bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photoprotection mutants of Arabidopsis thaliana acclimate to high light by increasing photosynthesis and specific antioxidants
Authors: GOLAN TALILA , MÜLLER‐MOULÉ PATRICIA , NIYOGI KRISHNA K. 
Published: January 2006

ABSTRACTBiochemical and physiological acclimation to different light environments is crucial for plant growth and survival. In high light (HL), feedback de‐excitation (qE) is a well‐known photoprotective mechanism that dissipates excess excitation energy in the light‐harvesting antenna of photosystem II (PSII) and relieves excitation pressure in the photosynthetic electron transport chain. The xanthophylls zeaxanthin (Z) and lutein (L) function in qE, but also have roles as antioxidants. Although several studies have shown that qE is important during short‐term fluctuations in light intensity, here we show that it is not required for the growth of Arabidopsis thaliana in prolonged HL conditions in the laboratory. Mutants that are deficient in qE alone, qE and Z synthesis, or in qE, Z synthesis and also L synthesis were able to grow at 1800 µmol photons m−2 s−1 and exhibited no major symptoms of photooxidative stress. The mutants (and wild type) acclimated to HL by increasing photosynthetic capacity and decreasing light harvesting, which together rendered qE less important for photoprotection. At a metabolite level, the HL‐grown mutants appeared to compensate for their remaining qE deficit with increased α‐tocopherol and ascorbate levels compared to the wild type. The specificity of this response provides insight into the relationship between qE and the antioxidant network in plants.
Safety of a SQ‐standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo‐controlled trial
Authors: Kleine‐Tebbe J. , Ribel M. , Herold D. A. 
Published: January 2006

Background:  Sublingual treatment of grass pollen induced rhinoconjunctivitis might provide easier access to specific immunotherapy (SIT) and minimize the risk of serious adverse events (AEs) compared to subcutaneous SIT.Aim of the study:  To identify a safe dose range for once‐daily administration of a grass allergen tablet in participants with grass pollen induced seasonal rhinoconjunctivitis.Methods:  A randomized, double blind, placebo‐controlled Phase I trial was conducted outside the grass pollen season. Seven dosage groups [25 000, 75 000, 150 000, 300 000, 500 000, 750 000, or 1 000 000 standardized quality tablet (SQ‐T)], consisting of 12 participants randomized either to active treatment or placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at intervals of approximately 1 week to allow for intermittent safety reviews.Results:  The grass allergen tablet did not cause any serious, systemic or significant (leading to withdrawal) AEs. The overall incidence of AEs was 74% (1013 events); all of mild or moderate intensity and most considered treatment‐related. The most frequently reported treatment‐related AEs, including irritation of the throat, and itching sensations in the mouth and ears, increased with dose. These were primarily mild in intensity, started shortly after medication intake and lasted for minutes to a few hours maximum. Objective oral findings were also dose‐dependent. No clinically significant observations were found in safety laboratory, vital signs and 12‐lead ECG.Conclusions:  A sublingual grass allergen tablet in doses up to 1 000 000 SQ‐T daily caused no serious or systemic AEs displaying a safety profile that allows further investigation as once‐daily self‐medication.
Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi‐centre, randomized, dose–response study
Authors: Werfel T. , Breuer K. , Ruéff F. , Przybilla B. , Worm M. , Grewe M. , Ruzicka T. , Brehler R. , Wolf H. , Schnitker J. , Kapp A. 
Published: January 2006

Background:  The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi‐centre, randomized dose–response trial, double‐blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed.Methods:  Eighty‐nine adults with a chronic course of atopic dermatitis, SCORAD ≥40 and allergic sensitization to house dust mites [CAP‐FEIA ≥3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ‐U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline.Results:  The SCORAD declined in the three dose groups in a dose‐dependent manner (P = 0.0368, Jonckheere–Terpstra test) and was significantly lower in the two high‐dose groups (2000, 20000 SQ‐U) compared with the low‐dose group of 20 SQ‐U (P = 0.0379, U‐test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel–Haenszel chi‐square test).Conclusions:  Allergen‐SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.
IgE reactivity to latex allergens among sensitized healthcare workers before and after immunotherapy with latex
Authors: Sastre J. , Raulf‐Heimsoth M. , Rihs H.‐P. , Fernández‐Nieto M. , Barber D. , Lombardero M. , Martín S. , Quirce S. 
Published: January 2006

