bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine expression during allergen‐induced late nasal responses: IL‐4 and IL‐5 mRNA is expressed early (at 6 h) predominantly by eosinophils
Authors: Nouri‐Aria K. T. , O'brien F. , Noble W. , Jabcobson M. R. , Rajakulasingam K. , Durham S. R. 
Published: March 2003

The production of TH2‐type cytokines [interleukin‐4 (IL‐4) and IL‐5] and tissue eosinophilia are characteristic features of allergic diseases. It was previously reported that at 24 h after allergen provocation, CD3+ T‐lymphocytes were the principal cell source of IL‐4 and IL‐5 mRNA transcripts in both atopic asthma and rhinitis.To investigate whether IL‐4 and IL‐5 mRNA are expressed earlier during late nasal responses and if so, which cell(s) are responsible.Nasal biopsies were obtained at 6 h after nasal allergen challenge and following a control challenge with the allergen diluent. Sections were immunostained for T‐lymphocytes (CD3+, CD4+) and eosinophils (EG2+). In situ hybridization was used to detect the number of cells expressing messenger RNA (mRNA) for IL‐4 and IL‐5.In patients with allergic rhinitis, eosinophils (EG2+ cells P = 0.006) but not T‐ cells (CD3+ cells) increased in the nasal mucosa at 6 h after allergen challenge. The number of cells expressing IL‐4 mRNA (P = 0.01) and IL‐5 mRNA (P = 0.05) also increased at 6 h. Co‐localization studies showed that 76% of IL‐4 mRNA+ cells and 77% of IL‐5 mRNA+ cells were eosinophils, whereas at this time point, T‐cells and mast cells accounted for ≤5% of mRNA expression; the identity of the remaining 20% of IL‐4 and IL‐5 mRNA+ cells was not determined. By use of immunohistology, cytokine protein expression at 6 h was confirmed for IL‐4 but not for IL‐5. No increases in T‐cells, eosinophils or cytokine expression were detected in non‐atopic subjects.Eosinophils represent an early source of IL‐4 which may contribute to TH2‐type responses during late nasal responses and ongoing allergic rhinitis.
Identification of vacuolar serine proteinase as a major allergen of Aspergillus fumigatus by immunoblotting and N‐terminal amino acid sequence analysis
Authors: Shen H.‐D. , Lin W.‐L. , Tam M. F. , Chou H. , Wang C.‐W. , Tsai J.‐J. , Wang S.‐R. , Han S.‐H. 
Published: March 2003

Aspergillus species are common airborne fungi that have been identified as causative agents of extrinsic bronchial asthma. More than 10 allergens from A. fumigatus have been recently characterized by cDNA cloning.The objective of this study is to identify A. fumigatus allergens through immunoblot analysis using sera from asthmatic patients.IgE‐binding components of A. fumigatus and IgE cross‐reactivity among allergens of different prevalent airborne fungal species were analysed by immunoblot and immunoblot inhibition, respectively, using sera from asthmatic patients. The N‐terminal amino acid sequences of major allergens identified were determined by Edman degradation.Among two batches (70 and 41 sera) of asthmatic sera tested, 19 (27%) and 14 (34%), respectively, have IgE immunoblot reactivity towards components of A. fumigatus. A 34‐kDa protein that reacts with IgE antibodies in 15 (79%) and 11 (79%) of the 19 and 14 positive samples, respectively, may be considered a major allergen of A. fumigatus. The N‐terminal amino acid sequences of the 34 kDa major allergen and the 30.5 and 30 kDa IgE‐binding components of A. fumigatus showed sequence identity to that of the vacuolar serine proteinase from A. fumigatus. The results from immunoblot inhibition show IgE cross‐reactivity among major allergens of A. fumigatus, P. notatum and P. oxalicum.Results obtained suggest that the 34 kDa major allergen of A. fumigatus may be a vacuolar serine proteinase. There is IgE cross‐reactivity among serine proteinase allergens of A. fumigatus, P. notatum and P. oxalicum.
Asthma, smoking and chronic cough in rural and urban adult communities in The Gambia
Authors: Walraven G. E. L. , Nyan O. A. , Van Der Sande M. A. B. , Banya W. A. S. , Ceesay S. M. , Milligan P. J. M. , McAdam K. P. W. J. 
Published: March 2003

