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Sent on Wednesday, 2010 Jul 14Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | PLoS Negl Trop Dis. 2010 Jul 6;4(7):e737.Phase II Evaluation of Sensitivity and Specificity of PCR and NASBA Followed by Oligochromatography for Diagnosis of Human African Trypanosomiasis in Clinical Samples from D.R. Congo and Uganda.Matovu E, Mugasa CM, Ekangu RA, Deborggraeve S, Lubega GW, Laurent T, Schoone GJ, Schallig HD, Büscher P.Department of Veterinary Parasitology and Microbiology, Makerere University, Kampala, Uganda. AbstractBACKGROUND: The polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) have been recently modified by coupling to oligochromatography (OC) for easy and fast visualisation of products. In this study we evaluate the sensitivity and specificity of the PCR-OC and NASBA-OC for diagnosis of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense human African trypanosomiasis (HAT). METHODOLOGY AND RESULTS: Both tests were evaluated in a case-control design on 143 HAT patients and 187 endemic controls from the Democratic Republic of Congo (DRC) and Uganda. The overall sensitivity of PCR-OC was 81.8% and the specificity was 96.8%. The PCR-OC showed a sensitivity and specificity of 82.4% and 99.2% on the specimens from DRC and 81.3% and 92.3% on those from Uganda. NASBA-OC yielded an overall sensitivity of 90.2%, and a specificity of 98.9%. The sensitivity and specificity of NASBA-OC on the specimens from DRC was 97.1% and 99.2%, respectively. On the specimens from Uganda we observed a sensitivity of 84.0% and a specificity of 98.5%. CONCLUSIONS/SIGNIFICANCE: The tests showed good sensitivity and specificity for the T. b. gambiense HAT in DRC but rather a low sensitivity for T. b. rhodesiense HAT in Uganda. |
PMID: 20625557 [PubMed - in process] | |
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2. | J Immunol. 2010 Jul 12. [Epub ahead of print]Stromal Cell-D erived CXCL12 and CCL8 Cooperate To Support Increased Development of Regulatory Dendritic Cells Following Leishmania Infection.Nguyen Hoang AT, Liu H, Juaréz J, Aziz N, Kaye PM, Svensson M.Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden. AbstractIn the immune system, stromal cells provide specialized niches that control hematopoiesis by coordinating the production of chemokines, adhesion molecules, and growth factors. Stromal cells also have anti-inflammatory effects, including support for the differentiation of hematopoietic progenitors into dendritic cells (DCs) with immune regulatory properties. Together, these observations suggest that the alterations in hematopoiesis commonly seen in infectious disease models, such as experimental visceral leishmaniasis in mice, might result from altered stromal cell function. We report in this study that the stromal cell-derived chemokines CXCL12 and CCL8 cooperate to attract hematopoietic progenitors with the potential to differentiate into regulatory DCs. We also show that infection of murine bone marrow stromal cells by Leishmania donovani enhanced their capacity to support the development of regulatory DCs, as well as their capacity to produce CCL8. Likewise, in experimental visceral leishmaniasis, CCL8 production was induced in splenic stromal cells, leading to an enhanced capacity to attract hematopoietic progenitor cells. Thus, intracellular parasitism of stromal cells modifies their capacity to recruit and support hematopoietic progenitor differentiation into regulatory DCs, and aberrant expression of CCL8 by diseased stromal tissue may be involved in the switch from resolving to persistent infection. |
PMID: 20624948 [PubMed - as supplied by publisher] | |
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3. | J Immunol. 2010 Jul 12. [Epub ahead of print]The Early Generation of a Heterogeneous CD4+ T Cell Response to Leishmania major.Colpitts SL, Scott P.Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. AbstractCD4(+) T cells are an essential component of both the primary and secondary immune response against the intracellular protozoan parasite Leishmania major. Our laboratory has previously shown that CD62L(high) IL-7R(high) central memory T (T(CM)) cells mediate protective immunity following secondary challenge. To determine when T(CM) cells develop, we examined the phenotype of Leishmania-specific CD4(+) T cells in the first 2 wk following infection. As expected, we identified a population of CD4(+) T cells present in the draining lymph node with the characteristics of effector T cells. However, in addition, a second population phenotypically resembling T(CM) cells emerged coincident with the effector population. These T cells, expressing CD62L, CCR7, and IL-7R, failed to produce IFN-gamma, but had the capacity to give rise to IFN-gamma-producing effector cells. Our studies also demonstrated that the degree of proliferation and the timing of lymph node entry impact T(CM) cell development. The early generation of T(CM) cells following L. major infection indicates that T(CM) cells may not only control secondary infections, but may also contribute to the control of the primary infection. |
