bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of aminopeptidase N and dipeptidyl peptidase IV in the healthy and asthmatic bronchus
Authors: Van Der Velden  , Wierenga‐Wolf  , Adriaansen‐Soeting  , Overbeek  , MÖller  , Hoogsteden  , Versnel  
Published: March 2003

BackgroundAsthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and chronic inflammation of the airways. Since peptides are able to produce many of the pathophysiological features which are characteristic of asthma, peptide‐mediated inflammation is thought to play a role in this disease. The effects of peptides are modulated by peptidases, which are able to degrade peptides, mostly resulting in their inactivation.ObjectivesIn this study, we investigated the distribution of two peptidases, aminopeptidase N and dipeptidyl peptidase IV, in the human bronchus and determined whether their expression was altered in allergic asthmatics.MethodsWe first determined the distribution of aminopeptidase N and dipeptidyl peptidase IV in the human bronchus using immuno‐ and enzymehistochemistry and compared this with the distribution of neutral endopeptidase. Secondly, the expression of aminopeptidase N and dipeptidyl peptidase IV was determined in bronchial biopsies of healthy subjects (n = 8) and allergic asthmatics (n = 12).ResultsAminopeptidase N was localized in connective tissue, blood vessels, gland ducts, perichondrium, nerves and leucocytes (mainly mononuclear phagocytes, dendritic cells, and eosinophils). Dipeptidyl peptidase IV was localized in serosal glands, blood vessels, and T cells. Immunohistochemistry and enzymehistochemistry gave similar results. Comparison of the expression of aminopeptidase N and dipeptidyl peptidase IV in bronchial biopsies of healthy controls and atopic asthmatics revealed no significant differences in the lamina propria. In contrast, in the bronchial epithelium of atopic asthmatics an increased number of aminopeptidase N‐positive cells could be found. Double‐staining identified these cells as L25+ dendritic cells and eosinophils.ConclusionsWe conclude that expression of aminopeptidase N and dipeptidyl peptidase IV is restricted to specific sites within the human bronchus. Furthermore, in the bronchial epithelium of allergic asthmatics an increased number of aminopeptidase N‐expressing dendritic cells and eosinophils can be found.
β2‐adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population
Authors: Dewar  , Wheatley  , Venn  , Morrison  , Britton  , Hall  
Published: March 2003

ObjectiveTo determine the association between the β2‐adrenoceptor polymorphisms at amino acids 16 and 27 and markers of allergic disease and asthma per se in a random adult population, and to determine the degree of linkage disequilibrium existing between polymorphisms at amino acid positions 16, 27, 164 and nucleic acid residue 523.MethodsWe measured serum IgE, skin‐prick test positivity, atopy, bronchial hyperreactivity, wheeze and asthma (self‐reported and doctor‐diagnosed), and determined β2‐adrenoceptor genotype by allele specific oligonucleotide hybridization, in 630 adults aged between 18 and 70, selected from the electoral role in a local health authority in Nottingham.ResultsHomozygotes for the Glycine 16 polymorphism had a significantly higher incidence of atopy (χ2 = 6.44 (Pearson's), P = 0.04). We also observed a significant association between the Glycine 16 allele and atopy (χ2 = 4.13 (Pearson's), P = 0.04), when we assumed the Glycine 16 allele to operate in a dominant mode. No other significant associations between β2‐adrenoceptor polymorphisms and markers of allergic disease and asthma per se were observed. Marked linkage disequilibrium exists between the β2‐adrenoceptor polymorphisms at amino acid 16 and 27 (D = 0.38, χ2P < 0.0001), and between the β2‐adrenoceptor polymorphisms at amino acid 27 and nucleic acid residue 523 (C‐A) (D = 0.36, χ2P < 0.0001).ConclusionThere is no consistent association between β2‐adrenoceptor polymorphisms and the risk of developing allergic disease or asthma per se in this adult sample. Marked linkage disequilibrium exists between the amino acid 16 and 27 polymorphisms, and also between the amino acid 27 polymorphism and the nucleic acid residue 523 (C‐A) polymorphism. This polymorphism accounts for the Ban 1 RFLP previously described at the β2‐adrenoceptor locus on chromosome 5q 31.
Indoor airborne fungal spores, house dampness and associations with environmental factors and respiratory health in children
Authors: Garrett  , Rayment  , Hooper  , Abramson  , Hooper  
Published: March 2003

