Delivery of the ibosome-inactivating protein, gelonin, to Iymphoma cells via CD22 and CD38 using bispecilic antibodies

It is well established that bispecific antibodies (BsAbs) can be used effectively in targeting the ribosome-inactivating protein (RIP), saporin, against neoplastic B cells. We have now extended this delivery system for use with gelonin. By measuring antigen-binding characteristics and epitope mapping a panel of anti-gelonin MAbs using the IAsys resonant mirror bisensor, we were able to rapidly select the most suitable for making BaAbs. The Fab’ fragments from these MAbs were chemically conjugated with Fab’ from either anti-CD22 or anti-CD38. Cytotoxicity assays showed that BsAbs were highly efficient at delivering gelonin to cultured Daudi cells and achieved levels of toxicity which correlated closely with the affinity of the BsAbs. Using pairs of anti-CD22 BsAbs we were able to generate bivalent BsAb-gelonin complexes which achieved IC50 values of 2 x 10 -11 M gelonin, a potency which is equivalent to that reached by saporin in this targeting system. However, because gelonin is 5-10 times less toxic than saporin, the therapeutic ratio for gelonin is superior, making it potentially a more useful agent for human treatment. Cytotoxicity assays and kinetic analysis showed that targeting gelonin via CD38 was 2-5 times less effective than delivery through CD22. However, with a pair of BsAbs designed to co-target gelonin via CD22 and CD38, the cytotoxicity achieved equalled that obtained with a pair of anti-CD22 BsAbs (IC50 = 1 x 10 -11 M). This important result suggests that the anti-CD38 helps bind the gelonin to the cell and is then ‘dragged’ or ‘piggy-backed’ into the cell by the anti-CD22 BsAb. The implication of these findings for cancer therapy is discussed. © 1995 Stockton Press. All rights reserved

Catabolic enzyme activities in relation to premigratory fattening and muscle hypertrophy in the gray catbird ( Dumetella carolinensis )

The flight muscles of the gray catbird ( Dumetella carolinensis ) were examined to determine if short term adjustments occur in the activity of key catabolic enzymes during preparation for long distance migration. The aerobic capacity of the pectoralis muscle as indicated by citrate synthase activity (CS) is among the highest reported for skeletal muscle (200 μmoles [min·g fresh mass] −1 at 25°C). The mass specific aerobic capacity as indicated by CS activity or cytochrome c concentration does not change during premigratory fattening (Fig. 2) or in relation to the muscle hypertrophy that occurs concomitantly. The maintenance of mass specific aerobic capacity indicates that the total aerobic capacity increases in proportion to the increase in muscle size. The augmented potential for total aerobic power output is considered an adaptation to meet the increased power requirements of flight due to the increased body mass. Additionally, the capacity to oxidize fatty acids, as indicated by β-hydroxyacyl-CoA dehydrogenase activity, approximately doubles during premigratory fattening (from 35 to 70 μmoles [min·g fresh mass] −1 at 25°C; Fig. 1A). This adaptation should favor fatty acid oxidation, thereby sparing carbohydrate and prolonging endurance. The activity of phosphofructokinase, a key glycolytic enzyme, does not change before migration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47125/1/360_2004_Article_BF01101461.pd

A catalog of files and microfilms of the German Foreign Ministry archives, 1920-1945 /

"Continues and completes the work of the Catalogue of German Foreign Ministry files and microfilms, 1867-1920, which was published by the American Historical Association in 1959.""Published as a joint project of the United States Department of State and the Hoover Institution on War, Revolution, and Peace."Mode of access: Internet