[leish-l] Fwd: Articles found by RefScout for your requests
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Subject: Articles found by RefScout for your requests
REQUEST: [ leishmaniasis ]
(14 articles match this request)
PMID: 15297055
TITLE: Immunostimulatory oligodeoxynucleotides are potent enhancers of
protective immunity in mice immunized with recombinant ORFF leishmanial
antigen.
AUTHORS: Poonam Tewary, Bindu Sukumaran, Shailendra Saxena, Rentala Madhubala
AFFILIATION: School of Life Sciences, Jawaharlal Nehru University, New Delhi
110067, India.
REFERENCE: Vaccine 2004 Aug 22(23-24):3053-60
Unmethylated CpG dinucleotides in bacterial DNA or synthetic
oligonucleotides (ODN) have proved as promising adjuvants for promotion
of T helper 1 (Th1) type immune response. The potent Th1 like immune
activation by CpG-ODNs suggests a possible utility for vaccination
against leishmaniasis. We therefore investigated the effect of ODN
containing immunostimulatory CG motifs as adjuvant with recombinant ORFF
(rORFF) leishmanial antigen. BALB/c mice were vaccinated with the rORFF
with or without CpG-ODN as adjuvant and then challenged with Leishmania
donovani metacyclic promastigotes. Administration of CpG-ODN alone
resulted in partial protection against challenge with L. donovani in
BALB/c mice. Combination of rORFF and CpG-ODN showed enhanced reduction
in parasite load (84%) when compared to rORFF (56%) vaccinated mice.
Immunization with rORFF alone did not induce the typical Th response
whereas co-administration of rORFF with CpG-ODN resulted in enhanced
production of immunoglobulin G2a and interferon gamma. Our results
further demonstrate that CpG-ODN alone or in combination with rORFF
resulted in a dose dependent increase of nitric oxide production in
activated macrophages. These studies suggest that CpG-ODN are promising
immune enhancers for vaccination against visceral leishmaniasis.
PMID: 15075349
TITLE: Leishmania major-mediated prevention of programmed cell death induction
in infected macrophages is associated with the repression of mitochondrial
release of cytochrome c.
AUTHORS: Khadija Akarid, Damien Arnoult, Juliette Micic-Polianski, Jamila Sif,
Jérôme Estaquier, Jean Claude Ameisen
AFFILIATION: INSERM/Université Paris 7, Faculté de Médecine Xavier Bichat,
16, Rue Henri Huchard, 75870 Paris Cedex 18, France.
REFERENCE: J Leukoc Biol 2004 Jul 76(1):95-103
Leishmania are obligate, intracellular parasites of macrophages in their
vertebrate hosts, including humans, in which they cause disease. Here,
we report that in vitro infection with Leishmania major protects murine
bone marrow-derived macrophages against programmed cell death (PCD)
induced by deprival of macrophage-colony stimulating factor and delays
PCD caused by treatment with staurosporine, a broad inducer of PCD. This
preventive effect was observed in macrophages from L. major-susceptible
BALB/c and L. major-resistant C57BL/6 mice, indicating that repression
of PCD did not depend on genetic background-specific regulation of T
helper cell type 1 (Th1)/Th2 cytokine secretion. Prevention of effector
caspase activation and PCD was associated with a repression of
mitochondrial release of cytochrome c and did not involve the nuclear
factor-kappaB pathway. The capacity of L. major to delay PCD induction
in the infected macrophages may have implications for Leishmania
pathogenesis by favoring the invasion of its host and the persistence of
the parasite in the infected cells.
PMID: 15199163
TITLE: SOCS5 is expressed in primary B and T lymphoid cells but is dispensable
for lymphocyte production and function.
AUTHORS: Christine Brender, Ruth Columbus, Donald Metcalf, Emanuela Handman,
Robyn Starr, Nick Huntington, David Tarlinton, Niels Ãdum, Sandra E Nicholson,
Nicos A Nicola, Douglas J Hilton, Warren S Alexander
AFFILIATION: The Walter and Eliza Hall Institute of Medical Research, Parkville,
Victoria 3050, Australia.
REFERENCE: Mol Cell Biol 2004 Jul 24(13):6094-103
Suppressors of cytokine signaling (SOCSs) are key regulators of cytokine
-induced responses in hematopoietic as well as nonhematopoietic cells.
