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Biomedical subjects

P Schmid-Grendelmeier

Publications and source records attributed to P Schmid-Grendelmeier.

At least 19 recordsLinked to original sources
PubMed2006

Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal allergen.

BACKGROUND: Alternaria alternata is one of the most important allergenic fungi worldwide. Mannitol dehydrogenase (MtDH) has previously been shown to be a major allergen of Cladosporium herbarum and cross-reactivity has been demonstrated for several fungal allergens. OBJECTIVE: The present study's objective was to clone the MtDH from an A. alternata cDNA library, express and purify the recombinant non-fusion protein and test its IgE-binding properties. Methods A cDNA library prepared from A. alternata hyphae and spores was screened for mannitol dehydrogenase by DNA hybridization with the radioactively labelled C. herbarum homologue as a probe. The resulting clone was sequenced and heterologously expressed in Escherichia coli as a recombinant non-fusion protein, which was purified to homogeneity and analysed for its IgE-binding capacity. RESULTS: The coding sequence of the full-length cDNA clone comprises 798 bp encoding a protein with a molecular mass of 28.6 kDa and a predicted pI of 5.88. Protein sequence analysis revealed an identity of 75% and a homology of 86% between the MtDHs of A. alternata and C. herbarum. The functional mannitol dehydrogenase was expressed in the E. coli strain BL21(DE3) transformed with the vector pMW172 and purified to homogeneity. The enzyme catalyses the NADPH-dependent conversion of d-fructose to d-mannitol. In IgE-ELISA and immunoblots, MtDH is recognized by 41% of A. alternata-allergic patients. In vivo immunoreactivity of the recombinant MtDH was verified by skin prick testing. Finally, inhibition-ELISA experiments confirmed cross-reactivity between the MtDHs of A. alternata and C. herbarum. CONCLUSION: Mannitol dehydrogenase (Alt a 8) represents an important new allergen of the ascomycete A. alternata that might be suitable for improving diagnostic and therapeutic procedures.

Allergens↗
PubMed2006

Coated textiles in the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing prevalence over the last few decades. Various factors are known to aggravate the disease. In particular, wool and synthetic fabrics with harsh textile fibres, aggressive detergents and climatic factors may exacerbate AD. Cutaneous superinfection, particularly with Staphylococcus aureus, is also recognized as an important factor in the elicitation and maintenance of skin inflammation and acute exacerbations of AD. The severity of AD correlates with S. aureus colonization of the skin. Beside the treatment of AD patients with creams and emollients, new developments in the textile industry may have therapeutic implications. Silk or silvercoated textiles show antimicrobial properties that can significantly reduce the burden of S. aureus, leading to a positive effect on AD. Silver products have been used as wound dressing, whereby silver has antiseptic properties, and drug resistance is hardly found. Padycare textiles consist of micromesh material containing woven silver filaments with a total silver content of 20%. In vitro studies of these silver-coated textiles demonstrated a significant decrease in S. aureus and Pseudomonas aeruginosa as well as Candida albicans. Silk has been increasingly implemented in medical treatment of AD thanks to its unique smoothness that reduces irritation. Silk can be coated with antimicrobials (Dermasilk). The combination of the smoothness of silk with an antimicrobial finish appears to make an ideal textile for patients suffering from AD.

Dermatitis, Atopic↗
PubMed2006

Antimicrobial silk clothing in the treatment of atopic dermatitis proves comparable to topical corticosteroid treatment.

BACKGROUND: Atopic dermatitis (AD) is aggravated by mechanical irritation and bacterial colonization. OBJECTIVE: This study compared the efficacy of an antimicrobial silk fabric (DermaSilk) with that of a topical corticosteroid in the treatment of AD. METHODS: Fifteen children were enrolled and wore a dress, where the left side was made of DermaSilk and the right side was made of cotton. The right arm and leg were treated daily with the corticosteroid mometasone for 7 days. The treatment efficacy was measured with a modified EASI (Eczema Area and Severity Index) and with an assessment by the patients/parents and by a physician. All patients were evaluated at baseline, as well as 7 and 21 days after the initial examination. RESULTS: All parameters showed that, irrespective of the treatment, there was a significant decrease of eczema after 7 days. No significant difference between DermaSilk-treated and corticosteroid-treated skin could be observed. CONCLUSION: DermaSilk showed potential to become an effective treatment of AD.

