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  1. Book ; Online ; Thesis: Induktion Borna-Disease-Virus-spezifischer Immunität durch Vakzinierung mit dendritischen Zellen

    Fassnacht, Ulrike

    2005  

    Author's details vorgelegt von Ulrike Fassnacht
    Language German
    Size Online-Ressource
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Diss--Freiburg (Breisgau), 2005
    Note Erscheinungsjahr an der Haupttitelstelle: 2003
    Database Former special subject collection: coastal and deep sea fishing

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  2. Book ; Online ; Thesis: Induktion Borna-Disease-Virus-spezifischer Immunität durch Vakzinierung mit dendritischen Zellen

    Fassnacht, Ulrike [Verfasser]

    2005  

    Author's details vorgelegt von Ulrike Fassnacht
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  3. Article: Immunization with dendritic cells can break immunological ignorance toward a persisting virus in the central nervous system and induce partial protection against intracerebral viral challenge.

    Fassnacht, Ulrike / Ackermann, Andreas / Staeheli, Peter / Hausmann, Jürgen

    The Journal of general virology

    2004  Volume 85, Issue Pt 8, Page(s) 2379–2387

    Abstract: Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropic Borna disease virus (BDV) in mice was evaluated. Certain ... ...

    Abstract Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropic Borna disease virus (BDV) in mice was evaluated. Certain strains of mice only rarely develop spontaneous neurological disease, despite massive BDV replication in the brain. Resistance to disease is due to immunological ignorance toward BDV antigen in the central nervous system. Ignorance in mice can be broken by immunization with DCs coated with TELEISSI, a peptide derived from the N protein of BDV, which represents the immunodominant cytotoxic T lymphocyte epitope in H-2(k) mice. Immunization with TELEISSI-coated DCs further induced solid protective immunity against intravenous challenge with a recombinant vaccinia virus expressing BDV-N. Interestingly, however, this immunization scheme induced only moderate protection against intracerebral challenge with BDV, suggesting that immune memory raised against a shared antigen may be sufficient to control a peripherally replicating virus, but not a highly neurotropic virus that is able to avoid activation of T cells. This difference might be due to the lack of BDV-specific CD4 T cells and/or inefficient reactivation of DC-primed, BDV-specific CD8 T cells by the locally restricted BDV infection. Thus, a successful vaccine against persistent viruses with strong neurotropism should probably induce antiviral CD8 (as well as CD4) T-cell responses and should favour the accumulation of virus-specific memory T cells in cervical lymph nodes.
    MeSH term(s) Animals ; Borna disease virus/immunology ; Brain/virology ; Dendritic Cells/immunology ; Immunization ; Immunologic Memory ; Mice ; Nucleocapsid Proteins/immunology ; Peptide Fragments/immunology
    Chemical Substances Nucleocapsid Proteins ; Peptide Fragments
    Language English
    Publishing date 2004-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/vir.0.80115-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: PKA catalytic subunit mutations in adrenocortical Cushing's adenoma impair association with the regulatory subunit.

    Calebiro, Davide / Hannawacker, Annette / Lyga, Sandra / Bathon, Kerstin / Zabel, Ulrike / Ronchi, Cristina / Beuschlein, Felix / Reincke, Martin / Lorenz, Kristina / Allolio, Bruno / Kisker, Caroline / Fassnacht, Martin / Lohse, Martin J

    Nature communications

    2014  Volume 5, Page(s) 5680

    Abstract: We recently identified a high prevalence of mutations affecting the catalytic (Cα) subunit of protein kinase A (PKA) in cortisol-secreting adrenocortical adenomas. The two identified mutations (Leu206Arg and Leu199_Cys200insTrp) are associated with ... ...

