bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphism of the immune‐braking gene CTLA‐4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases
Authors: Yang K. D. , Liu C.‐A. , Chang J.‐C. , Chuang H. , Ou C.‐Y. , Hsu T.‐Y. , Wang C.‐L. 
Published: January 2004

SummaryBackground
A variety of genes are related to allergic disorders in different ethnic populations. The genetic basis for the gender discrepancy of allergic diseases remains to be determined.Objective
This study was conducted to investigate whether IL‐4 promoter (−590 C/T) and cytotoxic T lymphocyte antigen 4 (CTLA‐4) (+49 A/G) polymorphisms were correlated with a gender discrepancy of total IgE levels and allergic diseases in a Chinese population.Methods
A total of 1333 participants aged 19–49 years were enrolled in this study. Allergic diseases were recognized by the presence of asthma, rhinitis or atopic dermatitis in conjunction with detectable specific IgE in the blood. Polymorphisms of IL‐4 promoter (−590) and CTLA‐4 (+49) were determined by restriction fragment length polymorphism.Results
Males or females with allergic diseases had higher total IgE levels than those without (P=0.000). Females with the A/A genotype in the CTLA‐4 (+49) position had significantly higher total IgE levels than those with A/G, and those with the G/G genotype had the lowest IgE levels (154.9 vs. 107.1 vs. 79.8 KU/L; mean log values: 1.79 vs. 1.65 vs. 1.54, P< 0.001). However, males with different genotypes in the CTLA‐4 (+49) position exhibited no difference in the total IgE levels. Females with allergic rhinitis had a significantly higher frequency of the A/A genotype in the CTLA‐4 (+49) polymorphism than those without atopic diseases (P=0.016). In contrast, males with and without allergic disorders exhibited no significant difference in the CTLA‐4 (+49) polymorphisms (P>0.05). The IL‐4 promoter (–590) polymorphisms, however, had no correlation with the total IgE levels or allergic diseases in either females or males.Conclusion
In females only, the CTLA‐4 (+49), but not the IL‐4 promoter (−590), polymorphism was significantly associated with elevation of total IgE levels and allergic rhinitis. Here, we have, for the first time, demonstrated a gender‐linked genetic relationship with allergic disease.
Provocation with adenosine 5′‐monophosphate, but not methacholine, induces sputum eosinophilia
Authors: Van den berge M. , Kerstjens H. A. M. , De reus D. M. , Koëter G. H. , Kauffman H. F. , Postma D. S. 
Published: January 2004

SummaryIntroduction
Bronchial hyper‐responsiveness is usually measured with direct stimuli such as methacholine (MCh) or histamine. Adenosine 5′‐monophosphate (AMP), which acts indirectly via the secondary release of mediators, is another stimulus to measure bronchial hyper‐responsiveness.Aim
To investigate whether provocation with inhaled AMP itself initiates an inflammatory response resulting in an influx of eosinophils into the airway lumen.Methods
We have included 21 non‐smoking atopic asthmatic subjects (mean FEV1 101% predicted, mean age 34 years). Each subject performed three sputum inductions on different days, at least seven days apart: one without previous provocation, one hour after PC20 methacholine, and one hour after PC20 AMP.Results
After provocation with AMP, but not methacholine, the percentage of sputum eosinophils increased significantly (from 1.9±0.5% to 4.5±1% (P<0.01) and 1.9±0.5% (P=0.89)). No changes in the percentages of neutrophils, lymphocytes, macrophages, or bronchial epithelial cells were found.Conclusion
A provocation test with AMP leads to an increased percentage of sputum eosinophils. This observation cannot be explained by a non‐specific response of the airways to a vigorous bronchoconstriction, since methacholine had no effect on inflammatory cells.
Prenatal and early postnatal environments are significant predictors of total immunoglobulin E concentration in Filipino adolescents
Authors: Mcdade T. W. , Kuzawa C. W. , Adair L. S. , Beck M. A. 
Published: January 2004