Background:  New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen‐specific immunotherapy (IT).Methods:  Twenty‐four healthcare workers (HCWs) – patients included in a latex IT study – were analysed, 16 in active treatment and eight in placebo. Sera were obtained at baseline and after 6 months of IT and analysed with immunoblotting and CAP System with eight single recombinant latex allergens (rHev b 1, 3, 5, 6.01, 8, 9, 10, 11, and a mix of rHev b1, 5, 6.01 and 8).Results:  After IT with latex, three patients in the active treatment group had new IgE sensitizations, one to Hev b 5, one to Hev b 11 and another to Hev b 6.01. No other significant variation in mean of specific IgE to latex or recombinant allergens were observed in patients who received placebo or active treatment. A significant (P = 0.012) negative correlation (−0.72) was observed between maximal tolerated dose and specific IgE to Hev b 6.01 at baseline. After IT, immunoblot analysis demonstrated a significant increase in IgE binding in a band of approximately 22 kDa (P = 0.032) that may correspond to Hev b 6.01. New or more intense bands appeared in seven patients of the active group, while in three subjects a reduction was observed.Conclusions:  Hev b 6.01 seems to be the most relevant latex allergen in HCWs. New or more intense IgE binding to latex allergenic components occurs during latex immunotherapy. However, the levels of specific IgE against these new components are low and do not seem to have clinical relevance.
Association between interleukin‐1 receptor antagonist gene and asthma‐related traits in a German adult population
Authors: Pattaro C. , Heinrich J. , Werner M. , de Marco R. , Wjst M. 
Published: January 2006

Background:  A recent study in German and Italian families associated variants in the interleukin‐1 receptor antagonist (IL1RA) gene with asthma. The aim of the present study was to further investigate the role of single nucleotide polymorphisms (SNPs) in the IL1RA gene in the development of atopy and lifelong asthma in a population‐based study.Methods:  DNA samples from the German centres of the European Community Respiratory Health Survey were analysed for genetic variants in the IL1RA gene and the development of asthma, atopy and bronchial hyperreactivity.Results:  Carriers of the rare G allele of SNP rs447713 had a significantly increased risk of developing asthma (P = 0.0013) and allergic sensitization (P = 0.0119). Carriers of the rare C allele of SNP rs3087271 had an increased risk of asthma (P = 0.0227) and high immunoglobulin E (IgE) levels (P = 0.0232). A haplotype built from eight SNPs in the IL1RA gene (A‐C‐A‐G‐A‐C‐G‐A) was associated with a higher prevalence of asthma (P = 0.007) and high total IgE (P = 0.02). Bronchial hyperreactivity was positively associated with the haplotype A‐C‐G‐G‐A‐C‐G‐C (P = 0.02) and negatively with the A‐C‐G‐G‐A‐C‐T‐C (P = 0.03).Conclusion:  A previously described association between IL1RA and asthma in families could be reproduced in a population‐based sample. The genetic variants of IL1RA gene do not to seem to affect asthma alone, but to act as modulators of asthma‐related traits as well, where different haplotypes drive the development of different phenotypes.
European birth cohort studies on asthma and atopic diseases: I. Comparison of study designs – a GA2LEN initiative
Authors: Keil T. , Kulig M. , Simpson A. , Custovic A. , Wickman M. , Kull I. , Lødrup Carlsen K. C. , Carlsen K. H. , Smit H. A. , Wijga A. H. , Schmid S. , Von Berg A. , Bollrath C. , Eller E. , Bindslev‐Jensen C. , Halken S. , Høst A. , Heinrich J. , Porta D. , Forastiere F. , Brunekreef B. , Krämer U. , Willich S. N. , Wahn U. , Lau S. ,   the working group of GALEN‐WP 1.5 ’Birth Cohorts’
Published: January 2006

