Bcl-xL rescues WEHI 231 B lymphocytes from oxidant-mediated death following diverse apoptotic stimuli.

Developing lymphocytes undergo extensive cell death during selection of the immune repertoire. We investigated the influence of bcl-xL, a member of the bcl-2 family of apoptosis regulatory genes, on apoptosis in a model system for negative selection in the B lymphoid lineage. Overexpression of bcl-xL in WEHI 231 immature mouse B cells blocked apoptosis triggered by cross-linking of surface IgM. bcl-xL-transfected cells were also resistant to apoptosis following incubation in low serum medium or exposure to gamma-irradiation, the sphingomyelin ceramide, or compounds that increase intracellular levels of oxidants. Remarkably, the addition of antioxidants (catalase, N-acetylcysteine, or pyruvate) alone rescued the native WEHI 231 cells from apoptosis while having only minor effects on the viability of cells overexpressing bcl-xL. Anti-IgM cross-linking, ceramide, and gamma-irradiation treatments elevated intracellular peroxide production, which was prevented by treatment with antioxidants. Cells overexpressing bcl-xL had a similar rise in intracellular oxidants as control cells, indicating that bcl-xL modifies the cell's response to oxidants while having no detectable influence on the endogenous production of oxidants following apoptotic stimuli. These data implicate bcl-xL as a potent death repressor in B lymphocytes and support the hypothesis that bcl-xL regulates survival decisions within susceptible cells by functioning downstream of oxidant production.

Recurrent genitourinary chlamydial infections in sexually active female adolescents.

To determine the recurrence rate of chlamydial infections, we initially screened an urban population of 1308 sexually active female adolescents for chlamydial infection at the urethral and endocervical sites; these young women were followed and had additional examinations for infection. Chlamydial infection was documented by tissue culture in 31.1% (407) of them at some time during the study. After appropriate antibiotic treatment, 68.3% (278/407) returned for test-of-cure cultures within 3 months of their initial infection; of those 278, a total of 254 had sterile cultures. These patients were followed to determine the recurrence rate of chlamydial infections. Of these 254 patients, 177 (69.7%) had one or more follow-up visits; 38.4% (68/177) had a recurrent chlamydial infection. The majority of recurrent infections were documented within 9 months of the initial infection. Recurrent infections with the same serovar were frequent, suggesting reinfection by untreated partners or possible relapse of the initial chlamydial infection. This high rate of recurrent infection suggests that female adolescents should be rescreened frequently for genitourinary chlamydial infections.