PMID: 20624946 [PubMed - as supplied by publisher] | |
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4. | J Immunol. 2010 Jul 12. [Epub ahead of print]Primed Antigen-Specific CD4+ T Cells Are Required for NK Cell Activation In Vivo upon Leishmania major Infection.Bihl F, Pecheur J, Bréart B, Poupon G, Cazareth J, Julia V, Glaichenhaus N, Braud VM.Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, Unité Mixte de Recherche 6097. AbstractThe ability of NK cells to rapidly produce IFN-gamma is an important innate mechanism of resistance to many pathogens including Leishmania major. Molecular and cellular components involved in NK cell activation in vivo are still poorly defined, although a central role for dendritic cells has been described. In this study, we demonstrate that Ag-specific CD4(+) T cells are required to initiate NK cell activation early on in draining lymph nodes of L. major-infected mice. We show that early IFN-gamma secretion by NK cells is controlled by IL-2 and IL-12 and is dependent on CD40/CD40L interaction. These findings suggest that newly primed Ag-specific CD4(+) T cells could directly activate NK cells through the secretion of IL-2 but also indirectly through the regulation of IL-12 secretion by dendritic cells. Our results reveal an unappreciated role for Ag-specific CD4(+) T cells in the initiation of NK cell activation in vivo upon L. major infection and demonstrate bidirectional regulations between innate and adaptive immunity. |
PMID: 20624944 [PubMed - as supplied by publisher] | |
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5. | Rev Bras Parasitol Vet. 2010 Jan-Mar;19(2):127-129.[Occurrence de Leishmania spp. in domestic cats from Araçatuba, SP.][Article in Portuguese] Bresciani KD, Serrano AC, Matos LV, Savani ES, D'Auria SR, Perri SH, Bonello FL, Coelho WM, Aoki CG, Costa AJ.Departamento de Apoio, Produção e Saúde Animal, Faculdade de Odontologia de Araçatuba - FOA, Universidade do Estado de São Paulo - UNESP, Rua Clóvis Pestana, 793, CEP 16050-680, Araçatuba - SP, Brazil. bresciani@fmva.unesp.br. AbstractThis study had the purpose to compare the occurrence of Leishmania spp. in felines through two methods (cytological and serological), as well as to associate the occurrence of this protozoan with the sex, age and breed variables. Serum samples from 283 domestic felines were processed by means of Indirect Immunofluorescence Reaction (IIR), and the direct parasitological test for linfonodes was also carried out in order to verify positivity for Leishmania spp. Occurrence of 0.7% (2/283) was observed in the tested felines by means of linfonode imprinting and no animal showed title of antibodies for Leishmania spp. The two positive females were mongrel, a young female and an adult female feline. From the obtained results, no statistically significant difference was observed as regards the sex, breed and age variables in this research (p > 0.05). Occurrence of Leishmania spp. in the cats of this study was low. Such low incidence suggests that these hosts has no epidemiological relevance in the study area. |
PMID: 20624352 [PubMed - as supplied by publisher] | |
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6. | Mol Microbiol. 