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  • 1
    Electronic Resource
    Electronic Resource
    Karlsburg Type I diabetes risk study of a general population: frequencies and interactions of the four major Type I diabetes-associated autoantibodies studied in 9419 schoolchildren (1999)
    Springer
    Diabetologia 42 (1999), S. 661-670 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I (insulin-dependent) diabetes ; prediction ; screening approach ; schoolchildren ; normal population ; autoantibodies ; GADA ; IA2A ; IAA ; ICA.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The Karlsburg Type I (insulin-dependent) diabetes risk study on schoolchildren aims to evaluate the predictive diagnostic value of diabetes-associated autoantibodies in the general population. Methods. We took capillary serum from 9419 schoolchildren, aged 6–17 years, for testing of autoantibodies (AAbs) to glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA2A) and insulin (IAA) by 125I-antigen binding. We also tested for autoantibodies to cytoplasmic islet cell antigens (ICA) immunohistochemically. Results. By testing of 9419 sera for the four AAbs at cut-off at or greater than the 98th centile for the radioassayed AAbs and at or greater than 10 Juvenile Diabetes Foundation (JDF) units for ICA, 8.1 % of schoolchildren had at least one AAb. We found that 3.04, 2.97, 2.35, and 0.86 % had IAA, GADA, IA2A or ICA, respectively. 7.3 % had only one AAb and 0.8 % (75) had two or more AAbs, reflecting a risk to develop diabetes. Thus, by primary screening by combined testing of GADA and IA2A, 98.7 % (74/75) would be identified. At high AAb levels, cut-off at or greater than the 99.8th centile and at or greater than 40 JDF units for ICA, 0.23 % (22/9419) of schoolchildren, similar to the disease prevalence of 0.3 %, had two or more AAbs. Ten of 17 children tested had reduced (p 〈 0.001) first-phase insulin secretion by intravenous glucose tolerance test. Six of 22 subjects developed Type I diabetes within a follow-up of 19 ± 10 months. Conclusion/interpretation. For children older than 5 years the combined anti-GAD/IA2 test with cut-off at or greater than the 98th centile should be used for primary screening followed by testing for IAA and ICA. Subjects at risk for diabetes have two or more AAbs at or greater than the 98th centile. Subjects at risk for rapid progression to Type I diabetes have two or more AAbs at or greater than the 99.8th centile. [Diabetologia (1999) 42: 661–670]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051213
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  • 2
    Electronic Resource
    Electronic Resource
    Organic light emitting devices based on vapor deposited films of end-capped sexithiophene: Evidence for Schottky barriers and transport limitations (1997)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 82 (1997), S. 3003-3013 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Light emitting devices with a sandwich structure: metal/EC6T/indium-tin-oxide, using end-capped sexithiophene (EC6T) as active organic material were fabricated by vapor deposition. Current and intensity of electroluminescence (EL) of the EC6T layers were measured as a function of voltage for various metals (Ca, Mg, Al, In, Ag) in a wide range of temperatures (4–300 K) and thicknesses of the EC6T layers (40–350 nm). External quantum efficiencies (10−6–10−3) and rectification ratios significantly depend on the metal contact which is compatible with a Schottky barrier. Electron injection from the metal at higher voltages correlates with the onset of significant EL. Current–voltage (I–V) curves exhibit a strong temperature and thickness dependence, mainly due to the charge transport across the EC6T layer. At low temperatures I–V curves show space charge limited currents. Modeling including double injection and trap states is performed. Results are discussed under the aspect of further device optimization. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.366138
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  • 3
    Electronic Resource
    Electronic Resource
    Antigenität von Polyestergefäßprothesen (Dacron) (1999)
    Springer
    Gefässchirurgie 4 (1999), S. 91-95 
    Details
    ISSN: 1434-3932
    Keywords: Schlüsselwörter Biokompatibilität ; Antigenität ; Polyester ; Kollagen ; Key words Biocompatibility ; Antigenicity ; Polyester ; Collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract At present there is neither an completely inert biomaterial available, nor does a universal test exist which objectively evaluates biocompatibility. One reason is the individuality of the host, especially with regard to the inflammatory response. Inflammation was found to induce biodegradation by hydrolysis or auto-oxidation of vascular prosthetic matrix after implantation. The present study was performed to investigate the specific humoral immune response after implantation of segments of a collagen-impregnated polyester prosthesis (Dacron) in Balb/c mice on experimental days 1, 18, 38, and 322. Serum antibody detection was performed by modified enzyme immunoassay using the prosthesis as a target. Specific polymer antibodies, enhanced by repeated implantations, could be detected in all mice which received grafts up to experimental day 322. These antibodies were not directed against the collagen coating. The antibody formation could be further enhanced by a combined administration of complete Freund's adjuvant together with the first implantation at experimental day 1. Results suggest that specific polymer antibodies, reflecting an inflammatory response, might be an additional parameter for biocompatibility testing of vascular prostheses.