Background Asthma is reported to be rare in traditional rural communities, but is thought to be increasing as lifestyles become more urbanized or ‘western’.Objectives A community‐based survey of non‐communicable diseases was conducted from October 1996 to June 1997, and included comparison of the prevalence of asthma, smoking and chronic cough in rural and urban Gambia.Methods A cluster sample survey was conducted in a random sample of rural and urban adults (≥ 15 years of age). Subjects were asked about respiratory symptoms using a locally adapted version based on the IULTD questionnaire. Spirometry (basal, methacholine provocation and reversibility with a bronchodilator) and skin prick tests were performed on a randomly selected subsample of all subjects and those who, when interviewed, said they wheezed or had been diagnosed as asthmatic by a doctor.Results Out of 2166 participants in the urban population, 4.1% reported having had wheezing or whistling in the chest in the previous 12 months, 3.6% reported doctor‐diagnosed asthma, and 0.6% chronic cough. In the rural population with 3223 participants these figures were 3.3%, 0.7% and 1.2%, respectively. Wheeze was more common in women, cough for 3 months of the year was more common in the age‐groups 45+. Those who reported that they currently smoked accounted for 34% in urban and 42% in rural men. Figures were much lower for women (1.5% and 6.0%). Seven out of 574 randomly selected subjects (1.4%) exhibited bronchial hyper‐responsiveness to methacholine challenge. Four of 133 (3.0%) people with self‐reported wheeze and 3/69 (4.3%) participants with doctor‐diagnosed asthma reacted positively on bronchial provocation with methacholine. There was a remarkably high prevalence of positive skin prick tests to aeroallergens: 38% in participants with a history of wheeze and 27% in those without.Conclusion The prevalence of wheeze (particularly in association with bronchial hyper‐responsiveness) was low in both rural and urban Gambia. This is in contrast to the relatively high prevalence of positive skin prick tests to aeroallergens (in both wheezers and non‐wheezers), questioning the mechanisms of interaction between allergy and asthma and the presence of protective factors against asthma in this West African population. The high smoking rates justify international concern about tobacco marketing in developing societies.
Age, sex, geographical and socio‐economic variations in admissions for anaphylaxis: analysis of four years of English hospital data.
Authors: Sheikh A. , Alves B. 
Published: March 2003

Background Although the most severe of the allergic disorders, the epidemiology of anaphylaxis remains poorly described. Hospital admissions for anaphylaxis in England more than doubled during the 1990s.Objective To provide baseline data for assessing future trends, and to assess whether there is sufficient regional variation in incidence to allow efficient testing of aetiological hypotheses, we sought to identify any age, sex, geographical and socio‐economic variations in hospital inpatient admissions for anaphylaxis.Methods We studied all emergency admissions for anaphylaxis to English NHS hospitals between 1991 and 1995. Poisson regression modelling was used to calculate rates of anaphylaxis admission per 100 000 emergency admissions by age, sex, deprivation and by residence in urban/rural, North/South and East/West England.Results Of the 13.5 million emergency inpatient admissions, 2323 patients had a primary diagnosis of anaphylaxis. Poisson regression analyses showed significant age, gender, geographical and socio‐economic variations in emergency admissions for anaphylaxis: adjusted Female rate ratio 1.19 (95% CI 1.09–1.29), South rate ratio 1.35 (95% CI 1.25–1.47), Rural rate ratio 1.35 (95% CI 1.17, 1.59), and Non‐deprived rate ratio 1.32 (95% CI 1.19, 1.46).Conclusion This study identifies striking national age, sex, geographical and socio‐economic variations in the incidence of inpatient admissions for anaphylaxis in England, affording important opportunities to generate and test aetiological hypotheses. Risk of anaphylaxis admission is considerably increased in females of child‐bearing age and those residing in southern, rural, and affluent areas are independent risk factors for anaphylaxis admission.
Characterization of ‘adult‐type’ mast cells derived from human bone marrow CD34+ cells cultured in the presence of stem cell factor and interleukin‐6. Interleukin‐4 is not required for constitutive expression of CD54, FcεRIα and chymase, and CD13 expression is reduced during differentiation
Authors: Shimizu Y. , Sakai K. , Miura T. , Narita T. , Tsukagoshi H. , Satoh Y. , Ishikawa S. , Morishita Y. , Takai S. , Miyazaki M. , Mori M. , Saito H. , Xia H. , Schwartz L. B. 
Published: March 2003

