Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells.

STAT5 transcription factors are involved in normal B lymphocyte development and in leukemogenesis. We show that the inhibition of STAT5A expression or activity in the NALM6, 697 and Reh leukemic pre-B cell lines, results in a higher spontaneous apoptosis and an increased FAS-induced cell death. However, the molecular mechanisms underlying the altered pre-B cell survival are unclear. We used a proteomic approach to identify proteins that are differentially regulated in cells expressing (NALM6Δ5A) or not a dominant negative form of STAT5A. Among the 14 proteins identified, six were involved in the control of the oxidative stress like glutathione (GSH) synthetase and DJ-1. Accordingly, we showed increased levels of reactive oxygen species (ROS) in NALM6Δ5A cells and suppression of the increased sensitivity to Fas-mediated apoptosis by the GSH tripeptide. Similar results were observed when NALM6 cells were treated with TAT-STAT5Δ5A fusion proteins or STAT5A shRNA. In addition, the 697 and Reh pre-B cells were found to share number of molecular changes observed in NALM6Δ5A cells including ROS generation, following inhibition of STAT5 expression or function. Our results point out to a hitherto undescribed link between STAT5 and oxidative stress and provide new insights into STAT5 functions and their roles in leukemogenesis.

[Use of an experimental Chlamydia trachomatis salpingitis model for evaluating the effectiveness of antibiotics and anti-inflammatory agents on fertility]. / Utilisation d'un modèle de salpingite expérimentale à Chlamydia trachomatis pour l'évaluation de l'efficacité des antibiotiques et des anti-inflammatoires sur la fertilité.

OBJECTIVES: An experimental model of Chlamydia trachomatis salpingitis was developed in mice to study the effect of combination antibiotic and antiinflammatory therapy on restoring fertility after tubal infection. METHODS: The mice were infected by injection via the ovarian bursa with a suspension containing a human strain of Chlamydia trachomatis sevar F. After treatment with antibiotics alone or in combination with antiinflammatory agents, fertility was studied at 4 months. RESULTS: With doxycycline and ofloxacine, there was not a significant difference in fertility between animals treated with antibiotics alone and those treated with antibiotics and antiinflammatory agents. However, a piroxicam and azythromycin combination improved fertility with a longer delay than with azythromycin alone. The most important factor appeared to be the antibiotic treatment. CONCLUSION: Associating an antiinflammatory agent was not shown to have a beneficial effect in reducing infertility after Chlamydia trachomatis salpingitis.

Use of an experimental model of chlamydial salpingitis in mice for the evaluation of activity of antibiotics and anti-inflammatory drugs on fertility.

An experimental animal model has been used to study the separate and combined use of antibiotics and anti-inflammatories in the treatment of salpingitis. The addition of an anti-inflammatory did not seem to help preserve fertility.

Establishment of hybridomas secreting monoclonal antibodies to Chlamydia psittaci.

Eleven stable anti-Chlamydia hybrid clones by fusions between X63-Ag8653 myelomas and immune splenocytes from Chlamydia psittaci immunized F1 (C57BL6 X BALB/c) mice have been established which react with the 12 reference Chlamydia strains (seven C. trachomatis and five C. psittaci. Ten of these monoclonal antibodies are directed against the genera-specific epitope (40,000 MW component) for which prolonged immunization seems to be responsible.

[Effect of various antiseptics on Chlamydia trachomatis]. / Action de différents antiseptiques sur Chlamydia trachomatis.

We compared the activity of different antiseptics (chlorhexidine, picloxidine dichlorhydrate, povidone-iodine, and noxythiolin) on Chlamydia trachomatis using two techniques. In the first, an antigenic preparation obtained from a Chlamydia trachomatis-infected cell culture was used. Different times of contact and different concentrations were studied. The antigen-antiseptic mixture was inoculated on healthy cell cultures and infected cells were counted 48 hours later. In the second technique, previously infected cells were incubated with antiseptics at different concentrations for 48 hours. Results are given as a percentage of infected cells. Chlorhexidine and picloxidine dichlorhydrate have a rapid action on Chlamydia trachomatis. Noxythiolin requires a longer period (2 hours) to be active. Povidone-iodine exhibits no activity on Chlamydia trachomatis.

[Kinetic study of the antibodies in OF 1 and C57Bl mice infected with Chlamydia trachomatis and Chlamydia psittaci. Its application to the interpretation of the serological results in human chlamydioses]. / Etude de al cinétique des anticorps chez les souris OF 1 et C 57 Bl infectées par Chlamydia trachomatis et Chlamydia psittaci. Application à l'interprétation des résultats sérologiques lors des chlamydioses humaines.

The kinetics of antibodies to C. trachomatis and C. psittaci was studied in OF 1 and inbred C 57 Bl mice, inoculated intravenously (IV) or intraperitoneally. Antibodies were detected by a micro-immunofluorescence (MIF) test. Antibody kinetics depends on many factors (genetic particularities of the mice, route of inoculation, chlamydial strain). The response is more specific when mice are inoculated with C. trachomatis than with C. psittaci; heterospecific antibodies appear later in C 57 Bl mice than in OF 1 mice inoculated IV with C. trachomatis. These results are used to explain the serological findings in 6 cases of human chlamydial infections. The type, species and genus specificities of antibody responses to chlamydial infections are discussed.

[Susceptibility of the macrophages of inbred strain mice to Chlamydia psittaci]. / Etude de la sensibilité des macrophages de souris de race pure á Chlamydia psittaci.

Chlamydia psittaci was injected in the peritoneal cavity of different strains of inbred mice. Not all of them develop a clinical disease; some, such as C 3 H, are very susceptible and died within 6 days. C 57 BL, however, are resistant even to a very high dose. We still do not know the exact mechanism of the natural resistance. This is the reason why we are trying to analyse the role of the macrophage. This cell is particularly important in C. psittaci infection, because it harbours the obligate intracellular organisms which multiply inside the cytoplasm. Peritoneal macrophages of three different strains of mice (C 3 H, AKR and C 57 BL) were cultured following Fauve's technique [4]. 48 h after, the macrophages were inoculated with a suspension of C. psittaci. Hela 229 were used as control. 48, 78 and 92 h after inoculation, amount of inclusion in each category of macrophages and Hela cells was determined. C 57 BL macrophages cultured from mice resistant to Chlamydia psittaci allowed the in vitro multiplication of the same bacteria: 72 h after inoculation, 100% of the macrophages were infected and a large inclusion could be seen. C 3 H macrophages cultured from mice very susceptible to Chlamydia psittaci seemed less susceptible in vitro than the C 57 BL macrophages; 72 h after inoculation, 50% only of the infected macrophages showed intracytoplasmic inclusion: AKR macrophages were also susceptible, although AKR mice recover from C. psittaci infection. In conclusion, the difference of susceptibility, as displayed by several strains of inbred mice infected by C. psittaci, cannot be explained by the difference of susceptibility of their macrophages.