    Notes: Zusammenfassung Bisher stehen keine komplett inerten Biomaterialien zur Verfügung und es existiert kein universeller Test zur Objektivierung der Biokompatibilität. Dies resultiert aus der individuellen Variabilität des Empfängerorganismus, insbesondere hinsichtlich der entzündlichen Reaktionsbereitschaft. Auch nach Implantation von Gefäßprothesen aus polymeren Biomaterialien kommt es zu einem chronischen Entzündungsprozeß. Dieser führt ursächlich durch Hydrolyse oder Autoxidation zur Biodegradation des Implantats. Mit unseren Untersuchungen galt es, eine möglicherweise bestehende, spezifische humorale Immunantwort nach Implantation von Segmenten einer kollagenimprägnierten Polyesterprothese (Dacron) in einem Tiermodell darzulegen. Balb/c-Mäusen wurde am 1., 18., 38. und 290. Versuchstag ein Prothesensegment intraperitoneal implantiert. Die Bestimmung der Serumantikörper erfolgte mit einem modifizierten Enzymimmunoassay unter Verwendung der Prothese als Target. Spezifische Antikörper gegen Polymere wurden nach wiederholter Implantation bei allen Tieren bis zum 322. Versuchstag nachgewiesen. Dabei konnte eine Antikörperbildung gegen die Kollagenimprägnierung ausgeschlossen werden. Die Antikörperbildung wurde durch den Zusatz von komplettem Freund-Adjuvans in Verbindung mit der ersten Implantation verstärkt. Der Nachweis von spezifischen Antikörpern gegen Polymere könnte zukünftig ein Parameter zur Testung der Biokompatibilität darstellen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00010549
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  • 4
    Electronic Resource
    Electronic Resource
    Murine monoclonal glutamic acid decarboxylase (GAD)65 antibodies recognize autoimmune-associated GAD epitope regions targeted in patients with type 1 diabetes mellitus and Stiff-man syndrome (1996)
    Springer
    Acta diabetologica 33 (1996), S. 225-231 
    Details
    ISSN: 1432-5233
    Keywords: Key words Murine monoclonal glutamate decarboxylase antibodies ; Autoantibodies ; Type 1 diabetes mellitus ; Stiff-man syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. Of the 44 monoclonals, 35 are specific for the GAD65 isoform, whereas 9 also react with GAD67. Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. The 125I-GAD binding of the GAD65 monoclonals reactive on Western blotting was significantly diminished by all 3 sera from Stiff-man syndrome patients but only by 3/30 (10%) sera from type 1 diabetic patients. In contrast, the 7 monoclonal antibodies reactive with a conformation-dependent GAD epitope were competitive with 83% of GAD-autoantibody-positive sera from these diabetic patients. Using chimeric GAD65/67 proteins, the epitope region targeted by these monoclonals was mapped to the middle of GAD65 (amino acids 221–442). This central conformation-dependent GAD region was also targeted by sera from patients with type 1 diabetes. In conclusion, our data show that even after common immunization of a nondiabetes-susceptible mouse strain, monoclonals were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4–17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the beta-cell destruction in type 1 diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02048548
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  • 5
    Electronic Resource
    Electronic Resource
    Murine monoclonal glutamic acid decarboxylase (GAD)65 antibodies recognize autoimmune-associated GAD epitope regions targeted in patients with type 1 diabetes mellitus and Stiff-man syndrome (1996)
    Springer
    Acta diabetologica 33 (1996), S. 225-231 
    Details
    ISSN: 1432-5233