BackgroundChildren living in a damp house are more likely to suffer from respiratory symptoms and it has been suggested that exposure to fungi is an important contributing factor. However, more knowledge about underlying mechanisms for the association are needed.ObjectiveTo identify associations between measures of house dampness, levels of airborne fungal spores, housing factors and health outcomes in children.MethodsEighty households with 148 children between 7 and 14 years of age were recruited in the Latrobe Valley, Victoria, Australia. Some 36% of participating children were asthmatic. Six sampling visits were made to each house between March 1994 and February 1995 on a 2‐monthly cycle. Samples for airborne total and viable fungal spores were collected from bedrooms, living rooms, kitchens and outdoors. A detailed dwelling characterization, using a questionnaire and inspection surveys, was carried out. Skin‐prick tests were performed with extracts of common aeroallergens and a respiratory questionnaire was completed for each child.ResultsLarge airborne fungal spore concentrations were recorded in association with: musty odour, water intrusion, high indoor humidity, limited ventilation through open windows, few extractor fans and failure to remove indoor mould growth. Visible mould growth or condensation evidence was associated with large concentrationsof Cladosporium spores, but not with large total spore concentrations. Penicillium exposure was a risk factor for asthma, while Aspergillus exposure was a risk factor for atopy. Fungal allergies were more common among children exposed to Cladosporium or Penicillium in winter or to musty odour. Respiratory symptoms were marginally more common with exposure to Cladosporium or total spores in winter.ConclusionIndoor exposure to certain fungal genera in winter was a risk factor for asthma, atopy and respiratory symptoms in children. On the other hand, no significant associations were seen between average viable or total spore concentrations and child health. Actual measurements of fungal spores predict health outcomes better than reported dampness.
Exclusion of chromosome 11q and the FcεRI‐β gene as aetiological factors in allergy and asthma in a population of Dutch asthmatic families
Authors: Amelung  , Postma  , XU  , Meyers  , Bleecker  
Published: March 2003

BackgroundThe β subunit of the high‐affinity receptor for IgE (FcεRI‐β) is localized to chromosome 11q13 and has been reported by Cookson et al. to be in close genetic linkage with a gene for atopy. A maternally inherited association was found between the presence of a variant of FcεRI‐β, Ile181Leu, and high total serum IgE levels (IgE  >  100 IU). In a previous study of 20 Dutch families, we found no evidence for linkage of atopy or bronchial hyperresponsiveness (BHR) to chromosome 11q.ObjectiveRecently segregation analysis in 92 families has given us evidence for two independent major loci accounting for 78% of the observed variance in total serum IgE levels, and linkage analysis using both sib‐pair and LOD score methods has identified one major locus for regulation of IgE levels and BHR near the cytokine gene complex on chromosome 5q. The objective of this study is to pursue the identification of the second major locus.MethodsWe have studied markers in the area of the high affinity IgE receptor (FcεRI‐β) on chromosome 11q (D11S1314, FcεRI‐β and D11S987) in 83 families for whom DNA was available. Furthermore, our families have been examined for variance in the FcεRI‐β gene, specifically for Leu181 and Leu181/Leu183 mutations.ResultsBy sib‐pair analysis, there is no evidence for linkage of total serum IgE levels or number of positive skin tests to these markers in our population. Similar negative results were obtained for affected sib‐pair analysis of BHR, with the exception of D11S1314, which was significant at P  =  0.046. The FcεR1‐β gene in 36 female probands, 44 male probands and 46 female spouses was sequenced for these mutations. For each of these 126 individuals sequencing of FcεRI‐β demonstrated a wild‐type sequence pattern, with no mutations found in anyone, male or female.ConclusionWe are unable to confirm the presence of significant mutations in FcεR1‐β gene in our population, and we cannot confirm that the FcεR1‐β gene is crucial to the pathogenesis of allergic inflammation in asthma.
Increased nitric oxide in nasal lavage fluid and nitrotyrosine formation in nasal mucosa — indices for severe perennial nasal allergy
Authors: Sato  , Fukuyama  , Sakai  , Nakazawa  
Published: March 2003

