Friday, July 31, 2009

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 -5 of 5

1: FASEB J. 2009 Jul 29. [Epub ahead of print]

Signal transducer and activator of transcription 1 in T cells plays an indispensable role in immunity to Leishmania major by mediating Th1 cell homing to the site of infection.

Barbi J, Snider HM, Bardhwaj N, Lezama-Dávila CM, Durbin JE, Satoskar AR.

*Department of Microbiology andCenter for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, USA; andDepartment of Pathology, Children's Hospital, Columbus, Ohio, USA.

The signal transducer and activator of transcription 1 (STAT1) signaling pathway mediates the biological functions of IFN-gamma. We have previously shown that the STAT1 pathway is indispensable for host resistance against Leishmania major infection. In this study, we examined the role of STAT1 in lymphocytes and specifically CD4(+) and CD8(+) T cells in mediating immunity against L. major by transferring T cells from wild-type (WT) and STAT1(-/-) C57BL/6 mice into Rag2(-/-) C57BL/6 mice. Rag2(-/-) mice reconstituted with unfractionated STAT1(-/-) splenocytes (B cells and T cells) failed to mount an efficient Th1 response after L. major infection, produced more IL-4, and developed large lesions full of parasites. In contrast, Rag2(-/-) mice reconstituted with WT (STAT1(+/+)) splenocytes mounted a Th1 response and developed self-resolving lesions. Studies using Rag2(-/-) recipients that received a combination of purified CD4(+) and CD8(+) T cells from WT or STAT1(-/-) mice revealed that STAT1 deficiency in CD4(+) T cells, but not in CD8(+) T cells, leads to development of chronic, nonhealing lesions and systemic dissemination of parasites into the spleen after L. major infection. Further studies using Rag2(-/-) recipients of WT Thy1.1(+) and STAT1(-/-) Thy1.2(+) T cells showed that STAT1 in CD4(+) T cells was not required for Th1 differentiation during L. major infection. However, it was critical for up-regulation of CXCR3 on CD4(+) T cells and their migration to the regional lymph node and the cutaneous site of infection. Together, these studies indicate that the STAT1 pathway in CD4(+) T cells plays a critical role in immunity against L. major by controlling the migration of Th1 cells to the site of infection rather than their generation. Further, they reveal an essential role for CD4(+) T cell STAT1 in preventing systemic dissemination of L. major infection.-Barbi, J., Snider, H. M., Bardhwaj, N., Lezama-Dávila, C. M., Durbin, J. E., Satoskar, A. R. Signal transducer and activator of transcription 1 in T cells plays an indispensable role in immunity to Leishmania major by mediating Th1 cell homing to the site of infection.

PMID: 19641143 [PubMed - as supplied by publisher]

2: Annu Rev Genet. 2009 Jul 29. [Epub ahead of print]

Genetic and Epigenetic Mechanisms Underlying Cell-Surface Variability in Protozoa and Fungi.

Verstrepen KJ, Fink GR.

1Laboratory for Systems Biology, VIB, B-3001 Leuven, Belgium and Centre of Microbial and Plant Genetics (CMPG), Genetics and Genomics Group, Department of Molecular and Microbial Systems, K.U. Leuven, Faculty of Applied Bioscience and Engineering, B-3001 Leuven, Belgium; email: kevin.verstrepen@biw.kuleuven.be.

Eukaryotic microorganisms have evolved ingenious mechanisms to generate variability at their cell surface, permitting differential adherence, rapid adaptation to changing environments, and evasion of immune surveillance. Fungi such as Saccharomyces cerevisiae and the pathogen, Candida albicans carry a family of mucin and adhesin genes that allow adhesion to various surfaces and tissues. Trypanosoma cruzi, T. brucei, and Plasmodium falciparum likewise contain large arsenals of different cell surface adhesion genes. In both yeasts and protozoa, silencing and differential expression of the gene family results in surface variability. Here, we discuss unexpected similarities in the structure and genomic location of the cell surface genes, the role of repeated DNA sequences, and the genetic and epigenetic mechanisms-all of which contribute to the remarkable cell surface variability in these highly divergent microbes. Expected final online publication date for the Annual Review of Genetics Volume 43 is October 28, 2009. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

PMID: 19640229 [PubMed - as supplied by publisher]

3: J Drug Target. 2009 Jul 29. [Epub ahead of print]

In vitro evaluation of surface functionalized gelatin nanoparticles for macrophage targeting in the therapy of visceral leishmaniasis.

Nahar M, Dubey V, Mishra D, Mishra PK, Dube A, Jain NK.

Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India.

The present study evaluates the potential of surface functionalized gelatin nanoparticles (f-GNPs) for efficient macrophage-specific delivery of amphotericin B (AmB) in the treatment of visceral leishmaniasis (VL). Further, the effect of spacer for macrophage targeting was also evaluated. Gelatin was functionalized either through conjugation to mannose via direct coupling (mGelatin) or via PEG spacer (m-Gelatin), and the synthesis was confirmed by FTIR. AmB-loaded f-GNPs, that is, mGNPs and m-GNPs prepared from mGelatin and m-Gelatin conjugates, respectively, were characterized. In vitro concanavalin A (Con-A) agglutination assay confirmed the availability of mannose on the surface of these f-GNPs. Kinetics of cellular uptake of AmB-loaded f-GNPs by J774A.1 macrophage cells assessed through flow cytometry demonstrated a steady increase and maximum cell-associated fluorescence was observed at 4h for m-GNPs and 6 h for m-GNPs. Measurement of cytotoxicity using Annexin-V-FITC/PI apoptosis assay delineated marginal changes (7-9%) in treated macrophages following 48 h incubation, establishing the safety of f-GNPs. m-GNPs showed a 5.4-fold reduction in IC(50) in comparison with plain AmB suggesting significant enhancement of antileishmanial activity. Our results indicate that f-GNPs could be a promising carrier for specific delivery of AmB to macrophages for effective treatment of VL. Furthermore, spacer contributed significantly in reducing the cytotoxicity as well as increasing the uptake and activity of f-GNPs.

PMID: 19640212 [PubMed - as supplied by publisher]

Patient Drug Information

4: Med Trop (Mars). 2008 Dec;68(6):634-6.

[Mucosal leishmaniasis by contiguity with a skin lesion: another case report from Tunisia]

[Article in French]

El Fékih N, Sliti N, Kharfi M, Trabelsi S, Khaled S, Fazaa B, Kamoun MR.

Service de dermatologie, Hôpital Charles Nicolle, Tunis, Tunisie. fekih.nadia@planet.tn

Three clinical forms of cutaneous leishmaniasis can be found in Tunisia, i.e. the sporadic form due to Leishmania infantum in the North, the zoonotic epidemic form due to Leishmania major in the center and Southwest, and the chronic cutaneous form due to Leishmania tropica in the South. Unlike cutaneous forms, mucosal involvement is uncommon. The purpose of this report is to describe another case of mucosal leishmaniasis due to contiguity with a skin lesion in a 54-years-old woman. The patient responded well to treatment with meglumine antimoniate.

PMID: 19639835 [PubMed - in process]

5: Med Trop (Mars). 2008 Dec;68(6):584-5.

[Treatment of leishmaniasis: Institut Pasteur, Paris, November 19, 2008]

[Article in French]

Janvier F.

Service de biologie médicale, Hôpital d'Instruction des Armées Bégin, St Mandé, France. janvierfred@hotmail.com

PMID: 19639821 [PubMed - in process]

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