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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  10. Deutscher Kongress für Versorgungsforschung; 18. GAA-Jahrestagung; 20111020-20111022; Köln; DOC11dkvf207 /20111012/
    Publication Date: 2011-10-12
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Keywords: tumor ; carcinoma ; MIGRATION ; IMMUNE-RESPONSE ; DUCTAL ADENOCARCINOMA ; collagen ; CCR5 ; Nab-paclitaxel ; CHEMOKINE RECEPTORS CXCR3 ; MATRIX ARCHITECTURE
    Abstract: PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive collagen-rich stroma. T cells that infiltrate pancreatic cancers frequently become trapped in the stroma and do not contact tumor cells. Here, we aimed to analyze how chemokines and extracellular matrix (ECM) collagen interact in mediating T-cell infiltration in PDAC. EXPERIMENTAL DESIGN: T-cell distribution and ECM structure within tumors were analyzed. Chemokine concentrations in human PDAC were compared with the levels of immune cell infiltration. We assessed the influences of selected chemokines and collagen on directed and random T-cell movement using in vitro migration systems. RESULTS: PDAC overproduced several T-cell-active chemokines, but their levels were not correlated with intratumoral T-cell infiltration. In the absence of collagen, directed migration of activated T cells was induced by chemokines. Interestingly, collagen itself promoted high migratory activity of T cells, but completely abolished chemokine-guided movement. This effect was not altered by a beta1-integrin blocking antibody. Activated T cells actively migrated in low-density collagen matrices, but migration was inhibited in dense collagen. Accordingly, T cells were heterogeneously distributed in the pancreatic cancer stroma, with the majority residing in areas of low-density collagen far from tumor clusters. CONCLUSION: The excessive desmoplasia in PDAC promotes T-cell migration by contact guidance, which abrogates tumor cell-directed movement. Furthermore, dense collagen networks represent a physical barrier, additionally rearranging T-cell distribution to favor tumor stroma. These mechanisms are mainly responsible for intrastromal T-cell trapping in pancreatic cancer and may hinder the development of T-cell-based immunotherapies.
    Type of Publication: Journal article published
    PubMed ID: 24763614
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  • 3
    Keywords: EXPRESSION ; SURVIVAL ; CELL ; Germany ; human ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; PROTEINS ; TISSUE ; HEART ; MICE ; INFECTION ; MECHANISM ; REDUCTION ; TRANSPLANTATION ; DOMAIN ; mechanisms ; T cell ; T-CELL ; knockout ; IDENTIFICATION ; gene expression ; affymetrix ; DAMAGE ; WILD-TYPE ; arteries ; WALL ; REJECTION ; ARTERY ; METALLOPROTEASE ; RECEPTORS ; MICROARRAY ANALYSIS ; chemokine ; ARCHITECTURE ; MATRIX ; INFILTRATION ; MATRIX METALLOPROTEINASES ; CCR5 ; ALLOGRAFT-REJECTION ; CHEMOKINE RECEPTORS
    Abstract: Experimental and human organ transplant studies suggest an important role for chemokine (C-C-motif) receptor-5 (CCR5) in the development of acute and chronic allograft rejection. Because early transplant damage can predispose allografts to chronic dysfunction, we sought to identify potential pathophysiologic mechanisms leading to allograft damage by using wild-type and Ccr5-deficient mice as recipients of fully MHC-mismatched heart and carotid-artery allografts. Gene expression in rejecting heart allografts was analyzed 2 and 6 days after transplantation using Affymetrix GeneChips. Microarray analysis led to identification of four metalloproteinase genes [matrix metalloproteinase (Mmp)3, Mmp12, Mmp13 and a disintegrin and metalloprotease domain (Adam)8] with significantly diminished intragraft mRNA expression in Ccr5-deficient mice at day 6. Accordingly, allografts from Ccr5-deficient mice showed less tissue remodeling and hence better preservation of the myocardial architecture compared with allografts from wild-type recipients. Moreover, survival of cardiac allografts was significantly increased in Ccr5-deficient mice. Carotid artery allografts from Ccr5-deficient recipients showed better tissue preservation, and significant reduction of neointima formation and CD3(+) T cell infiltration. Ccr5 appears to play an important role in transplant-associated arteriosclerosis that may involve metalloproteinase-mediated vessel wall remodeling. We conclude that early tissue remodeling may be a critical feature in the predisposition of allografts to the development of chronic dysfunction
