for allergenicity and allergens using two species of decapods (black tiger prawn and spiny lobster) as references. When analyzed by ELISA, sera from crustacean-allergic patients reacted to extracts from amphipod samples, although less potently than to the extracts from decapods. In IgE-immunoblotting, a 37-kDa protein was found to be the major allergen in amphipods. Based on the molecular mass and the cross-reactivity with decapod tropomyosin evidenced by inhibition ELISA and inhibition immunoblotting, the 37-kDa protein was identified as amphipod tropomyosin.

  19. Bystander immunotherapy as a strategy to control allergen-driven airway inflammation

    PubMed Central

    Navarro, Séverine; Lazzari, Anne; Kanda, Akira; Fleury, Sébastien; Dombrowicz, David; Glaichenhaus, Nicolas; Julia, Valérie

    2015-01-01

    Background Allergic asthma is a chronic inflammatory disease that is characterized by airway hyper responsiveness (AHR), infiltration of Th2 cells in lungs and high levels of circulating IgE. Allergen-specific immunotherapy (SIT), in which patients are rendered tolerant by exposure to steadily increasing doses of the allergen, is the only curative treatment to date. Unfortunately, SIT is not suitable for treating multi-sensitized patients, and some allergens are too immunogenic to be used in desensitization protocols. Objective To investigate whether, and to understand how, regulatory CD4+ T cells (Treg) specific for a third-party “drug” antigen could control allergic immune responses and lung inflammation. Methods Mice were tolerized to ovalbumin (OVA), sensitized to ragweed, and eventually challenged with aerosols of ragweed alone or ragweed and OVA together. Animals were then monitored for cardinal features of allergic asthma including AHR and infiltration of Th2 cells in lungs. In additional experiments aimed at elucidating the mechanisms of OVA-induced suppression, OVA-tolerized mice were sensitized with the LACK model antigen, challenged with LACK alone or LACK and OVA together, and LACK-specific T cells were visualized by flow cytometry. Results In both the ragweed and the LACK model, allergen-induced airway inflammation and AHR were strongly reduced in mice challenged with both the allergen and OVA compared to mice challenged with the allergen alone. OVA-induced protection did not result from competition between OVA and the allergen, was mediated by OVA-specific CD25+ Treg, required both CTLA-4 and ICOS signaling, and was partially dependent on IL-10. Bystander suppression was associated with reduced proliferation of allergen-specific Th2 cells and decreased numbers of airway DC migrating to the lungs. Conclusion Our results demonstrate that Treg specific for a third-party drug antigen could control allergic immune responses and lung inflammation when

  20. The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones

    PubMed Central

    Liu, Wallace H; Roemer, Sarah C; Zhou, Yeyun; Shen, Zih-Jie; Dennehey, Briana K; Balsbaugh, Jeremy L; Liddle, Jennifer C; Nemkov, Travis; Ahn, Natalie G; Hansen, Kirk C; Tyler, Jessica K; Churchill, Mair EA

    2016-01-01

    The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone not only binds H3/H4 with high affinity, but also promotes histone tetramerization independent of the other subunits. Moreover, we identify a minimal region in the C-terminus of Cac1, including the structured winged helix domain and glutamate/aspartate-rich domain, which is sufficient to induce (H3/H4)2 tetramerization. These findings reveal a key role of Cac1 in histone tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic replication. DOI: http://dx.doi.org/10.7554/eLife.18023.001 PMID:27690308

  1. A theoretical study on the structural and physical properties of the ground-state CaC

    NASA Astrophysics Data System (ADS)

    Qian, Yan; Wu, Haiping; Kan, Erjun; Lu, Ruifeng; Tan, Weishi; Deng, Kaiming

    2015-02-01

    Because of no experimental report on the half-metallic CaC theoretically found by Gao et al. in 2007, it is necessary to explore the nature of this fact, and the reason is revealed via density-functional theory study in this work. By a particle swarm structural search firstly, several CaC allotropes are found, including the half-metallic one with F-43m space group. Among the found compounds, six allotropes have the negative formation energies with Ccma, P4/mmm, Immm, Cm (8), Pmm2, and Cmmm space groups while the half-metallic one has positive formation energy of 2.67 eV. Furthermore, through the study on the dynamical properties of these six thermally stable CaC allotropes, only the one with P4/mmm symmetry exhibits dynamical stability. Based on the above fact, CaC with P4/mmm symmetry, instead of the F-43m one, perhaps can be experimentally synthesized due to both the thermodynamic and dynamically stabilities.

  2. Indoor Allergens and Allergic Respiratory Disease

    PubMed Central

    Chapman, Martin D.; Wünschmann, Sabina

    2016-01-01

    Purpose of review The purpose of this review is to evaluate the most recent findings on indoor allergens and their impact on allergic diseases. Recent findings Indoor allergens are present inside buildings (home, work environment, school), and given the chronic nature of the exposures, indoor allergies tend to be associated with the development of asthma. The most common indoor allergens are derived from dust mites, cockroaches, mammals (including wild rodents and pets), and fungi. The advent of molecular biology and proteomics has led to the identification, cloning, and expression of new indoor allergens, which have facilitated research to elucidate their role in allergic diseases. This review is an update on new allergens and their molecular features, together with the most recent reports on their avoidance for allergy prevention and their use for diagnosis and treatment. Summary Research progress on indoor allergens will result in the development of new diagnostic tools and design of coherent strategies for immunotherapy. PMID:27184001

  3. [Allergens causing respiratory allergy: the aeroallergens].

    PubMed

    Deschildre, A

    1999-01-01

    Aeroallergens play a major role in the pathogenesis of allergic diseases, particularly asthma and rhinitis. Indoor allergens, including house dust mites, domestic pets, cockroaches, and molds are of particular importance. Pollens are also recognized as a major source of allergens. The role of these different allergens varies with environment conditions, such as climatic factors, and degree of exposure. Knowledge about allergens has progressed, especially with recent molecular biology studies. Structure and function have been identified. These studies have provided explanations about the relationship between allergic sensitization, allergen exposure, and disease activity, about clinical observations such as allergic cross reactions, and improvement in the production of allergenic extracts (necessary to diagnosis and immunotherapy). Environmental control measures are of particular importance in the prevention and management of allergic diseases.

  4. Indoor Allergens and Allergic Respiratory Disease.

    PubMed

    Pomés, Anna; Chapman, Martin D; Wünschmann, Sabina

    2016-06-01

    The purpose of this review is to evaluate the most recent findings on indoor allergens and their impact on allergic diseases. Indoor allergens are present inside buildings (home, work environment, school), and given the chronic nature of the exposures, indoor allergies tend to be associated with the development of asthma. The most common indoor allergens are derived from dust mites, cockroaches, mammals (including wild rodents and pets), and fungi. The advent of molecular biology and proteomics has led to the identification, cloning, and expression of new indoor allergens, which have facilitated research to elucidate their role in allergic diseases. This review is an update on new allergens and their molecular features, together with the most recent reports on their avoidance for allergy prevention and their use for diagnosis and treatment. Research progress on indoor allergens will result in the development of new diagnostic tools and design of coherent strategies for immunotherapy.

  5. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    PubMed

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome.

  6. Food Allergens in Mattress Dust in Norwegian Homes - A Potentially Important Source of Allergen Exposure

    PubMed Central

    Bertelsen, Randi J.; Fæste, Christiane K.; Granum, Berit; Egaas, Eliann; London, Stephanie J.; Carlsen, Kai-Håkon; Carlsen, Karin C. Lødrup; Løvik, Martinus

    2014-01-01

    Background Sensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment. Objective To describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13 year old adolescents, and secondly to identify home characteristics associated with the presence of food allergen contamination in dust. Methods Food allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analyzed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models. Results Fish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (<100m2) than larger dwellings (≥130 m2); 63-71% of the small dwellings (n=24) had milk, peanut, and fish allergens in the samples compared to 33-44% of the larger dwellings (n=95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors; with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens. Conclusions and clinical relevance Food allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spend in the bedroom, mattress dust may be an important source of exposure to food allergens. PMID:24304208

  7. Baseline survey on functioning of abortion services in government approved CAC centers in three pilot districts of Nepal.

    PubMed

    Karki, C; Ojha, M; Rayamajhi, R T

    Abortion has been legalized in Nepal since September 2002 and under this law, Comprehensive Abortion Care (CAC) service is being provided through listed service providers and listed health facilities from 2004. Nepal Government has prioritized the national safe abortion program and is working with many government and non government partners for providing this service. Till date medical abortion services are not made available at any of the health facility. Government is now preparing to introduce this service in six selected pilot districts. This survey was carried out to assess the functioning of existing abortion services in 12 Government approved CAC sites of three districts. Direct observation of the functioning of these centers, assessment of physical facilities and service provider's skill was done. At the same time service provider's attitude and knowledge on CAC service and other abortion services were also assessed through semi structured interviews. Quality of record keeping and the feasibility of initiating the medical abortion service in these sites were also studied. Number of listed centers in six pilot districts was twenty nine. Study districts have 16 listed centers. Visited sites were twelve; four managed by Government and eight by non government organizations. Thirty three thousand nine hundred and twenty women have availed this service so far: only 4.76% of them received service from Government facilities. Marie Stopes International (MSI) topped the list in providing service to the maximum number of clients (75.64%) and Family planning association of Nepal (FPAN) was the second. MSI centre was also first to initiate the service. Government facilities provide 24 hours service unlike private facilities which are open only up to 5.00 pm. Cost for the service varies from rupees 900/- to rupees 1365/- and is cheaper at Government facilities. Private sectors have separate setups and Government have allocated some space within their already existing

  8. Ankle-brachial index (ABI), abdominal aortic calcification (AAC), and coronary artery calcification (CAC): the Jackson heart study.

    PubMed

    Tullos, Bobby W; Sung, Jung Hye; Lee, Jae Eun; Criqui, Michael H; Mitchell, Marc E; Taylor, Herman A

    2013-04-01

    To examine the associations of peripheral atherosclerosis, assessed by the ABI at baseline with the extent of AAC and with CAC measured by MDCT at follow-up examination in the Jackson Heart Study cohort. Four categories of ABI: <0.90, 0.90-0.99, 1.00-1.39; >1.40. Presence of CAC/AAC was defined as scoring above the 75th percentile among participants with non-zero CT calcium scores. We conducted multivariable log-binomial models for this analysis examining the relationship between ABI and the presence of CAC or AAC using normal ABI (1.0 ≤ ABI ≤ 1.39) as the reference group. We estimated prevalence ratios adjusted for age, smoking, HTN, DM, BMI, LDL, HDL, CRP, systolic and diastolic blood pressure, and use of lipid-lowering medication. There were 2,398 patients in this analysis (women: 65 %, average age 55 years). AAC scores were not significantly different between sex. CAC scores were significantly higher in males than females regardless of ABI groups. The prevalence of significant AAC was 1.7 times higher for ABI < 0.90 (PR = 1.70; 95 % CI = 1.26-2.28; p = 0.0004) and 1.57 times higher for ABI 0.90-0.99 (PR = 1.57; 95 % CI = 1.20-2.03; p = 0.0008) than the normal ABI; AAC prevalence did not differ between subjects with ABI > 1.40 compared to those with normal ABI. The prevalence of the significant CAC was higher for ABI < 0.90 (PR = 1.55; 95 % CI = 1.12-2.14; p value = 0.0081) and ABI 0.90-0.99 (PR = 1.60; 95 % CI = 1.05-2.46; p = 0.0402) compared to normal ABI; CAC prevalence did not differ between subjects with ABI > 1.40 compared to those with normal ABI. Lower ABI was significantly associated with the extent of AAC and CAC in this cohort. ABI can provide clinicians with an inexpensive additional tool to assess vascular health and cardiovascular risk without exposing the patient to ionizing radiation.

  9. Ankle-Brachial Index (ABI), Abdominal Aortic Calcification (AAC), and Coronary Artery Calcification (CAC): the Jackson Heart Study

    PubMed Central

    Tullos, Bobby W.; Sung, Jung Hye; Lee, Jae Eun; Criqui, Michael H.; Mitchell, Marc E.; Taylor, Herman A.

    2013-01-01

    Introduction To examine the associations of peripheral atherosclerosis, assessed by the ABI at baseline with the extent of AAC and with CAC measured by MDCT at follow-up examination in the Jackson Heart Study cohort. Methods Four categories of ABI: <0.90, 0.90–0.99, 1.00–1.39; >1.40. Presence of CAC/AAC was defined as scoring above the 75th percentile among participants with non-zero CT calcium scores. We conducted multivariable log-binomial models for this analysis examining the relationship between ABI and the presence of CAC or AAC using normal ABI (1.0 ≤ ABI ≤ 1.39) as the reference group. We estimated prevalence ratios adjusted for age, smoking, HTN, DM, BMI, LDL, HDL, CRP, systolic and diastolic blood pressure, and use of lipid-lowering medication. Results There were 2,398 patients in this analysis (women: 65%, average age 55 years). AAC scores were not significantly different between sex. CAC scores were significantly higher in males than females regardless of ABI groups. The prevalence of significant AAC was 1.7 times higher for ABI < 0.90 (PR=1.70; 95% CI=1.26–2.28; p=0.0004) and 1.57 times higher for ABI 0.90–0.99 (PR=1.57; 95% CI=1.20–2.03; p=0.0008) than the normal ABI; AAC prevalence did not differ between subjects with ABI > 1.40 compared to those with normal ABI. The prevalence of the significant CAC was higher for ABI <0.90 (PR=1.55; 95% CI=1.12–2.14; p-value=0.0081) and ABI 0.90–0.99 (PR=1.60; 95% CI=1.05–2.46; p=0.0402) compared to normal ABI; CAC prevalence did not differ between subjects with ABI > 1.40 compared to those with normal ABI Conclusion Lower ABI was significantly associated with the extent of AAC and CAC in this cohort. ABI can provide clinicians with an inexpensive additional tool to assess vascular health and cardiovascular risk without exposing the patient to ionizing radiation. PMID:23111408

  10. Monoclonal antibodies against Olea europaea major allergen: allergenic activity of affinity-purified allergen and depleted extract and development of a radioimmunoassay for the quantitation of the allergen.

    PubMed

    Lombardero, M; Quirce, S; Duffort, O; Barber, D; Carpizo, J; Chamorro, M J; Lezaun, A; Carreira, J

    1992-04-01

    Several monoclonal antibodies (MAbs) were raised against Olea europaea pollen-extract components. Two of these antibodies, named OL 2 and OL 7, recognize two nonoverlapping, nonrepeating epitopes on the olive-allergen Ole e I, as demonstrated by different techniques. The allergen was purified in a single step by MAb-based affinity chromatography, and the allergen revealed a band at molecular weight 20 kd as well as a minor band at 18 kd on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The contribution of allergen Ole e I to the allergenic activity of O. europaea pollen extracts was determined from the effect of allergen depletion by affinity chromatography on skin reactivity and a histamine-release test. The removal of allergen caused a large reduction in the activity of the preparation in 25 monospecific olive-allergic patients. In agreement, the affinity-purified allergen demonstrated a similar response when it was compared with the whole extract in these assays. The results indicated that Ole e I is by far the most important olive-pollen allergen. A two-site solid-phase radioimmunoassay was developed for the quantitation of the allergen Ole e I in mass units. The assay was based on the MAbs, OL 2 and OL 7, and had a detection limit in the nanogram range. A good correlation was found between allergenic activity, as determined by RAST inhibition, and allergen content in 18 olive-pollen extracts. This result indicates that the assay can be a good alternative to RAST inhibition for the standardization of O. europaea extracts.

  11. Characterization of Allergen Exposure in Homes

    DTIC Science & Technology

    1991-01-17

    dust mixture.6 Dust mite allergens have been associated causatively with asthma, atopic dermatitis , and rhini- tis. 7 Studies from several countries...Asthma: A Controlled Trial. The Lancet 1976; ***:333-335. 10. Tuft L. Importance of Inhalant Allergens in Atopic Dermatitis . The Journal of Investigative...Monoclonal Antibodies to the Major Feline Allergen Fel d 1. 1I. Single Step Affinity Purification of Fel d 1, N-Terminal Sequence Analysis, and Development of

  12. Peanut Allergens Attached With p-Aminobenzamidine Are More Resistant to Digestion than Native Allergens

    USDA-ARS?s Scientific Manuscript database

    Undigested foods are excreted rather than absorbed and therefore, peanut allergens, if undigested, may not cause an allergic reaction in peanut-allergic individuals. Our objective was to make peanut allergens more resistant to digestion by preparing allergen conjugates and demonstrating that the con...

  13. Allergen Avoidance in Allergic Asthma

    PubMed Central

    Cipriani, Francesca; Calamelli, Elisabetta; Ricci, Giampaolo

    2017-01-01

    Allergic asthma is the most frequent disease among the chronic respiratory disorders in pediatric age with an important social impact. In the last years, many efforts have been made to identify effective preventive approaches to get a better control of symptoms and to obtain the best future outcomes for the patients. In patients with allergic asthma triggered by the exposure to indoor allergens, the avoidance is the first intervention to prevent the appearance or the worsening of bronchial symptoms. This review article summarized the most recent evidence from literature about the efficacy of specific control interventions for the most important allergens. Even if a wide spectrum of interventions has been suggested and may help to reduce exposure to trigger allergy for sensitized patients suffering from respiratory allergy, evidence supporting the efficacy of these approaches is still weak and subject of controversy. However, the exposure control to specific airborne allergens is still widely recommended and may be effective as part of a holistic approach to reduce the severity of allergic respiratory symptoms in sensitized individuals. PMID:28540285

  14. [Profilins: allergens with clinical relevance].

    PubMed

    Landa-Pineda, César Manuel; Guidos-Fogelbach, Guillermo; Marchat-Marchau, Laurence; López-Hidalgo, Marisol; Arroyo-Becerra, Analilia; Sandino Reyes-López, César Augusto

    2013-01-01

    Profilins are small ubiquitous proteins of 12-19 kDa involved in actin dynamics. These proteins are found in all eukaryotic organisms studied to date. Profilins have aminoacid sequences and tridimensional structure highly conserved. Allergy patients to pollen frequently have symptoms of allergy when ingestion of plant-derived foods like fruits, vegetables, seeds, among others. This phenomenon is known as latex-pollen-fruit allergy and it's the main cause of oral allergy syndrome (OAS) which is attributed to the cross-reactivity. Allergens shared between different sources theses are called panallergens for example are profilins which representing at least 20% of all pollen allergic patients. This cross-reactivity is results from the high amino acid sequence identity of profilin from plants, which is between 70% and 85%, this may explain the exacerbation symptoms of allergic patients to profilins from plants. We described some characteristics which show us the important participation of the profilins in the sensitization of people allergic, especially to plants, fruits and pollen. We looked research aminoacid sequences of all allergenic profilins reported to date and these were analyzed. Profilins are important allergens that are underrated in clinical practice and contribute to cross-reactivity in sensitized individuals by profilins from other sources.

  15. Enhanced approaches for identifying Amadori products: application to peanut allergens

    PubMed Central

    Johnson, Katina L.; Williams, Jason G.; Maleki, Soheila J.; Hurlburt, Barry K.; London, Robert E.; Mueller, Geoffrey A.

    2016-01-01

    The dry roasting of peanuts is suggested to influence allergenic sensitization due to formation of advanced glycation end products (AGE) on peanut proteins. Identifying AGEs is technically challenging. The AGEs of a peanut allergen were probed with nanoLC-ESI-MS and MS/MS analyses. Amadori product ions matched to expected peptides and yielded fragments that included a loss of 3 waters and HCHO. Due to the paucity of b- and y-ions in the MS/MS spectrum, standard search algorithms do not perform well. Reactions with isotopically labeled sugars confirmed that the peptides contained Amadori products. An algorithm was developed based upon information content (Shannon entropy) and the loss of water and HCHO. Results with test data show that the algorithm finds the correct spectra with high precision, reducing the time needed to manually inspect data. Computational and technical improvements allowed better identification of the chemical differences between modified and unmodified proteins. PMID:26811263

  16. Cockroach allergen exposure and risk of asthma.

    PubMed

    Do, D C; Zhao, Y; Gao, P

    2016-04-01

    Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins have provided a basis for studying the mechanisms regarding cockroach allergen-induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen-presenting cell (APC) function in T-cell polarization, and cytokine production. Environmental pollutants, which often coexist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergen-induced innate immune responses, and the genetic basis for cockroach sensitization.

  17. Cockroach Allergen Exposure and Risk of Asthma

    PubMed Central

    Do, Danh C.; Zhao, Yilin; Gao, Peisong

    2015-01-01

    Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins has provided a basis for studying the mechanisms regarding cockroach allergens induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen presenting cell (APC) function in T cell polarization, and cytokine production. Environmental pollutants, which often co-exist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergens induced innate immune responses, and the genetic basis for cockroach sensitization. PMID:26706467

  18. Chapter 1: an overview of allergens.

    PubMed

    Shah, Rachna; Grammer, Leslie C

    2012-01-01

    Most allergens are proteins or glycoproteins that range in molecular weight from 5000 to 100,000 Da, although polysaccharides and low molecular weight substances also may be allergenic. Common allergens include pollens, fungal spores, house-dust mites, and animal epithelial materials but can also include drugs, biological products, and insect venoms. The allergic response is dependent on the route of exposure. If exposure is to an inhaled aeroallergen, the allergic response will be a respiratory reaction in nature. Ingested or injected exposure gives rise to gastrointestinal, cutaneous, or anaphylactic reactions. Size of pollen determines clinical manifestation of allergy. For example, particles between 20 and 60 μm in diameter can be carried in the wind and cause nasal and ocular symptoms (allergic rhinoconjunctivitis). Particles <7 μm can deposit in the airways and cause symptoms of asthma. Animals produce allergens in forms unique to each species. Cat allergen, most importantly Fel d 1, is found mainly in cat saliva, sebaceous glands in the skin, and in urine of male cats. It is buoyant and "sticky," which means it easily remains airborne and may last in a home for up to 6-9 months after the source is removed. Cat allergen adheres to clothes and can be found in public places such as schools. Dog allergen, particularly Can f 1, is present in dander, saliva, urine, and serum. There are allergens specific to dog breeds, but all breeds produce allergenic proteins (even poodles and "hairless" dogs).

  19. Extraction and analysis of coffee bean allergens.

    PubMed

    Lehrer, S B; Karr, R M; Salvaggio, J E

    1978-05-01

    Workers in the coffee industry can develop occupational allergic disease upon exposure to dust associated with coffee manufacturing. Since controversy exists as to the source or chemical nature of these allergens, the mouse model of reaginic antibody production was used to assess the potential sources of allergens in samples obtained from a local coffee manufacturing plant. Mice were immunized with extracts of coffee dust and beans and the resulting reaginic antibody response determined by the passive cutaneous anaphylaxis reaction. Cross-reacting allergens were detected in samples of coffee dust, cleaner can debris and green coffee beans, but not in chaff or roasted coffee beans. None of the allergens detected in coffee samples cross-reacted with extract of castor beans, although these extracts contained the potent castor bean allergen. Green coffee bean allergens partially purified by gel filtration were heterogeneous with respect to molecular size, although quite similar in their reactivity with reaginic antiserum. These results suggest that the green coffee bean is the major source of allergen in coffee manufacturing plants. This allergen is heterogeneous with respect to size and heat lability, and is immunochemically different from the castor bean allergen.

  20. Effect of ozone exposure on airway responses to inhaled allergen in asthmatic subjects.

    PubMed

    Chen, Lisa L; Tager, Ira B; Peden, David B; Christian, Dorothy L; Ferrando, Ronald E; Welch, Barbara S; Balmes, John R

    2004-06-01

    Controlled human exposure studies have produced conflicting results regarding the effect of ozone on the early bronchoconstrictor response to inhaled allergen in specifically sensitized asthmatic subjects. Spirometric parameters do not necessarily reflect the airway inflammatory effects of inhaled ozone or allergen. This study was designed to investigate whether exposure to ozone enhances the late airway inflammatory response, as well as the early bronchoconstrictor response, to inhaled house dust mite allergen in sensitized asthmatic subjects. Randomized, counter-balanced, cross-over study. Human exposure laboratory. Fourteen subjects were exposed to 0.2 ppm O(3) or filtered air, on separate days, for 1 h during exercise. After each exposure, the subjects were challenged with doubling doses of Dermatophagoides farinae (DF) allergen (provocative concentration of DF causing a 15% decrease in FEV(1) [PC(15)]). At 6 h after allergen challenge, bronchoscopy with BAL, proximal airway lavage (PAL), and endobronchial biopsy were performed. The second exposure/allergen challenge/bronchoscopy sequence was performed at least 4 weeks after the first sequence. No significant difference in cellular or biochemical markers of the late inflammatory response after allergen was found between the ozone and air exposures (although a trend toward increased neutrophils was noted after ozone exposure in the PAL fluid, p = 0.06). For the group as a whole, no significant difference in PC(15) was demonstrated after ozone exposure compared to air exposure. However, subjects with the greatest ozone-induced decrements in FEV(1) tended to have lower PC(15) values after ozone exposure. Exposure to a relatively low-level concentration of ozone does not enhance the late inflammatory or early bronchoconstrictor response to inhaled antigen in most allergic asthmatic subjects. Our results do suggest, however, that a subgroup of asthmatics may acquire increased sensitivity to aeroallergens after

  1. Treatment with grass allergen peptides improves symptoms of grass pollen-induced allergic rhinoconjunctivitis.

    PubMed

    Ellis, Anne K; Frankish, Charles W; O'Hehir, Robyn E; Armstrong, Kristen; Steacy, Lisa; Larché, Mark; Hafner, Roderick P

    2017-08-01

    Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC. We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively; P = .0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P = .0403) in patients with more symptomatic ARC. No safety signals were detected. Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  2. Novel mechanisms in immune tolerance to allergens during natural allergen exposure and allergen-specific immunotherapy.

