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Sent on Thursday, 2011 Apr 07Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | Eur J Immunol. 2011 Feb 11. doi: 10.1002/eji.201041056. [Epub ahead of print]c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection.Reinhard K, Huber M, Wostl C, Hellhund A, Toboldt A, Abass E, Casper B, Joeris T, Herr C, Bals R, Steinhoff U, Lohoff M, Visekruna A.Institute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany. AbstractRecent studies demonstrated the crucial role of c-Rel in directing regulatory T cell (Treg) lineage commitment and its involvement in T helper 1 (Th1) cell-mediated autoimmune inflammation. We thus wondered whether these opposite functions of c-Rel influence the course of antiparasitic immune responses against Leishmania major (L. major), an accepted model for the impact of T-cell subsets on disease outcome. Here we show that c-Rel deficient (rel(-/-) ) mice infected with L. major displayed dramatically exacerbated leishmaniasis and enhanced parasite burdens. In contrast to wildtype (WT) mice, interferon-γ (IFN-γ) and interleukin (IL)-17 production in response to L. major antigens was severely impaired. Reconstitution of Rag1 (-/-) T cell deficient mice with rel (-/-) CD4(+) T cells followed by L. major infection demonstrated that c-Rel deficient T cells mount normal Th1 responses and are able to contain the infection. Likewise, Th1 differentiation of naïve CD4(+) cells in vitro was normal. Notably, a selective defect in IL-12 and IL-23 production was observed in rel (-/-) dendritic cells compared to WT counterparts. In conclusion, our data suggest that expression of c-Rel in myeloid cells is essential for clearance of L. major and that this c-Rel-mediated effect is dominant over the lack of Tregs. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
PMID: 21469108 [PubMed - as supplied by publisher] | |
2. | Rev Soc Bras Med Trop. 2011 Apr 1:17-27. [Epub ahead of print]How effective is dog culling in controlling zoonotic visceral leishmaniasis?A critical evaluation of the science, politics and ethics behind this public health policy.Costa CH.Departamento de Medicina Comunitária, Universidade Federal do Piauí, Teresina, PI. AbstractINTRODUCTION: Zoonotic kala-azar, a lethal disease caused by protozoa of the genus Leishmania is considered out of control in parts of the world, particularly in Brazil, where transmission has spread to cities throughout most of the territory and mortality presents an increasing trend. Although a highly debatable measure, the Brazilian government regularly culls seropositive dogs to control the disease. Since control is failing, critical analysis concerning the actions focused on the canine reservoir was conducted. METHODS: In a review of the literature, a historical perspective focusing mainly on comparisons between the successful Chinese and Soviet strategies and the Brazilian approach is presented. In addition, analyses of the principal studies regarding the role of dogs as risk factors to humans and of the main intervention studies regarding the efficacy of the dog killing strategy were undertaken. Brazilian political reaction to a recently published systematic review that concluded that the dog culling program lacked efficiency and its effect on public policy were also reviewed. RESULTS: No firm evidence of the risk conferred by the presence of dogs to humans was verified; on the contrary, a lack of scientific support for the policy of killing dogs was confirmed. A bias for distorting scientific data towards maintaining the policy of culling animals was observed. CONCLUSIONS: Since there is no evidence that dog culling diminishes visceral leishmaniasis transmission, it should be abandoned as a control measure. Ethical considerations have been raised regarding distorting scientific results and the killing of animals despite minimal or absent scientific evidence. |
PMID: 21468480 [PubMed - as supplied by publisher] | |
