bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic urticaria: novel clinical and serological aspects
Authors: Asero R. , Tedeschi A. , Lorini M. , Salimbeni R. , Zanoletti T. , Miadonna A. 
Published: March 2003

Background Recently, distinct studies have shown that: (a) chronic idiopathic urticaria (CIU) is autoimmune in 30–50% of cases; (b) in patients with CIU the autologous serum skin test is inhibited by heparin; and (c) basophil histamine release induced in vitro by CIU sera maybe complement‐dependent.Objective To carry out a comprehensive clinical and serological study on CIU based upon these observations.Methods Three hundred and six adults with CIU underwent intradermal (ID) test with autologous serum; 57 of them with autologous heparinized plasma as well. Sera from 121 patients (plasmas from 17) were employed to induce in vitro histamine release from basophils of normal donors. The effects of heating (56 °C, 60 min), filtration through membrane, and preincubation with heparin were evaluated as well.Results Autologous serum and plasma induced a weal and flare reaction in 205 out of 306 (205/306; 67%) and in 8/57 (14%) patients, respectively. Positive plasma skin tests were observed only in patients showing strongly positive serum skin tests. Plasma did not elicit any skin reaction in 3/3 patients with dermatographism who showed a positive intradermal test with saline. Sera from 20/121 (16.5%) patients induced significant histamine release from basophils of normal donors. 19/20 sera were from patients with a positive intradermal test; thus, basophil histamine release assay was positive in 19/87 (21.8%) patients with a positive serum skin test. Heating at 56 °C × 1 h markedly reduced the histamine‐releasing activity of both serum and plasma from in vitro reactors. Ultrafiltered fractions > 100 kDa of both sera tested retained the histamine‐releasing activity, whereas fractions < 100 kDa were not able to induce any histamine release. Heparin dose‐dependently inhibited histamine release induced by sera and plasma, and by basophil agonists such as anti‐IgE, formyl‐methionyl‐leucyl‐phenilalanine, and interleukin (IL)‐3.Conclusions 67% of our patients with CIU showed a positive autologous serum skin test. Sera from about 20% of those positive on autologous serum skin test induced histamine release from normal basophils in vitro probably as a consequence of the presence of functional autoantibodies. The marked difference between in vivo and in vitro findings could reflect the existence of a mast cell‐specific histamine‐releasing factor which does not release histamine from basophils of healthy blood donors. However, it might be also the result of in vivo priming of patients' cutaneous mast cells or of heterogeneity of basophil donors. At least in some cases complement seems essential for histamine‐releasing activity of serum from patients with CIU. Heparin inhibits histamine release from both basophils (in vitro) and mast cells (in vivo), probably acting directly at a cellular level.
Eosinophils are activated in middle ear mucosa and middle ear effusion of patients with intractable otitis media associated with bronchial asthma
Authors: Iino Y. , Nagamine H. , Yabe T. , Matsutani S. 
Published: March 2003

Background Although patients with intractable otitis media associated with bronchial asthma have extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion, systematic histological and immunohistochemical studies have not been performed.Objectives To clarify the pathogenesis of middle ear diseases, we carried out immunohistochemical studies on middle ear specimens, particularly focusing on the characteristics of accumulated eosinophils.Methods Middle ear specimens obtained from eight adult patients and from 17 controls were immunohistochemically stained using monoclonal antibodies against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of eosinophil cationic protein (ECP) in middle ear effusion samples was also measured.Results In the asthmatic patients, severe round‐cell infiltration was observed in the submucosa and most of the EG1‐positive cells were also EG2‐positive. In the control patients, the mucosa showed a fibrotic change with a few inflammatory cells, and EG1‐ or EG2‐positive cells were quite few. The expression of IgE was found not only on the surface of mast cells but also within the plasma cells in the asthmatic patients, and the number of IgE‐positive cells was about twice as high as that of mast cells. A significantly higher concentration of ECP was noted in middle ear effusion obtained from the asthmatic patients than that from the control patients.Conclusion Most of the eosinophils in the middle ear mucosa and middle ear effusion were activated, resulting in degranulation and release of ECP, and local IgE production occurs in the middle ear mucosa, indicating that the intractable inflammation is closely associated with IgE‐mediated late phase response with eosinophil accumulation.
Maternal atopy and parity
Authors: Sunyer J. , Antó J. M. , Harris J. , Torrent M. , Vall O. , Cullinan P. , Newman‐Taylor A. 
Published: March 2003