    Abstract We recently identified a high prevalence of mutations affecting the catalytic (Cα) subunit of protein kinase A (PKA) in cortisol-secreting adrenocortical adenomas. The two identified mutations (Leu206Arg and Leu199_Cys200insTrp) are associated with increased PKA catalytic activity, but the underlying mechanisms are highly controversial. Here we utilize a combination of biochemical and optical assays, including fluorescence resonance energy transfer in living cells, to analyze the consequences of the two mutations with respect to the formation of the PKA holoenzyme and its regulation by cAMP. Our results indicate that neither mutant can form a stable PKA complex, due to the location of the mutations at the interface between the catalytic and the regulatory subunits. We conclude that the two mutations cause high basal catalytic activity and lack of regulation by cAMP through interference of complex formation between the regulatory and the catalytic subunits of PKA.
    MeSH term(s) Adrenal Cortex Neoplasms/enzymology ; Adrenal Cortex Neoplasms/genetics ; Adrenal Cortex Neoplasms/pathology ; Adrenocortical Adenoma/enzymology ; Adrenocortical Adenoma/genetics ; Adrenocortical Adenoma/pathology ; Catalytic Domain ; Cell Line, Tumor ; Cushing Syndrome/enzymology ; Cushing Syndrome/genetics ; Cushing Syndrome/pathology ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/chemistry ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/genetics ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/metabolism ; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/chemistry ; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/genetics ; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/metabolism ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/chemistry ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/genetics ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/metabolism ; Cyclic AMP-Dependent Protein Kinases/chemistry ; Cyclic AMP-Dependent Protein Kinases/genetics ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Humans ; Mutation ; Protein Binding ; Protein Stability
    Chemical Substances Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ; PRKAR1A protein, human ; PRKAR2B protein, human ; Cyclic AMP (E0399OZS9N) ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits (EC 2.7.11.11) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; PRKACA protein, human (EC 2.7.11.11)
    Language English
    Publishing date 2014-12-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms6680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Rationale und rationelle Diagnostik bei leichtem Schädel-Hirn-Trauma

    Fassnacht, Ulrike / van Velthoven, Vera / Schwab, Karl Otfried / Superti-Furga, Andrea / Korinthenberg, Rudolf

    Kinderärztliche Praxis

    2007  Volume 78, Issue 4, Page(s) 207

    Language German
    Document type Article
    ZDB-ID 209040-5
    ISSN 0023-1495 ; 1432-3605
    Database Current Contents Medicine

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  6. Article ; Online: Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome--revisiting the direct and indirect water deprivation tests.

    Fenske, Wiebke / Quinkler, Marcus / Lorenz, Daniela / Zopf, Kathrin / Haagen, Ulrike / Papassotiriou, Jana / Pfeiffer, Andreas F H / Fassnacht, Martin / Störk, Stefan / Allolio, Bruno

    The Journal of clinical endocrinology and metabolism

    2011  Volume 96, Issue 5, Page(s) 1506–1515

    Abstract: Background: The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia-polyuria syndrome. In theory, direct measurement of AVP is ... ...

    Abstract Background: The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia-polyuria syndrome. In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties.
    Objective: The aim of the study was to evaluate the utility of copeptin, a surrogate of AVP secretion, in the diagnostic work-up of the polyuria-polydipsia syndrome and to compare its performance with the current diagnostic standard.
    Setting and design: In two tertiary referral centers, 20 healthy subjects and 50 patients with polydipsia-polyuria syndrome underwent WDT with measurements of both plasma AVP and copeptin levels. The reference diagnosis was based on clinical information and treatment response.
    Results: Twenty-two patients (44%) were diagnosed with primary polydipsia, 17 (34%) with partial central diabetes insipidus (DI), nine (18%) with complete central DI, and two (4%) with nephrogenic DI. The indirect WDT led to a correct diagnosis in 35 of 50 patients (70%). The direct WDT with AVP or copeptin measurement correctly diagnosed 23 patients (46%) or 36 patients (72%), respectively. Baseline copeptin values greater than 20 pmol/liter identified patients with nephrogenic DI, and concentrations below 2.6 pmol/liter indicated complete central DI. The ratio between Δ copeptin (0800 to 1600 h) and serum sodium concentration at 1600 h yielded optimal diagnostic accuracy, allowing us to also discern partial central DI from primary polydipsia (sensitivity 86%, and specificity 100%).
    Conclusion: Copeptin holds promise as a diagnostic tool in the polyuria-polydipsia syndrome, improving significantly the diagnostic accuracy of the direct WDT.
    MeSH term(s) Adult ; Arginine Vasopressin/blood ; Diabetes Insipidus/diagnosis ; Diagnosis, Differential ; Female ; Glycopeptides/blood ; Humans ; Male ; Osmolar Concentration ; Polyuria/diagnosis ; Radioimmunoassay ; Reference Values ; Reproducibility of Results ; Syndrome ; Water Deprivation/physiology
    Chemical Substances Glycopeptides ; copeptins ; Arginine Vasopressin (113-79-1)
    Language English
    Publishing date 2011-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/jc.2010-2345
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome.

