Tuesday, June 23, 2009

What's new for 'Trypanosomatids' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

Sender's message:

Sent on Tuesday, 2009 Jun 23
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
Click here to view complete results in PubMed. (Results may change over time.)
To unsubscribe from these e-mail updates click here.



PubMed Results
Items 1 -10 of 18

1: Microsc Res Tech. 2009 Jun 19. [Epub ahead of print]

Structural study of the salivary glands of Anocentor nitens (Acari: Ixodidae) during the feeding cycle.

da Silva VC, Pinheiro NL, Ribeiro VR, de Carvalho RW, Scherer PO, Dos Santos MA, Dos Santos-Mallet JR.

Reference Laboratory for Entomological Surveillance of Leishmaniasis Vectors, Oswaldo Cruz Institute/FIOCRUZ, Av Brasil 4365, Rio de Janeiro-RJ, Brazil.

The salivary glands of Anocentor nitens (Neumann,1897) occur in pairs and are located in the anterolateral region of the general cavity, with milky white color and approximately equal sizes. They consist of a secretory portion and an excretion duct. In some glandular acini, all the cells had a basophilic appearance they were stained by hematoxylin, whereas others presented cells with different staining affinities. In this work, we describe the variations observed in these glands during the feeding cycle of ticks [after feeding (0 h) and successively at 24, 48, 72, 96, 120, and 144 h]. The cells stained by hematoxylin were shown to be more reactive to Alcian blue, thus demonstrating the presence of acid glycosaminoglycans, whereas those stained using eosin presented weak or no reaction. A strong reaction was found by the use of the periodic acid-Schiff (PAS) technique, thereby suggesting the presence of glycogen and/or glycoconjugates containing hexose, confirmed by using salivary amylase before PAS, with partial destaining of the slides. Continuing presence of residual staining in these cells suggests the presence of glycoconjugates containing hexose. Cells with nuclei of circular outline and few granules (of different sizes) were found in type II acini, 72 h after collection. Type I acini presented wide lumina and walls composed of larger numbers of cells of cubic to cylindrical shape. The pronounced degranulation shown in this study over the course of the feeding cycle was associated with the release of substances for oviposition. Microsc. Res. Tech., 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19544533 [PubMed - as supplied by publisher]

2: PLoS Pathog. 2009 Jun;5(6):e1000484. Epub 2009 Jun 19.

Vector transmission of leishmania abrogates vaccine-induced protective immunity.

Peters NC, Kimblin N, Secundino N, Kamhawi S, Lawyer P, Sacks DL.

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is "leishmanization," in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.

PMID: 19543375 [PubMed - in process]

3: Vet Rec. 2009 Jun 20;164(25):778-82.

Secondary immune-mediated thrombocytopenia in dogs naturally infected by Leishmania infantum.

Cortese L, Sica M, Piantedosi D, Ruggiero G, Pero ME, Terrazzano G, Mastellone V, Ciaramella P.

Department of Veterinary Clinical Sciences, Internal Medicine Section, Functions and Technologies, University of Naples Federico II, Via Delpino 1, 80137 Naples, Italy.

Forty-four dogs naturally infected by Leishmania infantum were divided into two groups: 20 thrombocytopenic dogs with fewer than 150 x 10(9) platelets/l, and 24 non-thrombocytopenic dogs with more than 200 x 10(9) platelets/l. Ten clinically healthy dogs were used as controls. A haematological profile was obtained and the dogs' serum was used to assess the presence of platelet-binding IgM and IgG antibodies using a flow cytometry technique. Nineteen of the 20 thrombocytopenic dogs, and 13 of the 24 non-thrombocytopenic dogs had detectable levels of platelet-binding immunoglobulins, but none of the control dogs did so. The differences were significantly different for both IgM and IgG platelet-binding antibodies.

PMID: 19542552 [PubMed - in process]

4: J Immunol. 2009 Jul 1;183(1):470-9.

Immunization with the DNA-encoding N-terminal domain of proteophosphoglycan of Leishmania donovani generates Th1-Type immunoprotective response against experimental visceral leishmaniasis.

Samant M, Gupta R, Kumari S, Misra P, Khare P, Kushawaha PK, Sahasrabuddhe AA, Dube A.

Central Drug Research Institute, Lucknow, India.

Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. The structure and function of PPGs have been reported to be species and stage specific as in the case of Leishmania major and Leishmania mexicana; there has been no such information available for Leishmania donovani. We have recently demonstrated that PPG is differentially expressed in sodium stibogluconate-sensitive and -resistant clinical isolates of L. donovani. To further elucidate the structure and function of the ppg gene of L. donovani, a partial sequence of its N-terminal domain of 1.6 kb containing the majority of antigenic determinants, was successfully cloned and expressed in prokaryotic as well as mammalian cells. We further evaluated the DNA-encoding N-terminal domain of the ppg gene as a vaccine in golden hamsters (Mesocricetus auratus) against the L. donovani challenge. The prophylactic efficacy to the tune of approximately 80% was observed in vaccinated hamsters and all of them could survive beyond 6 mo after challenge. The efficacy was supported by a surge in inducible NO synthase, IFN-gamma, TNF-alpha, and IL-12 mRNA levels along with extreme down-regulation of TGF-beta, IL-4, and IL-10. A rise in the level of Leishmania-specific IgG2 was also observed which was indicative of enhanced cellular immune response. The results suggest the N-terminal domain of L. donovani ppg as a potential DNA vaccine against visceral leishmaniasis.

