A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication.

Expression of camelid-derived, single-domain antibodies (VHs) within the cytoplasm of mammalian cells as "intrabodies" has opened up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein. The intrabody consists of two structurally defined VHs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site.

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication.

Expression of camelid-derived, single-domain antibodies (VHs) within the cytoplasm of mammalian cells as "intrabodies" has opened-up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein (RIP). The intrabody consists of two structurally defined VHs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site.

Ortho-substituted but not coplanar PCBs rapidly kill cerebellar granule cells.

Several PCB congeners were assessed for their cytotoxicity on cerebellar granule cells in an attempt to compare their structure-activity relationship as potential neurotoxicants and to assess the mechanisms associated with their toxicity. Flow cytometry was used to monitor the changes of a number of biochemical endpoints: membrane integrity, intracellular free calcium concentration ([Ca(2+)](i)), reactive oxygen species (ROS) production, mitochondrial membrane potential (Delta psi(m)), and cell size. The non-coplanar, ortho-substituted congeners, PCB 8 (2,4'-dichlorobiphenyl), PCB 28 (2,4,4'-trichlorobiphenyl), PCB 47 (2,4,2',4'-tetrachlorobiphenyl), and PCB 52 (2,5,2',5'-tetrachlorobiphenyl) (10 microM) killed neurons to different degrees within 30 min.