SummaryBackground
Recent evidence suggests that atopic disease may in part be mediated by fetal growth, as well as exposure to infectious disease early in life. Few studies have been able to evaluate these associations simultaneously, or to investigate prospectively the long‐term effects of early environments while adequately controlling for potentially confounding variables.Objective
To examine how prenatal growth and infectious disease in infancy are related to total IgE production in adolescence.Methods
Ninety‐nine adolescents (aged 14–15 years) were selected from a larger cohort study according to the following criteria: full‐term birth, currently healthy, and small‐for‐gestational age (N=53) or appropriate‐for‐gestational age (N=46). Plasma total IgE was measured with ELISA, and analysed in relation to anthropometric, nutritional, and environmental quality data collected prospectively beginning in the third trimester prior to birth.Results
Each episode of infectious morbidity recorded at bimonthly intervals in the first 6 months of life was associated with a 0.12 log IU/mL reduction in total IgE in adolescence (P=0.004). Prenatal undernutrition was associated with increased adolescent IgE, but only under conditions of an unsanitary household environment (P=0.002). Each additional kilogram gained per month in the first 6 months of life was associated with an increase in adolescent IgE of 0.74 log IU/mL (P=0.03). Each quartile increase in weekly household income at the time of blood sampling was associated with a 0.10 log IU/mL reduction in total IgE (P=0.02).Conclusion
Infectious disease in infancy, as well as interactions between prenatal and postnatal environments, appear to have long‐term effects on adolescent total IgE production. Future research should investigate the mechanisms behind these effects, and their implications for symptoms of atopic disease.
Cetirizine, an H1‐receptor antagonist, suppresses the expression of macrophage migration inhibitory factor: its potential anti‐inflammatory action
Authors: Shimizu T. , Nishihira J. , Watanabe H. , Abe R. , Ishibashi T. , Shimizu H. 
Published: January 2004

SummaryBackground
H1‐receptor antagonists are often effective in the treatment of allergic disorders such as atopic dermatitis. Cetirizine, a putative H1‐receptor antagonist, has recently been shown to have anti‐inflammatory properties through the inhibition of leucocyte recruitment and activation, and by the reduction of ICAM‐1 expression on keratinocytes.Objective
To further elucidate the anti‐inflammatory properties of cetirizine, we first examined its effects on antigen‐induced eosinophilia and neutrophila in vivo. We then examined the anti‐inflammatory effects of cetirizine on a human keratinocyte A431cell line.Methods
Mice were sensitized subcutaneously with ragweed pollen and were challenged intraperitoneally with the allergen. Cetirizine diluted in sterile water (0–20 mg/kg) or only sterile water was administered orally. Peritoneal cells were obtained at 8 and 24 h after challenge. The eosinophilia and neutrophilia induced by ragweed pollen extract were quantitated. Macrophage migration inhibitory factor (MIF), macrophage inflammatory protein 2 (MIP‐2) and eotaxin contents of peritoneal fluid were also measured by mouse ELISA. The effects of cetirizine on MIF‐induced IL‐8 production in A431 cells were examined by ELISA. The effects of cetirizine on MIF expression and production in A431 cells were examined by human MIF ELISA and Northern blot analysis.Results
Eosinophilia and neutrophilia induced by ragweed pollen extract were found to be significantly reduced in cetirizine‐treated mice (20 mg/kg). MIF, a pleuripotent cytokine, was significantly decreased at 8 and 24 h in the peritoneal fluid by cetirizine treatment. MIP‐2 and eotaxin were also decreased 8 and 24 h, respectively, after challenge in the peritoneal fluid with cetirizine treatment. MIF stimulates IL‐8 production in A431 cells. We found that MIF production in A431 cells was inhibited by 10 μm cetirizine. Consistent with this, cetirizine significantly inhibited MIF‐induced IL‐8 production.Conclusion
These results suggest that cetirizine exerts its anti‐inflammatory effects by inhibiting MIF as well as IL‐8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1‐receptor‐antagonistic function.
Asthma is associated with single‐nucleotide polymorphisms in ADAM33
Authors: Werner M. , Herbon N. , Gohlke H. , Altmüller J. , Knapp M. , Heinrich J. , Wjst M. 
Published: January 2004

