bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Principles of Conformation-Based Prion Inheritance
Authors: Chien Peter , Weissman Jonathan S. , DePace Angela H.
Published: March 2003

▪ Abstract  The prion hypothesis proposes that proteins can act as infectious agents. Originally formulated to explain transmissible spongiform encephalopathies (TSEs), the prion hypothesis has been extended with the finding that several non-Mendelian traits in fungi are due to heritable changes in protein conformation, which may in some cases be beneficial. Although much remains to be learned about the specific role of cellular cofactors, mechanistic parallels between the mammalian and yeast prion phenomena point to universal features of conformation-based infection and inheritance involving propagation of ordered β-sheet-rich protein aggregates commonly referred to as amyloid. Here we focus on two such features and discuss recent efforts to explain them in terms of the physical properties of amyloid-like aggregates. The first is prion strains, wherein chemically identical infectious particles cause distinct phenotypes. The second is barriers that often prohibit prion transmission between different species. There is increasing evidence suggesting that both of these can be manifestations of the same phenomenon: the ability of a protein to misfold into multiple self-propagating conformations. Even single mutations can change the spectrum of favored misfolded conformations. In turn, changes in amyloid conformation can shift the specificity of propagation and alter strain phenotypes. This model helps explain many common and otherwise puzzling features of prion inheritance as well as aspects of noninfectious diseases involving toxic misfolded proteins.
Monthly measurements of indoor allergens and the influence of housing type in a northeastern US city
Authors: Chew G.L. , Higgins K.M. , Gold D.R. , Muilenberg M.L. , Burge H.A. , Gold D.R.
Published: March 2003

Background: We examined seasonal variation of dust‐mite (Der f 1 and Der p 1), cat (Fel d 1), and cockroach (Bla g 1) allergens in Boston, while adjusting for other covariates. Limited data are available on seasonal patterns of indoor allergen concentrations for different geographic regions in the USA. Understanding within‐home seasonal variation of allergens is important epidemiologically and clinically.

Methods: From June 1995 to June 1996, dust samples were vacuumed monthly from the bed, bedroom floor, and kitchen of 20 homes. Indoor temperatures were measured monthly and used in calculating relative and absolute humidity. Monthly home characteristics questionnaires were completed by an adult resident of each home. Dust samples were assayed by enzyme‐linked immunosorbent assays.

Results: Der f 1 and Der p 1 in beds and floors peaked in the autumn months, Fel d 1 peaked in winter and spring, and Bla g 1 was highest in summer. Dust‐mite allergen concentrations were 1.9–2.4 times higher in autumn than spring, but the levels in beds were 19–31 times higher in houses than those in apartments. Although Fel d 1 levels in beds were 2.4 times higher in spring than summer, homes with cats had levels 224 times higher than those without cats. Similarly, Bla g 1 levels in kitchens were 2.1 times higher in summer than winter, but apartments had levels five times higher than those of houses.

Conclusions: Sampling season is a source of within‐home dust‐mite, cat, and cockroach allergen variation in the northeastern USA. However, the influence of housing type and owning a cat far outweighed the seasonal variation of these indoor allergens.

Abbreviations: SD: standard deviation; ELISA: enzyme‐linked immunosorbent assay; Aw: water activity; mAb: monoclonal antibody; BSA: bovine serum albumin; PBS: phosphate‐buffered saline; T: Tween 20 solution; BBS: borate‐buffered saline; LOD: limit of detection.
Allergen‐stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide
Authors: Nakstad B , Kähler H , Lyberg T , Nakstad B
Published: March 2003

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen‐induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA‐DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)‐4 and IL‐5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA‐DR and CD11a/CD18‐mediated interactions are also involved in T‐ and B‐cell functions. Birch‐pollen (BP) allergens induced CD154 expression on CD3‐positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA‐DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL‐5 and total IgE in BP‐supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.
Increased occurrence of IgE+ and FcεRI+ cells in adenoids from atopic children
Authors: Papatziamos G. , Hemlin C. , Van Der Ploeg I , Patwardhan A , Scheynius A
Published: March 2003

Background: To examine the influence of atopy on the different cell populations in adenoids, we investigated the presence of IgE+ cells, cells expressing the high‐affinity receptor for IgE (FcεRI), and various other cell populations in adenoid tissue, in atopic and nonatopic children with otitis media with effusion (OME) or adenoid hyperplasia (AH).

Methods: Cryostat sections of adenoids from 14 atopic and 16 nonatopic children suffering from long‐lasting OME (n=15) or obstructive AH (n=15) were investigated with immunohistochemical markers for T‐cell subsets, mast cells, eosinophils, plasma cells, CD25, CD1a, IgE, and FcεRI.

Results: Sensitization to allergens was correlated to an increase of IgE+ cells in the epithelium (P<0.01), the extrafollicular area (P<0.0001), and the follicles (P<0.001) of the adenoids and an increase of FcεRI+ cells in the extrafollicular area (P<0.01). A minority of the IgE+ cells were plasma cells. No significant differences in cells stained for IgE, FcεRI, or the other markers were observed between patients with OME and AH.

