Pozorišta u Vojvodini i u Srbiji od 1733. do 1874.

"Gajeći u prvom redu naš nacionalan repertoar, pozorišta su bila večita straža ideje našeg oslobođenja. I pored dužnosti da naš narod upoznaju s našom istorijom, naša su pozorišta, dajući predstave i iz hrvatskih narodnih komada, budila svest zbliženja i bratstva s Hrvatima. Takvim radom, pozorišta u Vojvodini i Srbiji, učinila su dakle mnogo, i ona su potpuno opravdala svoj zadatak u starije doba.

Production of Interferons and β-Chemokines by Placental Trophoblasts of HIV-1-Infected Women

Objective: The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the β-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-α (MIP-1α), and MIP-1β can block HIV-1 entry into cells by preventing the binding of the macrophage-trophic HIV-1 strains to the coreceptorCCR5. In this study the production of IFNs and β-chemokines by placental trophoblasts of HIV-1-infected women who were HIV-1 non-transmitters was examined. Methods: Placental trophoblastic cells were isolated from 29 HIV-1-infected and 10 control subjects. Supernatants of trophoblast cultures were tested for the production of IFNs and β-chemokines by enzyme linked immunosorbent assay (ELISA). Additionally, HIV-1-gag and IFN-β transcripts were determined by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results: All placental trophoblasts of HIV-1-infected women contained HIV-1-gag transcripts. There were no statistical differences in the median constitutive levels of IFN-α and IFN-γ produced by trophoblasts of HIV-1- infected and control subjects. In contrast, trophoblasts of HIV-1-infected women constitutively produced significantly higher levels of IFN-β protein than trophoblasts of control subjects. Furthermore, the median levels of β-chemokines produced by trophoblasts of HIV-infected and control women were similar. Conclusions: Since there was no correlation between the placental HIV load and the production of interferons or β-chemokines, the role of trophoblast-derived IFNs and β-chemokines in protecting the fetus from infection with HIV-1 is not clear

Preoperative Psoas Muscle Size Predicts Postoperative Delirium in Older Adults Undergoing Surgery: A Pilot Cohort Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136001/1/jgs14571.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136001/2/jgs14571_am.pd

Deregulated expression of CD40 ligand in HTLV-I infection: Distinct mechanisms of downregulation in HTLV-I-transformed cell lines and ATL patients

AbstractHTLV-I infection is associated with the development of adult T cell leukemia (ATL) and the neuroinflammatory disease HAM/TSP. There are quantitative and qualitative differences in the antiviral cytotoxic T cell (CTL) response in ATL and HAM/TSP although the underlying mechanisms are unclear. Here, we demonstrate that the HTLV-I Tax trans-activating protein is a transcriptional activator of CD40 ligand (CD40L), a critical regulator of dendritic cell maturation and adaptive immunity. Tax activates CD40L expression via a cyclosporin A insensitive pathway that is also independent of NF-κB. Although Tax upregulates CD40L gene expression, CD40L expression is absent in Tax-expressing HTLV-I-transformed cell lines via an epigenetic mechanism involving methylation. T lymphocytes cultured ex vivo from ATL patients, but not HAM/TSP or normal controls, exhibit a potent block in the induction of CD40L, but not CD69. However, the CD40L gene is not silenced by methylation in ATL patients, thus CD40L is downregulated by distinct mechanisms in HTLV-I-transformed cell lines and ATL patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Predicting Salesforce Reactions to New Territory Design According to Equity Theory Propositions

This paper analyzes the various parameters that affect the design of fair sales territories. Among these parameters are the effects of age, seniority, compensation schemes, and market structure. Since human motivation plays a part, there is considerable complexity in modeling the parameters

Sales management : concepts and cases, 10th ed./ Cron

xix, 345 hal,; 25 cm