SummaryBackground
The ADAM33 gene has recently been associated with asthma and bronchial hyper‐reactivity. It codes for a disintegrin and metalloproteinase that triggers intra‐ and extracellular signalling by protein shedding.Objective
We examined whether polymorphisms in ADAM33 are associated with asthma and related traits in two German populations.Methods
We genotyped 15 intragenic single‐nucleotide polymorphisms (SNPs) by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry of allele‐specific primer extension products. The transmission disequilibrium test was used for association analysis in the German asthma family study. Additionally, we tested for association of these SNPs in a case–control sample from the European Community Respiratory Health Study using Armitage's trend test.Results
In both studies, we found SNPs that were significantly associated with asthma and related traits. In the family study, significant associations were observed for the SNPs F+1, ST+4 and ST+5 (with the lowest P‐value for F+1, P=0.005). Remarkably, this association is seen even in the absence of linkage with two microsatellite markers from a previous genome scan either 3.1 million bases (Mb) up‐ or 5.6 Mb downstream. In the case–control study, SNP ST+7 (P=0.008) was significantly associated with asthma. Some of these SNPs overlapped with those found to be associated with elevated total IgE levels and bronchial hyper‐responsiveness.Conclusion
This study replicates the recently published association between asthma and ADAM33 gene variants. However, most of the associated SNPs were at non‐identical positions in the German, UK and US samples. As linkage disequilibrium is high among the tested SNPs, and there is no known functional polymorphism, either not‐tested variants in ADAM33, unknown regulatory elements or a gene in close proximity is responsible for this association.
Cytokine production in peripheral blood cells during and outside the pollen season in birch‐allergic patients and non‐allergic controls
Authors: Wosinska‐Becler K. , Plewako H. , Håkansson L. , Rak S. 
Published: January 2004

SummaryBackground
The naturally occurring pollen season permits observation of the kinetic changes in the process of allergic inflammation. We examined cytokine production in peripheral blood (PB) T cells and monocytes obtained from birch‐allergic patients both during and outside the pollen season.Methods
PB from 16 patients and six healthy controls was obtained during the alder pollen season, at the beginning and the peak of the birch pollen season and outside the pollen season. Mononuclear cells (MNC) were stimulated with allergen and polyclonal activators. For flow cytometric analysis, MNC were stained with monoclonal antibodies (MoAbs) against the cell surface markers CD3, CD8, CD14 and the intracellular cytokines IL‐4, IL‐5, IL‐10, IL‐12, IL‐13, granulocyte macrophage‐colony stimulating factor (GM‐CSF) and IFN‐γ.Results
In allergic patients, significant increases in clinical symptoms, use of medication, eosinophil numbers and birch‐specific IgE were found during the pollen season. In vitro allergen stimulation increased the number of GM‐CSF+ monocytes (P<0.01) and this increase was dependent on allergen exposure. The IL‐4/IFN‐γ ratio rose (P<0.001) at the peak of birch pollen season and the ratio correlated with symptom scores during the birch season. In the CD4+ cell population, the numbers of GM‐CSF+ cells were higher throughout the alder and birch seasons compared with outside the pollen season (P<0.05). No such changes were seen in the healthy controls.Conclusions
The main finding of our study was the increased percentage of GM‐CSF+ monocytes in atopic subjects compared with healthy controls. In allergic patients, natural seasonal pollen exposure resulted in increased numbers of GM‐CSF+ cells among both monocytes and CD4+ T cells. We have also shown that a seasonal change in Th2/Th1 cytokine ratio requires an adequate and prolonged allergen stimulation that is seen late in the pollen season.
Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea‐pigs
Authors: Leick‐maldonado E. A. , Kay F. U. , Leonhardt M. C. , Kasahara D. I. , Prado C. M. , Fernandes F. T. , Martins M. A. , Tibério I. F. L. C. 
Published: January 2004