Conclusions: Atopy is associated with increased numbers of IgE+ and FcεRI+ cells in adenoids irrespective of whether the child has OME or AH.
Dietary assessment in five cases of allergic reactions due to gastroallergic anisakiasis
Authors: Alonso A , Moreno‐Ancillo A , Daschner A , López‐Serrano M
Published: March 2003

Background: Anisakis simplex can cause allergic reactions in sensitized patients. Some of these reactions are related to acute parasitism, as is shown in gastroallergic anisakiasis (anisakiasis with digestive and predominantly allergic symptoms). At present, a nonseafood diet is recommended for all patients with any kind of A. simplex allergy. We wished to confirm the clinical suspicion that patients with allergic symptoms after ingestion of raw or undercooked seafood who are sensitized to A. simplex, and diagnosed with gastroallergic anisakiasis, can tolerate the ingestion of seafood when the parasites are dead and noninfective.

Methods: We included patients diagnosed with gastroallergic anisakiasis (positive skin prick test or/and serum specific IgE to A. simplex, with one or more parasites found by gastroscopy in the stomach). Patients included in the study gave written, informed consent. Specimens of A. simplex about 2 cm long were selected, placed in capsules, and frozen at −20°C for more than 48 h to make them noninfective. We administered 11 specimens to every patient at the hospital. If they tolerated the larvae, they were told to eat well‐frozen seafood (−20°C at least 48 h). After 6 months, the patients were re‐evaluated.

Results: Five patients accepted the challenge with noninfective A. simplex larvae. All tolerated the noninfective larvae. After eating deep‐frozen seafood for 6 months, no patient suffered a reaction.

Conclusions: In gastroallergic anisakiasis, the antigens of the live parasite probably cause the allergic symptoms. Patients with this disease can tolerate deep‐frozen seafood, in which the parasites are dead.
Sublingual‐swallow immunotherapy (SLIT) with a standardized five‐grass‐pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis
Authors: Pradalier A , Basset D , Couturier P , Claudel A , Wessel F , Galvain S , André C
Published: March 2003

Background: Recent studies have demonstrated the efficacy of sublingual‐swallow immunotherapy (SLIT) in seasonal and perennial rhinitis. Sublingual administration of solutions is not convenient for all patients. The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually, initially as drops, and then as tablets during maintenance therapy.

Methods: A total of 126 patients with grass‐pollen seasonal rhinitis were included in this double‐blind, randomized, placebo‐controlled trial. During the progression of doses phase, the five‐grass extract was given as sublingual drops from 1 to 100 IR/ml. Once the 100 IR dose was reached, the drops were replaced by a single 100‐IR sublingual tablet per day.

Results: Throughout the grass‐pollen season, patients in the active treatment group had significantly lower (P<0.05) total conjunctivitis and ocular redness scores. Rhinitis symptoms were not significantly different between the two groups. Patients given the active treatment were significantly (P<0.02) less likely to have asthma symptoms. The global medication score showed no significant difference between the two groups. A highly significant difference in favor of the active treatment group was seen in inhaled salbutamol use (P<0.01).

Conclusions: Clinical benefits achieved during the present study included significant improvements in conjunctivitis symptoms and prevention of asthma symptoms. The overall safety profile of the active treatment (drops or tablets) was good.
Cross‐reacting IgE and IgG antibodies to Pityrosporum ovale mannan and other yeasts in atopic dermatitis
Authors: Lintu P. , Kortekangas‐Savolainen O. , Kalimo K. , Savolainen J. , Terho E.O. , Lintu P. , Nermes M.
Published: March 2003

Atopic dermatitis (AD) patients often demonstrate positive skin prick test results and serum IgE antibodies to a range of different yeasts. This has been thought to be due to cross‐reactivity. In this study, the cross‐reactivity of IgE and IgG antibodies between mannan and crude antigens of Pityrosporum ovale, Candida albicans, and Saccharomycescerevisiae and crude antigens of Cryptococcus albidus and Rhodotorula rubra was examined by RAST and ELISA inhibition with two serum pools of AD patients. We found cross‐reacting IgE and IgG antibodies. In the IgE response, the main cross‐reacting pattern was the mannan region, although inhibition could be achieved also with crude antigens of C. albicans, S. cerevisiae, and, to some extent, C. albidus. P. ovale was the most potent inhibitor of IgE‐binding components, and against it the highest IgE antibody levels were detected in AD serum pools. In contrast, C. albicans was found to be the most important inducer of IgG antibodies, since the IgG level against P. ovale mannan in both AD serum pools was very low. Cross‐reacting antibodies were also seen in ELISA inhibition with both crude and mannan antigens, but since the IgG antibody level of P. ovale mannan in AD serum pools was low, further studies are needed to confirm the IgG results.
Prenatal factors and occurrence of rhinitis and eczema among offspring
Authors: Xu B , Pekkanen J , Järvelin M‐r
Published: March 2003

Background: It has recently been suggested that an atopic phenotype may already be programmed in utero. We examine here the association between prenatal factors and the subsequent development of allergic rhinitis and eczema among offspring.

Methods: The analyses were based on 8088 children in a population‐based prospective birth cohort started in northern Finland in 1985–6.

Results: The prevalences of allergic rhinitis and allergic eczema by the age of 7 years among 8088 children were 3.3% and 6.7%, respectively. The results indicate that low parity, febrile infections in pregnancy, and the use of contraceptives before pregnancy increased the risk of allergic disorders among children. Bleeding in the first trimester and a greater weight gain during pregnancy appeared to be risk factors for rhinitis only. Children whose mothers experienced infections in the first trimester had ORs of 2.65 (95% CI 1.50–4.69) for rhinitis and 1.63(95%CI1.00–2.69) for eczema after adjustment for potential confounders.