    Beuschlein, Felix / Fassnacht, Martin / Assié, Guillaume / Calebiro, Davide / Stratakis, Constantine A / Osswald, Andrea / Ronchi, Cristina L / Wieland, Thomas / Sbiera, Silviu / Faucz, Fabio R / Schaak, Katrin / Schmittfull, Anett / Schwarzmayr, Thomas / Barreau, Olivia / Vezzosi, Delphine / Rizk-Rabin, Marthe / Zabel, Ulrike / Szarek, Eva / Salpea, Paraskevi /
    Forlino, Antonella / Vetro, Annalisa / Zuffardi, Orsetta / Kisker, Caroline / Diener, Susanne / Meitinger, Thomas / Lohse, Martin J / Reincke, Martin / Bertherat, Jérome / Strom, Tim M / Allolio, Bruno

    The New England journal of medicine

    2014  Volume 370, Issue 11, Page(s) 1019–1028

    Abstract: Background: Corticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol-producing adrenal adenomas is not well understood.: Methods: We performed exome sequencing of ... ...

    Abstract Background: Corticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol-producing adrenal adenomas is not well understood.
    Methods: We performed exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated recurrent mutations in candidate genes in an additional 171 patients with adrenocortical tumors. We also performed genomewide copy-number analysis in 35 patients with cortisol-secreting bilateral adrenal hyperplasias. We studied the effects of these genetic defects both clinically and in vitro.
    Results: Exome sequencing revealed somatic mutations in PRKACA, which encodes the catalytic subunit of cyclic AMP-dependent protein kinase (protein kinase A [PKA]), in 8 of 10 adenomas (c.617A→C in 7 and c.595_596insCAC in 1). Overall, PRKACA somatic mutations were identified in 22 of 59 unilateral adenomas (37%) from patients with overt Cushing's syndrome; these mutations were not detectable in 40 patients with subclinical hypercortisolism or in 82 patients with other adrenal tumors. Among 35 patients with cortisol-producing hyperplasias, 5 (including 2 first-degree relatives) carried a germline copy-number gain (duplication) of the genomic region on chromosome 19 that includes PRKACA. In vitro studies showed impaired inhibition of both PKA catalytic subunit mutants by the PKA regulatory subunit, whereas cells from patients with germline chromosomal gains showed increased protein levels of the PKA catalytic subunit; in both instances, basal PKA activity was increased.
    Conclusions: Genetic alterations of the catalytic subunit of PKA were found to be associated with human disease. Germline duplications of this gene resulted in bilateral adrenal hyperplasias, whereas somatic PRKACA mutations resulted in unilateral cortisol-producing adrenal adenomas. (Funded by the European Commission Seventh Framework Program and others.).
    MeSH term(s) Adenoma/complications ; Adenoma/enzymology ; Adenoma/genetics ; Adrenal Gland Neoplasms/complications ; Adrenal Gland Neoplasms/enzymology ; Adrenal Gland Neoplasms/genetics ; Adrenal Hyperplasia, Congenital/genetics ; Adult ; Catalytic Domain ; Cushing Syndrome/enzymology ; Cushing Syndrome/etiology ; Cyclic AMP-Dependent Protein Kinases/chemistry ; Cyclic AMP-Dependent Protein Kinases/genetics ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Exome ; Germ-Line Mutation ; Humans ; Hydrocortisone/biosynthesis ; Middle Aged ; Mutation ; Protein Conformation ; Sequence Analysis, DNA
    Chemical Substances Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2014-02-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMoa1310359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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