bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo‐controlled, crossover trial
Authors: Brown S. G. A. , Haas M. A. , Black J. A. , Parameswaran A. , Woods G. M. , Heddle R. J. 
Published: May 2004

SummaryBackground
In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful.Objective
We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy.Methods
During a double‐blind randomized placebo‐controlled crossover trial of Myrmecia pilosula ant VIT the following venom‐specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL‐4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry.Results
Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL‐4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom‐induced leucocyte IL‐4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected.Conclusion
The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre‐incubation with IL‐3. None of the tests evaluated appear to be reliable markers of successful VIT.
Syndecan‐4‐dependent migration of human eosinophils
Authors: Feistritzer C. , Kaneider N. C. , Sturn D. H. , Wiedermann C. J. 
Published: May 2004

SummaryBackground
Heparan sulphate proteoglycans (HSPGs) are important participants in cell surface signalling and critical in controlling cell behaviour. They modulate inflammatory cell maturation and activation, leucocyte rolling, adhesion to endothelium as well as extravasation and chemotaxis. Whether eosinophil's function is affected has not yet been reported.Objective
We investigated the effects of transgenic, recombinant anti‐thrombin III and Kybernin P®, an anti‐thrombin III concentrate, as HSPG ligands on spontaneous and chemokine‐triggered migration of normal eosinophils from human peripheral blood in modified Boyden chamber micropore filter assays.Methods
Eosinophils from human peripheral blood were purified using magnetic antibody cell sorting. The signalling mechanisms required for anti‐thrombin‐dependent migration were studied using signalling enzyme blockers. Expression of HSPG core protein mRNA was studied by PCR.Results
Pre‐treatment of eosinophils with anti‐thrombin III inhibited chemotaxis toward optimal concentrations of eotaxin or RANTES (regulated upon activation normal T cell expressed and activated). In the absence of the chemokines, direct exposure to gradients of anti‐thrombin III stimulated eosinophil migration. The effects of anti‐thrombin III were abolished by pre‐treating cells with heparinase‐1, chondroitinase, sodium chlorate and anti‐syndecan‐4 antibodies. Syndecan‐4 gene expression in eosinophils was confirmed in PCR. In the presence of pentasaccharide, anti‐thrombin III lost its effect on the cells. Functional responses were also abrogated by inhibition of protein kinase C, phosphatidylinositol 3‐kinase and phosphodiesterase.Conclusion
Data indicate that anti‐thrombin III affects eosinophil motility via the effects of its heparin‐binding site on cell surface syndecan‐4. Ligation of syndecan‐4 with anti‐thrombin III induces eosinophil migration and deactivates motility toward chemokines. These observations suggest that syndecan‐4‐dependent signalling may control eosinophil locomotion.
Effect of Mycobacterium tuberculosis chaperonins on bronchial eosinophilia and hyper‐responsiveness in a murine model of allergic inflammation
Authors: Riffo‐Vasquez Y. , Spina D. , Page C. , Tormay P. , Singh M. , Henderson B. , Coates A. 
Published: May 2004

SummaryBackground
Epidemiological evidence suggests that infection with Mycobacterium tuberculosis protects children against asthma. Several laboratories have shown that, in mouse models of allergic inflammation, administration of the whole live tuberculosis vaccine, Mycobacterium bovis bacillus Calmette–Guerin (BCG), prevents ovalbumin (OVA)‐induced pulmonary eosinophilia.Objective
The aim of this study was to characterize specific M. tuberculosis molecules that are known to modulate immune responses to see if they affected pulmonary eosinophilia and bronchial hyper‐responsiveness.Methods
C57Bl/6 mice were sensitized to OVA on days 0 and 7 and subsequently challenged with OVA on day 14 over a 3‐day period. Pulmonary eosinophilia and bronchial hyper‐responsiveness were measured 24 h following the last antigen challenge. In some groups, mice were pre‐treated with M. tuberculosis or M. tuberculosis chaperonins (Cpns)60.1, 60.2 and 10, and the effect of this treatment on the allergic inflammatory response to aerosolized OVA was established.Results
We show that M. tuberculosis Cpns inhibit allergen‐induced pulmonary eosinophilia in the mouse. Of the three Cpns produced by M. tuberculosis, Cpn60.1, Cpn10 and Cpn60.2, the first two are effective in preventing eosinophilia when administered by the intra‐tracheal route. Furthermore, the increase in airways sensitivity to inhaled methacholine following OVA challenge of immunized mice was suppressed following treatment with Cpn60.1. The allergic inflammatory response was also characterized by an increase in Th2 cytokines IL‐4 and IL‐5 in bronchoalveolar lavage fluid, which was also suppressed following treatment with Cpn60.1.Conclusion
These data show that bacterial Cpns can suppress eosinophil recruitment and bronchial hyper‐responsiveness in a murine model of allergic inflammation.
Human leucocyte antigen polymorphisms in nut‐allergic patients in South Wales
Authors: Hand S. , Darke C. , Thompson J. , Stingl C. , Rolf S. , Jones K. P. , Davies B. H. 
Published: May 2004

