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  • 1
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The chromosomal region 19q13 has been found in linkage to allergic diseases in several genome-wide linkage screens. One candidate gene within this region is the gene coding for TGF-β1. Transforming growth factor (TGF)-β acts as an anti-inflammatory cytokine suppressing allergic inflammation and hyper-reactivity. However, in ongoing inflammation of the lungs it can induce fibrosis and airway remodelling as seen in chronic asthma. Several polymorphisms within TGF-β1 have been identified and one, −C509T, has been shown to be in association with elevated immunoglobulin E levels and severe bronchial asthma in different populations. However, other studies failed to confirm the association. The present study investigated two polymorphisms within the gene coding for TGF-β1, −C509T and G915C, and for their potential association with bronchial asthma in Caucasian children. Genotyping of these polymorphisms was performed by means of restriction fragment length polymorphisms in a population of 231 asthmatic children and a control population of 269 individuals. Statistical analyses made use of the Armitage's trend test. In addition haplotypes were calculated by arlequin. None of the two polymorphisms showed association with bronchial asthma. They were found to be in linkage disequilibrium. We conclude from our data that TGF-β1 is unlikely to represent a major gene in the development of bronchial asthma in the Caucasian population.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis (AD) in infancy. This study is part of a dietary clinical trial in a prospective cohort of healthy term newborns at risk of atopy. It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period. Eight hundred and sixty-five infants exclusively breast-fed, and 256 infants partially or exclusively formula-fed, were followed-up until the end of the first year following birth. AD and sensitization to milk and egg were considered as study end-points. The 1-year incidence of AD was compared between the two study groups. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given. In the breast-fed group, the adjusted OR for AD was 0.47 (95% CI 0.30–0.74). The strongest risk factor was the occurrence of AD in the subject's core family. The risk of infants with AD to be sensitized to milk was four times higher, and to egg eight times higher, than in infants without AD. Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence. We conclude that in infants at atopic risk, exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1399-3038
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to assess the association between keeping pets in early childhood and the occurrence of atopic dermatitis in an ongoing birth cohort followed up to the age of 2 years. We analyzed data of 4578 children in the intervention and observation part of an ongoing cohort study. The children were recruited at birth in the two study regions Wesel and Munich between January 1996 and June 1998. Information on atopic diseases and pet ownership was obtained by questionnaire at the child's first and second birthday. The logistic regression model showed a negative association between ‘keeping any pet’ and in particular ‘keeping dogs’ in the 1st year of life and the development of atopic dermatitis in the 1st and the 2nd years of life. The protective effects remained statistically significant after adjusting for several possible confounding variables (1st yearany pet OR 0.71, 95% CI [0.55;0.92], 1st yeardog OR 0.62, 95% CI [0.39;0.98], 2nd yearany pet OR 0.74, 95% CI [0.57;0.97], 2nd yeardog OR 0.63, 95% CI [0.40;0.98]). Ownership of small furred pets (hamster, rabbit and guinea pig) also showed a borderline protective effect for the 1st year. We assume an association between keeping pets and undefined environmental factor(s) that contribute protectively to the development of atopic dermatitis in early life, presumably by effects on the maturation of the immune system.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Interleukin (IL)-18 regulates the expression of the proinflammatory cytokine interferon (IFN)-γ. The present study sought to test the putative involvement of six different IL-18 gene polymorphisms in pre-disposition to destructive periodontal disease.Methods: A total of 123 patients with periodontitis and 121 healthy controls were genotyped for six IL-18 polymorphisms at position −656, −607, −137, +113, +127 and codon 35/3. Genotyping has been performed by PCR and restriction fragment length polymorphism analysis. The frequencies of alleles and genotypes as well of haplotypes within both study groups were compared using the Pearson Chi-square test at a level of significance of 5% (p〈0.05).Results: Coseggregation was found to be 100% for the two polymorphisms at position −656 and −607 as well as for the polymorphisms at position −137, +113, and +127. The distribution of genotypes for the IL-18 gene polymorphism at position −656/−607 (p=0.854), at position −137/+113/+127 (p=0.320), and at codon 35/3 (p=0.481) was not significantly different among periodontitis patients if compared with healthy control subjects. The distribution of haplotype combinations for the −607 and −137 polymorphism also showed not significant difference between the both study groups (p=0.545).Conclusion: Herein the six different IL-18 gene polymorphisms were not associated with destructive periodontal disease.
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  • 5
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Kindler's syndrome is a rare genodermatosis mainly characterized by the onset of skin blistering in early childhood, web formation of fingers and toes, photosensitivity, and progressive poikiloderma. There is still debate whether this disease represents a distinctive entity in the spectrum of congenital bullous poikilodermas or a variant of dystrophic epidermolysis bullosa.Objective:  To evaluate the recently proposed and debated characteristic immunohistochemical and ultrastructural features of Kindler's syndrome.Patient/methods:  Immunofluorescence (IF) antigen mapping and transmission electron microscopy (TEM) were performed on a skin specimen from non-sun-exposed inner aspect of the upper arm of a 49-year-old patient with characteristic clinical features of Kindler's syndrome.Results:  IF studies revealed focally an extensively broadened, partly reticular staining pattern in the dermoepidermal basement membrane zone (BMZ) with antibodies against laminin-5 and type IV as well as type VII collagen. Anti-α6 and β4 integrin staining revealed small gaps in the linear reactivity in the BMZ. Abundant keratin bodies, as detected by anti-immunoglobulin M (IgM) staining, were focally present in the dermis, indicating prominent epidermal apoptosis. This was verified by a histochemical apoptosis stain [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) reaction]. Transmission electron microscopic examination showed manifold reduplications of the lamina densa (with attached anchoring fibrils) as well as a keratin body surrounded by a fibroblast in the upper dermis.Conclusion:  We present characteristic immunohistochemical and ultrastructural features of Kindler's syndrome identical to those described by Shimizu et al. (Arch Dermatol 1997; 133: 1111) and provide evidence that Kindler's syndrome might primarily be an apoptotic disorder of basal keratinocytes.
