bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of inhalative corticosteroids on circulating Nerve Growth Factor, Brain‐Derived Neurotrophic Factor and Neurotrophin‐3 in allergic asthmatics
Authors: Noga O. , Hanf G. , Schäper C. , O'Connor A. , Kunkel G. 
Published: March 2003

Background The neurotrophins Nerve Growth Factor (NGF), Brain‐Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)‐3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper‐responsiveness and serum levels has been reported.Objective Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state.Methods Eighty‐seven volunteers were studied. Thirty‐eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti‐asthmatic treatment and 20 were age‐ and sex‐matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA.Results NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT‐3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly.Conclusions These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.
Hot, humid air increases cellular influx during the late‐phase response to nasal challenge with antigen
Authors: Assanasen P. , Baroody F. M. , Naureckas E. , Naclerio R. M. 
Published: March 2003

Background Inhalation of hot, humid air (HHA: 37 °C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen.Objective To investigate whether HHA inhibited the late‐phase response to nasal challenge with antigen and increased hyper‐responsiveness of the nasal mucosa to histamine.Methods Twenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2‐way cross‐over study. The subjects continuously breathed room air (25 °C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2‐h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed.Results Exposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen‐induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8‐fold increase in the eosinophil influx and a 15‐fold increase in the levels of eosinophil cationic protein during the late‐phase response compared to room air. There were no significant differences in nasal hyper‐responsiveness to histamine during either exposure.Conclusion HHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper‐responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation.
Breastfeeding duration is a risk factor for atopic eczema
Authors: Bergmann R. L. , Diepgen T. L. , Kuss O. , Bergmann K. E. , Kujat J. , Dudenhausen J. W. , Wahn U. ,   The MAS‐study group
Published: March 2003

Background The results of numerous studies on the influence of breastfeeding in the prevention of atopic disorders are often contradictory. One of the most important problems is confounding by other lifestyle factors.Objective The aim of the present study was to analyse the effect of any breastfeeding duration on the prevalence of atopic eczema in the first seven years of life taking into account other risk factors.Methods In an observational birth cohort study 1314 infants born in 1990 were followed‐up for seven years. At 3, 6, 12, 18, 24 months and every year thereafter, parents were interviewed and filled in questionnaires, children were examined and blood was taken for in vitro allergy tests. Generalized Estimation Equations (GEE)‐models were used to model risk factors for the prevalence of atopic eczema and for confounder adjustmentResults Breastfeeding was carried out for longer if at least one parent had eczema, the mother was older, did not smoke in pregnancy, and the family had a high social status. The prevalence of atopic eczema in the first seven years increased with each year of age (OR 1.05; 95% CI 1.01–1.09 for each year), with each additional month of breastfeeding (1.03; 1.00–1.06 for each additional month), with a history of parental atopic eczema (2.06; 1.38–3.08), and if other atopic signs and symptoms appeared, especially specific sensitization (1.53; 1.25–1.88), and asthma (1.41; 1.07–1.85). Although breastfeeding should be recommended for all infants, it does not prevent eczema in children with a genetic risk.Conclusion Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk
Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: a direct role for mast cells in skin fibrosis
Authors: Garbuzenko E. , Nagler A. , Pickholtz D. , Gillery P. , Reich R. , Maquart F.‐X. , Levi‐Schaffer F. 
Published: March 2003

