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  • 1
    Electronic Resource
    Electronic Resource
    Prostaglandin E2 suppresses phytohemagglutin-induced immune responses of normal human monoculear cells by decreasing intracellular glutathione generation, but not due to increased DNA strand breaks or apoptosis (1993)
    Springer
    Inflammation research 40 (1993), S. 191-199 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostaglandin E2 (PGE2) at concentrations more than 1×10−8 M markedly suppressed the cell proliferation and release of soluble molecules of interleukin-2 receptor (sIL-2R), CD4 (sCD4) and CD8 (sCD8) from phytohemagglutinin (PHA)-stimulated normal human mononuclear cells (MNC) in a dose-related manner. To further elucidate the subcellular mechanism of the inhibitory effect of PGE2 on PHA-stimulated MNC, intracellular concentration of glutathione (GSH) in PHA-stimulated MNC was sequentially measured from day 1 to day 3 by enzymic method. Furthermore, the effect of PGE2 on nuclear DNA including DNA strand breaks in alkali treatment and DNA fragmentation (apoptosis) of PHA-stimulated MNC were also measured. We found intracellular GSH levels were significantly decreased in the early stage of lymphocyte activation (day 1), but no evidence of increased DNA stand breaks or apoptotic process appeared in 3-day culture. In addition, butathione sulfoximine (a specific GSH inhibitor) and dibutyryl cyclic AMP also exhibited both proliferation inhibition and GSH-decreasing effect on PHA-stimulated MNC as well as PGE2. These results suggest that the immunosupressive effect of PGE2 is mediated by the decreased generation of intracellular GSH, but not by the increased DNA strand breaks or apoptotic mechanism in the cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01984061
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  • 2
    Electronic Resource
    Electronic Resource
    Interleukin-13 increases prostaglandin E2 (PGE2) production by normal human polymorphonuclear neutrophils by enhancing cyclooxygenase 2 (COX-2) gene expression (1998)
    Springer
    Inflammation research 47 (1998), S. 167-173 
    Details
    ISSN: 1420-908X
    Keywords: Key words: Interleukin 13 — Polymorphonuclear neutrophil — Prostaglandin E2— Cyclooxygenase 2 — Neutral esterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective: To investigate whether interleukin-13 (IL-13) can affect arachidonic acid metabolism and phagocytic activity of normal human polymorphonuclear neutrophils (PMN).¶Methods: Normal human PMN (1 × 106 cells/ml) were incubated with different concentrations of IL-13 (0.1–10 ng/ml) for a variety of times (30–120 min). Phagocytosis and intracellular cyclooxygenase-2 (COX-2) were detected by flow cytometry. The expression of COX-1 and COX-2 mRNA was detected by RT-PCR. The concentration of PGE2 in the PMN cultured supernatants was determined by EIA.¶Results: We found that IL-13 at an optimal concentration of 1 ng/ml significantly enhanced COX-2 gene expression and PGE2 production (121.57 ± 22.17 pg/ml in IL-13 stimulation vs. 73.16 ± 11.72 pg/ml in controls) by PMN. In addition, IL-13 stimulated PMN phagocytosis via increased complement receptor type 1 (CR1) and type 3 (CR3), but not IgG Fcγ receptor type 3 (FcγRIII). The cytoplasmic neutral esterase activity of PMN was also enhanced by IL-13 stimulation for 24 h.¶Conclusions: These results suggest that IL-13 can stimulate PMN and modulates the inflammatory reactions via the cyclooxygenase pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050312
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  • 3
    Electronic Resource
    Electronic Resource
    Finite elastoplastic deformation of an internally pressurized hollow sphere (1993)
    Springer
    Acta mechanica solida Sinica 6 (1993), S. 81-97 
    Details
    ISSN: 0894-9166
    Keywords: finite deformation ; dilatant soil ; cavity expansion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This paper considers large elastoplastic deformations of an internally pressurized hollow sphere of dilatant soil. A complete analytical solution for the expansion of a hollow sphere is developed. The soil is modelled as an elastic-perfectly plastic material obeying the Mohr-Coulomb yield criterion. A non-associated plastic flow rule is used and therefore the dilation of the material is fully taken into account. Closed form solutions are obtained for the stresses and the elastic-plastic deformations of arbitrary magnitude when a hollow sphere of soil is subjected to constant external pressure and monotonically increasing internal pressure. A selection of numerical results is presented to indicate the effects of various key parameters
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02207816
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  • 4
    Electronic Resource
    Electronic Resource
    Scleromyxoedema with prominent linear eruption and polyclonal gammopathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental dermatology 22 (1997), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.1997.tb02637.x
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  • 5
    Electronic Resource
    Electronic Resource
    The cytotoxic effect of neonatal lupus erythematosus and maternal sera on keratinocyte cultures is complement-dependent and can be augmented by ultraviolet irradiation (1996)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 135 (1996), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematostis (NLE). keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 ml/cm2 UVB irradiation on NLE keratinocytes induced a 2.5–3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxie effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxieity of the sera was enhanced on UVB-irradiated NLE keratinocytes. whereas it had no cytotoxie efects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1996.tb01165.x
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  • 6
    Electronic Resource
    Electronic Resource
    Pigmented eccrine poroma with enhanced endothelin-1 expression: implications for mechanism of hyperpigmentation (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06560.x
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  • 7
    Electronic Resource
    Electronic Resource