BackgroundThe nose contributes the large amount of nitric oxide (NO) to exhaled air. NO is a mediator of vasodilation and yields peroxynitrite (ONOO−) by reacting with superoxide (O−2). ONOO− attacks tyrosine residues to form nitrotyrosine.ObjectiveThe aim of this study was to examine the pathophysiological role of NO in nasal mucosa in patients with perennial nasal allergy.MethodsWe measured nitrite and nitrate (NO−2/NO−3) and 3′,5′‐guanosine monophosphate (cyclic GMP) in nasal lavage fluid, and also measured haemoglobin concentration in nasal mucosa as an indicator of blood volume in the patients and healthy volunteers. The deleterious role of NO was also investigated by measuring nitrotyrosine in nasal mucosa.ResultsThe NO−2/NO−3 concentration in the nasal lavage fluid was 39.5 ± 2.8 μM in healthy volunteers (n = 40), 42.4 ± 3.0 μM in patients with mild allergy (mild group, n = 32), and 88.7 ± 6.6 μM in patients with severe allergy (severe group, n = 61). In the patients whose symptoms were improved with treatment, NO−2/NO−3 levels decreased to 45.7 ± 10.4 μM. The concentration of cyclic GMP in nasal lavage fluid was higher in the severe group than in the healthy volunteers. The mucosal haemoglobin index was 88 ± 4 in the healthy volunteers, 67 ± 4 in the mild group, and 53 ± 2 in the severe group. The formation of nitrotyrosine was expressed 0.58 ± 0.10% to total tyrosine in the severe group (n = 11), but was not found in non‐allergy patients (n = 9).ConclusionsThe production of NO was increased in patients with perennial nasal allergy, but the blood flow in the nasal mucosa of patients was reduced. Nitrotyrosine formation suggests that there is a process of ONOO−‐induced damage in mucosa of patients with the perennial nasal allergy and this damage may limit the dilatation of blood vessels, despite the presence of excessive NO.
Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease
Authors: Kanazawa  , Shoji  , Yoshikawa  , Hirata  , Yoshikawa  
Published: March 2003

BackgroundNitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Though direct measurement of endogenous NO has been difficult in humans, we have recently found that measurement of NO derivatives in induced sputum may be useful for assessing airway inflammation in asthmatic patients.ObjectiveThis study was designed to determine the direct in vivo evidence of increased production of endogenous NO in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD).MethodsWe have investigated simultaneous assessment of NO using two non‐invasive methods, such as NO level in exhaled air and induced sputum, in these patients. We determined the concentration of stable end‐products of NO (nitrite plus nitrate) in induced sputum and exhaled NO concentration using a chemiluminescence analyser in 10 normal controls, 10 asthmatic patients and 11 patients with COPD, and evaluated whether endogenous NO levels correlate with percentage of neutrophils and interleukin‐8 (IL‐8) level in induced sputum in patients with COPD.ResultsWe found significantly higher concentrations of exhaled NO in patients with bronchial asthma (25.1 [5.1] p.p.b.) than in patients with COPD (12.1 [1.9] p.p.b.) and normal controls (5.2 [1.4] p.p.b.). However, higher concentrations of NO derivatives in induced sputum were found in patients with bronchial asthma (1190 [106] μmol/L) and COPD (950 [105] μmol/L) than in normal controls (514 [30] μmol/L). In patients with asthma, but not in those with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with concentrations of exhaled NO (r = 0.64, P < 0.05). Moreover, in patients with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with percentage of neutrophils (r = 0.71, P < 0.05) and IL‐8 level (r = 0.80, P < 0.01).ConclusionWe conclude the increased production of endogenous NO in patients with asthma and COPD, and that NO derivatives in induced sputum are more valuable than exhaled NO in assessing airway inflammation in patients with COPD.
Circulating CLA+ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal‐related T‐cell receptor variable segments
Authors: Torres  , Gonzalez  , Corzo  , Giron  , Carvajal  , Garcia  , Pinedo  , Martinez‐Valverde  , Blanca  , Santamaria  
Published: March 2003