Administration, Cutaneous↗
PubMed2006

Skin disorders among school children in rural Tanzania and an assessment of therapeutic needs.

Eight hundred and twenty primary school children were examined to assess the spectrum and prevalence of skin diseases in rural Tanzania. In all, 55% of the children had one or several skin disorders, but only 33% of all diagnoses in a cluster of 14% of the children required treatment. Tinea versicolor was found in 26.2%, pyoderma and dermatophytoses in less than 10%, while few children had scabies or eczematous lesions.

Child↗
PubMed2006

Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy.

BACKGROUND: Ultra-rush induction of immunotherapy with Hymenoptera venom is a reliable and efficacious alternative to the rush induction protocol, though not widely used in European countries yet. Its safety, however, has been intensively discussed over the last few years. The aim of this retrospective case study was to examine the rate of allergic side-effects during our four-hour ultra-rush hymenoptera venom induction regimen. We evaluated risk factors for observed side-effects such as age, gender, severity of previous insect sting reactions according to the H.L. Mueller classification, concentration of venom inducing positive skin tests, level of specific IgE, serum tryptase concentration, and hymenoptera venom used for treatment. METHODS: 67 outpatients with Hymenoptera venom allergy received 80 courses of ultra-rush immunotherapy. Diagnosis and selection of patients for venom immunotherapy were carried out according to the European Academy of Allergology and Clinical Immunology. We applied a four-hour regimen, and local or systemic reactions were documented. RESULTS: In 78 courses (97.5%) the maintenance dose of 111.1 microg was reached within 4 hours and it was tolerated in 82.5% without any hypersensitivity reaction. Allergic side-effects were observed in only 17.5% (n=14): four severe local reactions (5%), eight grade I (10%) and two grade II (2.5%) systemic reactions. There was no significant difference in the number of systemic reactions comparing patients receiving wasp or honeybee venom extract. The number of systemic reactions was neither higher in patients with a severe prior insect sting reaction (grade III or IV) nor dependent on age, gender, skin test reaction, level of specific IgE or tryptase. Epinephrine as rescue medication was never needed. Interestingly, patients with a severe prior wasp sting reaction showed a significantly lower incidence of allergic side-effects during ultra-rush immunotheraphy with wasp venom extract as compared to grade III or IV honeybee venom allergic patients. CONCLUSION: Our ultra-rush immunotherapy induction regimen shows a low incidence of systemic reactions. It proved to be safe and convenient for the patient, as it could be applied in a four-hour outpatient regimen.

Adolescent↗
PubMed2005

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗
PubMed2005

Ultrarush immunotherapy in a patient with occupational allergy to bumblebee venom (Bombus terrestris).

Bumblebee venom allergies, though uncommon among the broad public, pose a significant risk in plant industry and scientific occupation. Since a significant IgE cross-reactivity between bumblebee and honeybee venom has been described in several cases and bumblebee venom for immunotherapy has been available only from a few suppliers, SIT with honeybee venom was frequently used for bumblebee venom allergic patients in the past. We present the case of occupational bumblebee allergy in a biologist who developed anaphylactic reactions with subsequent stings. He was lacking cross-reactivity to honeybee venom, therefore we initiated immunotherapy with bumblebee venom extract. Two months after reaching the maintenance dose of 80 microg, the efficacy of the treatment was demonstrated by sting challenge.

Adult↗
PubMed2003

Altered intracellular expression of the chemokines MIP-1alpha, MIP-1beta and IL-8 by peripheral blood CD4+ and CD8+ T cells in mild allergic asthma.

