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11.
Ingrid Elise Amlie Hegertun Kristin Marie Sulheim Gundersen Elisabeth Kleppa Siphosenkosi Gift Zulu Svein Gunnar Gundersen Myra Taylor Jane D. Kvalsvig Eyrun Floerecke Kjetland 《PLoS neglected tropical diseases》2013,7(3)
Background
Schistosoma (S.) haematobium infection is a common cause of genital morbidity in adult women. Ova in the genital mucosal lining may cause lesions, bleeding, pain, discharge, and the damaged surfaces may pose a risk for HIV. In a heterogeneous schistosomiasis endemic area in South Africa, we sought to investigate if young girls had genital symptoms and if this was associated with urinary S. haematobium.Methodology
In a cross-sectional study of 18 randomly chosen primary schools, we included 1057 schoolgirls between the age of 10 and 12 years. We interviewed assenting girls, whose parents had consented to their participation and examined three urines from each of them for schistosome ova.Principal findings
One third of the girls reported to have a history of genital symptoms. Prior schistosomal infection was reported by 22% (226/1020), this was associated with current genital symptoms (p<0.001). In regression analysis the genital symptoms were significantly associated both with urinary schistosomiasis (p<0.001) and water contact (p<0.001).Conclusions
Even before sexually active age, a relatively large proportion of the participating girls had similar genital symptoms to those reported for adult genital schistosomiasis previously. Anti-schistosomal treatment should be considered at a young age in order to prevent chronic genital damage and secondary infections such as HIV, sexually transmitted diseases and other super-infections. 相似文献12.
13.
Elise P. Salerno Sofia M. Shea Walter C. Olson Gina R. Petroni Mark E. Smolkin Chantel McSkimming Kimberly A. Chianese-Bullock Craig L. Slingluff Jr. 《Cancer immunology, immunotherapy : CII》2013,62(7):1149-1159
We conducted a randomized clinical trial in 45 patients with resected AJCC stage IIB-IV melanoma to characterize cellular and molecular events at sites of immunization with incomplete Freund’s adjuvant (IFA) alone, or a melanoma vaccine in IFA. At a primary vaccine site, all patients received a multi-peptide melanoma vaccine in IFA. At a replicate vaccine site, which was biopsied, group 1 received IFA only; group 2 received vaccine in IFA. Lymphocytes isolated from replicate vaccine site microenvironments (VSME) were compared to time-matched peripheral blood mononuclear cells (PBMC) in ELISpot and flow cytometry assays. Compared to PBMC, the VSME had fewer naïve and greater proportions of effector memory CD8+ T cells (TCD8). The vast majority of TCD8 within the VSME were activated (CD69+), with a concentration of antigen-specific (tetramerpos) cells in the VSME, particularly in vaccine sites with peptide (group 2). CXCR3+ lymphocytes were concentrated in the VSME of all patients, suggesting IFA-induced chemokine recruitment. TCD8 expression of retention integrins αEβ7 and α1β1 was elevated in VSME, with the highest levels observed in antigen-specific cells in VSME containing peptide (group 2). TCD8 retained in the VSME of both groups were strikingly dysfunctional, with minimal IFN-γ production in response to peptide stimulation and few tetramerpos cells producing IFN-γ. These data suggest that vaccine-induced selective retention and dysfunction of antigen-specific TCD8 within VSME may represent a significant mechanism underlying transient immune responses and low clinical response rates to peptide vaccines administered in IFA. 相似文献
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15.
Sea stars are able to make firm but temporary attachments to various substrata by secretions released by their tube feet. After tube foot detachment, the adhesive secretions remain on the substratum as a footprint. Proteins presumably play a key role in sea star adhesion, as evidenced by the removal of footprints from surfaces after a treatment with trypsin. However, until now, characterisation was hampered by their high insolubility. In this study, a non-hydrolytic method was used to render most of the proteins constituting the adhesive footprints soluble. After analysis by SDS-PAGE, the proteins separated into about 25 bands, which ranged from 25 to 450 kDa in apparent molecular weight. Using mass spectrometry and a homology-database search, it was shown that several of the proteins are known intracellular proteins, presumably resulting from contamination of footprint material with tube foot epidermal cells. However, 11 protein bands, comprising the most abundant proteins, were not identified and might correspond to novel adhesive proteins. They were named ‘Sea star footprint proteins’ (Sfps). Tandem mass spectrometry analysis of the protein bands yielded 43 de novo-generated peptide sequences. Most of them were shared by several, if not all, Sfps. Polyclonal antibodies were raised against one of the peptides (HEASGEYYR from Sfp-115) and were used in immunoblotting. They specifically labelled Sfp-115 and other bands with lower apparent molecular weights. The different results suggest that all Sfps might belong to a single family of related proteins sharing similar motifs or, alternatively, they are the products of polymerization and/or degradation processes. 相似文献
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17.