    PubMed

    van de Veen, Willem; Wirz, Oliver F; Globinska, Anna; Akdis, Mübeccel

    2017-09-06

    Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a clinical tolerance-inducing and immune tolerance-inducing therapy for allergic diseases and represents a potentially curative method of treatment. AIT functions through multiple mechanisms including early desensitization of basophils and mast cells, regulating T-cell and B-cell responses, changing antibody isotypes, and decreasing activation, mediator release and affected tissue migration of eosinophils, basophils, and mast cells. Similar molecular and cellular mechanisms have been observed in subcutaneous AIT, sublingual AIT and peptide immunotherapy as well as natural tolerance to high doses of allergen exposure in beekeepers and cat owners. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Summary of the ACS symposium on Advances in Food Allergen Detection.

    PubMed

    Ross, Mark M; Jackson, Lauren

    2013-06-19

    A symposium titled "Advances in Food Allergen Detection" was held at the 243rd National Meeting of the American Chemical Society (ACS) in March 2012 in San Diego, CA, and was sponsored by the ACS Division of Agricultural and Food Chemistry. The purpose of the symposium was to convene the leaders in the food allergen analysis field for presentations on, and discussions of, the state of the art, new developments, and critical challenges in the detection and quantitation of allergenic proteins in foods. Twenty-five presentations were delivered by speakers representing academic, government, and industrial institutions in 10 countries. The presentations covered all aspects of food allergens, including a historical progress review, regulatory policies, clinical practices, food-processing effects, food production equipment cross-contamination and cleaning, and the performance of several food allergen analytical strategies and technologies. This paper is intended to provide a brief summary of the presentations as well as a record of the proceedings of the symposium, which was deemed a great success in advancing food allergen analysis.

  4. Electrochemical Affinity Biosensors Based on Disposable Screen-Printed Electrodes for Detection of Food Allergens

    PubMed Central

    Vasilescu, Alina; Nunes, Gilvanda; Hayat, Akhtar; Latif, Usman; Marty, Jean-Louis

    2016-01-01

    Food allergens are proteins from nuts and tree nuts, fish, shellfish, wheat, soy, eggs or milk which trigger severe adverse reactions in the human body, involving IgE-type antibodies. Sensitive detection of allergens in a large variety of food matrices has become increasingly important considering the emergence of functional foods and new food manufacturing technologies. For example, proteins such as casein from milk or lysozyme and ovalbumin from eggs are sometimes used as fining agents in the wine industry. Nonetheless, allergen detection in processed foods is a challenging endeavor, as allergen proteins are degraded during food processing steps involving heating or fermentation. Detection of food allergens was primarily achieved via Enzyme-Linked Immuno Assay (ELISA) or by chromatographic methods. With the advent of biosensors, electrochemical affinity-based biosensors such as those incorporating antibodies and aptamers as biorecognition elements were also reported in the literature. In this review paper, we highlight the success achieved in the design of electrochemical affinity biosensors based on disposable screen-printed electrodes towards detection of protein allergens. We will discuss the analytical figures of merit for various disposable screen-printed affinity sensors in relation to methodologies employed for immobilization of bioreceptors on transducer surface. PMID:27827963

  5. TSLP produced by keratinocytes promotes allergen sensitization through skin and thereby triggers atopic march in mice.

    PubMed

    Leyva-Castillo, Juan Manuel; Hener, Pierre; Jiang, Hua; Li, Mei

    2013-01-01

    Atopic dermatitis often precedes the development of asthma, a phenomenon known as "atopic march". An important role of allergen sensitization developed through barrier-defective skin has been recognized in the onset of atopic march; however, the underlying mechanism remains poorly understood. In this study, we use an experimental atopic march mouse model, in which the sensitization to allergen is achieved through barrier-impaired skin, followed by allergen challenge in the airway. By using thymic stromal lymphopoietin (TSLP)(iep-/-) mice in which the cytokine TSLP is selectively and inducibly ablated in epidermal keratinocytes, we demonstrate that keratinocytic TSLP, the expression of which is induced by skin barrier impairment, is essential for generating skin allergic inflammation and allergen-induced T helper type 2 response, for developing sensitization to allergen, and for triggering a subsequent allergic asthma. Furthermore, using TSLP(over) mice in which overexpression of keratinocytic TSLP is induced by skin topical application of MC903 (a vitamin D3 analog) in a dose-dependent manner, we show that keratinocytic TSLP levels are correlated with skin sensitization strength and asthma severity. Taken together, our study uncovers a crucial role of keratinocytic TSLP in the "atopic march" by promoting allergen sensitization occurring in barrier-impaired skin, which ultimately leads to allergic asthma.

  6. Establishment of Reference Doses for residues of allergenic foods: report of the VITAL Expert Panel.

    PubMed

    Taylor, Steve L; Baumert, Joseph L; Kruizinga, Astrid G; Remington, Benjamin C; Crevel, Rene W R; Brooke-Taylor, Simon; Allen, Katrina J; Houben, Geert

    2014-01-01

    In 2011, an expert panel was assembled to establish appropriate Reference Doses for allergenic food residues as a part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program of The Allergen Bureau of Australia & New Zealand (ABA). These Reference Doses would guide advisory labeling decisions for use on food labels. Individual NOAELs and LOAELs were obtained from clinical challenges of food-allergic subjects. Statistical dose-distribution models (log-normal, log-logistic, Weibull) were applied to the individual NOAELs and LOAELs for each allergenic food. The Reference Doses, in terms of mg of total protein from the allergenic food, were based upon either the ED01 (for peanut, cow's milk), the 95% lower confidence interval of the ED05 (for wheat, soybean, cashew, shrimp, sesame seed, mustard, and lupine), or both (egg, hazelnut) using all appropriate statistical dose-distribution models. Reference Doses were established for 11 allergenic foods ranging from 0.03 mg for egg protein to 10mg for shrimp protein. Reference Doses were not established for fish or celery due to poor model fits with existing data. Reference Doses were not established for other tree nuts beyond hazelnut and cashew because of the absence of data on NOAELs and LOAELs from individual subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics.

    PubMed

    Diamant, Z; Sidharta, P N; Singh, D; O'Connor, B J; Zuiker, R; Leaker, B R; Silkey, M; Dingemanse, J

    2014-08-01

    CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses. In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test. Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3-10 h) ) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments. Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders. © 2014 John Wiley & Sons Ltd.

  8. Computational analysis of the relationship between allergenicity and digestibility of allergenic proteins in simulated gastric fluid

    PubMed Central

    Jiang, Bingjun; Qu, Hong; Hu, Yuanlei; Ni, Ting; Lin, Zhongping

    2007-01-01

    Background Safety assessment of genetically modified (GM) food, with regard to allergenic potential of transgene-encoded xenoproteins, typically involves several different methods, evaluation by digestibility being one thereof. However, there are still debates about whether the allergenicity of food allergens is related to their resistance to digestion by the gastric fluid. The disagreements may in part stem from classification of allergens only by their sources, which we believe is inadequate, and the difficulties in achieving identical experimental conditions for studying digestion by simulated gastric fluid (SGF) so that results can be compared. Here, we reclassify allergenic food allergens into alimentary canal-sensitized (ACS) and non-alimentary canal-sensitized (NACS) allergens and use a computational model that simulates gastric fluid digestion to analyze the digestibilities of these two types. Results The model presented in this paper is as effective as SGF digestion experiments, but more stable and reproducible. On the basis of this model, food allergens are satisfactorily classified as ACS and NACS types by their pathways for sensitization; the former are relatively resistant to gastric fluid digestion while the later are relatively labile. Conclusion The results suggest that it is better to classify allergens into ACS and NACS types when understanding the relationship between their digestibility and allergenicity and the digestibility of a target foreign protein is a parameter for evaluating its allergenicity during safety assessments of GM food. PMID:17922925

  9. Guilt by intimate association: what makes an allergen an allergen?

    PubMed

    Karp, Christopher L

    2010-05-01

    Why specific, ubiquitous, otherwise innocuous environmental proteins tend to provoke maladaptive, T(H)2-polarized immune responses in susceptible hosts is a fundamental mechanistic question for those interested in the pathogenesis, therapy, and prevention of allergic disease. The current renaissance in the study of innate immunity has provided important insights into this question. The theme emerging from recent studies is that direct (dys)functional interactions with pathways of innate immune activation that evolved to signal the presence of microbial infection are central to the molecular basis for allergenicity. This article reviews these data. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  10. The allergenic significance of certain fungi rarely reported as allergens.

    PubMed

    Giannini, E H; Northey, W T; Leathers, C R

    1975-12-01

    The allergenic significance of seven different species of fungi was investigated. Included were Chlorophyllum molybdites, Podaxis pistillaris, Stemonitis ferruginea, Lycogala epidendrum, Fuligo septica, Ustilago maydis and Puccinia cynodontis. All of these fungi have wide distribution patterns and aerially disseminated spores but, because of their unique growth characteristics, are usually not reported in atmospheric fungal surveys. Seventy-eight patients were treated for dermal sensitivity to extracts of the organisms after the spores were extracted in 50% glycerinated Coca's solution. The results represent a six-month test period. Forty-four patients, representing 56% of the total number tested, demonstrated dermal reactivity toward one or more of the extracts.

  11. Influence of ultrasonic treatment on the allergenic properties of Shrimp ( Penaeus vannamei) Allergen

    NASA Astrophysics Data System (ADS)

    Li, Zhenxing; Lin, Hong; Cao, Limin

    2006-04-01

    The present study was undertaken to determine whether high intensity ultrasound could reduce the allergic properties of shrimp allergens. Reducing the allergenic properties of these allergens will be beneficial to allergic individuals. Samples of shrimp protein extract and shrimp muscle were treated by high-intensity ultrasound with water bathing at 0°C or 50°C for different time periods. The treated and untreated samples were then analyzed by SDS-PAGE, Western blots and competitive inhibition ELISA (Ci-ELISA) to determine the shrimp allergenicity. The results show that high-intensity ultrasound has no effect on allergenicity when the extracts were treated at 0°C. However, a significant decrease was observed in the level of the major shrimp allergen, Pen a 1, when the samples were treated at 50°C. In the determination of allergenicity with Ci-ELISA, a reduction in IgE binding was also observed.

  12. Critically appraised topic on adverse food reactions of companion animals (2): common food allergen sources in dogs and cats.

    PubMed

    Mueller, Ralf S; Olivry, Thierry; Prélaud, Pascal

    2016-01-12

    To diagnose cutaneous adverse food reactions (CAFRs) in dogs and cats, dietary restriction-provocation trials are performed. Knowing the most common offending food allergens for these species would help determining the order of food challenges to optimize the time to diagnosis. The search for, and review and analysis of the best evidence available as of January 16, 2015 suggests that the most likely food allergens contributing to canine CAFRs are beef, dairy products, chicken, and wheat. The most common food allergens in cats are beef, fish and chicken. In dogs and cats, after a period of dietary restriction leading to the complete remission of clinical signs, food challenges to diagnose CAFR should begin with beef and dairy products, the most commonly recognized food allergens in these two species.

  13. Allergen avoidance approaches in food allergy management.

    PubMed

    Koletzko, Sibylle; Koletzko, Berthold

    2009-01-01

    Dietary elimination of causative food ingredients, usually food proteins, is the basis of treating food hypersensitivity. Proper diagnostic assessment is essential to avoid burdening children with unnecessary dietary restrictions with potential adverse effects. Diagnosis requires a detailed history, allergen elimination, and re-challenge with suspected foods. Complete elimination of causative food components depends on professional counseling and training of the patient and family, and transparent labeling of food products. Elimination diets carry the risk of inducing insufficient supplies of critical nutrients with adverse effects on health and wellbeing, particularly in children with exclusion of foods that provide a major part of dietary supply and patients with multiple food allergies. Infants and young children with cow's milk allergy, who have not been fully breastfed, require milk substitutes based on extensively hydrolyzed protein or amino acids. Elimination diets must be supervised and monitored to a similar degree as drug treatments, and the need for continued dietary elimination should be reviewed on a regular basis and re-challenges considered.

  14. Developing a family-based HIV prevention intervention in rural Kenya: challenges in conducting community-based participatory research.

    PubMed

    Puffer, Eve S; Pian, Jessica; Sikkema, Kathleen J; Ogwang-Odhiambo, Rose A; Broverman, Sherryl A

    2013-04-01

    Community-Based Participatory research (CBPR) introduces new ethical challenges for HIV prevention studies in low-resource international settings. We describe a CBPR study in rural Kenya to develop and pilot a family-based HIV prevention and mental health promotion intervention. Academic partners (APs) worked with a community advisory committee (CAC) during formative research, intervention development, and a pilot trial. Ethical challenges emerged related to: negotiating power imbalances between APs and the CAC; CAC members' shifting roles as part of the CAC and wider community; and anticipated challenges in decision making about sustainability. Factors contributing to ethical dilemmas included low access to education, scarcity of financial resources, and the shortage of HIV-related services despite high prevalence.

  15. Developing a Family-Based HIV Prevention Intervention in Rural Kenya: Challenges in Conducting Community-Based Participatory Research

    PubMed Central

    Puffer, Eve S.; Pian, Jessica; Sikkema, Kathleen J.; Ogwang-Odhiambo, Rose A.; Broverman, Sherryl A.

    2013-01-01

    Community-based participatory research (CBPR) introduces new ethical challenges for HIV prevention studies in low-resource international settings. We describe a CBPR study in rural Kenya to develop and pilot a family-based HIV prevention and mental health promotion intervention. Academic partners (APs) worked with a community advisory committee (CAC) during formative research, intervention development, and a pilot trial. Ethical challenges emerged related to: negotiating power imbalances between APs and the CAC; CAC members’ shifting roles as part of the CAC and wider community; and anticipated challenges in decision making about sustainability. Factors contributing to ethical dilemmas included low access to education, scarcity of financial resources, and the shortage of HIV-related services despite high prevalence. PMID:23651936

  16. Evaluating variability of allergens in commodity crops.

    USDA-ARS?s Scientific Manuscript database

    Crops with significant food allergen issues, include legumes, peanut and soybean, cereal grains, such as wheat and maize, and tree nuts (walnut, Brazil nut, among other phylogenetically diverse species) (Teuber et al. 2006). Officially recognized allergenic proteins may include one or multiple prot...

  17. New structural information on food allergens (abstract)

    USDA-ARS?s Scientific Manuscript database

    A small number of protein families are responsible for food allergies suffered by the majority of allergy patients. What properties of these proteins make them allergens is not clear at present. Reliable methods for allergen prediction and mitigation are lacking. Most the immediate type of food alle...

  18. Reducing food allergenicity at the molecular level.

    USDA-ARS?s Scientific Manuscript database

    Food allergens are a significant worldwide public health issue. Estimates for the prevalence of food allergies are around 1-2 % of the total population and up to 8 % of children; although, the prevalence may vary between populations and age groups. Peanuts are one of the most allergenic foods. The...

  19. Superconducting graphene sheets in CaC6 enabled by phonon-mediated interband interactions

    NASA Astrophysics Data System (ADS)

    Yang, S.-L.; Sobota, J. A.; Howard, C. A.; Pickard, C. J.; Hashimoto, M.; Lu, D. H.; Mo, S.-K.; Kirchmann, P. S.; Shen, Z.-X.

    2014-03-01

    There is a great deal of fundamental and practical interest in the possibility of inducing superconductivity in a monolayer of graphene. But while bulk graphite can be made to superconduct when certain metal atoms are intercalated between its graphene sheets, the same has not been achieved in a single layer. Moreover, there is a considerable debate about the precise mechanism of superconductivity in intercalated graphite. Here we report angle-resolved photoelectron spectroscopy measurements of the superconducting graphite intercalation compound CaC6 that distinctly resolve both its intercalant-derived interlayer band and its graphene-derived π* band. Our results indicate the opening of a superconducting gap in the π* band and reveal a substantial contribution to the total electron-phonon-coupling strength from the π*-interlayer interband interaction. Combined with theoretical predictions, these results provide a complete account for the superconducting mechanism in graphite intercalation compounds and lend support to the idea of realizing superconducting graphene by creating an adatom superlattice.

  20. Superconducting graphene sheets in CaC6 enabled by phonon-mediated interband interactions

    PubMed Central

    Yang, S.-L.; Sobota, J. A.; Howard, C. A.; Pickard, C. J.; Hashimoto, M.; Lu, D. H.; Mo, S.-K.; Kirchmann, P. S.; Shen, Z.-X.

    2014-01-01

    There is a great deal of fundamental and practical interest in the possibility of inducing superconductivity in a monolayer of graphene. But while bulk graphite can be made to superconduct when certain metal atoms are intercalated between its graphene sheets, the same has not been achieved in a single layer. Moreover, there is a considerable debate about the precise mechanism of superconductivity in intercalated graphite. Here we report angle-resolved photoelectron spectroscopy measurements of the superconducting graphite intercalation compound CaC6 that distinctly resolve both its intercalant-derived interlayer band and its graphene-derived π* band. Our results indicate the opening of a superconducting gap in the π* band and reveal a substantial contribution to the total electron–phonon-coupling strength from the π*-interlayer interband interaction. Combined with theoretical predictions, these results provide a complete account for the superconducting mechanism in graphite intercalation compounds and lend support to the idea of realizing superconducting graphene by creating an adatom superlattice. PMID:24651261

  1. Superconducting graphene sheets in CaC6 enabled by phonon-mediated interband interactions.

    PubMed

    Yang, S-L; Sobota, J A; Howard, C A; Pickard, C J; Hashimoto, M; Lu, D H; Mo, S-K; Kirchmann, P S; Shen, Z-X

    2014-03-20

    There is a great deal of fundamental and practical interest in the possibility of inducing superconductivity in a monolayer of graphene. But while bulk graphite can be made to superconduct when certain metal atoms are intercalated between its graphene sheets, the same has not been achieved in a single layer. Moreover, there is a considerable debate about the precise mechanism of superconductivity in intercalated graphite. Here we report angle-resolved photoelectron spectroscopy measurements of the superconducting graphite intercalation compound CaC6 that distinctly resolve both its intercalant-derived interlayer band and its graphene-derived π* band. Our results indicate the opening of a superconducting gap in the π* band and reveal a substantial contribution to the total electron-phonon-coupling strength from the π*-interlayer interband interaction. Combined with theoretical predictions, these results provide a complete account for the superconducting mechanism in graphite intercalation compounds and lend support to the idea of realizing superconducting graphene by creating an adatom superlattice.

  2. Watermelon and ragweed share allergens.

    PubMed

    Enberg, R N; Leickly, F E; McCullough, J; Bailey, J; Ownby, D R

    1987-06-01

    A biotin-avidin amplified ELISA was used to measure antigen-specific IgE for ragweed, representative members of the gourd family (watermelon, cantaloupe, honeydew melon, zucchini, and cucumber), and banana in the sera of 192 allergic patients, each with an IgE greater than or equal to 180 microns/ml. Sixty-three percent (120/192) of the sera contained antiragweed IgE, and of these patients, 28% to 50% contained IgE specific for any single gourd family member. In contrast, no greater than 11% of the sera positive for a given gourd or banana were negative for ragweed. Correlations between ragweed and gourd-specific IgE levels were significant (p less than 0.001), and correlation coefficients between any two gourds exceeded 0.79. In an ELISA system, the extracts of watermelon and ragweed inhibited each other in a dose-dependent manner; the resulting nonparallel inhibition curves indicate that some, but not all, of the allergens in the two extracts are cross-reactive. Isoelectric focusing of watermelon and ragweed extracts in narrow range gel (pH 4 to 6) followed by immunoblotting demonstrated six watermelon allergen bands with isoelectric points identical to those of ragweed allergens. Several remaining bands in the two extracts had differing isoelectric points, however. Six of 26 patients interviewed with watermelon-specific IgE reported developing oropharyngeal symptoms (itching and/or swelling of the lips, tongue, or throat) after ingesting at least one of the study foods, whereas only one of 25 patients interviewed without detectable watermelon-specific IgE reported similar symptoms (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Allergens might trigger migraine attacks.

    PubMed

    Bektas, Hesna; Karabulut, Hayriye; Doganay, Beyza; Acar, Baran

    2017-03-01

    Migraine is a common primary headache disorder. The mechanisms underlying the onset of a migraine attack are not completely understood. Environmental changes and a number of other factors could induce migraine attacks. The aim of this study was to investigate the relationship between the frequency of migraine attacks and allergens. Migraine patients without aura, and healthy individuals similar in age and gender without a history of headache and allergy were prospectively included in the study. The duration of migraine, the frequency of migraine attacks, the medication history, and the symptoms during attacks were questioned. Migraine disability assessment score (MIDAS) and visual analog scale (VAS) scores were obtained. Allergen extracts including dust, fungi, insect, animal epithelium, pollens, and food allergens were applied for allergy tests. 49 migraine patients and 49 healthy individuals were enrolled in the study. There was no significant difference in terms of age and gender. The median migraine disease duration, the number of attacks in a month, and the duration of attacks were, respectively, 5.5 years (1-44), 4 (1-10) day/month, and 24 (4-72) h. The mean MIDAS grade was 2.45 ± 0.14 (1-4), and mean VAS score was 7.89 ± 0.27 (4-10). The positivity of allergy tests was 55.1 % (27/49) in the migraine group and 32.7 % (16/49) in the control group (p < 0.05). The allergy tests were positive for house dust, red birch, hazel tree, olive tree, nettle, and wheat. The frequency of migraine attacks was higher in allergy-test-positive patients than in negative ones in the migraine group (p = 0.001). The migraine patients who had frequent attacks should be examined for allergies.

  4. Assessment of environmental cockroach allergen exposure.

    PubMed

    Chew, Ginger L

    2012-10-01

    In the past, cockroach allergen exposure assessment mainly focused on settled dust in homes in low-income urban cities in the United States. That choice was not wrong; without measureable levels of cockroach allergen, it is difficult to show associations with any home characteristics, much less with health outcomes (e.g., allergy, asthma). However, recent studies in other suburban areas, schools, and other countries have elucidated the importance of cockroach allergen in these environments too. In addition, characterizing the underlying factors that give rise to cockroach allergen exposure (or protect against it) can lead to more targeted public health interventions. This review discusses different approaches to sampling indoor environments, interprets recent asthma and allergy studies, compares cockroach allergen levels from past studies with those of recent studies, and describes strategies for decreasing exposures.

  5. Public protection – reliable allergen risk management

    NASA Astrophysics Data System (ADS)

    Janković, V.; Popov Raljić, J.; Đorđević, V.

    2017-09-01

    Consumers with potentially fatal food allergies are dependent on correct product labelling to protect their health. The food industry is responsible for providing every detail consumers need to make informed decisions. Considering public health, food suppliers have to monitor the presence of allergens, prevent cross-contamination and label products accurately. Allergen labelling of food products, drinks and non pre-packed food and drink products is clearly defined with legal regulations. To achieve this, a complete understanding of each product’s allergenic ingredients is needed and cross-contamination of food with allergens must be avoided. Raw materials need to be checked, every ingredient must be verified and every single allergen has to be stipulated. A mislabeled product could be recalled at potential cost, financially damaging business and at the same time, negatively impacting brand and reputation.

  6. American contact dermatitis society core allergen series.

    PubMed

    Schalock, Peter C; Dunnick, Cory A; Nedorost, Susan; Brod, Bruce; Warshaw, Erin; Mowad, Christen

    2013-01-01

    Evidence for the effectiveness of patch testing and the need for an expanded series that provides experience and evidence-based suggestions for an extended patch testing series are examined in this review. Many of those testing with shorter allergen series are interested in expanding the spectrum of patch testing. The American Contact Dermatitis Society (ACDS) Core Allergen Series Group has arranged a group of suggested allergen groups that can be logically scaled up or down depending on the needs of the patch tester and the community being tested. This is not an "ACDS 80 Standard." We suggest a core group of allergens similar to the TRUE Test (SmartPractice, Phoenix, Ariz) with subsequent trays providing a greater breadth of coverage in a logical fashion, with more likely allergens being higher in the tray. For more extensive testing, specialty trays (ie, cosmetics, metals, plant, etc) are recommended.

