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Biomedical subjects

B Wüthrich

Publications and source records attributed to B Wüthrich.

At least 37 records · Page 2Linked to original sources
PubMed2002

Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01.

The aim of this study was to produce the Bet v 1-related major hazelnut allergen Cor a 1.0401 and variants thereof as recombinant allergens, and to compare their immuno-reactivity with the major hazel pollen allergen using sera of patients whose hazelnut allergy recently was confirmed by double-blind placebo-controlled food challenges (DBPCFC) in a multicenter study. Total RNA was isolated from immature hazelnuts and transcribed into cDNA. Full length coding DNA obtained by PCR-strategy was subcloned into pTYB11 vector and expressed in E. coli ER2566 cells. Native non-fusion target proteins were purified by DTT-induced self-cleavage of the intein-tagged N-terminal fusion proteins. IgE reactivity of the recombinant allergens was tested by enzyme allergosorbent test (EAST), EAST-inhibition, immunoblot-inhibition and histamine release assays. Four recombinant allergens were produced showing deduced amino acid sequence identities among each other of 97-99%, and were considered as variants Cor a 1.0401 (GenBank Accession no.: AF136945), Cor a 1.0402 (AF323973), Cor a 1.0403 (AF323974) and Cor a 1.0404 (AF323975). Cor a 1.0402 and 03 only differed in a C4S exchange. Cor a 1.0404 had a unique proline residue in position 99. Surprisingly, only 63% identity was revealed with hazel pollen Cor a 1. EAST with 43 sera of patients with positive DBPCFC to hazelnut indicated IgE reactivity to Cor a 1.0401 in 95% of the sera, to Cor a 1.0402 in 93%, to Cor a 1.0403 in 91%, and in only 74% of the sera to the proline variant Cor a 1.0404. The allergenic activity of the four variants was confirmed by histamine release assays in 15 hazelnut-allergic patients stimulated with the four variants and controls. Eleven sera were positive with extract from native hazelnut, 13 with rCor a 1.0401, 12 with rCor a 1.0402, 11 with rCor a 1.0403, and only two with rCor a 1.0404 containing the proline exchange. The high IgE binding variant Cor a 1.0401 showed only partial IgE cross-reactivity with pollen Cor a 1. IgE-binding and histamine release capacity led to a concordant ranking of the allergenic activity of the recombinant variants: Cor a 1.0401>Cor a 1.0402 and 03>Cor a 1.0404 (the proline variant). Similar results for Cor a 1.0402 and 03 suggest a minor influence in IgE binding of cysteine in position 4, whereas proline in position 99 appears to be responsible for the decrease in IgE reactivity in Cor a 1.0404. It appears that the epitopes of hazelnut Cor a 1.04 are less related to pollen Cor a 1 than to Bet v 1 from birch pollen. Low IgE binding variants or mutants of Cor a 1.04 are candidate compounds for developing a novel and safe approach of specific immunotherapy of hazelnut allergy.

Allergens↗
PubMed2002

Influence of food processing on the allergenicity of celery: DBPCFC with celery spice and cooked celery in patients with celery allergy.

BACKGROUND: Celery root is often consumed in a processed form as a cooked vegetable or as a spice. So far, however, there has been no information about the allergenicity of processed celery in celery-allergic patients. METHODS: In 12 patients with a history of allergic reactions to raw or raw and cooked celery, double-blind placebo-controlled food challenges (DBPCFCs) with raw celery (n = 10), cooked celery (110 degrees C/15 min; n = 11), and celery spice (n = 5) were performed. Nine patients underwent an open mucosal challenge with four samples of canned celery retorted at Co-values (cooking effect) of 7.45-76.07 (corresponding to the time periods in minutes at a thermal influence of 100 degrees C). IgE immunoblot analysis of celery extract was performed with sera of all challenged patients. The thermal stability of celery allergen was investigated by enzyme allergosorbent test (EAST) inhibition. Furthermore, intraperitoneal immunization of mice followed by a rat basophil leukemia (RBL) cell mediator release assay was used as a biological in vitro model to assess the allergenicity of processed celery. RESULTS: Six out of 11 patients showed a positive DBPCFC to cooked celery and five out of five patients to celery spice. Allergenicity of celery was preserved in four patients with a positive DBPCFC to cooked celery even if celery was treated at a Co-value of 76.07. Patients with positive DBPCFC to cooked celery reacted to known celery allergens (Api g 1, Api g 4, cross-reactive carbohydrate determinants CCD). EAST inhibition showed that heat resistance of celery allergens decreases in the following order: CCD > Api g 4 > Api g 1. Accordingly, five of six patients with a positive DBPCFC to cooked celery were sensitized to profilin and/or CCD. The murine model reflected the reactivity of patients sensitized to the major allergen Api g 1. CONCLUSIONS: 1) In a subset of patients with a positive DBPCFC to cooked celery, celery remains allergenic even after extended thermal treatment (76.07 min/100 degrees C). 2) Celery spice is allergenic for patients with an allergy to raw celery. 3) RBL cells sensitized with mouse IgE to raw celery may serve as a useful tool for screening the potential allergenicity of heat-processed products containing celery.

