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  • 1
    Keywords: CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; Germany ; IN-VIVO ; PATHWAY ; SYSTEM ; SYSTEMS ; liver ; EFFICIENCY ; MICE ; ACTIVATION ; IFN-GAMMA ; INDUCTION ; ANTIGEN ; ANTIGENS ; DENDRITIC CELLS ; T-CELL ; T-CELLS ; TOLERANCE ; BONE-MARROW ; MATURATION ; knockout ; MOUSE ; LINE ; DEGRADATION ; IMMUNITY ; NAIVE ; CYTOTOXICITY ; CROSS-PRESENTATION ; endothelial cells ; PH ; development ; KNOCKOUT MICE ; CYTOKINE PRODUCTION ; CELL TOLERANCE ; dendritic cell ; INDUCE ; T cell tolerance ; KUPFFER CELLS ; ADOPTIVE TRANSFER ; CD8 T cell tolerance ; ENDOTOXIN ; oral tolerance ; scavenger endothelial cells
    Abstract: After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver simisoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2k(b) by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2k(b)-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2(-/-) knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-gamma in CD8 T cells. Using a new transgenic mouse line expressing H-2k(b) only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2K(b)-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens
    Type of Publication: Journal article published
    PubMed ID: 16163670
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  • 2
    Abstract: OBJECTIVE: Based on findings in animal models of autoimmune optic nerve inflammation, we have assessed the safety and efficacy of erythropoietin in patients presenting with a first episode of optic neuritis. METHODS: Patients with optic neuritis who attended the University Hospitals of Homburg/Saar, Gottingen, or Hamburg (Germany) were included in this double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov, NCT00355095). They were randomly assigned to groups receiving either 33,000IU recombinant human erythropoietin intravenously daily for 3 days or placebo as an add-on therapy to methylprednisolone. The primary outcome parameter was change in retinal nerve fiber layer (RNFL) thickness after 16 weeks. Secondary outcome parameters included optic nerve atrophy as assessed by magnetic resonance imaging, and changes in visual acuity, visual field, and visual evoked potentials (VEPs). RESULTS: Forty patients were assigned to the treatment groups (21/19 erythropoietin/placebo). Safety monitoring revealed no relevant issues. Thirty-seven patients (20/17 erythropoietin/placebo) were analyzed for the primary endpoint according to the intention-to-treat protocol. RNFL thinning was less apparent after erythropoietin treatment. Thickness of the RNFL decreased by a median of 7.5mum by week 16 (mean +/- standard deviation, 10.55 +/- 17.54mum) compared to a median of 16.0mum (22.65 +/- 29.18mum) in the placebo group (p = 0.0357). Decrease in retrobulbar diameter of the optic nerve was smaller in the erythropoietin group (p = 0.0112). VEP latencies at week 16 were shorter in erythropoietin-treated patients than in the placebo group (p = 0.0011). Testing of visual functions revealed trends toward an improved outcome after erythropoietin treatment. INTERPRETATION: These results give the first indications that erythropoietin might be neuroprotective in optic neuritis.
    Type of Publication: Journal article published
    PubMed ID: 22926853
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  • 3
  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  1. Kongress der Deutschen Gesellschaft für Essstörungen e.V. (DGESS); 20071108-20071110; Prien am Chiemsee; DOC07dgessV18 /20071024/
    Publication Date: 2007-10-24
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
    Keywords: RECEPTOR ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; Germany ; IN-VIVO ; VIVO ; liver ; GENE ; GENE-EXPRESSION ; DIFFERENTIATION ; ACTIVATION ; CUTTING EDGE ; INFECTION ; INDUCTION ; DENDRITIC CELLS ; T-CELLS ; TOLERANCE ; bone marrow ; BONE-MARROW ; STIMULATION ; MOUSE ; DELIVERY ; CLONAL EXPANSION ; VIRAL-INFECTION ; CROSS-PRESENTATION ; endothelial cells ; EFFECTOR FUNCTION ; RIG-I ; T cell immunity ; HEPATITIS-B VIRUS ; MURINE CYTOMEGALOVIRUS-INFECTION ; TOLEROGENIC DENDRITIC CELLS
    Abstract: BACKGROUND & AIMS: Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8(+) T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8(+) T-cell activation upon such stimulation. METHODS: Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo relevance of the findings was confirmed with bone-marrow chimeric animals. RESULTS: LSECs expressed numerous pattern recognition receptors that allowed for sentinel function, but ligand-induced activation of these receptors was not sufficient to overcome tolerance induction of CD8(+) T cells. Importantly, viral infection with murine cytomegalovirus caused functional maturation of antigen-presenting LSECs and was sufficient to promote antigen-specific differentiation into effector CD8(+) T cells in the absence of dendritic cells and independent of CD80/86. CONCLUSIONS: These results shed new light on the generation of organ-specific immunity and may contribute to overcoming tolerance in relevant situations, such as cancer
    Type of Publication: Journal article published
    PubMed ID: 19737567
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  • 6
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The study distinctly shows that structural changes take place in the silicate framework during the swelling process of glasses in aqueous solutions. The presence of a modified Q3 group is evidence for the exchange of protons and sodium ions; condensation reactions also take place. Using various techniques (1H NMR, infrared spectroscopy and thermal analysis) it has been demonstrated that water is present in the hydrated glass not only in the form of H2O molecules and silanol groups, but also in different structures of these two species. A molar H2O:SiOH ratio was found of approximately 1:1 (in agreement with the assumption that H3O+ ions of the solution and sodium ions of the glass are exchanged and ≡ SiOH and H2O are formed from the hydroxonium ions).
