Natural killer cells and malaria

Summary:  Malaria, caused by the infection with parasites of the germs Plasmodium , is one of the three most important infectious diseases worldwide, along with tuberculosis and infection with human immunodeficiency virus. Natural killer (NK) cells are lymphocytes classically involved in the early defense against viral infections and intracytoplasmic bacterial infections and are also implicated during the course of tumor development and allogeneic transplantation. These cells display important cytotoxic activity and produce high levels of proinflammatory cytokines. In both mouse and human models of malaria, NK cells appear to be a major source of interferon-γ during the early phase of infection. In humans, indirect signaling through monocytes/macrophages required to optimally stimulate NK cell activity. However, the in vivo functions of NK cells during malaria are still enigmatic, and many issues remain to be dissected, such as the molecular basis of the direct recognition of iRBCs by NK cells.     

Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage- derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage- derived cell line was sensitive to the growth inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.      

Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype in breast carcinoma cell lines

We have previously observed in vitro that some stromal proteinases (MMP-2, MT1-MMP) were expressed or activated by invasive carcinoma cell lines exhibiting mesenchymal features, presumably acquired through an epithelial to mesenchymal transition (EMT). To examine the potential contribution of c-ets-1 to this phenotype, we have compared here the expression of c-ets-1 with invasiveness in vitro and expression of vimentin, E-cadherin, uPA, MMP-1 and MMP-3 in a panel of human breast cancer cell lines. Our results clearly demonstrate an association between c-ets-1 expression and the invasive, EMT-derived phenotype, which is typified by the expression of vimentin and the lack of E-cadherin. While absent from the two non-invasive, vimentin-negative cell lines, c-ets-1 was abundantly expressed in all the four vimentin-positive lines. However, we could not find a clear quantitative or qualitative relationship between the expression of c-ets-1 and the three proteinases known to be regulated by c-ets-1, except that when they were expressed, it was only in the invasive c-ets-1-positive lines. UPA mRNAs were found in three of the four vimentin-positive lines, MMP-1 in two of the four, and MMP-3 could not be detected in any of the cell lines. Intriguingly, MDA-MB-435 cells, which exhibit the highest metastatic potential of these cell lines in nude mice, expressed vimentin and c-ets-1, but lacked expression of these three proteinases, at least under the culture conditions employed. Taken together, our results show that c-ets-1 expression is associated with an invasive, EMT-derived phenotype in breast cancer cells, although it is apparently not sufficient to ensure the expression of uPA, MMP-1 or MMP-3, in the vimentin-positive cells. Such proteases regulation is undoubtedly qualified by the cellular context. This study therefore advances our understanding of the molecular regulation of invasiveness in EMT-associated carcinoma progression, and suggests that c-ets-1 may contribute to the invasive phenotype in carcinoma cells.     

Spermatocytic seminoma. A clinicopathological and immunohistochemical study of 7 cases

Spermatocytic seminoma is an uncommon tumor, representing less than 1% of the testicular tumors, occurring most often in old patients. We report 7 cases of this entity. The average age at presentation was 66 years. Tumors had a polymorphic appearance with small, intermediate and large cells, and "spireme" figures. They were pure, with no sarcomatous component. In all cases, the tumor was limited to the testis. In the peritumoral tissue, there was no intratubular germ cell proliferation, and no atrophic testis. Immunostaining was negative for all the classical antibodies tested (cytokeratins, PLAP, lymphoid markers), but all the cases expressed c-kit (100%). This membranous positivity was focal in 4 cases, very strong, and diffuse in the 3 others. Spermatocytic seminoma must be recognized, because its favorable evolution in absence of a sarcomatous component. Adequate treatment consists of orchidectomy alone. Positive staining for c-kit may be helpful for the diagnosis of spermatocytic seminoma.     

Translational accuracy and sexual differentiation in Chlamydomonas reinhardtii

Summary A renewal of ribosomes has been previously reported to occur during gametogenesis in C. reinhardtii. In order to further characterize these new ribosomes, we performed pulse-labelling experiments on whole cells of C. reinhardtii, during gametogenesis and in the presence of various aminoglycosides known to alter translational accuracy: Hygromycin and Paromomycin are assumed to increase the rate of translational errors at the level of 80S and 70S ribosomes whereas Kasugamycin is assumed to induce the opposite effect. Three lines of evidence support an increased inaccuracy in protein translation during gametogenesis: (1) gamete cells displayed a higher sensitivity than vegetative cells to Hygromycin and Paromomycin; 4 g/ml Hygromycin cancelled cytoplasmic protein synthesis in gametes but not in vegetative cells; Paromomycin induced the synthesis of new polypeptides of high molecular weight and of nuclear origin in gametes but not in vegetative cells. In addition, chloroplast protein synthesis was more sensitive to Hygromycin and Paromomycin in gametes than in vegetative cells. (2) Kasugamycin-sensitive alterations of thylakoid membranes were detected during gametogenesis. (3) ³⁵S-misincorporation in the OEE3 polypeptide, of nuclear origin and normally devoid of sulphur containing amino acids, was more than three times higher in gametes than in vegetative cells. This increase was prevented by Kasugamycin, suggesting that 80S translation in gametes was more inaccurate than in vegetative cells. The possible significance of these changes occurring during gametogenic differentiation is discussed in light of the importance of a modulation of translational accuracy at particular stages of the life cycle in other lower eukaryotes.Abbreviations Hm Hygromycin B - Pm Paromomycin - Ks Kasugamycin - CAP Chloramphenicol - OEE Oxygen evolving enhancer     

Nasotracheal enterococcal carriage and resistomes: detection of optrA-, poxtA- and cfrD-carrying strains in migratory birds,livestock, pets,and in-contact humans in Spain

European Journal of Clinical Microbiology & Infectious Diseases - This study determined the carriage rates and antimicrobial resistance (AMR) genes of enterococci from...