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Sat Feb 18 11:22:33 BRST 2006
approximately 500,000 military personnel from the United States who
participated in Operation Desert Storm had leishmaniasis involving
internal organs diagnosed at Walter Reed Army Medical Center. In at
least five of the cases, the species of the infecting parasite was
Leishmania tropica (previously known as L. tropica minor), a parasite
more commonly associated with cutaneous than with visceral leishmaniasis.
PMID: 3927140
TITLE: Cutaneous leishmaniasis--Ohio.
REFERENCE: MMWR Morb Mortal Wkly Rep 1985 Aug 34(33):515-6
REQUEST: [ leishmania ]
(21 articles match this request. 8 articles matching other requests removed)
PMID: 15936759
TITLE: Genomic DNA macroarrays as a tool for analysis of gene expression in
Leishmania.
AUTHORS: Luis Quijada, Manuel Soto, José M Requena
AFFILIATION: Centro de BiologÃa Molecular "Severo Ochoa," Lab CV-401,
Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
REFERENCE: Exp Parasitol 2005 Sep 111(1):64-70
Gene-array technologies have been applied in a wide number of organisms
to study gene expression profiling under several physiological and
experimental conditions. Gene-array implementations combined with the
information arising from emerging genome sequencing projects are
expected to be in the near future a major tool to characterize genes
involved in different processes. So far, gene expression profile studies
in trypanosomatids have been performed in microarrays that use a glass
support to immobilize fragments of genomic DNA followed by fluorescent
detection. Here, we wanted to test the potential of genomic DNA
macroarrays of Leishmania infantum using nylon membranes and radioactive
detection. Nylon macroarrays present a number of advantages since the
processing of the membranes is based on standard Southern blotting
protocols familiar to molecular biologists, and the data acquisition
equipment is available to most research institutions. Nylon macroarrays
were employed to search for genes showing increased mRNA abundance
during an axenic differentiation of L. infantum promastigotes to
amastigotes. Several clones were rescued and, after validation by
Northern blot assays, these L. infantum sequences were used to screen
the Leishmania major gene database. The L. major contigs with high
homology to the L. infantum sequences allowed a consistent
identification of the regulated genes.
PMID: 15970286
TITLE: Leishmania major and Leishmania tropica: I the in vitro effects of an
immunomodulator, S(2)-Complex.
AUTHORS: Yassir M Al-Mulla Hummadi, Rafid A Najim, Nada M Al-Bashir
AFFILIATION: Department of Pharmacology, College of Medicine, University of
Baghdad, P.O. Box 61208, Baghdad 12114, Iraq.
REFERENCE: Exp Parasitol 2005 Sep 111(1):47-54
This study was undertaken to try to determine the possible anti-
leishmanial activity of S(2)-Complex, an organic complex of copper
chloride, ascorbic acid, and nicotinamide. The promastigotes, axenic
amastigotes, and intracellular amastigotes of both Leishmania major and
Leishmania tropica were incubated with different concentrations of S(2)-
Complex. The EC(50) for each form was calculated. Results show that all
forms of the parasites were dose dependently inhibited by S(2)-Complex.
The promastigotes of both parasites were the most resistant with highest
EC(50) followed by axenic amastigotes. While intracellular amastigotes
were the most sensitive with the lowest EC(50).These results indicate
that S(2)-Complex has a direct anti-leishmanial effect. When mice were
treated with S(2)-Complex or BCG for four days before harvesting the
macrophages, and the macrophages infected with both L. major and L.
tropica, they showed increased phagocytosis and increased parasite
killing. The results of S(2)-Complex were not statistically different
from the immunomodulating agent BCG. These results indicate that S(2)-
Complex has an immunomodulating effect in addition to the direct anti-
leishmanial effect.
PMID: 16055738
TITLE: Characterization of a Multisubunit Transcription Factor Complex Essential
for Spliced-Leader RNA Gene Transcription in Trypanosoma brucei.
AUTHORS: Bernd Schimanski, Tu N Nguyen, Arthur Günzl
AFFILIATION: Department of Genetics and Developmental Biology, University of
Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3710.
gunzl at uchc.edu.
REFERENCE: Mol Cell Biol 2005 Aug 25(16):7303-13
In the unicellular human parasites Trypanosoma brucei, Trypanosoma cruzi
, and Leishmania spp., the spliced-leader (SL) RNA is a key molecule in
gene expression donating its 5'-terminal region in SL addition trans
splicing of nuclear pre-mRNA. While there is no evidence that this
process exists in mammals, it is obligatory in mRNA maturation of
trypanosomatid parasites. Hence, throughout their life cycle, these
organisms crucially depend on high levels of SL RNA synthesis. As
putative SL RNA gene transcription factors, a partially characterized
small nuclear RNA-activating protein complex (SNAP(c)) and the TATA-
binding protein related factor 4 (TRF4) have been identified thus far.