SummaryBackground In vitro‐derived human mast cells exhibit different properties, depending in part on the source of progenitor cells. Most investigations have used fetal liver, cord blood or peripheral blood. Few have used adult bone marrow.Objective Human mast cells derived in vitro from the CD34+ progenitors in bone marrow and cord blood that had been cultured with recombinant human stem cell factor (rhSCF) and recombinant human interleukin‐6 (rhIL‐6) were compared.Methods and results After 12 weeks of culture, nearly all of the cells were mast cells, and nearly all of these had cytoplasmic granules containing both tryptase and chymase (MCTC type), stained metachromatically with acidic toluidine blue, and expressed CD117 on the cell surface. Both tryptase protein and mRNA were detected by two weeks of culture. Chymase mRNA and protein were detected at 4 weeks but not at 2 weeks of culture. By 12 weeks, chymase content per cell, measured by ELISA, was significantly higher (P < 0.05) in human bone marrow‐derived mast cells (HBMMC) (5.6 ± 0.9 pg) than in cord blood‐derived mast cells (CBMC) (2.4 ± 0.9 pg), whereas histamine and tryptase levels were not significantly different. Of the cluster designations tested, CD29, CD49d, CD51 and CD61 were strongly expressed on HBMMC. CD54 and FcεRIα also were expressed constitutively. Approximately half of CD34‐sorted cells at day 0 were CD13+ and this diminished as mast cell maturation occurred. Electron microscopy revealed that 12‐week‐old HBMMC had many secretory granules that contained spherical electron dense cores surrounded by electron lucent space, consistent with previous reports of immature MCTC cells developing in vivo.Conclusions CD34+ progenitors of human bone marrow are a rich source of mast cell progenitors capable of expressing granule and surface markers of mature mast cells in the presence of rhSCF and rhIL‐6.
Liposome‐entrapped D. pteronyssinus vaccination in mild asthma patients: effect of 1‐year double‐blind, placebo‐controlled trial on inflammation, bronchial hyper‐responsiveness and immediate and late bronchial responses to the allergen
Authors: Alvarez M. J. , Echechipía S. , García B. , Tabar A. I. , Martín S. , Rico P. , Olaguibel J. M. 
Published: March 2003

SummaryBackground Allergen vaccination is effective in mite‐allergic asthma. Liposomes are immunological adjuvants that can act as allergen carriers.Objective To evaluate the immunological and functional effects of a liposome‐entrapped D. pteronyssinus vaccine on mite monosensitive, mild asthma patients.Methods A double‐blind, placebo‐controlled trial was conducted on 26 asthma patients who randomly received vaccination or placebo for 1 year. The levels of exposure to Der p 1 allergen were constant during the study. Allergen bronchial challenge was made at the beginning (T0) and after 1 year of treatment (T12). The day before and 24 h after the allergen provocation, patients were challenged with methacholine (Mth) (until FEV1 fell by 40%) and blood and sputum samples were obtained. Dose–response curves to Mth were evaluated in terms of Mth‐PD20 (dose of Mth that induced 20% drop in FEV1), slope (Mth‐DRS) and level of plateau. Blood and sputum eosinophils and serum levels of eosinophil cationic protein (ECP) and intercellular adhesion molecule‐1 (ICAM‐1) were measured.Results Groups were comparable at the start of the trial. At T12, previous to the allergen challenge, the active group showed higher values of both FEV1 and Mth‐PD20 and lower values of Mth‐DRS. The number of patients presenting a level of plateau increased in the active group (from two to four) and decreased in the placebo group (from two to one). At T12, before the allergen challenge, serum ECP levels increased in the placebo group and blood eosinophils showed a trend towards lower numbers in the active one. The immediate response and the changes in Mth‐DRS values, sputum eosinophils and serum ECP levels following the allergen challenge were attenuated in the active group.Conclusion Liposome‐entrapped D. Pteronyssinus vaccination: (i)  protects mild asthma patients from the worsening of asthma due to sustained mite exposure; and (ii) reduces the functional and inflammatory changes induced by allergen bronchial provocation.
Blood basophil numbers in chronic ordinary urticaria and healthy controls: diurnal variation, influence of loratadine and prednisolone and relationship to disease activity
Authors: Grattan C. E. H. , Dawn G. , Gibbs S. , Francis D. M. 
Published: March 2003

