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  • 1
    ISSN: 1432-0584
    Keywords: B-cell activation ; Reverse hemolytic plaque assay ; Polyclonal B-cell activators ; B-Zell-Aktivierung ; Plaque Assay ; polyklonale B-Zell-Aktivatoren
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The kinetics of Pokeweed mitogen-induced transformation of human B-lymphocytes into immunoglobulin-secreting cells were examined in a reverse hemolytic plaque assay using protein A-coated sheep red blood cells as indicator cells. Peak responses occurred consistently after 6–8 days of incubation. After determination of the optimal experimental conditions the RHPA was found to be a reliable tool to estimate ISC in vitro; the technique was also found to be applicable for experiments surveying the B-cell response of an individual over a period of months. The PWM-induced transformation of B cells was absolutely T-cell-dependent. Other substances known as typical T-cell mitogens were also tested for polyclonal B-cell activation and some of them showed significant responses. Further experiments have shown that co-cultivation of non-HLA identical cells did not increase the number of plaques in unstimulated cultures whereas the addition of PWM leads to the generation of ISC within the expected range. These findings open a wide field of application of the RHPA in experimental and clinical immunology.
    Notes: Zusammenfassung Mit Hilfe eines Plaque Assays wurde die Kinetik der durch Pokeweed Mitogen induzierten Transformation menschlicher B-Lymphozyten in Immunglobulin-sezernierende Zellen untersucht. Als Indikatorzellen dienten Schafserythrozyten, an die Protein A gekoppelt war. Die maximale Stimulation wurde in allen Experimenten nach einer Kulturdauer von 6–8 Tagen erreicht. Nach Optimierung der Versuchsbedingungen erwies sich dieser Plaque Assay als ausgezeichnete Methode zur quantitativen Bestimmung der Anzahl Ig-sezernierender Zellen vitro; er war außerdem gut geeignet, die B-Zellfunktion eines Individuums über mehrere Monate zu verfolgen. Die Ergebnisse haben gezeigt, daß die durch Pokeweed Mitogen bewirkte B-Zellaktivierung an das Vorhandensein von Helfer-T-Zellen gebunden war. Außerdem konnte mit anderen, typischen T-Zellmitogenen, ebenfalls eine polyklonale B-Zellaktivierung bewirkt werden. — In weiteren Experimenten wurde gezeigt, daß die Ko-Kultivierung von Lymphozyten zweier nicht HLA-identischer Spender nicht zu einer B-Zellaktivierung führt; nach Stimulierung mit Pokeweed Mitogen wurde auch in diesen Kulturen eine Aktivierung gefunden, die dem erwarteten Ausmaß entsprach. Diese Befunde lassen den Schluß zu, daß mit dieser Technik wertvolle Ergebnisse in der experimentellen und klinischen Immunologie gewonnen werden können.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Lymphozyten-Aktivierung ; menschliche Lymphozyten-Subpopulationen ; Monozytenfunktion ; Lymphocyte activation ; Human lymphocyte subpopulations ; Monocyte function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Cowan I strain Staphylococcus aureus bacteria were found to be mitogenic for human peripheral and cord blood lymphocytes. Experiments with lymphocyte subpopulations obtained by nylon wool filtration and/or E-rosette separation revealed that T-lymphocytes are the main target cells, whereas isolated B cells did not respond significantly. Further experiments suggested that B cells could be activated in the presence of mitomycin-treated T cells. Null cell-enriched lymphocyte suspensions could be stimulated by Con A but not by the bacteria or by PHA.