  7. Assessment of Environmental Cockroach Allergen Exposure

    PubMed Central

    Chew, Ginger L.

    2016-01-01

    In the past, cockroach allergen exposure assessment mainly focused on settled dust in homes in low-income urban cities in the United States. That choice was not wrong; without measureable levels of cockroach allergen, it is difficult to show associations with any home characteristics much less with health outcomes (e.g., allergy, asthma). However, recent studies in other suburban areas, schools, and other countries have elucidated the importance of cockroach allergen in these environments too. In addition, characterizing the underlying factors that give rise to cockroach allergen exposure (or protect against it) can lead to more targeted public health interventions. This review discusses different approaches to sampling indoor environments, interprets recent asthma and allergy studies, compares cockroach allergen levels from past studies with those of recent studies, and describes strategies to decrease exposures. PMID:22825884

  8. Comparison of international food allergen labeling regulations.

    PubMed

    Gendel, Steven M

    2012-07-01

    Food allergy is a significant public health issue worldwide. Regulatory risk management strategies for allergic consumers have focused on providing information about the presence of food allergens through label declarations. A number of countries and regulatory bodies have recognized the importance of providing this information by enacting laws, regulations or standards for food allergen labeling of "priority allergens". However, different governments and organizations have taken different approaches to identifying these "priority allergens" and to designing labeling declaration regulatory frameworks. The increasing volume of the international food trade suggests that there would be value in supporting sensitive consumers by harmonizing (to the extent possible) these regulatory frameworks. As a first step toward this goal, an inventory of allergen labeling regulations was assembled and analyzed to identify commonalities, differences, and future needs.

  9. Can the use of HEPA cleaners in homes of asthmatic children and adolescents sensitized to cat and dog allergens decrease bronchial hyperresponsiveness and allergen contents in solid dust?

    PubMed

    Sulser, Claudia; Schulz, Gabriele; Wagner, Petra; Sommerfeld, Christine; Keil, Thomas; Reich, Andreas; Wahn, Ulrich; Lau, Susanne

    2009-01-01

    Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR). In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples. Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV(1) after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR. Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study. (c) 2008 S. Karger AG, Basel.

  10. Mass spectrometry-based identification of allergens from Curvularia pallescens, a prevalent aerospore in India.

    PubMed

    Dey, Debarati; Saha, Bodhisattwa; Sircar, Gaurab; Ghosal, Kavita; Bhattacharya, Swati Gupta

    2016-07-01

    The worldwide prevalence of fungal allergy in recent years has augmented mining allergens from yet unexplored ones. Curvularia pallescens (CP) being a dominant aerospore in India and a major sensitiser on a wide range of allergic population, pose a serious threat to human health. Therefore, we aimed to identify novel allergens from CP in our present study. A cohort of 22 CP-sensitised patients was selected by positive Skin prick grade. Individual sera exhibited elevated specific IgE level and significant histamine release on a challenge with antigenic extract of CP. First gel-based profiling of CP proteome was done by 1- and 2-dimensional gel. Parallel 1- and 2-dimensional immunoblot were performed applying individual as well as pooled patient sera. Identification of the sero-reactive spots from the 2-dimensional gel was found to be challenging as CP was not previously sequenced. Hence, mass spectrometry-based proteomic workflow consisting of conventional database search was not alone sufficient. Therefore, de novo sequencing preceded homology search was implemented for further identification. Altogether 11 allergenic proteins including Brn-1, vacuolar protease, and fructose-bis-phosphate aldolase were identified with high statistical confidence (p<0.05). This is the first study to report on any allergens from CP. This kind of proteome-based analysis provided a catalogue of CP allergens that would lead an improved way of diagnosis and therapy of CP-related allergy.

  11. Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. 5. Opioid receptor binding properties of N-((4'-phenyl)-phenethyl) analogues of 8-CAC.

    PubMed

    VanAlstine, Melissa A; Wentland, Mark P; Cohen, Dana J; Bidlack, Jean M

    2007-12-01

    A series of aryl-containing N-monosubstituted analogues of the lead compound 8-[N-((4'-phenyl)-phenethyl)]-carboxamidocyclazocine were synthesized and evaluated to probe a putative hydrophobic binding pocket of opioid receptors. Very high binding affinity to the mu opioid receptor was achieved though the N-(2-(4'-methoxybiphenyl-4-yl)ethyl) analogue of 8-CAC. High binding affinity to mu and very high binding affinity to kappa opioid receptors was observed for the N-(3-bromophenethyl) analogue of 8-CAC. High binding affinity to all three opioid receptors were observed for the N-(2-naphthylethyl) analogue of 8-CAC.

  12. Advances in upper airway diseases and allergen immunotherapy.

    PubMed

    Nelson, Harold S

    2004-04-01

    Evidence for one airway continues to accumulate. Nasal allergen challenges increase lower airway inflammation, and nasal corticosteroid treatment reduces lower airway inflammation. Allergic respiratory inflammation might even spread systemically to involve nonrespiratory organs. Eosinophilic enteritis and eosinophilic esophagitis are reported during pollen seasons in patients with seasonal allergic rhinitis. Chronic hypertrophic sinusitis (CHS) is found in the majority of patients with asthma. Like asthma, the histology of CHS is characterized by epithelial damage, basement membrane thickening, and eosinophilic inflammation. The damaged epithelium might explain the acute bacterial exacerbations seen in patients with CHS. Studies have extended evidence of the safety and efficacy of the second- and third-generation antihistamines to younger children and to patients with perennial rhinitis but continue to show improvement of symptom scores over that seen with placebo of less than 20%. Studies on antihistamine use in the first trimester in nearly 500 women (65% taking loratadine) revealed no increase in the complications of pregnancy or congenital anomalies. Positive skin prick test responses to birch in asymptomatic young adults predicted later development of clinical allergic rhinitis. A dose response was demonstrated for immunotherapy with cat dander extract. The best results were in subjects receiving a dose containing 15 microg of the major cat allergen Fel d 1 (equivalent to approximately 2500 bioequivalent allergen units). Both topical intranasal immunotherapy and high-dose sublingual immunotherapy have been repeatedly proved to be safe and effective in double-blind, placebo-controlled studies. CD4+CD25+ regulatory T cells secreting IL-10, TGF-beta, or both appear important in normal individuals and in patients treated with allergen immunotherapy in maintaining or restoring normal T(H)1/T(H)2 balance and overall suppression of both phenotypes.

  13. Carbohydrate modified ultrafine ceramic nanoparticles for allergen immunotherapy.

    PubMed

    Pandey, Ravi Shankar; Sahu, Satish; Sudheesh, M S; Madan, Jitender; Kumar, Manoj; Dixit, Vinod Kumar

    2011-08-01

    The uses of drug-delivery systems in allergen specific immunotherapy appear to be a promising approach due to their ability to act as adjuvants, transport the allergens to immune-competent cells and tissues and reduce the number of administrations. The aim of this work was to evaluate the carbohydrate modified ultrafine ceramic core based nanoparticles (aquasomes) as adjuvant/delivery vehicle in specific immunotherapy using ovalbumin (OVA) as an allergen model. Prepared nanoparticles were characterized for size, shape, zeta potential, antigen integrity, surface adsorption efficiency and in vitro release. The humoral and cellular-induced immune responses generated by OVA adsorbed aquasomes were studied by two intradermal immunizations in BALB/c mice. OVA sensitized mice were treated with OVA adsorbed aquasomes and OVA adsorbed aluminum hydroxide following established protocol. Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated. Developed aquasomes possessed a negative zeta potential (-11.3 mV) and an average size of 47 nm with OVA adsorption efficiency of ~60.2 μg mg(-1) of hydroxyapatite core. In vivo immune response after two intradermal injections with OVA adsorbed aquasomes resulted in a mixed Th1/Th2-type immune response. OVA-sensitized mice model, treatment with OVA adsorbed aquasomes elicited lower levels of IgE (p<0.05), serum histamine and higher survival rate in comparison with alum adsorbed OVA. Symptoms of anaphylactic shock in OVA aquasome-treated mice were weaker than the one induced in the alum adsorbed OVA group. Results from this study demonstrate the valuable use of aquasomes in allergen immunotherapy. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Allergenic extracts to diagnose and treat sensitivity to insect venoms and inhaled allergens.

    PubMed

    Khurana, Taruna; Bridgewater, Jennifer L; Rabin, Ronald L

    2017-05-01

    To review allergenic extracts used to diagnose or treat insect allergies, including how the extracts are manufactured and their measurements of potency or concentration. Peer-reviewed articles derived from searching PubMed (National Center for Biotechnology Information) about insect allergies and extract preparation. Encyclopedia of Life (http://www.eol.org/) and http://allergome.org/ were also referenced for background information on insects and associated allergens. Search terms used for the PubMed searches included insect allergens and allergies, Apidae, Vespidae, fire ants, cockroach allergies, insect allergen extract preparation, and standardization. Humans may be sensitized to insect allergens by inhalation or through stings. Cockroaches and moths are predominantly responsible for inhalation insect allergy and are a major indoor allergen in urban settings. Bees, fire ants, and wasps are responsible for sting allergy. In the United States, there are multiple insect allergen products commercially available that are regulated by the US Food and Drug Administration. Of those extracts, honeybee venom and insect venom proteins are standardized with measurements of potency. The remaining insect allergen extracts are nonstandardized products that do not have potency measurements. Sensitization to inhalational and stinging insect allergens is reported worldwide. Crude insect allergen extracts are used for diagnosis and specific immunotherapy. A variety of source materials are used by different manufacturers to prepare these extracts, which may result in qualitative differences that are not reflected in measurements of potency or protein concentration. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Recent development in recombinant food allergen production (abstract)

    USDA-ARS?s Scientific Manuscript database

    Whether for understanding the properties of food allergens or for manufacturing vaccines for allergen-specific immunotherapy, well characterized pure allergens are required. This often necessitate the use of recombinant technology in obtaining food allergens due to the very low amounts of their natu...

  16. Effects of NO2 and Ozone on Pollen Allergenicity

    PubMed Central

    Frank, Ulrike; Ernst, Dieter

    2016-01-01

    This mini-review summarizes the available data of the air pollutants NO2 and ozone on allergenic pollen from different plant species, focusing on potentially allergenic components of the pollen, such as allergen content, protein release, IgE-binding, or protein modification. Various in vivo and in vitro studies on allergenic pollen are shown and discussed. PMID:26870080

  17. Skin Barrier Function and Allergens.

    PubMed

    Engebretsen, Kristiane Aasen; Thyssen, Jacob Pontoppidan

    2016-01-01

    The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization (CS) and allergy following increased penetration of potential allergens. However, the relationship between common dermatoses such as psoriasis, atopic dermatitis (AD) and irritant contact dermatitis (ICD) and the development of contact allergy (CA) is complex, and depends on immunologic responses and skin barrier status. Psoriasis has traditionally been regarded a Th1-dominated disease, but the discovery of Th17 cells and IL-17 provides new and interesting information regarding the pathogenesis of the disease. Research suggests an inverse relationship between psoriasis and CA, possibly due to increased levels of Th17 cells and its associated cytokines. As for AD, a positive association to CS has been established in epidemiological studies, but is still unresolved. Experimental studies show, however, an inverse relationship between AD and CS. The opposing and antagonistic influences of Th1 (CS) and Th2 (AD) have been proposed as an explanation. Finally, there is convincing evidence that exposure to irritants increases the risk of CS, and patients with ICD are, therefore, at great risk of developing CA. Skin irritation leads to the release of IL-1 and TNF-α, which affects the function of antigen-presenting cells and promotes their migration to local lymph nodes, thus increasing the probability of CS and ultimately the development of CA.

  18. Structural basis underlying CAC RNA recognition by the RRM domain of dimeric RNA-binding protein RBPMS.

    PubMed

    Teplova, Marianna; Farazi, Thalia A; Tuschl, Thomas; Patel, Dinshaw J

    2016-01-01

    RNA-binding protein with multiple splicing (designated RBPMS) is a higher vertebrate mRNA-binding protein containing a single RNA recognition motif (RRM). RBPMS has been shown to be involved in mRNA transport, localization and stability, with key roles in axon guidance, smooth muscle plasticity, as well as regulation of cancer cell proliferation and migration. We report on structure-function studies of the RRM domain of RBPMS bound to a CAC-containing single-stranded RNA. These results provide insights into potential topologies of complexes formed by the RBPMS RRM domain and the tandem CAC repeat binding sites as detected by photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation. These studies establish that the RRM domain of RBPMS forms a symmetrical dimer in the free state, with each monomer binding sequence-specifically to all three nucleotides of a CAC segment in the RNA bound state. Structure-guided mutations within the dimerization and RNA-binding interfaces of RBPMS RRM on RNA complex formation resulted in both disruption of dimerization and a decrease in RNA-binding affinity as observed by size exclusion chromatography and isothermal titration calorimetry. As anticipated from biochemical binding studies, over-expression of dimerization or RNA-binding mutants of Flag-HA-tagged RBPMS were no longer able to track with stress granules in HEK293 cells, thereby documenting the deleterious effects of such mutations in vivo.

  19. Long term results of the use of compression anastomosis clips (CAC) in gastrointestinal surgery – the first report.

    PubMed

    Kuśnierz, Katarzyna; Lampe, Paweł

    2015-06-01

    The aim of the study was to present the first long-term results on the clinical use of compression anastomosis clips (CAC) in upper and lower gastrointestinal tract anastomoses. The study included 50 patients who underwent anastomosis of the upper (n = 32) or lower GI tract (n = 18) with the use of CAC. In the period of 6-7 months after the surgery, patients underwent endoscopic examination and computed tomography evaluation of the anastomosis. Each anastomosis was evaluated macro and microscopically. The width of anastomoses was evaluated using a 4-point-scale for grading stenosis. Of the 50 patients who underwent anastomosis with compression anastomosis clip, 28 (56%) patients reported to the follow-up examination within 190-209 days of the execution of the anastomosis. Among the 22 patients who did not report to the study, 18 (36%) patients died within 91-154 days from the execution of the anastomosis (mean 122 days), 4 (8%) patients were impossible to contact after discharge from hospital. Two mild stenoses (I0) were diagnosed; 1 of them was found in the gastroenterostomy and 1 in Braun enteroenterostomy. Microscopic changes were diagnosed in 4 anastomoses (3 gastroenterostomies, 1 Braun enteroenterostomy). Anastomoses were well-formed and wide, scars in the line of anastomoses were thin. During the period of 6 months after the anastomoses performed using CAC have been formed, they were evaluated as unobstructed and functioning properly; therefore, they can be safely performed within the upper and lower gastrointestinal tract.

  20. Solubility at the molecular level: development of a critical aggregation concentration (CAC) assay for estimating compound monomer solubility.

    PubMed

    Wang, Jie; Matayoshi, Edmund

    2012-07-01

    In drug discovery research the formation of soluble compound aggregates is a major cause of false positives, false negatives, and distorted values in High-Throughput Screening assays that measure either binding or functional activity. These aggregation-based artifacts lead to serious distortions in the SAR which are critical to successful lead optimization. In this work we introduce a new approach by which the "critical aggregation concentration" (CAC) is determined, thereby overcoming limitations inherent to traditional solubility methods and enabling estimation of small molecule monomer solubility. The theoretical and experimental basis of a new confocal Static Light Scattering plate reader assay is presented. Tests conducted with model systems, commercial compounds, and Abbott library compounds show that the CAC assay can measure aqueous monomer solubilities reproducibly and reliably, achieving a sensitivity of ~0.2 μm, which is an improvement of approximately two orders of magnitude over nephelometry. Determination of compound monomer solubilities in a screening format is possible for the first time with the cSLS-CAC methodology. It is currently in routine use in Abbott's drug discovery program, and has enabled identification of many compound induced artifacts in binding or activity assays that are missed by traditional kinetic solubility measurements.

  1. Design of an Efficient CAC for a Broadband DVB-S/DVB-RCS Satellite Access Network

    NASA Astrophysics Data System (ADS)

    Inzerilli, Tiziano; Montozzi, Simone

    2003-07-01

    This paper deals with efficient utilization of network resources in an advanced broadband satellite access system. It proposes a technique for admission control of IP streams with guaranteed QoS which does not interfere with the particular BoD (Bandwidth on Demand) algorithm that handles access to uplink bandwidth, an essential part of a DVB- RCS architecture. This feature of the admission control greatly simplify its integration in the satellite network. The purpose of this admission control algorithm in particular is to suitably and dynamically configure the overall traffic control parameters, in the access terminal of the user and service segment, with a simple approach which does not introduces limitations and/or constraints to the BoD algorithm. Performance of the proposed algorithm is evaluated thorugh Opnet simulations using an ad-hoc platform modeling DVB-based satellite access.The results presented in this paper were obtained within SATIP6 project, which is sponsored within the 5th EU Research Programme, IST. The aims of the project are to evaluate and demonstrate key issues of the integration of satellite-based access networks into the Internet in order to support multimedia services over wide areas. The satellite link layer is based on DVB-S on the forward link and DVB-RCS on the return link. Adaptation and optimization of the DVB-RCS access standard in order to support QoS provision are central issues of the project. They are handled through an integration of Connection Admission Control (CAC), Traffic Shaping and Policing techniques.

  2. Will genetically modified foods be allergenic?

    PubMed

    Taylor, S L; Hefle, S L

    2001-05-01

    Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources. Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.

  3. The hammock: a reservoir of allergens

    PubMed Central

    Rego, Francisca X M; Giavina-Bianchi, Pedro; Kalil, Jorge; Arruda, L. Karla; Toledo-Barros, Myrthes

    2011-01-01

    INTRODUCTION: Asthma affects approximately 10% of the world's population. Sensitization to allergens is an important risk factor, and exposure to allergens is associated with disease severity. METHODS: We performed skin tests to evaluate allergen sensitization to mites, cockroaches, cats, dogs, and molds in 73 asthmatic patients. Enzyme Linked Immunosorbent Assay was used to assay the mite and cockroach allergens found in dust from the bedding, hammocks, bedroom floors, living rooms, and kitchens of 29 patients and 14 controls. RESULTS: Fifty patients (68.5%) had positive skin test responses. There were positive responses to D. pteronyssinus (52.0%), B. tropicalis (53.4%), T. putrescentiae (15.0%), E. maynei (12.3%), L. destructor (8.2%), B. germanica (20.5%), P. americana (21.9%), Felis catus (10.9%), C. herbarium (2.7%), A. alternata (4.1%), and P. notatun (1.3%). The exposure to mite and cockroach allergens was similar in the patients and the controls. The Dermatophagoides pteronyssinus Group 1 levels were highest in the beds and hammocks. The Blattella germanica Group 1 levels were highest in the kitchens, living rooms and hammocks. DISCUSSION: The positive skin tests to mites, cockroaches and cats were consistent with previous studies. D pteronyssinus was the most prevalent home dust mite, and hammocks were a source of allergens. To improve asthma prophylaxis, it is important to determine its association with mite allergen exposure in hammocks. PMID:21876974

  4. [Incidence of hypersensitivity to mycotic and mite allergens].

    PubMed

    Akhapkina, I G; Krakhanenkova, S N; Mamlenkova, E A; Dobronravova, E V; Shushpanova, E N

    2009-07-01

    Scratch tests were used to study the rate of sensitization to house dust mite allergens, mold and yeast-like fungi among the patients of an allergological center. It was found that 12.69 of the patients showed hypersensitivity only to one allergen. Combined forms of sensitization to two allergens or more were detected in 87.31% of the patients. Sensitization to mycotic allergens is more frequently encountered (82.84%) than that to house dust mite allergens (67.16%).

  5. Distribution of peanut allergen in the environment.

    PubMed

    Perry, Tamara T; Conover-Walker, Mary Kay; Pomés, Anna; Chapman, Martin D; Wood, Robert A

    2004-05-01

    Patients with peanut allergy can have serious reactions to very small quantities of peanut allergen and often go to extreme measures to avoid potential contact with this allergen. The purpose of this study was to detect peanut allergen under various environmental conditions and examine the effectiveness of cleaning agents for allergen removal. A monoclonal-based ELISA for Arachis hypogaea allergen 1 (Ara h 1; range of detection, 30-2000 ng/mL) was used to assess peanut contamination on cafeteria tables and other surfaces in schools, the presence of residual peanut protein after using various cleaning products on hands and tabletops, and airborne peanut allergen during the consumption of several forms of peanut. After hand washing with liquid soap, bar soap, or commercial wipes, Ara h 1 was undetectable. Plain water and antibacterial hand sanitizer left detectable Ara h 1 on 3 of 12 and 6 of 12 hands, respectively. Common household cleaning agents removed peanut allergen from tabletops, except dishwashing liquid, which left Ara h 1 on 4 of 12 tables. Of the 6 area preschools and schools evaluated, Ara h 1 was found on 1 of 13 water fountains, 0 of 22 desks, and 0 of 36 cafeteria tables. Airborne Ara h 1 was undetectable in simulated real-life situations when participants consumed peanut butter, shelled peanuts, and unshelled peanuts. The major peanut allergen, Ara h 1, is relatively easily cleaned from hands and tabletops with common cleaning agents and does not appear to be widely distributed in preschools and schools. We were not able to detect airborne allergen in many simulated environments.

  6. Rubber: new allergens and preventive measures.

    PubMed

    Crepy, Marie-Noëlle

    2016-12-01

    Natural rubber latex (NRL) and rubber accelerators are well-known causes of occupational skin diseases. The latest epidemiological data on rubber allergy show that rubber additives are still among the allergens most strongly associated with occupational contact dermatitis, however, a decrease in NRL allergy has been confirmed. A review of recent publications on rubber allergens based on the Pubmed database is presented. New glove manufacturing processes have been developed, such as low-protein natural rubber gloves, vulcanisation accelerator-free gloves, or specific-purpose gloves containing antimicrobial agents or moisturisers. Several websites provide information on allergens found in gloves and/or glove choice according to occupation.

  7. Allergenic fragments of ryegrass (Lolium perenne) pollen allergen Lol p IV.

    PubMed

    Jaggi, K S; Ekramoddoullah, A K; Kisil, F T

    1989-01-01

    To facilitate studies on establishing the nature of structure/function relationships of allergens, ryegrass pollen allergen, Lol p IV, was cleaved into smaller fragments by cyanogen bromide (CNBr) and the resulting peptides were further digested with trypsin. The resulting peptides were then fractionated by high performance liquid chromatography (HPLC) on a C-18 reverse phase column. The allergenic activity of the HPLC fractions was evaluated in terms of their ability to inhibit the binding of 125I-Lol p IV to serum IgE antibodies of a grass-allergic patient. Many of these fractions inhibited the binding between the native allergen and IgE antibodies in a dose-dependent manner. The inhibitions were specific, i.e., the fractions did not inhibit the binding between 125I-Lol p I (a group-I ryegrass pollen allergen) and the IgE antibodies present in the allergic human serum. The possibility that the allergenic peptide fractions were contaminated by the native undegraded allergen, which might have accounted for the observed inhibition, was ruled out by the fact that the native allergen could not be detected by SDS-PAGE and the elution profiles of allergenically active peptides did not coincide with that of native allergen. One of the allergenic sites recognized by monoclonal antibody (Mab) 90, i.e., site A, was located in HPLC fractions 90-100 while another allergenic site B (recognized by Mab 12) appeared to be lost following the sequential digestion of Lol p IV with CNBr and trypsin.