PMID: 19542458 [PubMed - in process]

5: Eukaryot Cell. 2009 Jun 19. [Epub ahead of print]

Special Sm core complex functions in assembly of the U2 small nuclear ribonucleoprotein of Trypanosoma brucei.

Preußer C, Palfi Z, Bindereif A.

Institute of Biochemistry, Justus Liebig University of Giessen, D-35392 Giessen, Germany.

Processing of polycistronic pre-mRNAs in trypanosomes requires spliceosomal small ribonucleoprotein complexes (snRNPs) U1, U2, U4/U6, U5, and SL, each of which contains a core of seven Sm proteins. Recently we reported first evidence for a core variation in spliceosomal snRNPs; specifically, in the trypanosome U2 snRNP two of the canonical Sm proteins, SmB and SmD3, are replaced by two U2-specific Sm proteins, Sm15K and Sm16.5K. Here we identify the U2-specific, nuclear-localized U2B'' protein from Trypanosoma brucei. U2B'' interacts with a second U2 snRNP protein, U2-40K (U2A'), which in turn contacts the U2-specific Sm16.5K/15K subcomplex. Together they form a high-affinity, U2-specific binding complex. This trypanosome-specific assembly differs from the mammalian system and provides a functional role of the Sm core variation found in the trypanosomal U2 snRNP.

PMID: 19542313 [PubMed - as supplied by publisher]

6: Eukaryot Cell. 2009 Jun 19. [Epub ahead of print]

Adaptations in the glucose metabolism of procyclic Trypanosoma brucei isolated from tsetse flies and during differentiation of bloodstream forms.

van Grinsven KW, Van Den Abbeele J, Van den Bossche P, van Hellemond JJ, Tielens AG.

Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands; Department of Parasitology, Unit of Entomology, Institute of Tropical Medicine Antwerp, B-2000 Antwerp, Belgium; Department of Animal Health, Institute of Tropical Medicine Antwerp, B-2000 Antwerp, Belgium; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, Onderstepoort, South Africa; and Department of Medical Microbiology & Infectious Diseases, ErasmusMC University Medical Center, 3015 GD Rotterdam, The Netherlands.

Procyclic forms of Trypanosoma brucei isolated from midguts of infected tsetse flies, or freshly transformed from a strain that is close to field isolates, do not use a complete Krebs cycle. Furthermore, short-stumpy bloodstream forms produce acetate and are apparently metabolically pre-adapted to adequate functioning in the tsetse fly.

PMID: 19542311 [PubMed - as supplied by publisher]

7: J Med Microbiol. 2009 Jun 18. [Epub ahead of print]

N-chlorotaurine shows high in vitro activity against promastigotes and amastigotes of Leishmania spp.

Fürnkranz U, Nagl M, Gottardi W, Matt U, Aspöck H, Walochnik J.

1 Medical University of Vienna, Austria;

Protozoan parasites of the genus Leishmania are the causative agents of life threatening visceral, as well as of cutaneous and mucocutaneous leishmaniosis. First-line drugs are antimonials, but toxicity and resistance in some endemic areas are serious problems. In the current study, the anti-leishmanial activity of the weak oxidant N-chlorotaurine (NCT) was investigated. NCT is a derivative of the amino acid taurine produced by granulocytes and monocytes during the oxidative burst, but can also be synthesized chemically and used topically as an antiseptic at a concentration of 1% (55 mM) in vivo. NCT susceptibility tests were performed in vitro with promastigotes and amastigotes of Leishmania infantum and L. donovani, respectively. Since NH4Cl is known to increase the activity of NCT by formation of monochloramine (NH2Cl), co-treatment assays were included in the study. Mean EC50s after 1 h of treatment were 5.94 mM for L. infantum and 9.8 mM for L. donovani promastigotes. Co-treatment with 5.5 mM NCT plus 19 mM NH4Cl led to complete killing of promastigotes of both strains within 15 min. Amastigotes were already inactivated by treatment with 2 mM NCT alone. The results of this study indicate a high potential of NCT against Leishmania spp.

PMID: 19541788 [PubMed - as supplied by publisher]

8: RNA. 2009 Jun 18. [Epub ahead of print]

Identification of the HIT-45 protein from Trypanosoma brucei as an FHIT protein/dinucleoside triphosphatase: Substrate specificity studies on the recombinant and endogenous proteins.

Banerjee H, Palenchar JB, Lukaszewicz M, Bojarska E, Stepinski J, Jemielity J, Guranowski A, Ng S, Wah DA, Darzynkiewicz E, Bellofatto V.

Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey 07103, USA.