Conclusions: Obstetric complications and infection in pregnancy may increase the risk of allergic disorders among the offspring.
Evaluation of acoustic rhinometry in a nasal provocation test with allergen
Authors: Ganslmayer M. , Spertini F. , Terrien M.‐H. , Leimgruber A. , Rahm F. , Mosimann B.
Published: March 2003

Background: The objective was to validate acoustic rhinometry (AR) in a nasal challenge with allergen.

Methods: Nasal response to allergen provocation was based on clinical and symptom scores, cross‐sectional changes of the nasal mucosa as measured by AR with the Rhinoklack® system, and peak nasal inspiratory flow (PNIF), in atopic and nonatopic volunteers.

Results: After allergen challenge, mean variation in minimal cross‐sectional area (ΔMCA), as measured by AR, or in peak nasal inspiratory flow (ΔPNIF) in nonatopic volunteers, was −0.4±14.3% and 5.2±15.7%, respectively, compared to baseline. This allowed the determination of a reaction threshold of −29% for ΔMCA and of −26% for ΔPNIF. All but one of the 30 atopic patients reached the AR reaction threshold, whereas all patients reached the PNIF reaction threshold. AR and PNIF closely correlated with clinical and symptom scores for nasal congestion, since there was no significant difference at reaction threshold between both methods.

Conclusions: In an allergen provocation test, AR appears to be as specific and sensitive as peak nasal inspiratory flow, with the advantage of being independent of the patient's active cooperation. Discrepancies between both methods emphasize the role of nasal cavity anatomy in measuring nasal congestion by AR.
A case of allergy to cow's milk hydrolysate
Authors: Nilsson C. , Lilja G. , Öman H. , Halldén G. , Härfast B. , Lundberg M.
Published: March 2003

We here report a girl, now 3 years old, who has suffered from severe food allergy since her first year of life. She was strongly allergic to cow's milk, and had high levels of IgE antibody (AB) to casein (210 kU/l), β‐lactoglobulin (43 kU/l), and α‐lactalbumin (23 kU/l) at 12 months of age. In addition, at the same age, she showed positive (2–4+) skin prick reactions to both unboiled and boiled formulas (Profylac, Nutramigen, and Neocate), besides being positive in RAST to Nutramigen (0.6 kU/l). During the first 3 years, IgE Ab levels against casein and Nutramigen increased to 310 and 1.6 kU/l, respectively. Furthermore, at 3 years of age, she had positive RAST to 14 of 15 tested food allergens, being negative only to codfish. Assessment of eosinophil‐related markers revealed high total eosinophil count, increased eosinophil activity, and a low ratio of interferon (IFN)‐γ:IL‐5, indicating enhanced IL‐5 production. The food allergy was correlated to poor weight gain and increasing problems with atopic allergy in the airways.
Comparison of methods to assess airborne rat and mouse allergen levels. II. Factors influencing antigen detection
Authors: Renström A , Gordon S , Hollander A , Spithoven J , Larsson PH , Venables KM , Heederik D , Malmberg P
Published: March 2003

Potential factors influencing antigen detection in immunoassays for measuring rat or mouse aeroallergen (i.e., assay setup, antigen specificities, standard extracts used, and antigen decay) were investigated in a three‐country study (the UK, The Netherlands, Sweden). An inhibition enzyme immunoassay (EIA) setup gave nominal rat urinary allergen (RUA) sample values seven times higher than a sandwich EIA setup utilizing identical antibodies and standards. In immunoblotting experiments, pooled patient serum and polyclonal rabbit antibodies partly detected different rat antigens; monoclonal antibody specificity could not be determined. Immunoblot detection of mouse urinary antigens (MUA) by the polyclonal rabbit antibodies from all laboratories was similar. In both the RUA and the MUA assays, urinary antigen standards were detected with similar potency, except purified Rat n 1, which was an inefficient inhibitor in the RUA RAST inhibition. In the sandwich EIA RUA assays, a rat room‐dust extract was detected with 700–800‐fold less sensitivity than rat urine, whereas in the RAST RUA assay, dust inhibited equally with rat urine. Simulated decay did not decrease the potency of urinary antigen in any assay. Thus, assay setup and choice of detection antibodies strongly influence the nominal allergen levels. We recommend the use of standardized and characterized antibodies and standard extracts in sandwich EIAs to measure airborne rodent urinary allergens.

Abbreviations: NHLI: National Heart and Lung Institute, London, UK; WAU: Wageningen Agricultural University, Wageningen, The Netherlands; NIWL: National Institute for Working Life, Solna, Sweden; Ab: antibody; mAb: monoclonal antibody; EIA: enzyme immunoassay; RAST: radioallergosorbent test; RIA: radioimmunoassay; MUA: mouse urinary allergen; RUA: rat urinary allergen; BSA: bovine serum albumin; HSA: human serum albumin; PBS: phosphate‐buffered saline; PTFE: polytetrafluoroethylene (Teflon); TBS: Tris‐buffered saline.
Increased risk of allergy in children due to formaldehyde exposure in homes
Authors: Garrett MH , Hooper MA , Hooper BM , Rayment PR , Abramson MJ
Published: March 2003

Background: Formaldehyde levels were measured in 80 houses in the Latrobe Valley, Victoria, Australia. An association between exposure to formaldehyde and sensitization to common aeroallergens has been suggested from animal trials, but no epidemiologic studies have tested this hypothesis.