SOCS1 and SOCS3 have been shown to modulate T-cell responses, whereas
the roles of other SOCS family members in the regulation of lymphocyte
function are less clear. Here, we report the generation of mice with a
targeted disruption of the Socs5 gene. Socs5(-/-) mice were born in a
normal Mendelian ratio and were healthy and fertile. We found that SOCS5
is expressed in primary B and T cells in wild-type mice. However, no
abnormalities in the lymphocyte compartment were seen in SOCS5-deficient
mice. We examined antigen- and cytokine-induced proliferative responses
in B and T cells in the absence of SOCS5 and found no deviations from
the responses seen in wild-type cells. Because SOCS5 has been implicated
in Th1 differentiation, we also investigated the importance of SOCS5 in
T helper cell responses. Unexpectedly, SOCS5-deficient CD4 T cells
showed no abnormalities in Th1/Th2 differentiation and Socs5(-/-) mice
showed normal resistance to infection with Leishmania major. Therefore,
although SOCS5 is expressed in primary B and T cells, it appears to be
dispensable for the regulation of lymphocyte function.
PMID: 14985787
TITLE: IL-18 gene therapy develops Th1-type immune responses in Leishmania
major-infected BALB/c mice: is the effect mediated by the CpG signaling TLR9?
AUTHORS: Y Li, K Ishii, H Hisaeda, S Hamano, M Zhang, K Nakanishi, T Yoshimoto,
H Hemmi, K Takeda, S Akira, Y Iwakura, K Himeno
AFFILIATION: Department of Microbiology and Immunology, Graduate School of
Medical Sciences, Kyushu University, Fukuoka, Japan.
REFERENCE: Gene Ther 2004 Jun 11(11):941-8
IL-18 regulates either Th1 or Th2 responses depending on the cytokine
microenvironment. Administration of recombinant IL-18 (rIL-18) alone
does not promote Th1 response, but rather induces Th2 response and
exacerbates Leishmania major infection in susceptible BALB/c mice. Here
, we treated BALB/c mice with an IL-18-expressing plasmid by using a
gene gun weekly after L. major infection. This gene therapy resulted in
improved pathogenic process and preferential induction of Th1 responses
by inducing the expression of IL-12 p40, but treatment with rIL-18 did
not. Notably, simultaneous administration of rIL-18 with an empty
plasmid vector rendered BALB/c mice resistant to the infection, despite
the fact that treatment with either rIL-18 alone or the plasmid vector
alone did not influence the susceptibility. The synergistic role of the
vector with rIL-18 was found to depend on CpG motifs, which enhanced
expression of proinflammatory cytokines, especially IL-12, from APCs
through Toll-like receptor (TLR) 9 ligation. Treatment with methylated
plasmid vector in which CpG was disrupted could no longer prevent the
disease development in coadministration with rIL-18. Taken together, IL-
18 gene therapy was shown to develop Th1-type protective immunity in L.
major-infected BALB/c mice without the requirement of exogenous IL-12,
probably via CpG-TLR9 signaling pathway.
PMID: 15110400
TITLE: Sero-epidemiological study of canine Leishmania spp. infection in the
municipality of Alijó (Alto Douro, Portugal).
AUTHORS: LuÃs Cardoso, Manuela Rodrigues, Helder Santos, Gerard J Schoone,
Pedro Carreta, Eugénio Varejão, Birgit van Benthem, M Odete Afonso, Carlos
Alves-Pires, Saul J Semião-Santos, Jorge Rodrigues, Henk D F H Schallig
AFFILIATION: Department of Hygiene and Animal Health, CECAV, University of
Trás-os-Montes e Alto Douro, 5001-911 Vila Real, Portugal. lcardoso at utad.pt
REFERENCE: Vet Parasitol 2004 May 121(1-2):21-32
Visceral leishmaniosis caused by Leishmania infantum is a zoonotic
disease in the Mediterranean basin. We report an epidemiological survey
carried out in dogs from the municipality of Alijó in the endemic
region of Alto Douro (north Portugal). Performance of the direct
agglutination test (DAT) was assessed in 205 matching samples of blood
collected on filter paper and serum. A high degree of agreement (97.6%;
k = 0.83) was found between the results obtained from both types of
samples. DAT was then used to test more blood on filter paper (B-FP)
samples from other dogs of the same municipality. The detected sero-
prevalence was 18.7% (288/1540), with values ranging from 0.0 to 81.1%
in each of the 19 parishes of Alijó. Three distinct geographical zones
of mean sero-prevalence could be defined: northwestern (2.5%),
intermediate (11.4%) and southern (49.9%). No statistically significant
difference was observed between male (19.1%) and female (17.8%) sero-
prevalences (P = 0.560). Dogs of 9-11 years of age showed the highest
sero-prevalence (28.4%), but all the other age-intervals (0-2, 3-5, 6-8
and 12-17 years) presented values (15.0-22.3%) not significantly
different from the mean of the whole study population. Risk factors for
canine Leishmania infection were age and geographical zone. Only 5.9% of
the sero-positive animals had clinical signs of canine leishmaniosis
and the overall prevalence of disease was 1.1%. This study validates the
use of B-FP samples and confirms DAT as a simple and sensitive
serological test to evaluate the level of canine Leishmania infection in
areas of high sero-prevalence.