2010 Jul 6. [Epub ahead of print]Histone deacetylases play distinct roles in telomeric VSG expr ession site silencing in African trypanosomes.Wang QP, Kawahara T, Horn D.London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. AbstractSummary African trypanosomes evade the host immune response through antigenic variation, which is achieved by periodically expressing different variant surface glycoproteins (VSGs). VSG expression is monoallic such that only one of approximately fifteen telomeric VSG expression sites (ESs) is transcribed at a time. Epigenetic regulation is involved in VSG control but our understanding of the mechanisms involved remains incomplete. Histone deacetylases (HDACs) are potential drug targets for diseases caused by protozoan parasites. Here, using recombinant expression we show that the essential Trypanosoma brucei deacetylases, DAC1 (class I) and DAC3 (class II) display HDAC activity. Both DAC1 and DAC3 are nuclear proteins in the bloodstream stage parasite, while only DAC3 remains concentrated in the nucleus in insect-stage cells. Consistent with developmentally regulated localization, DAC1 antagonizes SIR2rp1-dependent telomeric silencing only in the bloodstream form, indicating a conserved role in the control of silent chromatin domains. In contrast, DAC3 is specifically required for silencing at VSG ES promoters in both bloodstream and insect-stage cells. We conclude that DAC1 and DAC3 play distinct roles in subtelomeric gene silencing and that DAC3 represents the first readily druggable target linked to VSG expression site control in the African trypanosome. |
PMID: 20624217 [PubMed - as supplied by publisher] | |
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7. | Clin Infect Dis. 2010 Jul 12. [Epub ahead of print]Designing and Reporting Clinical Trials on Treatments for Cutaneous Leishmaniasis.González U, Pinart M, Reveiz L, Rengifo-Pardo M, Tweed J, Macaya A, Alvar J.Department of Dermatology, Research Unit for Evidence-based Dermatology, Hospital Plató, Barcelona, Spain; 2Cochrane Collaborator Center, Sanitas Institute of Research, Bogotá, Colombia; 3Cochrane Skin Group, University of Nottingham, Nottingham, United Kingdom; 4Department of Dermatology, Bellvitge Hospital, Barcelona, Spain; 5Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland. AbstractCutaneous leishmaniasis is considered to be one of the most neglected and serious parasitic infectious skin diseases in many developing countries. We have assessed the design and reporting of randomized, controlled trials evaluating treatments included in 2 Cochrane systematic reviews on cutaneous leishmaniasis. The analysis of the methodological quality identified some potential bias that can make it difficult to determine whether truly effective therapies exist for this disease. We found important weaknesses in the adequacy and transparency of randomization, loss of participants, causative Leishmania species, outcome measures, and follow-up times. Given these distorting effects on the evidence base, we propose guidelines for authors who wish to conduct clinical trials aimed at the development of effective therapies in cutaneous leishmaniasis. The recommendations in this report will hopefully deserve the attention of the World Health Organization and assist in the planning and prioritization of global strategies for improving the interpretation and replication of clinical research on cutaneous leishmaniasis. |
PMID: 20624067 [PubMed - as supplied by publisher] | |
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8. | Phytother Res. 2010 Jul 7. [Epub ahead of print]Antiprotozoal activity of Melampyrum arvense and its metabolites.Kirmizibekmez H, Atay I, Kaiser M, Brun R, Cartagena MM, Carballeira NM, Yesilada E, Tasdemir D.Department of Pharmacognosy, Faculty of Pharmacy, University of Yeditepe, 34755 Kayisdagi, Istanbul, Turkey. AbstractAn activity guided isolation of the H(2)O subextract of the crude extract of Melampyrum arvense L. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8-epi-loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7-O-beta-glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9-O-beta-glucopyranoside (9); and benzoic acid (10). beta-Sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the CHCl(3) subextract. The structures of the isolates were elucidated by spectroscopic methods, while the composition of 12 was identified by GC-MS after methylation. Luteolin (7) appeared as the most active compound against Trypanosoma brucei rhodesiense and Leishmania donovani (IC(50) values 3.8 and 3.0 mug/mL). Luteolin 7-O-beta-glucopyranoside (8) displayed the best antiplasmodial activity against Plasmodium falciparum (IC(50) value 2.9 mug/mL). This is the first detailed phytochemical study on Turkish M. arvense and the first report of the antiprotozoal effect of Melampyrum species and its constituents. Copyright (c) 2010 John Wiley & Sons, Ltd. |
PMID: 20623589 [PubMed - as supplied by publisher] | |