Methods: A total of 148 children 7–14 years of age were included in the study, 53 of whom were asthmatic. Formaldehyde measurements were performed on four occasions between March 1994 and February 1995 with passive samplers. A respiratory questionnaire was completed, and skin prick tests were performed.

Results: The median indoor formaldehyde level was 15.8 μg/m3(12.6 ppb), with a maximum of 139 μg/m3 (111 ppb). There was an association between formaldehyde exposure and atopy, and the adjusted odds ratio was 1.40 (0.98–2.00, 95% CI) with an increase in bedroom formaldehyde levels of 10 μg/m3. Furthermore, more severe allergic sensitization was demonstrated with increasing formaldehyde exposure. On the other hand, there was no significant increase in the adjusted risk of asthma or respiratory symptoms with formaldehyde exposure. However, among children suffering from respiratory symptoms, more frequent symptoms were noted in those exposed to higher formaldehyde levels.

Conclusions: Low‐level exposure to indoor formaldehyde may increase the risk of allergic sensitization to common aeroallergens in children.
Vocal cord dysfunction in a child
Authors: Juliá Jc , Martorell A , Cerdá Jc , Alvarez V , Armengot Ma , Lluch R , Boluda Cf
Published: March 2003

Vocal cord dysfunction (VCD) involves paradoxical adduction of the vocal cord during the respiratory cycle. This usually occurs during inspiration, but can also be seen in expiration. Vocal cord appositioning produces airflow obstruction sufficient to cause wheezing, shortness of breath, chest tightness, and coughing. These symptoms often imitate the respiratory alterations of asthma, thus leading to inappropriate treatment; intubation or tracheotomy may prove necessary. An 11‐year‐old girl was admitted with intractable dyspnea. She had been diagnosed with atopic asthma, although she failed to respond to an increase in antiasthma medication, including high‐dose oral steroids. Flow‐volume loops were abnormal, with evidence of variable extrathoracic airway obstruction, manifested as a flat inspiratory loop. No structural abnormalities were seen with either computed tomography (CT) or magnetic resonance imaging (MRI). Fibroscopy revealed paradoxical adduction of the vocal cords during the respiratory cycle, no obstructive disorder being observed. After the diagnosis of VCD, the clinical manifestations resolved with psychiatric treatment. Adduction was not demonstrable at repeat fibroscopy after treatment. VCD may simulate bronchial asthma; it may also be associated with that disorder, thus masking the diagnosis. It should be suspected in patients with recurrent wheezing who fail to respond to usual asthma treament. An early diagnosis avoids unnecessary aggressive management. Treatment should consist of respiratory and phonatory exercises; psychotherapy may be useful.
Analysis of hsp70 gene polymorphism in allergic asthma
Authors: Aron Y , Busson M , Polla BS , Dusser D , Lockhart A , Swierczewski E , Favatier F
Published: March 2003

Background: Allergic asthma is a multifactorial and probably multigenic inflammatory disease of the upper airways, and has been associated with the HLA class II alleles DR4 and DR7. Here we investigated possible associations with other polymorphic susceptibility/resistance genes located within the major histocompatibility complex, i.e., the genes coding the major 70‐kDa heat‐shock proteins (HSP; Hsp70) hsp70–1, hsp70–2, and hsp70‐HOM, whose products are overexpressed in the bronchi of asthmatic patients.

Methods: Genomic DNA was extracted from peripheral blood lymphocytes or buccal epithelial cells of 48 patients with allergic asthma and 31 selected nonatopic control subjects, in whom we previously reported a strong association of atopy with DR4/DR7 alleles.Results: No evidence was found for an independent role of hsp70 gene polymorphism in susceptibility to allergic asthma. However, hsp70 alleles might be involved in extended haplotypes of HLA markers.

Conclusions: Our data suggest that Hsp70 overexpression in asthma results from complex interactions between environmental exposures and genetic background rather than from specific genetic variations in hsp70 genes.
Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy
Authors: Ciprandi G , Tosca M , Passalacqua G , Canonica GW , Ricca V , Landi M
Published: March 2003

Background: Allergic reaction is characterized by a complex inflammatory process. Some of the new antihistamines have antiallergic effects and can affect the inflammatory cell recruitment via adhesion molecule downregulation. We aimed to assess in a 12‐month study whether continuous treatment with an antihistamine (terfenadine) can reduce respiratory symptoms and local inflammation in children with mite allergy.

Methods: The study was double‐blind and placebo‐controlled: it involved two parallel groups of children suffering from rhinoconjunctivitis and/or mild intermittent asthma due to mite allergy. They received either terfenadine (1 mg/kg per body weight per day) or placebo for 1 year. Nasal, conjunctival, and bronchial symptoms were recorded by diary cards; at each of the programmed control visits, a nasal scraping for inflammatory cells and ICAM‐1 was performed. Some additional clinical parameters were also recorded: days of school absence, extra visits for acute respiratory symptoms, and days of hospital admission.

Results: Only children treated with terfenadine achieved significant control of symptoms (P<0.05 in 8 out of 12 months) and allergic inflammation, as shown by inflammatory cell infiltrate and ICAM‐1 expression at nasal level (P<0.001), and had significantly fewer extra visits and school absences than the placebo group (P<0.03). No side‐effects were reported in either group.

