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  • 2000-2004  (11)
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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 29 (2004), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although the precise aetiology of lichen sclerosus is unknown, evidence for an autoimmune basis to the disorder is emerging. Indeed, circulating IgG autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been demonstrated in the sera of about 75% of affected individuals. To assess this humoral immune response further, immunoblotting was performed using bacterial recombinant proteins spanning different domains of the ECM1 protein. The aim was to identify autoantibody-reactive sites recognized by 90 lichen sclerosus sera. The subclass distribution of anti-ECM1 IgG autoantibodies was also determined in 54 lichen sclerosus sera. Immunoblotting showed that the IgG autoantibodies from lichen sclerosus patients recognize multiple antigenic reactive sites on the ECM1 protein within both the amino terminus (50/90, 55.6%) and the protein loop cysteine-rich repeat domains (54/90, 60%), although few sera (7/90, 7.8%) had antibodies to the carboxyl terminus of ECM1. IgG subclass analysis revealed that the anti-ECM1 autoantibodies belong predominantly to the IgG2 subclass (48/54, 88.9%), either IgG2 alone (28/54, 51.9%) or in combination with one or more other IgG subclasses. No correlation was found between the site(s) of the ECM1 epitopes or the anti-ECM1 IgG profile and any specific clinical parameters. Nevertheless, characterization of anti-ECM1 antibodies does provide further insight into humoral immune responses and understanding disease mechanisms in lichen sclerosus.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 27 (2002), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary We report a 51-year-old man with a 20-year history of chronic plaque psoriasis who developed an autoimmune subepidermal blistering eruption that had clinical features of bullous pemphigoid, erythema multiforme and epidermolysis bullosa acquisita. Investigations revealed a 1 : 400 titre circulating and in vivo bound IgG autoantibody that mapped to the dermal side of 1 m NaCl-split skin and localized to the lower lamina lucida/upper lamina densa on immunogold electron microscopy. Immunoblotting, using dermal extracts, showed serum binding to antigens of ≈ 200- and ≈ 260 kDa. Indirect immunofluorescence microscopy, using the patient's serum on archival skin sections taken from selected individuals with different forms of inherited epidermolysis bullosa as substrate, showed normal basement membrane labelling on all samples apart from recessive dystrophic epidermolysis bullosa skin (with inherent mutations in the type VII collagen gene): in these cases there was a complete absence of immunostaining. Clinically, the patient responded rapidly to combination treatment with intravenous immunoglobulin and oral corticosteroids, dapsone and mycophenolate mofetil. Autoimmune subepidermal blistering has been reported in other patients with psoriasis, although no specific target antigen has ever been determined. Our study provides preliminary evidence that, for this patient at least, the autoantibody may be targeted against a skin component closely associated with type VII collagen (the epidermolysis bullosa acquisita antigen). Therefore, we propose the term ‘psoriasis bullosa acquisita’ for this and possibly other patients with similar skin eruptions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 28 (2003), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Lipoid proteinosis is an autosomal recessive condition associated with variable scarring and infiltration of skin and mucosae. The disorder has recently been shown to result from loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1) on 1q21. Extracellular matrix protein 1 has important physiological and biological roles in aspects of epidermal differentiation, binding of dermal collagens and proteoglycans, and in regulation of angiogenesis. Thus far pathogenic mutations have been described in 16 different families with lipoid proteinosis throughout the world. In this report, we describe the clinico-pathological features of a 10-year-old boy with lipoid proteinosis from a consanguineous Libyan family. By direct sequencing of the affected individual's genomic DNA, we identified a homozygous nonsense mutation in exon 2 of the ECM1 gene, Q32X. This mutation is the most 5′ of all ECM1 mutations described thus far and is predicted to ablate the ECM1a, ECM1b and ECM1c splice variants of the ECM1 gene and to result in a severe clinical phenotype. Sequencing of DNA from the affected individual's five siblings revealed that four were heterozygous carriers of Q32X, findings that have important implications for genetic counselling given the high frequency of consanguineous marriages in Libya.