AbstractBackground
Leukotriene receptor antagonists have been demonstrated in several studies to possess bronchodilating and anti‐inflammatory properties in asthma. However, there are few experimental studies performed to compare the effects of anti‐leukotrienes and glucocorticoids, most used anti‐inflammatory agents in asthma. In the present study, we evaluated the effects of treatment with dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an experimental model of allergen‐induced chronic airway inflammation in guinea‐pigs (GP).Methods
GP were submitted to increasing concentrations of aerosols of ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated daily with dexamethasone, montelukast or saline solution. After this period, GP were anaesthetized, tracheostomized, mechanically ventilated and challenged with OVA aerosol.Results
Maximal changes of respiratory system resistance and elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001), but not by montelukast treatment. Neither dexamethasone nor montelukast significantly influenced bronchial oedema formation. Dexamethasone but not montelukast induced a decrease in mononuclear cells in airways (P<0.001). Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of exhaled nitric oxide (P<0.025).Conclusion
Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration.
Diversity of asparagus allergy: clinical and immunological features
Authors: Tabar A. I. , Alvarez‐puebla M. J. , Gomez B. , Sanchez‐monge R. , García B. E. , Echechipia S. , Olaguibel J. M. , Salcedo G. 
Published: January 2004

SummaryBackground
Asparagus (Asparagus officinalis) is an extensively grown and consumed vegetable. To a lesser extent than other Liliaceae vegetables, allergic contact dermatitis (ACD) due to asparagus has been reported. However, only a few case reports of asparagus IgE‐mediated allergy have been published. In a previous study, we demonstrated that two lipid transfer proteins (LTPs) (Aspa o 1.01 and Aspa o 1.02) were relevant allergens of asparagus.Objective
We retrospectively analysed the 27 patients diagnosed with asparagus allergy during the last 5 years. All of them reported adverse symptoms after either asparagus ingestion or handling. We describe their clinical features and evaluate whether they were associated to immunological findings (immunoblot pattern and skin reactivity to LTPs).Methods
Patients underwent skin prick and patch tests with standard panels of vegetables and aeroallergens. Besides crude asparagus extract, two purified LTPs were prick and patch tested. Total and specific IgE measurements and asparagus extract IgE immunoblotting were performed. Patients reporting asthma symptoms underwent specific inhalation challenge to asparagus.Results
Of the 27 subjects, eight had ACD, 17 had IgE‐mediated allergy and two had both ACD‐ and IgE‐mediated allergy. Positive patch tests with the crude asparagus extract but not with LTPs were observed in subjects with ACD (n=10). Of 19 patients with IgE‐mediated disease, 10 had contact urticaria after asparagus handling. Of them, five subjects and five others without skin allergy showed respiratory symptoms; of them, eight were diagnosed with occupational asthma confirmed by positive asparagus inhalation challenge, whereas the remaining two had isolated rhinitis. Four patients suffered from immediate allergic reactions related to asparagus ingestion (food allergy); three of them reported anaphylaxis whereas the other had oral allergic syndrome. Positive IgE immunoblotting (bands of 15 and 45–70 kDa) was observed in 10 subjects. Of 10 subjects with positive prick test to LTPs, six showed bands at 15 kDa. Either IgE‐binding bands or positive prick tests to LTPs were observed in asthma (62%) and anaphylaxis (67%).Conclusion
Asparagus is a relevant source of occupational allergy inducing ACD and also IgE‐mediated reactions. Severe disease (anaphylaxis or asthma) is common and LTPs seem to play a major role. The clinical relevance of LTP sensitization among patients with mild disease or symptom‐free subjects should be addressed in prospective studies.
The Resident Choice Scale: a measure to assess opportunities for self‐determination in residential settings
Authors: Hatton C. , Emerson E. , Robertson J. , Gregory N. , Kessissoglou S. , Walsh P. N. 
Published: January 2004