Background Family size and high birth order were related to the prevalence of hayfever and positive skin prick test. However, this association may be explained by maternal atopy. We examined the relationship between maternal atopy and the number of offspring in three European cohorts of pregnant women.Methods The mothers and their children (n = 1487) were recruited for the Asthma Multi‐centre Infants Cohort Study (AMICS). The three concurrent cohorts (Ashford, Kent (UK); Menorca island (Spain) and Barcelona city (Spain) followed the same research protocol. Maternal and paternal atopy was identified by skin prick tests at different times at the three centres.Results Maternal atopy was inversely related to the number of offspring, an association which occurred in each of the three cohorts and remained when atopy was defined separately for individual allergens (a positive response to testing with either Der p 1 or grass pollen) and which was not confounded by maternal age, smoking nor social class (the adjusted odds ratios were 0.71, 0.79 and 0.26 for increasing number of offspring, P = 0.002). Neither maternal asthma (P = 0.43) nor paternal atopy (P = 0.58) were associated with the number of offspring. Maternal atopy was not related to reproductive outcomes.Conclusions The association between maternal atopy and parity challenges the role of family size on child atopy, which should be studied in other populations.
The allergenic yeast Malassezia furfur induces maturation of human dendritic cells
Authors: Buentke E. , Heffler L. C. , Wallin R. P. A. , Löfman C. , Ljunggren H. G. , Scheynius A. 
Published: March 2003

Background The yeast Malassezia furfur (M. furfur), present in the normal microflora of human skin, can act as an allergen that incites specific IgE reactivity and T cell proliferation in atopic dermatitis (AD) patients. The role of antigen presenting dendritic cells (DCs) in the onset and maintenance of AD is not well established.Objective The objective of the present study was to assess whether the interaction of M. furfur with human DCs will result in DC maturation, cytokine production and lymphocyte proliferation.Methods Monocyte‐derived dendritic cells (MDDCs) were generated from human peripheral blood. Immature MDDCs were cultured with or without M. furfur or plastic beads, and with or without CD40L stimulation. Interaction of yeast cells by MDDCs was studied by time‐lapse photography and cytokines were detected in culture supernatants with ELISA. The ability of MDDCs pre‐incubated with M. furfur to induce proliferation in autologous lymphocytes was measured by [3H]‐thymidine incorporation.Results Time‐lapse photography showed that the majority of immature MDDCs internalized whole M. furfur yeast cells within 1 h. The presence of M. furfur induced maturation (CD83 expression) of MDDCs, and up‐regulation of the costimulatory molecules CD80 and CD86. Production of TNF‐α, IL‐1β and IL‐18 by MDDCs increased significantly (P < 0.05 for TNF‐α and IL‐1β, and P < 0.01 for IL‐18) after the addition of M. furfur, while IL‐10 and IL‐12p70 levels remained unaltered. The CD40L‐stimulated IL12p70 production by MDDCs was decreased in the presence of M. furfur (P < 0.05). Finally, immature MDDCs pre‐incubated with M. furfur induced a proliferative response in autologous CD14‐depleted peripheral blood mononuclear cells, in a dose‐dependent manner.Conclusion The data indicate that immature MDDCs can internalize the opportunistic yeast M. furfur. This process was associated with MDDC maturation, production of pro‐inflammatory and immunoregulatory cytokines, which might favour induction of a Th2‐type immune response, and a capacity to stimulate lymphocyte proliferation. This chain of events most likely contributes to the inflammatory reaction in AD.
Airway epithelial cells promote transmigration of eosinophils in a new three‐dimensional chemotaxis model
Authors: Kato Y. , Fujisawa T. , Shibano M. , Saito T. , Gatto W. , Kamiya H. , Hirai K. , Sumida M. , Yoshie O. 
Published: March 2003

