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  • 11
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Pediatric allergy and immunology 8 (1997), S. 0 
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is an increasing interest in the concept that respiratory tract infections during early childhood may in some circumstances confer protection against sensitisalion 10 ueroallergens, via “bystander” stimulation of Th-1 associated immune functions in the regional lymph nodes draining the airway mucosa. We hypothesise below that this phenomenon may be but one component of a broader process operative during early postnatal life, in which generalised contact with the microbial environment plays an obligatory role in stimulating the functional maturation of the Th-1 arm of the immune response. We argue further that one of the most potent sources of such stimulation is provided by the normal commensal flora of the gasirointesiinal tract, which is establish during early infancy.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The study below comprises prospective analysis of patterns of allergen-specific T-cell reactivity in a cohort of 23 children bled at'regular intervals from 6–10 weeks to 2 years of age, together with cross sectional studies on panels of cord and adult blood samples. The results indicate reciprocal patterns of responses to dietary and inhalant allergens, the former being frequent in infancy but rare in adults, whereas the latter are preserved and expand between infancy and adulthood. These findings are consistent with a recently proposed model for the development of immunity to environmental allergens which involves allergen-driven T-cell “selection” during early life leading to deletion of food allergen-specific T-cells via the induction of specific anergy, with concomitant selection and ultimately expansion of mutually exclusive TH-1-like or TH-2-like reactivity to inhalant allergens via Immune Deviation mechanisms.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Pediatric allergy and immunology 1 (1990), S. 0 
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The early postnatal period has been identified as a time of increased risk lor primary sensitisation to aeroallergens. The expression of the allergic phenotype is predominantly genetically determined but is influenced by a myriad of environmental factors. The underlying mechanisms for allergic sensitisation to inhalant allergens have been investigated in both humans and experimental animal models. Data from the literature in both these areas are in agreement that the nature of the initial response of the T-cell arm of the immune system to first encounters with an aero-allergen can potentially determine whether allergic sensitisation will occur and be manifest in later life as allergic respiratory disease. The combination of exposure to environmental “risk factors” along with the immaturity of the mucosal component of the infant's immune system may provide a basis for the increased risk of allergic sensitisation in early childhood.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 26 (2001), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tear gas is used throughout the World for control of riots and civil disobedience. CS gas as used by the UK police force is issued as a ‘spray’ and is 5% CS in methylisobutylketone (MIBK), a potent irritant. Assaults on police officers in forces issued with CS spray have fallen significantly over the past 3 years, whilst having risen in areas without it. Thus, CS gas appears to be an effective deterrent. However, significant cutaneous reactions can occur as a result of exposure. We report a severe contact dermatitis to CS gas to highlight the clinical features. The nature of CS gas and potential cutaneous adverse reactions are discussed.
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background It is widely held that in vitro T cell responses to allergens are more prominent in atopic than in normal individuals, though this conclusion is based upon culture techniques which fail to detect proliferative responses in a significant minority of atopies and many normals.Objectives: Study allergen-specific proliferative responses of T cells cultured in serum-free medium (SFM). Examine associations between atopic status, age and T cell reactivity.Methods Initially, peripheral blood mononuclear cells were stimulated with allergens or antigens in SFM, and compared with cells cultured in RPMI + 10% fetal calf serum or human AB serum. Subsequently, T cell reactivity was studied in 34 adults (20–49 years), 27 children (2–13 years), and 19 infants (≤ 10 weeks) using SFM alone. Results Compared with serum-supplemented medium, SFM enhanced net T cell proliferation, both in bulk culture and when cloning at limiting dilution. In many subjects, SFM unmasked T cell reactivity to allergens which was not otherwise evident, and lowered the threshold allergen levels required for in vitro T cell triggering. For most allergens, T cell proliferative responses did not differ between adults who had specific IgE, and those who did not. The most vigorous responses observed were to ubiquitous inhalant allergens, which stimulated T cells from close to 100% of adults and children, and over 60% of infants. In contrast, responses to the ‘vaccine’ antigen tetanus toxoid were completely absent in the latter age group, but present in the majority of adults and children.Conclusions These findings suggest that the extent of active T cell recognition of environmental allergens has been hitherto underestimated, and further that these responses may frequently be initiated in very early life. Additionally, these findings reinforce the notion that qualitative (as opposed to quantitative) variations in specific T cell reactivity ultimately determine allergen responder phenotype.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent in vitro studies suggest that IgE production in adults is co-ordinately regulated by negative signals from γIFN-producing CD4+ T-helper-1 (TH-1) and positive signals from IL-4 producing (TH-2) T-cells. Additionally, seroepidemiological evidence has pinpointed infancy as the period of maximum lifetime risk for T-cell sensitization to ubiquitous environmental antigens. The present study sought to elucidate the relationship between these observations, by examination of CD4+ T-cell function in normal children and those genetically at‘high risk’ for atopy, spanning the age range (up to 4 years) in which IgE responses to environmental allergens is typically manifest. Immunocompetent T-cell precursor frequencies (determined by cloning at limiting dilution) were markedly reduced in ‘high risk’ children relative to normals (0.53.0.29 vs 0.26.0.19; P= 0.0025). Consistent with reports from other laboratories employing bulk T-cell culture techniques, the γIFN producing capacity of CD4+ T-cell clones from both groups of children were markedly reduced relative to adults, and was lowest in the high risk group (P〈0.02). IL-4 production by CD4+ T-cell clones from the normal children was within the adult range, but again was significantly lower in the high risk group (P〈0.00005). This indicates that initial immune responses to environmental allergens in early childhood occur against a background of maturational ‘deficiency’ in CD4+ T-cell function, and suggests the possibility that variations in the rate of postnatal maturation of T-cell competence may be a contributing factor in the development of differing patterns of immunological responsiveness to environmental allergens.