Background Mast cells, the key cells of immediate hypersensitivity type reactions, have also been postulated to have a central role in influencing tissue remodelling and fibrosis occurring in the skin.Objective Our aim was to investigate the direct role of human mast cells (HMC) in skin fibrotic processes, by assessing the effects of the addition of the human mast cell line HMC‐1 to human skin fibroblasts, and to identify the responsible mediators.Methods HMC‐1 sonicates were added to human skin fibroblasts and the following parameters were evaluated: proliferation ([3H]‐thymidine), collagen synthesis ([3H] proline), activity of matrix metalloproteinases (MMPs) (zymography) and tissue inhibitors of metalloproteinases (TIMPs) (reverse zymography), and collagen gel contraction.Results HMC‐1 sonicate increased significantly both proliferation and collagen production in the human skin fibroblasts and these properties were not affected by heating of the sonicate (56 °C, 30 min, or 100 °C, 3 min). Two main mast cell mediators, histamine and tryptase, were found to be responsible for the increase in fibroblast proliferation and collagen production. HMC‐1 sonicate did not display any pre‐formed gelatinase activity, and its addition to the fibroblasts did not change their pro‐MMP‐2 and MMP‐2 activity. On the other hand, HMC‐1 were found to possess TIMP‐1 and TIMP‐2. Addition of HMC‐1 had no effect on fibroblasts TIMP‐1 but induced a dose‐dependent increase of TIMP‐2 activity. In addition, HMC‐1 sonicate seeded together with the fibroblasts in tri‐dimensional collagen gel significantly enhanced their contraction.Conclusion We have shown that human mast cells, by granule‐stored and therefore quickly releasable mediators, increase human skin fibroblast proliferation, collagen synthesis, TIMP‐2 and collagen gel contraction. Therefore, mast cells have a direct and potentiating role in skin remodelling and fibrosis.
Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey
Authors: Jarvis D. , Chinn S. , Potts J. , Burney P. ,   the European Community Respiratory Health Survey
Published: March 2003

SummaryBackground There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese.Objective To determine the association of body mass index with respiratory symptoms and atopy in young adultsMethod Information collected from 15 454 participants in the European Community Respiratory Health Survey, a multicentre cross‐sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy.Results Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20–24.99 (OR in men 1.85, 95% confidence interval 1.41–2.42; OR in women 2.03, 95% confidence interval 1.59–2.58). Similar associations were observed for other symptoms suggestive of asthma. Body mass index was not associated with ‘hayfever or nasal allergies’, specific IgE to house dust mite, grass or cat or with total IgE in men or women.Conclusion Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.
Personal exposure to house dust mite allergen in bed: nasal air sampling and reservoir allergen levels
Authors: Gore R. B. , Hadi E. A. , Craven M. , Smillie F. I. , O'Meara T. J. , Tovey E. R. , Woodcock A. , Custovic A. 
Published: March 2003

SummaryBackground Assessment of personal exposure to dust mite allergen has relied on proxy measures. Only recently has a means to directly measure inhaled allergen particle number become available (the intra‐nasal air sampler).Objective To quantify inspired dust mite group 1 and group 2 allergen‐bearing particles in bed in undisturbed conditions prior to sleep by nasal air sampling and to investigate the relationship between inhaled particles and reservoir allergen levels.Methods Twelve volunteers wore nasal samplers in bed for 6 evenings, nose‐breathing in undisturbed conditions. Allergen‐bearing particles (‘halos’) were detected by immunostaining for Der p 1, Der p 2, or Der p 1 and Der p 2 together, and counted by light microscopy. Count data were square root transformed for analysis of variance. Mattress dust samples were assayed for Der p 1 and Der p 2 concentrations.Results Square root detransformed mean particle counts per 30‐min sample were: Der p 1, 4.22; Der p 2, 5.9; Der p 1 + Der p 2, 4.87; and for all samples, 5.01, with no difference between the groups. With replicate samples, halo number correlated significantly with mattress allergen concentrations (Der p 1 r = 0.80, P < 0.01; Der p 2 r = 0.68, P < 0.02).Conclusion Nasal air sampling can be used to quantify nocturnal Der p exposure in undisturbed conditions in an area with moderate exposure to mite allergen and can provide a direct measure of inhaled mite allergen. The choice of either Der p 1 or Der p 2 is appropriate for this purpose.
Eosinophil cationic protein is stored in, but not produced by, peripheral blood neutrophils
Authors: Byström J. , Garcia R. C. , Håkansson L. , Karawajczyk M. , Moberg L. , Soukka J. , Venge P. 
Published: March 2003