SummaryBackground Prominent infiltration of eosinophils in airway mucosa is the pathognomonic sign of asthma. The role of airway epithelial cells in eosinophil infiltration, however, has not been fully elucidated.Objective The aim of this study is to develop a new in vitro transmigration system composed of airway epithelial cells and extracellular matrix, and to investigate the role of airway epithelial cells in eosinophil infiltration.Methods A layer of type I collagen gel was formed in Netwell™, and BEAS‐2B bronchial epithelial cells were cultured on the gel. Then the wells covered with epithelial monolayer were filled with medium, inverted, and new upper chambers were constructed on the gel side by applying a ring cap. After further incubation with or without exogenous cytokines for 48 h, eosinophils or neutrophils were loaded in upper chambers (the gel side) and cells transmigrated to lower chambers (the epithelial cell side) were counted. Immunohistochemical analyses were also performed.Results While a simple collagen gel hardly promoted eosinophil migration even in the presence of eotaxin or RANTES, significant numbers of eosinophils migrated to lower chambers in the presence of the epithelial cells. Replacement of medium in the lower chamber (the epithelial cell side) with fresh medium, addition of exogenous eotaxin or RANTES in the upper chamber (the gel side), or pre‐treatment of eosinophils with anti‐CCR3 all inhibited transmigration. We found that the epithelial cells produced and deposited extracellular matrix proteins such as type IV collagen onto the type I collagen gel. Separately, we found that type IV collagen itself was capable of enhancing eotaxin‐induced eosinophil migration in a standard chemotaxis assay. Neutrophils also efficiently migrated in the present transmigration system. Pre‐treatment of epithelial cells with TNF‐α and IL‐4 enhanced eosinophil transmigration, while that of neutrophils was enhanced by TNF‐α but suppressed by IL‐4.Conclusion By utilizing a new in vitro transmigration system mimicking the airway mucosa, we have demonstrated that airway epithelial cells play an essential role in transmigration of eosinophils and that multiple factors such as chemokines, extracellular matrix proteins and exogenous inflammatory cytokines are involved in efficient transmigration.
Paradoxical low nasal nitric oxide in nasal polyposis
Authors: Colantonio D. , Brouillette L. , Parikh A. , Scadding G. K. 
Published: March 2003

SummaryBackground Nitric oxide (NO) is synthesized in the respiratory tract. Three isoforms of NO synthase have been described in man, with the inducible form related to inflammatory disease. In the paranasal sinuses constitutive production of nitric oxide has been demonstrated, with levels of 20–25 p.p.m. being found in sinus puncture. Nasal polyposis is a chronic inflammatory condition in which inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp epithelium.Objectives 1. Measurement of upper airway nitric oxide in nasal polyposis patients compared with those with allergic rhinitis, and with normal controls. 2. To assess the effect of polyp treatment on nasal NO levels.Methods NO levels (parts per billion) were measured in nasal and pulmonary exhaled air using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the chemiluminescence principle. Eighty‐two patients were studied: 44 with rhinitis, but without polyps, and 38 with nasal polyps. NO levels were compared with those of 20 normal controls. In 23 further polyp patients, levels were measured pre‐ and post‐treatment and the changes were compared with alterations in polyp size, as assessed by rigid nasendoscopy.Results Nasal NO levels were significantly lower (Kruskal–Wallis, P = 0.000, χ2 = 27.5, d.f. = 3) in patients with polyps than those found in uncomplicated allergic rhinitis. NO levels were correlated directly with extent of polyposis as graded by the Lund‐McKay index. Successful treatment, with reduction in polyp volume, was associated with a rise in NO levels (P = 0.042).Conclusion NO levels are low in nasal polyposis, despite high levels of iNOS, possibly related to blockage of the ostiomeatal complex and failure of NO generated constitutively in the sinuses to reach the nasal airway. A rise in the NO levels is seen with successful polyp treatment, and is proportional to the reduction in endoscopically assessed polyp size, suggesting that with both medical and surgical therapy, the ostiomeatal complex obstruction is decreasing. We propose the following scenario. Nasal NO levels are the result of two processes: inducible NO production by inflamed nasal mucosa plus constitutive sinus mucosal production, detectable in normals. In uncomplicated allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO levels fall because sinus NO makes the major contribution.
The descriptive epidemiology of house dust mite‐specific and total immunoglobin E in England using a nationally representative sample
Authors: Court C. S. , Cook D. G. , Strachan D. P. 
Published: March 2003