Background:  The reasons for the rise in asthma and allergies remain unclear. To identify risk or protective factors, it is essential to carry out longitudinal epidemiological studies, preferably birth cohort studies. In Europe, several birth cohort studies on asthma and atopic diseases have been initiated over the last two decades.Aim:  One of the work packages within the Global Allergy and Asthma European Network (GA2LEN) project was designed to identify and compare European birth cohorts on asthma and atopic diseases. The present review (part I) describes their objectives, study settings, recruitment process and follow‐up rates. A subsequent review (part II) will compare outcome and exposure parameters.Methods:  For each birth cohort, we collected detailed information regarding recruitment process, study setting, baseline data (pregnancy, birth, parents/siblings) as well as follow‐up rates, outcome and exposure parameters at each time point.Results:  We identified and assessed 18 European birth cohorts on asthma, allergic rhinitis and eczema. Six of these studies also focused on food allergies. The birth cohorts were mostly initiated in the 1990s with predominantly urban/metropolitan settings. Many studies were able to maintain high follow‐up rates, even after five or more years.Conclusions:  Due to the unique cooperation within the GA2LEN project a common database was established containing study characteristics of European birth cohorts on asthma and atopic diseases. This can be used as a basis for evaluating the possibility to pool data and perform meta‐analyses, as well as to recommend criteria for conducting future birth cohorts.
Polymorphisms of the GSTM1 and GSTT1 genes in patients with allergic diseases in the Czech population
Authors: Holla L. I. , Stejskalova A. , Vasku A. 
Published: January 2006

Background:  Allergic diseases belong to the most common chronic disorders affecting mankind and their prevalence in population is increasing. Several studies have indicated that oxidative stress impairs pulmonary function and makes existing asthma worse. Members of the glutathione‐S‐transferase (GST) superfamily of genes are important in protection of cells from reactive oxygen species.Aims of the study:  Relationships among allergic diseases including asthma and variations in the GST mu (GSTM1) and GST theta (GSTT1) genes were investigated in 1006 Caucasian subjects.Methods:  The multiplex polymerase chain reaction protocol was used for simultaneous amplification of both genes for molecular analysis. Genotype frequencies among patients and controls were assessed and the associations of the genotypes with intermediary phenotypes of allergy were statistically determined.Results:  The frequencies of GST null genotypes did not differ significantly between patients with allergic diseases (or asthma alone) and healthy controls. However, when compared with patients homozygous or heterozygous for GSTM1 functional allele, asthmatics carrying both GSTM1 null alleles displayed significantly worse lung function, assessed by forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio (Tiffenau index), (P < 0.01).Conclusions:  Genetic polymorphisms of the GSTM1 and GSTT1 genes, both individually and in combination, were not associated with the development of allergic diseases including asthma in the Czech population, the GSTM1 gene variability, however, may influence lung functions in our asthmatics.
The effect of β2‐adrenoceptor haplotypes on bronchial hyper‐responsiveness in patients with asthma
Authors: Wilson A. M. , Gray R. D. , Hall I. P. , Lipworth B. J. 
Published: January 2006