SummaryBackground Eosinophil cationic protein (ECP) is an eosinophil‐derived protein, which has been shown to be present in circulating neutrophils.Objective To establish whether ECP is produced or internalized by peripheral blood neutrophils.Methods This was done using microscopy, flow cytometry, fractionation of cells and RT‐PCR techniques.Results No ECP mRNA was detected after extensive cell purification to eliminate all traces of contaminating eosinophils. Examination of immunostained neutrophils by light, confocal, electron microscopy together with cell fraction experiments, established that ECP is present intracellularly and is mostly associated to cell granules. Uptake studies by flow cytometry and by using both cold and radiolabelled ECP showed that it is internalized by neutrophils and stored in some proportion in their primary granules. Upon stimulation with serum‐treated Sephadex particles, the internalized ECP was partially released from cells.Conclusion ECP is not produced but can be internalized by circulating neutrophils, which take it from the environment and partially store it in their primary granules.
Long‐range destruction of Der p 1 using experimental and commercially available ionizers
Authors: Goodman N. , Hughes J. F. 
Published: March 2003

SummaryBackground To reduce the risk of sensitization and the elicitation of allergy symptoms, it is important to reduce the level of allergens in the home. It has previously been demonstrated that corona discharge, the process by which ionizers produce ions, can destroy the major house dust mite allergen Der p 1.Objective In this paper the denaturing efficacy of an experimental ionizer and two commercially available products are evaluated.Methods The first test was conducted in an electrically grounded chamber with samples of Der p 1 placed in various positions for 1, 2 and 3 weeks. The second test was conducted in situ in an unoccupied, furnished office room for 1 week. Der p 1 concentration was quantified by two‐site monoclonal antibody enzyme‐linked immunosorbent assay (ELISA).Results All ionizers in both tests caused significant reductions in allergen concentration (P < 0.05), reaching a maximum of 92% with the experimental ionizer in the chamber after 3 weeks. The percentage reductions observed in situ with the experimental and the larger commercial ionizer were similar, reaching a maximum of 32% at a distance of 4 m away from the experimental ionizer after 1 week of exposure.Conclusion With a revised protocol for use, air ionizers may offer a simple, efficient and inexpensive way to reduce allergen levels in the domestic environment.
Exogenous interleukin‐16 inhibits antigen‐induced airway hyper‐reactivity, eosinophilia and Th2‐type cytokine production in mice
Authors: De Bie J. J. , Jonker E. H. , Henricks P. A. J. , Hoevenaars J. , Little F. F. , Cruikshank W. W. , Nijkamp F. P. , Van Oosterhout A. J. M. 
Published: March 2003

SummaryBackground IL‐16 has been described as a natural soluble CD4‐ligand with immunosuppressive effects in vitro. However, little is known about the effect of IL‐16 on immune responses in vivo.Objective In the present study, we examined the effect of IL‐16 administration in a murine model of allergic asthma. Next, we determined whether these effects were mediated by modulation of CD4+ T lymphocytes.Methods and results Intraperitoneal administration of IL‐16 completely inhibits antigen‐induced airway hyper‐responsiveness and largely decreases the number of eosinophils in bronchoalveolar lavage fluid (> 90%) and airway tissue of ovalbumin‐sensitized and challenged mice. Firstly, it appears that thoracic lymph node cells isolated from in vivo IL‐16‐treated ovalbumin‐challenged animals produce less IL‐4 (77%) and IL‐5 (85%) upon antigenic re‐stimulation, when compared to vehicle‐treated mice. Secondly, pre‐incubation of lymphocytes with IL‐16 in vitro reduces antigen‐induced proliferation (55%) and Th2‐type cytokine production (IL‐4; 56%, IL‐5; 77%). Thirdly, the presence of IL‐16 during priming cultures of TCR transgenic T cells (DO11.10), reduces IL‐4 (33%) and IL‐5 (35%), but not IL‐10 and IFNγ levels upon re‐stimulation.Conclusion It can be concluded that IL‐16 has potent immunosuppressive effects on a Th2‐dominated allergic airway response.
Mast cells and T cells in Kimura's disease express increased levels of interleukin‐4, interleukin‐5, eotaxin and RANTES
Authors: Kimura Y. , Pawankar R. , Aoki M. , Niimi Y. , Kawana S. 
Published: March 2003