Here, by tagging TRF4 with a novel epitope combination termed PTP, we
tandem affinity purified from crude T. brucei extracts a stable and
transcriptionally active complex of six proteins. Besides TRF4 these
were identified as extremely divergent subunits of SNAP(c) and of
transcription factor IIA (TFIIA). The latter finding was unexpected
since genome databases of trypanosomatid parasites appeared to lack
general class II transcription factors. As we demonstrate, the TRF4/SNAP
(c)/TFIIA complex binds specifically to the SL RNA gene promoter
upstream sequence element and is absolutely essential for SL RNA gene
transcription in vitro.
PMID: 16042563
TITLE: ARL1 has an essential role in Trypanosoma brucei.
AUTHORS: H P Price, D Goulding, D F Smith
AFFILIATION: Immunology and Infection Unit, Department of Biology, Hull York
Medical School, University of York, Heslington, York YO10 5YW, U.K.
REFERENCE: Biochem Soc Trans 2005 Aug 33(Pt 4):643-5
Myristoyl-CoA protein:NMT (N-myristoyl transferase) catalyses the N-
myristoylation of cellular proteins with a range of functions and is
essential for viability in the protozoan parasites, Leishmania major and
Trypanosoma brucei. In our investigations to define the essential
downstream targets of NMT, we have focused on the ARF (ADP-ribosylation
factor) family of proteins, as growth arrest in Saccharomyces cerevisiae
mutants with reduced NMT activity correlates with decreased
modification of members of this group of proteins. We have identified
nine ARF/ARLs (where ARL stands for ARF-like) encoded in the T. brucei
and T. cruzi genomes and ten in L. major. The T. brucei ARL1 protein is
expressed only in the mammalian bloodstream form of the parasite, in
which it is localized to the Golgi apparatus. RNAi (RNA interference)
has been used to demonstrate that ARL1 is essential for viability in
these infective cells. Before cell death, depletion of ARL1 protein
results in disintegration of the Golgi structure and a delay in
exocytosis of the abundant GPI (glycosylphosphatidylinositol)-anchored
VSG (variant surface glycoprotein) to the parasite surface.
PMID: 16048936
TITLE: Production and Characterization of Stable Amphotericin-Resistant
Amastigotes and Promastigotes of Leishmania mexicana.
AUTHORS: Hamdan I Al-Mohammed, Michael L Chance, Paul A Bates
AFFILIATION: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3
5QA, United Kingdom. pbates at liverpool.ac.uk.
REFERENCE: Antimicrob Agents Chemother 2005 Aug 49(8):3274-80
The sensitivities of Leishmania mexicana amastigote and promastigote
forms to amphotericin B were investigated in vitro and found to be
strongly influenced by the culture media used. When differences in
culture media were minimized, there was no significant difference in the
50% inhibitory concentration values between the two life cycle stages.
Stable amphotericin B-resistant amastigote and promastigote lines were
produced by the application of increasing drug pressure to long-term
cultures. Lines capable of growth in concentrations of amphotericin B
lethal to normal parasites were produced. Compared to normal parasites,
these amphotericin-resistant lines showed marked differences in membrane
sterol compositions, with very high levels of 4,14,dimethyl-cholesta-8,
24-dienol and other methyl sterols. They also showed a consistent
morphological feature, the presence of multilamellar membrane-like
material in the flagellar pocket, revealed by transmission electron
microscopy. Amphotericin-resistant parasites were capable of infecting
BALB/c mice, but the resulting lesion growth was slower than that after
infection with normal parasites. However, unlike normal parasites, the
amphotericin-resistant parasites were unaffected by experimental
chemotherapy with amphotericin B. These results show that amphotericin B
resistance could arise as a result of increased clinical use of
amphotericin B therapy.
PMID: 15996670
TITLE: Identification of a DNA fragment that increases mitotic stability of
episomal linear DNAs in Leishmania major.
