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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 1; DOC041 /20051206/
    Publication Date: 2005-12-07
    Description: Einleitung: Die Fanconi-Anämie ist eine seltene, autosomal-rezessiv vererbte Erkankung, die durch eine schwere Knochenmarksaplasie und multiple Fehlbildungen charakterisiert ist. Die Inzidenz beträgt 1/300000 Lebendgeburten. Typisch ist eine vermehrte Chromosomenbrüchigkeit mit einer erhöhten Inzidenz an Leukämien und Plattenepithelkarzinomen vor allem im Kopf-Hals- sowie im Urogenitalbereich. Auch die unter Umständen notwendige allogene Knochenmarkstransplantation führt zu einer Erhöhung der Inzidenz unter anderem von Plattenepithelkarzinomen. In der Literatur sind bis dato 44 Fälle beschrieben. Fall: Im Oktober 2004 wurde uns von der Kinderklinik ein 13-jähriges Mädchen mit bekannter Fanconi-Anämie und Z.n. allogener Knochenmarkstransplantation 2002 zugewiesen. Die Patientin stellte sich wegen eines seit 3 Wochen bestehenden Ulkus im Bereich des linken Zungenrandes vor. Die histologische Aufarbeitung der gewonnenen Proben ergab ein invasiv-wachsendes, mäßig bis hoch-differenziertes Plattenepithelkarzinom. Zervikale Lymphknotenmetastasen liessen sich sonographisch nicht nachweisen. Es erfolgte eine lokale Nachresektion des T1-Tumors zur definitiven Sanierung. Fazit: Im Vergleich zur Normalbevölkerung ist die Inzidenz von Kopf-Hals-Tumoren bei Fanconi-Anämie mit Hauptlokalisation der Zunge deutlich erhöht. Diese treten in der Regel im jungen Erwachsenenalter auf. Die hier vorgestellte Patientin ist die zweitjüngste der bisher veröffentlichten Fälle. Die Therapie der Wahl besteht in einer operativen Sanierung. Radiatio und Chemotherapie sind bei diesen Patienten mit einer erhöhten Morbidität und Mortalität verbunden. Bei Patienten mit einer Fanconi-Anämie sollte bei Beschwerden im HNO-Bereich frühzeitig ein Karzinom ausgeschlossen werden.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 2
    Keywords: CELLS ; Germany ; human ; INHIBITION ; SITE ; COMPLEX ; COMPLEXES ; DOMAIN ; ANTIGEN ; T-CELLS ; BINDING ; GLYCOPROTEIN ; TRANSPORT ; CELL-LINE ; antigen presentation ; DOMAINS ; ENDOPLASMIC-RETICULUM ; MAJOR HISTOCOMPATIBILITY COMPLEX ; CLASS-I MOLECULES ; BINDING-SITE ; function ; BLOCKADE ; TAP ; cytomegalovirus ; INHIBITS PEPTIDE TRANSLOCATION ; PROTEIN ICP47 ; VACCINIA VIRUS
    Abstract: The endoplasmic reticulum-resident human cytomegalovirus glycoprotein US6 (gpUS6) inhibits peptide translocation by the transporter associated with antigen processing ( TAP) to prevent loading of major histocompatibility complex class I molecules and antigen presentation to CD8+ T cells. TAP is formed by two subunits, TAP1 and TAP2, each containing one multispanning transmembrane domain (TMD) and a cytosolic nucleotide binding domain. Here we reported that the blockade of TAP by gpUS6 is species-restricted, i.e. gpUS6 inhibits human TAP but not rat TAP. Co-expression of human and rat subunits of TAP demonstrates independent binding of gpUS6 to human TAP1 and TAP2, whereas gpUS6 does not bind to rat TAP subunits. gpUS6 associates with preformed TAP1/2 heterodimers but not with unassembled TAP subunits. To locate domains of TAP required for gpUS6 binding and function, we took advantage of reciprocal human/rat intrachain TAP chimeras. Each TAP subunit forms two contact sites within its TMD interacting with gpUS6. The dominant gpUS6-binding site on TAP2 maps to an N-terminal loop, whereas inhibition of peptide transport is mediated by a C-terminal loop of the TMD. For TAP1, two gpUS6 binding domains are formed by loops of the C-terminal TMD. The domain required for TAP inactivation is built by a distal loop of the C-terminal TMD, indicating a topology of TAP1 comprising 10 endoplasmic reticulum transmembrane segments. By forming multimeric complexes, gpUS6 reaches the distant target domains to arrest peptide transport. The data revealed a nonanalogous multipolar bridging of the TAP TMDs by gpUS6
    Type of Publication: Journal article published
    PubMed ID: 16356928
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR); 20160831-20160903; Frankfurt am Main; DOCKR.08 /20160829/
    Publication Date: 2016-08-29
    Keywords: JIA Malignome Methotrexat ; Etanercept ; ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
    Keywords: EXPRESSION ; CELL ; MOLECULES ; ESCHERICHIA-COLI ; MHC CLASS-I ; ENDOPLASMIC-RETICULUM ; TRANSPORTER ; IMMUNE EVASION ; INFECTED CELLS ; ANTIGEN-PROCESSING TAP ; HEAVY-CHAINS ; US6 GLYCOPROTEIN
    Abstract: Major histocompatibility complex class I (MHC I) molecules present antigenic peptides for CD8(+) T-cell recognition. Prior to cell surface expression, proper MHC I loading is conducted by the peptide-loading complex (PLC), composed of the MHC I heavy chain (HC) and beta(2)-microglobulin (beta(2)m), the peptide transporter TAP, and several chaperones, including tapasin. Tapasin connects peptide-receptive MHC I molecules to the PLC, thereby facilitating loading of high-affinity peptides onto MHC I. To cope with CD8(+) T-cell responses, human cytomegalovirus (HCMV) encodes several posttranslational strategies inhibiting peptide transport and MHC I biogenesis which have been studied extensively in transfected cells. Here we analyzed assembly of the PLC in naturally HCMV-infected fibroblasts throughout the protracted replication cycle. MHC I incorporation into the PLC was absent early in HCMV infection. Subsequently, tapasin neosynthesis became strongly reduced, while tapasin steady-state levels diminished only slowly in infected cells, revealing a blocked synthesis rather than degradation. Tapasin mRNA levels were continuously downregulated during infection, while tapasin transcripts remained stable and long-lived. Taking advantage of a novel method by which de novo transcribed RNA is selectively labeled and analyzed, an immediate decline of tapasin transcription was seen, followed by downregulation of TAP2 and TAP1 gene expression. However, upon forced expression of tapasin in HCMV-infected cells, repair of MHC I incorporation into the PLC was relatively inefficient, suggesting an additional level of HCMV interference. The data presented here document a two-pronged coordinated attack on tapasin function by HCMV