  8. Mouse allergen is the major allergen of public health relevance in Baltimore City.

    PubMed

    Ahluwalia, Sharon K; Peng, Roger D; Breysse, Patrick N; Diette, Gregory B; Curtin-Brosnan, Jean; Aloe, Charles; Matsui, Elizabeth C

    2013-10-01

    Cockroach and mouse allergens have both been implicated as causes in inner-city asthma morbidity in multicenter studies, but whether both allergens are clinically relevant within specific inner-city communities is unclear. Our study aimed to identify relevant allergens in Baltimore City. One hundred forty-four children (5-17 years old) with asthma underwent skin prick tests at baseline and had clinical data collected at baseline and 3, 6, 9, and 12 months. Home settled dust samples were collected at the same time points for quantification of indoor allergens. Participants were grouped based on their sensitization and exposure status to each allergen. All analyses were adjusted for age, sex, and serum total IgE level. Forty-one percent were mouse sensitized/exposed, and 41% were cockroach sensitized/exposed based on bedroom floor exposure data. Mouse sensitization/exposure was associated with acute care visits, decreased FEV1/forced vital capacity percentage values, fraction of exhaled nitric oxide levels, and bronchodilator reversibility. Cockroach sensitization/exposure was only associated with acute care visits and bronchodilator reversibility when exposure was defined by using bedroom floor allergen levels. Mouse-specific IgE levels were associated with poor asthma health across a range of outcomes, whereas cockroach-specific IgE levels were not. The relationships between asthma outcomes and mouse allergen were independent of cockroach allergen. Although sensitization/exposure to both mouse and cockroach was generally associated with worse asthma, mouse sensitization/exposure was the primary contributor to these relationships. In a community with high levels of both mouse and cockroach allergens, mouse allergen appears to be more strongly and consistently associated with poor asthma outcomes than cockroach allergen. Community-level asthma interventions in Baltimore should prioritize reducing mouse allergen exposure. Copyright © 2013 American Academy of Allergy

  9. Hypoallergens for allergen-specific immunotherapy by directed molecular evolution of mite group 2 allergens.

    PubMed

    Gafvelin, Guro; Parmley, Stephen; Neimert-Andersson, Theresa; Blank, Ulrich; Eriksson, Tove L J; van Hage, Marianne; Punnonen, Juha

    2007-02-09

    Allergen-specific immunotherapy is the only treatment that provides long lasting relief of allergic symptoms. Currently, it is based on repeated administration of allergen extracts. To improve the safety and efficacy of allergen extract-based immunotherapy, application of hypoallergens, i.e. modified allergens with reduced IgE binding capacity but retained T-cell reactivity, has been proposed. It may, however, be difficult to predict how to modify an allergen to create a hypoallergen. Directed molecular evolution by DNA shuffling and screening provides a means by which to evolve proteins having novel or improved functional properties without knowledge of structure-function relationships of the target molecules. With the aim to generate hypoallergens we applied multigene DNA shuffling on three group 2 dust mite allergen genes, two isoforms of Lep d 2 and Gly d 2. DNA shuffling yielded a library of genes from which encoded shuffled allergens were expressed and screened. A positive selection was made for full-length, high-expressing clones, and screening for low binding to IgE from mite allergic patients was performed using an IgE bead-based binding assay. Nine selected shuffled allergens revealed 80-fold reduced to completely abolished IgE binding compared with the parental allergens in IgE binding competition experiments. Two hypoallergen candidates stimulated allergen-specific T-cell proliferation and cytokine production at comparable levels as the wild-type allergens in patient peripheral blood mononuclear cell cultures. The two candidates also induced blocking Lep d 2-specific IgG antibodies in immunized mice. We conclude that directed molecular evolution is a powerful approach to generate hypoallergens for potential use in allergen-specific immunotherapy.

  10. De-novo Onset of Eosinophilic Esophagitis After Large Volume Allergen Exposures

    PubMed Central

    Wolf, W. Asher; Jerath, Maya R.; Dellon, Evan S.

    2013-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition believed to have an allergic component, but the timing of the initial allergen triggers that cause the disease is poorly understood. While the clinical presentation of EoE is often of longstanding symptoms, in animal models, acute exposure to an allergen challenge successfully produces EoE. In this report, we present three cases of individuals who developed esophageal eosinophilia and EoE shortly after a clearly identified exposure to aeroallergens. These cases highlight the allergic etiology of EoE, and provide a link from humans to the previously described experimental mechanisms. PMID:23799220

  11. Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses in adult Drosophila brain.

    PubMed

    Gu, Huaiyu; Jiang, Shaojuan Amy; Campusano, Jorge M; Iniguez, Jorge; Su, Hailing; Hoang, Andy An; Lavian, Monica; Sun, Xicui; O'Dowd, Diane K

    2009-01-01

    Voltage-gated calcium channels containing alpha1 subunits encoded by Ca(v)2 family genes are critical in regulating release of neurotransmitter at chemical synapses. In Drosophila, cac is the only Ca(v)2-type gene. Cacophony (CAC) channels are localized in motor neuron terminals where they have been shown to mediate evoked, but not AP-independent, release of glutamate at the larval neuromuscular junction (NMJ). Cultured embryonic neurons also express CAC channels, but there is no information about the properties of CAC-mediated currents in adult brain nor how these channels regulate transmission in central neural circuits where fast excitatory synaptic transmission is predominantly cholinergic. Here we report that wild-type neurons cultured from late stage pupal brains and antennal lobe projection neurons (PNs) examined in adult brains, express calcium currents with two components: a slow-inactivating current sensitive to the spider toxin Plectreurys toxin II (PLTXII) and a fast-inactivating PLTXII-resistant component. CAC channels are the major contributors to the slow-inactivating PLTXII-sensitive current based on selective reduction of this component in hypomorphic cac mutants (NT27 and TS3). Another characteristic of cac mutant neurons both in culture and in whole brain recordings is a reduced cholinergic miniature excitatory postsynaptic current frequency that is mimicked in wild-type neurons by acute application of PLTXII. These data demonstrate that cac encoded Ca(v)2-type calcium channels regulate action potential (AP)-independent release of neurotransmitter at excitatory cholinergic synapses in the adult brain, a function not predicted from studies at the larval NMJ.

  12. Beneficial cross-protection of allergen-specific immunotherapy on airway eosinophilia using unrelated or a partial repertoire of allergen(s) implicated in experimental feline asthma.

    PubMed

    Reinero, Carol; Lee-Fowler, Tekla; Chang, Chee-Hoon; Cohn, Leah; Declue, Amy

    2012-06-01

    The study hypothesis was that in experimentally asthmatic cats rush immunotherapy (RIT) using allergens not completely matched with sensitizing allergen(s) would at least partially attenuate the asthmatic phenotype and modulate the aberrant immune response. In phase I, cats sensitized to Bermuda grass allergen (BGA), house dust mite allergen (HDMA) or placebo received BGA RIT. In phase II, cats dually sensitized to BGA and HDMA received RIT using BGA, HDMA or placebo. Efficacy of RIT was assessed using percentage bronchoalveolar lavage fluid (BALF) eosinophils. Additionally, a variety of immunologic assays were performed. Eosinophilic airway inflammation significantly decreased over time in asthmatic cats given RIT using sensitizing allergen or unrelated allergen (P<0.001). In dually sensitized cats, single allergen RIT but not placebo reduced airway eosinophilia (P=0.038). Differences in allergen-specific lymphocyte proliferation, in the number of IL-10 producing cells and in the percentage T regulatory cells were detected between asthmatic cats getting RIT and controls. Cross-protection manifested by reduced airway eosinophilia was noted in cats treated with RIT allergens which did not completely match allergen used in asthma induction. However, the mechanism of immunologic tolerance may differ when improperly matched allergens to the sensitizing allergens are used in RIT.

  13. Distinct Contributory Factors Determine Basophil-Allergen Sensitivity in Grass Pollen Rhinitis and in Anaphylactic Wasp Venom Allergy.

    PubMed

    Korošec, Peter; Šilar, Mira; Kopač, Peter; Eržen, Renato; Zidarn, Mihaela; Košnik, Mitja

    2016-01-01

    We sought to determine whether basophil-allergen sensitivity could be transferred to donor basophils by passive IgE sensitisation in allergic rhinitis and anaphylactic Hymenoptera venom hypersensitivity. We studied 15 wasp venom-, 19 grass pollen- and 2 house dust mite-allergic patients, 2 healthy donors, and 8 wasp venom-allergic donors. In all subjects, we first evaluated the initial basophil response to wasp venom, grass pollen, or house dust mite allergen. Donor basophils were then stripped, sensitised with the different patients' serum IgE, and challenged with the corresponding allergen. The CD63 response of donor basophils was then compared with initial basophil responses. In wasp venom-allergic subjects, the IgE transfer did not reflect the initial basophil-allergen sensitivity, because the venom IgE of subjects with high or low basophil sensitivity induced comparable responsiveness in healthy donor basophils. Furthermore, vice versa, when we sensitised the donor basophils of wasp venom-allergic individuals with different wasp venom or house dust mite IgE, we demonstrated that their response was predictable by their initial basophil allergen sensitivity. In the rhinitis allergy model, the IgE transfer correlated with the patients' initial basophil responsiveness because the grass pollen IgE of the subjects with high basophil allergen sensitivity induced significantly higher responsiveness of donor basophils than the IgE of subjects with initially low basophil allergen sensitivity. Our results suggest that basophil allergen sensitivity evaluated by flow-cytometric CD63 analysis depends on two distinct contribution factors. In anaphylactic Hymenoptera allergy, the major factor was intrinsic cellular sensitivity, whereas in pollen allergy, the major factor was allergen-specific IgE on the cell surface. © 2016 S. Karger AG, Basel.

  14. Fuzzy logic for personalized healthcare and diagnostics: FuzzyApp--a fuzzy logic based allergen-protein predictor.

    PubMed

    Saravanan, Vijayakumar; Lakshmi, P T V

    2014-09-01

    The path to personalized medicine demands the use of new and customized biopharmaceutical products containing modified proteins. Hence, assessment of these products for allergenicity becomes mandatory before they are introduced as therapeutics. Despite the availability of different tools to predict the allergenicity of proteins, it remains challenging to predict the allergens and nonallergens, when they share significant sequence similarity with known nonallergens and allergens, respectively. Hence, we propose "FuzzyApp," a novel fuzzy rule based system to evaluate the quality of the query protein to be an allergen. It measures the allergenicity of the protein based on the fuzzy IF-THEN rules derived from five different modules. On various datasets, FuzzyApp outperformed other existing methods and retained balance between sensitivity and specificity, with positive Mathew's correlation coefficient. The high specificity of allergen-like putative nonallergens (APN) revealed the FuzzyApp's capability in distinguishing the APN from allergens. In addition, the error analysis and whole proteome dataset analysis suggest the efficiency and consistency of the proposed method. Further, FuzzyApp predicted the Tropomyosin from various allergenic and nonallergenic sources accurately. The web service created allows batch sequence submission, and outputs the result as readable sentences rather than values alone, which assists the user in understanding why and what features are responsible for the prediction. FuzzyApp is implemented using PERL CGI and is freely accessible at http://fuzzyapp.bicpu.edu.in/predict.php . We suggest the use of Fuzzy logic has much potential in biomarker and personalized medicine research to enhance predictive capabilities of post-genomics diagnostics.

  15. Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial).

    PubMed

    Vossen, Liv M; Schurgers, Leon J; van Varik, Bernard J; Kietselaer, Bas L J H; Vermeer, Cees; Meeder, Johannes G; Rahel, Braim M; van Cauteren, Yvonne J M; Hoffland, Ge A; Rennenberg, Roger J M W; Reesink, Koen D; de Leeuw, Peter W; Kroon, Abraham A

    2015-10-28

    Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.

  16. The self-assemble of natural cyclodextrins in aqueous solutions: Application of miniature permeation studies for critical aggregation concentration (cac) determinations.

    PubMed

    Saokham, Phennapha; Sá Couto, André; Ryzhakov, Alexey; Loftsson, Thorsteinn

    2016-05-30

    Permeation techniques can be applied to determine the critical aggregation concentration (cac) of natural cyclodextrins (CDs) in aqueous solutions although the method is both laborious and time consuming. In the present study, the permeation technique was modified and the influence of osmotic pressure, sampling time, CD concentration and molecular weight-cut off (MWCO) of the membrane were investigated in two different permeation units, that is Franz diffusion cells and Slide-A-Lyzer™ MINI Dialysis. While both the osmotic pressure and CD concentration affect the steady state flux in both permeation units, effects of sampling time and the MWCO of the mounted membrane were only observed in the Franz diffusion cells. The osmotic effect was negligible in the Slide-A-Lyzer™ MINI Dialysis units. The modified permeation technique using Slide-A-Lyzer™ MINI Dialysis units was then used to determine the cac of natural CDs in water. The cac of αCD, βCD and γCD was 1.19±0.17, 0.69±0.05 and 0.93±0.04% (w/v), respectively. The results indicated that the cac values depended on their intrinsic solubility. Moreover, the cac value of γCD in aqueous hydrocortisone/γCD inclusion complex solution was identical to the γCD cac value determined in pure water. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Photocatalytic degradation of an azo dye Sunset Yellow under UV-A light using TiO2/CAC composite catalysts

    NASA Astrophysics Data System (ADS)

    Rajamanickam, D.; Shanthi, M.

    2014-07-01

    The photocatalytic activity and the promoting effect of titania (TiO2) by commercial activated carbon (CAC) for removing the pollutant in wastewater were investigated. The TiO2/CAC composite photocatalysts with various ratios of CAC to TiO2 were prepared by sol-gel method. The catalyst was characterized by X-ray diffraction (XRD), high resolution scanning electron microscope (HR-SEM), energy dispersive spectra (EDS), diffuse reflectance spectra (DRS), photoluminescence spectra (PL), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) surface area measurement methods. The photocatalytic activity of TiO2/CAC was investigated for the degradation of Sunset Yellow (SY) in aqueous solution using UV-A light. The TiO2/CAC is found to be more efficient than prepared TiO2 and TiO2-P25 at pH 7 for the mineralization of SY. The synergism between TiO2 and CAC may increase the catalytic activity. The effects of operational parameters such as the amount of photocatalyst, dye concentration and initial pH on photo mineralization of SY have been analyzed. The mineralization of SY has been confirmed by COD measurements. The catalyst is found to be reusable.

  18. Efficacy of NiTi Hand CAC 30 for jejunojejunostomy in gastric cancer surgery: results from a multicenter prospective randomized trial.

    PubMed

    Hur, Hoon; Kim, Hyung Ho; Hyung, Woo Jin; Cho, Gyu Seok; Kim, Wook; Ryo, Seung Wan; Han, Sang-Uk

    2011-06-01

    Although a novel technique for the performance of intestinal sutureless anastomosis using a compression device has recently been investigated, it has not yet received widespread acceptance. We performed a multicenter prospective randomized trial in order to determine the clinical efficacy of the NiTi Hand CAC 30, a type of compression anastomosis clip (CAC), for jejunojejunostomy in gastric cancer surgery. Forty-seven patients from 6 institutions, who were diagnosed with gastric adenocarcinoma, were enrolled; these patients were randomized to a CAC group and a hand-sewn (control) group. Three patients dropped out for various reasons, and results for 44 patients were finally analyzed. The CAC group consisted of 20 patients, and there were 24 patients in the control group. Anastomosis time, the primary endpoint of this trial, was shorter in the CAC group than in the control group (P < 0.001). However, total operation times (P = 0.055) did not differ. All reconstructions were completed by Roux-en-Y anastomosis, and the complication rates of the two groups did not differ (P = 0.908); however, jejunojejunostomy leakage occurred in two patients in the CAC group. Our prospective multicenter clinical trial showed that the use of the NiTi Hand CAC™ 30 for jejunojejunostomy in gastric cancer surgery was feasible and could reduce anastomosis time. However, considering that there were two cases of leakage, extended use of the NiTi Hand CAC™ 30 should be carefully applied.

  19. Photocatalytic degradation of an azo dye Sunset Yellow under UV-A light using TiO2/CAC composite catalysts.

    PubMed

    Rajamanickam, D; Shanthi, M

    2014-07-15

    The photocatalytic activity and the promoting effect of titania (TiO2) by commercial activated carbon (CAC) for removing the pollutant in wastewater were investigated. The TiO2/CAC composite photocatalysts with various ratios of CAC to TiO2 were prepared by sol-gel method. The catalyst was characterized by X-ray diffraction (XRD), high resolution scanning electron microscope (HR-SEM), energy dispersive spectra (EDS), diffuse reflectance spectra (DRS), photoluminescence spectra (PL), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) surface area measurement methods. The photocatalytic activity of TiO2/CAC was investigated for the degradation of Sunset Yellow (SY) in aqueous solution using UV-A light. The TiO2/CAC is found to be more efficient than prepared TiO2 and TiO2-P25 at pH 7 for the mineralization of SY. The synergism between TiO2 and CAC may increase the catalytic activity. The effects of operational parameters such as the amount of photocatalyst, dye concentration and initial pH on photo mineralization of SY have been analyzed. The mineralization of SY has been confirmed by COD measurements. The catalyst is found to be reusable. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial)

    PubMed Central

    Vossen, Liv M.; Schurgers, Leon J.; van Varik, Bernard J.; Kietselaer, Bas L. J. H.; Vermeer, Cees; Meeder, Johannes G.; Rahel, Braim M.; van Cauteren, Yvonne J. M.; Hoffland, Ge A.; Rennenberg, Roger J. M. W.; Reesink, Koen D.; de Leeuw, Peter W.; Kroon, Abraham A.

    2015-01-01

    Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD. PMID:26516910

  1. The effects of dietary supplementation with fish oil lipids on the airways response to inhaled allergen in bronchial asthma.

    PubMed

    Arm, J P; Horton, C E; Spur, B W; Mencia-Huerta, J M; Lee, T H

    1989-06-01

    The effects of dietary supplementation with fish oil lipids on the airways responses to allergen and neutrophil biochemistry and function have been studied in 17 atopic asthmatic subjects. Nine subjects received 18 capsules of Max-EPA (3.2 g eicosapentaenoic acid and 2.2 g docosahexaenoic acid) a day and eight subjects received identical capsules containing olive oil, for 10 wk in a double-blind fashion. There were no differences between prediet values and those observed after dietary supplementation with Max-EPA or placebo in the dose of allergen causing an acute asthmatic response as assessed by a 35% fall in specific airways conductance (PD35), the extinction dose of allergen on skin prick testing, the histamine PD35, or the total serum IgE concentrations. Twelve of the 17 subjects developed late asthmatic responses after allergen challenge prediet. Six of these subjects received Max-EPA, and six received placebo capsules. As compared to prediet values, the magnitude of the allergen-induced late asthmatic response was significantly attenuated from 2 to 7 h after allergen challenge following dietary supplementation with Max-EPA (p less than 0.005) but not with placebo. The attenuation of the late response was not accompanied by any significant change in the clinical severity of disease as assessed by diurnal peak expiratory flow rates, symptom scores, or bronchodilator drug usage.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. [Animal models for assessment of GMO allergenicity: advantages and limitations].

    PubMed

    Adel-Patient, K; Wal, J M

    2004-03-01

    Incidence of IgE-mediated allergic reactions to foods is increasing as well as the severity of associated symptoms and numerous foods are now incriminated, probably in relation with modifications of dietary habits and increased exposure to new or modified food ingredients. Therefore, the introduction on the market of food composed of or derived from genetically modified organisms (GMOs) raised the question of their potential allergenicity. Particularly with regards to the allergenicity of a newly expressed protein, it is necessary to obtain, from several steps in the risk assessment process, a cumulative body of evidence which minimises any uncertainty. This may include the use of animal model despite no fully reliable validated model is available yet. Such animal models should allow to address 3 major issues: Is the novel protein a sensitizer, i.e. does it possess intrinsic properties that allow to sensitize a predisposed individual? Is the protein an elicitor i.e. is it able to elicit an allergic reaction in a sensitised individual? And is the protein an adjuvant, i.e. can it facilitate or enhance the sensitisation to an other protein? Animal models under investigation currently include mice, rats and guinea pigs but models such as dogs and swine also appeared a few years ago. The aim is to mimic the mechanism and characteristics of the sensitisation phase and/or the elicitation phase of the allergic reaction as it occurs in atopic humans. They are necessary because sensitisation studies can obviously not be done in human and because in vitro tests cannot reproduce the complexity of the immune system. We propose a mouse model which mimics both phases of the allergic reaction. It has permitted to evidence that biochemical and clinical manifestations occuring during the active phases of the allergic reaction differ according to the structure of the allergen used for the challenge. This may allow to compare the allergenic potential of a genetically modified protein

  3. Inactivation of allergens and toxins.

    PubMed

    Morandini, Piero

    2010-11-30

    Plants are replete with thousands of proteins and small molecules, many of which are species-specific, poisonous or dangerous. Over time humans have learned to avoid dangerous plants or inactivate many toxic components in food plants, but there is still room for ameliorating food crops (and plants in general) in terms of their allergens and toxins content, especially in their edible parts. Inactivation at the genetic rather than physical or chemical level has many advantages and classical genetic approaches have resulted in significant reduction of toxin content. The capacity, offered by genetic engineering, of turning off (inactivating) specific genes has opened up the possibility of altering the plant content in a far more precise manner than previously available. Different levels of intervention (genes coding for toxins/allergens or for enzymes, transporters or regulators involved in their metabolism) are possible and there are several tools for inactivating genes, both direct (using chemical and physical mutagens, insertion of transposons and other genetic elements) and indirect (antisense RNA, RNA interference, microRNA, eventually leading to gene silencing). Each level/strategy has specific advantages and disadvantages (speed, costs, selectivity, stability, reversibility, frequency of desired genotype and regulatory regime). Paradigmatic examples from classical and transgenic approaches are discussed to emphasize the need to revise the present regulatory process. Reducing the content of natural toxins is a trade-off process: the lesser the content of natural toxins, the higher the susceptibility of a plant to pests and therefore the stronger the need to protect plants. As a consequence, more specific pesticides like Bt are needed to substitute for general pesticides.

  4. Treatment of cockroach allergen asthma model with imatinib attenuates airway responses.

    PubMed

    Berlin, Aaron A; Lukacs, Nicholas W

    2005-01-01

    In the present study it was determined whether a pharmacologic approach to blocking receptor tyrosine kinase-mediated activation during allergic airway responses could be beneficial. To examine these responses, allergic mice were given a single oral dose of imatinib at clinically relevant concentrations, ranging from 0.05 to 50 mg/kg, by oral gavages just before allergen challenge. The reduction in the allergen-induced responses was significant and centered on reducing overall inflammation as well as pulmonary cytokine levels. In particular, the treatment of the mice with imatinib significantly attenuated airway hyperreactivity and peribronchial eosinophil accumulation, and significantly reduced Th2 cytokines, interleukin-4 and interleukin-13. In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals. Together these data demonstrate that the pharmacologic inhibitor imatinib may provide a clinically attractive therapy for allergic, asthmatic responses.

  5. Allergen immunotherapy for allergic respiratory diseases

    PubMed Central

    Cappella, Antonio; Durham, Stephen R.

    2012-01-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy. PMID:23095870

  6. Genetic engineering of allergens for immunotherapy.

    PubMed

    Bonura, Angela; Colombo, Paolo

    2009-06-01

    Allergen-specific immunotherapy was introduced into clinical practice at the beginning of the 20(th) century and its efficacy in the treatment of seasonal allergic rhinitis has been confirmed in many clinical studies which have shown that it can prevent the onset of new sensitizations to different allergens and reduces the development of asthma in patients with allergic rhinitis. Progress in molecular cloning and characterization of allergens have made it possible to produce single recombinant allergens whose immunological properties have been tested in vitro and in vivo and have demonstrated that they retain properties resembling their natural counterpart. Several rational approaches are being developed to improve the efficacy of SIT by reducing immunoglobulin IgE-mediated adverse reactions. Some of these molecules have been tested in the clinic, demonstrating the feasibility of using biotechnology-derived products as new standardized, improved and safer therapeutic compositions.

  7. [Governmental batch sample testing of allergen products].

    PubMed

    Bartel, D; Führer, F; Vieths, S

    2012-03-01

    Allergen products for specific immunotherapy of type I allergies were first authorized for the German market in the 1970s. In addition to finished products manufactured in advance and in batches, so-called named patient products have recently been defined as Medicinal Products by the German Medicinal Products Act ("Arzneimittelgesetz", AMG 14th Revision 2005). Some allergen products previously marketed as named patient products are now required to obtain marketing authorization according to the German ordinance for therapy allergens. Products have to be batch released by the competent German Federal Agency, the Paul-Ehrlich-Institut (PEI). Samples of product batches are delivered to the PEI in order to perform experimental quality controls. With regard to named patient products, PEI tests batch samples of the bulk extract preparations used for manufacturing of the respective, named patient products. The institute releases approximately 2,800 allergen product batches annually.

  8. Allergen immunotherapy for allergic respiratory diseases.

    PubMed

    Cappella, Antonio; Durham, Stephen R

    2012-10-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy.

  9. Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma.

    PubMed

    Chen, Ruchong; Smith, Steven G; Salter, Brittany; El-Gammal, Amani; Oliveria, John Paul; Obminski, Caitlin; Watson, Rick; O'Byrne, Paul M; Gauvreau, Gail M; Sehmi, Roma

    2017-09-15

    Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma. Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge. ILC2 (lin(-)FcεRI(-)CD45(+)CD127(+)ST2(+)) and CD4(+)T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4(+) T cells was investigated in vitro. A significant increase in total, IL-5(+), IL-13(+), and CRTH2(+) ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5(+), and IL-13(+), but not CRTH2(+), CD4(+) T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4(+) cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5(+) ILC2 at all time points and allergen-induced changes in IL-5(+) CD4(+) cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types. Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4(+) T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.

