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Sent on Wednesday, 2009 Mar 25Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
- 1: Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):169-74.
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Vaccination with Trichinella spirallis antigens increases CD8+ peripheral T cells and enhances the Th2 immune response in Leishmania infantum challenged mice.
Department of Biological Chemistry, School of Medicine, Aristotle University, Thessaloniki, Greece.
In this study we investigate the effect of Trichinella spiralis vaccination on immune responses elicited in BALB/c mice challenged subcutaneously with 0.5 x 10 6 of Leishmania infantum promastigotes. Secretion of specific anti-L. infantum antibodies and changes in the number of CD4+, CD8+ T cell and CD19+ B cells in the peripheral blood were tested for the evaluation of immune responses. Immunization with low amounts of T. spiralis antigens induced depression in anti-Leishmania specific antibodies of the IgG1 isotype, while no changes in the number of CD4+ and CD8+ T cell subpopulations or CD19+ B cells were observed. In contrast, high amounts of T. spiralis antigens induced an enhancement in anti-Leishmania specific antibodies of total IgG and IgG1 isotype, increase of CD8+ T cell number and activation of CD19+ B cells, indicated by the co-expression of CD69 marker. Our results suggest that immunization with a certain dose of T. spiralis antigens in experimentally challenged mice with L. infantum leads to an increase of peripheral CD8+ T cells which are responsible for the control of L. infantum infection, although a simultaneous enhancement in Th2-type of immune response is also observed.
PMID: 19309564 [PubMed - in process]
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- Establishment of resistance to Leishmania major infection in susceptible BALB/c mice requires parasite-specific CD8+ T cells. [Int Immunol. 1991]
- Leishmania cytosolic silent information regulatory protein 2 deacetylase induces murine B-cell differentiation and in vivo production of specific antibodies. [Immunology. 2006]
- ReviewAnti-leishmania effector functions of CD4+ Th1 cells and early events instructing Th2 cell development and susceptibility to Leishmania major in BALB/c mice. [Adv Exp Med Biol. 1998]
- ReviewDistinct immunological states in murine cutaneous leishmaniasis by immunising with different amounts of antigen: the generation of beneficial, potentially harmful, harmful and potentially extremely harmful states. [Behring Inst Mitt. 1997]
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Searching for novel cell cycle regulators in Trypanosoma brucei with an RNA interference screen.
ABSTRACT: BACKGROUND: The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes Human African Trypanosomiasis. Its cell cycle is complex and not fully understood at the molecular level. The T. brucei genome contains over 6000 protein coding genes with >50% having no predicted function. A small scale RNA interference (RNAi) screen was carried out in Trypanosoma brucei to evaluate the prospects for identifying novel cycle regulators. RESULTS: Procyclic form T. brucei were transfected with a genomic RNAi library and 204 clones isolated. However, only 76 RNAi clones were found to target a protein coding gene of potential interest. These clones were screened for defects in proliferation and cell cycle progression following RNAi induction. Sixteen clones exhibited proliferation defects upon RNAi induction, with eight clones displaying potential cell cycle defects. To confirm the phenotypes, new RNAi cell lines were generated and characterised for five genes targeted in these clones. While we confirmed that the targeted genes are essential for proliferation, we were unable to unambiguously classify them as cell cycle regulators. CONCLUSIONS: Our study identified genes essential for proliferation, but did not, as hoped, identify novel cell cycle regulators. Screening of the RNAi library for essential genes was extremely labour-intensive, which was compounded by the suboptimal quality of the library. For such a screening method to be viable for a large scale or genome wide screen, a new, significantly improved RNAi library will be required, and automated phenotyping approaches will need to be incorporated.
PMID: 19309510 [PubMed - as supplied by publisher]
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- Chromosome-wide analysis of gene function by RNA interference in the african trypanosome. [Eukaryot Cell. 2006]
- TbAGO1, an argonaute protein required for RNA interference, is involved in mitosis and chromosome segregation in Trypanosoma brucei. [BMC Biol. 2003]
- Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray. [Mol Biochem Parasitol. 2002]
- ReviewCell cycle regulation in Trypanosoma brucei. [Mol Biochem Parasitol. 2007]
- ReviewRNA interference takes flight: a new RNAi screen reveals cell cycle regulators in Drosophila cells. [Trends Endocrinol Metab. 2006]
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Drug screening by crossing membranes: a novel approach to identification of trypanocides.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK.