BACKGROUND: The ability of chemokines to regulate Th1 and Th2 responses suggests a role in the pathogenesis of atopic disorders such as allergic asthma where Th2 response dominance has been observed. Although the impact of allergic asthma on local chemokine production in the lung has been the subject of investigation, little is know about the influence of disease progression on peripheral chemokine production. We now report use of whole blood culture and flow cytometry to assess the influence of mild allergic asthma on peripheral T-cell chemokine expression. METHODS: Study participants included patients with mild allergic asthma (n = 7) and nonasthmatic controls (n = 7). Following in vitro stimulation of peripheral venous blood with phorbol 12-myristate acetate (PMA) and ionomycin, flow cytometry was used to estimate the percentage of CD4+ and CD8+ T cells producing a number of chemokines, including macrophage inflammatory proteins MIP-1alpha and MIP-1beta, RANTES (regulated on activation, T-cell expressed and secreted), monocytic chemotactic protein-1 (MCP)-1, and interleukin (IL)-8, or the cytokines interferon (IFN)-gamma and IL-4. Serum levels of MIP-1alpha, MIP-1beta, RANTES, MCP-1, IL-8, IFN-gamma and IL-4 were also assessed by quantitative ELISA. RESULTS: Intracellular expression of MIP-1beta by CD4+ and CD8+ T cells from allergic asthmatics was significantly reduced in comparison to that observed for nonasthmatics (median = 2.29% (1.75-3.50) vs 4.57% (3.38-6.64), P = 0.05; 14.20% (13.18-17.88) vs 44.10% (30.38-48.70), P = 0.01). Similarly, intracellular expression of MIP-1alpha by CD8+ T cells from allergic asthmatics was also significantly lower (3.67% (1.17-5.42) vs 17.10% (4.97-20.43), P = 0.05). Conversely, IL-8 expression by both CD4+ and CD8+ T cells from allergic asthmatics demonstrated significant enhancement (9.93% (7.77-11.28) vs 4.14% (3.61-7.11), P = 0.05; 8.40% (6.97-10.04) vs 4.98% (3.37-6.08), P = 0.05). Examination of intracellular IFN-gamma and IL-4 revealed no significant difference in the expression of either cytokine by CD4+ T-cells from allergic asthmatics and nonasthmatics. In contrast, expression of IFN-gamma was significantly reduced in CD8+ T-cells from allergic asthmatics (24.60% (21.08-32.50) vs 48.40% (41.50-55.28), P = 0.01). CONCLUSIONS: The occurrence in mild allergic asthma of peripheral T-cell chemokine expression suggestive of a diminished Th1 response, coinciding with marginal change in cytokine profiles indicative of a Th2 response bias, confirms the importance of chemokine involvement in the etiology of allergic asthma. The ability to use whole blood culture to estimate chemokine expression in T cell subsets may ultimately provide a practical means to evaluate disease status and to monitor early intervention therapies which target chemokines.

Adult↗
PubMed2003

Nuclear transport factor 2 represents a novel cross-reactive fungal allergen.

BACKGROUND: Ubiquitously occuring moulds are important allergenic sources known to elicit IgE-mediated allergic diseases and to share cross-reactive allergens. Limited information is available about the molecular structures involved in cross-reactivity. We aimed to clone and characterize cross-reactive mould allergens. METHODS: Phage surface-displayed Alternaria alternata and Cladosporium herbarum cDNA libraries were screened using sera from Aspergillus fumigatus-sensitized patients. Inserts encoding putative allergens were sequenced, and recombinant proteins used to demonstrate cross-reactivity by inhibition experiments and skin test. Three-dimensional homology models of cloned putative nuclear transport factor 2 (NTF2) were constructed based on known NTF2 structure to corroborate the functional and structural properties of the novel allergens. RESULTS: After six rounds of affinity selection, the libraries were enriched for clones displaying allergens. Sequencing of inserts showed that some clones derived from Alternaria alternata and Cladosporium herbarum contain open reading frames predicting proteins of 124 and 125 amino acids corresponding to NTF2. The recombinant proteins were able to bind and cross-inhibit IgE binding and to elicit type I skin reactions in mould-sensitized individuals, demonstrating the allergenicity of the proteins. CONCLUSIONS: NTF2 represents a novel cross-reactive fungal allergen as demonstrated by sequence homology, three-dimensional modelling, inhibition experiments and skin test reactivity.

Allergens↗
PubMed2003

Immunoglobulin E-binding and skin test reactivity to hydrophobin HCh-1 from Cladosporium herbarum, the first allergenic cell wall component of fungi.

