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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 98 (1978), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The percentages of lymphocytes carrying different classes of membrane-bound Ig, and lymphocytes forming rosettes with sheep erythrocytes (E-RFC), as well as lymphocytes with receptor for the Fc-part of IgG (EA-RFC) were determined in 19 patients with atopic dermatitis. Lymphocyte suspensions were also stained with a specific rabbit anti-human T-lymphocyte antiserum. Furthermore, the serum concentration of IgG, IgA, IgM and IgE and the complement factors C3 and C4 were measured. A small but significant increase in lymphocytes with membrane-bound IgE and an increase in the serum concentration of IgE and complement factor C4 were observed. A decrease in the percentages of lymphocytes with receptors for sheep erythrocytes (E-RFC) was also found. The percentages of lymphocytes that stained with the anti-T antiserum correlated well with the percentages of lymphocytes forming rosettes with sheep erythrocytes. In one patient we found increased IgE positive lymphocytes, increased IgE serum concentration and a decreased T-cell number.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Contact dermatitis 42 (2000), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin-12 (IL-12) has previously been suggested as playing a major rôle in the activation of cytotoxic lymphocytes. Recent reports indicate that cytotoxic CD8+ cells are critically involved in the elicitation phase of contact hypersensitivity reactions. In this study, the in situ expression of IL-12 was investigated in normal human skin and in allergic contact dermatitis by immunohistochemistry. Skin biopsy specimens were obtained from allergic patch test reactions after 3 days, and from normal skin in 8 subjects. In contrast to normal skin, a strong enhancement of IL-12 immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. IL-12 immunoreactivity was mainly located in the cytoplasm of dermal dendritic cells and macrophages as well as of some Langerhans cells. IL-12-positive cells were often found in close apposition to lymphocytes. Furthermore, positive immunostaining was also detected in keratinocytes at sites of marked exocytosis and spongiosis in the epidermis. In conclusion, the enhanced in situ expression of IL-12 may contribute to the activation of cytotoxic lymphocytes and thereby represent an important factor in the pathogenesis of contact hypersensitivity reactions in humans.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 21 (1985), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human epidermal cell suspensions (EC) were obtained by the suction blister technique and enzyme digestion. EC were irradiated in microtitre plates with doses up to 510 mJ/cm2 (2.6 minimal erythemal dose (MED)) by means of fluorescent light bulbs emitting a 280-320 nm continuous spectrum with a peak at 310 nm. Purified allogeneic T cells were added to the EC immediately or 24 h after radiation. Irradiated EC were pulsed with purified protein derivative (PPD) for 90 min immediately or 24 h after radiation and then cocultured with purified autologous T cells. PPD-pulsed EC were also irradiated before being cocultured with autologous T cells. Pretreatment of EC suspensions with anti-DR antiserum plus complement abolished both the alloactivating and the antigen-presenting capacity, indicating that the DR-positive Langerhans cells are mainly responsible for these functions. There were no differences in the number of DR-positive cells in EC before or immediately after radiation. A statistically significant and UV-dose-dependent reduction of the alloactivating ability of EC was found both when allogeneic T cells were added immediately and when they were added 24 h after radiation. Likewise, a significant and dose-dependent reduction of the PPD-specific T-cell response was obtained in cultures when using irradiated EC that were PPD-pulsed immediately or 24 h after radiation. EC that were first PPD-pulsed and then irradiated induced a significantly increased T-cell response after low UV doses (1 or 2 MED), whereas higher doses induced a significant reduction of the T-cell responses.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 11 (1980), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human epidermis was separated from dermis by means of a suction blister device and dissociated with trypsin. The epidermal cell suspensions obtained contained 3–5% Langerhans cells as judged by immunofluorescence staining of the cells with a rabbit anti-DR antiserum. The epidermal cells were co-cultured with purified allogeneic T cells and with autologous T cells with or without PPD of tuberculin. A strong T-cell response to allogeneic epidermal cells was obtained, as was a strong T-cell response to PPD, provided autologous epidermal cells were also present. Pre-treatment of the epidermal cells with anti-DR antiserum plus complement abolished both these responses. These data indicate that epidermal cells are able to substitute for macrophages both in the allo-activating and in the antigen-presenting function. Since the responsible cells were DR-positive, it is highly probable that the cells responsible for these functions are the Langerhans cells.