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Berlin Brandenburg

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  • 1
    In: Transplantation, 2000, Vol.69(9), pp.1977-1981
    Description: BACKGROUND.: Prostaglandin E2 (PGE2) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE2-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE2 release. METHODS.: Endothelial cells (HUVEC) were activated by either allogeneic CD4 or CD8 T cells, or by the cytokines interleukin-1 or γ-interferon. Using an enzyme-linked immunosorbent assay, we analyzed PGE2 release of the activated HUVEC in the presence of MMF, cyclosporine, or tacrolimus. As verapamil and mibefradil also possess immunosuppressive properties, they were included in the study as well. RESULTS.: Activation of HUVEC with interleukin-1 or T cells resulted in a drastic accumulation of PGE2 in the supernatant. Cyclosporine or tacrolimus had no effect on PGE2 release. However, Ca channel blockers, when applied at higher dosages, caused a significant increase in PGE2. Interestingly, MMF strongly diminished the PGE2 level in the cell culture supernatant in a concentration-dependent manner. CONCLUSION.: The results demonstrate an inhibitory effect of MMF on PGE2 production, which may lower the benefits of the PGE2-triggered immune response after organ transplantation.
    Keywords: Endothelium ; Cytokines ; Lymphocytes T ; Immunosuppression ; Transplantation ; Interleukin 1 ; ^G-Interferon ; Prostaglandin E2 ; Mycophenolate Mofetil ; Clinical ; Man ; Immunology ; Gamma -Interferon ; Immunology ; Man ; Mycophenolate Mofetil ; Prostaglandin E2;
    ISSN: 0041-1337
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  • 2
    In: Transplantation, 2000, Vol.69(4), pp.588-597
    Description: BACKGROUND.: Cyclosporine A (CsA) and tacrolimus prevent proliferation but not transendothelial migration of alloreactive lymphocytes into donor organs. As a result, serious adverse effects, such as nephrotoxicity and neurotoxicity, have been observed under CsA/tacrolimus therapy. The incorporation of new drugs with infiltration blocking properties might enhance the efficacy of the current immunosuppressive protocol, allowing lower CsA/tacrolimus dosage. Because Ca plays a critical role in cell-cell interaction, the Ca-channel blocker verapamil might be a good cany.didate for supporting CsA/tacrolimus-based therap METHODS.: A T-cell endothelial cell coculture model or immobilized immunoglobulin G globulin chimeras were employed to investigate how S- and R- verapamil interfere with the lymphocytic infiltration process. The expression and arrangement of membranous adhesion receptors and cytoskeletal F-actin filaments were analyzed by fluorometric method in the presence of. verapamil. RESULTS.: Both verapamil enantiomers strongly inhibited lymphocyte infiltration. CD4 and CD8 T-cells were influenced to a similar extent with regard to horizontal locomotion (CD4=CD8), but to a different extent with regard to adhesion and penetration (CD4 〉 CD8). Moreover, penetration was blocked to a higher extent than was adhesion. ID50-values were 31 μM (CD4-adhesion) and 11 μM (CD4-penetration). Verapamil reduced P-selectin expression on endothelial cells and effectively down-regulated binding of T-cells to immobilized P-selectin immunoglobulin G globulins (ID50=4.4 μM; CD4). A verapamil-induced reduction of intracellular F-actin in T-lymphocytes was proven to be mainly responsible for diminished cell locomotion. CONCLUSIONS.: The prevention of CD4 T-cell penetration by verapamil might argue for its use as an adjunct to CsA/tacrolimus-based immunosuppressive therapy.
    Keywords: Immunosuppression ; Endothelium ; Lymphocytes T ; Immunosuppressive Agents ; Cell Motility ; Verapamil ; Calcium Channel Blockers ; Experimental ; Function ; Immunology ; Calcium Channel Blockers ; Cell Motility ; Immunology ; Verapamil;
    ISSN: 0041-1337
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  • 3
    Language: English
    In: The Journal of biological chemistry, 27 December 2013, Vol.288(52), pp.37204-15
    Description: Apoptosis and autophagy are fundamental homeostatic processes in eukaryotic organisms fulfilling essential roles in development and adaptation. Recently, the anti-apoptotic factor Bcl-2 has been reported to also inhibit autophagy, thus establishing a potential link between these pathways, but the mechanistic details are only beginning to emerge. Here we show that Bcl-2 directly binds to the phagophore-associated protein GABARAP. NMR experiments revealed that the interaction critically depends on a three-residue segment (EWD) of Bcl-2 adjacent to the BH4 region, which is anchored to one of the two hydrophobic pockets on the GABARAP molecule. This is at variance with the majority of GABARAP interaction partners identified previously, which occupy both hydrophobic pockets simultaneously. Bcl-2 affinity could also be detected for GEC1, but not for other mammalian Atg8 homologs. Finally, we provide evidence that overexpression of Bcl-2 inhibits lipidation of GABARAP, a key step in autophagosome formation, possibly via competition with the lipid conjugation machinery. These results support the regulatory role of Bcl-2 in autophagy and define GABARAP as a novel interaction partner involved in this intricate connection.