BackgroundAtopic dermatitis is an allergic T‐cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte‐associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response.ObjectiveTo study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus‐related TCR Vβ segments.MethodsPeripheral blood T cells were stained with HECA‐452 (anti‐CLA) and a panel of TCR Vβ specific monoclonal antibodies and analysed by flow cytometry.ResultsAtopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vβ2 and Vβ5.1 segments in the CLA+ but not in the CLA− subset. These TCR Vβs are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA‐DR+ expression by CLA+ Vβ5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vβ and HLA‐DR phenotype in circulating CLA+ T lymphocytes.ConclusionOur data indicate that circulating skin‐homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vβ segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.
Regional variations in grass pollen seasons in the UK, long‐term trends and forecast models
Authors: Emberlin  , Mullins  , Corden  , Jones  , Millington  , Brooke  , Savage  
Published: March 2003

BackgroundThree sites in the UK have daily records of pollen spanning several decades, giving the longest data sets worldwide. Previous research on London data revealed decreasing severity of grass pollen seasons. This is often taken as a model for the whole country but comparisons with Derby and Cardiff, in different regions of local climate and land‐use, emphasize the need for regional studies.ObjectiveThe grass pollen seasons were analysed for three contrasting long‐term sites to provide regional insight into the changing incidence of hay fever.MethodsPollen was monitored by volumetric instruments using standard techniques. Data have been taken from 1961 to 1993 to examine variation in grass pollen seasons in relation to land‐use changes, cumulative temperatures and rainfall. Models were developed to predict total seasonal catches.ResultsAt Cardiff the annual counts and severity increased in the 1960s, declined in the 1970s and rose again in the 1980s. At Derby and London the annual counts and severity declined but at different rates. Start dates have tended to become earlier at Cardiff and Derby, but later at London. Trends in annual counts and severity are similar to changes in grassland areas but they cannot be accounted for entirely by these. Weather in spring and early summer has tended to become warmer but there are no sustained patterns in June and July. No trends are apparent in the rainfall records for these months. The maximum explanation (r2≥ 95%) in forecast models was obtained using 10‐day aggregates of weather.ConclusionThe contrasting patterns both in the pollen records and land‐use changes between the three sites emphasize the need for regional data. The predictive models achieved a high degree of explanation enabling pollen season severity to be forecast with high confidence shortly before the start date.
Carob is not allergenic in peanut‐allergic subjects
Authors: Fiocchi  , Restani  , Travaini  , Decet  , Gaiaschi  , Bernardo  , Riva  
Published: March 2003

BackgroundThe antigenic potential of proteins from the carob bean, a member of the legume family used as a food additive, have not so far been investigated and legumes share antigenic proteins with peanut, a potent trigger of anaphylaxis.ObjectiveTo assess the carob protein determinants of sensitization in peanut‐allergic children.MethodsIn a prospective, double‐blind, placebo‐controlled study 12 patients (median age 9.5 years) with a history of hyperreactivity to peanut (anaphylaxis) were assessed. Skin prick tests with a commercial peanut allergen, raw carob pulp, raw and cooked carob cotyledon formula were used to confirm the history. RAST for peanuts and cooked carob were used to evaluate sensitization to these proteins. Carob‐specific IgE were identified by immunoblotting analyses. Allergic reactivity was evaluated during double‐blind placebo‐controlled food challenges (DBPCFC; 5.5 g carob extract and cooked carob cotyledon formula).ResultsPeanut allergen‐induced skin prick test positivity in all children (confirmed during double‐blinded challenge in 6/12 patients), carob pulp in 3/12 patients, raw carob bean in 6/12, and cooked carob cotyledon formula in none. RAST were positive for peanut in all cases but negative for carob beans in 9/12 cases. Immunoblot analyses found peanut‐specific IgE in all cases and raw carob bean‐specific IgE in eight cases. Carob allergens were identified in the 17.5, 48, and 66 kDa MW bands. The least allergenic density was found for cooked carob proteins. There was no clinical reactivity with either raw or cooked carob during DBPCFC.ConclusionsThese data suggest that carob‐specific sensitization, apparent both in vitro and in SPTs, can be concordant with peanut allergy and that cooked carob can be ingested by children who are allergic to peanuts. That heat‐processing deactivates carob protein allergenicity has dietary implications for polyallergic children.
Cow's milk protein‐specific IgE concentrations in two age groups of milk‐allergic children and in children achieving clinical tolerance
Authors: SICHERER  , SAMPSON  
Published: March 2003