SummaryBackground The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis.Methods Manual basophil counts using a toluidine blue stain and automated 5‐part differentials (Coulter® Gen. S™) were performed at 4‐hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7.Results There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/µL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9 (1.9), P < 0.001). Loratadine did not influence them. UAS fell on treatment (3.3 (0.4) baseline, 1.4 (0.5) on loratadine and 0.5 (0.2) on prednisolone with loratadine, P < 0.001). There was a negative linear correlation between basophil numbers and UAS in untreated chronic urticaria patients (P = 0.001, Spearman rank correlation). Manual and automated basophil counts showed poor agreement. Lymphocyte numbers were lower in chronic urticaria than healthy controls. Neutrophils increased whereas lymphocytes and eosinophils decreased in all subjects on prednisolone. They were unaffected by loratadine.Conclusion The results are consistent with the hypothesis that circulating basophils may be recruited from blood into urticarial weals during disease activity. Automated counts are not suitable for assessing basophil numbers in chronic urticaria. The relevance of reduced lymphocyte numbers in chronic urticaria needs to be explored.
The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children
Authors: Van Amsterdam J. G. C. , Janssen N. A. H. , De Meer G. , Fischer P. H. , Nierkens S. , Van Loveren H. , Opperhuizen A. , Steerenberg P. A. , Brunekreef B. 
Published: March 2003

SummaryBackground Exhaled nitric oxide (NO) has been proposed as novel a non‐invasive marker of airway inflammation.Objective The level of exhaled NO was determined in a random sample of school children (7–12 years old) with the aim of investigating the relationship between exhaled NO and sensitization to common allergens.Results In the 450 children tested by skin prick tests (SPT), the prevalence of sensitization was 29.5% (overall), 21.9% (sensitization to indoor allergens), and 15.0% (sensitization to outdoor allergens). Regression analysis showed that levels of exhaled nitric oxide were closely associated with various measures of sensitization to aeroallergens. Sensitization to indoor allergens was associated with higher levels of exhaled NO (eNO) than sensitization to outdoor allergens when assessed by IgE but not when assessed by SPT. Children with reported wheeze in the past 12 months had much stronger associations between sensitization and eNO than children without wheeze.Conclusion We conclude that allergic sensitization is strongly associated with increased levels of exhaled NO, especially in children with wheeze.
Fetal exposure to intact immunoglobulin E occurs via the gastrointestinal tract
Authors: Thornton C. A. , Holloway J. A. , Popplewell E. J. , Shute J. K. , Boughton J. , Warner J. O. 
Published: March 2003

SummaryBackground Consideration of the evolutionary significance of IgE might provide insight into the immunological interactions occurring in utero and during early post‐natal life that regulate later atopic disease.Objective We postulated that the fetal gut is exposed to intact amniotic fluid IgE that might interact with local IgE receptors.Methods IgE levels in matched maternal blood and amniotic fluid (n = 47) or breast milk (n = 15) collected from pregnant women in the UK (Southampton) and Brazil (Sao Paulo) were studied. Expression of IgE receptors, FcɛRI and FcɛRII (CD23), in fetal gastrointestinal tract (n = 19) and skin (n = 11) was examined immunohistochemically.Results Human amniotic fluid at 16–18 weeks' gestation contained intact IgE at levels that increased as maternal circulating levels increased (Spearman's ρ = 0.897; P < 0.001). Circulating IgE levels from women in Sao Paulo, Brazil, associated positively not only with term (> 37 weeks' gestation) amniotic fluid (ρ = 0.993; P < 0.001) but also breast milk IgE levels (ρ = 0.785; P = 0.001). Maternal levels of IgE did not change significantly over pregnancy and fetal circulating levels of IgE were very low (< 0.6 IU/mL). Low‐affinity IgE receptors (CD23) were expressed in lymphoid follicles of the fetal gut from 16 weeks of gestation (6/8), but not from 11 to 16 weeks (0/11) or in the skin.Conclusion Amniotic fluid contains intact IgE that might bind to CD23+ cells within the lymphoid follicles of the fetal gastrointestinal tract. The evolutionary significance of these interactions might be to prepare the immune system for helminthic parasite exposure at birth via IgE‐mediated antigen focusing, or ‘education’ of the developing immune system about the prevailing extrauterine environment. However, at present in societies where helminthosis is not a significant health issue, this pathway may still be operational and associated with the development of atopic disease.
Rifampicin-induced lupus erythematosus
Authors: Patel G. K. , Anstey A. V. 
Published: March 2003