  10. Investigation on possible allergenicity of 19 different commercial enzymes used in the food industry.

    PubMed

    Bindslev-Jensen, Carsten; Skov, Per Stahl; Roggen, Erwin L; Hvass, Peter; Brinch, Ditte Sidelmann

    2006-11-01

    The aim of the study was to investigate the safety to allergic patients of 19 commercially available and authority-approved enzymes used in the food industry. Enzymes produced by genetically modified organisms were included. Four hundred consecutive adult patients with a diagnosed allergy to inhalation allergens, food allergens, bee or wasp were included. All had at least one positive skin prick test to the above allergens. Skin prick testing with the 19 enzymes was performed on the forearm and if positive (in 13 patients), in vitro histamine release from blood basophils were performed. Patients with positive results in skin prick test were subsequently reinvestigated with further purified enzymes and finally challenged orally with the enzymes in a double-blind, placebo-controlled protocol. Only one reaction to a placebo challenge was seen. In some instances a positive skin prick test result or a positive histamine release was seen elicited by the enzymes, but since none of the patients were positive to any of the commercial enzymes in the subsequent oral challenges using exaggerated dosages of the enzymes compared to normal daily intake, the findings are without clinical relevance. A wide variety of enzyme classes and origins was included in the study. Because there were no allergenic findings of clinical relevance it is concluded that ingestion of food enzymes in general is not considered to be a concern with regard to food allergy.

  11. Next generation of food allergen quantification using mass spectrometric systems.

    PubMed

    Koeberl, Martina; Clarke, Dean; Lopata, Andreas L

    2014-08-01

    Food allergies are increasing worldwide and becoming a public health concern. Food legislation requires detailed declarations of potential allergens in food products and therefore an increased capability to analyze for the presence of food allergens. Currently, antibody-based methods are mainly utilized to quantify allergens; however, these methods have several disadvantages. Recently, mass spectrometry (MS) techniques have been developed and applied to food allergen analysis. At present, 46 allergens from 11 different food sources have been characterized using different MS approaches and some specific signature peptides have been published. However, quantification of allergens using MS is not routinely employed. This review compares the different aspects of food allergen quantification using advanced MS techniques including multiple reaction monitoring. The latter provides low limits of quantification for multiple allergens in simple or complex food matrices, while being robust and reproducible. This review provides an overview of current approaches to analyze food allergens, with specific focus on MS systems and applications.

  12. Recombinant allergens for diagnosis of cockroach allergy.

    PubMed

    Arruda, L Karla; Barbosa, Michelle C R; Santos, Ana Beatriz R; Moreno, Adriana S; Chapman, Martin D; Pomés, Anna

    2014-04-01

    Molecular cloning of cockroach allergens and their expression as recombinant proteins have allowed a better understanding of the mechanisms of cockroach allergic disease. Recombinant cockroach allergens have been used for skin testing or in vitro methods to measure IgE antibody levels in serum. Early studies evaluating selected U.S. patients revealed that a cocktail of four cockroach allergens, Bla g 1, Bla g 2, Bla g 4, and Bla g 5, would identify 95 % of cockroach allergic patients. More recent studies pointed to an important role of sensitization to tropomyosin among certain populations, and suggested that a cocktail of five allergens Bla g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and Bla g 7, and/or Per a 7, would be expected to diagnose 50- 64 % of cockroach-allergic patients worldwide. Variation in IgE reactivity profiles could be in part due to IgE responses to cross-reactive homologous allergens from different origins. The availability of purified natural or recombinant cockroach allergens provides the capacity to improve diagnosis of cockroach allergy and to develop novel forms of immunotherapy for cockroach-allergic patients.

  13. AllerML: markup language for allergens.

    PubMed

    Ivanciuc, Ovidiu; Gendel, Steven M; Power, Trevor D; Schein, Catherine H; Braun, Werner

    2011-06-01

    Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis.

  14. Breed-specific dog-dandruff allergens.

    PubMed

    Lindgren, S; Belin, L; Dreborg, S; Einarsson, R; Påhlman, I

    1988-08-01

    Fifty-one patients with clinical history of dog allergy were skin prick tested with eight individual standardized dog breed-allergen preparations, one mixed breed-allergen preparation (Poodle/Alsatian), dog-serum albumin, and histamine hydrochloride, 1 mg/ml. All extracts were characterized by crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis with a pool of sera from patients clinically sensitive to dog. The dog-breed extracts contained common antigens/allergens, as well as components represented only in one or two dog-breed extracts. The concentration corresponding 1000 BU/ml varied from 16 to 100 micrograms of protein per milliliter. The sensitivity of skin prick test was 67% to 88% for the various dog breed-allergen preparations, but only 18% for dog-serum albumin. Significant difference between the skin test response to different dog breed-allergen preparations indicating dog breed-specific allergens was obtained in 15% of the patients. There was no significant correlation between skin prick test results and symptoms related to a specific dog breed.

  15. Proteomic analysis of wheat flour allergens.

    PubMed

    Akagawa, Mitsugu; Handoyo, Tri; Ishii, Takeshi; Kumazawa, Shigenori; Morita, Naofumi; Suyama, Kyozo

    2007-08-22

    Wheat can cause severe IgE-mediated systematic reactions, but knowledge on relevant wheat allergens at the molecular level is scanty. The aim of the present study was to achieve a more detailed and comprehensive characterization of the wheat allergens involved in food allergy to wheat using proteomic strategies, referred to as "allergenomics". Whole flour proteins were separated by two-dimensional gel electrophoresis with isoelectric focusing and lithium dodecyl sulfate-polyacrylamide gel electrophoresis. Then, IgE-binding proteins were detected by immunoblotting with sera of patients with a food allergy to wheat. After tryptic digestion, the peptides of IgE-binding proteins were analyzed by matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry. In this study, we identified four previously reported wheat allergens or their sequentially homologous proteins [serpin, alpha-amylase inhibitor, gamma-gliadin, and low molecular weight (LMW) glutenin] by a database search. As a result of the high resolution of two-dimensional gel electrophoresis, nine subunits of LMW glutenins were identified as the most predominant IgE-binding antigens. The two-dimensional allergen map can be beneficial in many ways. It could be used, for example, for precise diagnosis of wheat-allergic patients and assessment of wheat allergens in food. Additionally, we compared allergenomics to conventional biochemical methods and evaluated the usefulness of a proteomic strategy for identifying putative allergens to wheat allergy.

  16. Recombinant Allergens for Diagnosis of Cockroach Allergy

    PubMed Central

    Barbosa, Michelle C. R.; Santos, Ana Beatriz R.; Moreno, Adriana S.; Chapman, Martin D.; Pomés, Anna

    2014-01-01

    Molecular cloning of cockroach allergens and their expression as recombinant proteins have allowed a better understanding of the mechanisms of cockroach allergic disease. Recombinant cockroach allergens have been used for skin testing or in vitro methods to measure IgE antibody levels in serum. Early studies evaluating selected U.S. patients revealed that a cocktail of four cockroach allergens, Bla g 1, Bla g 2, Bla g 4, and Bla g 5, would identify 95 % of cockroach allergic patients. More recent studies pointed to an important role of sensitization to tropomyosin among certain populations, and suggested that a cocktail of five allergens Bla g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and Bla g 7, and/or Per a 7, would be expected to diagnose 50–64 % of cockroach-allergic patients worldwide. Variation in IgE reactivity profiles could be in part due to IgE responses to cross-reactive homologous allergens from different origins. The availability of purified natural or recombinant cockroach allergens provides the capacity to improve diagnosis of cockroach allergy and to develop novel forms of immunotherapy for cockroach-allergic patients. PMID:24563284

  17. Removing peanut allergens by tannic acid.

    PubMed

    Chung, Si-Yin; Reed, Shawndrika

    2012-10-01

    Tannic acid (TA) forms insoluble complexes with proteins. The aims here were to remove major peanut allergens as insoluble TA complexes and determine if they would dissociate and release the allergens at pH 2 and 8 (gut pH). Release of the allergens in the gut could lead to absorption and consequently an allergic reaction. TA (0.25, 0.5, 1, and 2 mg/ml) was added to a peanut butter extract (5 mg/ml; pH 7.2), stirred, and centrifuged. The precipitates were then suspended in buffer at pH 2, centrifuged, re-suspended at pH 8, and centrifuged. Supernatants from each step were analysed by SDS-PAGE, ELISA, and Western blots. The effect of NaCl (1M) on complexes was also determined. Results showed that complexes formed at a TA concentration >0.5 mg/ml did not release major peanut allergens at pH 2 and 8, regardless of 1M NaCl being present or not. IgE binding of the extracts was reduced substantially, especially at a TA concentration of 1-2 mg/ml. Animal or clinical studies are still needed before TA can find an application in the development of low-allergen peanut products/beverages or the removal of peanut allergens due to accidental ingestion. Published by Elsevier Ltd.

  18. High pressure effects on allergen food proteins.

    PubMed

    Somkuti, Judit; Smeller, László

    2013-12-15

    There are several proteins, which can cause allergic reaction if they are inhaled or ingested. Our everyday food can also contain such proteins. Food allergy is an IgE-mediated immune disorder, a growing health problem of great public concern. High pressure is known to affect the structure of proteins; typically few hundred MPa pressure can lead to denaturation. That is why several trials have been performed to alter the structure of the allergen proteins by high pressure, in order to reduce its allergenicity. Studies have been performed both on simple protein solutions and on complex food systems. Here we review those allergens which have been investigated under or after high pressure treatment by methods capable of detecting changes in the secondary and tertiary structure of the proteins. We focus on those allergenic proteins, whose structural changes were investigated by spectroscopic methods under pressure in correlation with the observed allergenicity (IgE binding) changes. According to this criterion we selected the following allergen proteins: Mal d 1 and Mal d 3 (apple), Bos d 5 (milk), Dau c 1 (carrot), Gal d 2 (egg), Ara h 2 and Ara h 6 (peanut), and Gad m 1 (cod). Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Advances in allergen-specific immunotherapy.

    PubMed

    Passalacqua, Giovanni; Compalati, Enrico; Canonica, Giorgio Walter

    2009-12-01

    After several decades of controversies, allergen specific immunotherapy (SIT) was recognized as an effective treatment for respiratory and hymenoptera allergy by the World Health Organization in 1998. SIT involves the administration (usually subcutaneous) of increasing doses of allergen in order to achieve a hyposensitization. Moreover, SIT is the only allergen-specific treatment capable of modifying the natural history of the disease. During the last 25 years, there was an impressive development of basic and clinical research in the field of SIT, with the goal of improving the safety, the efficacy and ameliorating the knowledge on the mechanisms of action. In this regard, the sublingual route (SLIT) was extensively studied and, recently, validated. SLIT can be considered a milestone in the history of SIT, since it is expected to change the clinical practice. In parallel, the growing detailed knowledge of the immunological mechanisms of SIT has provided the opportunity to explore new forms of specific hyposensitization, such as the use of adjuvants (bacterial and DNA-based), recombinant and engineered allergens, allergenic peptides and chimeric molecules. The last frontier seems to be the manipulation of genoma with replicons and allergen-encoding plasmids.

  20. AllerML: Markup Language for Allergens

    PubMed Central

    Ivanciuc, Ovidiu; Gendel, Steven M.; Power, Trevor D.; Schein, Catherine H.; Braun, Werner

    2011-01-01

    Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. PMID:21420460

  1. Patients choice for method of early abortion among comprehensive abortion care (CAC) clients at Kathmandu Medical College Teaching Hospital (KMCTH).

    PubMed

    Saha, R; Shrestha, N S; Koirala, B; Kandel, P; Shrestha, S

    2007-01-01

    The over all objective of the study was to determine different methods of abortion opted by CAC clients at KMCTH. The specific objective of the study was to know the reasons for pregnancy termination and to know the reasons opted for either medical or surgical method of abortion. A hospital based prospective study was carried out for a period of six months at KMCTH from 1st January 2006 to 31st June 2006. All the patient undergoing CAC services were included for the study. Clients were provided with written and verbal information regarding the methods of terminating early abortion and its associated complications. After that they were asked to give their informed choice and decision. All the pertinent information was entered on pre-structured questionnaire. During the study period a total of 100 patients underwent CAC services. The commonest reason for termination pregnancy was no desire for additional children (60%) followed by youngest child too small or short spacing (21%). 74% of the patients opted for surgical abortion, 23% patient opted for medical abortion and 3% of the patient remain undecided. Reasons for favouring surgical method of abortion was that surgical abortion is complete (35), repeated visits are avoided (18), quick (10) would be with service provider and feel safe (5), lack of expectancy (2) side effect of medical treatment (1), twin pregnancy (1), easy (1), fear of pain (1). Medical method of abortion was favoured due to fear of surgery (9), easy and less painful (8) and maintains privacy (6). Factors affecting the choice of abortion method appear to be numerous and complex. Providers need to be sensitive to differences in women's values and life circumstances when counselling them about an abortion method. In particular, providers should incorporate into their counselling sessions what women need to know about the characteristics of abortion methods and help women to identify what is the best option for them. Key words: Early abortion medical

  2. The Role of Allergen Exposure and Avoidance in Asthma

    PubMed Central

    Baxi, Sachin N.; Phipatanakul, Wanda

    2010-01-01

    Allergy testing and avoidance of allergens plays an important role in asthma control. Increased allergen exposure, in genetically susceptible individuals, can lead to allergic sensitization. Continued allergen exposure can increase the risk of asthma and other allergic diseases. In a patient with persistent asthma, identification of indoor and outdoor allergens and subsequent avoidance can improve symptoms. Often times, a patient will have multiple allergies and the avoidance plan should target all positive allergens. Several studies have shown that successful allergen remediation includes a comprehensive approach including education, cleaning, physical barriers and maintaining these practices. PMID:20568555

  3. Inhibiting Peanut Allergen Digestion with p-Aminobenzamidine Attached to the Allergens

    USDA-ARS?s Scientific Manuscript database

    Peanut allergens can be digested into peptide fragments despite being known as resistant proteins. Once absorbed, the peptide fragments from digested allergens could bind to immunoglobulin E (IgE) antibodies and cause an allergic reaction in allergic individuals. To reduce peanut allergy, one approa...

  4. Effect of oleic acid on the allergenic properties of peanut and cashew allergens

    USDA-ARS?s Scientific Manuscript database

    Oleic acid is the major fatty acid in peanuts and cashews. There is limited information about its effect on peanut and cashew allergens during heating. The objective was to determine if heat treatment with oleic acid changes the allergenic properties of these nut proteins. Peanut and cashew protein...

  5. Early allergen exposure and atopic eczema.

    PubMed

    Harris, J M; Williams, H C; White, C; Moffat, S; Mills, P; Newman Taylor, A J; Cullinan, P

    2007-04-01

    The relationship between exposure to indoor aeroallergens in early life and subsequent eczema is unclear. We have previously failed to show any significant associations between early life exposure to house dust mite and cat fur allergens and either sensitization to these allergens or wheeze. We have also previously reported a lower prevalence of parent-reported, doctor-diagnosed eczema by age 2 years for children exposed to higher concentrations of house dust mite, but no other associations with other definitions of eczema or for exposure to cat allergen. To extend the exposure-response analysis of allergen exposure and eczema outcomes measured up to age 8 years, and to investigate the role of other genetic and environmental determinants. A total of 593 children (92 x 4% of those eligible) born to all newly pregnant women attending one of three general practitioner surgeries in Ashford, Kent, were followed from birth to age 8 years. Concentrations of house dust mite and cat allergen were measured in dust samples collected from the home at 8 weeks after birth. The risk of subsequent eczema as defined by the U.K. diagnostic criteria was determined according to different levels (quintiles) of allergen exposure at birth. By age 8 years, 150 (25 x 3%) children had met the diagnostic criteria for eczema at least once. Visible flexural dermatitis was recorded at least once for 129 (28 x 0%). As in other studies, parental allergic history was positively associated with most eczema outcomes, as were higher maternal education and less crowded homes. No clear linear associations between early exposure to house dust mite or cat allergen were found, regardless of the definition of eczema used. The risk of eczema appeared to increase for the three lowest quintiles of house dust mite allergen exposure (odds ratio, OR 1 x 37 for third quintile compared with first), and then to fall for the two highest quintiles (OR 0 x 66 and 0 x 71) even after controlling for confounding factors

  6. Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.

    PubMed

    Fernandez, A; Mills, E N C; Lovik, M; Spoek, A; Germini, A; Mikalsen, A; Wal, J M

    2013-12-01

    Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Sensitive detection of major food allergens in breast milk: first gateway for allergenic contact during breastfeeding.

    PubMed

    Pastor-Vargas, C; Maroto, A S; Díaz-Perales, A; Villaba, M; Casillas Diaz, N; Vivanco, F; Cuesta-Herranz, J

    2015-08-01

    Food allergy is recognized as a major public health issue, especially in early childhood. It has been hypothesized that early sensitization to food allergens maybe due to their ingestion as components dissolved in the milk during the breastfeeding, explaining reaction to a food, which has never been taken before. Thus, the aim of this work has been to detect the presence of the food allergens in breast milk by microarray technology. We produced a homemade microarray with antibodies produced against major food allergens. The antibody microarray was incubated with breast milk from 14 women collected from Fundación Jiménez Díaz Hospital. In this way, we demonstrated the presence of major foods allergens in breast milk. The analysis of allergens presented in breast milk could be a useful tool in allergy prevention and could provide us a key data on the role of this feeding in tolerance induction or sensitization in children.

  8. Is high pressure treatment able to modify the allergenicity of the largemouth bass allergens?

    NASA Astrophysics Data System (ADS)

    Liu, Chu-Yi; Tao, Sha; Liu, Rong; Chen, Fu-Sheng; Xue, Wen-Tong

    2012-12-01

    The aim of this paper is to study the influence of high pressure treatment on the structural changes and allergenicity of largemouth bass. We treated the allergens at 100, 200, 300 and 400 MPa for 15 min and at 300 MPa for 5, 10, 15, 20 and 30 min at 20 °C. The treated samples from largemouth bass were tested for their IgE-binding properties by combining Sodium dodecyl sulfate-Polyacrylamide gel electrophoresis (SDS-PAGE) with western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Circular dichroism analysis was performed to characterize the structural change. In summary, we can determine that the greatest structure changes were found for samples treated by 400 MPa for 15 min. High pressure treatment did change the structure, subunit composition and molecular weight of largemouth bass allergens, but it did not change the allergenicity of the allergens.

  9. Expression, purification, and characterization of almond (Prunus dulcis) allergen Pru du 4

    USDA-ARS?s Scientific Manuscript database

    Biochemical characterizations of food allergens are required for understanding the allergenicity of food allergens. Such studies require a relatively large amount of highly purified allergens. Profilins from numerous species are known to be allergens, including food allergens, such as almond (Prunus...

  10. The spectrum of olive pollen allergens.

    PubMed

    Rodríguez, R; Villalba, M; Monsalve, R I; Batanero, E

    2001-07-01

    Olive pollen is one of the most important causes of seasonal respiratory allergy in Mediterranean countries, where this tree is intensely cultivated. Among the high number of protein allergens detected in this pollen, 8 - Ole e 1 to Ole e 8 - have been isolated and characterized. Ole e 1 is the most frequent sensitizing agent, affecting more than 70% of the patients suffering of olive pollinosis, although others, such as Ole e 4 and Ole e 7, have also been shown to be major allergens. In this context, the prevalence of many olive pollen allergens seems to be dependent on the geographical area where the sensitized patients live. Some of the olive allergens have been revealed as members of known protein families: profilin (Ole e 2), Ca(2+)-binding proteins (Ole e 3 and Ole e 8), superoxide dismutase (Ole e 5) and lipid transfer protein (Ole e 7). No biological function has been demonstrated for Ole e 1, whereas Ole e 4 and Ole e 6 are new proteins without homology to known sequences from databases. cDNAs encoding for Ole e 1, Ole e 3 and Ole e 8 have been overproduced in heterologous systems. The recombinant products were correctly folded and exhibited the functional activities of the natural allergens. In addition to the Oleaceae family, other species, such as Gramineae or Betulaceae, contain pollen allergens structurally or immunologically related to those of the olive tree. This fact allows to detect and evaluate antigenic cross-reactivities involving olive allergens. The aim of this research is the development of new diagnostic tools for olive pollinosis and new approaches to improve the classical immunotherapy.

  11. Allergens of the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Westwood, Greg S; Huang, Shih-Wen; Keyhani, Nemat O

    2005-01-11

    BACKGROUND: Beauveria bassiana is an important entomopathogenic fungus currently under development as a bio-control agent for a variety of insect pests. Although reported to be non-toxic to vertebrates, the potential allergenicity of Beauveria species has not been widely studied. METHODS: IgE-reactivity studies were performed using sera from patients displaying mould hypersensitivity by immunoblot and immunoblot inhibition. Skin reactivity to B. bassiana extracts was measured using intradermal skin testing. RESULTS: Immunoblots of fungal extracts with pooled as well as individual sera showed a distribution of IgE reactive proteins present in B. bassiana crude extracts. Proteinase K digestion of extracts resulted in loss of IgE reactive epitopes, whereas EndoH and PNGaseF (glycosidase) treatments resulted in minor changes in IgE reactive banding patterns as determined by Western blots. Immunoblot inhibitions experiments showed complete loss of IgE-binding using self protein, and partial inhibition using extracts from common allergenic fungi including; Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, Candida albicans, Epicoccum purpurascens, and Penicillium notatum. Several proteins including a strongly reactive band with an approximate molecular mass of 35 kDa was uninhibited by any of the tested extracts, and may represent B. bassiana specific allergens. Intradermal skin testing confirmed the in vitro results, demonstrating allergenic reactions in a number of individuals, including those who have had occupational exposure to B. bassiana. CONCLUSIONS: Beauveria bassiana possesses numerous IgE reactive proteins, some of which are cross-reactive among allergens from other fungi. A strongly reactive potential B. bassiana specific allergen (35 kDa) was identified. Intradermal skin testing confirmed the allergenic potential of B. bassiana.

  12. Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness

    PubMed Central

    2013-01-01

    Background Allergen-specific immunotherapy has been demonstrated to have potential for the treatment of allergic diseases. Transgenic animals are currently the best available bioreactors to produce recombinant proteins, which can be secreted in milk. It has not been clearly demonstrated whether milk from transgenic animals expressing recombinant allergens has immunomodulatory effects on allergic asthma. Methods We aimed to determine whether the oral administration of milk containing a mite allergen can down-regulate allergen-specific airway inflammation. Transgenic CD-1 mice that express a recombinant group 2 allergen from Dermatophagoides pteronyssinus (Dp2) in their milk were generated using an embryonic gene-microinjection technique. Mouse pups were fed transgenic Dp2-containing milk or wild-type milk. Subsequently, these mice were sensitized and challenged with Dp2 to induce allergic airway inflammation. Results Upon sensitization and challenge, mice fed transgenic Dp2 milk had decreased T-helper 2 (Th2) and increased T-helper 1 (Th1) responses in the airway compared with mice fed wild-type milk. Moreover, pre-treatment with transgenic Dp2 milk attenuated airway inflammation and decreased airway hyper-responsiveness. Conclusions This study provides new evidence that oral administration of transgenic milk containing the Dp2 allergen down-regulated and moderately protected against allergic airway inflammation. Milk from transgenic animals expressing allergens may have potential use in the prevention of allergic asthma. PMID:23763898

  13. Temporal role of chemokines in a murine model of cockroach allergen-induced airway hyperreactivity and eosinophilia.

    PubMed

    Campbell, E M; Kunkel, S L; Strieter, R M; Lukacs, N W

    1998-12-15

    The increase in inner-city asthma among children appears to be due to allergic responses to several allergens. Recent studies have demonstrated that Ags derived from cockroaches are especially prominent in these settings and a significant health concern for the induction of asthma in children. In the present study, we have outlined the development of a murine model of cockroach allergen-induced airway disease and assessed specific mechanisms of the response, which resembles atopic human asthma. The allergic responses in this model include allergen-specific airway eosinophilia and significantly altered airway physiology, which directly correlates with inflammation. We have further utilized this allergen to establish primary and secondary rechallenge stages of late phase hyperreactivity exacerbation. This latter stage is characterized by greater changes in airway physiology than the primary stage, and it is likely due to the preexisting peribronchial inflammation present at the time of the second allergen rechallenge. We have identified specific roles for CC chemokines during these stages, with MIP-1alpha being an important eosinophil attractant during the primary stage and eotaxin during the secondary rechallenge stage. The development of these models allows the evaluation of mediators involved in both stages of cockroach allergen challenge, as well as the testing of specific therapeutic modalities.

  14. The type of sensitizing allergen can affect the evolution of respiratory allergy.

    PubMed

    Marogna, M; Massolo, A; Berra, D; Zanon, P; Chiodini, E; Canonica, G W; Passalacqua, G

    2006-10-01

    Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. The different type of allergen influences the course of the disease, as well as the use of immunotherapy.

  15. Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach allergen-induced asthma.