Trypanosomes are a group of protozoan parasites that inflict huge health and economic burdens across the globe. The African trypanosome, Trypanosoma brucei, the causative agent of sleeping sickness, has a highly sophisticated mechanism of antigenic variation that facilitates chronic survival in the mammalian host, and also all but eliminates any realistic hope for vaccination-based control. However, trypanosomes are also highly divergent organisms, with many biochemical processes setting them apart from their hosts, and there remains great optimism that these features may be exploited for development of new drugs. Unfortunately, the compounds that are in use at present are decades old and resistance has emerged. The article in this issue of the Biochemical Journal by Patham et al., a joint team from the universities of Pittsburgh and Georgia, represents one approach to exploiting this divergence. The authors of the study have exploited novel aspects of the biochemistry within the system for translocation of nascent polypeptides across the endoplasmic reticulum membrane to identify three compounds that are able to inhibit the process. They then demonstrate that these same compounds are both trypanocidal, but well tolerated by human tissue culture cells. These observations may present interesting new leads in the fight against trypanosomiasis, and potentially identify a new target that can be explored for therapeutic potential.
PMID: 19309311 [PubMed - in process]
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- ReviewDrug resistance in Trypanosoma brucei spp., the causative agents of sleeping sickness in man and nagana in cattle. [Microbes Infect. 2001]
- ReviewTargeting of toxic compounds to the trypanosome's interior. [Adv Parasitol. 2006]
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Synthetic nonamer peptides derived from insect defensin mediate the killing of African trypanosomes in axenic culture.
National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki, 305-8634, Japan, kitani@affrc.go.jp.
Synthetic antimicrobial 9-mer peptides (designated as peptides A and B) designed on the basis of insect defensins and their effects on the growth of African trypanosomes were examined using two isolates of Trypanosoma congolense, IL1180 and IL3338, and two isolates of Trypanosoma brucei brucei, ILTat1.1and GUTat 3.1, under axenic culture conditions. Both peptides inhibited the growth of all bloodstream form (BSF) trypanosomes at 200-400 mug/mL in the complete growth medium, with peptide A being more potent than peptide B. In addition, these peptides exhibited efficient killing at 5-20 mug/mL on BSF trypanosomes suspended in phosphate-buffered saline, whereas procyclic insect forms in the same medium were more refractory to the killing. Electron microscopy revealed that the peptides induced severe defects in the cell membrane integrity of the parasites. The insect defensin-based peptides up to either 200 or 400 mug/mL showed no cell killing or growth inhibition on NIH3T3 murine fibroblasts. The results suggest that the design of suitable synthetic insect defensin-based 9-mer peptides might provide potential novel trypanocidal drugs.
PMID: 19308456 [PubMed - as supplied by publisher]
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- Killing of African trypanosomes by antimicrobial peptides. [J Infect Dis. 2003]
- ReviewMajor surface glycoproteins of procyclic stage African trypanosomes. [Exp Parasitol. 1994]
- ReviewRegulation of vsg expression site transcription and switching in Trypanosoma brucei. [Mol Biochem Parasitol. 1998]
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Intracellular localization of the ABCC proteins of Leishmania and their role in resistance to antimonials.
Centre de Recherche en Infectiologie et Division de Microbiologie, Université Laval, Québec, Canada, G1V 4G2.
The ABCC proteins subfamily is composed of nine members in Leishmania. We report that all of these proteins have an intracellular localization and that the overexpression of at least four members, ABCC3, ABCC4, ABCC5 and ABCC7 can confer resistance to antimonials, the first-line drug against Leishmania.
PMID: 19307364 [PubMed - as supplied by publisher]
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- ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. [Cancer Res. 2005]
- Role of the ABC transporter PRP1 (ABCC7) in pentamidine resistance in Leishmania amastigotes. [Antimicrob Agents Chemother. 2007]
- ReviewCellular export of drugs and signaling molecules by the ATP-binding cassette transporters MRP4 (ABCC4) and MRP5 (ABCC5). [Drug Metab Rev. 2005]
- Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. [Biochem J. 2002]
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- Comment on:
- Trans R Soc Trop Med Hyg. 2008 Apr;102(4):306-7.
Comment on: Diagnosing central nervous system trypanosomiasis: two stage or not to stage.
PMID: 18692858 [PubMed - indexed for MEDLINE]
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- ReviewDiagnosing central nervous system trypanosomiasis: two stage or not to stage? [Trans R Soc Trop Med Hyg. 2008]
- ReviewHuman African trypanosomiasis of the CNS: current issues and challenges. [J Clin Invest. 2004]
- ReviewDiagnostic and neuropathogenesis issues in human African trypanosomiasis. [Int J Parasitol. 2006]
- Review[Criteria for diagnosis of the neurological stage of human African trypanosomiasis: update and perspectives] [Med Trop (Mars). 2008]
- A link between chemokine levels and disease severity in human African trypanosomiasis. [Int J Parasitol. 2006]
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