Conclusions: The present study demonstrates that continuous terfenadine treatment (1 mg/kg body weight per day) could decrease respiratory symptoms and allergic inflammation, and it had an additional antiallergic effect in reducing ICAM‐1 expression on nasal epithelial cells. Therefore, the present results confirm the efficacy of a long‐term therapeutic strategy in controlling allergic inflammation.
Immunologic mechanisms in hypersensitivity reactions to metal ions: an overview
Authors: Büdinger Lioba , Hertl Michael , Büdinger Lioba
Published: March 2003

Metal ions such as Ni2+, Co2+, Cu2+, or Cr3+ are haptens with a high immunogenic potential, as contact dermatitis caused by ionic metals occurs in about 10–15% of the human population. Since alloys containing Ni2+, Co2+, and Cr3+ are components of implants in replacement surgery, dentures, orthodontic wires, and various other devices, adverse reactions to metal ions create serious problems in practical medicine as incompatibility reactions to metal‐containing biomaterials. On the other hand, contact dermatitis to metal ions such as Ni2+ is a well‐established model for studying the molecular mechanisms involved in the recognition of haptens by the immune system. Although many investigations have been performed to elucidate the molecular interactions causing contact hypersensitivity in man, many aspects remain to be clarified. This review will focus on the experimental data accumulated so far on the immunologic mechanisms responsible for the recognition of metal ions by T cells and eliciting adverse immune reactions causing contact dermatitis.
Identification of bovine IgG as a major cross‐reactive vertebrate meat allergen
Authors: Ayuso R. , Lehrer S. B. , Lopez M. , Reese G. , Ibañez M. D. , Esteban M. Martin , Ownby D. R. , Schwartz H.
Published: March 2003

Background: Although beef is a main source of protein in Western diets, very little has been published on allergic reactions to beef or the main allergens implicated in these reactions. The aim was to evaluate the IgE antibody response to beef in suspected meat‐allergic subjects and assess cross‐reactivity of beef with other vertebrate meats.

Methods: Fifty‐seven sera from suspected meat‐allergic subjects were tested by grid blot for specific IgE antibodies to vertebrate meats (beef, lamb, pork, venison, and chicken), and the patterns of recognition of meat proteins were assessed by immunoblot studies.

Results: A 160‐kDa band, identified as bovine IgG, was detected in raw beef in 83% (10/12) of beef‐allergic subjects but in only 24% of the beef‐tolerant subjects. IgE reactivity to a band of similar mol. mass was detected also in lamb and venison, but rarely in pork or chicken. Complete inhibition of the IgE reactivity to the bovine IgG was obtained with lamb, venison, and milk. IgE reactivity to this band also completely disappeared when beef or lamb extracts were separated under reducing conditions, indicating conformational epitopes.

Conclusions: Bovine IgG appears to be a major cross‐reacting meat allergen that could predict beef allergy. Further studies with oral IgG challenges should be performed to document the conclusion that in vitro reactivity correlates with clinical hypersensitivity. The role of bovine IgG in other bovine products such as milk, dander, or hair must also be studied, and the hypothesis that it is a cross‐reacting allergen with other mammalian products validated.
Evidence of eosinophil, neutrophil, and mast‐cell mediators in the effusion of OME patients with and without atopy
Authors: Hurst D. S. , Venge P.
Published: March 2003

Background: This study was designed to measure the involvement of eosinophils, neutrophils, and mast cells in the middle ear of patients with OME and to see whether that inflammatory response differed depending on whether or not the patient was atopic.

Methods: Levels of ECP, MPO, and tryptase were measured in effusion from 97 patients whose atopic status was determined by in vitro testing with 12 inhalants and five foods.

Results: Seventy‐nine of 97 OME patients (81%) were atopic, among whom 86% (68/79) had elevated levels of effusion ECP, and 64% (23/36) had elevated tryptase. Mean ECP was 166 μg/l vs 3.38 μg/l, mean MPO was 6231 μg/l vs 116 μg/l, and mean tryptase was 4.8 μg/l vs 1.34 μg/l in atopic vs nonatopic ears. Total serum IgE did not differ between atopics and nonatopics (P=0.28).

Conclusions: The inflammatory response by eosinophils, neutrophils, and mast cells in the middle ear was distinctly different between atopic and nonatopic patients (P<0.001). This study provides evidence that eosinophils and mast cells, both essential to a Th‐2 driven immune response, are present in the majority of ears with chronic OME, and supports the hypothesis that middle‐ear mucosa, like that of the rest of the upper respiratory tract, is capable of an allergic response.
Indoor air pollutants in schools: nasal patency and biomarkers in nasal lavage
Authors: Norbäck D. , Wålinder R. , Wieslander G. , Smedje G. , Erwall C. , Venge P.
Published: March 2003

Background: There is growing concern about the respiratory health aspects of the indoor air quality in schools.

Methods: A standardized investigation, including nasal lavage (NAL), measurement of the nasal cavity by acoustic rhinometry, and hygienic measurements of airborne pollutants was performed in classrooms, outside the pollen season. All 279 school personnel working in the main buildings of 12 randomly selected primary schools in an urban community in central Sweden (Uppsala) were invited to enroll in the study; 234 (84%) participated. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme, and albumin were analyzed in NAL. Crude statistical analysis, as well as multiple regression analysis, was performed, controlling for room temperature, age, sex, current smoking, and a history of atopy.