    PubMed

    Berlin, Aaron A; Hogaboam, Cory M; Lukacs, Nicholas W

    2006-06-01

    The progression and severity of chronic asthma likely depends upon the intensity of the damage and remodeling of the tissue. We have developed a chronic model of allergic asthma using multiple cockroach allergen challenges. Using this clinically relevant allergen we have established significant peribronchial fibrosis and mucus overproduction. These remodeling events are accompanied by intense peribronchial inflammation, including lymphocytes and eosinophils. A cytokine that has been identified as having a prominent role in short-term allergic events, stem cell factor (SCF), appears to have a significant role in this late-stage process. Using our polyclonal antibody specific for SCF administered into the airways of mice during the final allergen challenges, we find a significant effect on the chronic peribronchial allergen-induced fibrotic remodeling. This was characterized by reduced inflammation, especially eosinophils, as well as reduced hydroxyproline levels in anti-SCF compared to control antibody-treated animals. In addition, when we examined chemokines associated with the chronic disease and neutralized SCF in vivo we observed a corresponding decrease in CCL6 and CCL17. Using an inhibitor, imatinib mesylate, that blocks SCF/c-kit-associated RTK, we find similar results as with anti-SCF for attenuating AHR and fibrotic changes, suggesting that a potential clinical treatment for chronic asthma already exists related to this pathway. These results further support the potential use of SCF/c-kit inhibition for targeting chronic severe asthmatic responses.

  16. Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury.

    PubMed

    Jung, Chien-Cheng; Su, Huey-Jen

    2016-05-01

    The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury.

  17. Pressure induced polymerization of acetylide anions in CaC2 and 107 fold enhancement of electrical conductivity

    DOE PAGES

    Zheng, Haiyan; Wang, Lijuan; Li, Kuo; ...

    2016-08-17

    Transformation between different types of carbon–carbon bonding in carbides often results in a dramatic change of physical and chemical properties. Under external pressure, unsaturated carbon atoms form new covalent bonds regardless of the electrostatic repulsion. It was predicted that calcium acetylide (also known as calcium carbide, CaC2) polymerizes to form calcium polyacetylide, calcium polyacenide and calcium graphenide under high pressure. In this work, the phase transitions of CaC2 under external pressure were systematically investigated, and the amorphous phase was studied in detail for the first time. Polycarbide anions like C66– are identified with gas chromatography-mass spectrometry and several other techniques,more » which evidences the pressure induced polymerization of the acetylide anions and suggests the existence of the polyacenide fragment. Additionally, the process of polymerization is accompanied with a 107 fold enhancement of the electrical conductivity. As a result, the polymerization of acetylide anions demonstrates that high pressure compression is a viable route to synthesize novel metal polycarbides and materials with extended carbon networks, while shedding light on the synthesis of more complicated metal organics.« less

  18. Ab-initio study of p magnetism in CaN and CaC monolayers on Cu(001)

    NASA Astrophysics Data System (ADS)

    Akbarzadeh, Hadi; Zahedifar, Maedeh; Nourbakhsh, Zahra; Hashemifar, S. Javad

    2014-03-01

    Ab-initio calculations are performed to study the p ferromagnetic CaC and CaN compounds in the zinc-blend (zb) and rock-salt (rs) structures and their monolayers on Cu(001). It is observed that within the generalized gradient functional both structures of the bulk compounds are half-metal, while the rs structure exhibits higher stability. It is argued the strong interatomic exchange interaction in these systems controls the splitting of the spin resolved bond points while it has no considerable effect on total bond strength. In contrast to the bulk compounds, the CaC and CaN monolayers on Cu(001) generally favor the zb structure and the anion terminated monolayers are more stable than the cation terminated ones. On the other hand, the anion terminated systems are non- or weak magnetic systems while the less stable cation terminated layers exhibit strong magnetization. In the case of CaN monolayer on Cu(001), the nudged elastic band calculations show an activation barrier of 1.18 eV per CaN unit between the higher energy ferromagnetic and the stable nonmagnetic terminations. Therefore, epitaxial growth of a Ca terminated CaN thin film on Cu (001) is likely a practical way to form a novel half-metal/metal junction.

  19. Update in the Mechanisms of Allergen-Specific Immunotheraphy

    PubMed Central

    Akkoc, Tunc; Akdis, Mübeccel

    2011-01-01

    Allergic diseases represent a complex innate and adoptive immune response to natural environmental allergens with Th2-type T cells and allergen-specific IgE predominance. Allergen-specific immunotherapy is the most effective therapeutic approach for disregulated immune response towards allergens by enhancing immune tolerance mechanisms. The main aim of immunotherapy is the generation of allergen nonresponsive or tolerant T cells in sensitized patients and downregulation of predominant T cell- and IgE-mediated immune responses. During allergen-specific immunotherapy, T regulatory cells are generated, which secrete IL-10 and induce allergen-specific B cells for the production of IgG4 antibodies. These mechanisms induce tolerance to antigens that reduces allergic symptoms. Although current knowledge highlights the role of T regulatory cell-mediated immunetolerance, definite mechanisms that lead to a successful clinical outcomes of allergen-specific immunotherapy still remains an open area of research. PMID:21217920

  20. 78 FR 66011 - Allergenic Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ..., perennial rye, Timothy, and Kentucky bluegrass mixed pollens allergen extract tablet for sublingual use... recommendations on the safety and efficacy of Grastek, a Timothy grass pollen allergen extract tablet...

  1. 76 FR 59406 - Allergenic Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... medical literature concerning the use of non-standardized allergen extracts in the diagnosis and treatment... Scientific and Medical Literature and Information on Non-Standardized Allergen Extracts in the Diagnosis...

  2. Inhalation of diesel exhaust enhances allergen-related eosinophil recruitment and airway hyperresponsiveness in mice.

    PubMed

    Takano, H; Ichinose, T; Miyabara, Y; Shibuya, T; Lim, H B; Yoshikawa, T; Sagai, M

    1998-06-01

    We have previously shown that intratracheal instillation of suspension of diesel exhaust particles enhances allergen-related eosinophilic airway inflammation, airway hyperresponsiveness, and local expression of interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present study was designed to elucidate the effects of daily inhalation of diesel exhaust (DE) on the allergen-related respiratory disease. ICR mice were exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen-related eosinophil recruitment to the submucosal layers of the airways and to the bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the lung in a dose-dependent manner compared to exposure to clean air. There were strong correlations between the number of eosinophils in bronchoalveolar lavage (BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue supernatants. In addition, the increases in eosinophil recruitment and local cytokine expression were accompanied by goblet cell proliferation in the bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In contrast, the control mice exposed for 40 weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no eosinophil recruitment to the submucosal layers of the airways nor to the bronchoalveolar space and few goblet cells in the bronchial epithelium. The present study provides experimental evidence that daily inhalation of DE can enhance allergen-related respiratory diseases such as allergic asthma. This effect may be mediated by the enhanced local expression of IL-5 and GM-CSF. Increased ambient levels of DE may be implicated in the increasing prevalence of bronchial asthma in recent years.

  3. Evaluation of the Allergenicity Potential of TcPR-10 Protein from Theobroma cacao

    PubMed Central

    Cardoso, Thyago Hermylly Santana; Pirovani, Carlos Priminho; Micheli, Fabienne; Noronha, Fátima Soares Motta; Alves, Andréa Catão; Faria, Ana Maria Caetano; da Silva Gesteira, Abelmon

    2012-01-01

    Background The pathogenesis related protein PR10 (TcPR-10), obtained from the Theobroma cacao-Moniliophthora perniciosa interaction library, presents antifungal activity against M. perniciosa and acts in vitro as a ribonuclease. However, despite its biotechnological potential, the TcPR-10 has the P-loop motif similar to those of some allergenic proteins such as Bet v 1 (Betula verrucosa) and Pru av 1 (Prunus avium). The insertion of mutations in this motif can produce proteins with reduced allergenic power. The objective of the present work was to evaluate the allergenic potential of the wild type and mutant recombinant TcPR-10 using bioinformatics tools and immunological assays. Methodology/Principal Findings Mutant substitutions (T10P, I30V, H45S) were inserted in the TcPR-10 gene by site-directed mutagenesis, cloned into pET28a and expressed in Escherichia coli BL21(DE3) cells. Changes in molecular surface caused by the mutant substitutions was evaluated by comparative protein modeling using the three-dimensional structure of the major cherry allergen, Pru av 1 as a template. The immunological assays were carried out in 8–12 week old female BALB/c mice. The mice were sensitized with the proteins (wild type and mutants) via subcutaneous and challenged intranasal for induction of allergic airway inflammation. Conclusions/Significance We showed that the wild TcPR-10 protein has allergenic potential, whereas the insertion of mutations produced proteins with reduced capacity of IgE production and cellular infiltration in the lungs. On the other hand, in vitro assays show that the TcPR-10 mutants still present antifungal and ribonuclease activity against M. perniciosa RNA. In conclusion, the mutant proteins present less allergenic potential than the wild TcPR-10, without the loss of interesting biotechnological properties. PMID:22768037

  4. Modifications of allergenicity linked to food technologies.

    PubMed

    Moneret-Vautrin, D A

    1998-01-01

    The prevalence of food allergies (FA) has increased over the past fifteen years. The reasons suggested are changes in dietary behaviour and the evolution of food technologies. New cases of FA have been described with chayote, rambutan, arguta, pumpkin seeds, custard apple, and with mycoproteins from Fusarium.... Additives using food proteins are at high risk: caseinates, lysozyme, cochineal red, papaïn, alpha-amylase, lactase etc. Heating can reduce allergenicity or create neo-allergens, as well as storage, inducing the synthesis of allergenic stress or PR proteins. Aeroallergens (miles, moulds) contaminate foods and can induce allergic reactions. Involuntary contamination by peanut proteins on production lines is a problem which is not yet solved. Genetically modified plants are at risk of allergenicity, requiring methodological steps of investigations: the comparison of the amino-acid sequence of the transferred protein with the sequence of known allergens, the evaluation of thermo degradability and of the denaturation by pepsin and trypsin are required, as well as the study with sera from patients allergic to the plant producing the gene. The combination of enzymatic hydrolysis, heating, or the development of genetically modified plants may offer new alternatives towards hypoallergenic foods (57 references).

  5. Allergenic potential and enzymatic resistance of buckwheat

    PubMed Central

    Lee, Sujin; Han, Youngshin; Do, Jeong-Ryong

    2013-01-01

    Buckwheat is known as a health food but is one of the major food allergens triggering potentially fatal anaphylaxis in Asia, especially in Japan and Korea. This study was conducted to investigate the characteristic of enzymatic resistance of buckwheat protein and allergenic potential. Enzymatic resistance of buckwheat protein was performed with in vitro digestibility test in simulated gastric fluid (SGF), pH 1.2, using pepsin and simulated intestinal fluid (SIF) using chymotrypsin. Reactivity of buckwheat proteins to human IgE was performed using six allergic patients sensitized to buckwheat. Buckwheat's IgE levels were measured using the Phadia UniCAP-system. Buckwheat protein, 16 kDa, still remained after 30 min treatment of pepsin on SDS-PAGE. Even though 16 kDa almost disappeared after 60 min treatment, two out of the six buckwheat patients' sera showed reactivity to hydrolysate after 60 min treatment, indicating that allergenicity still remained. In simulated intestinal fluid (SIF) using chymotrypsin, buckwheat protein, 24 kDa, showed resistance to hydrolysis with chymotrypsin on SDS-PAGE, and still had allergenicity based on the result of ELISA. Our results suggest that buckwheat proteins have strong resistance to enzyme degradation. This may be attributed in part to the allergenic potential of buckwheat. Further study should be continued regarding buckwheat allergy. PMID:23423876

  6. Pollensomes as Natural Vehicles for Pollen Allergens.

    PubMed

    Prado, Noela; De Linares, Concepción; Sanz, María L; Gamboa, Pedro; Villalba, Mayte; Rodríguez, Rosalía; Batanero, Eva

    2015-07-15

    Olive (Olea europaea) pollen constitutes one of the most important allergen sources in the Mediterranean countries and some areas of the United States, South Africa, and Australia. Recently, we provided evidence that olive pollen releases nanovesicles of respirable size, named generically pollensomes, during in vitro germination. Olive pollensomes contain allergens, such as Ole e 1, Ole e 11, and Ole e 12, suggesting a possible role in allergy. The aim of this study was to assess the contribution of pollensomes to the allergic reaction. We show that pollensomes exhibit allergenic activity in terms of patients' IgE-binding capacity, human basophil activation, and positive skin reaction in sensitized patients. Furthermore, allergen-containing pollensomes have been isolated from three clinically relevant nonphylogenetically related species: birch (Betula verrucosa), pine (Pinus sylvestris), and ryegrass (Lolium perenne). Most interesting, pollensomes were isolated from aerobiological samples collected with an eight-stage cascade impactor collector, indicating that pollensomes secretion is a naturally occurring phenomenon. Our findings indicate that pollensomes may represent widespread vehicles for pollen allergens, with potential implications in the allergic reaction.

  7. Mechanisms of allergen-specific immunotherapy

    PubMed Central

    2012-01-01

    Allergen-specific immunotherapy (allergen-SIT) is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg) cells and inducible IL-10- and TGF-β-producing type 1 Treg (Tr1) cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro-inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non-inflammatory antibodies particularly IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases. PMID:22409879

  8. Structure and function of milk allergens.

    PubMed

    Wal, J M

    2001-01-01

    Proteins (CMP) involved in milk allergy are numerous and heterogeneous, with very few structural or functional common features. This heterogeneity is complicated by their genetic polymorphism, resulting in several variants for each protein. These variants are characterized by point substitutions of amino acids or by deletions of peptide fragments of varying size or by post-translational modifications such as phosphorylation or glycosylation. All of these modifications may affect allergenicity. No common molecular structure can be associated with allergenicity, although some homologous regions such as casein phospho-peptides can explain an IgE cross-reactivity. Three-dimensional structure is an important feature in CMP allergenicity but denatured and linear epitopes are also involved. Epitopes are numerous and widely spread along the CMP molecule. They may be located in hydrophobic parts of the molecule where they are inaccessible for IgE antibodies in the native conformation of the protein but become bioavailable after digestive processes. Peptides as short as ca. 12-14 amino acid residues may account for a significant part of the allergenicity of the whole molecule, which justifies the need to be careful before proposing any CMP hydrolysate for highly allergenic children.

  9. Indoor determinants of dustborne allergens in Mexican homes

    PubMed Central

    Hernández-Cadena, Leticia; Zeldin, Darryl C.; Sever, Michelle L.; Sly, Peter D.; London, Stephanie J.; Escamilla-Nuñez, María Consuelo; Romieu, Isabelle

    2015-01-01

    Exposure to indoor allergens represents a significant risk factor for allergies and asthma in several parts of the world. In Mexico, few studies have evaluated indoor allergens, including cat, dog, and mouse allergens and the factors that predict their presence. This study evaluates the main environmental and household predictors of high prenatal allergen levels and multiple allergen exposures in a birth cohort from Mexico City. A cross-sectional study was conducted as part of a birth cohort study of 1094 infants recruited during pregnancy and followed until delivery. We collected dust samples in a subset of 264 homes and assessed environmental factors. Der p 1, Der f 1, dust mite group 2, Fel d 1, Can f 1, Rat n 1, Mus m 1, and Bla g 2 concentrations in dust samples were measured using immunoassays. To define detectable allergen levels, the lowest limits of detection for each allergen were taken as cutoff points. Overall allergen exposure was considered high when four or more allergens exceeded detectable levels in the same household. Logistic regression was used for predictive models. Eighty-five percent of homes had at least one allergen in dust over the detection limit, 52.1% had high exposure (four or more allergens above detectable limits), and 11.7% of homes had detectable levels for more than eight allergens. Der p 1, Der p 2, Mus m 1, and Fel d 1 were the most frequent allergens detected. Each allergen had both common and distinct predictors. The main predictors of a high multiple allergen index were the size of the home, pesticide use, mother's age, mother as homemaker, and season. Increased indoor environmental allergen exposure is mainly related to sociodemographic factors and household cleaning. PMID:25715241

  10. Origin and Functional Prediction of Pollen Allergens in Plants.

    PubMed

    Chen, Miaolin; Xu, Jie; Devis, Deborah; Shi, Jianxin; Ren, Kang; Searle, Iain; Zhang, Dabing

    2016-09-01

    Pollen allergies have long been a major pandemic health problem for human. However, the evolutionary events and biological function of pollen allergens in plants remain largely unknown. Here, we report the genome-wide prediction of pollen allergens and their biological function in the dicotyledonous model plant Arabidopsis (Arabidopsis thaliana) and the monocotyledonous model plant rice (Oryza sativa). In total, 145 and 107 pollen allergens were predicted from rice and Arabidopsis, respectively. These pollen allergens are putatively involved in stress responses and metabolic processes such as cell wall metabolism during pollen development. Interestingly, these putative pollen allergen genes were derived from large gene families and became diversified during evolution. Sequence analysis across 25 plant species from green alga to angiosperms suggest that about 40% of putative pollen allergenic proteins existed in both lower and higher plants, while other allergens emerged during evolution. Although a high proportion of gene duplication has been observed among allergen-coding genes, our data show that these genes might have undergone purifying selection during evolution. We also observed that epitopes of an allergen might have a biological function, as revealed by comprehensive analysis of two known allergens, expansin and profilin. This implies a crucial role of conserved amino acid residues in both in planta biological function and allergenicity. Finally, a model explaining how pollen allergens were generated and maintained in plants is proposed. Prediction and systematic analysis of pollen allergens in model plants suggest that pollen allergens were evolved by gene duplication and then functional specification. This study provides insight into the phylogenetic and evolutionary scenario of pollen allergens that will be helpful to future characterization and epitope screening of pollen allergens. © 2016 American Society of Plant Biologists. All rights reserved.

  11. Indoor determinants of dustborne allergens in Mexican homes.

    PubMed

    Hernández-Cadena, Leticia; Zeldin, Darryl C; Barraza-Villarreal, Albino; Sever, Michelle L; Sly, Peter D; London, Stephanie J; Escamilla-Nuñez, María Consuelo; Romieu, Isabelle

    2015-01-01

    Exposure to indoor allergens represents a significant risk factor for allergies and asthma in several parts of the world. In Mexico, few studies have evaluated indoor allergens, including cat, dog, and mouse allergens and the factors that predict their presence. This study evaluates the main environmental and household predictors of high prenatal allergen levels and multiple allergen exposures in a birth cohort from Mexico City. A cross-sectional study was conducted as part of a birth cohort study of 1094 infants recruited during pregnancy and followed until delivery. We collected dust samples in a subset of 264 homes and assessed environmental factors. Der p 1, Der f 1, dust mite group 2, Fel d 1, Can f 1, Rat n 1, Mus m 1, and Bla g 2 concentrations in dust samples were measured using immunoassays. To define detectable allergen levels, the lowest limits of detection for each allergen were taken as cutoff points. Overall allergen exposure was considered high when four or more allergens exceeded detectable levels in the same household. Logistic regression was used for predictive models. Eighty-five percent of homes had at least one allergen in dust over the detection limit, 52.1% had high exposure (four or more allergens above detectable limits), and 11.7% of homes had detectable levels for more than eight allergens. Der p 1, Der p 2, Mus m 1, and Fel d 1 were the most frequent allergens detected. Each allergen had both common and distinct predictors. The main predictors of a high multiple allergen index were the size of the home, pesticide use, mother's age, mother as homemaker, and season. Increased indoor environmental allergen exposure is mainly related to sociodemographic factors and household cleaning.

  12. Evaluation of allergenic potency by REAST inhibition. A new tool for the standardization of allergenic extracts.

    PubMed

    Falagiani, P; Mistrello, G; Rapisarda, G; Festa, A; Cislaghi, C; Zanoni, D

    1994-08-01

    The potency of allergenic extracts can be determined in vitro by RAST inhibition, and this has become the preferred method for the standardization of allergens. A disadvantage of this technique is the impossibility of obtaining data about allergens bound to the solid phase, i.e., the counterpart of the inhibiting extract. The REAST (reverse enzyme allergosorbent test) is based on the capture of IgE by a specific antibody bound to microtiter wells, the reaction of captured IgE with biotinylated allergen and the development of a colour reaction by subsequent addition of streptavidin-peroxidase and chromogenic substrate. The addition of an allergen extract in a dose-response fashion competes with the biotinylated allergen and inhibits the test. In the present study REAST inhibition has been evaluated with Dermatophagoides pteronyssinus, Parietaria judaica and mixed grass pollen extracts. The correlation of REAST inhibition with RAST inhibition and both intra-assay and inter-assay reproducibility have been evaluated. REAST inhibition is a potentially valuable new tool for the standardization of allergenic extracts.

  13. Crosslinking of peanut allergen Ara h 2 by polyphenol oxidase: digestibility and potential allergenicity assessment.

    PubMed

    Wu, Zhihua; Lian, Jun; Han, Yuanlong; Zhou, Ningling; Li, Xin; Yang, Anshu; Tong, Ping; Chen, Hongbing

    2016-08-01

    Peanut is one of the eight major food allergens. Its allergen, Ara h 2, can be recognized by over 90% of serum IgE samples from peanut-allergic patients. Therefore, reducing the allergenicity of Ara h 2 is especially important. In the present study, polyphenol oxidase (PPO), a protein cross-linking reaction catalyst that acts on tyrosine residue, was used to modify Ara h 2. After crosslinking, the microstructure, digestibility, IgG binding capability and IgE binding capability of Ara h 2 were analyzed. Cross-linking decreased the potential allergenicity of Ara h 2 by masking the allergen epitope, while the antigenicity of Ara h 2 changed slightly. After crosslinking, the apparent diameter of Ara h 2 was altered from 300 to 1700 nm or 220 nm, indicating that polymerization could either be inter- or intramolecular. Regarding digestibility, crosslinked Ara h 2 was relatively more easily digested by gastric fluid compared with the untreated Ara h 2, but much more difficult in the intestinal fluid. The crosslinking reaction catalyzed by PPO, as a non-thermal process, may be beneficial for avoiding food allergy. The reaction could mask allergen epitopes, decreasing the allergenicity of Ara h 2. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  14. Allergenic components in three different species of Penicillium: crossreactivity among major allergens.

    PubMed

    Shen, H D; Lin, W L; Tsai, J J; Liaw, S F; Han, S H

    1996-04-01

    Penicillium species have been considered as important causative agents of extrinsic bronchial asthma. However, little is known about the allergens of these ubiquitous airborne fungal species. This study compares the allergenic profiles and allergenic crossreactivity among allergens of three prevalent airborne Penicillium species. IgE-binding Penicillium components were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)-immunoblotting using sera from 67 asthmatic patients. The presence of allergenic crossreactivity was analysed by immunoblot inhibition. Among the 67 serum samples tested, 15, 14 and 11 samples showed IgE reactivity to components of P. citrinum, P. notatum and P. brevicompactum, respectively. All 15 P. citrinum-positive serum samples showed IgE-binding to a 33 kDa extract component of this species. Thirteen (93%) of the 14 P. notatum-positive serum samples and 10 (91%) of the 11 P. brevicompactum-positive sera also showed IgE reactivity to components with a molecular weight of about 33 kDa in individual Penicillium species. All of the 10 P. brevicompactum 33 kDa component-positive serum samples showed IgE reactivity to the 33 kDa components of the other two Penicillium species tested. Dose-dependent inhibition of IgE-binding to these major allergens was observed when the positive serum sample was absorbed with different amounts of individual allergenic extract as well as with different amounts of extracts prepared from the other two Penicillium species. Although different allergenic profiles were observed in the three different Penicillium species tested, results showed that there was an IgE crossreactivity among the 33 kDa group major allergens of P. citrinum, P. notatum and P. brevicompactum.

  15. Allergenic proteins of natural rubber latex.

    PubMed

    Yeang, H Y; Arif, Siti Arija M; Yusof, Faridah; Sunderasan, E

    2002-05-01

    As the living cytoplasm of laticiferous cells, Hevea brasiliensis latex is a rich blend of organic substances that include a mélange of proteins. A small number of these proteins have given rise to the problem of latex allergy. The salient characteristics of H. brasiliensis latex allergens that are recognized by the International Union of Immunological Societies (IUIS) are reviewed. These are the proteins associated with the rubber particles, the cytosolic C-serum proteins and the B-serum proteins that originate mainly from the lutoids. Procedures for the isolation and purification of latex allergens are discussed, from latex collection in the field to various preparative approaches adopted in the laboratory. As interest in recombinant latex allergens increases, there is a need to validate recombinant proteins to ascertain equivalence with their native counterparts when used in immunological studies, diagnostics, and immunotherapy.