3. | Mol Biosyst. 2011 Apr 6. [Epub ahead of print]MISS-Prot: web server for self/non-self discrimination of protein residue networks in parasites; theory and experiments in Fasciola peptides and Anisakis allergens.González-Díaz H, Muíño L, Anadón AM, Romaris F, Prado-Prado FJ, Munteanu CR, Dorado J, Sierra AP, Mezo M, González-Warleta M, Gárate T, Ubeira FM.Department of Microbiology & Parasitology, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain. gonzalezdiazh@yahoo.es. AbstractInfections caused by human parasites (HPs) affect the poorest 500 million people worldwide but chemotherapy has become expensive, toxic, and/or less effective due to drug resistance. On the other hand, many 3D structures in Protein Data Bank (PDB) remain without function annotation. We need theoretical models to quickly predict biologically relevant Parasite Self Proteins (PSP), which are expressed differentially in a given parasite and are dissimilar to proteins expressed in other parasites and have a high probability to become new vaccines (unique sequence) or drug targets (unique 3D structure). We present herein a model for PSPs in eight different HPs (Ascaris, Entamoeba, Fasciola, Giardia, Leishmania, Plasmodium, Trypanosoma, and Toxoplasma) with 90% accuracy for 15 341 training and validation cases. The model combines protein residue networks, Markov Chain Models (MCM) and Artificial Neural Networks (ANN). The input parameters are the spectral moments of the Markov transition matrix for electrostatic interactions associated with the protein residue complex network calculated with the MARCH-INSIDE software. We implemented this model in a new web-server called MISS-Prot (MARCH-INSIDE Scores for Self-Proteins). MISS-Prot was programmed using PHP/HTML/Python and MARCH-INSIDE routines and is freely available at: . This server is easy to use by non-experts in Bioinformatics who can carry out automatic online upload and prediction with 3D structures deposited at PDB (mode 1). We can also study outcomes of Peptide Mass Fingerprinting (PMFs) and MS/MS for query proteins with unknown 3D structures (mode 2). We illustrated the use of MISS-Prot in experimental and/or theoretical studies of peptides from Fasciola hepatica cathepsin proteases or present on 10 Anisakis simplex allergens (Ani s 1 to Ani s 10). In doing so, we combined electrophoresis (1DE), MALDI-TOF Mass Spectroscopy, and MASCOT to seek sequences, Molecular Mechanics + Molecular Dynamics (MM/MD) to generate 3D structures and MISS-Prot to predict PSP scores. MISS-Prot also allows the prediction of PSP proteins in 16 additional species including parasite hosts, fungi pathogens, disease transmission vectors, and biotechnologically relevant organisms. |
PMID: 21468430 [PubMed - as supplied by publisher] | |
4. | PLoS Negl Trop Dis. 2011 Mar 29;5(3):e943.Vaccines for the Leishmaniases: Proposals for a Research Agenda.The Working Group on Research Priorities for Development of Leishmaniasis Vaccines, Costa CH, Peters NC, Maruyama SR, de Brito EC Jr, de Miranda Santos IK. |
PMID: 21468307 [PubMed - as supplied by publisher] | |
5. | J Biol Chem. 2011 Apr 5. [Epub ahead of print]A zinc finger protein, TbZC3H20, stabilises two developmentally regulated mRNAs in Trypanosomes.Ling AS, Trotter JR, Hendriks EF.Imperial College London, United Kingdom. AbstractCCCH zinc finger proteins (ZC3Hs) are a novel class of RNA binding protein involved in post-transcriptional mechanisms controlling gene expression. We show TbZC3H20 from Trypanosoma brucei, the causative agent of sleeping sickness and other diseases, stabilises two developmentally regulated transcripts encoding a mitochondrial carrier protein (MCP12) and trans-sialidase (TS-like E). TbZC3H20 is shown to be an RNA binding protein, which is enriched in insect procyclic form T. brucei, and is the first ZC3H discovered controlling gene expression through modulating mRNA abundance in trypanosomes. Previous studies have demonstrated that RNA recognition motif-containing and PUF family RNA binding proteins can control gene expression by stabilising specific target mRNA levels. This work is the first to describe a ZC3H stabilising, rather than destabilising, target mRNAs as a regulatory mechanism and the first report of a ZC3H regulating a gene encoding a mitochondrial protein. This suggests a broader role for ZC3Hs in post-transcriptional regulation of gene expression than previously thought. |
PMID: 21467035 [PubMed - as supplied by publisher] | |