PMID: 15180316
TITLE: Sequence variation of the cytochrome b gene of various human infecting
members of the genus Leishmania and their phylogeny.
AUTHORS: G E Luyo-Acero, H Uezato, M Oshiro, K Takei, K Kariya, K Katakura, E
Gomez-Landires, Y Hashiguchi, S Nonaka
AFFILIATION: Department of Dermatology, Faculty of Medicine, University of the
Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0125, Japan.
REFERENCE: Parasitology 2004 May 128(Pt 5):483-91
The Cytochrome b (Cyt b) gene has proved to be useful for identification
and classification of many mammals and plants. In order to evaluate the
utility of this gene for discrimination of Leishmania parasites as well
as for exploring their phylogenetic relationships, we determined the
nucleotide sequences of the Cyt b gene from 13 human-infecting
Leishmania species (14 strains) from the New and Old Worlds. The Cyt b
genes, approximately 1080 base pairs, were found to be A/T rich, and
their 5' terminal-editing regions were highly conserved. The nucleotide
sequence variation among them was enough to discriminate parasite
species; 245 nucleotide positions were polymorphic and 190 positions
were parsimony informative. The phylogenetic relationships based on this
gene, showed good agreement with the classification of Lainson &
Shaw (1987) except for the inclusion of L. (L.) major in the L. (L.)
tropica complex and the placement of L. tarentolae in another genus.
These data show that the Cyt b gene is useful for phylogenetic study of
Leishmania parasites.
PMID: 15293561
TITLE: Combination of ascorbate and alpha-tocopherol as a preventive therapy
against structural and functional defects of erythrocytes in visceral
leishmaniasis.
AUTHORS: Gargi Sen, Rupa Mukhopadhaya, Jharna Ghosal, Tuli Biswas
AFFILIATION: Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road,
Kolkata 700032, India.
REFERENCE: Free Radic Res 2004 May 38(5):527-34
The redox unbalance in erythrocytes has been found to contribute
significantly in the development of anemia in visceral leishmaniasis (VL
). The present study revealed enhanced production of reactive oxygen
species (ROS) and gradual depletion of alpha-tocopherol and ascorbate in
the erythrocytes of infected animals. The response of erythrocytes to
chronic treatment with antioxidants was studied in hamsters during
leishmanial infection. Treatment with a combination of alpha-tocopherol
and ascorbate proved to be the most effective preventive for the
proteolytic degradation of erythrocyte membrane. Erythrocytes from
infected animals were thermally more sensitive compared to the control
ones. Combination of both antioxidants was most successful in resisting
heat induced structural defects in the cells. Cross-linking of membrane
proteins subsequent to oxidative damage in the red cells was accompanied
by the formation of high molecular weight protein band at the top of
the resolving gel in the presence of the cross-linking agent
dimethyladepimidate (DMA). Marked inhibition of cross-linking was
observed with combination of both antioxidants. Treatment with alpha-
tocopherol and ascorbate together could withstand osmotic lysis of
erythrocytes in the infected animals very efficiently. Decreased
hemoglobin (Hb) level was successfully replenished and was coupled with
significant increase in the life span of red cells after treating the
animals with both antioxidants. Results indicate better efficacy of the
combination therapy with alpha-tocopherol and ascorbate in protecting
the erythrocytes from structural and functional damages during
leishmanial infection.
PMID: 15287582
TITLE: Type I signal peptidase from Leishmania is a target of the immune
response in human cutaneous and visceral leishmaniasis.