AUTHORS: Liane Casagrande, Jeronimo C Ruiz, Stephen M Beverley, Angela K Cruz
AFFILIATION: Departamento de Biologia Celular e Molecular e Bioagentes
Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
REFERENCE: Int J Parasitol 2005 Aug 35(9):973-80
The centromere is a specialized region of eukaryotic chromosomes, the
site of kinetochore formation, spindle attachment and regulation of
chromosome segregation during mitotic and meiotic cell divisions. To
identify sequences which increase mitotic stability and/or act as
potential centromeres in Leishmania major, we first generated libraries
of Leishmania linear artificial chromosomes (LACs) bearing 30kb inserts
of randomly selected genomic DNAs. These were introduced into parasites
, and then their stability was assessed following a period of 10
passages of growth in the absence of selective pressure. Approximately
80% of the 108 transfectants tested lost their LACs promptly and only 20
% of the recombinants were retained; of these six showed strong but
partial stability (maintained in 30-46% of cells). Mapping and
sequencing of one clone (cSC10), which confers the highest degree of
maintenance, revealed the presence of a sequence that was found within
another stable episome, and which is dispersed in the genome of L. major
. The implications of these data to the possible mechanisms of
chromosomal maintenance are discussed.
PMID: 16020722
TITLE: Trypanosomatid genomes. Introduction.
AUTHORS: Caroline Ash, Barbara R Jasny
REFERENCE: Science 2005 Jul 309(5733):399
PMID: 16020727
TITLE: The trypanosomatid genomes: plates.
REFERENCE: Science 2005 Jul 309(5733):423-34
PMID: 15899186
TITLE: [Spontaneous rupture of the spleen in a patient with visceral
leishmaniasis]
AUTHORS: Rosa Elvira Rovira, José Ramón DÃaz-Gómez, Xelo Lapuebla, MarÃa
Carmen Aguar
REFERENCE: Enferm Infecc Microbiol Clin 2005 May 23(5):327
PMID: 16051534
TITLE: Influence of the vehicle on the properties and efficacy of microparticles
containing amphotericin B.
AUTHORS: J A Sánchez-Brunete, M A Dea, S Rama, F Bolás, J M Alunda, S
Torrado-Santiago, J J Torrado
AFFILIATION: Department of Pharmacy and Pharmaceutical Technology, Faculty of
Pharmacy, Complutense University, Madrid, 28040, Spain.
REFERENCE: J Drug Target 2005 May 13(4):225-33
New microparticles containing amphotericin B (AMB) have been developed
and manufactured by spray drying. To this end albumin, polylactic-co-
glycolic acids (PLGA) and poly(sebacic anhydride) have been employed as
drug carriers. The selection of the solvent used to disperse the drug
and the vehicle before spray drying was critical on production yields
and physical properties of the microparticles. Once particle size,
morphology and dispersability in some aqueous media were shown to be
acceptable for an intravenous administration, in vivo efficacy was
evaluated and compared with the reference medicine Fungizone((R)).
Microparticles prepared with albumin, albumin heated at a high
temperature, some kinds of PLGA or polyanhydride, as well as Fungizone((
R)), were tested in an experimental hamster model of infection with
Leishmania infantum, by evaluating the evolution of parasitic burdens in
spleen, liver and antibody responses. After the injection of three
doses corresponding to 2 mg of AMB per kilogram each, diverse reactions
were reported depending on the vehicle. The best dispersability,
reduction of parasites and antibody response were achieved when the
treatment was performed with AMB in albumin microspheres.
PMID: 16052032
TITLE: Assigning functions to genes: identification of S-phase expressed genes
in Leishmania major based on post-transcriptional control elements.
AUTHORS: Aviad Zick, Itay Onn, Rachel Bezalel, Hanah Margalit, Joseph Shlomai
AFFILIATION: Department of Parasitology, The Kuvin Center for the Study of
Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical
School, Jerusalem 91120, Israel.
REFERENCE: Nucleic Acids Res 2005 33(13):4235-42
Assigning functions to genes is one of the major challenges of the post-
genomic era. Usually, functions are assigned based on similarity of the
coding sequences to sequences of known genes, or by identification of
transcriptional cis-regulatory elements that are known to be associated
with specific pathways or conditions. In trypanosomatids, where
regulation of gene expression takes place mainly at the post-
transcriptional level, new approaches for function assignment are needed
. Here we demonstrate the identification of novel S-phase expressed
genes in Leishmania major, based on a post-transcriptional control
element that was recognized in Crithidia fasciculata as involved in the
cell cycle-dependent expression of several nuclear and mitochondrial S-
phase expressed genes. Hypothesizing that a similar regulatory mechanism
is manifested in L.major, we have applied a computational search for
similar control elements in the genome of L.major. Our computational
scan yielded 132 genes, of which 33% are homologues of known DNA
metabolism genes and 63% lack any annotation. Experimental testing of
seven of these genes revealed that their mRNAs cycle throughout the cell
cycle, reaching a maximum level during S-phase or just prior to it. It
is suggested that screening for post-transcriptional control elements
associated with a specific function provides an efficient method for
assigning functions to trypanosomatid genes.
