Une nouvelle observation d’une métastase testiculaire d’un adénocarcinome prostatique: Aspects diagnostiques et éthiopathogéniques

Testicular metastases from prostatic adenocarcinoma are rare. They are often asymptomatic and diagnosed incidentally or at autopsy after orchidectomy in more advanced stages of the disease. The authors report a new case and review the diagnosis and aetiopathogenesis of these metastases. A 67-year-old patient with prostatic adenocarcinoma presented with painless right testicular mass for two months with no inflammatory signs. Germ cell tumour serum markers were negative. Scrotal ultrasound showed a large testicular tumour measuring 7×4×3cm. Histological examination revealed a solid non-differentiated tumour, not suggestive of primary testicular tumour. The immunohistochemical panel confirmed the prostate as the primary site due to the positivity of cytokeratins, PSA and PSAP and the negativity of classical markers of germ cell tumours. Testicular metastases from prostatic adenocarcinoma are rare, but their incidence is currently on the increase. They are often asymptomatic and discovered after pulpectomy. This diagnosis must be considered in the case of a testicular mass in patients over the age of 50 with a history of prostatic adenocarcinoma. The diagnosis was established after orchidectomy by histological examination and immunohistochemical tests.     

Natural and manipulated populations of the treehole mosquito, Ochlerotatus triseriatus, at its northernmost range limit in southern Ontario, Canada.

Ochlerotatus triseriatus, the eastern treehole mosquito, reaches its northernmost range limit in the extreme southeast of Canada. As a known vector of West Nile and La Crosse encephalitis viruses and a potential vector of eastern equine encephalitis, its population biology is of interest. In southern Ontario, high larval densities occur in urban woodlots within sugar maple and American beech treehole communities comprising rotifers, nematode worms, mites, other dipterans, and scirtid beetles. Treehole water was characterized by low dissolved oxygen levels and seasonally variable pH and temperature, with the latter being most influential on local populations. Densities were significantly higher (up to 503 larvae 100 ml(-1)) in tree holes close to the forest floor (<1 m) and in experimental tree holes seeded with autumn-shed maple leaves as opposed to leaves of black oak and beech. In this locality, weekly sampling showed Oc. triseriatus to be multivoltine, with mass egg hatching beginning under coldwater (<10 degrees C) conditions in March/April, and thereafter producing three successful generations with a possible, less successful fourth in late summer. Some 1st instar larvae were present in water as cold as 0.7 degree C. Compared with larval psychodids living in the same tree hole, population losses of Oc. triseriatus due to washout during major rainfall events were negligible despite high flowthrough of water derived from stemflow.     

CD16 promotes Escherichia coli sepsis through an FcR gamma inhibitory pathway that prevents phagocytosis and facilitates inflammation

Sepsis, a leading cause of death worldwide, involves proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here we show that the FcRgamma adaptor, an immunoreceptor tyrosine-based activation motif (ITAM)-bearing signal transduction subunit of the Fc receptor family, has a deleterious effect on sepsis. FcRgamma(-/-) mice show increased survival during peritonitis, owing to markedly increased E. coli phagocytosis and killing and to lower production of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. The FcRgamma-associated receptor that inhibits E. coli phagocytosis is FcgammaRIII (also called CD16), and its absence protects mice from sepsis. FcgammaRIII binds E. coli, and this interaction induces FcRgamma phosphorylation, recruitment of the tyrosine phosphatase SHP-1 and phosphatidylinositide-3 kinase (PI3K) dephosphorylation. Decreased PI3K activity inhibits E. coli phagocytosis and increases TNF-alpha production through Toll-like receptor 4. We identified the phagocytic receptor negatively regulated by FcRgamma on macrophages as the class A scavenger receptor MARCO. E. coli-FcgammaRIII interaction induces the recruitment of SHP-1 to MARCO, thereby inhibiting E. coli phagocytosis. Thus, by binding FcgammaRIII, E. coli triggers an inhibitory FcRgamma pathway that both impairs MARCO-mediated bacterial clearance and activates TNF-alpha secretion.     