    Keywords: Murine monoclonal glutamate decarboxylase antibodies ; Autoantibodies ; Type 1 diabetes mellitus ; Stiff-man syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. Of the 44 monoclonals, 35 are specific for the GAD65 isoform, whereas 9 also react with GAD67. Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. The125I-GAD binding of the GAD65 monoclonals reactive on Western blotting was significantly diminished by all 3 sera from Stiff-man syndrome patients but only by 3/30 (10%) sera from type 1 diabetic patients. In contrast, the 7 monoclonal antibodies reactive with a conformation-dependent GAD epitope were competitive with 83% of GAD-autoantibody-positive sera from these diabetic patients. Using chimeric GAD65/67 proteins, the epitope region targeted by these monoclonals was mapped to the middle of GAD65 (amino acids 221–442). This central conformation-dependent GAD region was also targeted by sera from patients with type 1 diabetes. In conclusion, our data show that evne after common immunization of a nondiabetes-susceptible mouse strain, monoclonals were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4–17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the bete-cell destruction in type 1 diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02048548
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  • 6
    Electronic Resource
    Electronic Resource
    Impact of metabolic activity of beta cells on cytokine-induced damage and recovery of rat pancreatic islets (1995)
    Springer
    Acta diabetologica 32 (1995), S. 217-224 
    Details
    ISSN: 1432-5233
    Keywords: Cytokine ; Islet of Langerhans ; Insulin secretion ; Nitrite ; Heat shock proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of beta cell activity on cytokineinduced functional and structural impairments as well as the ability of those damaged cells to recover were investigated. Rat islets cultured for 4 days in the presence of 5, 10, and 30 mmol/l glucose were exposed to interferon-γ (IFN, 500 U/ml) and tumor necrosis factor-α (TNF, 250 U/ml) for the last 24 h. After cytokine removal islets were allowed to recover spontaneously in culture medium containing 10 mmol/l glucose for a further 7 days. Cytokines significantly inhibited insulin release into culture medium, insulin storage, glucose-stimulated insulin secretion, protein, and DNA synthesis. In the presence of cytokines there was a six- to eightfold increase in nitrite production by the islets. The functional impairments were more pronounced in metabolically stimulated beta cells. In addition, cytokines caused membrane alterations as indicated by increased spontaneous chromium-51 release. The cytokines specifically induced the synthesis of two proteins (72 and 88 kDa, respectively). By immunoblotting, the 72-kDa protein was identified as heat shock protein. After a 1-week recovery period, insulin storage and stimulated insulin secretion of cytokine-treated islets were still significantly diminished. However, protein and DNA synthesis of cytokine-exposed islets returned to pre-exposure levels. In conclusion, high beta cell activity increases islet susceptibility to TNF+IFN. Cytokine-induced, longlasting, inhibitory effects are primarily directed to betacell-specific functions, while general vital cell functions clearly recover after cytokine removal. The induction of certain proteins and the increased protein synthesis and replication rate after cytokine removal might reflect activated repair processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00576253
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  • 7
    Electronic Resource
    Electronic Resource
    An analysis of 1983 observations of facular contrast with an extreme limb photometer (1996)
    Springer
    Solar physics 168 (1996), S. 259-272 
    Details
    ISSN: 1573-093X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Analysis of facular contrast ΔI/I qs from Extreme Limb Photometer (ELP) data of the summer of 1983 yield a mean contrast of 0.91 ± 0.19% and 1.57 ± 0.16% for apertures 1 and 2 located at μ= 0.198 and at μ = 0.111, respectively. The ratio of the mean contrast in the outer aperture (closer to the limb) to that of the inner one is 1.71 ± 0.40, indicating an increase in the mean facular contrast toward the limb. This result is in agreement with observations made in 1975, 1979, and 1982. The errors are dominated by the random presence of solar active regions. The combined results from all seasons follow an approximately μ −1 curve. Facular excess solar oblateness signals for 1983 are 33.8 ± 6.6 arc ms and 16.5 ± 2.1 arc ms for ELP apertures 1 and 2, respectively, in reasonable agreement with the 1983 excess solar oblateness results of Dicke, Kuhn, and Libbrecht (1985).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00148054
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