6. | Arch Pathol Lab Med. 2011 Apr;135(4):478-82.Clinical, histopathologic, and cytologic diagnosis of mucosal leishmaniasis and literature review.Daneshbod Y, Oryan A, Davarmanesh M, Shirian S, Negahban S, Aledavood A, Davarpanah MA, Soleimanpoor H, Daneshbod K.AbstractAbstract Context.-Mucosal leishmaniasis (ML) is a rare disease in the world, even in endemic areas such as Iran. Clinical, histologic, or cytologic assessment may help in the diagnosis of ML. Objective.-To describe clinical, histologic, and cytologic findings in ML. Design.-Review of our files showed 11 patients diagnosed with ML, of whom 7 patients had oral lesions, 1 of whom was a known patient with oral leishmaniasis with recurrence of oral lesions; 2 had laryngeal lesions; and 3 had nasal lesions. One case of laryngeal leishmaniasis was a recurrence of prior oral lesions. Cytologic smears were prepared by scraping the lesions with a scalpel or cytobrush. Histology on the biopsies was done for 7 patients. In 2 patients with nasal lesions, exfoliative cytology was made by washing the nasal cavity. Smears were both air dried and fixed in alcohol and stained. Results.-Cytologic findings showed free Leishman-Donovan bodies, intrahistiocytic Leishman-Donovan bodies, atypical organisms, granuloma, acute and chronic inflammatory cells, histiocytes, multinucleated giant cells, mast cells, binucleated histiocytes (Reed-Sternberg-like cells), and plasma cells. In 6 of the patients, biopsy was inconclusive and in subsequent cytology the organism was detected. In 3 cases, findings from clinical and cytologic examinations were suggestive for leishmaniasis; however, with response to treatment, the diagnosis was confirmed. In 5 patients a malignant tumor was suspected because of clinical or histologic findings, but cytology helped to diagnose leishmaniasis. Conclusions.-Clinically or histologically, ML can be mistaken for benign and malignant lesions. Scraping or exfoliative cytology is an easy, reliable, and cost-effective method for diagnosing ML. Thus, clinical, histologic, and cytologic features together may help in ML diagnosis. |
PMID: 21466365 [PubMed - in process] | |
7. | J Parasitol. 2011 Feb;97(1):140-3. Epub 2010 Sep 3.Evaluation of a rapid immunochromatographic dipstick test for detection of antibodies to Trypanosoma cruzi in dogs experimentally infected with isolates obtained from opossums (Didelphis virginiana), armadillos (Dasypus novemcinctus), and dogs (Canis familiaris) from the United States.Rosypal AC, Hill R, Lewis S, Barr SC, Valadas S, Gennari SM, Lindsay DS.Department of Natural Sciences and Mathematics, College of Science, Technology, Engineering and Mathematics, Johnson C Smith University, Charlotte, North Carolina 28216, USA. acrosypal@jcsu.edu AbstractDogs are reservoir hosts for Trypanosoma cruzi , the causative agent of American trypanosomiasis. A rapid immunochromatographic dipstick test (ICT) is available commercially for canine serological testing. The ICT was developed with the use of sera from South American dogs, but it is not routinely used in the United States. We evaluated the utility of the ICT in detecting anti-T. cruzi antibodies in dogs from the United States. Dogs (N = 64) were experimentally infected with United States' isolates of T. cruzi from an opossum (Didelphis virginiana), an armadillo (Dasypus novemcinctus), and a domestic dog (Canis familiaris), and were tested after experimental infection. Sera from uninfected United States dogs (n = 79; hemaculture negative) were used as negative controls. In a blind study, sera were tested by the ICT and compared to the indirect immunofluorescent antibody test with the use of Brazil-strain epimastigotes as antigen. The sensitivity of the ICT was 91% and the specificity was 98% in dogs experimentally infected with United States isolates. Our study indicates that the ICT could be a useful screening tool for serological surveillance of canine T. cruzi exposure in the United States. |
PMID: 21348621 [PubMed - indexed for MEDLINE] | |
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8. | Mol Microbiol. 2011 Jan;79(1):50-62. doi: 10.1111/j.1365-2958.2010.07429.x. Epub 2010 Oct 28.Defining the role of a FYVE domain in the localizati on and activity of a cAMP phosphodiesterase implicated in osmoregulation in Trypanosoma cruzi.Schoijet AC, Miranda K, Medeiros LC, de Souza W, Flawiá MM, Torres HN, Pignataro OP, Docampo R, Alonso GD.Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina. AbstractIntracellular levels of cyclic nucleotide second messengers are regulated predominantly by a large superfamily of phosphodiesterases (PDEs). Trypanosoma cruzi, the causative agent of Chagas disease, encodes four different PDE families. One of these PDEs, T. cruzi PDE C2 (TcrPDEC2) has been characterized as a FYVE domain containing protein. Here, we report a novel role for TcrPDEC2 in osmoregulation in T. cruzi and reveal the relevance of its FYVE domain. Our data show that treatment of epimastigotes with TcrPDEC2 inhibitors improves their regulatory volume decrease, whereas cells overexpressing this enzyme are