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  • 6
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A variety of melanoma-associated antigens have been identified that mediate adhesion, growth, proteolysis, and modulation of immune response. However, the mechanisms by which human normal melanocytes become malignant are not clearly understood. Among the most consistent observations is the up-regulation of fibroblast growth factor-2 (FGF-2) and of the adhesion molecules β3 integrin and Mel-CAM during melanoma progression. To evaluate the potential role of FGF-2, β3 integrin and Mel-CAM in melanoma development we overexpressed FGF-2, β3 integrin and Mel-CAM in normal human melanocytes using replication-deficient adenoviruses as a gene delivery vehicle. Fibroblast growth factor-2 overexpressing melanocytes in monolayer culture displayed cytological atypia. Furthermore, in human skin reconstructs where the physiological milieu is recreated in vitro, FGF-2-overexpressing melanocytes exhibited marked proliferation, upwards migration, cluster formation and type IV collagen expression within the epidermal compartment, simulating early radial growth phase melanoma. In contrast, overexpression of β3 integrin and/or Mel-CAM in melanocytes did not affect their biological behaviour in human skin reconstructs. The described results of the current and previous studies emphasise the key role of FGF-2 in melanoma development and progression, underscoring the promise of FGF-2 as a target for therapy.
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  • 7
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 54 (1999), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 54 (1999), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Contact allergy to methyldibromo glutaronitrile (MDBGN), often combined with phenoxyethanol (PE) (e.g., Euxyl K 400®), increased throughout the 1990s in Europe. Consequently, in 2003, the European Commission banned its use in leave-on products, where its use concentration was considered too high and the non-sensitizing use concentration as yet unknown. The 2 objectives of the study are (a) to find a maximum non-eliciting concentration in a leave-on product in MDBGN/PE-sensitized patients, which could possibly also be considered safe regarding induction and (b) to find the best patch test concentration for MDBGN. We, therefore, performed a use-related test (ROAT) in patients sensitized to MDBGN/PE (n = 39) with 3 concentrations of MDBGN/PE (50, 100 and 250 p.p.m. MDBGN, respectively). A subset of these patients (n = 24) was later patch-tested with various concentrations (0.1, 0.2, 0.3 and 0.5% MDBGN, respectively). 15 patients (38%, 95% confidence interval (CI) = 23–55%) had a negative and 24 (62%; 95% CI = 45–77%) a positive overall repeated open application test (ROAT) result. 13 reacted to the lowest (50 p.p.m.), 8 to the middle (100 p.p.m.) and 3 to the highest concentration (250 p.p.m.) only. In those 13 reacting to the lowest ROAT concentration, dermatitis developed within a few days (1–7). The strength of the initial and the confirmatory patch test result, respectively, and the outcome of the ROAT were positively associated. Of the 24 patients with a use and confirmatory patch test, 15 reacted to 0.1% MDBGN, 16 to 0.2%, 17 to 0.3% and 22 to 0.5%. With the patch test concentration of 0.5%, the number of ROAT-negative patients but patch-test-positive patients increases considerably, particularly due to + reactions. A maximum sensitivity of 94% (95% CI = 70–100%) is reached with a patch test concentration of 0.2%, and is not further improved by increasing the concentration. However, the specificity decreases dramatically from 88 (95% CI = 47–100%) with 0.2% to a mere 12.5% (95% CI = 0–53%) with 0.5%. It can be concluded (a) that for MDBGN 0.2% is very likely the best patch test concentration and (b) that 50 p.p.m. in a leave-on product can elicit contact dermatitis in sensitized persons. We were, therefore, unable to find a safe, still microbicidal, concentration for leave-on products. By contrast, with other contact allergens, dose–response use tests may be able to identify a non-eliciting concentration, which could give valuable clues to a non-inducing (i.e., safe) concentration in products.
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  • 10
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Thiuram mix is tested in the standard series at a test concentration of 1% pet. The single thiurams (DPTD, TMTD, TMTM, TETD), however, are usually tested at 0.25% pet. in Germany. In other countries, the individual components of thiuram mix are tested at 1% pet. The German Contact Dermatitis Research Group (DKG) compared both patch test concentrations in 530 patients in order to find out if (i) a significant number of positive patch tests are missed by testing at the lower concentration, (ii) problems with irritant test reactions occur by increasing the test concentration to 1%, and (iii) the sensitivity of the thiuram mix rises when the breakdown test is done with the higher concentration. Slightly more positive reactions were seen with the higher concentration, but this increase did not reach statistical significance. The reaction index, as a measure for the relation of positive to irritant and/or questionable reactions, remained unchanged for the individual thiurams. The sensitivity of the mix also did not change when the breakdown test was performed with 1% pet. instead of 0.25% pet. Thus, we conclude that both concentrations are of equal diagnostic value in patch testing.
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