AbstractBackground  A 26‐item Resident Choice Scale was designed to assess service practices for promoting resident choice.Method  The staff working with 560 UK/Irish adults with intellectual disability were interviewed. Specific examples of practices promoting resident choice were requested and independently rated by the interviewer.Results  The interrater reliability of Resident Choice items was found to be acceptable (subsample n = 50). The psychometric properties of the Resident Choice Scale total score and scores on eight subscales were also acceptable. Consistently strong associations were found between greater resident choice and greater resident ability and, to a lesser extent, fewer resident challenging behaviours. Few associations were found between resident choice and autism or mental health problems. Even when controlling for resident ability and challenging behaviour, consistent associations were found between greater resident choice and the concurrent variables of greater community presence, fewer institutional practices, and greater user self‐reported satisfaction (subsample n = 50).Conclusions  Taken together, this pattern of results indicates that the Resident Choice Scale shows promise as a measure of the environmental opportunities available for adults with intellectual disability to exercise self‐determination. Areas for future research testing the reliability and validity of the Resident Choice Scale are outlined.
General practitioners’ educational needs in intellectual disability health
Authors: Phillips A. , Morrison J. , Davis R. W. 
Published: January 2004

AbstractBackground  The community general practitioner (GP) has a central role in the provision of primary health care to people with intellectual disability (ID) as an indirect result of deinstitutionalization in Australia. This population, however, continues to experience poor health care compared to the general population. The current paper describes results from a questionnaire that aimed to identify the perceptions of practising GPs on the standards of health care for people with ID, the adequacy of prior training, and their interest in further education in relation to nine health care areas.Method  A questionnaire was posted to a selective sample of 1272 practising GPs in Victoria selected from a database from the Centre for Developmental Disability Health Victoria and the Victorian Medical Directory of GPs registered with the Australian Medical Association. Data were available for 252 respondents with a response rate of 28.5%.Results  The health areas in which many GPs reported to be inadequately trained were the same as those areas that were perceived as being of a poor standard. These areas were behavioural or psychiatric conditions, human relations and sexuality issues, complex medical problems, and preventative and primary health care. Ninety four per cent of respondents were interested in further education in at least one of the nine health care areas, with the most frequently nominated areas being behavioural or psychiatric conditions, syndrome‐specific medical problems, human relations and sexuality issues and collaboration with government services. General practitioners did not nominate complex medical problems or preventative and primary health care for further education as frequently as they identified care in these areas to be substandard and their prior training inadequate.Conclusions  The findings from the current research are discussed in relation to the implications for development of educational programmes based on learning needs identified by the GP. The most frequently nominated health care areas in all three questions were behavioural or psychiatric conditions and human relations and sexuality issues. Reasons for incongruence between the frequency of responses for complex medical problems and preventative and primary health care are explored.
Cognitive abilities and genotype in a population‐based sample of people with Prader–Willi syndrome
Authors: Whittington J. , Holland A. , Webb T. , Butler J. , Clarke D. , Boer H. 
Published: January 2004

AbstractBackground  Prader–Willi syndrome (PWS) is characterized by extreme floppiness at birth, impaired sexual development, short stature, severe over‐eating, characteristic physical features and learning disabilities (LD). Impaired social cognition, literal mindedness and cognitive inflexibility are also present. The syndrome has two main genetic subtypes that both result in the failure of expression of maternally imprinted genes on chromosome 15 at the locus q11‐13.Methods  Through multiple sources, we attempted to identify all people with PWS living in one health region in the UK. Additional people with PWS identified in other regions were also recruited to augment the study sample. A comparison group of people with LD as a result of aetiologies other than PWS was also identified. All people from these three groups, over age three, who gave their consent, were assessed using tests of ability and attainment. In addition, their main carers were interviewed using a semistructured interview. Blood samples for genetic diagnosis were obtained from all consenting participants.Findings  The IQ distribution of the population sample was approximately normal with a mean IQ 40 points below that of the general population. There were systematic differences between the two main genetic subtypes. Those with disomies differed in cognitive profiles from both those with deletions and the comparison LD group (the latter two groups were very similar) in terms of better verbal abilities and impaired coding ability. Some people with PWS deletions had strong visuospatial skills.Interpretation  We propose that the normal distribution of IQ, shifted downwards relative to that of the general population, is the result of a global effect on IQ of the PWS gene(s), and that the different cognitive profile seen in those with chromosome 15 maternal disomies is a specific effect of a gene, or genes, on chromosome 15 which is differentially either expressed or not expressed in those with disomies relative to those with deletions. One hypothesis is that these subtle cognitive differences are a manifestation of the genetic influences of gender‐specific imprinted genes on cerebral lateralization. This requires further investigation.