    Type of Publication: Journal article published
    PubMed ID: 15307189
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  • 4
    Keywords: APOPTOSIS ; CELLS ; EXPRESSION ; IN-VITRO ; SURVIVAL ; Germany ; COMPLEX ; MECHANISM ; AUTOIMMUNE-DISEASE ; signal transduction ; BONE-MARROW ; ADHESION ; MONOCLONAL-ANTIBODIES ; STEM-CELLS ; rodent ; CD44 ; ACUTE MYELOID-LEUKEMIA ; MEDIATED APOPTOSIS ; PP2A ; PROTEIN PHOSPHATASE 2A ; CD44 LIGATION
    Abstract: A blockade of CD44 can interfere with haematopoietic and leukemic stem cell homing, the latter being considered as a therapeutic option in haematological malignancies. We here aimed to explore the molecular mechanism underlying the therapeutic efficacy of anti-CD44. We noted that in irradiated mice reconstituted with a bone marrow cell transplant, anti-CD44 exerts a stronger effect on haematopoietic reconstitution than on T lymphoma (EL4) growth. Nonetheless, in the non-reconstituted mouse anti-CD44 suffices for a prolonged survival of EL4-bearing mice, where anti-CD44-prohibited homing actively drives EL4 cells into apoptosis. In vitro, a CD44 occupancy results in a 2-4-fold increase in apoptotic EL4 cells. Death receptor expression (CD95, TRAIL, TNFRI) remains unaltered and CD95 cross-linking-mediated apoptosis is not affected. Instead, CD44 ligation promotes mitochondrial depolarization that is accompanied by caspase-9 cleavage and is inhibited in the presence of a caspase-9 inhibitor. Apoptosis becomes initiated by activation of CD44-associated phosphatase 2A (PP2A) and proceeds via ERK1/2 dephosphorylation without ERK1/2 degradation. Accordingly, CD44-induced apoptosis could be mimicked by ERK1/2 inhibition, that also promotes EL4 cell apoptosis through the mitochondrial pathway. Thus, during haematopoietic stem cell reconstitution care should be taken not to interfere by a blockade of CD44 with haematopoiesis, which could be circumvented by selectively targeting leukemic CD44 isoforms. Beyond homing/settlement in the bone marrow niche, anti-CD44 drives leukemic T cells into apoptosis via the mitochondrial death pathway by CD44 associating with PP2A. Uncovering this new pathway of CD44-induced leukemic cell death provides new options of therapeutic interference
    Type of Publication: Journal article published
    PubMed ID: 19765170
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  • 5
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Die Dejodierung vonL-Dijodtyrosin ohne und mit Pyruvatzusatz wurde bei 16 Frühgeburtenplacenten mens VII bis VIII, 10 Interruptioplacenten der 9.–12. Graviditätswoche und 15 Placenten präeklamptischer Gebärender sowie von der Decidua der 16 Frühgeburtenplacenten und von 10 Präeklampsieplacenten untersucht. Pro Gramm Placenta wurde im Mittel ohne Pyruvat von den Frühgeburtenplacenten 54,9±54,9 nMol Jodid, mit Pyruvat 51,0±60,3 nMol Jodid, von den Interruptioplacenten ohne Pyruvat 207±137 nMol Jodid, mit Pyruvat 126±78,8 nMol Jodid und von den Präeklampsieplacenten ohne Pyruvat 20,6±18,7 und mit Pyruvat 20,4±19,4 nMol Jodid freigesetzt. Die Dejodierungsrate pro Gramm Decidua ergab im Mittel für die Frühgeburtenplacenten ohne Pyruvat 59,1±56,2 nMol Jodid, mit Pyruvat 53,7±66,8 nMol Jodid und für die Präeklampsieplacenten ohne Pyruvat 17,4±19,2 nMol Jodid und mit Pyruvat 18,8±14,4 nMol Jodid. Die Ergebnisse werden diskutiert.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Analytical chemistry 43 (1971), S. 1938-1939 