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Transforming growth factor (TGF) -β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-β are biologically latent complexes, activation is essential for TGF-β-mediated cellular responses in vitro and in vivo. Objectives Here we report the response of the TGF-β regulation system to 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. Results 1,25(OH)2D3 caused a dose-dependent induction of latent and active TGF-β1 proteins in both cell cultures. The increases were significant over 72 h, but not within 48 h after stimulation. The time course of TGF-β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF-β2 and -β3, other mammalian isoforms , were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Co-incubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-β1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-β1 protein production. The late induction of TGF-β1 mRNA was partially blocked by adding isoform-specific antibodies to TGF-β1, -β2 and -β3, indicating TGF-β autoregulation. Despite these marked responses, there were no significant differences in the TGF-β expression between normal and psoriatic fibroblasts. Conclusions These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-β regulation in local dermal fibroblasts.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 73 (2002), S. 1169-1176 
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: A three-channel heterodyne O-mode reflectometer system has been developed for density fluctuation measurements on the JT-60U tokamak. The system consists of one fixed channel with a frequency of 34 GHz and two selectable frequency channels with frequencies in the range of 34–40 and 48–50 GHz in order to measure the change of fluctuation amplitude, fluctuation coherence, and movement of the cutoff layer during the discharge. The reflectometer system has now become a standard diagnostic for density fluctuation measurements on JT-60U covering both core and edge plasma regions. The capabilities of the system are illustrated for three experimental cases: edge transport barriers in H-mode plasmas, internal transport barriers in reversed shear plasmas, and fast turbulence burst at the onset of multifaceted asymmetric radiation from the edge. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 28 (2003), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Lichen planus pemphigoides (LPP) and pemphigoid nodularis are rare clinical variants of bullous pemphigoid (BP), which are characterized by histological findings of lichen planus (LP) and nodular prurigo, respectively, and the finding of linear deposits of IgG and/or C3 at the basement membrane zone in perilesional skin. In both cases bullae may arise at the site of pre-existing LP-like or nodular prurigo-like eruptions, and clinically uninvolved skin. The disease spectrum of LPP and pemphigoid nodularis differs from that of classical BP phenotype, and their presentations are often indolent. LPP may predominantly affect a younger age group and is responsive to standard treatments used in acquired autoimmune bullous diseases, while pemphigoid nodularis is more common in elderly women and is relatively resistant to therapy. We describe a patient who had LPP for nearly two decades and subsequently developed a nodular eruption with a concurrently detected antibullous pemphigoid antigen 2 (BP180) autoantibody. His overall clinicopathological features were indicative of LPP evolving into another BP variant, pemphigoid nodularis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Recent epidemiological studies indicate that antibiotic use in infancy may be associated with an increased risk of developing atopy. Our previous work on animals demonstrated that kanamycin use during infancy promotes a shift in the Th1/Th2 balance towards a Th2-dominant immunity.Objective The first purpose of this study is to clarify whether or not the supplementation of intestinal bacteria can reverse such a Th2-skewed response induced by neonatal antibiotic use. The second objective is to elucidate the contribution of genetic factors to antibiotic-induced immune-deviation.Methods BALB/c or C57BL/6 mice at 3 weeks of age were orally administered 600 µg/day of kanamycin sulphate for seven consecutive days. Thereafter, the mice were inoculated with one type of intestinal bacterial species: Enterococcus faecalis, Lactobacillus acidophilus or Bacteroides vulgatus. Blood samples were collected 10 weeks after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on Th1/Th2 balance was evaluated based on in vivo antibody levels.Results A kanamycin-induced elevation of the serum IgE levels was reversed by the supplementation with Enterococcus faecalis, and to a lesser extent by that with Lactobacillus acidophilus. The IgE/IgG2a ratio in the mice supplemented with Enterococcus faecalis significantly decreased in comparison with that in the kanamycin-treated mice without any bacterial supplementation, while such a ratio was enhanced in the mice inoculated with Bacteroides vulgatus. No antibiotic-induced Th2-skewed response was seen in C57BL/6 mice that are genetically biased towards Th1-dominant immunity.Conclusion These results suggest that adequate probiotic intervention after antibiotic treatment may improve the intestinal ecosystem, and thereby prevent the Th2-shifted immunity induced by neonatal antibiotic use. In addition, the difference of genetic backgrounds also contributes to such an antibiotic-induced Th2-skewed response.