BackgroundIgE‐mediated cow's milk protein allergy (CMPA) is usually outgrown in children by the age of 3 years. The immunological responses to cow's milk proteins in children who achieve tolerance, in comparison with those who remain allergic, however, are not well described.ObjectiveTo compare the level of cow's milk protein‐specific IgE among children with documented CMPA under the age of 3 years, another group over the age of 9 years (persistent allergy), and in another group of children in whom clinical tolerance developed.MethodsStored sera from children with CMPA were analysed for IgE antibodies specific for whole cow's milk, casein, whey, α‐lactalbumin (ALA), β‐lactoglobulin (BLG), and bovine serum albumin (BSA) using the Pharmacia CAP System FEIA.ResultsWithin each group of CMPA children, the concentration of specific IgE antibody to casein proteins was not significantly different from that to whey proteins. However, children in the group with CMPA over 9 years of age had significantly greater concentrations of whole milk (P = 0.02) and casein‐specific (P = 0.04) IgE antibodies compared with the group of children with CMPA under age 3 years. Children under the age of 3 years had a higher median concentration of casein‐specific IgE (20.2 vs. 5.5, P = 0.04) than another group of 11 children (mean age 3.5 years), who later lost their milk allergy. Out of 16 children who lost sensitivity to milk, 75% had milk‐specific IgE levels below 14.3 kUA/L (median, 1.3 kUA/L).ConclusionsAlthough a dominant allergenic milk protein fraction was not identified within either of the two age groups, those with persistent CMPA over age 9 years had significantly elevated levels of milk and casein‐specific IgE compared with younger children with CMPA.
Assessment of eosinophil granule proteins in various body fluids: is there a relation to clinical variables in childhood asthma?
Authors: KOLLER  , HALMERBAUER  , FRISCHER  , ROITHNER  
Published: March 2003

BackgroundThe eosinophil plays a central role in the inflammatory process in bronchial asthma. Recent studies have indicated that the assessment of eosinophil‐derived proteins in various body fluids could be used for monitoring disease activity of childhood asthma. Till now, no study exists which compared the levels of eosinophil‐derived proteins in various body fluids such as serum, nasal lavage fluid (NALF) and urine.ObjectiveTo investigate whether eosinophil granule proteins in different compartments were correlated and whether there is a relationship betweeen disease activity, pulmonary function and bronchial hyperreactivity.MethodsTwenty‐eight children with atopic bronchial asthma were recruited. Serum, NALF and urine samples were obtained and assessed for eosinophil cationic protein (ECP) and eosinophil protein X (EPX). The levels of eosinophil proteins were analysed for a relationship with lung function variables, bronchial hyperreactivity and disease activity. Eleven healthy control subjects were used as controls.ResultsMedian ECP and EPX concentrations in serum (31.4 and 74.8 μg/L vs 15.8 and 24.3 μg/L, respectively), NALF (9.9 and 44.9 μg/L vs 0 and 2.5 μg/L, respectively) and urine (49.4 vs 16.5 μg/mmol creatinine) were significantly raised in children with bronchial asthma compared with healthy control subjects. In addition, ECP and EPX levels in serum and urine samples were significantly higher in symptomatic patients compared with asymptomatic subjects with asthma. Although no relationship between eosinophil‐derived proteins in serum, NALF or urine and the level of nonspecific bronchial hyperreactivity could be detected, the concentrations of EPX in serum and urine were correlated with variables of pulmonary function.ConclusionOur findings demonstrate increased eosinophil activity in serum, NALF and urine derived from children with bronchial asthma. Due to the relationship between levels of eosinophil proteins in serum/urine samples and lung function, as well as significant concentration differences between symptomatic and asymptomatic asthmatic children, the assessment of eosinophil proteins in serum or urine samples appear to be more appropriate in monitoring disease activity than measurement of ECP or EPX in NALF. Thus, the determination of serum ECP/EPX or urinary EPX may be preferentially used in monitoring eosinophilic inflammation in childhood asthma.