SummaryBackground
Peanuts and tree nuts are among the most common foods provoking severe allergic reactions including fatal anaphylaxis. However, little is known of the underlying genetic and immunological mechanisms involved.Objective
Based on findings in other allergic diseases, we have investigated whether specific human leucocyte antigens (HLA) are associated with nut allergy.Method
Eighty‐four patients presenting at the allergy clinic with symptoms of nut allergy were typed for the HLA Class I (HLA‐A and B) and Class II (HLA‐DRB1 and DQB1) loci by PCR using sequence‐specific primers. Carriage frequencies were compared with 82 atopic non‐nut‐allergic subjects and 1798 random blood donors.Results
The frequency of HLA‐B*07 (28.57%) and DRB1*11 (15.48%) was increased in the nut‐allergic patients compared to the atopic controls (12.20% and 3.66%, respectively) but not when compared to the blood donors (28.86% and 10.12%). DRB1*13 and DQB1*06 were both increased in frequency in the nut allergy patients over both the atopic and blood donor controls. However, none of these increased frequencies were significant when corrected for the number of comparisons undertaken.Conclusion
At HLA ‘2‐digit resolution’ and with undifferentiated patients with nut allergy, there are no major disturbances in the frequency of HLA‐A, B, DRB1 or DQB1 types. However, the difference in frequency of HLA‐DRB1*11 between the nut allergy patients and the atopic controls merits further investigation as this may represent an important phenotypic relationship.
Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma
Authors: Jongepier H. , Boezen H. M. , Dijkstra A. , Howard T. D. , Vonk J. M. , Koppelman G. H. , Zheng S. L. , Meyers D. A. , Bleecker E. R. , Postma D. S. 
Published: May 2004

SummaryBackground
Asthma is a genetically complex disease characterized by respiratory symptoms, intermittent airway obstruction and airway hyper‐responsiveness due to airway inflammation and remodelling. The ADAM33 gene is associated with asthma and airway hyper‐responsiveness and is postulated as a gene for airway remodelling.Objective
To investigate whether polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in patients with asthma.Methods
In a cohort of 200 asthma patients followed over 20 years, eight single nucleotide polymorphisms of the ADAM33 gene were analysed to estimate their effect on annual FEV1 decline.Results
The rare allele of the S_2 polymorphism was significantly associated with excess decline in FEV1 (P<0.05).Conclusion
These findings suggest that a variant in ADAM33 is not only important in the development of asthma but also in disease progression, possibly related to enhanced airway remodelling.
Efficacy of birch‐pollen immunotherapy on cross‐reactive food allergy confirmed by skin tests and double‐blind food challenges
Authors: Bolhaar S. T. H. P. , Tiemessen M. M. , Zuidmeer L. , Van Leeuwen A. , Hoffmann‐Sommergruber K. , Bruijnzeel‐Koomen C. A. F. M. , Taams L. S. , Knol E. F. , Van Hoffen E. , Van Ree R. , Knulst A. C. 
Published: May 2004