SummaryBackground Previous studies have shown that IgE levels vary according to factors such as age, gender and smoking but most studies have been small and none have been based on a nationally representative sample.Objectives To investigate the influence of epidemiological factors on serum total IgE and house dust mite‐specific IgE levels.Methods An interviewer‐led questionnaire was carried out and blood samples taken from 24 952 people aged 11 and over as part of the 1995 and 1996 Health Surveys for England. Serum total IgE and house dust mite‐specific IgE were measured.Results Both total and house dust mite‐specific IgE were more frequently raised in men and in younger age groups. After adjusting for age and sex, raised total IgE was more common in current smokers and non‐white ethnic groups and was not related to social class. The higher levels in non‐white ethnic groups was not explained by smoking, urban living or being born outside the UK. Whilst total IgE levels declined in older age groups in non‐smokers, among smokers they increased across successive age groups from 50 years onwards. In contrast, following adjustment for age and sex, raised house dust mite IgE was more common in non‐manual workers and in some non‐white ethnic groups but was not related to smoking.Conclusions This large nationwide study provides further confirmation of differing epidemiological patterns for total serum IgE and allergen‐specific sensitization. Indicative ranges for ‘usual’ values for a wide range of ages among men and women in England are given.
Relationship between sensitization to citrus red mite (Panonychus citri) and the prevalence of atopic diseases in adolescents living near citrus orchards
Authors: Kim S. ‐H. , Kim Y. ‐K. , Lee M. ‐H. , Hong S. ‐C. , Bae J. ‐M. , Min K. ‐U. , Kim Y. ‐Y. , Cho S. ‐H. 
Published: March 2003

SummaryBackgroundRecent investigations have demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in citrus fruit farmers with asthma and rhinitis and a common sensitizing allergen in children living near citrus orchards.ObjectiveTo evaluate the sensitization rate to CRM and the association between sensitization to CRM and atopic diseases, such as athma, allergic rhinitis and atopic dermatitis, in adolescents living in rural areas with citrus orchards.MethodsA total of 2005 adolescents (aged from 16 to 18 years) living in rural areas with citrus orchards were enrolled. Subjects were evaluated by a questionnaire and a skin prick test with 11 common aeroallergens including CRM.ResultsThe prevalences of current wheeze, rhinoconjuntivitis, and eczema on the questionnaire were 13.0%, 13.6%, and 8.8%, respectively. On skin prick tests, the most common sensitizing allergen was CRM [20.6%], followed byDermatophagoides pteronyssinus(18.5%),D. farinae(14.6%) and cockroach (9.8%). The prevalence of current eczema was significantly associated with the sensitization to CRM (OR = 1.9, 95% CI 1.3–2.9), although the prevalence of current wheeze and rhinoconjunctivitis was not associated with it. Among adolescents living near citrus orchards, however, the prevalences of current wheeze and rhinoconjuncitivitis were significantly higher in those with sensitization to only CRM than in those without sensitization to any allergens (20.3% vs. 14.1% and 20.3% vs. 15.0%,P < 0.05, respectively).ConclusionCRM is the most common sensitizing allergen in adolescents living in rural areas with citrus orchards, and sensitization to CRM was significantly associated with the prevalence of atopic dermatitis.
Comparison between the native glycosylated and the recombinant Cup a1 allergen: role of carbohydrates in the histamine release from basophils
Authors: Iacovacci P. , Afferni C. , Butteroni C. , Pironi L. , Puggioni E. M. R. , Orlandi A. , Barletta B. , Tinghino R. , Ariano R. , Panzani R. C. , Di Felice G. , Pini C. 
Published: March 2003

SummaryBackground Cypress pollinosis is an important cause of respiratory allergies. Recently, the Cupressus arizonica major allergen, Cup a1, has been cloned and expressed. The native counterpart of this allergen has been purified and characterized by our group. It has been suggested that sugar moieties play a role in the in vitro IgE binding on Cupressus arizonica pollen extract.Objective To characterize the immunoreactivity of the recombinant major allergen in comparison with its native counterpart. To evaluate the role of carbohydrate moieties in the IgE‐mediated in vitro histamine release from basophils by using the native glycosylated Cup a1 as compared with the recombinant one.Methods Recombinant Cup a1 was expressed in E. coli. IgE reactivity of Cupressaceae‐allergic patients on the native as well as the recombinant molecule was investigated by immunoblotting, ELISA experiments and histamine release test from passively sensitized basophils.Results Fourteen out of 17 Cup a1‐positive sera had IgE antibodies reactive with the native molecule only and lost their reactivity after periodate deglycosylation of the allergen. Moreover, only native molecule was capable of inducing histamine release by this group of sera. Both the recombinant and the native molecules were recognized by three out of the 17 sera and were equally capable of triggering degranulation.Conclusion A large number of sera reactive with the major allergen recognize carbohydrate epitopes only. IgE from these sera are able to induce histamine release from basophils and they might play a functional role in the clinical symptoms of allergy.
Age‐related T cell responses to allergens in childhood
Authors: Smart J. M. , Suphioglu C. , Kemp A. S. 
Published: March 2003