AUTHORS: Sima Rafati, Ali-Hatef Salmanian, Tahere Taheri, Slavica Masina, Cedric
Schaff, Yasaman Taslimi, Nicolas Fasel
AFFILIATION: Department of Immunology, Pasteur Institute of Iran, P.O. Box
11365-6699, Tehran, Iran. s_rafat at yahoo.com
REFERENCE: Mol Biochem Parasitol 2004 May 135(1):13-20
The gene encoding type I signal peptidase (Lmjsp) has been cloned from
Leishmania major. Lmjsp encodes a protein of 180 amino residues with a
predicted molecular mass of 20.5 kDa. Comparison of the protein sequence
with those of known type I signal peptidases indicates homology in five
conserved domains A-E which are known to be important, or essential,
for catalytic activity. Southern blot hybridisation analysis indicates
that there is a single copy of the Lmjsp gene. A recombinant SPase
protein and a synthetic peptide of the L. major signal peptidase were
used to examine the presence of specific antibodies in sera from either
recovered or active individuals of both cutaneous and visceral
leishmaniasis. This evaluation demonstrated that sera from cutaneous and
visceral forms of leishmaniasis are highly reactive to both the
recombinant and synthetic signal peptidase antigens. Therefore, the
Leishmania signal peptidase, albeit localised intracellularly, is a
significant target of the Leishmania specific immune response and
highlights its potential use for serodiagnosis of cutaneous and visceral
leishmaniasis.
PMID: 15151143
TITLE: Extracellular matrix alterations in experimental murine Leishmania (L.)
amazonensis infection.
AUTHORS: A L Abreu-Silva, K S Calabrese, R A Mortara, R C Tedesco, F O Cardoso,
L O P Carvalho, S C Gonçalves da Costa
AFFILIATION: Departamento de Patologia da Universidade Estadual do Maranhão,
São LuÃs, Maranhão, Brasil.
REFERENCE: Parasitology 2004 Apr 128(Pt 4):385-90
Here we describe extracellular matrix alterations in footpad lesions and
draining lymph nodes caused by Leishmania (L.) amazonensis in mouse
strains with distinct susceptibilities to this parasite: BALB/c (
susceptible), C57BL/6 (intermediate), and DBA/2 (resistant). Changes in
ECM were observed mainly in BALB/c mice that, in general, presented
tissue damage associated with high parasite burden. Under polarized
light, Sirius Red revealed type I collagen that was predominant in the
primary lesion in all strains studied at the early phase of infection,
but gradually decreased and was replaced by abundant type III collagen
fibres in chronic phase lesions. The presence of type III collagen
seemed to provide support to inflammatory cells, mainly vacuolated and
parasitized macrophages. Laminin expression was not altered during
infection by L. (L.) amazonensis in any of the mouse strains studied.
Furthermore, the decreased fibronectin expression, in all strains, in
areas where amastigotes have been found, indicated that this decline was
also not related to the genetic background.
PMID: 15296351
TITLE: Unsuspected peritoneal leishmaniasis in an HIV-positive woman with
ovarian cancer.
AUTHORS: Shyama Jain, Prashant Sharma, Ruchika Gupta, Neeta Kumar
REFERENCE: Acta Cytol 2004 Jul-Aug 48(4):583-4
PMID: 15293532
TITLE: Leishmaniasis in patients with chronic renal failure: a diagnostic and
therapeutic challenge for the clinician.
AUTHORS: Paolo Maggi, Vito Gaudiano, Marina Valente, Angela Latorraca, Rocco L
Cavaliere, Massimo Marroni, Angela M V Larocca, Giuliano Stagni, Teodoro Lopez,
Giuseppe Pastore
AFFILIATION: Clinic for Infectious Diseases, University of Bari, Bari, Italy.
p_maggi at yahoo.com
REFERENCE: J Nephrol 2004 Mar-Apr 17(2):296-301
BACKGROUND: The role of leishmaniasis in dialyzed or transplanted
patients for chronic renal failure is generally neglected. In this study
, the authors present a series of three cases of leishmaniasis (one
visceral, one mucous and one muco-visceral) in patients with end-stage
renal failure characterized by an atypical presentation and/or
resistance to therapy. CASE DESCRIPTION: Two patients had an atypical
infection: the first patient demonstrated a mucosal form, while the
second had visceral and mucosal involvement. These two presentations are
very rare and, to the best of our knowledge, other autoctonous disease
cases have never been described in Italy. In the first patient, a cycle
of oral itraconazole was scarcely effective and poorly tolerated, while
treatment with 15% topical paromomycin sulfate was successful. Patients
two and three failed to respond to meglumine antimonate and amphotericin
B lipid complex. A second cycle with liposomal amphotericin B was
effective in both cases. In addition, a superior safety profile for
liposomal amphotericin B in comparison with the lipid complex
amphotericin B was observed. CONCLUSIONS: These three cases highlight
the problem of leishmaniasis in both renal transplanted and dialyzed
patients and suggest that this infection could be far from infrequent in
addition to being resistant to therapies. Leishmaniasis should be
considered in the differential diagnosis of fevers of unknown origin and
mucosal lesions in these patients, even in countries not at risk for
mucosal leishmaniasis.
