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  • glutamic acid decarboxylase  (2)
  • healthy volunteers  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Expression of the 64 kDa/glutamic acid decarboxylase rat islet cell autoantigen is influenced by the rate of insulin secretion (1992)
    Springer
    Diabetologia 35 (1992), S. 490-493 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Autoantigen ; glutamic acid decarboxylase ; insulin secretion ; diazoxide ; islet cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary This study examined the relationship between insulin secretion and expression of the 64 kDa/glutamic acid decarboxylase autoantigen in pancreatic islets. Islets isolated from Wistar rats were cultured for 3 days under different conditions: in 5.5 mmol/l glucose with or without a-ketoisocaproic acid or glipizide and in 28 mmol/l glucose with or without diazoxide. The 64 kDa/glutamic acid decarboxylase autoantigen was precipitated from lysates of [35S]-methionine-labelled islets with sera from patients with Type 1 (insulin-dependent) diabetes mellitus and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. In parallel, insulin contents of the islets and the media were determined as well as the rates of glucose-stimulated (pro)insulin biosynthesis. α-Ketoisocaproic acid and glipi zide were found to stimulate the expression of the 64 kDa/glutamic acid decarboxylase autoantigen and also the rate of insulin secretion. Diazoxide on the other hand reduced the rate of the 64 kDa/glutamic acid decarboxylase autoantigen synthesis in parallel with an inhibition of glucose-stimulated insulin release. Under most of the conditions employed, (pro)insulin biosynthesis was not affected. The correlation found between the rate of insulin release and expression of the 64 kDa/glutamic acid decarboxylase auto-antigen might provide an explanation for the earlier observed relationship between the functional demands on the Beta cells and their rate of destruction which may result in diabetes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02342450
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  • 2
    Digitale Medien
    Digitale Medien
    Human autoantibodies react with glutamic acid decarboxylase antigen in human and rat but not in mouse pancreatic islets (1993)
    Springer
    Diabetologia 36 (1993), S. 39-46 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Type 1 (insulin-dependent) diabetes mellitus ; autoantigen ; glutamic acid decarboxylase ; NOD mouse ; islets of Langerhans
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The presence of one of the major targets for auto-antibodies in Type 1 (insulin-dependent) diabetes mellitus, the enzyme glutamic acid decarboxylase, was studied in human, rat and mouse pancreatic tissue using immunoprecipitation and immunohistochemical techniques. Immunoprecipitation of glutamic acid decarboxylase was attempted with lysates of [35S]-methionine-labelled rat or mouse pancreatic islets using two different glutamic acid decarboxylase antisera, one mouse monoclonal antibody raised against the 65 kDa isoform of the enzyme, sera from six patients with Type 1 diabetes, one patient with stiff-man syndrome and sera from 19 non-obese diabetic mice. The same sera were used for immunoperoxidase staining of cryosections of human, rat or mouse pancreas. Using patient sera glutamic acid decarboxylase was detected by immunoprecipitations from isolated rat islets but not from islets of five different mouse strains tested, including the non-obese diabetic mouse. When using the non-obese diabetic mouse sera, glutamic acid decarboxylase could not be detected in either rat or mouse tissue. Immunoperoxidase staining demonstrated high levels of glutamic acid decarboxylase in human and rat pancreatic islets but low levels in mouse islets. Direct measurements of enzyme activity showed glutamic acid decarboxylase to be present in mouse islets at a level of about 40% of that in rat islets, and subsequent Western blot analyses indicated that mouse islets express the 67 kDa isoform, whereas in rat islets both the 67 and 65 kDa isoforms are present. The species difference at the level of one of the major islet cell autoantigens in Type 1 diabetes thus indicates that human or rat and mouse islets, respectively, express immunologically distinct forms of glutamic acid decarboxylase and differ in their way of regulating the enzyme production.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00399091
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  • 3
    Digitale Medien
    Digitale Medien
    An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 459-463 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Key words Corticosteroids; systemic effects ; plasma cortisol suppression ; white blood cell count ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18–29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a 20 h period after drug administration (after a single dose and after the last of seven doses) and area under the curve (AUC0–20) for plasma cortisol and white blood cell (WBC) counts was calculated. Results: The present study shows that multiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) resulted in a marked cortisol suppression from placebo which, at 55%, was more than double that seen with a single dose (25% suppression). Multiple dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression in plasma cortisol compared with a suppression of 26% with a single dose. The increase in systemic activity of FP after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts. Conclusion: The results of the present study confirm previous findings with regard to the more marked systemic effect of FP following multiple dosing as compared with a single dose. This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002280050050
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  • 4
    Digitale Medien
    Digitale Medien
    An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 459-463 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Corticosteroids ; systemic effects ; plasma cortisol suppression ; white blood cell count ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18–29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a 20 h period after drug administration (after a single dose and after the last of seven doses) and area under the curve (AUC0–20) for plasma cortisol and white blood cell (WBC) counts was calculated. Results: The present study shows that multiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) resulted in a marked cortisol suppression from placebo which, at 55%, was more than double that seen with a single dose (25% suppression). Multiple dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression in plasma cortisol compared with a suppression of 26% with a single dose. The increase in systemic activity of FP after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts. Conclusion: The results of the present study confirm previous findings with regard to the more marked systemic effect of FP following multiple dosing as compared with a single dose. This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00195931
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