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Cluster Analysis has been shown to be partially suitable for the classification of glasses. The expansion of the clusters on the Seger's diagram allows an investigation of the influence of the different glass components. Variation of the SiO2 content results in a smaller change of properties than variation of the Na2O/RO relationship. Principal Component Analysis is convenient for showing correlations between the composition of the examined glasses, the glass structure parameters, and the different electrode properties.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pest science 43 (1970), S. 128-128 
    ISSN: 1612-4766
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-2451
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Ein Krankengut von mehr als 70 Patienten mit verschiedensten Malignomen wurde nach Gabe von67Ga-Citrat szintigraphisch untersucht, nachdem in letzter Zeit Berichte über die Eignung dieses Tracers zur Erfassung von Malignomen erschienen waren. Außerdem wurde ein vergleichbares Kollektiv von Patienten mit gutartigen Erkrankungen mit67Ga szintigraphiert, um die diagnostische Aussagekraft der Untersuchungsmethode zu prüfen. Dabei ergab sich, daß Malignome, die einer intensiven Strahlentherapie vor der Untersuchung unterzogen worden waren, keine67Ga-Anreicherung erkennen ließen. Bei Ausschluß der bestrahlten Geschwülste fanden wir dagegen in mehr als 90% der untersuchten Malignome eine deutliche67Ga-Speicherung, während nur eine einzige gutartige Läsion67Ga aufnahm (abszedierendeMastitis). Die somit sehr vielversprechenden Ergebnisse werden in ihrer Bedeutung für die chirurgische Tumordiagnostik besprochen.
    Notes: Summary After recent reports on the suitability of67Ga-citrate as a tracer element for the detection of malignant growths, we examined over 70 patients with various malignant tumours scintigraphically by injecting doses of67Ga citrate. At the same time a comparable group of patients with non-malignant disease were also scanned with67Ga to test the the diagnostic reliability of this examination method. This revealed that malignant tumours which had undergone an intense course of radiotherapy prior to the examination did not show any67Ga enrichment. Excluding the growths treated by radiation, however, we found a distinct67Ga uptake in more than 90% of the malignant tumours examined, while only one benign lesion took up67Ga (suppurative mastitis). These very promising results and their significance for tumour surgery are discussed.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Computing 20 (1978), S. 189-205 
    ISSN: 1436-5057
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Description / Table of Contents: Zusammenfassung Eines der am besten beschriebenen Modelle kombinatorischer Optimierung ist das Scheduling Problem, bei dem eine endliche Anzahl von Tätigkeiten auf einer festen Anzahl von Maschinen so ausgeführt werden muß, daß eine gegebene Zielfunktion minimiert wird. Jede Tätigkeit benötigt charakteristische Daten wie Bearbeitungszeit, Fertigsteillungstermin, Strafkosten und technologische Nachfolgebeziehungen. Ein algebraischer Ansatz für die Zielfunktion führt zu einem allgemeinen Problem, das alle in der Literatur bekannten klassischen Fälle von Summen und Maximum Zielfunktionen einschließt. Durch die Lösung eines algebraischen Transportproblems wird eine untere Schranke für den Zielfunktionswert bestimmt. Um eine Optimallösung zu erhalten, verwenden wir ein Branch and Bound Verfahren. Weiterhin betrachten wir das allgemeine Job Shop Scheduling Problem mit algebraischer Zielfunktion.
    Notes: Abstract One of the well-studied models of combinatorial optimization is the scheduling problem dealing with a finite set of tasks, which have to be executed on a fixed number of machines so that a given objective is minimized. Each task requires a set of characteristic data like operating time, due date, penalty cost and technological requirements. An algebraic approach to the objective leads to a general problem which includes all classical cases of sum and bottleneck objectives known in literature. By solving an algebraic transportation problem a lower bound for the objective value can be determined. To obtain an optimal solution we employ a branch and bound procedure. Furthermore we consider the general job shop scheduling problem with algebraic objective function.
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