    A novel missense mutation in the COL7A1 gene underlies epidermolysis bullosa pruriginosa (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 29 (2004), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Epidermolysis bullosa (EB) pruriginosa is a subtype of dominant dystrophic EB (DDEB), characterized by severe pruritus and blistering localized to the extensor surface of the extremities. EB pruriginosa exhibits extensive clinical heterogeneity with variable expression and delayed age of onset. Mutations in the COL7A1 gene, especially in glycine residues within Gly-X-Y repeats, have been shown to cause this form of DDEB. Here, we report a novel COL7A1 mutation in a Taiwanese pedigree with EB pruriginosa. Using PCR and direct sequence analysis we have identified a G→T transversion at nucleotide 7097 in exon 92 of COL7A1, converting a glycine residue to valine (G2366V). The mutation resides within a consecutive, uninterrupted stretch of 17 Gly-X-Y residues in the triple-helical domain of type VII collagen. Interestingly, an affected member of this family also displayed elevated IgE levels, previously reported in some patients with this disorder. Our finding further implicates COL7A1 mutation in the pathogenesis of EB pruriginosa and underscores the heterogeneous clinical symptoms of glycine mutations in DDEB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.2004.01495.x
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  • 8
    Electronic Resource
    Electronic Resource
    Abnormal Splenic and Thymic IL-4 and TNF-α Expression in MRL-lpr/lpr Mice (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 41 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The MRL-lpr/lpr and MRL-++ mice were studied for the expression of cytokines in the spleen, lymph node., thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-a expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-++ mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1α, IL-6 and TNF-a in serum than MRL-++ mice. Interestingly, in MRL-lpr/lpr but not MRL-++ mice, the IL-6 concentration in culture supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-l/? were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-++ mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-α expression may predispose the development of autoimmune reactions. The expression of IL-1ß and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03548.x
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  • 9
    Electronic Resource
    Electronic Resource
    FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Vitiligo is an acquired pigmentary disorder characterized by depigmentation of skin and hair. As the pathogenesis of this disease is still obscure, the treatment of vitiligo has generally been unsatisfactory and often disappointing. Topical tacrolimus (FK506) ointment has recently been added to the armamentarium against this pigmentary disorder. Despite its clinical efficacy, the underlying mechanisms of how topical tacrolimus induces repigmentation in vitiligo have rarely been investigated. As tacrolimus ointment is applied directly to the skin, its impact on keratinocytes (KCs) requires thorough investigation.Objectives  To investigate the effects of FK506 on melanocyte (MC) and melanoblast (MB) growth via KCs.Methods  Cultured MCs and MBs were treated with supernatant of KC cultures conditioned with various concentrations of FK506. The impact of supernatant on MCs and MBs was assessed in terms of its effect on MC/MB proliferation, melanin formation and cell migration. The activities of matrix metalloproteinase (MMP)-2 and MMP-9, known for their influence on cell migration, were evaluated. The concentrations of MC/MB growth factors in the KC supernatant were also determined.Results  Results demonstrated that proliferation of both MCs and MBs was significantly enhanced by FK506-treated KC supernatant. In addition, the concentration of stem cell factor in KC supernatant increased dose-dependently with FK506 treatment. The supernatant from FK506-treated KC culture showed a significant increase in MMP-9 activity.Conclusions  Our study provides in vitro evidence demonstrating that direct interaction between FK506 and KCs creates a favourable milieu for MC growth and migration. Furthermore, our findings provide a possible mechanism explaining how tacrolimus ointment induces repigmentation in patients with vitiligo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06739.x
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  • 10
    Electronic Resource
    Electronic Resource
    FK506 independently upregulates transforming growth factor β and downregulates inducible nitric oxide synthase in cultured human keratinocytes: possible mechanisms of how tacrolimus ointment interacts with atopic skin (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 151 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Tacrolimus ointment (FK506) has been used in recent years for the treatment of atopic dermatitis (AD), with favourable results. Most of the therapeutic efficacy of FK506 in AD has been attributed to its immunomodulatory effects on different immune cell types, but its effects on keratinocytes (KCs) have rarely been discussed. Studies have shown that low expression of transforming growth factor (TGF)-β and high expression of nitric oxide synthase (NOS) are implicated in the pathogenesis of AD.Objectives  To investigate the direct effects of FK506 on KCs in terms of TGF-β and inducible NOS (iNOS), and to explore the interactions between TGF-β and iNOS in the KC system.Methods  Cultured human KCs treated with different concentrations of FK506 were used for investigation. The changes in the KC system induced by FK506 were documented in terms of TGF-β and iNOS using enzyme-linked immunosorbent assay and Western blotting techniques, respectively. The gene expression of both TGF-β and iNOS was also determined. A certain amount of tumour necrosis factor (TNF)-α was introduced to mimic atopic skin in vivo.Results  Our results showed that the release of TGF-β was upregulated in FK506-treated KCs, particularly in the presence of TNF-α, while the expression of iNOS was downregulated. The gene expression of iNOS was also downregulated, as shown by reverse transcriptase–polymerase chain reaction analysis. However, the addition of TNF-α did not further downregulate the expression of iNOS protein, suggesting that FK506 may regulate TGF-β and iNOS through different pathways.Conclusions  Our findings indicate that the direct effects of FK506 on KCs probably contribute to its therapeutic efficacy in the treatment of AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.06109.x
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