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: SUMMARY –Paired short loins from carcasses representing five degrees of marbling, slight through slightly abundant, were randomly assigned one from each pair to air and vacuum aging in a 35°F cooler before cutting into New York steaks and prepackaging for display. Half of the packaged steaks were held in a dark cooler at 35 ± 2°F for 24 hr before being placed in a lighted, open-top display case; the orher half was put immediately into the display case. Color description and color desirability of all steaks were evaluated daily by a three-member panel. Case life was terminated when a visible spot resulting from formation of metmyoglobin appeared on the surface of the meat. Vacuum-aged short loins had a higher yield of trimmed retail cuts than air-aged short loins. There was no difference in case shrink attributable to type of aging. The steaks held in a dark cooler for 24 hr had 23.8 hr less case life than those put immediately into the lighted display case. Degree of marbling had a significant positive linear effect on color description scores at 24 and 48 hr post-cutting, but did not affect color desirability score. Marbling had a significant curvilinear effect on case life with slight (the least) and slightly abundant (the greatest) amounts having the shortest case life.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Monoclonal antibodies which react against T-cell subpopulations and Langerhans' cells were used to examine the phenotype of immunocompetent cells in oral lichen planus. Immunomorphologically, the stromal infiltrate of this condition considerably resembled the delayed type of immune reaction. Although all subpopulations of immunocompetent cells were present in the stromal infiltrate, Langerhans' cells (OKT-6 positive, HLA-DR positive) and suppressor/cytotoxic T-lymphocytes (OKT-3 positive, OKT-4 negative, OKT-8 positive, HLA-DR positive) predominated. Our immunohistological findings support the suggestion that aggregations of T-lymphocytes are responsible for the cytotoxic processes which occur within the squamous epithelium in oral lichen planus.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1572-879X
    Keywords: chemical waves ; surface diffusion ; NO reduction ; Rh ; Pt ; composite surfaces ; automotive catalytic converter ; scanning photoelectron microscopy ; photoemission electron microscopy ; PEEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The catalytic reduction of NO with H2 or CO and the O2+H2 reaction have been investigated at low pressure (p 〈 10-3 mbar) on microstructured bimetallic Pt(100)/Rh and Pt(100)/Ti surfaces prepared by lithographic techniques. Photoemission electron microscopy (PEEM) was the spatially resolving technique used. It is shown that diffusional coupling leads to dynamic effects which are size-dependent and thus can be controlled through the design of the surface microstructure. In connection with periodic parameter forcing these dynamic effects can potentially be exploited to improve the yield and selectivity of catalytic reactions.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1572-879X
    Keywords: catalytic CO oxidation ; kinetic oscillations ; in situ X-ray diffraction ; supported catalysts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In situ X-ray diffraction experiments have been conducted during rate oscillations of catalytic CO oxidation on a supported Pt catalyst, EuroPt-1. The measurements which were carried out at atmospheric pressure with flow rates of ∼ 200 ml/min showed that the non-isothermal oscillations in the reaction rate were accompanied by periodic intensity variations of a Bragg peak. A Debye function analysis of beam profiles recorded at the two extrema of the oscillations revealed that the Pt catalyst undergoes a periodic oxidation and reduction during rate oscillations. The diffraction experiments are therefore considered to be the first experimental proof that the oxide model proposed originally by Sales, Turner and Maple to explain rate oscillations in the CO + O2 reaction at atmospheric pressure is in fact correct.
    Type of Medium: Electronic Resource
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