BACKGROUND: For many years, fungal spores have been recognized as potential causes of respiratory allergies. All fungal allergens cloned so far represent either secreted or cytoplasmatic proteins, but nothing is known about the involvement of fungal surface proteins in allergic diseases. METHODS: A phage surface displayed cDNA-library from the mould Cladosporium herbarum was constructed and phage displaying IgE-binding proteins were selectively enriched with immobilized serum IgE from C. herbarum-sensitized individuals. Inserts encoding putative allergens were sequenced, subcloned and used to produce recombinant proteins. Allergenicity of the proteins was evaluated by IgE binding in Western blots, enzyme-linked immunosorbent assay (ELISA) and skin prick test in a total of 84 patients sensitized to either C. herbarum or Aspergillus fumigatus and three healthy controls. RESULTS: After four rounds of affinity selection, the cDNA-library was enriched for clones displaying IgE-binding molecules. Sequencing of inserts showed that one clone contained an open reading frame predicting a protein of 105 amino acids and a calculated molecular weight of 10.5 kDa showing the classical signature of members of the hydrophobin family. The recombinant protein, termed HCh-1, was able to bind IgE from six patients sensitized to fungi in vitro. Two of those patients were also included in a skin prick test survey and showed strong type I skin reactions to HCh-1, demonstrating the allergenic nature of C. herbarum hydrophobin and indicating a prevalence of sensitization in the range of 8-9%. In contrast, the hydrophobin HYP1 from Aspergillus fumigatus was not recognized by the sera of the same patients and controls investigated with HCh-1. CONCLUSION: C. herbarum hydrophobin represents the first component of the cell wall of fungi demonstrated to act as a rare but clinically relevant allergen in vitro and in vivo.

Allergens↗
PubMed2003

In vitro and in vivo allergenicity of recombinant Bet v 1 compared to the reactivity of natural birch pollen extract.

BACKGROUND: Diagnostic procedures using natural extracts show only limited quantitative correlation between in vivo and in vitro results. Highly pure recombinant allergens might show more predictive findings. OBJECTIVE: The aim of this study was to compare natural birch pollen extract (BPE) and recombinant Betula verrucosa (rBet v 1) for their diagnostic value comparing skin prick tests (SPTS) and nasal provocation tests (NPTS) with specific IgE in the serum. METHODS: Thirty-four patients allergic to birch pollen and five healthy controls were investigated. SPT and NPT were performed with BPE and rBet v 1 at different concentrations. Specific serum IgE was measured by the Pharmacia CAP system. RESULTS: Commercial BPE and rBet v 1 (10 micro g/mL) were able to elicit similar allergenic reactions in vivo and IgE binding in vitro. SPT reflects immediate-type allergy as determined by NPT to a higher degree than specific IgE, for both reagents. To cause allergic reactions in NPT, higher amounts of rBet v 1 were needed than for skin tests and the sensitivity was lower than with BPE. CONCLUSION: rBet v 1 alone is sufficient for a reliable diagnosis of birch pollen allergy in most patients and induces comparable skin test reactivity as BPE, but less allergic reactions in nasal provocations.

Adult↗
PubMed2003

The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated ("extrinsic") and the nonallergic ("intrinsic") AEDS.

According to the position paper from the EAACI nomenclature task force, the term "Atopic eczema/dermatitis syndrome" (AEDS) should be used as the "umbrella" term to cover the different subtypes of atopic dermatitis (AD). The new nomenclature (AEDS) underlines the fact that AD is not one, single disease, but rather an aggregation of several diseases with certain clinical characteristics in common. The so-called "intrinsic" type of AD (now termed nonallergic AEDS) fulfills the most commonly used diagnostic criteria for AD. These patients have no associated respiratory diseases, such as bronchial asthma or allergic rhinitis, show normal total serum IgE levels, no specific IgE, and negative skin-prick tests to aeroallergens or foods. Immunologic differences between the IgE-associated type of AD and the nonallergic type can be found in the cell and cytokine pattern in peripheral blood and in the affected skin, and also by phenotyping characterization of epidermal dendritic cells. The current explanation of this distinction is based on differences in genetics and/or environmental conditions. The classification into an allergic, IgE-associated (AAEDS) and a nonallergic type (NAAEDS) at each stage of life, i.e., infancy, childhood, teenage, and adult, is essential for the allergological management of patients as to allergen avoidance, secondary allergy prevention, and immunotherapy. The risk of an "atopy march" is significantly lower in children with the non-IgE-associated type.

Adolescent↗
PubMed2001

Idiopathic localized unilateral hyperhidrosis: case report of successful treatment with botulinum toxin type A and review of the literature.