    Type of Publication: Journal article published
    PubMed ID: 21248040
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  • 5
    ISSN: 1573-904X
    Keywords: MECC ; bile salts ; partition coefficient ; interaction ; drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The general properties of micellar electrokinetic capillary chromatography (MECC) were utilized to characterize the strength of interactions between bile salts and biological active substances. Methods. For that purpose various bile salts were used as micellar pseudostationary phase in the background electrolyte. Furthermore, a physicochemical model was applied and the effective partition coefficients between micellar and water phase were calculated in order to evaluate the strength of interactions between bile acids and the drugs. Results. It was found that the interactions between the selected drugs and bile salts depend both on the lipohilicity of the drugs and on the charge of the components. Only hydrophobic, cationic drugs such as quinine and propranolol are able to interact with these surface-active agents. Conclusions. MECC is a valuable methode to characterize interactions such occurring between drugs and bile salts.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-904X
    Keywords: penetration ; step-scan FT-IR photoacoustic spectroscopy ; multilayer membrane ; diffusion coefficient ; clotrimazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this study was to elucidate the potential use of the step-scan FT-IR photoacoustic spectroscopy (PAS) for the nondestructive determination of drug penetration into membranes. Methods. The penetration of clotrimazole from a 10% (w/w) suspension in Vaseline® into a dodecanol-collodion acceptor membrane was studied by three methods: the step-scan FT-IR PAS with a phase modulation, a multilayer membrane system, and a modified libration model. Based on Fick's second law, the diffusion coefficient of the drug in the membrane was derived by numerical fitting of the experimental data. Results. The three methods applied provided almost the same diffusion coefficient D = 2.2 10-9 cm2/s for clotrimazole in the membrane. Because of the non-destructive mode of operation, the accuracy of results obtained by FT-IR PAS is much better than that attainable by other two methods. Conclusions. Step-scan FT-IR photoacoustic spectroscopy in conjunction with a phase modulation is useful to determine the penetration of drug through membranes. The fact that samples can be investigated without elaborate preparation is an advantage of this spectroscopic technique.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Protoplasma 19 (1933), S. 541-564 
    ISSN: 1615-6102
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 26 (1991), S. 463-467 
    ISSN: 0030-493X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A quadrupole, quistor, quadrupole tandem mass spectrometer allowing selected ion/selected molecule reactions was built. The quistor will be used as a reaction chamber for the study of organic ion-molecule reactions. Ions are generated in a differentially pumped ion source, quadrupole mass selected and injected into the quistor. The ions are trapped in the quistor by the combined action of a deceleration lens, the presence of helium buffer gas and the quistor RF field. As a first test of the performance of the instrument, the reaction rate constant of the reaction of O2+· with methane was measured to be 5 × 10-12 cm3s-1. This is in good agreement with literature values, indicating that the ions are near thermal equilibrium after a few milliseconds of trapping time.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied climatology 3 (1951), S. 110-122 
    ISSN: 1434-4483
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Description / Table of Contents: Summary The results of measurements of upperwinds at the coast of the Channel at an altitude of 1, 5 and 10 km for the period from 1941 till 1943 by means of electrical wireless direction-finding are given for the months, the quarters of a year and for the whole year.
    Abstract: Résumé On représente les résultats des observations du vent en altitude obtenues au moyen de gonio-sondages à la côte de la Manche, pour les mois, les trimestres et pour l'année à 1, 5 et 10 km d'altitude, pour la période de 1941 à 1943.
    Notes: Zusammenfassung Es werden für den Zeitraum 1941 bis 1943 die Ergebnisse der Höhenwindmessungen an der Küste des Ärmelkanals mit Hilfe elektrischer Peilungen für Vierteljahre, für das ganze Jahr und für die einzelnen Monate für die Höhe 1, 5 und 10 km dargestellt.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1436-2449
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Summary The cationic polymerization of isobutyl vinyl ether in liquid sulfur dioxide at several temperatures was initiated by the trityl halides, Ph3C-Cl and Ph3C-Br. The low molecular weight products obtained were investigated by reverse phase chromatography. RPC diagrams indicate that every chain carries trityl groups. These results are considered to be proof positive for initiation by direct trityl addition to monomer in cationic vinyl ether polymerization.
    Type of Medium: Electronic Resource
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