    Notes: Zusammenfassung Staphylococcus aureus-Bakterien des Stammes Cowan I sind in der Lage, periphere menschliche Lymphozyten sowie Lymphozyten des Nabelvenenblutes in vitro zu stimulieren. Versuche mit Lymphozyten-Subpopuiationen, die mit Hilfe der Nylonsäulen-Trennung und/oder der E-RosettenTrennung gewonnen wurden, haben gezeigt, daß in erster Linie T-Lymphozyten aktiviert werden; isolierte B-Zellen wurden nicht stimuliert. Weitere Experimente lassen jedoch vermuten, daß B-Lymphozyten dann aktiviert werden, wenn Mitomycin-behandelte T-Zellen in den Kulturen vorhanden sind. Lymphozyten-Subpopulationen, die angereichert Null-Zellen enthielten, konnten zwar durch Con A, nicht aber durch die Bakterien oder durch PHA stimuliert werden.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0738
    Keywords: Teratogenicity in vivo ; Retinol ; Pharmacokinetics ; all-trans Retinoic acid ; Biotransformation ; Alcohol dehydrogenase ; 4-Methylpyrazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral administration of retinol (50 mg/kg) to NMRI mice on day 11 of gestation (vaginal plug = day 0) led to the metabolic formation of high quantities of all-trans retinoic acid and all-trans-4-oxoretinoic acid, both known as potent teratogenic agents in the mouse. A 96% reduction of the area under the concentration-versus-timecurve (AUC) of metabolically generated alltrans retinoic acid in maternal plasma, and an 84% decrease in the embryonic AUC were observed when mice had been pretreated with the alcohol dehydrogenase inhibitor 4-methylpyrazole. A similar reduction was observed for the major metabolite of all-trans retinoic acid in the mouse, all-trans-4-oxoretinoic acid. However, 4-methylpyrazole pretreatment decreased the AUC of retinol by 10% in maternal plasma and 15% in embryo. Treatment with retinol alone resulted in 55.6%, 43.9% and 56.0% skeletal anomalies of the forelimbs, hindlimbs and craniofacial structures, respectively. Pretreatment with 4-methylpyrazole lowered the retinol induced skeletal defects to 31.3%, 24.0% and 31.3%, respectively, in the forelimb, hindlimb and craniofacial region. Typical retinoid-induced malformations for gestational day 11, e.g. bent or reduced zeugopod or stylopod elements, or cleft palate, were significantly reduced by 4-methylpyrazole pretreatment but were still detected in significantly higher prevalence than in control mice. These data suggest that the teratogenic activity of a single high dose of vitamin A in mouse is partially but not exclusively dependent on the metabolic activation of retinol to all -trans retinoic acid. Thus it could be hypothesized that retinol is either a proximate teratogen or a coteratogen with all -trans retinoic acid.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0738
    Keywords: Ethylmethanesulfonate ; Teratogenicity ; NMRI mice ; Dose-response relationships ; DNA alkylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The directly acting monofunctional alkylating agent ethylmethanesulfonate is a potent teratogen in NMRI mice. Inspection of skeletal abnormalities revealed a clear-cut phase specificity of the teratogenic outcome, especially of the limb malformations, after single intraperitoneal injections on days 9, 10, 11 or 12 of pregnancy. Dose-response studies were performed using single i.p. treatment of day 11. A computer program was developed for probit transformation of the data and maximum-likelihood estimation of the dose-response curves, including standard deviations and comparison of the slopes. Some arguments are presented for the hypothesis that the teratogenicity of simple alkylating agents is quantitatively correlated to a well-defined DNA alkylation rate of embryonic cells at the O6-guanine site.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 52 (1983), S. 45-69 
    ISSN: 1432-0738
    Keywords: Acetoxymethyl-methylnitrosamine ; Teratogenicity ; NMRI mice ; Dose-response relationship ; DNA alkylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acetoxymethyl-methylnitrosamine, the acetate ester of the presumed reactive metabolite of dimethylnitrosamine, is an effective teratogen in NMRI mice. An unusual phenomenon of application route specificity and a pronounced phase specificity of the teratogenic effects induced are demonstrated. Dose-response relationships are established. Some further arguments are given to support the basic hypothesis that the teratogenicity of alkylating agents is closely correlated to the DNA alkylation rate of embryonic cells.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1440
    Keywords: Lymphocyte transformation ; hydrocortisone treatment ; whole-body irradiation ; Lymphocytentransformation ; Hydrocortison-Therapie Ganzkörperbestrahlung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Hydrocortisonbehandlung und Ganzkörperbestrahlung führen bei C57 Bl-Mäusen zu einer starken Reduktion der Zellzahlen in Thymus und Milz. Die resistenten Zellpopulationen sind durch PHA, PWM und Con A deutlich besser stimulierbar als Milz- und Thymuszellen unbehandelter Mäuse, wobei die mitogene Wirkung der getesteten Substanzen sehr unterschiedlich ist. Die Ergebnisse stützen die Annahme, daß cortison- und strahlenresistente Zellpopulationen die immunkompetenten Zellen enthalten.
    Notes: Summary Hydrocortisone treatment as well as wholebody irradiation cause marked cellular depletion in thymus and spleen from C57 Bl mice. The resistant cell populations were found to respond better to PHA, PWM and Con A than spleen- and thymus-cell populations of untreated mice. Great differences in reactivity in the various cell populations to the three mitogens were observed. The results support the hypothesis that the immunological competent cells are among the cortisone-resistant as well as among the radioresistant cell populations.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 288 (1975), S. 7-16 
    ISSN: 1432-1912
    Keywords: Hydroxyurea ; Mammalian Embryo ; Nucleic Acid ; in vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 14C-u-glucose and 32P-phosphate were given intravenously to pregnant rats, treated and untreated with hydroxyurea (HU). The incorporation of radio-activity into a variety of cell components of the embryo was measured. With this double-labelling technique it is possible to survey the effects of embryotoxic drugs on various pathways in mammalian embryos in vivo. Onset, extent and duration of the metabolic changes were measured after application of “non-teratogenic” and teratogenic doses of hydroxyurea (HU). 3 hrs after application of hydroxyurea only DNA synthesis is affected, whereas after 5 hrs RNA synthesis is also inhibited.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Infection 15 (1987), S. 261-262 
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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