SummaryBackground
The effect of birch‐pollen immunotherapy (IT) on cross‐reactive food allergies is controversial.Objective
The aim of this study was to investigate the effect of birch‐pollen IT on apple allergy and to evaluate recombinant allergens and double‐blind placebo‐controlled food challenges (DBPCFCs) as monitoring tools.Methods
Twenty‐five adult birch‐pollen‐ and apple‐allergic patients were randomly divided into two groups, either receiving birch‐pollen IT or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple, natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT) were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1). Clinical outcome was evaluated by DBPCFC. CD4+CD25+ regulatory T cells (Tregs) were isolated from peripheral blood and tested in functional assays.Results
Birch‐pollen IT resulted in a significant decrease of SPT reactivity for rBet v 1 (30‐fold) and rMal d 1 (10‐fold) already after 3 months. IgG4 antibodies were potently induced against Bet v 1, displaying cross‐reactivity to Mal d 1. Visual analogue scale scores decreased >10‐fold in 9/13 patients of the IT group, with three patients converting to negative. In the control group, no decrease was observed. Birch‐pollen IT did not lead to detectable changes in the number or function of the CD4+CD25+ Tregs.Conclusions
This trial supports the claims that birch‐pollen IT also decreases allergy to foods containing Bet v 1‐homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful tools for monitoring the effect of birch‐pollen IT on linked food allergies.
Double‐stranded RNA activates RANTES gene transcription through co‐operation of nuclear factor‐κB and interferon regulatory factors in human airway epithelial cells
Authors: Ieki K. , Matsukura S. , Kokubu F. , Kimura T. , Kuga H. , Kawaguchi M. , Odaka M. , Suzuki S. , Watanabe S. , Takeuchi H. , Schleimer R. P. , Adachi M. 
Published: May 2004

SummaryBackground
Regulated on activation, normal T cells expressed and secreted (RANTES) is a member of the CC chemokine family and contributes to viral‐induced airway inflammation including exacerbations of asthma. Double‐stranded RNA (dsRNA) is known to be synthesized during replication of many viruses and a ligand of Toll‐like receptor 3. We hypothesized that dsRNA may mimic viral infection and induce RANTES expression in airway epithelial cells.Objective
We first confirmed that dsRNA up‐regulated RANTES mRNA and protein synthesis in the airway epithelial cells. We next focused our studies on the transcriptional regulation of RANTES.Methods
Airway epithelial cell line BEAS‐2B and normal human bronchial epithelial cells were used in vitro study. Levels of RANTES mRNA and protein expression were determined with RT‐PCR and ELISA. Mechanisms of transcriptional regulation were assessed by electrophoretic mobility shift assay and dual luciferase assay using RANTES promoter‐luciferase reporter plasmids.Results
Activation of nuclear factor‐κB (NF‐κB) was confirmed by nuclear protein binding to a DNA probe derived from the RANTES promoter. Activity of the RANTES promoter was increased by dsRNA. The stimulation with dsRNA was partially inhibited in plasmids mutated at either of the binding sites for NF‐κB or IFN regulatory factors (IRFs). When both sites were mutated, the activation was totally abrogated.Conclusion
These results imply that dsRNA activates NF‐κB and IRFs and these transcription factors activate transcription of the RANTES promoter and its protein expression in airway epithelial cells.
Prevalence and associated factors of atopic dermatitis symptoms in rural and urban Ethiopia
Authors: Yemaneberhan H. , Flohr C. , Lewis S. A. , Bekele Z. , Parry E. , Williams H. C. , Britton J. , Venn A. 
Published: May 2004