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 19 (1989), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this report we have employed an alternative tissue-sectioning procedure which provides a plan view of intra-epithelial cell populations within the airway wall. Immunoperoxidase staining of such sections for class II MHC (Ia) antigen revealed the presence of a highly developed intra-epithelial network of Ia-positive dendritic cells, which was not evident employing conventional cross- or longitudinal tissue sections. This finding has important implications for the study of mechanisms underlying allergic and infectious diseases of the respiratory tract.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Inhaled corticosteroids may produce systemic effects which include decreased hypothalamic pituitary-adrenal (HPA) axis activity. Four tests of HPA axis function were assessed in 12 healthy volunteers, during inhalation of two actuations of beclomethasone dipropionate (250 μg) aerosol four times daily for 15 days, to determine the most appropriate test for this effect of inhaled corticosteroids. Measurement of basal adrenal activity showed that both 24-hr urinary free cortisol and 0900 hr plasma cortisol were decreased by the fourth day of steroid treatment. All 12 subjects had decreases in basal adrenal activity. Overall the 24-hr urinary free cortisol showed the greater change, with mean pre-steroid baseline values of 497 and 515 nmol/24 hr reduced to 167 nmol/24 hr on the ninth day of treatment (P 〈 0.001). The single-dose metyrapone test showed marked changes in each of the six subjects tested. The mean 11-deoxycortisol response was 96 nmol/l on the eleventh day of treatment, compared to baseline and eighth-day post-treatment values of 439 and 407 nmol/1 respectively (P 〈 0.001). In contrast, no consistent treatment-related changes were observed with the short tetracosactrin test. Only two out of six subjects had an abnormal short tetracosactrin test, although all showed a decrease in basal adrenal activity. From these results, the 24-hr urinary free cortisol and single-dose metyrapone test at 0600 hr are recommended to assess the effect of inhaled glucocorticoids on the HPA axis. The short tetracosactrin test failed to detect an effect from the same dose of inhaled beclomethasone dipropionate and cannot therefore be recommended to exclude the systemic effect of an inhaled steroid.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 29 (1999), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent evidence suggests that the development of chronic allergic respiratory disease is a biphasic process. Phase 1 commonly occurs during early childhood and in many instances appears to be initiated in utero. This involves initial priming of the Th-cell system against ubiquitous environmental allergens, and subsequent reshaping of these responses during infancy into Th1- or Th2-polarized immunological memory. The second phase of the process comprises the repeated expression of Th2-polarized allergen-specific immunity at the level of the airway mucosa, producing cumulative damage to local tissue resulting ultimately in phenotypic changes including development of airways hyperreactivity. It is also clear that this second phase occurs in only a relatively small subset of subjects who develop long-term Th2-polarized allergen-specific immunity, given that the majority of skin prick test positive subjects do not develop chronic airways disease. This suggests that an additional set of control mechanisms, which regulate the intensity/duration of local Th-cell responses within airway mucosal tissues, may play an important role in the ultimate expression of chronic immunoinflammatory disease in the airways in ‘at risk’ atopic subjects.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background There is increasing evidence that the T-cell reactivity to environmental allergens underlying expression of allergic disease in adulthood, develops initially during childhood. However, there is little information available on the kinetics of these early responses, or on the patterns of cytokine production during this period.Objective The purpose of this study was twofold: to obtain further information on the reported differences between responses to food versus inhalant allergens during early childhood, and to ascertain the age-range over which T-cell responses to inhalant allergens become polarized towards the TH2 cytokine profile, in potentially atopic children.Methods In vitro cytokine responses to house dust mite (HDM) and egg (OVA) were assessed by semiquantitative RT-PCR in panels of 2- and 5-year-old children and adults; lymphoproliferative responses to OVA were subjected to epitope analysis.Results At age 2 years IL-4/IL-5 responses to HDM grouped with positive atopic family history, and by age 5 years cytokine responses correlated strongly with individual SPT reactivity to HDM. In contrast, OVA responses were restricted to weak and transient IL-5 signals in the 2-year-old family history positive group. Lymphoproliferation assays performed in parallel indicate a log-scale greater postnatal expansion of T-cell reactivity to the inhalant allergen; preliminary epitope analysis of OVA responses indicate that the number of OVA epitopes recognised decrease during early childhood.Conclusions Inhalant allergen-specific in vitro cytokine production associated with positive skin-prick test (SPT) reactions, one of the hallmarks of adult atopy, manifests in children at or before 5 years of age; additionally, cytokine responses in SPT negative 5 year-olds are restricted to IFNγ, as per normal adults. In contrast, T-cell responses to a typical food allergen appear to be deleted during early childhood.
    Type of Medium: Electronic Resource
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