  16. Clinical use of adjuvants in allergen-immunotherapy.

    PubMed

    Klimek, L; Schmidt-Weber, C B; Kramer, M F; Skinner, M A; Heath, M D

    2017-02-04

    Introduction Allergen-specific Immunotherapy (AIT) is the only available treatment aimed to tackle the underlying causes of allergy. The active components of subcutaneous vaccines traditionally consist of natural or modified allergen extracts which can be combined with adjuvant platforms. In recent years new targets have been further developed in an attempt to raise the safety and efficacy profile of AIT. Areas Covered In this review, we discuss the desirable attributes of adjuvants and delivery systems from empiricism to rational design, for current and future clinical applications in AIT. Expert Summary The introduction of novel adjuvants, in combination with active targets, has been demonstrated to reduce side-effects of AIT, increase clinical efficacy of allergy treatment and reduce the number of doses. The evolution of vaccine development for AIT is entering a phase of scientific progress that challenges dogmas. Over the past century the traditional concept of immunotherapy, entailing long-course administration of native extract preparations and first generation adjuvants has seen evolution in the past decade from proof-of-concept to clinical development pipelines encompassing the advent of second generation adjuvants and delivery systems that form essential components of modern AIT development.

  17. Ant allergens and hypersensitivity reactions in response to ant stings.

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

    Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments.

  18. Multiplex detection of food allergens and gluten.

    PubMed

    Cho, Chung Y; Nowatzke, William; Oliver, Kerry; Garber, Eric A E

    2015-05-01

    To help safeguard the food supply and detect the presence of undeclared food allergens and gluten, most producers and regulatory agencies rely on commercial test kits. Most of these are ELISAs with a few being PCR-based. These methods are very sensitive and analyte specific, requiring different assays to detect each of the different food allergens. Mass spectrometry offers an alternative approach whereby multiple allergens may be detected simultaneously. However, mass spectrometry requires expensive equipment, highly trained analysts, and several years before a quantitative approach can be achieved. Using multianalyte profiling (xMAP®) technology, a commercial multiplex test kit based on the use of established antibodies was developed for the simultaneous detection of up to 14 different food allergens plus gluten. The assay simultaneously detects crustacean seafood, egg, gluten, milk, peanut, soy, and nine tree nuts (almond, Brazil nut, cashew, coconut, hazelnut, macadamia, pine nut, pistachio, and walnut). By simultaneously performing multiple tests (typically two) for each analyte, this magnetic bead-based assay offers built-in confirmatory analyses without the need for additional resources. Twenty-five of the assays were performed on buffer extracted samples, while five were conducted on samples extracted using reduced-denatured conditions. Thus, complete analysis for all 14 allergens and gluten requires only two wells of a 96-well microtiter plate. This makes it possible to include in a single analytical run up to 48 samples. All 30 bead sets in this multiplex assay detected 5 ng/mL of food allergen and gluten with responses greater than background. In addition, 26 of the bead sets displayed signal/noise ratios of five or greater. The bead-based design makes this 30-plex assay expandable to incorporate new antibodies and capture/detector methodologies by ascribing these new detectors to any of the unassigned bead sets that are commercially available.

  19. Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis.

    PubMed

    Weido, A J; Reece, L M; Alam, R; Cook, C K; Sim, T C

    1996-11-01

    Allergen-induced nasal responses are associated with the recovery of proinflammatory mediators and cytokines. In recent years, a distinct group of chemotactic cytokines, chemokines, has been the focus of intense investigation as to their possible role in the pathogenesis of allergic diseases. Although corticosteroids have been known to be effective in the treatment of allergic diseases, their mechanism(s) of action has not been fully elucidated. To study the effect of topical fluticasone on the recovery of chemokines (IL-8, MIP-1 alpha, and RANTES) and other cytokines (IL-1 beta, IL-6, and GM-CSF) from nasal mucosa following allergen challenge. To correlate the improvement of rhinitis symptoms with cytokine levels during early-phase and late-phase allergic responses. A randomized, double-blind, placebo-controlled crossover study of fluticasone propionate, 200 micrograms q d, was performed in ten subjects with allergic rhinitis. Allergen challenge was administered after 1 week of treatment. Nasal secretions were collected immediately after challenge and during the late-phase reactions; symptom scores were recorded simultaneously. Nasal cytokines were assayed by specific ELISA. The allergen challenge caused early-phase and late-phase allergic reactions and increased recovery of IL-1 beta, IL-6, IL-8, RANTES, MIP-1 alpha, and GM-CSF from the nasal mucosa. Intranasal fluticasone inhibited the allergen-induced increase in nasal symptoms. This was associated with decreases in cytokine recovery. A significant correlation was observed between decreases in cytokine levels and in symptom scores after treatment. Our results suggest that treatment with topical fluticasone propionate inhibits allergen-induced nasal responses and the associated increase in the production/secretion of chemokines and other proinflammatory cytokines.

  20. Early surgical outcomes of NiTi endoluminal compression anastomotic clip (NiTi CAC 30) use in patients with gastrointestinal malignancy.

    PubMed

    Kim, Hyoung Ran; Lee, Woo Yong; Jung, Kyung Uk; Yun, Hae-Ran; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Chun, Ho-Kyung

    2012-06-01

    The NiTi endoluminal Compression Anastomotic Clip (CAC™) 30 (NiTi CAC 30) (NiTi Alloys Technologies, Ltd., Netanya, Israel) is a new device with shape-memory characteristics. We aimed to investigate the safety and early surgical outcomes of NiTi CAC 30 for intestinal anastomosis in patients with gastrointestinal malignancy. Fifty patients operated on with NiTi CAC 30 were matched for sex, age, body mass index, operation type (open versus laparoscopy), operation name, and anastomosis type with patients in a control group operated on with a stapling device between November 2009 and May 2010. Early clinical outcomes were investigated. One misfired case of NiTi CAC 30 was excluded. Between the two groups, no significant differences were observed in demographics except for previous abdominal operation history. The results of early clinical outcomes were investigated, including operation time, estimated blood loss, time to first flatus, first defecation, and discharge, and complications. No differences were noted. Postoperatively, migration started in 1 patient between 3 and 5 days, 11 patients between 6 to 7 days, and 37 patients after 8 days. The expulsion of 31 cases occurred between 2 and 3 weeks, postoperatively. The NiTi CAC 30 was expulsed within 1 week in 4 patients and between 1 to 2 weeks in 8 patients. An expulsion occurred in 1 case at over 4 weeks. No problems related to early migration and expulsion were observed, and no anastomotic leakage and bleeding occurred. Intestinal anastomosis with the NiTi CAC 30 was safe and feasible without anastomotic leakage and reoperation compared with the stapling technique.

  1. Allergen-Specific Immunotherapy in Food Anaphylaxis

    PubMed Central

    2008-01-01

    Specific immunotherapy (SIT) protocols for nutritional allergens have only recently been established with a focus on oral allergy syndrome because of pollen cross-reacting antibodies. For these patients, a substantial number of studies have been published suggesting benefits from SIT. The situation in true anaphylaxis to food allergens such as peanut allergy is more complex, and therapeutic strategies are based on individual protocols rather than controlled studies. However, in defined cases, SIT represents a promising approach for a durable protection from life-threatening risks after accidental ingestion. PMID:23283385

  2. The contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat.

    PubMed

    Kuper, C Frieke; Stierum, Rob H; Boorsma, Andre; Schijf, Marcel A; Prinsen, Menk; Bruijntjes, Joost P; Bloksma, Nanne; Arts, Josje H E

    2008-04-18

    All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%, day 7) and a head/nose-only inhalation challenge of 27mg/m3 of DNCB (15 min, day 21), using a protocol that successfully identified chemical respiratory allergens. Skin allergy to DNCB was examined in BN rats and Th1-prone Wistar rats in a local lymph node assay followed by a topical patch challenge of 0.1% DNCB. Sensitization of BN rats via the skin induced DNCB-specific IgG in serum, but not in all animals, and an increased number of CD4+ cells in the lung parenchyma. Subsequent inhalation challenge with DNCB did not provoke apneas or allergic inflammation (signs of respiratory allergy) in the BN rats. However, microarray analysis of mRNA isolated from the lung revealed upregulation of the genes for Ccl2 (MCP-1), Ccl4 (MIP-1beta), Ccl7 and Ccl17. Skin challenge induced considerably less skin irritation and allergic dermatitis in the BN rat than in the Wistar rat. In conclusion, the Th2-prone BN rat appeared less sensitive to DNCB than the Wistar rat; nevertheless, DNCB induced allergic inflammation in the skin of BN rats but even a relatively high challenge concentration did not induce allergy in the respiratory tract, although genes associated with allergy were upregulated in lung tissue.

  3. Soybean flour asthma: detection of allergens by immunoblotting

    SciTech Connect

    Bush, R.K.; Schroeckenstein, D.; Meier-Davis, S.; Balmes, J.; Rempel, D.

    1988-08-01

    A 43-year-old woman developed asthma 6 years after beginning work in a food-processing plant in which soybean flour was used as a protein extender. Symptoms of sneezing, coughing, and wheezing would begin within minutes of exposure to soybean flour and resolve 2 hours after exposure ceased. Skin tests were positive to a soy extract prepared from the flour. Airway hyperreactivity was confirmed by a positive bronchial challenge to methacholine. Bronchial challenge with soybean flour produced an immediate increase in specific airway resistance from 5.0 to 22.7 L. cm of H2O/L/sec. There was no response to challenge with lactose. The patient's allergic response to soy-flour extract was further characterized by several immunologic methods. IgE binding to soy-flour protein by direct RAST was 5.98 times that of a normal control serum. The soy-flour extract was separated by dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty-four protein bands were detected in the crude soy-flour extract. After immunoblotting and subsequent autoradiography, nine proteins with molecular weights ranging from 54,500 to 14,875 were found. Cross-reactivity studies with other legumes demonstrated apparent immunologic identity between a component in green pea extract and a soybean protein with a molecular weight of 17,000. The clinical significance of this cross-reactivity is not known. We conclude that in this case of occupational asthma to soybean flour, multiple allergens were involved. Immunoblotting may be useful in identifying the allergens involved in occupational asthma.

  4. Effects of age and allergen-induced airway inflammation in cats: radiographic and cytologic correlation.

    PubMed

    Kirschvink, Nathalie; Kersnak, Emilie; Leemans, Jérôme; Delvaux, François; Clercx, Cécile; Snaps, Frédéric; Gustin, Pascal

    2007-11-01

    Thoracic radiography is an important diagnostic tool for feline respiratory medicine. The aim of this study was (1) to assess age-related changes of thoracic radiographic views in healthy young cats and (2) to test if experimentally-induced bronchial inflammation by inhaling Ascaris suum (AS) allergens leads to radiographic changes after single or repeated exposures. Healthy cats (n=15-30) aged between 6 and 30 months were evaluated. Eight healthy cats and eight AS-sensitised cats, respectively, inhaled sterile saline or allergen. Radiographs were taken 24h before, and 6, 24 and 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed after the last radiographic examination. AS-sensitised cats underwent three further allergen challenges at 3-month intervals. The radiographic evaluation was based on a scoring system considering bronchial, interstitial and alveolar patterns. A significant age-related increase in interstitial and total radiographic score was detected in healthy cats older than 18 months and in healthy cats older than 24 months. Whilst saline inhalation did not affect radiographic scores, a single AS challenge induced significant changes of all scores within 6-24h. A significant positive correlation between radiographic scores and BAL neutrophils and eosinophils was found. Repeated AS challenges did not induce irreversible changes in radiographic scores.

  5. Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4-dependent dermal dendritic cells.

    PubMed

    Deckers, Julie; Sichien, Dorine; Plantinga, Maud; Van Moorleghem, Justine; Vanheerswynghels, Manon; Hoste, Esther; Malissen, Bernard; Dombrowicz, David; Guilliams, Martin; De Bosscher, Karolien; Lambrecht, Bart N; Hammad, Hamida

    2017-02-09

    Exposure to allergens, such as house dust mite (HDM), through the skin often precedes allergic inflammation in the lung. It was proposed that TH2 sensitization through the skin occurs when skin barrier function is disrupted by, for example, genetic predisposition, mechanical damage, or the enzymatic activity of allergens. We sought to study how HDM applied to unmanipulated skin leads to TH2 sensitization and to study which antigen-presenting cells mediate this process. HDM was applied epicutaneously by painting HDM on unmanipulated ear skin or under an occlusive tape. HDM challenge was through the nose. Mouse strains lacking different dendritic cell (DC) populations were used, and 1-DER T cells carrying a transgenic T-cell receptor reactive to Der p 1 allergen were used as a readout for antigen presentation. The TH2-inducing capacity of sorted skin-derived DC subsets was determined by means of adoptive transfer to naive mice. Epicutaneous HDM application led to TH2 sensitization and eosinophilic airway inflammation upon intranasal HDM challenge. Skin sensitization did not require prior skin damage or enzymatic activity within HDM extract, yet was facilitated by applying the allergen under an occlusive tape. Primary proliferation of 1-DER T cells occurred only in the regional skin-draining lymph nodes. Epicutaneous sensitization was found to be driven by 2 variants of interferon regulatory factor 4-dependent dermal type 2 conventional DC subsets and not by epidermal Langerhans cells. These findings identify skin type 2 conventional DCs as crucial players in TH2 sensitization to common inhaled allergens that enter the body through the skin and can provoke features of allergic asthma. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Measurement of airborne mite allergen exposure in individual subjects.

    PubMed

    Sakaguchi, M; Inouye, S; Sasaki, R; Hashimoto, M; Kobayashi, C; Yasueda, H

    1996-05-01

    To evaluate the extent of personal exposure to airborne mite allergens, subjects were asked to carry a personal air sampler when in their houses. The level of Der 1 allergen trapped by the sampler was measured with a highly sensitive immunoassay. There were great variations in airborne Der 1 exposure in each subject. When used bedding was replaced with new allergen-free bedding, we detected a decrease in the allergen level. The use of new bedding seems to be an effective measure for reducing airborne mite allergen exposure.

  7. Prioritisation of allergenic foods with respect to public health relevance: Report from an ILSI Europe Food Allergy Task Force Expert Group.

    PubMed

    Houben, Geert; Burney, Peter; Chan, Chun-Han; Crevel, René; Dubois, Anthony; Faludi, Roland; Klein Entink, Rinke; Knulst, André; Taylor, Steve; Ronsmans, Stefan

    2016-03-01

    Regulators and risk managers in general need to decide whether an allergenic food or ingredient is of such public health importance that it needs to be actively managed. There is therefore a need to scale the relative allergenicity of foods and ingredients according to the hazards they pose. Objective criteria increase transparency and trust in this decision-making process and its conclusions. This paper proposes a framework that allows categorisation and prioritisation of allergenic foods according to their public health importance. The challenge is to find a basis on which the allergenicity of foods can best be described and a method to combine the relevant measures of allergenicity into a scoring system that prioritises allergenic foods on the basis of their public health relevance. The framework is designed in accordance with the generic risk analysis principles used in food safety and can be used by regulators to decide whether or not a specific allergenic food or ingredient is of sufficient public health importance that it warrants regulation (i.e. mandatory labelling) when used in the production of food products.

  8. Behaviour of chemical respiratory allergens in novel predictive methods for skin sensitisation.

    PubMed

    Basketter, David; Poole, Alan; Kimber, Ian

    2017-03-06

    Asthma resulting from sensitisation of the respiratory tract to chemicals is an important occupational health issue, presenting many toxicological challenges. Most importantly there are no recognised predictive methods for respiratory allergens. Nevertheless, it has been found that all known chemical respiratory allergens elicit positive responses in assays for skin sensitising chemicals. Thus, chemicals failing to induce a positive response in skin sensitisation assays such as the local lymph node assay (LLNA) lack not only skin sensitising activity, but also the potential to cause respiratory sensitisation. However, it is unclear whether it will be possible to regard chemicals that are negative in in vitro skin sensitisation tests also as lacking respiratory sensitising activity. To address this, the behaviour of chemical respiratory allergens in the LLNA and in recently validated non-animal tests for skin sensitisation have been examined. Most chemical respiratory allergens are positive in one or more newly validated non-animal test methods, although the situation varies between individual assays. The use of an integrated testing strategy could provide a basis for recognition of most respiratory sensitising chemicals. However, a more complete picture of the performance characteristics of such tests is required before specific recommendations can be made.

  9. Potential allergenicity research of Cry1C protein from genetically modified rice.

    PubMed

    Cao, Sishuo; He, Xiaoyun; Xu, Wentao; Luo, Yunbo; Ran, Wenjun; Liang, Lixing; Dai, Yunqing; Huang, Kunlun

    2012-07-01

    With the development of genetically modified crops, there has been a growing interest in available approaches to assess the potential allergenicity of novel gene products. We were not sure whether Cry1C could induce allergy. We examined the protein with three other proteins to determine the potential allergenicity of Cry1C protein from genetically modified rice. Female Brown Norway (BN) rats received 0.1 mg peanut agglutinin (PNA), 1mg potato acid phosphatase (PAP), 1mg ovalbumin (OVA) or 5 mg purified Cry1C protein dissolved in 1 mL water by daily gavage for 42 days to test potential allergenicity. Ten days after the last gavage, rats were orally challenged with antigens, and physiologic and immunologic responses were studied. In contrast to sensitization with PNA, PAP and OVA Cry1C protein did not induce antigen-specific IgG2a in BN rats. Cytokine expression, serum IgE and histamine levels and the number of eosinophils and mast cells in the blood of Cry1C group rats were comparable to the control group rats, which were treated with water alone. As Cry1C did not show any allergenicity, we make the following conclusion that the protein could be safety used in rice or other plants.

  10. Allergen immunotherapy: how to balance the different views from pulmonologists and allergists?

    PubMed

    Incorvaia, Cristoforo; Fuiano, Nicola; Frati, Franco

    2012-08-01

    Allergen immunotherapy (AIT) is the treatment characterizing the allergological approach to respiratory allergy. Unfortunately, most available data from the literature and current practice indicate that pulmonologists do no consider AIT when choosing the treatment strategy in patients with asthma. Indeed AIT, from its introduction in 1911 to nowadays, was unceasingly improved and has accumulated clear evidence on its effectiveness. Moreover, AIT has a characteristic not shared by drugs in the capacity to modify the natural history of asthma, due to its immunologic mechanisms of actions, and thus also works after the treatment withdrawal. This also makes AIT a clearly cost-effective treatment over time. It is surprising that pulmonologists, for whom asthma is a major disease to manage, do not consider AIT when choosing the optimal treatment in single patients. The insufficient information on AIT and the availability of allergen extracts with less than good quality are likely to be the most important factors influencing such an attitude. The current development of standardized, pharmaceutical-grade products for AIT seems capable of making allergen extracts comparable to drugs and to stimulate a rethinking of AIT's role in the treatment of asthma in pulmonologists. A reappraisal of the significance of the allergen-specific bronchial challenge could represent a further factor suggesting AIT as a reliable option.

  11. Safety of engineered allergen-specific immunotherapy vaccines

    PubMed Central

    Focke-Tejkl, Margarete; Valenta, Rudolf

    2015-01-01

    Purpose of review The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines. Recent findings In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule. Summary Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines. PMID:22885888

  12. [Elimination of airborne allergens from the household environment].

    PubMed

    de Blay, F; Casel, S; Colas, F; Spirlet, F; Pauli, G

    2000-02-01

    Exposure to allergens could be either a risk factor of sensitization and nonspecific hyperresponsiveness in genetically predisposed patients or a risk of onset of asthma attack in certain allergic asthma. During the past 20 years, in western countries the houses have become higher and the number of furred pets have increased and have been more kept inside the house which makes probable that exposure to indoor aeroallergen has increased. The development of new methods of allergen measurements allows a more precise identification of allergen source and reservoirs, an assessment of allergen exposure and a monitoring of allergen eviction methods. Concerning mite allergens, controlled studies which showed a clinical efficacy are those with a global mite eviction and at least a 6 months follow-up for cat and dog allergens, high efficiency-filters air cleaners or vacuum-cleaners are able to reduce airborne cat or dog allergen levels. According to the increasing number of papers about allergen eviction, it seems logical to propose allergen eviction as "first line treatment" of allergic asthma. In the future, it would be interesting to develop biological markers to identify more accurately patients who have a clinical improvement after allergen eviction.

  13. Animal Allergens and Their Presence in the Environment

    PubMed Central

    Zahradnik, Eva; Raulf, Monika

    2014-01-01

    Exposure to animal allergens is a major risk factor for sensitization and allergic diseases. Besides mites and cockroaches, the most important animal allergens are derived from mammals. Cat and dog allergies affect the general population; whereas, allergies to rodents or cattle is an occupational problem. Exposure to animal allergens is not limited to direct contact to animals. Based on their aerodynamic properties, mammalian allergens easily become airborne, attach to clothing and hair, and can be spread from one environment to another. For example, the major cat allergen Fel d 1 was frequently found in homes without pets and in public buildings, including schools, day-care centers, and hospitals. Allergen concentrations in a particular environment showed high variability depending on numerous factors. Assessment of allergen exposure levels is a stepwise process that involves dust collection, allergen quantification, and data analysis. Whereas a number of different dust sampling strategies are used, ELISA assays have prevailed in the last years as the standard technique for quantification of allergen concentrations. This review focuses on allergens arising from domestic, farm, and laboratory animals and describes the ubiquity of mammalian allergens in the human environment. It includes an overview of exposure assessment studies carried out in different indoor settings (homes, schools, workplaces) using numerous sampling and analytical methods and summarizes significant factors influencing exposure levels. However, methodological differences among studies have contributed to the variability of the findings and make comparisons between studies difficult. Therefore, a general standardization of methods is needed and recommended. PMID:24624129

  14. Allergens labeling on French processed foods - an Oqali study.

    PubMed

    Battisti, Charlène; Chambefort, Amélie; Digaud, Olivier; Duplessis, Barbara; Perrin, Cécile; Volatier, Jean-Luc; Gauvreau-Béziat, Julie; Menard, Céline

    2017-07-01

    The French Observatory of Food Quality (Oqali) aims at collecting all nutritional data provided on labels of processed foods (nutritional information and composition), at branded products level, in order to follow nutritional labeling changes over time. This study carries out an overview of allergens labeling frequencies by distinguishing allergens used in recipes from those listed on precautionary statements, for the fourteen allergen categories for which labeling is mandatory according to European legislation. 17,309 products were collected, between 2008 and 2012, from 26 food categories. Products were classified per family and type of brand (national brands, retailer brands, entry-level retailer brands, hard discount, and specialized retailer brands). Allergenic ingredients were identified from ingredients lists and precautionary statements. 73% of the 17,309 products studied contained at least one allergen in their ingredients list and 39% had a precautionary statement for one or more allergens. Milk (53%), gluten (41%), and egg (22%) were the most commonly used allergens in ingredients lists. For precautionary statement, nuts (20%), egg (14%), peanut (13%), soybean (12%), and milk (11%) were the most common allergens listed. Precautionary statement was most frequently found among first-price products (hard discount and entry-level retailer brands). National brands seemed to use it less frequently. For all these results, differences depended both on food categories and allergen categories. This study will enable to follow allergens labeling and their use as ingredients over time, particularly by assessing an hypothetical increase in allergens presence in processed food.

  15. Crystal structure of peanut (Arachis hypogaea) allergen Ara h 5.

    PubMed

    Wang, Yang; Fu, Tong-Jen; Howard, Andrew; Kothary, Mahendra H; McHugh, Tara H; Zhang, Yuzhu

    2013-02-20

    Profilins from numerous species are known to be allergens, including food allergens, such as peanut ( Arachis hypogaea ) allergen Ara h 5, and pollen allergens, such as birch allergen Bet v 2. Patients with pollen allergy can also cross-react to peanut. Structural characterization of allergens will allow a better understanding of the allergenicity of food allergens and their cross-reactivities. The three-dimensional structures of most known food allergens remain to be elucidated. Here, we report the first crystallographic study of a food allergen in the profilin family. The structure of peanut allergen Ara h 5 was determined, and the resolution of the final refined structure was 1.1 Å. Structure alignment revealed that Ara h 5 is more similar to Bet v 2 than to Hev b 8, although sequence alignment suggested that Ara h 5 is more closely related to Hev b 8 than to Bet v 2, indicating that homology-model-based prediction of immunoglobulin E epitopes needs to be interpreted with caution.

  16. An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

    SciTech Connect

    Lee, Jun Ho; Kim, Tae Hyung; Kim, Hyuk Soon; Kim, A-Ram; Kim, Do-Kyun; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Her, Erk; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

    2015-06-15

    Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC{sub 50}, ~ 3.8 μM) and human mast cells (IC{sub 50}, ~ 3.0 μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED{sub 50} 27.9 mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells. - Highlights: • The anti-allergic effect of 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, was measured. • CAC-0982 reversibly suppressed the activation of mast cells by IgE and antigen. • CAC-0982 inhibited passive cutaneous anaphylaxis in mice. • CAC-0982 suppresses mast cells through inhibition of Fyn activation in mast cells.