Background:  The β2‐adrenoceptor exhibits genetic polymorphism which may be clinically relevant in terms of treatment response or bronchial hyper‐responsiveness (BHR). The combined effect of these genotypes, or the haplotype, has not been fully characterized in terms of BHR.Methods:  We performed a retrospective analysis of the effects of haplotypes of amino acid substitution at position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients.Results:  There was a significant (P < 0.05) overall effect for forced expiratory volume (FEV1) but not after correction for steroid dose and atopic status. There were no significant differences for BHR to methacholine or AMP between the different haplotypes and no difference between the numbers of patients with or without clinically relevant BHR. Methacholine PD20 geometric mean‐fold difference was 1.63 (95% CI: 0.95–2.80) between Arg–Arg/Gln–Gln and Gly–Gly/Gln–Gln and 1.26 (95% CI: 0.75–2.11) between Gly–Gly/Gln–Gln and Gly–Gly/Glu–Glu.Conclusions:  The degree of BHR to indirect and direct stimuli does not differ between β2‐adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients presenting with asthma. Although β2‐adrenoceptor haplotypes do not predict BHR they may be important in predicting response to bronchodilator therapy.
Risk factors for asthma in young adults: a co‐twin control study
Authors: Thomsen S. F. , Ulrik C. S. , Kyvik K. O. , Larsen K. , Skadhauge L. R. , Steffensen I. E. , Duffy D. L. , Backer V. 
Published: January 2006

Background:  The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8‐year period.Methods:  From the birth cohorts 1953–1982 of the Danish Twin Registry, 6090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire‐based study in 1994 participated in a similar follow‐up study in 2002. Subjects were regarded incident asthma cases when responding affirmatively to the question ‘Do you have, or have you ever had asthma'? in 2002. Pairs in which only one twin developed asthma – discordant pairs – were identified and conditional logistic regression was applied to detect effects of risk factors.Results:  A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3.16, 95% CI: 1.29–7.73, P = 0.007) and exercise (OR for inactivity = 0.35, 95% CI: 0.13–0.91, P = 0.023) were significantly associated with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44–4.13, P = 0.001), eczema (OR = 1.96, 95% CI: 1.02–3.78, P = 0.040), female sex (OR between males and females = 0.54, 95% CI: 0.36–0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02–1.20, P = 0.009) were significant predictors of asthma.Conclusions:  Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma.
Twelve‐year follow‐up after discontinuation of preseasonal grass pollen immunotherapy in childhood
Authors: Eng P. A. , Borer‐Reinhold M. , Heijnen I. A. F. M. , Gnehm H. P. E. 
Published: January 2006

Background:  In a previous controlled study, we demonstrated that preseasonal grass pollen immunotherapy for 3 years was effective in children. Moreover, a significant clinical benefit could still be observed 6 years after discontinuation of specific immunotherapy (SIT). In the current study, we examined the same group of patients again to investigate whether there is a prolonged benefit 12 years after SIT is stopped.Methods:  Twenty‐two patients with previous SIT (from 1989 through 1991) or standardized seasonal pharmacotherapy only were prospectively followed during the grass pollen season of 2003. Primary end points were symptom score, medication use, and combined symptom and medication score. In addition, skin prick test reactivity, development of new sensitizations, and prevalence of seasonal asthma were evaluated.Results:  Total hay fever symptom score (P < 0.03), use of medication (P < 0.05), and combined symptom and medication score (P < 0.03) remained lower in patients with previous SIT when compared with the control group. Decreased immediate skin response to grass pollen returned 12 years after cessation of SIT. The percentage of new sensitization, however, continued to be significantly smaller in patients with previous SIT (58%) compared with the controls (100%, P < 0.05). There was a tendency for lower prevalence of seasonal asthma in the post‐SIT group (P = 0.08).Conclusion:  This prospective controlled prolonged follow‐up study demonstrates the ongoing clinical benefit 12 years after discontinuation of SIT. Furthermore, the reduction in onset of new sensitization, which was found 6 years after discontinuation of SIT, is sustained 6 years later.
The role of Foxp3+ T cells in long‐term efficacy of prophylactic and therapeutic mucosal tolerance induction in mice
Authors: Winkler B. , Hufnagl K. , Spittler A. , Ploder M. , Kállay E. , Vrtala S. , Valenta R. , Kundi M. , Renz H. , Wiedermann U. 
Published: January 2006

