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  • 2000-2004  (5)
  • 1985-1989
  • 1915-1919
  • 2004  (3)
  • 2001  (2)
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  • 2000-2004  (5)
  • 1985-1989
  • 1915-1919
Year
  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The interaction with adhesion molecules expressed by vascular endothelium is the first step in lymphocyte infiltration into tissues. At both cutaneous and mucosal sites interleukin-10 (IL-10), IL-12 and transforming growth factor (TGF)-β are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and αE integrin (CD103) may be expressed. Unlike CLA, CD103 is not believed to play a role in tissue-specific homing but may help to retain T cells within epithelial layers. We have previously shown that IL-12 alone can together with an unknown cofactor increase the expression of CLA. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells. While IL-12 increased superantigen-stimulated expression of CLA, this cytokine strongly inhibited the CD103 expression, and a combination of IL-12 and TGF-β completely abrogated the induced CD103 expression. Conversely, IL-10 suppressed CLA but increased CD103 expression.These findings indicate that, in addition to suppressing the development of Th1-mediated inflammatory responses, IL-10 may also inhibit the migration of CD8+ T cells into the skin while IL-12 promotes such migration. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12, and the balance between these cytokines could influence the T-cell migration of inflammatory cells into epithelial tissues.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The association of psoriasis with throat infections by streptococcus pyogenes suggests a potential antigenic target for the T cells that are known to infiltrate dermis and epidermis of psoriatic skin. Streptococcal M protein shares an extensive sequence homology with human epidermal keratins. Keratins 16 (K16) and 17 (K17) are mostly absent from uninvolved skin but are upregulated in psoriatic lesions. There is increasing evidence that CD8+ T cells play an important effector role in psoriasis and M protein-primed T cells may recognize these shared epitopes in skin via molecular mimicry. To identify candidate epitopes, peptides with sequences from K17 were selected on the basis of predicted binding to HLA-Cw6 and sequence similarities with M6 protein. Matched peptides from the sequence of M6 protein and a set of peptides with poor predicted binding were also selected. Cw6+ individuals with psoriasis and Cw6+ healthy controls, having a family history of psoriasis, were recruited. PBMCs were incubated with the peptide antigens. T-cell activation in the CD4+, CD8+ and later the skin-homing cutaneous lymphocyte-associated antigen (CLA)-expressing subset of CD8+ T cells was evaluated by CD69 expression and intracellular IFN-γ accumulation using flow cytometry. We demonstrate that Cw6+ psoriasis patients had significant CD8+ T-cell IFN-γ responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA+) subset of CD8+ T cells. CD4+ T cells showed only borderline responses. CD8+ T cells from Cw6 + nonpsoriatic individuals responded to some M6 peptides but very rarely to K17 peptides, and this also applied to the CLA+CD8+ subset. These findings indicate that psoriatic individuals have CD8+ T cells that recognize keratin self-antigens and that epitopes shared by streptococcal M protein and human keratin may be targets for the CD8+ T cells that infiltrate psoriatic skin lesions.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The ATP-binding cassette (ABC) transporter superfamily is one of the most widespread of all gene families and currently has in excess of 1100 members in organisms ranging from the Archaea to man. The movement of the diverse solutes of ABC transporters has been accepted as being strictly unidirectional, with recent models indicating that they are irreversible. However, contrary to this paradigm, we show that three solute-binding protein-dependent (SBP) ABC transporters of amino acids, i.e. the general amino acid permease (Aap) and the branched-chain amino acid permease (Bra) of Rhizobium leguminosarum and the histidine permease (His) of Salmonella typhimurium, are bidirectional, being responsible for efflux in addition to the uptake of solutes. The net solute movement measured for an ABC transporter depends on the rates of uptake and efflux, which are independent; a plateau is reached when both are saturated. SBP ABC transporters promote active uptake because, although the Vmax values for uptake and efflux are not significantly different, there is a 103−104 higher affinity for uptake of solute compared with efflux. Therefore, the SBP ABC transporters are able to support a substantial concentration gradient and provide a net uptake of solutes into bacterial cells.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Water and environment journal 15 (2001), S. 0 
    ISSN: 1747-6593
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Water companies in England and Wales produce reports using environmental performance indicators which have been developed in-house. However, there is no recognised methodology for the development of these indicators, and an analysis of available guidance led to the proposal of an appropriate model. This model was tested by semi-structured interviews of water-company managers, and a questionnaire was completed by managers from other industries. The responses from the interviews supported the inclusive, quality-driven approach advocated by the model, and indicated a need to examine (a) the style of management, (b) the staffing structure in water companies, (c) the connection between environmental management systems and indicator development, (d) types of objectives and targets, and (e) the use of indicators as public-relations tools. The result is a methodology for indicator development which can be applied by managers in industry.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The main recommendations for the use of ciclosporin in the management of psoriasis are: (i) intermittent short courses (average of 12 weeks duration) of ciclosporin are preferable; (ii) ciclosporin should be given in the dose range 2·5–5·0 mg kg−1 day−1 (doses greater than 5·0 mg kg−1 day−1 should only be given in exceptional circumstances); (iii) treatment regimens should be tailored to the needs of each patient; (iv) selection of patients should take into account psychosocial disability, as well as clinical extent of disease and failure of previous treatment; (v) each patient's renal function (as measured by serum creatinine) should be thoroughly assessed before and during treatment; (vi) each patient's blood pressure should be carefully monitored before and during treatment; (vii) adherence to treatment guidelines substantially reduces the risk of adverse events; (viii) long-term continuous ciclosporin therapy may be appropriate in a subgroup of patients; however, duration of treatment should be kept below 2 years whenever possible; and (ix) when long-term continuous ciclosporin therapy is necessary, annual evaluation of glomerular filtration rate may be useful to accurately monitor renal function.
    Type of Medium: Electronic Resource
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