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear.Objective In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients.Methods During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests.Results Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4+ and/or CD8+ T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4+ T cells dominated; a higher percentage of circulating CD8+ T cells was found in patients with bullous skin reactions or hepatic involvement.Conclusion Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8+ T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4+ cells elicits mainly maculo-papular reactions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 7 (1998), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CDla, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-α and IFN-γ) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CDla, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non-melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5-aminolaevulinic acid (5-ALA)-based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein-I/ret (MT-ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5-ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT-ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5-ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5-ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT-ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT-ret melanoma cells are vulnerable to 5-ALA PDT in vitro, malignant MT-ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The rapidly increasing incidence and mortality rate of malignant melanoma, together with the lack of efficient treatment of the late stages, makes it a serious threat to public health. Innovative new treatments are needed. The proteins of the ras-family of proto-oncogenes, functioning as relay switches for signalling pathways between cell surface and nucleus, are involved in cell proliferation, differentiation, apoptosis and transformation. If over-expressed or mutated they can induce and/or maintain a transformed state of a cell. Codon 61 mutations of N-ras seem to be involved in melanoma development on sun exposed sites. In order to induce an immune response towards mutated N-ras proteins we performed a phase 1 feasibility study. Ten melanoma patients were immunized intradermally 6 times with N-ras peptides (residue 49–73) with 4 codon 61 mutations using GM-CSF as adjuvant. HLA typing was not used as an inclusion criterion. Eight patients responded with strong delayed type hypersensitivity reactions. In 2 of the patients an in vitro response to the vaccine could also be detected. The specificity of the reaction could be confirmed by cloning of peptide-specific CD4 positive T cells from peripheral blood of the patients. Intradermal injection of ras peptides using GM-CSF as adjuvant is simple to perform and seems to be efficient in inducing cellular immune responses. Since a majority of the patients showed positive skin reactions and 2 of the patients analysed showed a T-helper response to this melanoma specific antigen, these promiscuous HLA class II binding mutant ras peptides may be candidates for inclusion into vaccine cocktails containing various established CTL epitopes.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 35 (1996), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent data suggest a key rôle for IL-1β in the induction phase of allergic contact dermatitis. In the present study, (he protein levels of IL-1β were measured in skin lymph derived from normal untreated skin as well as from irritant and allergic (induction and elicitation phase) contact dermatitis. IL-1β increased in the course of both types of contact dermatitis, displaying the highest levels in irritant CD. Using a reverse transcriptase-polymerase chain reaction, low signal strength of IL-1β mRNA was demonstrated in lymph cells derived from normal skin and allergic CD. In lymph cells collected 2 × daily during the induction phase of allergic contact dermatitis, no upregulation of the IL-1β mRNA signal was found. Isolated CD 1a+ lymph cells derived from normal skin us welt as from the induction and elicitation phase of allergic contact dermatitis did not express IL-1β mRNA. Our results demonstrate that in human skin lymph, the IL-1β p profiles do not discriminate between irritant and allergic contact dermatitis and that besides resident epidermal and dermal cells, circulating lymph cells may also contribute to 1L-1β protein production.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  In several clinical trials the topical application of pimecrolimus was shown to be effective in the treatment of atopic dermatitis (AD). By targeting calcineurin-dependent signaling pathways, pimecrolimus controls cytokine gene expression. The purpose of this study was to investigate the effect of pimecrolimus on the inflammatory infiltrate and cytokine expression pattern in AD upon topical therapy.Methods:  From 10 patients with acute AD, skin biopsies as well as immunophenotype and cytokine production of peripheral blood mononuclear cells (PBMC) were examined before and 3 weeks after therapy.Results:  The clinical improvement was associated with a marked regression of histopathological features. In particular, the density of the inflammatory infiltrate mostly containing lymphocytes and eosinophils declined. By double immunofluorescent staining, a reduced expression of the T helper (Th) 2 cytokines interleukin (IL)-5, IL-10, and IL-13 in both CD4+ and CD8+ T cells was demonstrated after therapy. Pimecrolimus therapy was also associated with a reduced expression of the Th1 cytokine interferon (IFN)-γ. Interestingly, the numbers of epidermal CD1a+ dendritic cells increased following treatment. In the peripheral blood, a decrease of lymphocytes and eosinophils was noticed, but the distribution of lymphocyte subpopulations and their capacity of cytokine production did not change.Conclusions:  Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.
    Type of Medium: Electronic Resource
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