unaffected by the same inhibitors. Consistent with these results, TcrPDEC2 localizes to the contractile vacuole complex, showing strong labelling in the region corresponding to the spongiome. Furthermore, transgenic parasites overexpressing a truncated version of TcrPDEC2 without the FYVE domain show a failure in its targeting to the contractile vacuole complex and a marked decrease in PDE activity, supporting the importance of this domain to the localization and activity of TcrPDEC2. Taking together, the results here presented are consistent with the importance of the cyclic AMP signalling pathway in regulatory volume decrease and implicate TcrPDEC2 as a specifically localized PDE involved in osmoregulation in T. cruzi. © 2010 Blackwell Publishing Ltd. |
PMID: 21166893 [PubMed - indexed for MEDLINE] | |
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9. | Singapore Med J. 2010 Oct;51(10):806-12.A cross-sectional study of the clinical profile and aetiological spectrum of pancytopenia in a tertiary care centre.Santra G, Das BK.Department of Medicine, Medical College and Hospital Kolkata, 88 College Street, Kolkata 700073, India. g.santra@yahoo.com AbstractINTRODUCTION: Pancytopenia is a common haematological problem. It is suspected when a patient presents with anaemia, prolonged fever and a bleeding tendency. Pancytopenia has multiple causes, but the frequency of these causes has been reported in a limited number of studies. The present study was conducted to assess the aetiological pattern, clinical profile and bone marrow morphology of pancytopenia patients. METHODS: A total of 111 adult pancytopenia patients aged 13 to 65 years were studied during a one-year period to determine their clinical features, peripheral blood pictures and bone marrow morphologies. The aetiological pattern was assessed through the relevant investigations in the respective patients. RESULTS: 45.95 percent of the pancytopenic patients had a hypocellular marrow, while 54.05 percent had normocellular or hypercellular marrow. Idiopathic aplastic anaemia (20.72 percent) was the commonest cause of pancytopenia, followed by hypersplenism due to chronic liver disease (11.71 percent). Other important causes were kala-azar (nine percent), megaloblastic anaemia, systemic lupus erythematosus (SLE), infections and drug inducement. Infections such as kala-azar, falciparum malaria and enteric fever, megaloblastic anaemia as well as SLE were found to be treatable and reversible causes of pancytopenia. CONCLUSION: As a large number of pancytopenic patients have a reversible aetiology, early and proper diagnosis may be life-saving. |
PMID: 21103817 [PubMed - indexed for MEDLINE] | |
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10. | Rev Bras Parasitol Vet. 2010 Apr-Jun;19(2):112-8.Antigenic characterization of Trypanosoma evansi using sera from experimentally and naturally infected bovines, equines, dogs, and coatis.Aquino LP, Machado RZ, Lemos KR, Marques LC, Garcia MV, Borges GP.Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista -- UNESP - SP, Brazil. AbstractThe present research investigated the presence of T. evansi antibodies in animals from the subregion of Nhecolandia, in the Pantanal Sul-mato-grossense, by means of an enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence antibody test (IFAT), and the pattern of polypeptide recognition by sera from experimentally and naturally infected hosts using Western blotting. Serum samples were obtained from bovines (n = 102), horses (n = 98), and dogs (n = 55), and from 32 free-ranging coatis (Nasua nasua). None of the bovines were found positive, while sera from 16 dogs (29%) and 23 horses (23.4%) were positive by ELISA. Sera from 8 coatis (25%) were found positive using IFAT. Western blotting revealed major polypeptides of T. evansi with molecular weight ranging from 74 to 38 kDa. The polypeptides of 66, 48-46, and 38 kDa were identified by sera from experimentally infected bovines, donkeys, dogs, and coatis. The 48-46 and 38 kDa bands were mainly recognized in chronic phase of infection. The antigen with apparent molecular weight of 66 kDa, revealed by antibodies from all experimental animals, was also recognized in sera of horses and dogs from the Pantanal. The 48-46 kDa polypeptide was identified by antibodies from all naturally infected animals and must be further evaluated for use in specific diagnosis of T. evansi infection. |
PMID: 20624349 [PubMed - indexed for MEDLINE] | |
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