The minimum information required for reporting a molecular interaction experiment (MIMIx)

A wealth of molecular interaction data is available in the literature, ranging from large-scale datasets to a single interaction confirmed by several different techniques. These data are all too often reported either as free text or in tables of variable format, and are often missing key pieces of information essential for a full understanding of the experiment. Here we propose MIMIx, the minimum information required for reporting a molecular interaction experiment. Adherence to these reporting guidelines will result in publications of increased clarity and usefulness to the scientific community and will support the rapid, systematic capture of molecular interaction data in public databases, thereby improving access to valuable interaction data.     

Lipophosphoramidates as lipidic part of lipospermines for gene delivery

The DNA compacting properties of polyamines (especially spermine) are well-known, hence the use of spermine as the cationic part in several synthetic DNA carriers. Here, we describe the synthesis of modified spermines, with a "lipophosphoramidate" as the lipidic part, and their use for efficient in vitro transfection. Physicochemical measurements (particle size, zeta potentials, pKa determination) and gel retardation assays were also performed. Theoretical membrane-disrupting ability was established by FRET. Taken together, our results indicate that lipophosphoramidates constitute an interesting alternative to "classical" lipidic parts of cationic lipids used as DNA carriers.     

Reprint of "Structural and mechanistic aspects of Amt/Rh proteins" [J. Struct. Biol. 158 (2007) 472-481

Amt/Rh proteins, which mediate movement of ammonium across cell membranes, are spread throughout the three kingdoms of life. Most functional studies on various members of the family have been performed using cellular assays in heterologous expression systems, which are, however, not very well suited for detailed mechanistic studies. Although now generally considered to be ammonia conducting channels, based on a number of experimental studies and structural insights, the possibility remains that some plant Amts facilitate net ammonium ion transport. The Escherichia coli channel AmtB has become the model system of choice for analysis of the mechanism of ammonia conductance, increasingly also through molecular dynamics simulations. Further progress in a more detailed mechanistic understanding of these proteins requires a reliable in vitro assay using purified protein, allowing quantitative kinetic measurements under a variety of experimental conditions for different Amt/Rh proteins, including mutants. Here, we critically review the existing functional data in the context of the most interesting and unresolved mechanistic questions and we present our results, obtained using an in vitro assay set up with the purified E. coli channel AmtB.     

How NOD2 mutations predispose to Crohn's disease?

NOD2 mutations are associated with the development of granulomatous inflammatory diseases, such as early-onset sarcoidosis (EOS), Blau syndrome (BS) and Crohn's disease (CD). As a pathogen-recognition molecule for muramyl dipeptide (MDP), NOD2 controls both innate and adaptive immune responses, through the regulation of cytokines, chemokines and antimicrobial peptides production. Notably, Nod2-deficient mice experienced increased susceptibility to enteric infection and to antigen-specific colitis. Furthermore, mutant mice bearing the orthologue of the major CD-associated NOD2^3020ins allele showed increased susceptibility to DSS-induced colitis. However, many questions remain open. (i) Is antimicrobial function deficiency sufficient to initiate the development of CD? (ii) How impaired and mutant NOD2 might lead to increased adaptive immune response? (iii) How do the other disease-associated NOD2 mutations contribute to the development of chronic intestinal inflammation? Whatever the relevant mechanism(s), it provides a casual link between abnormal bacterial sensing and development of inflammatory disorders. Further work should now focus on restoring abnormal NOD2 function by modulating antimicrobial function and regulatory mechanisms of the adaptive immune system.     

Natural antibody--complement dependent neutralization of bovine herpesvirus 4 by human serum

In contrast to most gammaherpesviruses, Bovine herpesvirus 4 (BoHV-4) has a broad range of host species both in vitro and in vivo. Several in vitro studies demonstrated that some human cell lines are sensitive or even permissive to BoHV-4. These observations led to the hypothesis that cross-species transmission of BoHV-4 could lead to human infections. In the present study, we investigate the sensitivity of BoHV-4 to neutralization by na?ve human sera in order to determine if humans exhibit innate anti-viral activities against this virus. Our results demonstrate that human sera from na?ve individuals, in contrast to the sera of na?ve subjects from various animal species, neutralize BoHV-4 efficiently. A series of complementary experiments were performed to unravel the mechanism(s) of this neutralization. The data obtained in this study demonstrates that human serum neutralizes BoHV-4 in a complement dependent manner activated by natural antibodies raised against the Galalpha1-3Galbeta1-4GlcNAc-R epitope expressed by bovine cells.