PMID: 15286825
TITLE: Azithromycin in the treatment of mucosal leishmaniasis.
AUTHORS: Mario León Silva-Vergara, Luciana de Almeida Silva, Frederico Ricardo
Zago Maneira, Achilles Gustavo da Silva, AluÃzio Prata
AFFILIATION: Departamento de ClÃnica Médica, Faculdade de Medicina do
Triângulo Mineiro, Uberaba, MG, Brazil. dip_fmtm at mednet.com.br
REFERENCE: Rev Inst Med Trop Sao Paulo 2004 May-Jun 46(3):175-7
This report describes three elderly patients with mucosal form of
American tegumentary leishmaniasis associated with chronic cardiopathy.
Due to the known toxicity of classical drugs with activity against
Leishmania sp., the patients received three oral courses of azithromycin
therapy in single 500 mg daily dose during ten days, every other month
. All lesions healed after the third series. One of the patients
relapsed and a new series of azithromycin was prescribed. Azithromycin
may be an alternative drug for the treatment of leishmaniasis in special
situations due to its optimal mucosal and intraphagocyte concentration
, single daily posology, high tolerance and oral administration. The
mechanism of this drug on Leishmania sp. is unknown at present.
PMID: 15300285
TITLE: [Health education: teaching about American tegumentary leishmaniasis]
AUTHORS: Claudia Maria Antunes Uchôa, Cathia Maria Barrientos Serra, Ciléia de
Melo Magalhães Cd, Roger Magno Macedo da Silva, LetÃcia Pinto Figliuolo,
Cristianni Antunes Leal, Maria de Fátima Madeira Md
AFFILIATION: Departamento de Microbiologia e Parasitologia, Instituto
Biomédico, Universidade Federal Fluminense, Niterói, Brasil.
REFERENCE: Cad Saude Publica 2004 Jul-Aug 20(4):935-41
Knowledge on the circulation of American tegumentary leishmaniasis (ATL
) and perception by the local population are highly relevant for
developing a control program, since they mobilize the community for
effective health measures. This work aimed to orient primary school
teachers and pupils (grades 1 through 4) in the public school system in
Maricá, Rio de Janeiro State, Brazil, on ATL, using talks, posters, and
leaflets with an interactive approach. Talks were given in seven
municipal schools, and activities were held with 1,314 pupils and 56
teachers. Leaflets were distributed to the pupils with activities to
help consolidate the content. Two months later one school was chosen for
post-evaluation. Of the 213 pupils who had attended the talk, 198
answered a questionnaire, of whom 178 (89.9%) could remember the disease
and 125 (63.1%) provided correct answers on transmission. Thus,
informed children and teachers can function as information disseminators
in health within their community and are therefore capable of
contributing to control of endemic diseases.
PMID: 15239308
TITLE: Susceptibility status of Phlebotomus argentipes to insecticides in
districts Vaishaii and Patna (Bihar).
AUTHORS: R C Dhiman, K Raghavendra, Vijay Kumar, S Kesari, Kamal Kishore
AFFILIATION: Malaria Research Centre, Delhi.
REFERENCE: J Commun Dis 2003 Mar 35(1):49-51
REQUEST: [ leishmania ]
(13 articles match this request. 4 articles matching other requests removed)
PMID: 15294929
TITLE: Regulatory cells and infectious agents: detentes cordiale and contraire.
AUTHORS: Barry T Rouse, Susmit Suvas
AFFILIATION: Department of Microbiology, University of Tennessee, Knoxville, TN
37996.