SummaryBackground T cell priming, as determined by allergen‐induced proliferative responses, is believed to occur principally in early childhood in both atopic and non‐atopic infants under the influence of multiple factors including environmental allergen exposure. It is considered that T cell priming with expansion of Th2 cells is a crucial factor in the development of atopic disease.Objective To examine T cell priming to commonly encountered allergens in childhood in relation to age.Methods In a cross‐sectional study T cell proliferation in relation to age was examined for three common allergens, ovalbumin (OVA), house dust mite (HDM) and rye grass pollen (RYE), in atopic and non‐atopic children. The effect of age on Th1 (IFN‐γ) and Th2 (IL‐5 and IL‐13) cytokine production in response to these allergens was investigated to examine the possibility of immune deviation with time.Results A significant increase in T cell proliferation with age was observed with RYE among atopic children only. However, the same was not observed with the two other allergens studied (i.e. OVA and HDM). In addition, RYE‐induced (but not HDM or OVA) cytokine production showed an increased Th2 deviation with age as reflected in the increasing IL‐5/IFN‐γ and IL‐13/IFN‐γ ratios only among the atopic subjects with rye grass pollen sensitivity.Conclusion These findings suggest that grass pollen sensitivity in childhood is accompanied by a progressive accumulation of allergen‐primed T cells and progressive deviation of the allergen‐induced cytokine response towards a Th2 response in atopic subjects throughout childhood.
Absence of immunoglobulin E synthesis and airway eosinophilia by vaccination with plasmid DNA encoding ProDer p 1
Authors: Jacquet A. , Magi M. , Haumont M. , Jurado M. , Garcia L. , Bollen A. 
Published: March 2003

SummaryBackground Various studies have shown that immunization with naked DNA encoding allergens induces T helper 1(Th1)‐biased non‐allergic responses.Objective To evaluate the polarization of the immune responses induced by vaccinations with plasmid DNA encoding the major mite allergen precursor ProDer p 1.Methods A DNA vaccine was constructed on the basis of a synthetic cDNA encoding ProDer p 1 with optimized codon usage. The immunogenicity of ProDer p 1 DNA in CBA/J mice was compared with that of purified natural Der p 1 or recombinant ProDer p 1 adjuvanted with alum. Vaccinated mice were subsequently exposed to aerosolized house dust mite extracts to provoke airway inflammation. The presence of inflammatory cells was examined in bronchoalveolar lavage (BAL) fluids and allergen‐specific T cell reactivity was measured.Results Naive mice immunized with ProDer p 1 DNA developed Th1 immune responses characterized by high titres of specific IgG2a antibodies, low titres of specific IgG1 and, remarkably, the absence of anti‐ProDer p 1 IgE. No specific responses were observed in animals vaccinated with the blank DNA vector. By contrast, natural Der p 1 or recombinant ProDer p 1 adsorbed to alum induced pronounced Th2 allergic responses with strong specific IgG1 and IgE titres. Spleen cells from DNA ProDer p 1‐vaccinated mice secreted high levels of IFN‐γ and low production of IL‐5. Conversely, both adjuvanted allergens stimulated typical Th2‐type cytokine profile characterized by high and low levels of IL‐5 and IFN‐γ, respectively. Whereas BAL eosinophilia was clearly observed in Der p 1‐immunized animals, ProDer p 1 DNA as well as ProDer p 1 vaccinations prevented airway eosinophil infiltrations.Conclusions These results suggest that vaccination with DNA encoding ProDer p 1 effectively fails to induce the allergen‐induced IgE synthesis and airway cell infiltration. Plasmid DNA encoding ProDer p 1 may provide a novel approach for the treatment of house dust mite allergy.