Results: Most classrooms (83%) did not meet the Swedish ventilation standards. A lower degree of nasal patency was found at higher concentrations of respirable dust, nitrogen dioxide (NO2), formaldehyde, and total molds, and in the presence of Aspergillus sp. in the classroom air. The most consistent findings were observed for formaldehyde, NO2, and Aspergillus sp., related to both decreased nasal patency and increase of ECP and lysozyme in NAL. The presence of yeast was associated with an increase of ECP and lysozyme in NAL, but was not related to nasal patency.

Conclusions: Ventilation flow was below current hygienic standards in the classrooms. Air pollutants in the classroom air may influence nasal patency and inflammatory response in the nasal mucosa.
Polymorphisms at the glutathione S‐transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation
Authors: Spiteri M. A. , Bianco A. , Strange R. C. , Fryer A. A.
Published: March 2003

A common feature of environmental irritants is their ability to cause local inflammation which could alter airway function. The principal targets of such injury are the epithelial cells lining the airway passages and the lower respiratory gas‐exchange areas. While host atopy is a recognized risk factor for airway inflammation, atopy alone cannot cause asthma. We hypothesize that susceptibility to persistent airway inflammation in atopic individuals is characterized by an inherited deficiency in the effectiveness of detoxification of inhaled irritants and products of oxidative stress such as reactive oxygen species (ROS). Our case‐control studies show that polymorphisms at the glutathione S‐transferase, GSTP1, locus on chromosome 11q13 may account for variation in host response to oxidative stress, a key component of airway inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic subjects compared with nonatopic subjects. Trend analysis also shows a significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile) genotype frequency with increasing severity of airflow obstruction/bronchial hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus in airway inflammation is entirely novel: however, GST are recognized as a supergene family of enzymes critical in 1) cell protection from the toxic products of ROS‐mediated reactions, 2) modulation of eicosanoid synthesis.
New perspectives in asthma treatment
Authors: Pelaia G. , Vatrella A. , Calabrese C. , Mazzarella G. , Marsico S.A.
Published: March 2003

The recent advances in the knowledge of the basic mechanisms underlying asthmatic inflammation have significantly contributed to the delineation of new therapeutic perspectives for asthma. There are currently three main approaches to the development of novel antiasthma treatments:

improvement in existing classes of drugs

identification of new compounds able to interfere with the complex network of proinflammatory mediators, cytokines, chemokines, and adhesion molecules involved in the pathogenesis of asthma

utilization of new forms of immunotherapy aimed at blocking the unbalanced Th2 response which characterizes the pathophysiology of asthma.

Such a remarkable expansion in available therapeutic options will probably allow us, over the next decade, to treat asthma by more selectively targeting the pathogenetic events responsible for this widespread airway disease.
PCR‐based cloning, isolation, and IgE‐binding properties of recombinant latex profilin (rHev b 8)
Authors: Rihs H‐P. , Chen Z. , Rozynek P. , Baur X. , Lundberg M. , Cremer R.
Published: March 2003

Background: Profilin (Hev b 8) in natural rubber latex (NRL) has been assumed to be an important allergen. Since latex profilin has a molecular mass similar to two other latex allergens (Hev b 1 and Hev b 6.03) in the 14‐kDa range, it is difficult to obtain sufficient amounts of purified native profilin for investigations and diagnostics. The present study aimed to produce recombinant latex profilin (rHev b 8) and study its IgE‐binding reactivity.

Methods: A profilin‐specific cDNA encoding the latex profilin from Hevea brasiliensis leaves was synthesized and subcloned, and the rHev b 8 was overexpressed in fusion with the maltose‐binding protein (MBP) in E. coli. The IgE‐binding reactivity of rHev b 8 was studied by immunoblotting, immunoblot inhibition experiments, and the Pharmacia CAP method, with 25 sera from health‐care workers with latex allergy and 17 sera from latex‐sensitive spina bifida patients.

Results: rHev b 8 was found to have 131 amino acids and a sequence identity of 75% with birch profilin (Bet v 2). Analysis by the CAP system revealed the presence of rHev b 8‐specific IgE antibodies in two out of 17 sera from spina bifida patients and in five out of 25 sera (20%) from health‐care workers. Two subjects of the latter group with rHev b 8‐specific IgE showed negative results in the skin prick tests with tree‐pollen extracts and had no IgE to rBet v 2, indicating the presence of IgE‐binding epitopes on the Hev b 8‐molecule which do not cross‐react with birch profilin. Immunoblot inhibition assays using MBP‐rHev b 8 as inhibitor confirmed the presence of latex profilin in the NRL extract. IgE binding to the native latex profilin could be completely inhibited by the MBP‐rHev b 8.

Conclusions: Latex profilin represents a minor allergen in NRL and may have IgE‐binding epitopes different from Bet v 2.
Dendritic cell number is related to IL‐4 expression in the airways of atopic asthmatic subjects
Authors: Bertorelli G. , Bocchino V. , Zhuo X. , Zanini A. , Bernini M. V. , Damia R. , Di Comite V. , Grima P. , Olivieri D.
Published: March 2003

Background: Airway dendritic cells are essential for stimulating naive T cells in response to inhaled antigen and for the development of allergic sensitization. IL‐4 in vitro can distinguish dendritic cell lines from peripheral blood mononuclear cells. Our study had the following aims:

to compare the distribution of CD1a+ dendritic cells and IL‐4+ cells, in the bronchial mucosa of asthmatics and controls

to determine the relationship between the numbers of CD1a+ dendritic cells and IL‐4+ cells in the bronchial mucosa of asthmatics

to determine whether CD1a+ cells express the IL‐4 receptor.