Adult↗
PubMed2002

Allergens in celery and zucchini.

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.

Allergens↗
PubMed2001

Cross-reactivity within the profilin panallergen family investigated by comparison of recombinant profilins from pear (Pyr c 4), cherry (Pru av 4) and celery (Api g 4) with birch pollen profilin Bet v 2.

Profilin is a panallergen which is recognised by IgE from about 20% of birch pollen- and plant food-allergic patients. Little is known about epitope diversity among these homologous proteins, and about the correlation between IgE-cross-reactivity and allergenic reactivity. Plant food profilins from pear (Pyr c 4) and cherry (Pru av 4) were cloned by polymerase chain reaction and produced in Escherichia coli BL21. The profilins were purified as non-fusion proteins by affinity chromatography on poly-(L-proline)-Sepharose and characterized by immunoblotting, IgE-inhibition experiments and histamine release assays. The coding regions of the cDNA of pear and cherry profilin were identified as a 393 bp open reading frame. The deduced amino acid sequences showed high identities with birch pollen profilin Bet v 2 (76-83%) and other allergenic plant profilins. Pyr c 4 and Pru av 4 were investigated for their immunological properties in comparison with profilins from celery (Api g 4) and birch pollen (Bet v 2). Fourty-three of 49 patients (88%), preselected for an IgE-reactivity with Bet v 2 showed specific IgE-antibodies to the recombinant pear protein, 92% of the sera were positive with the recombinant cherry allergen and 80% of the sera were reactive with the celery protein. Inhibition experiments showed a strong cross-reactivity of IgE with profilins from plant food and birch pollen. However, IgE binding profiles also indicated the presence of epitope differences among related profilins. All investigated profilins, Pyr c 4, Pru av 4, Api g 4 and Bet v 2, presented almost identical allergenic properties in cellular mediator release tests. Therefore, cross-reactivities between related profilins may explain pollen-related allergy to food in a minority of patients. The nucleotide sequences reported have been submitted to the Genbank database under accession numbers AF129424 (Pyr c 4) and AF129425 (Pru av 4).

Allergens↗
PubMed2001

[Drug reaction to terbinafine simulating an acute generalized exanthematous pustulosis].

Oral terbinafine (Lamisil) is a widely used and effective therapy of dermatophyte infections. A 20-year-old patient was treated with oral terbinafine for an inguinal-scrotal fungal infection and developed an acute generalized exanthematic pustulosis (AGEP) and fever. Histological examination of skin biopsy revealed subcorneal and spongiform pustules. The diagnosis of an AGEP induced by terbinafine was established based on the history, clinical manifestations, and laboratory findings. Clinical features, differential diagnosis, causative drugs, and the therapy of AGEP are discussed and the literature on cases of terbinafine-induced AGEP is reviewed.

Adult↗
PubMed2001

Air pollutants enhance rhinoconjunctivitis symptoms in pollen-allergic individuals.

BACKGROUND: Little is know about the relation of airborne pollen allergens to nasal and ocular symptoms in combination with air pollutants. OBJECTIVE: The hypothesis was that air pollutants exacerbate allergic symptoms of the nose and eyes during the pollen season. In addition, the use of allergen measurements instead of pollen counts should be tested. METHODS: Fifteen pollen-allergic, nonsmoking subjects with weak reactivity of the airways recorded rhinoconjunctival symptoms and medication every morning and evening throughout the pollen season. Symptoms were compared with air pollutants (nitrogen oxide [NOx], particulate matter smaller than 10 microm, and ozone) and birch and grass pollen counts or, alternatively, to airborne birch and grass allergens determined using ELISA-techniques. A multiple linear regression model was used which controlled for autocorrelation of the residuals of the time series (Cochrane-Orcutt approach). This model was applied to each subject individually, followed by calculations of summary scores for the group. RESULTS: Air pollution levels were moderate, often meeting air quality standards. Effect estimates (increase of score with 10-fold increase of concentration) were NOx = 1.06, P < 0.01; ozone = 1.59, P < 0.01; and pollen = 0.48, P < 0.001. Using allergen concentrations instead of pollen counts resulted in similar effect estimates. Using particulate matter smaller than 10 microm instead of NOx gave comparable but less consistent results. CONCLUSIONS: Symptoms were related to moderate levels of pollutants, suggesting that rhinoconjunctival tissue is very sensitive to irritant stimuli during an ongoing allergic inflammation, and that susceptibility toward allergens might be increased in areas with increased levels of air pollutants. Allergen measurements seem equally usable as pollen counts to investigate rhinoconjunctivitis.