A new member of the FHIT protein family, designated HIT-45, has been identified in the African trypanosome Trypanosoma brucei. Recombinant HIT-45 proteins were purified from trypanosomal and bacterial protein expression systems and analyzed for substrate specificity using various dinucleoside polyphosphates, including those that contain the 5'-mRNA cap, i.e., m(7)GMP. This enzyme exhibited typical dinucleoside triphosphatase activity (EC 3.6.1.29), having its highest specificity for diadenosine triphosphate (ApppA). However, the trypanosome enzyme contains a unique amino-terminal extension, and hydrolysis of cap dinucleotides with monomethylated guanosine or dimethylated guanosine always yielded m(7)GMP (or m(2,7)GMP) as one of the reaction products. Interestingly, m(7)Gpppm(3) (N6, N6, 2'O)A was preferred among the methylated substrates. This hypermethylated dinucleotide is unique to trypanosomes and may be an intermediate in the decay of cap 4, i.e., m(7)Gpppm(3) (N6, N6, 2'O)Apm(2'O)Apm(2'O)Cpm(2) (N3, 2'O)U, that occurs in these organisms.

PMID: 19541768 [PubMed - as supplied by publisher]

9: Prostaglandins Leukot Essent Fatty Acids. 2009 Jun 19. [Epub ahead of print]

Malnutrition promotes prostaglandin over leukotriene production and dysregulates eicosanoid-cytokine crosstalk in activated resident macrophages.

Anstead GM, Zhang Q, Melby PC.

Research Service, Audie L. Murphy Memorial Veterans Hospital, South Texas Veterans Health Care System, USA; Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

We previously described a murine model of malnutrition that mimicked features of moderate human malnutrition, and led to increased dissemination of Leishmania donovani. In this study, we investigated the effect of malnutrition on macrophage production of cytokines, prostaglandins (PGs), and leukotrienes (LTs). Using either LPS or calcium ionophore A23187 as a stimulus, macrophages from the malnourished mice produced a 3-fold higher PG/LT ((PGE(2)+6-keto-PGF(1alpha))/(LTB(4)+cysteinyl leukotrienes)) ratio than macrophages from well-nourished mice. LPS-stimulated macrophages from the malnourished mice produced decreased levels of TNF-alpha, GM-CSF, and IL-10, but similar levels of IL-6 and NO compared to well-nourished mice. A complex crosstalk between the eicosanoids and cytokines in the LPS-stimulated macrophages from the malnourished mice was evident by the following: (1) high levels of PG secretion despite low levels of TNF-alpha; (2) supplemental IL-10 modulated the excessive PG production; (3) GM-CSF rectified the PG/LT ratio, but did not correct the abnormal cytokine profile; and (4) inhibitors of cyclooxygenase decreased the PG/LT ratio, but did not affect TNF-alpha. Thus, in this model of malnutrition, there is a relative increase in anti-inflammatory PGs compared to pro-inflammatory LTs, which may contribute to immunodeficiency.

PMID: 19541468 [PubMed - as supplied by publisher]

10: J Allergy Clin Immunol. 2009 Jun 19. [Epub ahead of print]

Fibronectin is a T(H)1-specific molecule in human subjects.

Sandig H, McDonald J, Gilmour J, Arno M, Lee TH, Cousins DJ.

Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, Guy's Hospital, London, United Kingdom.

BACKGROUND: T(H)1 cell-mediated immunity is essential for host defense against a variety of intracellular pathogens, such as mycobacteria, salmonella, and Leishmania species. A major T(H)1-mediated effector mechanism involves the IFN-gamma-induced killing of the pathogen by infected macrophages. OBJECTIVES: The range of known T(H)1-specific effector molecules is limited, especially in human subjects. We sought to identify novel effector molecules that might be involved in T(H)1-mediated pathogen clearance. METHODS: We performed microarray-based analysis of human T(H)1 and T(H)2 cells to identify T(H)1-specific molecules. These analyses identified the extracellular matrix molecule fibronectin as a highly expressed T(H)1-specific molecule. We examined the expression of fibronectin in a variety of human cell types by using real-time RT-PCR, ELISA, and Western blotting. We also studied the role of fibronectin in modulating monocyte phenotype using in vitro culture. RESULTS: We show that human T(H)1 cells constitutively express and secrete fibronectin after in vitro differentiation from naive precursors. Furthermore, we demonstrate that ex vivo human T(H)1 cells selectively express fibronectin when compared with T(H)2 cells. The predominant isoform of fibronectin expressed by T(H)1 cells contains additional domains of the protein responsible for alpha4beta1 integrin binding and activation of Toll-like receptor 4. We show that treatment of monocytes with T(H)1 cell-derived fibronectin induces expression of the proinflammatory cytokine IL-6 while inhibiting IL-10 expression. CONCLUSIONS: Because fibronectin also plays a major role in the attachment and opsonization of numerous intracellular pathogens, we propose that it might be a critical molecule produced by T(H)1 cells involved in pathogen eradication.

PMID: 19541353 [PubMed - as supplied by publisher]

Posted by at

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)