SummaryBackground Kimura's disease (KD) is a chronic inflammatory disorder characterized by tumours in the head and neck region, enlarged lymph nodes, increased eosinophil counts and high serum IgE. Mast cells are known to play a central role in IgE‐mediated allergic diseases through the release of inflammatory mediators like IL‐4, IL‐5 and chemokines. We hypothesized that mast cells may play a role in the pathogenesis of KD by regulating eosinophilic infiltration and IgE synthesis.Objective In order to investigate the role of mast cells in the pathogenesis of KD, we examined the expression of cytokines/chemokines in the lesions of KD.Methods We examined the number of tryptase+ cells, EG2+ cells, CD3+ cells, IL‐4+ cells, IL‐5+ cells, eotaxin+ cells, RANTES+ cells and CCR3+ cells in five specimens of KD versus normal tissues by immunohistochemistry. The sources of IL‐4, IL‐5, eotaxin and RANTES and the expression of CCR3 were examined by immunostaining of serial sections with antibodies to IL‐4, IL‐5, eotaxin, RANTES and CCR3, and antibodies to tryptase, ECP (EG2) and CD3.Results Mast cells, activated eosinophils, T cells, IL‐4+ cells, IL‐5+ cells, eotaxin+ cells, RANTES+ cells and CCR3+ cells were all increased in the lesions of KD as compared with those in normal tissue. Mast cells and T cells were the major source of IL‐4, whereas mast cells, T cells and activated eosinophils were the main source of IL‐5. Mast cells, T cells and activated eosinophils were the main source of eotaxin and RANTES.Conclusions The number of IL‐4, IL‐5, eotaxin and RANTES‐expressing mast cells and T cells were increased in the lesions of KD. As mast cells are lesional resident cells, these cells may play an important role in the pathogenesis of KD by regulating IgE synthesis and orchestrating eosinophilic infiltration.
The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma
Authors: Hamilton L. M. , Torres‐Lozano C. , Puddicombe S. M. , Richter A. , Kimber I. , Dearman R. J. , Vrugt B. , Aalbers R. , Holgate S. T. , Djukanović R. , Wilson S. J. , Davies D. E. 
Published: March 2003

SummaryBackground The extent of epithelial injury in asthma is reflected by expression of the epidermal growth factor receptor (EGFR), which is increased in proportion to disease severity and is corticosteroid refractory. Although the EGFR is involved in epithelial growth and differentiation, it is unknown whether it also contributes to the inflammatory response in asthma.Objectives Because severe asthma is characterized by neutrophilic inflammation, we investigated the relationship between EGFR activation and production of IL‐8 and macrophage inhibitory protein‐1 alpha (MIP‐1α) using in vitro culture models and examined the association between epithelial expression of IL‐8 and EGFR in bronchial biopsies from asthmatic subjects.Methods H292 or primary bronchial epithelial cells were exposed to EGF or H2O2 to achieve ligand‐dependent and ligand‐independent EGFR activation; IL‐8 mRNA was measured by real‐time PCR and IL‐8 and MIP‐1α protein measured by enzyme‐linked immunosorbent assay (ELISA). Epithelial IL‐8 and EGFR expression in bronchial biopsies from asthmatic subjects was examined by immunohistochemistry and quantified by image analysis.Results Using H292 cells, EGF and H2O2 increased IL‐8 gene expression and release and this was completely suppressed by the EGFR‐selective tyrosine kinase inhibitor, AG1478, but only partially by dexamethasone. MIP‐1α release was not stimulated by EGF, whereas H2O2 caused a 1.8‐fold increase and this was insensitive to AG1478. EGF also significantly stimulated IL‐8 release from asthmatic or normal primary epithelial cell cultures established from bronchial brushings. In bronchial biopsies, epithelial IL‐8, MIP‐1α, EGFR and submucosal neutrophils were all significantly increased in severe compared to mild disease and there was a strong correlation between EGFR and IL‐8 expression (r = 0.70, P < 0.001).Conclusions These results suggest that in severe asthma, epithelial damage has the potential to contribute to neutrophilic inflammation through enhanced production of IL‐8 via EGFR‐ dependent mechanisms.
Keratinocyte adhesion and the missing link: from Dowling–Meara to Hay–WellsSt John's Hospital Dermatological Society Annual Oration 2000
Authors: McGrath J. A. 
Published: March 2003