BACKGROUND: Localized unilateral hyperhidrosis (LUH) is a rare disorder of unknown origin. We describe a patient with LUH on the forearm, where a fracture was identified as a past injury. OBSERVATIONS: We treated the patient with botulinum toxin type A injections, and he was complaint free during the 6 months after treatment. In addition, the initially strong positive results of the iodine starch test (Minor sweat test) were negative in the affected region after treatment. CONCLUSIONS: This relatively new therapeutic modality already established for axillary, palmar, and plantar hyperhidrosis seems to be efficient in LUH. As the former therapeutic approaches are rather disappointing, and as botulinum toxin type A locally applied shows limited adverse effects, we think a trial of botulinum toxin type A is justified in cases of LUH, even as a first-line treatment. In addition, the literature considering localization and causes of LUH is reviewed.

Adult↗
PubMed2001

[Reticular pigmented anomaly of the flexures. Dowling-Degos disease of the intertrigo type in association with acne inversa].

Reticulated pigmented anomaly of the flexures (Dowling-Degos disease) is a rare autosomal-dominant genodermatosis with variable penetrance that is characterized by reticulated hyperpigmentation of the flexures. Acne inversa has been previously described in the literature under several synonyms, such as acne triad, acne tetrad and hidradenitis suppurativa. Acne inversa is an inflammation affecting the pilosebaceous units of the flexures. We report a case of Dowling-Degos disease in association with acne inversa. The association of these diseases has been described several times and it appears not to be coincidental. Pathogenetic mechanisms leading to this coincidence are discussed.

Acne Vulgaris↗
PubMed2001

[Pollen as the cause of allergies].

Pollinosis or hay fever is the most common allergic disease in Switzerland. For symptoms during spring pollens of birch and related trees (alder, hazel) and also ash tree are responsible, while hay fever during summer is mainly caused by pollens of grasses, rye and mugwort. These main plant pollen allergens, relevant cross-reactivities with other pollen and food allergens are reviewed in this article. The well-established methods of pollen-counting in Switzerland allow to define the varying amounts of measurable pollen depending on geographic and climatic conditions. Similarly clinical symptoms, the diagnostic work-up of pollen allergies and therapeutic aspects including preventive measures, symptomatic therapy and specific immunotherapy are presented. Finally, occupational and travelling aspects of pollinosis are briefly discussed.

Diagnosis, Differential↗
PubMed2001

Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis.

BACKGROUND: Activation and skin-selective homing of T cells and effector functions in the skin represent sequential events in the pathogenesis of atopic dermatitis and allergic contact dermatitis. OBJECTIVE: T cell-mediated keratinocyte apoptosis plays a key pathogenetic role in the formation of eczematous dermatitis. IFN-gamma released from activated T cells upregulates Fas on ke-ratinocytes, which renders them susceptible to apoptosis. The lethal hit is given to keratinocytes by means of Fas ligand expressed on the T-cell surface or released to the inflammatory microenvironment. We sought to investigate whether drugs used for the treatment of eczematous disorders interfere with this pathogenic pathway. METHODS: T cell-mediated, Fas-induced keratinocyte apoptosis in a keratinocyte-T cell coculture system serves as an in vitro model of eczematous dermatitis. We tested, in this model, whether immunomodulatory agents (dexamethasone, cyclosporine A, rapamycine, tacrolimus/FK506, intravenous immunoglobulin [IVIG], and theophylline) are able to inhibit apoptosis of keratinocytes. Additionally, skin biopsy specimens from patients with untreated and successfully treated eczematous dermatitis were evaluated for keratinocyte apoptosis. RESULTS: Dexamethasone, cyclosporine A, FK506, rapamycine, and IVIG are inhibitors of keratinocyte apoptosis induced by activated T cells. This effect is mediated by 2 major mechanisms directed on T cells or keratinocytes. T-cell activation was mainly inhibited by dexamethasone, FK506, cyclosporine A, and rapamycine. Interestingly, high-dose dexamethasone and IVIG directly inhibited Fas-mediated keratinocyte apoptosis. In vivo keratinocyte apoptosis was significantly reduced after successful topical treatment of eczematous lesions. CONCLUSION: These results demonstrate mechanisms of action of current treatment approaches and provide a future for more focused therapeutic applications.

Acute Disease↗