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      Immunohistological studies on neoplasms of female and male Onchocerca volvulus: filarial origin and absence of Wolbachia from tumor cells

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          SUMMARY

          Up to 5% of untreated female Onchocerca volvulus filariae develop potentially fatal pleomorphic neoplasms, whose incidence is increased following ivermectin treatment. We studied the occurrence of 8 filarial proteins and of Wolbachia endobacteria in the tumor cells. Onchocercomas from patients, untreated and treated with antibiotics and anthelminthics, were examined by immunohistology. Neoplasms were diagnosed in 112 of 3587 female and in 2 of 1570 male O. volvulus. The following proteins and other compounds of O. volvulus were expressed in the cells of the neoplasms: glutathione S-transferase 1, lysosomal aspartic protease, cAMP-dependent protein kinase, alpha-enolase, aspartate aminotransferase, ankyrin E1, tropomyosin, heat shock protein 60, transforming growth factor-beta, and prostaglandin E 2. These findings prove the filarial origin of the neoplasms and confirm the pleomorphism of the tumor cells. Signs indicating malignancy of the neoplasms are described. Wolbachia were observed in the hypodermis, oocytes, and embryos of tumor-harbouring filariae using antibodies against Wolbachia surface protein, Wolbachia HtrA-type serine protease, and Wolbachia aspartate aminotransferase. In contrast, Wolbachia were not found in the cells of the neoplasms. Further, neoplasm-containing worms were not observed after more than 10 months after the start of sufficient treatment with doxycycline or doxycycline plus ivermectin.

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          Draft genome of the filarial nematode parasite Brugia malayi.

          Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the approximately 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict approximately 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during approximately 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.
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            Tetracyclines: nonantibiotic properties and their clinical implications.

            Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.
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              Somatic stem cell niche tropism in Wolbachia.

              Wolbachia are intracellular bacteria found in the reproductive tissue of all major groups of arthropods. They are transmitted vertically from the female hosts to their offspring, in a pattern analogous to mitochondria inheritance. But Wolbachia phylogeny does not parallel that of the host, indicating that horizontal infectious transmission must also occur. Insect parasitoids are considered the most likely vectors, but the mechanism for horizontal transfer is largely unknown. Here we show that newly introduced Wolbachia cross several tissues and infect the germline of the adult Drosophila melanogaster female. Through investigation of bacterial migration patterns during the course of infection, we found that Wolbachia reach the germline through the somatic stem cell niche in the D. melanogaster germarium. In addition, our data suggest that Wolbachia are highly abundant in the somatic stem cell niche of long-term infected hosts, implying that this location may also contribute to efficient vertical transmission. This is, to our knowledge, the first report of an intracellular parasite displaying tropism for a stem cell niche.
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                Author and article information

                Journal
                Parasitology
                PAR
                Parasitology
                Cambridge University Press (Cambridge, UK )
                0031-1820
                1469-8161
                April 2010
                04 March 2010
                : 137
                : 5
                : 841-854
                Affiliations
                [1 ]Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany
                [2 ]Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany
                [3 ]Washington University School of Medicine, Infectious Disease Division, Campus Mailbox 8051, 660 S Euclid Ave, St Louis, MO 63110, USA
                [4 ]Institute of Animal Physiology, University of Münster, Hindenburgplatz 55, D-48143 Münster, Germany
                [5 ]DIPAV, Sezione di Patologia Generale e Parassitologia, Università degli Studi di Milano, Via Celoria 10, I-20133 Milano, Italy
                [6 ]Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                Author notes
                [* ]Corresponding author: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany. Tel: +49 40 42818 530. Fax: +49 40 42818 400. E-mail: nbrattig@ 123456bni-hamburg.de
                Article
                S0031182009992010 99201
                10.1017/S0031182009992010
                2925449
                20199697
                d6891a38-8db7-485e-9a8f-3ddd17789f1c
                Copyright © Cambridge University Press 2010 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use.

                The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence < http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use.

                History
                : 24 September 2009
                : 24 November 2009
                : 26 November 2009
                Page count
                Pages: 14
                Categories
                Research Article

                Parasitology
                endobacteria,doxycycline,ivermectin,germ cell tumor,wolbachia,neoplasm of filariae,filariae,onchocerca volvulus

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