SummaryBackground
Allergic diseases, including atopic dermatitis (AD), are increasingly becoming a clinical problem in developing countries.Objective
We investigated the prevalence of AD symptoms and the effects of potential environmental aetiologies in rural and urban areas of Jimma in southwestern Ethiopia.Methods
Information on allergic disease symptoms and lifestyle factors was gathered in an interviewer‐led cross‐sectional questionnaire‐based population survey of 9844 urban and 3032 rural participants of all ages. A one‐in‐four subsample underwent skin prick testing for hypersensitivity to Dermatophagoides pteronyssinus, mixed threshings, and aspergillus.Results
Around 95% of those eligible took part in the survey. Lifetime cumulative prevalence of AD symptoms was generally low with an overall prevalence of 1.2%, but was higher in the urban (1.5%) than in the rural area (0.3%; odds ratio (OR)=4.45 [95% CI 2.34–8.47]). AD symptoms were strongly associated with wheeze (adjusted OR=22.03 [15.45–31.42]) and rhinitis symptoms (61.94 [42.66–89.95]). Of several environmental exposures assessed, residence in a house made of brick (rather than mud) walls with wooden (rather than clay) floor, exposure to cigarette smoke as a child, having lived outside of Jimma in the past, and being of the Tigrean ethnic group were associated with an increased risk of AD symptoms.Conclusion
Although the overall prevalence of AD symptoms was low in this Ethiopian population, a marked urban–rural gradient was evident. Lifestyle factors linked to urbanization were associated with an increased risk of AD symptoms.
Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis
Authors: Goetghebuer T. , Isles K. , Moore C. , Thomson A. , Kwiatkowski D. , Hull J. 
Published: May 2004

SummaryBackground
The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL‐8‐promoter region is associated with susceptibility to severe bronchiolitis.Objective
The purpose of this study was to assess the association between wheezing post‐bronchiolitis and the genetic variant of IL‐8 gene.Methods
We collected data from 134 children who had suffered from bronchiolitis, enrolled in our previous study. The occurrence of wheezing post‐bronchiolitis was recorded from a questionnaire sent by post. The association between the genotype and wheezing phenotype was assessed by family‐based and case–control approaches.Results
Family‐based association showed that the IL‐8 variant was transmitted significantly more often than expected in the children who wheezed after the episode of bronchiolitis (transmission=56%, P=0.02). This effect was not observed in the group of children who had bronchiolitis but did not go on to wheeze. Moreover, the variant was significantly more frequent in post‐bronchiolitis wheezers compared with the general population (odds ratio=1.6, 95% confidence interval 1.0–2.6).Conclusion
These preliminary results suggest that there is a genetic predisposition to wheeze following severe RSV bronchiolitis.
Increased macrophage‐derived chemokine in exhaled breath condensate and plasma from children with asthma
Authors: Leung T. F. , Wong G. W. K. , Ko F. W. S. , Lam C. W. K. , Fok T. F. 
Published: May 2004

SummaryBackground
Type 2 helper T lymphocyte‐specific chemokines including macrophage‐derived chemokine (MDC), thymus and activation‐regulated chemokine (TARC) and eotaxin are important mediators for allergic airway inflammation.Objective
We investigated whether these chemokines can be detected in exhaled breath condensate (EBC) and their relation to childhood asthma.Methods
Asthmatics recruited from paediatric clinics of a university teaching hospital were classified into intermittent asthma (IA) and persistent asthma (PA) according to Global Initiative for Asthma guidelines. EBC was collected by a disposable collection kit, whereas fractional exhaled nitric oxide (FENO) was measured by a chemiluminescence analyser. Concentrations of MDC, TARC and eotaxin in both EBC and plasma were measured using sandwich enzyme immunoassay. The intra‐subject reproducibility of exhaled chemokine measurements was determined by co‐efficients of variation (CV).Results
Forty‐eight patients with PA, 36 children with IA and 18 controls were recruited. MDC and eotaxin were present in EBC from nearly all subjects, whereas TARC could be measured in EBC from 33 (32%) subjects only. The median MDC concentration in EBC was higher in PA (117 pg/mL) as compared with IA (106 pg/mL) and controls (105 pg/mL; P=0.003 for both). The median plasma MDC concentration in PA (648 pg/mL) was also higher than that in IA (520 pg/mL; P=0.002) and controls (490 pg/mL; P=0.008). The median plasma TARC concentration was also increased in PA as compared with IA (72 pg/mL vs. 35 pg/mL; P=0.004). MDC concentrations in EBC were lower in patients with PA who received high‐dose inhaled corticosteroid (P=0.005). FENO was significantly higher in asthmatics than controls (P<0.0001), but it was not associated with chemokines in EBC or plasma. The mean (range) CV for measuring MDC, TARC and eotaxin in EBC (n=6) were 5.5 (2.0−7.2%), 8.8 (3.6−14.4%) and 5.2 (2.8−7.9%), respectively.Conclusions
Our results suggest that MDC in EBC and MDC and TARC in plasma are increased in children with PA as compared with IA or control. MDC concentrations in EBC are suppressed in patients on high‐dose inhaled corticosteroid treatment.
Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen‐season model of allergic rhinitis
Authors: Ahlström‐Emanuelsson C. , Andersson M. , Persson C. , Schrewelius C. , Greiff L. 
Published: May 2004