Background:  Mucosal tolerance induction is suggested as treatment strategy for allergic diseases. Using a murine model of birch pollen (BP) allergy we investigated the long‐term efficacy and the underlying mechanisms of mucosal tolerance induction with two structurally different molecules in a prophylactic and in a therapeutic set‐up.Methods:  The three‐dimensional major BP allergen Bet v 1 or a nonconformational hypoallergenic fragment thereof was intranasally applied before (prophylaxis) or after sensitization (therapy).Results:  In the prophylactic application both the Bet v 1 allergen and the fragment prevented allergic sensitization, and this effect lasted for 1 year. In the therapeutic approach established allergic immune responses were also suppressed after treatment with either of the molecules. However, a long‐lasting curative effect (6 months) was only achieved with the Bet v 1 allergen but not with the Bet v 1 fragment.Real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) analysis of splenocytes revealed that tolerance induction with the Bet v 1 allergen was associated with enhanced expression of transforming growth factor (TGF)‐β, interleukin (IL)‐10, and Foxp3 mRNA in CD4+ T cells, whereas treatment with the fragment led to the induction of either Foxp3 (prophylaxis) or IL‐10 (therapy) alone.Conclusion:  From these data we concluded (i) that the mechanisms underlying peripheral tolerance are linked to the conformation of the antigen, (ii) that mucosal tolerance is mediated by separate regulatory cell subsets, and (iii) that the long‐term efficacy of immunosuppression is associated with the presence of Foxp3+ T cells.
A new in vitro model for the study of pig‐to‐human vascular hyperacute rejection
Authors: Bennet William , Sundberg Berit , Elgue Graciela , Larsson Rolf , Korsgren Olle , Nilsson Bo 
Published: January 2006

Abstract: Studies on vascular hyperacute xenograft rejection (HAR) are usually conducted in vitro on cultured endothelial cells (EC) exposed to human serum, in complex whole organ perfusion models using heparinized blood or in vivo models. Here we describe a new model allowing perfusion of pig vessels with human whole blood without anticoagulants.Segments of the porcine iliac artery were connected to circular polyvinyl chloride (PVC) tubing, whose inner surface was conjugated with immobilized heparin. The vessels were perfused with 7 to 8 ml of fresh, non‐anticoagulated human blood by rocking of the tubing device for 5, 15 or 60 min in an incubator at 37°C. Human iliac arteries (n = 4) were perfused with fresh human ABO‐compatible blood as controls.Perfusion of human vessels resulted in changes in the blood and plasma parameters similar to those in the PVC control loop. Overall, perfusion of the porcine vessels generated high levels of C3a, sC5b‐9 and thrombin–anti‐thrombin (TAT). Platelet consumption was near total (97.2 ± 1.2%; “high” responders) in six of 13 vessels perfused and only moderate (55.8 ± 9.9%; “low” responders) in the remaining seven vessels. The “high” responder vessel group showed a significantly higher platelet reduction, neutrophil loss and monocyte consumption and higher C3a and TAT factor at 60 min compared with the human vessels. The “low” responder porcine vessel group also generated significantly higher TAT levels at 60 min compared with the human vessels, but lower levels compared with the “high” responder porcine vessel group. Immunohistochemical examination of perfused porcine vessels revealed binding of human IgM, IgG, IgA, C1q, C3, fibrin and platelets at 5 min. The binding of these proteins was even stronger at 15 and 60 min, and at 60 min C9 could also be detected. Addition of soluble complement receptor 1 (sCR1) to the blood resulted in a significant reduction in C3a and sC5b‐9 (P = 0.046 and P = 0.046, respectively). However, sCR1 did not reduce C1q, C3c or C5 staining, but did abolish C9 binding to the endothelium.In conclusion, in vitro perfusion of porcine vessel segments with non‐heparinized, fresh human blood triggered events characterizing HAR. The small quantity of blood and xenogenic tissue that is needed makes this model ideal for investigations of the mechanisms and treatments of rejections associated with xenogeneic pig‐to‐human xenotransplantation.