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101.
Stefania Parlato Roberto Bruni Paola Fragapane Debora Salerno Cinzia Marcantonio Paola Borghi Paola Tataseo Anna Rita Ciccaglione Carlo Presutti Giulia Romagnoli Irene Bozzoni Filippo Belardelli Lucia Gabriele 《PloS one》2013,8(8)
Type I interferon (IFN-I) have emerged as crucial mediators of cellular signals controlling DC differentiation and function. Human DC differentiated from monocytes in the presence of IFN-α (IFN-α DC) show a partially mature phenotype and a special capability of stimulating CD4+ T cell and cross-priming CD8+ T cells. Likewise, plasmacytoid DC (pDC) are blood DC highly specialized in the production of IFN-α in response to viruses and other danger signals, whose functional features may be shaped by IFN-I. Here, we investigated the molecular mechanisms stimulated by IFN-α in driving human monocyte-derived DC differentiation and performed parallel studies on peripheral unstimulated and IFN-α-treated pDC. A specific miRNA signature was induced in IFN-α DC and selected miRNAs, among which miR-23a and miR-125b, proved to be negatively associated with up-modulation of Blimp-1 occurring during IFN-α-driven DC differentiation. Of note, monocyte-derived IFN-α DC and in vitro IFN-α-treated pDC shared a restricted pattern of miRNAs regulating Blimp-1 expression as well as some similar phenotypic, molecular and functional hallmarks, supporting the existence of a potential relationship between these DC populations. On the whole, these data uncover a new role of Blimp-1 in human DC differentiation driven by IFN-α and identify Blimp-1 as an IFN-α-mediated key regulator potentially accounting for shared functional features between IFN-α DC and pDC. 相似文献
102.
Michael Edlinger Nicole Concin Hans Concin Gabriele Nagel Hanno Ulmer Georg Göbel 《Cancer epidemiology》2013,37(2):156-161
Background: Lifestyle seems to play an important role in endometrial cancer mortality, but it remains unclear which biomarkers are involved. The aim of this study was to assess the extent of the association between lifestyle-related biomarkers and the survival of endometrial cancer patients. Methods: A sub-cohort of 242 endometrial cancer patients, from a population-based study of the more than 90,000 female participants of the Vorarlberg Health Monitoring and Promotion Programme, was followed for a median duration of twelve years. Besides age, tumour staging, and histology, also pre-diagnostic levels of body mass index, blood pressure, triglycerides, total cholesterol, glucose, gamma-glutamyltransferase (GGT), and serum uric acid were analysed in Cox proportional hazards regression models to estimate multivariate mortality risks. Results: During follow-up 89 deaths occurred of which 49 were cancer-related. Survival was associated with age, tumour stage, and histology. Of the biomarkers, log10-transformed GGT showed a large effect on cancer-related mortality (HR = 3.35, 95% CI 1.12–10.03), whereas the other parameters did not appear with significant effects after adjustment for the other factors. Conclusion: Elevated level of GGT, a lifestyle-related marker, was associated with poor survival among endometrial cancer patients. 相似文献
103.
Alfredo Vizzini Angela Lantieri Gianfranco Medardi Enrico Ercole Gabriele Cacialli 《Mycological Progress》2016,15(8):883-901
This study was focused on species of Peziza belonging to the “P. ammophila” complex, using both morphological and molecular approaches. Molecular and morphological analyses showed that several taxa are hidden under the name “ammophila” and, as a consequence, two additional species and one form are established: P. hellenica sp. nov., P. oceanica sp. nov. and P. ammophila f. megaspora f. nov. On the basis of the data that we have, these taxa seem to be related to some geographical areas; P. ammophila appears to be prevalent in northern, central and southern Europe, its f. megaspora is distributed in France and in the Netherlands, P. hellenica comes from Greece and P. oceanica from New Zealand. A cryptic species, not yet circumscribed satisfactorily, is described as P. deceptiva ad int. Moreover, the problem concerning the identification of P. ammophila is raised, the species is epitypified with a sequenced collection from Sicily (Italy) and a key to the species of the complex is provided. 相似文献
104.
Association between a school‐based intervention and adiposity outcomes in adolescents: The Italian “EAT” project
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105.
Christian Burri Patrick D. Yeramian James L. Allen Ada Merolle Kazadi Kyanza Serge Alain Mpanya Pascal Lutumba Victor Kande Betu Ku Mesu Constantin Miaka Mia Bilenge Jean-Pierre Fina Lubaki Alfred Mpoo Mpoto Mark Thompson Blaise Fungula Munungu Francisco Manuel Théophilo Josenando Sonja C. Bernhard Carol A. Olson Johannes Blum Richard R. Tidwell Gabriele Pohlig 《PLoS neglected tropical diseases》2016,10(2)
Background
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.Methods
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Findings/Conclusion
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. 相似文献106.
Gabriele Pohlig Sonja C. Bernhard Johannes Blum Christian Burri Alain Mpanya Jean-Pierre Fina Lubaki Alfred Mpoo Mpoto Blaise Fungula Munungu Patrick Mangoni N’tombe Gratias Kambau Manesa Deo Pierre Nsele Mutantu Florent Mbo Kuikumbi Alain Fukinsia Mintwo Augustin Kayeye Munungi Amadeu Dala Stephen Macharia Constantin Miaka Mia Bilenge Victor Kande Betu Ku Mesu Jose Ramon Franco Ndinga Dieyi Dituvanga Richard R. Tidwell Carol A. Olson 《PLoS neglected tropical diseases》2016,10(2)
Background
Sleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine.Methods
This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included.The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.Findings/Conclusions
The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity. 相似文献107.
108.
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110.
The Plasmodium falciparum blood stages acquire factor H family proteins to evade destruction by human complement
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Che J. Ngwa Meike Kiesow Rainer Fischer Peter F. Zipfel Christine Skerka Gabriele Pradel 《Cellular microbiology》2016,18(4):573-590
The acquisition of regulatory proteins is a means of blood‐borne pathogens to avoid destruction by the human complement. We recently showed that the gametes of the human malaria parasite Plasmodium falciparum bind factor H (FH) from the blood meal of the mosquito vector to assure successful sexual reproduction, which takes places in the mosquito midgut. While these findings provided a first glimpse of a complex mechanism used by Plasmodium to control the host immune attack, it is hitherto not known, how the pathogenic blood stages of the malaria parasite evade destruction by the human complement. We now show that the human complement system represents a severe threat for the replicating blood stages, particularly for the reinvading merozoites, with complement factor C3b accumulating on the surfaces of the intraerythrocytic schizonts as well as of free merozoites. C3b accumulation initiates terminal complement complex formation, in consequence resulting in blood stage lysis. To inactivate C3b, the parasites bind FH as well as related proteins FHL‐1 and CFHR‐1 to their surface, and FH binding is trypsin‐resistant. Schizonts acquire FH via two contact sites, which involve CCP modules 5 and 20. Blockage of FH‐mediated protection via anti‐FH antibodies results in significantly impaired blood stage replication, pointing to the plasmodial complement evasion machinery as a promising malaria vaccine target. 相似文献