Adult↗
PubMed2001

[Epidemiology of allergies in Switzerland].

The Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was carried out during 1991-1993 in eight Swiss areas with different environmental characteristics. The cross-sectional examination included 9651 adults, aged 18-60 years, who all participated in a detailed interview. In 8357 subjects complete allergy skin and in-vitro tests were available in addition. The prevalence of atopic sensitization (positive skin prick test to any of the tested inhalant allergens and/or a positive Phadiatop as an in-vitro screening test for atopy) was 32.3%, with a higher prevalence in males (35.7%) than in females (28.8%). Skin sensitization was predominantly caused by grass pollen (12.7%), followed by house dust mite (8.9%), silver birch pollen (7.9%) and cat epithelia (3.8%). 11.1% suffered from current hay fever, 6.8% from asthma, 4.5% from atopic asthma. Smokers had statistically significant (p < 0.001) higher mean serum IgE concentrations (geometric mean 39.7 kU/l) than nonsmokers (27.2 kU/l), In Phadiatop positive subjects, the IgE levels were highest, with a mean of 104.3 kU/l (99.0-109.8). The SCARPOL Study (Swiss Study on Childhood Allergy and Respiratory Symptoms with respect to Air Pollution and Climate) ist based on a sample of 4470 children from 10 different areas who completed parenteral questionnaire. 35.7% of the 2879 children who underwent skin prick testing were sensitized to at least one tested aeroallergen, 22.5% to gras pollen, 12.4% to house dust mites, 11.4% to birch pollen and 6.4% to cat epithelia. 17% of the 13- to 15-year-old (8th grade) suffered from hayfever. The prevalence of asthma (ever) for the whole sample was 9%, without differences between the age groups. The lifetime prevalence of atopic dermatitis was 13% and the current prevalence 8%. The risk of eczema was higher in Swiss children than in children of immigrants, in infants with a birthweight below 2500 g, in children with a positive family history of atopic dermatitis, and in children from higher socioeconomic classes. Farm children (n = 133) living in a rural area suffer less frequently from pollinosis (2.4%) and bronchial asthma (1.6%) than children (n = 966) with no direct contact to agriculture, but living in the same area (prevalence of hayfever 18.3%, of asthma 9.1%). This figures are similar to results from former East and Western Germany and from the former USSR and Baltic areas. These large Swiss epidemiologic studies confirmed both, the high prevalence of atopy and atopic diseases, and the health impact of moderate air pollution levels and of factors associated with the 'western lifestyle'.

Adolescent↗
PubMed2001

[Therapy of neurodermatitis (atopic dermatitis)].

Atopic dermatitis is a chronic-relapsing disease that often requires an individualized therapeutic approach. There are various treatment options that address known pathogenetic pathways and, when used in combination, are often very successfull. In view of the fact that a unifying pathogenic concept as well as a therapeutic regimen is not available to this very day, preventative measures that should be introduced in very early childhood. Therefore, one very important goal in treatment is to identify and eliminate triggering factors which include irritants, allergens and cutaneous bacterial, viral or fungial infections. The mainstay of therapy today are external emmollients, which when used appropriately, can reduce the need for systemic treatments. The reconvalescence can be speeded up by auxilliary therapies such as UVA or UVB, psychotherapeutical strategies such as stress reduction as well as so-called climate-("Klima") therapy.

Administration, Topical↗
PubMed2001

Hidden peanut allergens detected in various foods: findings and legal measures.

BACKGROUND: Undeclared allergens in foodstuffs represent a major health problem for sensitized persons. Until recently, most food control authorities were not in the position to monitor hidden allergens and to take legal measures against their presence in foodstuffs. METHODS: In this study, we employed human sera-based immunoassay techniques, enabling semiquantitative detection and identification of peanut allergens in a variety of foodstuffs. RESULTS: This study showed the presence of undeclared allergens in products belonging to various food categories, such as cereals, cookies, cakes, and snacks. The detection limit for peanut contamination was in most instances less than 50 mg peanut material per kg, i.e., less than about 5 mg peanut allergens per kg. We legally objected to products with more than one part per thousand or 1000 mg/kg of peanut contamination. CONCLUSIONS: In most cases, food producers, confronted with our results, were able to detect and eliminate the sources of the contamination. They implemented measures to prevent the presence of hidden peanut allergens in their products, increasing food safety for sensitized persons and overall food quality.

Allergens↗