Abstract
Rifampicin has been prescribed throughout the world for over 20 years, yet only four cases of rifampicin-induced lupus erythematosus (LE) have been reported. Rifampicin-induced LE is associated with combination therapy with clarithromycin or ciprofloxacin. These drugs are all metabolized through the cytochrome P450 liver enzyme system and combined usage may lead to higher rifampicin blood levels. Drug-induced LE differs from systemic LE; cutaneous manifestations, although uncommon, are an important clue to the diagnosis. We report a case of rifampicin-induced LE presenting with florid cutaneous features.
The surface epithelium of recurrent infected palatine tonsils is rich in γδ T cells
Authors: Olofsson K , Hellström S , Hammarström M L 
Published: March 2003

AbstractUsing a large panel of MoAbs in quantitative morphometric analysis of immunohistochemically stained tissue sections, we compared the frequency and distribution of immune cells in palatine tonsils from patients with recurrent tonsillitis (RT) and patients with idiopathic tonsillar hypertrophy (ITH). We found that differences between the two patient groups in leucocyte populations were limited to the surface epithelium, whereas the cellular composition of interfollicular and follicular areas was similar. Most intraepithelial lymphocytes were CD8+ T cells in both groups. However, the number of intraepithelial T cells was significantly higher in RT compared with ITH. This was due to a selective increase in the number of intraepithelial CD8+γδ T cells utilizing Vδ1 and Vγ9. In both patient groups the majority of the intraepithelial γδ T cells expressed Vδ1 and Vγ9. Subepithelially, γδ T cells utilizing Vγ9 dominated over cells utilizing Vγ8, while equal proportions expressed Vδ1 and Vδ2. These results suggest that cells utilizing the otherwise rare combination Vδ1/Vγ9 in their T cell receptors (TCR) may constitute a major γδ T cell population in palatine tonsils and are probably reactive to antigens specific to the tonsillar milieu. Furthermore, they indicate that preferentially this γδ T cell subpopulation is involved in immune reactions within the surface epithelium in RT. We speculate that γδ T cells are involved in clearing infectious bacteria at the tonsillar surface and in limiting inflammatory responses in the tonsils. Both local expansion and infiltration of blood cells probably contribute to the high numbers of γδ T cells in RT patients.
The role of IL-13 in IgE synthesis by allergic asthma patients
Authors: Van Der Pouw Kraan T C T M , Van Der Zee J S , Boeije L C M , De Groot E R , Stapel S O , Aarden L A 
Published: March 2003

AbstractIgE antibodies play a crucial role in allergic type I reactions. Only IL-4 and IL-13 are able to induce an immunoglobulin isotype switch to IgE in B cells. A major question is to what extent these cytokines contribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production of IgE is dependent on endogenously produced IL-4 and IL-13. In cultures of purified T and B cells from allergic asthma patients and non-atopic controls, T cells were polyclonally stimulated to obtain IL-4, IL-13 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When neutralizing IL-4 antibodies were included during culture, the production of IgE was dramatically inhibited in both patients and controls (production of IgE was reduced to 12%). However, neutralization of IL-13 led to a significantly stronger inhibition of IgE production in the patient group: production of IgE was reduced to 23 ± 3% versus 50 ± 10% in the control group. Corresponding with these results, we also observed a higher production of IL-13 by the patients, while the production of IL-4 was not significantly different. A more detailed analysis of the production of IL-13 revealed that patients' T cells were less sensitive to a negative signal controlling IL-13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma patients is more dependent on IL-13 than in non-atopics, due to enhanced IL-13 production and to enhanced IgE production in response to IL-13.