Methods: Twenty atopic asthmatic and eight normal subjects were studied. In each subject, bronchoscopy with bronchial biopsies was performed. CD1a, IL‐4, and IL‐4 receptor expressions were evaluated by immunohistochemistry.

Results: The number of CD1a+ and IL‐4+ cells was significantly higher in asthmatics than controls. The number of CD1a+ cells was positively correlated to the number of IL‐4+ cells. Bronchial biopsy serial section studies showed that CD1a+ cells express the receptor for IL‐4.

Conclusions: These results suggest that an increased amount of IL‐4 may play a physiopathologic role in maintaining the dendritic cell pool in vivo. Therefore, because of possible IL‐4 activity on antigen‐presenting cells in T‐cell immune responses to allergens, an important new role of IL‐4 in asthma inflammation can be envisaged.
Identification of four novel potato (Solanum tuberosum) allergens belonging to the family of soybean trypsin inhibitors
Authors: Seppälä U. , Majamaa H. , Turjanmaa K. , Helin J. , Reunala T. , Kalkkinen N. , Palosuo T.
Published: March 2003

Background: We have previously identified patatin (Sol t 1) of potato tubers as a major food allergen among atopic children. In addition to Sol t 1, concomitant IgE binding to other, then unidentified, potato proteins was observed.

Methods: Purification and identification of the putative allergens were done by both standard and advanced methods of protein chemistry. The patient series comprised 39 children with positive skin prick test (SPT) to raw potato. Immunoblotting and ELISA were used to examine IgE‐binding ability and skin prick testing to assess in vivo reactivity of the purified potato proteins.

Results: Four IgE‐binding potato proteins with molecular masses ranging from 16 to 20 kDa were purified and identified as cathepsin D‐, cysteine‐, and aspartic protease inhibitors belonging to the family of soybean trypsin inhibitors (Kunitz type). The proteins were designated Sol t 2, Sol t 3.0101, Sol t 3.0102, and Sol t 4. In ELISA, 51% of the sera of the 39 atopic children showed specific IgE to Sol t 2, 43% to Sol t 3.0101, 58% to Sol t 3.0102, and 67% to Sol t 4, respectively. All these four allergens were able to produce positive wheal‐and‐flare responses in SPT.

Conclusions: In addition to Sol t 1, potato tubers contain several proteins belonging to the family of soybean trypsin inhibitors against which atopic children with positive SPT responses to raw potato have in vitro and in vivo reactive IgE antibodies.
Calreticulin is an interleukin‐3‐sensitive calcium‐binding protein in human basophil leukocytes
Authors: Lyngholm M. J. , Nielsen H. V. , Holm M. , Schiøtz P. O. , Johnsen A. H.
Published: March 2003

Background: IL‐3 enhances basophil histamine release upon stimulation with any known secretagogue. The molecular mechanism behind this regulation is not known, although some observations suggest that IL‐3 modulates the calcium part of the signal transduction mechanism. The inhibitory action of glucocorticoids on basophils can be reversed by stimulation with IL‐3.

Methods: Calcium‐binding proteins in the basophil cell line KU812 were identified by two‐dimensional gel electrophoresis, Calcium‐overlay assay, N‐terminal sequence analysis, and mass spectometry. The presence of the same proteins in purified human basophil leukocytes was established by comigration of KU812 and human basophil proteins on the two‐dimensional gels. The expression of the calcium‐binding proteins in the absence and presence of IL‐3 and/or anti‐IgE was determined by densitometric measurement of the spots on the two‐dimensional gels.

Results: Calreticulin was identified on the two‐dimensional gel of KU812 proteins. A protein with exactly the same migration pattern was found on the gels of proteins from purified human basophils. Immunoblotting with a specific anti‐human calreticulin antibody confirmed that this protein was calreticulin. Subsequent analysis showed that the expression of calreticulin in the basophils is upregulated twofold upon stimulation with rhIL‐3, even in doses below those needed for enhancement of histamine release.

Conclusions: The expression of calreticulin in human basophil leukocytes is regulated by IL‐3. Calreticulin is known to modulate IP3‐dependent Ca2+ influx in different cell systems, and calreticulin overexpression inhibits steroid‐induced transcriptional activation. Therefore, modulation of calreticulin expression may be one mechanism by which IL‐3 exerts its effects on human basophils.
A baker's occupational allergy to flour moth (Ephestia kuehniella)
Authors: Mäkinen‐Kiljunen S. , Mussalo‐Rauhamaa H. , Petman L. , Rinne J. , Haahtela T.
Published: March 2003

Background: Allergy to insects is common. However, few reports cover occupational sensitization to flour moth (Ephestia [syn. Anagasta] kuehniella). We describe a baker who suffered from IgE‐mediated occupational respiratory allergy to flour moth.

Methods: The skin prick test (SPT) and serum IgE tests were used to evaluate the patient's sensitivity to flour moth. Allergen cross‐reactivity with mites was evaluated in IgE‐inhibition studies. Clinical sensitivity was evaluated by nasal challenge test. Pulmonary function tests were repeatedly monitored.