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9. | Gene. 2010 Jul 8. [Epub ahead of print]Cloning, characterization and subcellular localization of a Trypanosoma cruzi argonaute protein defining a new subfamily distinctive of trypanosomatids.Garcia Silva MR, Tosar JP, Frugier M, Pantano S, Bonilla B, Esteban L, Serra E, Rovira C, Robello C, Cayota A.Functional Genomics Unit, Institut Pasteur de Montevideo, Mataojo 2020 CP11400 Montevideo, Uruguay. AbstractOver the last years an expanding family of small non-coding RNAs (sRNA) has been identified in eukaryotic genomes which behave as sequence-specific triggers for mRNA degradation, translation repression, heterochromatin formation and genome stability. To achieve their effectors functions, sRNAs associate with members of the Argonaute protein family. Argonaute proteins are segregated into three paralogous groups: the AGO-like subfamily, the PIWI-like subfamily, and the WAGO subfamily (for Worm specific AGO). Detailed phylogenetic analysis of the small RNA-related machinery components revealed that they can be traced back to the common ancestor of eukaryotes. However, this machinery seems to be lost or excessively simplified in some unicellular organisms such as Saccharomyces cerevisiae, Trypanosoma cruzi, Leishmania major and Plasmodium falciparum which are unable to utilize dsRNA to trigger degradation of target RNAs. We reported here a unique ORF encoding for an AGO/PIWI protein in Trypanosoma cruzi which was expressed in all stages of its life cycle at the transcript as well as the protein level. Database search for remote homologues, revealed the presence of a divergent PAZ domain adjacent to the well supported PIWI domain. Our results strongly suggested that this unique AGO/PIWI protein from T. cruzi is a canonical Argonaute in terms of its domain architecture. We propose to reclassify all Argonaute members from trypanosomatids as a distinctive phylogenetic group representing a new subfamily of Argonaute proteins and propose the generic designation of AGO/PIWI-tryp to identify them. Inside the Trypanosomatid-specific node, AGO/PIWI-tryps were clearly segregated into two paralog groups designated as AGO-tryp and PIWI-tryp according to the presence or absence of a functional link with RNAi-related phenomena respectively. Copyright © 2010. Published by Elsevier B.V. |
PMID: 20621168 [PubMed - as supplied by publisher] | |
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10. | Soc Sci Med. 2010 Jun 23. [Epub ahead of print]Conflict and human African trypano somiasis.Berrang-Ford L, Lundine J, Breau S.McGill University, Geography, 805 Sherbrooke Street Ouest, Burnside Hall Rm. 705, Montreal, QC, Canada H3A 2K6. AbstractHuman African Trypanosomiasis (HAT) has reemerged in sub-Saharan Africa as a disease of major public health importance. The success of HAT elimination in sub-Saharan Africa is subject to the feasibility of controlling, eliminating, or mitigating the determinants of incidence in affected countries. Conflict has been widely recognized and cited as a contributing factor to the resurgence of HAT in many countries, as well as to continuing HAT incidence in politically unstable and resource-poor regions. Despite extensive anecdotal and qualitative recognition of the role of conflict, there has been no quantitative research of this topic at the population level in affected African countries. We characterize the qualitative and quantitative associations between HAT incidence and conflict-related processes in HAT-affected African countries over the past 30 years. HAT and conflict-related data were collected for 35 affected countries in sub-Saharan Africa for the years 1976-2004. Descriptive and univariate inferential statistics, as well as negative binomial regression modeling, are used to assess the associations between HAT and conflict. A space-time scan statistic is used to identify significant incidence clusters. Clusters of HAT incidence over the past 30 years have predominantly coincided with periods of conflict or socio-political instability. HAT cases occurred significantly more often in countries and during years with conflict, high political terror, and internationalized civil war. The results indicate a lag period between the start of conflict events and a peak in incidence of approximately 10 years. We recommend explicit consideration and quantification of socio-political measures such as conflict and terror indices in GIS (Geographic Information Systems)-based risk assessments for HAT policy and intervention. Copyright © 2010 Elsevier Ltd. All rights reserved. |
PMID: 20619948 [PubMed - as supplied by publisher] | |
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