SummaryBackground
Rofleponide palmitate is an esterified glucocorticosteroid pro‐drug with a promising pre‐clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro‐drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide.Objective
To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen‐season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide).Methods
During the pollen‐free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 μg and an aqueous solution of budesonide 128 μg once daily for 10 days in a double‐blind, placebo‐controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen‐challenge series, when symptoms were established and when the treatment had lasted for 8–10 days, were used in the analysis.Results
Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01–0.001). There was no overall difference in efficacy between rofleponide palmitate 400 μg and budesonide 128 μg.Conclusions
Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 μg of rofleponide palmitate is similar to that of 128 μg of budesonide in the pollen‐season model used in this study.
A novel regulatory pathway of sulfate uptake in Arabidopsis roots: implication of CRE1/WOL/AHK4‐mediated cytokinin‐dependent regulation
Authors: Maruyama‐Nakashita Akiko , Nakamura Yumiko , Yamaya Tomoyuki , Takahashi Hideki 
Published: May 2004

SummaryCytokinin is an adenine derivative plant hormone that generally regulates plant cell division and differentiation in conjunction with auxin. We report that a major cue for the negative regulation of sulfur acquisition is executed by cytokinin response 1 (CRE1)/wooden leg (WOL)/Arabidopsis histidine kinase 4 (AHK4) cytokinin receptor in Arabidopsis root. We constructed a green fluorescent protein (GFP) reporter system that generally displays the expression of the high‐affinity sulfate transporter SULTR1;2 in Arabidopsis roots. GFP under the control of SULTR1;2 promoter showed typical sulfur responses that correlate with the changes in SULTR1;2 mRNA levels; accumulation of GFP was induced by sulfur limitation (−S), but was repressed in the presence of reduced sulfur compounds. Among the plant hormones tested, cytokinin significantly downregulated the expression of SULTR1;2. SULTR1;1 conducting sulfate uptake in sultr1;2 mutant was similarly downregulated by cytokinin. Downregulation of SULTR1;1 and SULTR1;2 by cytokinin correlated with the decrease in sulfate uptake activities in roots. The effect of cytokinin on sulfate uptake was moderated in the cre1‐1 mutant, providing genetic evidence for involvement of CRE1/WOL/AHK4 in the negative regulation of high‐affinity sulfate transporters. These data demonstrated the physiological importance of the cytokinin‐dependent regulatory pathway in acquisition of sulfate in roots. Our results suggested that two different modes of regulation, represented as the −S induction and the cytokinin‐dependent repression of sulfate transporters, independently control the uptake of sulfate in Arabidopsis roots.
The Fine Structure of the Harderian Gland in the Ostrich (Struthio camelus)
Authors: Altunay H. , Kozlu T. 
Published: May 2004

SummaryThe Harderian gland of the ostrich (Struthio camelus) is a tubuloalveolar gland containing holocrine secreting epithelial cells. The gland epithelium is composed of two different cell types, which can be classified as type I and type II. These cells contain dense secretory vesicles in their cytoplasm and they are connected laterally with desmosomes. At the basal site of these cells, myoepithelial cells are present. Plasma cells are observed in the subepithelial region of the gland. In the interlobular trabeculae, forming the gland stroma, fibroblasts, blood vessels and nerve fibres are included. Another important finding in the ostrich Harderian gland is the presence of homogeneous material.