    Keywords: Apoptosis ; Autophagy ; Bcl-2 ; Gabarap ; Lc3 ; Lipidation ; NMR ; Protein-Protein Interactions ; Adaptor Proteins, Signal Transducing -- Metabolism ; Autophagy -- Physiology ; Cytoskeletal Proteins -- Metabolism ; Lipoylation -- Physiology ; Membrane Proteins -- Metabolism ; Microtubule-Associated Proteins -- Metabolism ; Proto-Oncogene Proteins C-Bcl-2 -- Metabolism
    E-ISSN: 1083-351X
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  • 4
    Language: English
    In: The Journal of infectious diseases, 01 December 2014, Vol.210(11), pp.1700-10
    Description: Epithelioid, foam, and multinucleated giant cells (MNGCs) are characteristics of tuberculosis granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection. We employed flow cytometry and microscopy to assess cellular phenotype and phagocytosis. Immune assays allowed quantification of cytokines and chemokines, whereas gene microarray technology was applied to estimate global transcriptome alterations. Immunohistochemical investigations of tuberculosis granulomas substantiated our findings at the site of infection. Monocytes differentiated in presence of platelets (MP-Macs) acquired a foamy, epithelioid appearance and gave rise to MNGCs (MP-MNGCs). MP-Macs up-regulated activation markers, phagocytosed mycobacteria, and released abundant interleukin 10. Upon extended culture, MP-Macs shared transcriptional features with epithelioid cells and M2 macrophages and up-regulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active tuberculosis patients. The platelet-specific CD42b antigen was detected in MP-Macs, likewise in macrophages, MNGCs, and epithelioid cells within tuberculosis granulomas, along with the platelet aggregation-inducing factor PDPN. Platelets drive macrophage differentiation into MNGCs with characteristics of epithelioid, foam, and giant cells observed in tuberculosis granulomas. Our data define platelets as novel participants in tuberculosis pathogenesis.
    Keywords: Cxcl5 ; Macrophage ; Multinucleated Giant Cell ; Platelet ; Tuberculosis ; Immunomodulation ; Blood Platelets -- Metabolism ; Foam Cells -- Immunology ; Monocytes -- Immunology ; Mycobacterium -- Immunology
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 5
    Language: English
    In: Energy Policy, Feb, 2014, Vol.65, p.185-197
    Keywords: Electric Power Generation -- Planning ; Electric Power Generation -- Environmental Aspects ; Electric Power Systems -- Design And Construction ; Electric Power Systems -- Europe ; Renewable Energy -- Planning
    ISSN: 0301-4215
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: Vaccine, 14 December 2012, Vol.30(52), pp.7608-7614
    Description: ► Macrophages infected with recombinant (r) BCG become apoptotic. ► Apoptotic vesicles contain antigenic cargo. ► Engulfment of apoptotic vesicles by dendritic cells results in crosspriming. ► Crosspriming leads to better T cell stimulation. ► Superior protection by rBCG involves crosspriming. The recombinant BCG Δ :: (rBCG) vaccine candidate is more efficient than parental BCG (pBCG) against tuberculosis (TB) in preclinical models. Evidence exists for superior CD4 and CD8 T cell stimulation. Although the responsible immune mechanisms are incompletely understood, crosspriming of CD8 T cells has been proposed as a major mechanism underlying better protection of rBCG over pBCG. The present study investigates the role of apoptotic vesicles from pBCG- and rBCG-infected macrophages in crosspriming. Apoptotic vesicles were isolated from pBCG- and rBCG-infected mouse macrophages. The priming potential of the isolated vesicles was evaluated in terms of dendritic cell activation and specific T cell stimulation. Apoptotic vesicles from both pBCG- and rBCG-infected macrophages activated dendritic cells but to a different degree. Overall, rBCG-infected apoptotic vesicles induced more profound CD4 and CD8 T cell responses as compared to pBCG. These data support the notion that the improved vaccine efficacy of rBCG rests on enhanced crosspriming as a consequence of stronger apoptosis.
    Keywords: Mycobacterium ; Apoptotic Vesicles ; T Helper Cells ; Crosspriming ; Dendritic Cells ; Medicine ; Biology ; Veterinary Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0264-410X
    E-ISSN: 1873-2518
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  • 7
    In: Chemical Communications, 2012, Vol.48(82), pp.10222-10224
    Description: Ladder type 1D coordination polymers were synthesised with the aim to improve the spin crossover properties of the iron( ii ) complexes following the concepts of crystal engineering. A wide hysteresis loop (34 K) was observed if rigid linkers were used. The first X-ray structure for a 1D iron( ii ) ladder is reported.
