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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Hair loss following skin inflammation may in part be mediated by keratinocyte (KC) apoptosis. While the effects of different cytokines or other apoptosis stimulating agents such as interferon (IFN)-γ or tumour necrosis factor (TNF)-α on KC apoptosis in vitro have been addressed in several studies, little is known about the effects of proinflammatory cytokines on KC apoptosis in vivo. Objectives To study the effects of intradermally injected TNF-α, interleukin (IL)-1β and IFN-γ on KC apoptosis in the back skin of C57BL/6 mice. Methods Apoptosis in epidermal and hair bulb KCs was analysed by immunohistology using TUNEL staining. Results Injection of TNF-α induced a significantly higher number of apoptotic cells within the epidermis than vehicle; all three proinflammatory cytokines together further increased their number. Intrafollicular hair bulb KCs were much more susceptible to apoptosis induction by TNF-α or IL-1β; their injection significantly upregulated apoptosis after 6 h, which was further increased after 24 h. The combination of all cytokines together accelerated intrafollicular apoptosis after 6 h by doubling the number of apoptotic cells per hair bulb, compared with the effects of TNF-α or IL-1β alone. Conclusions These data suggest that programmed cell death of proliferating KCs in vivo can be induced by proinflammatory cytokines.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 142 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The immunology of the hair follicle, its relationship with the ‘skin immune system’ and its role in hair diseases remain biologically intriguing and clinically important. In this study, we analysed the immunoreactivity patterns of 15 immunodermatological markers to determine the cellular composition and immune privilege of the human hair follicle immune system in anagen VI (growth phase). The most prominent cells located in or around the hair follicle were Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells, whereas B cells, natural killer cells and γδ T cells were found very rarely. Langerhans cells (CD1a+, major histocompatibility complex, MHC class II+), and T cells (CD4+ or CD8+) were predominantly distributed in the distal hair follicle epithelium, whereas macrophages (CD68+, MHC class II+) and mast cells (Giemsa+) were located in the perifollicular connective tissue sheath. Transmission electron microscopy confirmed low numbers of immune cells in the proximal hair follicle epithelium, and very few macrophages and Langerhans cells were seen in the dermal papilla. Melanophages were observed in the connective tissue sheath and dermal papilla. MHC class I (HLA-A, -B, -C) and β2-microglobulin immunoreactivity was found on most skin cells, but was substantially reduced on isthmus keratinocytes and virtually absent in the proximal hair follicle epithelium. Apart from the absence of Fas ligand immunoreactivity, the sharply reduced numbers of T cells and Langerhans cells, and the virtual absence of MHC class I expression all suggest that the anagen proximal hair follicle constitutes an area of immune privilege within the hair follicle immune system, whose collapse may be crucial for the pathogenesis of alopecia areata.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 490-495 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Capsid-binding drugs that inhibit the first stage of picornaviral uncoating were used to select drug-resistant mutants of the Sabin strain of poliovirus type 3. Such mutants provide information about parts of the capsid that are important for functions blocked by the drugs, and also about pathways to drug resistance. Amino-acid substitutions allowing virus to produce progeny in the presence of drug were mapped to 13 different residues occupying three distinct locations: (I) the canyon base; (II) the lining of the drug-binding pocket; and (III) the base of the protomer. These loci might be thought of as action points for transmitting the uncoating signal from receptor, through the pocket, and to the base of the protomer. All of the mutations in a special class of drug-dependent mutants were clustered at site (III) and all were hyperlabile, i.e., uncoated spontaneously (without receptor) at growth temperature unless prevented from doing so by the presence of drug in the pocket. Thus, site (III) seems to represent a kind of thermostat which regulates the temperature at which the uncoating transition (release of VP4 to form A particles) is triggered.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 50 (1994), S. 351-354 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: It is of considerable interest to separate the processes of viral infectivity and virion assembly. Until recently this has only been possible with viruses that could be disassembled and reassembled in vitro. Even in these cases it was difficult to establish the authenticity of reassembled capsid protein because of possible irreversible damage that may have occurred to the protein during disassembly. An ideal method for the study of virus assembly is a protein expression system in which conditions are appropriate for spontaneous particle formation from freshly synthesized polypeptides. The baculovirus expression system has proven to be an excellent means to this end. Recently, this approach has been used to study the T = 3 Flock House insect virus and it has been demonstrated that subunits with the wild-type protein sequence, and with site-specific mutations that prevent particle maturation, will assemble and crystallize. This same approach has now been used at Purdue to study the T = 4 Nudaurelia ω capensis insect virus. There is no cell culture system currently available for the study of NωV, thus the expression system provides the first opportunity to study assembly under controlled conditions.
    Type of Medium: Electronic Resource
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