Capping and internalization of a monoclonal antibody-surface antigen complex: a possible mode of interaction of monoclonal antibodies and tumor cells

Our results demonstrate that upon incubation of 125I-3G5 (a monoclonal IgM against a membrane ganglioside antigen on RINm5F cells) with rat insulinoma RINm5F cell monolayers at 37 degrees C, the IgM is rapidly internalized. Cell-bound radioactivity, detectable within 10 to 15 minutes, reaches a peak at 4 hours. By 24 hours the intracellular radioactivity has decreased to about 37.5% of the 4-hour value, accompanied by an increase in free 125I in the incubation medium. The incubation of 125I-3G5 with RINm5F cell monolayers at 4 degrees C shows that this series of events is inhibited by low temperature. Microautoradiography confirms these events indicating the presence of radiolabeled antibody on the plasma membrane as well as distinct capping processes and diffuse radioactive deposits within the cells as early as 5 to 10 minutes after initiating incubation at 37 degrees C. Electron microscopy autoradiography provides a detailed demonstration of the capping phenomenon and of endocytic vacuoles, followed at later times by the distribution of radioactive deposits throughout the cell. This model constituted by the capping of the 125I-3G5-ganglioside complex on rat insulinoma RINm5F cells may be useful in elucidating a possible mode of interaction of monoclonal antibodies and tumor cells.     

Prostaglandin A1 inhibition of chondrosarcoma growth

The effects of various prostaglandins (PG) on the in vitro synthesis of macromolecules by two transplantable chondrosarcomas were studied. Prostaglandin A₁ markedly inhibited the incorporation of radioactive precursors into chondromucoprotein, total protein, RNA and DNA of both a well differentiated rat chondrosarcoma and a poorly differentiated murine chondrosarcoma. PGE₁ and PGF_1α had no effects on the synthesis of macromolecules by either tumor. PGA₁ inhibitory effects occurred over a dose range of 1 to 25 μg/ml. PGA₁ had no effect on the synthesis of macromolecules by liver. The data indicate that malignant transformation of cartilage cells does not alter their responsiveness to PGA₁.     

Evolution of antibiotic resistance genes: the DNA sequence of a kanamycin resistance gene from Staphylococcus aureus

The kanamycin resistance gene from Staphylococcus aureus has been sequenced and its structure compared with similar genes isolated from Streptomyces fradiae and from two transposons, Tn5 and Tn903, originally isolated from Klebsiella pneumoniae and Salmonella typhimurium, respectively. The genes are all homologous but, since their common ancestor, have undergone extensive divergence, with more than 43% divergence between the closest pair. The phylogeny of the genes cannot be made congruent to the phylogeny of the taxa from which they were isolated without requiring rather improbable differences in rates. One is therefore led to conclude that there have been multiple occurrences of gene transfer between these species. Thus, although they are homologous, they are neither orthologous nor paralogous. It is suggested that homologous genes of this type be called xenologous.