Jimmy Stalin Karim Harhouri Lucas Hubert Caroline Subrini Daniel Lafitte Jean-Claude Lissitzky Nadia Elganfoud Stéphane Robert Alexandrine Foucault-Bertaud Elise Kaspi Florence Sabatier Michel Aurrand-Lions Nathalie Bardin Lars Holmgren Fran?oise Dignat-George Marcel Blot-Chabaud 《The Journal of biological chemistry》2013,288(13):8991-9000
The melanoma cell adhesion molecule (CD146) contains a circulating proteolytic variant (sCD146), which is involved in inflammation and angiogenesis. Its circulating level is modulated in different pathologies, but its intracellular transduction pathways are still largely unknown. Using peptide pulldown and mass spectrometry, we identified angiomotin as a sCD146-associated protein in endothelial progenitor cells (EPC). Interaction between angiomotin and sCD146 was confirmed by enzyme-linked immunosorbent assay (ELISA), homogeneous time-resolved fluorescence, and binding of sCD146 on both immobilized recombinant angiomotin and angiomotin-transfected cells. Silencing angiomotin in EPC inhibited sCD146 angiogenic effects, i.e. EPC migration, proliferation, and capacity to form capillary-like structures in Matrigel. In addition, sCD146 effects were inhibited by the angiomotin inhibitor angiostatin and competition with recombinant angiomotin. Finally, binding of sCD146 on angiomotin triggered the activation of several transduction pathways that were identified by antibody array. These results delineate a novel signaling pathway where sCD146 binds to angiomotin to stimulate a proangiogenic response. This result is important to find novel target cells of sCD146 and for the development of therapeutic strategies based on EPC in the treatment of ischemic diseases. 相似文献
18.
François Bilodeau Murray D. Bailey Punit K. Bhardwaj Josée Bordeleau Pat Forgione Michel Garneau Elise Ghiro Vida Gorys Ted Halmos Eric S. Jolicoeur Mélissa Leblanc Christopher T. Lemke Julie Naud Jeff O’Meara Peter W. White Montse Llinàs-Brunet 《Bioorganic & medicinal chemistry letters》2013,23(14):4267-4271
In this report we describe the synthesis and evaluation of diverse 4-arylproline analogs as HCV NS3 protease inhibitors. Introduction of this novel P2 moiety opened up new SAR and, in combination with a synthetic approach providing a versatile handle, allowed for efficient exploitation of this novel series of NS3 protease inhibitors. Multiple structural modifications of the aryl group at the 4-proline, guided by structural analysis, led to the identification of analogs which were very potent in both enzymatic and cell based assays. The impact of this systematic SAR on different drug properties is reported. 相似文献
19.
Anne Décor Chantal Grand-Maître Oliver Hucke Jeff O’Meara Cyrille Kuhn Léa Constantineau -Forget Christian Brochu Eric Malenfant Mégan Bertrand-Laperle Josée Bordeleau Elise Ghiro Marc Pesant Gulrez Fazal Vida Gorys Michael Little Colette Boucher Sylvain Bordeleau Pascal Turcotte Annick Gauthier 《Bioorganic & medicinal chemistry letters》2013,23(13):3841-3847
We describe here the design, synthesis and biological evaluation of antiviral compounds acting against human rhinovirus (HRV). A series of aminothiazoles demonstrated pan-activity against the HRV genotypes screened and productive structure–activity relationships. A comprehensive investigational library was designed and performed allowing the identification of potent compounds with lower molecular weight and improved ADME profile. 31d-1, 31d-2, 31f showed good exposures in CD-1 mice. The mechanism of action was discovered to be a host target: the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIß). The identification of the pan-HRV active compound 31f combined with a structurally distinct literature compound T-00127-HEV1 allowed the assessment of target related tolerability of inhibiting this kinase for a short period of time in order to prevent HRV replication. 相似文献
20.
Elise Huchard Alice Baniel Susanne Schliehe‐Diecks Peter M. Kappeler 《Molecular ecology》2013,22(15):4071-4086
Sexual selection theory suggests that choice for partners carrying dissimilar genes at the major histocompatibility complex (MHC) may play a role in maintaining genetic variation in animal populations by limiting inbreeding or improving the immunity of future offspring. However, it is often difficult to establish whether the observed MHC dissimilarity among mates drives mate choice or represents a by‐product of inbreeding avoidance based on MHC‐independent cues. Here, we used 454‐sequencing and a 10‐year study of wild grey mouse lemurs (Microcebus murinus), small, solitary primates from western Madagascar, to compare the relative importance on the mate choice of two MHC class II genes, DRB and DQB, that are equally variable but display contrasting patterns of selection at the molecular level, with DRB under stronger diversifying selection. We further assessed the effect of the genetic relatedness and of the spatial distance among candidate mates on the detection of MHC‐dependent mate choice. Our results reveal inbreeding avoidance, along with disassortative mate choice at DRB, but not at DQB. DRB‐disassortative mate choice remains detectable after excluding all related dyads (characterized by a relatedness coefficient r > 0), but varies slightly with the spatial distance among candidate mates. These findings suggest that the observed deviations from random mate choice at MHC are driven by functionally important MHC genes (like DRB) rather than passively resulting from inbreeding avoidance and further emphasize the need for taking into account the spatial and genetic structure of the population in correlative tests of MHC‐dependent mate choice. 相似文献