    Keywords: Ferrous Compounds -- Chemistry ; Polymers -- Chemistry;
    ISSN: 1359-7345
    E-ISSN: 1364-548X
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  • 8
    Language: English
    In: Science of the Total Environment, 31 December 2017, Vol.607-608, pp.623-632
    Description: The CO surface-atmosphere exchange of an unirrigated, extensive green roof in Berlin, Germany was measured by means of the eddy covariance method over a full annual cycle. The present analysis focusses on the cumulative green roof net ecosystem exchange of CO (NEE), on its seasonal variation and on green roof physiological characteristics by applying a canopy (A-g ) model. The green roof was a carbon sink with an annual cumulative NEE of − 313 g CO m year , equivalent to − 85 g C m year . Three established CO flux gap-filling methods were applied to estimate NEE and to study the performance during different meteorological situations. A best estimate NEE time series was established, which chooses the gap filling method with the highest performance. During dry periods daytime carbon uptake was shown to decline linearly with substrate moisture below a threshold of 0.05 m m , whereas night-time respiration was unaffected by substrate moisture variation. The roof turned into a temporary C source during dry conditions in summer 2015. We conclude that the carbon uptake of the present green roof can be optimized when substrate moisture is kept above 0.05 m m .
    Keywords: Co2 Uptake ; Dry Periods ; A-Gs Model ; Carbon Sequestration ; Urban ; Environmental Sciences ; Biology ; Public Health
    ISSN: 0048-9697
    E-ISSN: 1879-1026
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  • 9
    Language: English
    In: Science of the Total Environment, 15 January 2017, Vol.577, pp.220-230
    Description: Green roofs are discussed as a promising type of green infrastructure to lower heat stress in cities. In order to enhance evaporative cooling, green roofs should ideally have similar Bowen ratio (β = sensible heat flux/latent heat flux) characteristics such as rural sites, especially during summer periods with high air temperatures. We use the eddy-covariance (EC) method to quantify the energy balance of an 8600 m extensive, non-irrigated green roof at the Berlin Brandenburg Airport, Germany over a full annual cycle. To understand the influence of water availability on green roof-atmosphere energy exchange, we studied dry and wet periods and looked into functional relationships between leaf area, volumetric water content (VWC) of the substrate, shortwave radiation and β. The surface energy balance was dominated by turbulent heat fluxes in comparison to conductive substrate heat fluxes. The Bowen ratio was slightly below unity on average but highly variable due to ambient meteorology and substrate water availability, i.e. β increased to 2 in the summer season. During dry periods mean daytime β was 3, which is comparable to typical values of urban instead of rural sites. In contrast, mean daytime β was 0.3 during wet periods. Following a summer wet period the green roof maximum daily evapotranspiration (ET) was 3.3 mm, which is a threefold increase with respect to the mean summer ET. A multiple regression model indicated that the substrate VWC at the present site has to be 〉 0.11 m m during summer high insolation periods (〉 500 W m ) in order to maintain favourable green roof energy partitioning, i.e. mid-day β 〈 1. The microclimate benefit of urban green roofs can be significantly optimised by using sustainable irrigation approaches.
    Keywords: Bowen Ratio ; Evapotranspiration ; Green Infrastructure ; Extensive Roof Greening ; Leaf Area ; Environmental Sciences ; Biology ; Public Health
    ISSN: 0048-9697
    E-ISSN: 1879-1026
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  • 10
    Language: English
    In: Atmospheric Environment, 2009, Vol.43(34), pp.5518-5525
    Description: Mobile measurements of ambient noise and particle number concentrations were carried out within an urban residential area in Essen, Germany, during summer 2008. A busy major road with a traffic intensity of about 44,000 vehicles per day was situated within the study area. The spatio-temporal distribution of noise and particles was closely coupled to road traffic on the major road. Total particle number concentrations in proximity to the main road were on average between 25,000 cm and 35,000 cm while sound levels reached 70–78 dB(A). These estimates were more than double-fold (factor 2.4) in comparison to the urban residential background. At a 50 m distance off the road particle number concentrations were decaying to about 50% of the initial value. The measurements were characterised by close spatial correlation between total particle number concentration and ambient noise with correlation coefficients of up to  = 0.74. However, during one measurement day coupling between both quantities was weak due to higher turbulent mixing within the canopy layer and a change in ambient wind directions. Enhanced dilution of particle emission from road traffic by turbulent mixing and ‘decoupling’ from the influence of road traffic are believed to be responsible.
    Keywords: Urban Aerosol ; Particle Number ; Micrometeorology ; Turbulence ; Noise ; Engineering ; Environmental Sciences
    ISSN: 1352-2310
    E-ISSN: 1873-2844
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