Abstract
Maintaining a protective barrier against the environment is an essential function of normal skin. Critical to this role are several structural proteins and glycoproteins that contribute to adhesive junctions linking adjacent keratinocytes and basal keratinocytes to the underlying dermis, as well as other regulatory proteins involved in aspects of epidermal development, differentiation and proliferation. Inherited abnormalities in the genes that encode these components may give rise to a range of genodermatoses, many of which are characterized structurally by a ‘missing’ or perturbed adhesive link and clinically by congenital skin blistering. This oration reviews some of the original clinical descriptions and observations made in this field, as well as providing an update on the corresponding recent molecular discoveries. The emphasis is on contributions made by past and present members of the St John's Hospital Dermatological Society.
Complexities of applying nasal tolerance induction as a therapy for ongoing relapsing experimental autoimmune encephalomyelitis (EAE) in DA rats
Authors: Bai X F , Li H L , Shi F D , Liu J Q , Xiao B G , Van Der Meide P H , Link H 
Published: March 2003

AbstractEAE is an autoimmune disease of the central nervous system (CNS) that serves as an experimental model for the human inflammatory demyelinating disease multiple sclerosis (MS). Antigen-based immunotherapy including soluble antigen administration via feeding has been shown to be successful in treating EAE in rodents. In the present study, we explore nasal administration of small amounts of myelin basic protein (MBP) as a potential means of treatment of protracted, relapsing EAE (PR-EAE) in a novel DA rat system. We found that nasal administration of MBP prevented EAE induced with whole spinal cord homogenate + Freund's incomplete adjuvant (FIA), and strongly down-regulated levels of MBP-reactive interferon-gamma (IFN-γ)-secreting Th1-like cells. However, in rats with ongoing PR-EAE receiving the same regimen of MBP, a trend of aggravated disease was recorded, in conjunction with augmented levels of MBP-reactive IFN-γ-secreting Th1-like splenocytes during the acute phase of EAE. These data have implications for the clinical application of nasal tolerance to autoimmune diseases.
Blockade of IL-12 during the induction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis
Authors: Malfait A M , Butler D M , Presky D H , Maini R N , Brennan F M , Feldmann M 
Published: March 2003

SUMMARYThe effect of blocking IL-12, a potent inducer of interferon-gamma (IFN-γ) and promoter of Th1 cell responses, during the induction phase of CIA was investigated. Arthritis was elicited in male DBA/1 mice by immunizing with type II collagen (CII) in Freund's complete adjuvant. Neutralizing anti-IL-12 antibodies were administered twice weekly from CII immunization. It was found that administration of anti-IL-12 from immunization until the onset of clinical arthritis did not lower the incidence of arthritis, but dramatically attenuated the severity of the disease, both clinically and histopathologically. This regime was associated with reduced IFN-γ levels produced by ex vivo CII-stimulated draining lymph node cells, and with diminished spontaneous ex vivo production of tumour necrosis factor (TNF), IL-6 and IL-10 by freshly isolated synovial cells. Total anti-CII antibody serum levels in these mice were lower than in the controls, but there was no change in the IgG2a/IgG1 ratio. These findings confirm that IL-12 has a major role in the induction of murine CIA and suggests that this disease is propagated, in part, by cells of the Th1 phenotype.