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 151 (2004), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Bullous pemphigoid (BP) is the most common subepidermal immunobullous disease, characterized by circulating IgG autoantibodies targeting BP180 and BP230 hemidesmosomal proteins. Several immunological studies have demonstrated that the membrane proximal noncollagenous domain NC16a of BP180 is the immunodominant region targeted by BP autoantibodies. Recently, a commercial BP180 NC16a-specific enzyme-linked immunosorbent assay (ELISA) has become available for detecting pathogenic anti-BP180 autoantibodies in BP sera. However, it remains unclear whether the diagnostic potential of the ELISA is equivalent to that of the ‘gold-standard’ diagnostic technique of immunofluorescence (IF).Objectives  To examine the usefulness of a commercially available BP180-NC16a ELISA in the initial serodiagnosis of BP.Methods  Sera from a large cohort of patients with BP (n = 102) and control subjects (age- and sex-matched normal volunteers, n = 60; pemphigus foliaceus, n = 18; pemphigus vulgaris, n = 16) were assayed by BP180-NC16a ELISA. All BP sera were obtained at presentation before initiation of systemic immunosuppressive therapy. The values of IgG antibody levels measured by ELISA were compared with those measured by indirect IF on salt-split skin.Results  Receiver operating characteristic analysis was used to calculate the cut-off value for the ELISA in the diagnosis of BP which maximizes both sensitivity and specificity, and to estimate the diagnostic accuracy of the ELISA as represented by the area under the curve (AUC = 0·965). A cut-off value of 9 was associated with a sensitivity of 89% (91 of 102 BP sera showed a positive result) and a specificity of 98%. Fifty-eight of 60 normal controls and all the pemphigus sera showed a negative result. There was a correlation between the mean ELISA values and indirect IF titres (Spearman rank correlation 0·286; P = 0·004).Conclusions  Our results suggest that the BP180-NC16a ELISA is a useful tool for the detection of pathogenic anti-BP180 IgG autoantibodies at the initial disease stage of BP. Because it is not only highly sensitive and specific, but is also easy to perform, is objective, and semiquantitative, the ELISA may provide valuable information for the accurate and reliable serodiagnosis of BP.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 149 (2003), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 148 (2003), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background Identification of antigens by immunoblotting techniques, using epidermal and dermal extracts, is regarded as essential for making a definitive diagnosis in autoimmune bullous diseases (AIBDs). These procedures involve epidermal–dermal separation for subsequent protein extraction, which may result in partial loss of some antigenic polypeptides and changes in the conformational epitopes targeted by autoantibodies in AIBDs. It may therefore be necessary to use different substrates for consistent results. Objectives To evaluate the usefulness of human placental amnion extract as a substrate for immunoblotting in the diagnosis of AIBDs. Methods We checked the structural components of the desmosomes and basement membrane zone (BMZ) of amnion by electron microscopy. Using immunofluorescence and immunoblotting techniques, we tested the amnion immunoreactivity with antibodies to desmosomal and BMZ proteins, and with sera from 76 patients with AIBDs including pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid (BP), pemphigoid gestationis, linear IgA bullous dermatosis, epidermolysis bullosa acquisita, paraneoplastic pemphigus and mucous membrane pemphigoid. Results The desmosomes and BMZ of the amnion tissue were ultrastructurally similar to those in skin. Antigen mapping confirmed that amnion contains all the proteins that were recognized by a panel of monoclonal and polyclonal antibodies. Immunoblotting showed that the antibodies clearly detected bands corresponding to desmogleins 1 and 3, desmocollins 1 and 2, desmoplakins 1 and 2, three subunits (α3, β3 and γ2) of laminin 5, BP antigens 1 and 2, the 97-kDa LAD antigen and type VII collagen. In addition, most of the patient sera (82%) reacted exclusively with their respective antigens. Conclusions Harvesting proteins from amnion does not require epidermal–dermal separation, and a sufficient yield of desmosomal and hemidesmosomal proteins can be obtained. Therefore, amnion may be a more reliable source of substrate than skin samples for immunoblot analysis of AIBDs.
    Type of Medium: Electronic Resource
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