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  • 1
    ISSN: 1432-0851
    Keywords: Microdistribution ; Radioantibodies ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inaccessibility of radiolabeled antibody to poorly vascularized regions of solid tumors may reduce the therapeutic efficacy of these macromolecules. Theoretical mathematical models have predicted that increasing the protein dose administered would reduce the heterogeneity of radioantibody distribution. This investigation was undertaken to evaluate this hypothesis in experimental animal models. We have utilized the technique of macroautoradiography to demonstrate an increase in tumor penetration of the lower-affinity125I-labeled NP-4 or higher-affinity Immu-14 anti-carcinoembryonic antigen (anti-CEA) mAbs into small (60.25—0.4 g) and large (0.8–1.5 g) GW-39 and LS174T human colonic xenografts, grown subcutaneously in the nude mouse, when 400 µg unlabeled antibody is administered simultaneously with 10 µg (100 µCi) radioantibody. Further increases in protein to 800 µg result in a reduction in total tumor uptake of the antibody. These differences in mAb distribution could be visualized as early as 1 day after antibody injection. Improved mAb penetration was also achieved for the Mu-9 anti-CSAp (anti-mucin) antibody using 800 µg unlabeled antibody. An irrelevant antibody (AFP-7-31) was found to be homogeneously distributed 3 days after injection, even at a low protein dose. Attempts to improve mAb penetration by increasing the protein dose in the GS-2 colorectal tumor, a model that has low NP-4 accretion as a result physiological barriers separating antibody from antigen, were not successful. These results suggest that a more homogeneous distribution of radioantibody can be achieved by carefully selecting a dose of unlabeled antibody to coadminister. Work is currently in progress to determine the effect of improved tumor distribution of radioantibody on the therapeutic potential of a single dose of radioantibody.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Liver/small bowel transplantation ; Tolerance ; Dendritic cells ; Kupffer cells ; Antigen-presenting cells ; Chimerism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The predictive value of chimerism was evaluated in three different transplantation models in the rat without immunosuppression: small bowel- (SBTx), liver- (LTx), and liver/small bowel transplantation (LSBTx) were performed in the Brown Norway (BN)-to-Lewis- (LEW) strain combination. Immunohistochemistry and flow cytometry were used to identify donor cells in the recipient's spleen. Their number did not change significantly during transient rejection or tolerance after LTx and LSBTx. However, the amount of donor-derived nonparenchymal cells within the liver allograft including antigen-presenting cells (APCs), such as dendritic and Kupffer cells, clearly mirrored the recipient's immune status: as expected, their number decreased during rejection, but recovered considerably during and after tolerance induction. We conclude that donor cells in the periphery of the recipient correlate with the presence of the allograft, but do not seem to influence graft acceptance actively. However, the kinetics of the detected donor APC population in the liver suggests their important role in modifying the recipient's immune response towards tolerance.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Hydrobiologia 78 (1981), S. 107-112 
    ISSN: 1573-5117
    Keywords: Aquatic macrophytes ; consumption ; caddis larvae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Larvae of Potamophylax cingulatus (Steph.) (Trichoptera) which are polyphagous herbi- and detritivorous, were used as test organism to investigate the palatability of aquatic and terrestrial macrophytes. In 7 out of 9 plant pairs the consumption rate was low on the species growing in or close to water. The consumption rate was negatively correlated with the nitrogen content of the plant. It is argued that the majority of the aquatic plants produce secondary plant substances, which reduce the attacks by aquatic herbivores. A restricted distribution, the long time of exposure to herbivores, as well as the relatively large probability of being discovered at the border of an inhabitable area, are factors suggested to have influenced the development of chemical defence mechanisms in aquatic macrophytes.
    Type of Medium: Electronic Resource
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