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  • 1
    ISSN: 1432-1211
    Keywords: Key words Skin ; Genetics ; TNFA ; ¶Inflammation ; PCR-RFLP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) α-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for theTNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Endothelial leucocyte adhesion molecule-1 (ELAM-1) is a recently described endothelial surface glycoprotein which is inducible by interleukin 1 (IL-1). tumour necrosis factor-alpha (TNF-α) or bacterial lipopolysaccharide (LPS). Using an immunohistochemical technique and a monoclonal antibody (1.2B6) specific for ELAM-1 we have found marked vascular endothelial expression of ELAM-1 in many cutaneous inflammatory disorders, including allergic contact dermatitis, atopic dermatitis and psoriasis, and in dermal infiltrates associated with benign, premalignant and malignant keratinocyte proliferation. In normal skin, minimal levels of ELAM-1 expression were detected. In psoriasis, double immunoenzyme staining studies revealed a close spatial relationship between ELAM-1 expression and neutrophil margination, suggesting a functional link. Recombinant human interferon-7 (30 μg) injected intradermally in normal adult human volunteers did not substantially upregulate ELAM-1 in contrast to its marked effect on intercellular adhesion molecule-1 (ICAM-1) expression, indicating that this cytokine is probably not involved in ELAM-1 induction in vivo. These results indicate that ELAM-1 is widely induced in cutaneous inflammation with a time course of expression that is longer than that observed in vitro.As ELAM-1 acts as an adhesion ligand for neutrophils. and perhaps monocytes. the expression of this molecule in cutaneous lesions is likely to he an indication of the ability of vascular endothelium to recruit these cells from the circulation. Furthermore, the cytokine inducibility of ELAM-1 is indirect evidence for functional interactions between perivascular mononuclear cells, other resident cells and the blood vessel wall.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Experiments were performed to examine the hypothesis that the surface expression of HLA-DR by keratinocytes in certain disease states is conferred by the activity of gamma-interferon, derived from dermal activated T lymphocytes. In vivo studies revealed a spatial relationship between keratinocyte HLA-DR expression and activated T lymphocytes within the dermal inflammatory infiltrate. In vitro studies confirmed that gamma-interferon can induce keratinocyte synthesis of HLA-DR. These results suggest that, in vivo, gamma-interferon produced by activated T lymphocytes induces keratinocyte HLA-DR synthesis and expression.
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  • 4
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Several cutaneous disorders are characterized by keratinocyte expression of HLA-DR. Using an immunohistochemical assay we have observed that expression is maximal where the dermal lymphocytic infiltrate is most intense. This finding is consistent with induction of keratinocyte HLA-DR expression by gamma-interferon, released by activated T-lymphocytes. In atopic dermatitis and psoriasis, where T-lymphocytes are also observed within the infiltrate, keratinocytes do not express HLA-DR.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: PSORS1 on chromosome 6p21.3, which contains the MHC, is a major susceptibility locus for psoriasis vulgaris. This region is characterized by strong linkage disequilibrium and contains the corneodesmosin (CSDN) gene, an attractive candidate for psoriasis susceptibility based on its putative biological function in keratinocyte adhesion, and HLA-Cw6, an established marker for psoriasis susceptibility. We compared two genetically independent populations in order to define the major psoriasis susceptibility gene, a British Caucasian population comprising parent–offspring trios analysed by the transmission disequilibrium test (TDT) and a Japanese case–control population. All individuals were investigated for CDSN polymorphism (+619, +1236, +1240 and +1243) and HLA-C association. Our data confirms strong association with HLA-Cw6 and CDSN allele 5 (+619T, +1240G, +1243C) in the Caucasian cohort (TDT, P = 5.4 × 10−6) and in addition defines this region further by identifying a high-risk CDSN haplotype (allele 5 and +1236T, P = 8.5 × 10−8). In contrast no association was observed in the Japanese cohort for any HLA-C or CDSN alleles. This data supports a role for the CDSN gene in Caucasian populations with psoriasis. However the lack of association with HLA-Cw6 and CDSN alleles in Japanese psoriasis patients may be because Japanese patients exhibit a form of psoriasis similar to late onset or Type II psoriasis vulgaris in contrast to early onset or Type I disease characterizing our Caucasian population.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The use of combination oral therapies in the management of severe psoriasis is gaining increasing acceptance. We report the concurrent use of mycophenolate mofetil (MMF) (maximum dose 3.0 g daily) with low-dose cyclosporin (mean dose 2.5 mg/kg/day) in nine patients with severe psoriasis. All had previously failed on other systemic therapies. They were all initially on treatment with cyclosporin alone which had either failed to clear their psoriasis or they were unable to tolerate higher doses. After the addition of MMF there was good clinical improvement in three patients and moderate disease control in a further four patients after a follow-up period of 3–11 months, with no additional evidence of toxicity at the doses used. We believe that MMF may be useful in some psoriatic patients unresponsive to or intolerant of other treatments or who are at risk of developing nephrotoxicity at higher doses of cyclosporin.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Reduced bone mineral density (BMD), the major risk factor for osteoporotic fracture, has been linked to palmoplantar pustular psoriasis, but no significant studies have examined BMD in chronic plaque psoriasis (CPP). In this study, in-patients with severe CPP had their BMD measured at the nondominant hip and lumbar spine using dual energy X-ray absorbtiometry. Ten male and 10 female Caucasian patients were recruited, with a mean age of 47 years (range 20–71 years). There were no significant differences in BMD between patients and controls. However, patients with psoriatic arthropathy in addition to CPP had a significantly lower mean lumbar spine Z-score (− 1.16) than those without arthropathy (+1.38, P = 0.015). Neither previous nor current treatment with systemic steroids, retinoids or methotrexate significantly affected BMD. We found no evidence that patients with CPP, despite risk factors, have a significantly low BMD, although the subgroup with joint involvement appear be at significantly higher risk of osteoporosis and may therefore require preventative treatment.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Exorex is a new topical formulation for the treatment of psoriasis; it contains 1% coal tar and a synthetic analogue resembling components identified in banana skin (a complex of esterified essential fatty acids). To determine whether the esterified essential fatty acid complex confers any therapeutic advantage over coal tar alone, patients with chronic plaque psoriasis (n = 20) were entered into a double-blind, randomized, right/left comparison of Exorex, and Exorex without the essential fatty acid component (known hereafter as coal tar control) for 8 weeks. Target plaques were scored (0–4) for erythema, desquamation and infiltration at day 0 and at 2 week intervals throughout the study. No significant differences were detected between Exorex and coal tar control with respect to changes in the summed scores at baseline and following 8 weeks of treatment (mean difference in summed score changes from baseline between Exorex and coal tar control 0.2, 95% confidence interval − 0.44 to 0.84; P = 0.52) or in the area under the response–time curve (P = 0.16). Mean percentage improvement in summed scores of target plaques were 53.9% (SE = 4%) and 56.1% (SE = 4.9%) for Exorex and coal tar control, respectively. Results suggest that the complex of esterified essential fatty acids is not exerting any clinically important therapeutic effect in the treatment of chronic plaque psoriasis.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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