REFERENCE: J Immunol 2004 Aug 173(4):2211-5
This brief review describes the types of interactions that occur between
CD4(+)CD25(+) regulatory T cells (Treg) and microbial pathogens. These
interactions range from one of mutual benefit (détente cordiale) such
as occurs in Leishmania major infection of resistant mouse strains, to
instances where the Treg response appears to mainly favor the pathogen
and be detrimental to the host (détente contraire). Examples of the
latter include chronic persistent infections with retroviruses, perhaps
including HIV, and hepatitis C virus. The Treg response also hampers the
effectiveness of immunity against some acute virus infections such as
HSV. Evidence is also discussed showing that Treg can play a benevolent
role to limit the severity of bystander tissue damage in circumstances
where the immune response to pathogens is immunopathological. Finally,
emerging approaches are discussed that either blunt or activate Treg and
that could be used practically to manage host-pathogen interaction.
PMID: 15294090
TITLE: IL-5-Induced Eosinophils Suppress the Growth of Leishmania amazonensis In
Vivo and Kill Promastigotes In Vitro in Response to Either IL-4 or IFN-gamma.
AUTHORS: Yoshiya Watanabe, Emi Hamaguchi-Tsuru, Norihito Morimoto, Youhei
Nishio, Ken-Ichi Yagyu, Yuko Konishi, Mari Tominaga, Jun-Ichi Miyazaki, Masato
Furuya, Akira Tominaga
AFFILIATION: Department of Molecular and Cellular Biology, and Institute for
Laboratory Animals, Kochi Medical School, Kochi University, Nankoku City, Kochi
783-8505, Japan.
REFERENCE: DNA Cell Biol 2004 Jul 23(7):412-8
In IL-5 transgenic mice (C3H/HeN-TgN(IL-5)-Imeg), in which 50% of
peripheral blood leukocytes are eosinophils, the development of
infection by Leishmania amazonensis was clearly suppressed. To determine
mechanistically how this protozoan parasite is killed, we performed in
vitro killing experiments. Either IL-4 or IFN-gamma effectively
stimulated eosinophils to kill Leishmania amazonensis promastigotes, and
most of the killing was inhibited by catalase but not by the NO
inhibitor L-N(5)-(1-iminoethyl)-ornithine, suggesting that hydrogen
peroxide is responsible for the killing of L. amazonensis by eosinophils
. There was no significant degranulation of eosinophils in the culture,
because eosinophil peroxidase was not detected in culture supernatants
when L. amazonensis promastigotes were killed by activated eosinophils.
Such resistance was also observed in BALB/c mice, which are highly
susceptible to L. amazonensis. Expression plasmids for IL-4, IL-5, and
IFN-gamma were transferred into muscle by electroporation in vivo
starting 1 week before infection. Expression plasmid for IL-5 was most
effective in slowing the development of infection among three expression
plasmids. Expression plasmid for IL-4 was slightly effective and that
for IFN-gamma had no effect on the progress of disease. These results
suggest that IL-5 gene transfer into muscle by electroporation is useful
as a supplementary protection method against L. amazonensis infection.
PMID: 15287590
TITLE: Sequences required for the flagellar targeting of an integral membrane
protein.
AUTHORS: Marina Ignatushchenko Abdel Nasser, Scott M Landfear
AFFILIATION: Department of Molecular Microbiology and Immunology, Oregon Health
and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098,
USA.
REFERENCE: Mol Biochem Parasitol 2004 May 135(1):89-100
Previous studies have established that the ISO1 glucose transporter of
Leishmania enriettii resides primarily in the flagellar membrane,
whereas the ISO2 glucose transporter is located in the pellicular plasma
membrane surrounding the cell body. This pronounced difference in
subcellular targeting is conferred by the NH2-terminal domain of the
transporters, since this is the only region of the two permeases that
differs in sequence. Analysis of the 130 residue NH2-terminal domain of
ISO1 using multiple terminal deletion mutants and various internal
deletion mutants established that a sequence located between amino acids
84 and 100 of this domain is required for flagellar trafficking. In
addition, chimeras between ISO1 and ISO2 indicated that the region
between residues 110 and 118 of ISO1 is also required for flagellar
targeting. These results imply that flagellar targeting information for
this integral membrane protein does not constitute a simple linear
sequence of amino acids but is at least bipartite in structure.
PMID: 15287594
TITLE: Substrate specificity of the Leishmania donovani myo-inositol
transporter: critical role of inositol C-2, C-3 and C-5 hydroxyl groups.
AUTHORS: Tyler P Mongan, Sudhandiran Ganapasam, Stephen B Hobbs, Andreas
Seyfang
AFFILIATION: Department of Biochemistry and Molecular Biology, Medical College
of Georgia, