Biomedical subjects
T Costello
Publications and source records attributed to T Costello.
Transport of infectious reovirus into bile: class II major histocompatibility antigen-bearing cells determine reovirus transport.
We have previously demonstrated that mammalian reovirus type 1 enters the bile and gut lumen after systemic administration. In the present study, we showed that Kupffer cell uptake is essential for the transport of reovirus into the bile. Furthermore, class II major histocompatibility antigen (I-A)-bearing cells are a major determinant for the transit of reovirus from the hepatic environment, as well as from the intestine, during the course of systemic infection. These findings may provide an approach to the control of viral pathogens that cause systemic disease by selective utilization or modification of I-A-bearing cells.
Reovirus type 1 is secreted into the bile.
Reovirus type 1, known to be a cause of systemic and intestinal disease in mice, is secreted into the bile of adult A/J mice after viremia. Virus found in the bile in concentrations higher than those in blood may indicate that reovirus type 1 is actively transported into the bile. The transport of virus was independent of levels of virus-specific immunoglobulin A antibody. Modifications of the virus that occurred during transport did not discernibly affect the infectivity of the virus. Entry of virus into the bile may be an important mechanism by which an enteric virus that produces systemic disease reenters the intestine for transmission.
Chemosensitization: do thiols matter?
It is well known that endogenous sulfhydryls are radioprotective in mammalian cells. Their comparable role in chemotherapeutic drug toxicity has been known for almost as long but less well defined. Thiol depletion as a mechanism responsible for enhanced cytotoxicity of melphalan was assayed by pretreatment of cells in vitro with misonidazole and buthionine sulfoximine (BSO). Hypoxic cell sensitizers, such as MISO, deplete endogenous thiols by metabolic activation under hypoxic conditions to thiol reactive intermediates, whereas BSO specifically inhibits a key enzyme in the synthesis of glutathione. For a given level of thiol reduction, sensitization to melphalan was far greater by preincubation with MISO than it was for BSO. This indicated that thiol reduction itself was not the sole factor involved in chemosensitization by MISO. As evidence that the method of thiol depletion predisposes to the expression of biological damage, it was shown that cells preincubated with MISO were appreciably more vulnerable to oxidative stress than those exposed to BSO. BSO was shown to totally inhibit the repair of damage from a preincubation treatment with MISO, demonstrating that recovery is dependent upon thiol regeneration. Thiol depletion "per se" is a good qualitative but not necessarily a quantitative indicator of chemosensitization--the biological and biochemical function of the thiol depleting agents used influences further drug interactions. The results of the study with these two agents suggest that thiols may play a potentially more critical role in the repair rather than the initiation of drug-induced damage.