********************************************************************************************************************
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PMID: 10490990
TITLE: Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses
without inhibiting activation of STAT1.
AUTHORS: L M Ting, A C Kim, A Cattamanchi, J D Ernst
AFFILIATION: Division of Infectious Diseases, University of California, San
Francisco 94143, USA.
REFERENCE: J Immunol 1999 Oct 163(7):3898-906
IFN-gamma activates macrophages to kill diverse intracellular pathogens
, but does not activate human macrophages to kill virulent Mycobacterium
tuberculosis. We tested the hypothesis that this is due to inhibition
of IFN-gamma signaling by M. tuberculosis and found that M. tuberculosis
infection of human macrophages blocks several responses to IFN-gamma,
including killing of Toxoplasma gondii and induction of FcgammaRI. The
inhibitory effect of M. tuberculosis is directed at transcription of IFN
-gamma-responsive genes, but does not affect proximal steps in the Janus
kinase-STAT pathway, as STAT1alpha tyrosine and serine phosphorylation
, dimerization, nuclear translocation, and DNA binding are intact in M.
tuberculosis-infected cells. In contrast, there is a marked decrease in
IFN-gamma-induced association of STAT1 with the transcriptional
coactivators CREB binding protein and p300 in M. tuberculosis-infected
macrophages, indicating that M. tuberculosis directly or indirectly
disrupts this protein-protein interaction that is essential for
transcriptional responses to IFN-gamma. Gamma-irradiated M. tuberculosis
and isolated cell walls reproduce the effects of live bacteria,
indicating that the bacterial component(s) that initiates inhibition of
IFN-gamma responses is constitutively expressed. Although
lipoarabinomannan has been found to exert effects on macrophages, it
does not account for the inhibitory effects of cell walls. These results
indicate that one mechanism for M. tuberculosis to evade the human
immune response is to inhibit the IFN-gamma signaling pathway, and that
the mechanism of inhibition is distinct from that reported for
Leishmania donovani or CMV, in that it targets the interaction of STAT1
with the basal transcriptional apparatus.
PMID: 10362548
TITLE: Isolation of tubulin polyglutamylase from Crithidia; binding to
microtubules and tubulin, and glutamylation of mammalian brain alpha- and
beta-tubulins.
AUTHORS: S Westermann, A Schneider, E K Horn, K Weber
AFFILIATION: Max Planck Institute for Biophysical Chemistry, Department of
Biochemistry, Am Fassberg 11, Germany.
REFERENCE: J Cell Sci 1999 Jul 112 ( Pt 13)():2185-93
Trypanosomatids have a striking cage-like arrangement of submembraneous
microtubules. We previously showed that alpha- and beta- tubulins of
these stable microtubules are extensively modified by polyglutamylation
. Cytoskeletal microtubular preparations obtained by Triton extraction
of Leishmania tarentolae and Crithidia fasciculata retain an enzymatic
activity that incorporates radioactive glutamic acid in a Mg2+-ATP-
dependent manner into alpha- and beta-tubulins. The tubulin
polyglutamylase is extracted by 0.25 M salt. The Crithidia enzyme can be
purified by ATP-affinity chromatography, glycerol-gradient
centrifugation and ion-exchange chromatography. After extraction from
the microtubular cytoskeleton the glutamylase forms a complex with
alphabeta tubulin, but behaves after removal of tubulin as a globular
protein with a molecular mass of 38x10(3). In highly enriched fractions
a corresponding band is the major polypeptide visible in SDS-PAGE. The
enzyme from Crithidia recognises mammalian brain tubulin, where it
incorporates glutamic acid preferentially into the more acidic variants
of both alpha- and beta-tubulins. Synthetic peptides with an
oligoglutamyl side chain, corresponding to the carboxy-terminal end of
brain alpha- and beta-tubulins, are accepted by the enzyme, albeit at
low efficiency. The polyglutamylase elongates the side chain by up to 3
and 5 residues, respectively. Other properties of the tubulin
polyglutamylase are also discussed.
REQUEST: [ sand fly ]
(1 article matches this request. 1 article matching other requests removed)
REQUEST: [ sandfly ]
(0 articles match this request)
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