Results: SPT with flour moth gave a 6‐mm wheal, and an elevated level of flour moth‐specific IgE was measured in the patient's serum (1.9 PRU/ml, RAST class 2). Immunoblotting with the patient's serum revealed at least seven heavy IgE‐binding bands with molecular masses of 22, 35, 43, 53, 65, 77, and >86 kDa in the extract of flour moth. Allergen cross‐reactivity with mites was demonstrated in inhibition studies. Immediate‐type allergy to flour moth was confirmed by nasal challenge. Increased daily variability of PEF values was observed during workplace exposure.

Conclusions: A baker's occupational respiratory allergy to flour moth was confirmed.
Epidemiology of food allergy/food intolerance in adults: associations with other manifestations of atopy
Authors: Schäfer T. , Böhler E. , Ruhdorfer S. , Weigl L. , Wessner D. , Heinrich J. , Filipiak B. , Wichmann H‐E. , Ring J.
Published: March 2003

Background: Food allergy and food intolerance (FA/FI) are believed to be frequent medical problems; however, information from epidemiologic studies in adults is scarce. The objective was to determine the frequency of FA/FI and allergic sensitization to food in a large adult sample. Furthermore, the associations between FA/FI and other outcomes of atopy were studied.

Methods: Within a population‐based, nested, case‐control study, a standardized interview was performed to obtain detailed information on FA/FI and the history of atopic diseases. In addition, a skin prick test with 10 common food and nine aeroallergens was performed.

Results: Overall, 20.8% of the 1537 studied subjects (50.4% female, age median 50 years) reported FA/FI (women 27.5%, men 14.0%; OR 2.35, CI 1.80–3.08). Nuts, fruits, and milk most frequently led to adverse effects, and the sites of manifestation were oral (42.9%), skin (28.7%), gastrointestinal (13.0%), systemic (3.2%), and multiple (12.2%). One‐quarter of the subjects (25.1%) were sensitized to at least one food allergen in the prick test, with hazelnut (17.8%), celery (14.6%), and peanut (11.1%) accounting for most of the positive reactions. The corresponding frequency estimates for the representative study base (n=4178) were 15.5% for reported adverse reactions and 16.8% for allergic sensitization. Relevant concomitant sensitization to food and aeroallergens was observed. Food‐allergic subjects (positive history and sensitization to corresponding allergen) suffered significantly more often from urticaria, asthma, atopic eczema, and especially hay fever (73.1%) than controls (3.0%). Furthermore, hay fever was treated significantly more often in subjects who suffered from concomitant food allergy.

Conclusions: FA/FI in adults is frequently reported and associated with other manifestations of atopy. Hay fever in conjunction with FA/FI tends to be clinically more severe since therapeutic needs are enhanced.
Effects of in vitro treatment with fluticasone propionate on natural killer and lymphokine‐induced killer activity in asthmatic and healthy individuals
Authors: Di Lorenzo G. , Esposito Pellitteri M. , Drago A. , Di Blasi P. , Candore G. , Balistreri C. , Listì F. , Caruso C.
Published: March 2003

Background: Topical corticosteroids are beneficial in the treatment of allergic respiratory disorders; they exert effects on a number of cells involved in allergic inflammatory reactions. On the other hand, major histocompatibility complex (MHC)‐unrestricted cytotoxicity (i.e., natural killer [NK] cell activity) may play a role in the inflammatory allergic reaction. The objective was to gain insight into the mechanisms of the therapeutic effects of fluticasone propionate (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore, we evaluated the NK and lymphokine‐activated killer (LAK) activity of effector cells in vitro treated or not with FP.

Methods: Evaluations were made on peripheral blood mononuclear cells (PBMNCs), obtained from healthy volunteers (n=10) and from asthmatic atopic subjects (n=10) with allergy to Parietaria.

Results: Asthmatic patients had significantly increased NK activity (P=0.0008), and interleukin (IL)‐2‐ (P=0.0005) and interferon (IFN)‐α‐induced LAK activities (P=0.0005). In both groups, FP 10−7 M significantly reduced NK activity (P<0.0001), IL‐2‐induced LAK activity (P<0.0001), and IFN‐α‐induced LAK activity (P<0.0001). Similar results were obtained with FP 10−8 M.

Conclusions: Since MHC‐unrestricted cytotoxicity has been implicated in the development of allergen‐induced eosinophilic airway inflammation, inhibition of NK and LAK activity by FP may contribute to the steroid therapeutic effect in asthma.
Characterization of cross‐reacting allergens in mango fruit
Authors: Paschke A. , Kinder H. , Zunker K. , Wigotzki M. , Steinhart H. , Weßbecher R. , Vieluf I.
Published: March 2003

Background: Allergic reactions to mango fruit have become increasingly important. A cross‐reaction between mango fruit, various other foods, and respiratory allergens has been assumed but not investigated until now.

Methods: The sera of nine patients were used to characterize cross‐reacting allergens in mango fruits by EAST inhibition and immunoblot inhibition.

Results and Conclusions: EAST inhibition and immunoblot inhibition demonstrated that cross‐reactions between mango fruits, mugwort pollen, birch pollen, celery, and carrot are based on allergens related to Bet v 1 and Art v 1, the major allergens of birch and mugwort pollen, respectively.