  17. First-principles insights into p magnetism in CaC and CaN ionic compounds

    NASA Astrophysics Data System (ADS)

    Nourbakhsh, Zahra; Hashemifar, S. Javad; Akbarzadeh, Hadi

    2013-09-01

    Density functional-pseudopotential calculations are employed for more understanding of the exchange interaction in the novel p ferromagnetic CaC and CaN compounds in the rock-salt, zinc-blende, wurtzite and NiAs structures. It is observed that the generalized gradient functional give rises to a half-metallic or nearly half-metallic electronic structure for these systems. Comparing the structural properties in the ferromagnetic and nonmagnetic states clarifies that the bonding properties are almost independent of the exchange interaction in these systems. It is observed that the interatomic exchange interaction in these systems is quite strong and controls the splitting of the spin resolved bond points. The non-local Hartree-Fock based exchange correction is found to enhance the half-metallic behavior of the systems while preserving their equilibrium volume and compressibility.

  18. CAC Score Improves Coronary and CV Risk Assessment Above Statin Indication by ESC and AHA/ACC Primary Prevention Guidelines.

    PubMed

    Mahabadi, Amir A; Möhlenkamp, Stefan; Lehmann, Nils; Kälsch, Hagen; Dykun, Iryna; Pundt, Noreen; Moebus, Susanne; Jöckel, Karl-Heinz; Erbel, Raimund

    2017-02-01

    The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. In 3,745 subjects (59 ± 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (<100) was common in subjects with statin indication by both guidelines (59% for ESC, 62% for AHA/ACC). During 10.4 ± 2.0 years of follow-up, 131 myocardial infarctions occurred. For ESC recommendations, CAC score differentiated risk for subjects without (1.0 [95% confidence interval (CI): 0.4 to 1.5] vs. 6.5 [95% CI: 4.1 to 8.9] coronary events per 1,000 person-years for CAC 0 vs. ≥100) and with statin indication (2.6 [95% CI: 0.6 to 4.7] vs. 9.9 [95% CI: 7.3 to 12.5] per 1,000 person-years for CAC 0 vs. ≥100). Likewise, CAC score stratified proportions experiencing events subjects with statin indication according to AHA/ACC (2.7 [95% CI: 1.1 to 4.2] vs. 9.1 [95% CI: 7.0 to 11.0] per 1,000 person-years for CAC 0 vs. ≥100), whereas event rate in subjects without statin indication was low (1.1 [95% CI: 0.65 to 1.68] per 1,000 person-years). Current ESC and AHA/ACC guidelines lead to markedly different recommendation regarding statin therapy in a

  19. Pepino mosaic virus infection of tomato affects allergen expression, but not the allergenic potential of fruits.

    PubMed

    Welter, Saskia; Dölle, Sabine; Lehmann, Karola; Schwarz, Dietmar; Weckwerth, Wolfram; Worm, Margitta; Franken, Philipp

    2013-01-01

    The plant pathogen Pepino mosaic virus (PepMV) is a major disease of greenhouse tomato crops worldwide. Plant pathogens can induce expression of defence- or pathogenesis-related proteins, including identified allergens. Therefore we hypothesised that PepMV infection results in the expression of allergens leading to a higher allergenic potential of tomato fruits. Transcript level analyses showed differential expression of 17 known and putative tomato fruit allergen encoding genes at early and late time points after PepMV inoculation, but no general induction was detected. Immunoblot analyses were conducted and IgEs from a serum pool of tomato allergic subjects reacted with 20 proteins, of which ten have not yet been described. In parallel, skin prick tests with a group of tomato allergic subjects did not show a general difference between PepMV infected and non-infected tomato fruits and basophil activation tests confirmed these results. In summary, PepMV infection of tomato plants can lead to long-lasting up-regulation of particular allergens in fruits, but the hypothesis that this results in a higher allergenic potential of the fruits proved invalid.

  20. Pepino mosaic virus Infection of Tomato Affects Allergen Expression, but Not the Allergenic Potential of Fruits

    PubMed Central

    Welter, Saskia; Dölle, Sabine; Lehmann, Karola; Schwarz, Dietmar; Weckwerth, Wolfram; Worm, Margitta; Franken, Philipp

    2013-01-01

    The plant pathogen Pepino mosaic virus (PepMV) is a major disease of greenhouse tomato crops worldwide. Plant pathogens can induce expression of defence- or pathogenesis-related proteins, including identified allergens. Therefore we hypothesised that PepMV infection results in the expression of allergens leading to a higher allergenic potential of tomato fruits. Transcript level analyses showed differential expression of 17 known and putative tomato fruit allergen encoding genes at early and late time points after PepMV inoculation, but no general induction was detected. Immunoblot analyses were conducted and IgEs from a serum pool of tomato allergic subjects reacted with 20 proteins, of which ten have not yet been described. In parallel, skin prick tests with a group of tomato allergic subjects did not show a general difference between PepMV infected and non-infected tomato fruits and basophil activation tests confirmed these results. In summary, PepMV infection of tomato plants can lead to long-lasting up-regulation of particular allergens in fruits, but the hypothesis that this results in a higher allergenic potential of the fruits proved invalid. PMID:23762294

  1. Effects of Maillard reaction on allergenicity of buckwheat allergen Fag t 3 during thermal processing.

    PubMed

    Yang, Zhen-Huang; Li, Chen; Li, Yu-Ying; Wang, Zhuan-Hua

    2013-04-01

    Fag t 3 is a major allergenic protein in tartary buckwheat. The Maillard reaction commonly occurs in food processing, but few studies have been conducted on the influence of thermal processing on the allergenic potential of buckwheat allergen. The aim of the present study was to investigate the effects of autologous plant polysaccharides on the immunoreactivity of buckwheat Fag t 3 (11S globulin) following the Maillard reaction. Fag t 3 and crude polysaccharides were prepared from tartary buckwheat (Fagopyrum tataricum) flour. After heating, the polysaccharides were covalently linked to Fag t 3 via a Maillard reaction, and the IgE/IgG-binding properties of Fag t 3 decreased dramatically, with significant changes also being observed in the electrophoretic mobility, secondary structure and solubility of the glycated Fag t 3. The great influence of glycation on IgE/IgG binding to Fag t 3 was correlated with a significant change in the structure and epitopes of the allergenic protein. These data indicated that conjugation of polysaccharides to Fag t 3 markedly reduced the allergen's immunoreactivity. Glycation that occurs via the Maillard reaction during the processing of buckwheat food may be an efficient method to reduce Fag t 3 allergenicity. © 2012 Society of Chemical Industry.

  2. Allergenic proteins in Urtica dioica, a member of the Urticaceae allergenic family.

    PubMed

    Vega-Maray, Ana María; Fernández-González, Delia; Valencia-Barrera, Rosa; Suárez-Cervera, María

    2006-09-01

    Allergy to the pollen of flowering plant species significantly affects the health of people in many parts of the world. Pollens of related genera usually share common antigens and are often, but not always, cross-reactive. Several studies have shown that Parietaria pollen is one of the most common causes of pollinosis in the Mediterranean area, whereas Urtica has no allergenic significance. To report on the localization of Parietaria judaica major allergen in Urtica dioica pollen grains and on the detection of allergenic proteins in U. dioica pollen grains during the hydration-activation process. A combination of transmission electron microscopy and immunocytochemical methods was used to locate allergenic proteins in U. dioica pollen grains after different periods of hydration-activation using the anti-Par j 1 (4.1.3.) monoclonal antibody and serum samples from allergic patients. No significant labeling was noted for Parj 1 allergen after 10, 15, and 20 minutes in the walls and cytoplasm. Slight labeling was observed for allergic proteins in the walls of U. dioica after 10 minutes of hydration, and no significant labeling was found after 15 and 20 minutes of hydration. Immunocytochemical methods confirmed the absence of cross-reactivity between 2 related genera, Parietaria and Urtica, and the lowest allergenic potential of U. dioica.

  3. Toxicology of protein allergenicity: prediction and characterization.

    PubMed

    Kimber, I; Kerkvliet, N I; Taylor, S L; Astwood, J D; Sarlo, K; Dearman, R J

    1999-04-01

    The ability of exogenous proteins to cause respiratory and gastrointestinal allergy, and sometimes systemic anaphylactic reactions, is well known. What is not clear however, are the properties that confer on proteins the ability to induce allergic sensitization. With an expansion in the use of enzymes for industrial applications and consumer products, and a substantial and growing investment in the development of transgenic crop plants that express novel proteins introduced from other sources, the issue of protein allergenicity has assumed considerable toxicological significance. There is a need now for methods that will allow the accurate identification and characterization of potential protein allergens and for estimation of relative potency as a first step towards risk assessment. To address some of these issues, and to review progress that has been made in the toxicological investigation of respiratory and gastrointestinal allergy induced by proteins, a workshop, entitled the Toxicology of Protein Allergenicity: Prediction and Characterization, was convened at the 37th Annual Conference of the Society of Toxicology in Seattle, Washington (1998). The subject of protein allergenicity is considered here in the context of presentations made at that workshop.

  4. Cross-reactions among hair dye allergens.

    PubMed

    Basketter, David A; English, John

    2009-01-01

    p-Phenylenediamine (PPD) is an important hair dye allergen, but there remains a reasonable suspicion that other hair dye chemicals may also be responsible for a proportion of the clinical burden of hair dye allergy. To assess to what extent presently assessed additional patch test agents contribute to the diagnosis of non-PPD hair dye allergy. A retrospective analysis was conducted of patch test results with hair dye allergens, focusing on the extent to which patients who were positive for allergic reactions to other hair dye allergens also had a concomitant positive reaction to PPD. For the hair dye allergens other than p-toluenediamine (PTD), reactions in the absence of a concomitant positive reaction to PPD were very rare. Positive reactors to PTD were also positive for reactions to PPD in 5 of every 6 cases. Pyrogallol positives often occurred in the absence of a PPD positive, but were never judged to be of clinical relevance. Hair dye chemicals other than PPD may be of importance, but the presently tested materials, with the possible exception of PTD, are normally positive only when a PPD-positive reaction is also present, suggesting that their use in patch testing in hair dye allergy is likely to be of limited value.

  5. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIEA

    EPA Science Inventory

    The goal of this project is the identification and characterization of allergens from the fungus M. Anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaerosol contamination. One of ...

  6. ASSESSING ALLERGENICITY OF INDOOR AIR FUNGAL CONTAMINANTS

    EPA Science Inventory

    Assessing Allergenicity of Indoor Air Fungal Contaminants
    M D W Ward1, M E Viana2, N Haykal-Coates1, L B Copeland1, S H Gavett1, and MJ K Selgrade1. 1US EPA, ORD, NHEERL, RTP, NC, USA. 2NCSU, CVM, Raleigh, NC, USA.
    Rationale: The indoor environment has increased in impor...

  7. Optical fiber sensor for allergen detection

    NASA Astrophysics Data System (ADS)

    Bendoula, R.; Wacogne, B.; Giust, R.; Cherioux, F.; Sandoz, P.; Gharbi, T.

    2005-08-01

    The sensor is dedicated to the detection of allergens. We use a biochemical reaction in the vicinity of the core of an optical fiber which modifies the propagation conditions of the optical wave by evanescent coupling. The detection involves a intrinsic optical fiber Fabry-Perot interferometer.

  8. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIEA

    EPA Science Inventory

    The goal of this project is the identification and characterization of allergens from the fungus M. Anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaerosol contamination. One of ...

  9. Characteristics of candidates for allergen immunotherapy

    PubMed Central

    Incorvaia, Cristoforo; dell'Albani, Ilaria; Masieri, Simonetta; Cavaliere, Carmine; Puccinelli, Paola; Frati, Franco

    2013-01-01

    Allergic rhinitis (AR) may be cured by allergen immunotherapy (AIT). However, patient characteristics for prescribing AIT are not well defined. This study aimed at evaluating the patient's profile to be a candidate for AIT in a cohort of patients suffering from AR, evaluated in 20 Italian Allergy or Ear, Nose, and Throat Centers. The study has been performed on 198 patients (98 men; mean age, 26.8 years) with AR (assessed by Allergic Rhinitis and Its Impact on Asthma [ARIA] criteria). The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, and patient's perception of symptoms and drug use were evaluated. Patients were subdivided in AIT-treated and without AIT (as controls) subgroups. Most of the patients (69.7%) had persistent AR with moderate–severe symptoms. The mean number of sensitization was 3.4. ARIA classification and sensitization number did not affect AIT choice, but the type of allergen was relevant. AIT-treated patients had milder symptoms than controls if assessed by doctors, but AIT patients perceived more severe symptoms and larger drug use than controls. This study shows that the choice of AIT is based on patient's perception and type of allergen, but number of sensitizations, symptom severity assessed by doctors, and ARIA classification are not relevant factors. The key message might be that it is always relevant to pay attention to the complaints referred by the patient. PMID:24124641

  10. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIAE

    EPA Science Inventory

    Introduction

    The goal of this project is the identification and characterization of allergens from the fungus Metarhizium anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaer...

  11. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIAE

    EPA Science Inventory

    Introduction

    The goal of this project is the identification and characterization of allergens from the fungus Metarhizium anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaer...

  12. ASSESSING ALLERGENICITY OF INDOOR AIR FUNGAL CONTAMINANTS

    EPA Science Inventory

    Assessing Allergenicity of Indoor Air Fungal Contaminants
    M D W Ward1, M E Viana2, N Haykal-Coates1, L B Copeland1, S H Gavett1, and MJ K Selgrade1. 1US EPA, ORD, NHEERL, RTP, NC, USA. 2NCSU, CVM, Raleigh, NC, USA.
    Rationale: The indoor environment has increased in impor...

  13. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Allergenic Products. 680.1 Section 680.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... pelts, feathers, hairs, and danders shall be collected in a manner that will minimize contamination...

  14. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Allergenic Products. 680.1 Section 680.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... pelts, feathers, hairs, and danders shall be collected in a manner that will minimize contamination...

  15. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Allergenic Products. 680.1 Section 680.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... pelts, feathers, hairs, and danders shall be collected in a manner that will minimize contamination...

  16. 21 CFR 680.1 - Allergenic Products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Allergenic Products. 680.1 Section 680.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... pelts, feathers, hairs, and danders shall be collected in a manner that will minimize contamination...

  17. The allergen profile of beech and oak pollen.

    PubMed

    Egger, C; Focke, M; Bircher, A J; Scherer, K; Mothes-Luksch, N; Horak, F; Valenta, R

    2008-10-01

    Beech and oak pollen are potential allergen sources with a world-wide distribution. We aimed to characterize the allergen profile of beech and oak pollen and to study cross-reactivities with birch and grass pollen allergens. Sera from tree pollen-allergic patients with evidence for beech and oak pollen sensitization from Basel, Switzerland, (n=23) and sera from birch pollen-allergic patients from Vienna, Austria, (n=26) were compared in immunoblot experiments for IgE reactivity to birch (Betula pendula syn. verrucosa), beech (Fagus sylvatica) and oak (Quercus alba) pollen allergens. Subsequently, beech and oak pollen allergens were characterized by IgE inhibition experiments with purified recombinant and natural allergens and with allergen-specific antibody probes. Birch-, beech- and oak pollen-specific IgE levels were determined by ELISA. Beech and oak pollen contain allergens that cross-react with the birch pollen allergens Bet v 1, Bet v 2 and Bet v 4 and with the berberine bridge enzyme-like allergen Phl p 4 from timothy grass pollen. Sera from Swiss and Austrian patients exhibited similar IgE reactivity profiles to birch, beech and oak pollen extracts. IgE levels to beech and oak pollen allergens were lower than those to birch pollen allergens. IgE reactivity to beech pollen is mainly due to cross-reactivity with birch pollen allergens, and a Phl p 4-like molecule represented another predominant IgE-reactive structure in oak pollen. The characterization of beech and oak pollen allergens and their cross-reactivity is important for the diagnosis and treatment of beech and oak pollen allergy.

  18. Is food allergen analysis flawed? Health and supply chain risks and a proposed framework to address urgent analytical needs.

    PubMed

    Walker, M J; Burns, D T; Elliott, C T; Gowland, M H; Mills, E N Clare

    2016-01-07

    Food allergy is an increasing problem for those affected, their families or carers, the food industry and for regulators. The food supply chain is highly vulnerable to fraud involving food allergens, risking fatalities and severe reputational damage to the food industry. Many facets are being pursued to ameliorate the difficulties including better food labelling and the concept of thresholds of elicitation of allergy symptoms as risk management tools. These efforts depend to a high degree on the ability reliably to detect and quantify food allergens; yet all current analytical approaches exhibit severe deficiencies that jeopardise accurate results being produced particularly in terms of the risks of false positive and false negative reporting. If we fail to realise the promise of current risk assessment and risk management of food allergens through lack of the ability to measure food allergens reproducibly and with traceability to an international unit of measurement, the analytical community will have failed a significant societal challenge. Three distinct but interrelated areas of analytical work are urgently needed to address the substantial gaps identified: (a) a coordinated international programme for the production of properly characterised clinically relevant reference materials and calibrants for food allergen analysis; (b) an international programme to widen the scope of proteomics and genomics bioinformatics for the genera containing the major allergens to address problems in ELISA, MS and DNA methods; (c) the initiation of a coordinated international programme leading to reference methods for allergen proteins that provide results traceable to the SI. This article describes in more detail food allergy, the risks of inapplicable or flawed allergen analyses with examples and a proposed framework, including clinically relevant incurred allergen concentrations, to address the currently unmet and urgently required analytical requirements. Support for the

  19. The role of inhalant food allergens in occupational asthma.

    PubMed

    Cartier, André

    2010-09-01

    Workers handling food products and derivatives are at increased risk of developing occupational asthma. Exposure to food allergens occurs primarily through inhalation of dust, steam, vapors, and aerosolized proteins generated during cutting, scrubbing or cleaning, cooking or boiling, and drying activities. Suspicion of the diagnosis of occupational asthma should lead to proper investigation to confirm the diagnosis objectively. Most inhaled food allergy is IgE mediated, and skin prick tests or specific IgE tests are useful tools to support the diagnosis, but objective evidence of asthma by monitoring of peak expiratory flows at and off work or specific inhalation challenges offers a better diagnostic value. This article provides a list of the various foods, food additives, and contaminants that have been associated with occupational asthma.

  20. [Allergens used in skin tests in Mexico].

    PubMed

    Larenas Linnemann, Désirée; Arias Cruz, Alfredo; Guidos Fogelbach, Guillermo Arturo; Cid del Prado, Mari Lou

    2009-01-01

    Immunotherapy is the only recognized causal treatment for allergies. It is prepared on an individual basis, based on the patient's clinical history and the result of the skin prick test (SPT). An adequate composition of the allergens with which to test the patient is crucial for an optimal diagnosis. To know allergens used in tests in allergy practices in Mexico. A national survey among all members of the Colegio Mexicano de Inmunología Clínica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras Especialistas en Inmunología Clínica y Alergia (COMPEDIA) was carried out. In a second phase respondents were asked to send in the composition of a routine SPT in their clinic. The results are presented descriptively and the frequency is calculated by which certain allergen is tested in the interviewed practices. A survey response rate of 61 (17%) was obtained and 54% showed their SPT content. Weeds' representation in the SPT seems adequate; Atriplex is tested in all allergy practices. Some trees that show cross-reactivity might be eliminated from the SPT, but 20% doesn't test for Cynodon nor Holcus, and 25% doesn't for important allergens as cat, dog and cockroach. House dust and tobacco are still tested with certain frequency. The selection of which allergens to test in a SPT is based on multiple data, that change continuously with new investigations and discoveries. Our specialty is the most indicated--and obligated--to adjust constantly to these changes to have the best diagnostic tool to detect specific allergies.

  1. Dehydrated egg white: an allergen source for improving efficacy and safety in the diagnosis and treatment for egg allergy.

    PubMed

    Escudero, Carmelo; Sánchez-García, Silvia; Rodríguez del Río, Pablo; Pastor-Vargas, Carlos; García-Fernández, Cristina; Pérez-Rangel, Inmaculada; Ramírez-Jiménez, Antonio; Ibáñez, María Dolores

    2013-05-01

    Raw and cooked eggs are used as allergens in oral food challenge (OFC). Raw egg is the best option, as it keeps proteins intact and retains their allergenicity, albeit microbiologically safe manipulation is difficult. Therefore, the use of dehydrated egg white (DEW) could improve the efficacy and safety profile of OFC. The aim of the study was to compare the allergenicity of DEW, a product that undergoes a double heat treatment (pasteurization and drying), with that of raw egg white (REW) and determine the efficacy of DEW in the diagnosis of egg allergy. We conducted a prospective study of 40 egg-allergic patients who visited our outpatient clinic. Each patient underwent OFC with DEW and REW to determine the correlation between the tests. DEW and REW extracts were analyzed using SDS-PAGE. We compared the allergenicity of both extracts using IgE immunoblotting with a serum pool from patients with positive OFC results. Ten patients (25%) had positive OFC results with both DEW and REW, and the doses that triggered an allergic reaction in each patient were similar (p > 0.05). All 30 patients (75%) with a negative OFC result with DEW also had negative OFC results with REW. SDS-PAGE and IgE immunoblotting revealed that the protein composition and IgE-binding capacity of both extracts were virtually identical. This is the first time that it is shown that the allergenicity of commercially available DEW is equivalent to raw egg whites. In vivo and in vitro tests showed that processing of DEW does not affect the allergenicity of egg proteins. DEW is an effective and microbiologically safer source of allergen for the diagnosis of egg allergy. Furthermore, DEW can be used in egg oral immunotherapy. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  2. Protease inhibitor reduces airway response and underlying inflammation in cockroach allergen-induced murine model.

    PubMed

    Saw, Sanjay; Arora, Naveen

    2015-04-01

    Protease(s) enhances airway inflammation and allergic cascade. In the present study, effect of a serine protease inhibitor was evaluated in mouse model of airway disease. Mice were sensitized with cockroach extract (CE) or Per a 10 and treated with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) 1 h before or after challenge to measure airway response. Mice were euthanized to collect bronchoalveolar lavage fluid (BALF), blood, and lung to evaluate inflammation. AEBSF treatment significantly reduced the AHR in allergen-challenged mice in dose-dependent manner (p≤ 0.01). IgE (p≤0.05) and Th2 cytokines (p≤0.05) were significantly reduced in treated mice. AEBSF treatment lowered total cell (p≤0.05), eosinophil (p≤0.05), and neutrophil (p≤0.05) in BALF and lung tissue. Oxidative stress parameters were impaired on treatment in allergen-challenged mice (p≤0.05). AEBSF had therapeutic effect in allergen-induced airway resistance and underling inflammation and had potential for combination or as add-on therapy for respiratory diseases.

  3. Potential health risk of allergenic pollen with climate change associated spreading capacity: Ragweed and olive sensitization in two German federal states.

    PubMed

    Höflich, Conny; Balakirski, Galina; Hajdu, Zuzanna; Baron, Jens Malte; Kaiser, Lorraine; Czaja, Katharina; Merk, Hans F; Gerdsen, Sarah; Strassen, Ulrich; Bas, Murat; Bier, Henning; Dott, Wolfgang; Mücke, Hans-Guido; Straff, Wolfgang; Chaker, Adam; Röseler, Stefani

    2016-05-01

    Global climate changes may influence the geographical spread of allergenic plants thus causing new allergen challenges. Allergy patients from two German federal states were compared for their status quo sensitization to ragweed, an establishing allergen, olive, a non-established allergen, and the native allergens birch, mugwort, and ash. Between 2011 and 2013, 476 adult allergy patients per region were recruited. Patients completed a questionnaire, participated in a medical interview, and underwent skin prick testing and blood withdrawal for analysis of specific IgE to allergen components (ISAC technology). Data on regional pollen load from 2006 to 2011 were acquired from the German Pollen Information Service Foundation. Prick test reactivity to ragweed and ash, respectively, was lower in Bavaria than in NRW (ragweed: p=0.001, aOR=0.54; ash: p=0.001, aOR=0.59), whereas prick test reactivity to olive was higher (p=0.000, aOR=3.09). Prick test reactivity to birch and mugwort, respectively, did not significantly differ. 1% (1/127) of patients with prick test reactivity to ragweed showed sIgE to Amb a 1, and 65% (86/132) of olive-but-not-ash reactive patients showed sIgE to Ole e 1 (NRW: 67%, Bavaria: 65%; p=0.823, OR=0.91). Regional differences in sensitization pattern were neither explainable by cross-reactivity to pollen pan-allergens nor non-exposure variables nor by reported plant population or pollen data. Spread of ragweed and particularly olive may result in prompt occurrence of allergic symptoms. Early identification of invasive allergens due to climate change does need time and spatial close meshed measurement of respective indicator allergens and sensitization pattern. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  4. Hb East Timor [β80(EF4)Asn→His, AAC>CAC (HBB c.241A>C)], a variant hemoglobin associated with normal hematology.