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  • 1
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The lbi (lipopolysaccharide biosynthesis interfering) RNA of phage Acm1, an untranslated RNA transcript of 97 nucleotides, previously shown to affect O-polysaccharide biosynthesis in various Escherichia coli strains, was found to downregulate the synthesis of the d-galactan II component of the O-specific polysaccharide in Klebsiella pneumoniae serotype O1. Enzymatic and Pb2+ probing experiments revealed that lbi RNA consists of two consecutive stem–loop structures, the 5′-proximal hairpin loop of 15 nucleotides being particularly accessible to single strand-specific probes. Based on the assumption that the 5′-proximal hairpin loop may be involved in an antisense interaction with cellular target RNAs, we randomly mutagenized one or two of its central nucleotides. Expression of mutated lbi RNA variants in K. pneumoniae serotype O1 relieved at least partly the repression of d-galactan II formation. In addition, a truncated version of lbi RNA lacking the 3′-proximal hairpin loop was almost as efficient as the wild-type RNA in downregulating d-galactan II synthesis. The results obtained indicate that the 5′-proximal hairpin loop of lbi RNA functions as a key structural element in the mechanism leading to the inhibition of d-galactan II biosynthesis in K. pneumoniae serotype O1.
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  • 2
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Basophile Granulozyten ; Atopische Dermatitis ; Late Phase Reaction ; Allergische Kontaktdermatitis ; Jones-Mote-Reaktion ; Key words Basophilic leukocytes ; Atopic dermatitis ; Late phase reaction ; Allergic contact dermatitis ; Jones-Mote reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Basophilic leukocytes are effector cells of the peripheral blood. They have several morphological and functional characteristics in common with tissue mast cells, such as expression of the high-affinity IgE receptor (FcɛRI) and a high content of histamine within their granules. Functional comparison of human basophils and human mast cells isolated from different tissues revealed marked heterogeneity of mediator release after incubation with different secretagogues. Owing to their wide range of surface receptors, their (pro)inflammatory mediators released after activation, their mobility, and their rapid turnover, basophils appear basically to be potent effector cells, which migrate transiently into the skin during IgE-mediated (and/or IgE-independent) inflammatory reactions. The present paper reviews recent findings on the possible role of basophils for different immune reactions of the skin. Inhibition of basophil (and/or mast cell) activity seems to be necessary for both effective prophylaxis and therapy of allergic and inflammatory skin diseases. To date, however, the pharmacological modulation of mediator release from basophils lacks potent clinically useful compounds that can suppress the cellular response, since mast cell stabilizers such as cromoglycate and nedocromil are not effective. With a view to the development of active compounds, further in vitro studies should focus on the mechanisms of cell activation.
    Notes: Zusammenfassung Basophile Granulozyten sind primär in der Zirkulation befindliche Zellen, die wegen einiger wichtiger morphologischer und funktioneller Gemeinsamkeiten wie z.B. der Expression des hochaffinen IgE-Rezeptors (Fc ɛ RI) und des hohen, granulaassoziierten Histamingehaltes häufig als Pendant von Gewebemastzellen bezeichnet werden. Exakte, vergleichende Studien an humanen Basophilen und humanen Mastzellen verschiedener Gewebearten konnten jedoch eine ausgeprägte Heterogenität insbesondere hinsichtlich einer Mediatorfreisetzung durch unterschiedliche Stimuli aufzeigen. Durch ihre unterschiedlichen Oberflächenrezeptoren, ihre nach Aktivierung freisetzbaren (pro)inflammatorischen Mediatoren, die kurzfristige Mobilisierbarkeit und den schnellen Turnover erscheinen sie prinzipiell geeignet, als Effektorzellen bei IgE-vermittelten (aber auch IgE-unabhängigen) entzündlichen Reaktionen passager in die Haut einzuwandern. Die vorliegende Arbeit faßt neuere Erkenntnisse über eine mögliche pathogenetische Beteiligung von basophilen Granulozyten an verschiedenen Immunreaktionen der Haut zusammen. Eine pharmakologische Beeinflussung der Basophilen- wie der Mastzellaktivität ist aus Gründen einer wirksamen Prophylaxe bzw. Therapie allergischer und entzündlicher Reaktionen der Haut mit Mediatorfreisetzung aus diesen Zellen notwendig und sinnvoll. Bislang sind klinisch jedoch noch keine Substanzen im Einsatz, welche diese Aufgabe erfüllen können, da Mastzellstabilisatoren wie Cromoglycinsäure und Nedocromil speziell an Basophilen unwirksam sind. Voraussetzung für eine Entwicklung solcher Substanzen ist eine genaue Kenntnis und In-vitro-Untersuchung der Zellaktivierungsvorgänge.
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  • 3
    ISSN: 1432-069X
    Keywords: Key words Skin mast cells ; Basophils ; Cytokines ; Priming ; Allergic inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell priming and stimulation of different cytokines (which include chemokines and growth factors) are typical features of human basophils. Recently, it has been shown that the macrophage chemotactic protein-1 (MCP-1), RANTES and macrophage inflammatory protein-1α (MIP-1α) are potent direct secretagogues for human basophils and that interleukin-3 (IL-3), IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are priming factors for subsequent potentiation of mediator release from basophils induced by different stimuli. This observation may be clinically important for the activation and recruitment of inflammatory cells in different immune responses of the skin (e.g. late-phase reactions). The aim of the present study was to investigate whether cytokines and chemokines are also capable of priming or stimulating isolated human skin mast cells (SMC). SMC were either stimulated directly with the cytokines alone or preincubated with these factors for 10 min before being activated with suboptimal concentrations of anti-IgE, A23187 or substance P. IL-3, IL-5, GM-CSF, platelet factor-4 (PF-4), IL-8, MCP-1 and MIP-1α (each at concentrations of 1 ng/ml to 1 μg/ml, log steps) did not significantly modulate histamine release from SMC induced by the three different secretagogues. RANTES exhibited a weak but significant potentiating effect on IgE-mediated activation. Stem cell factor (SCF) as a positive control was able to prime mast cell histamine release strongly. In addition, PF-4, MCP-1, RANTES and MIP-1α were incapable of inducing direct histamine release from SMC. In experiments with isolated human peripheral basophils, however, we observed potent Fc ε RI-mediated priming effects evoked through IL-3, IL-5, and GM-CSF. We conclude that SMC derived from healthy donors are not targets of (immuno)modulatory factors that prime or stimulate basophils.
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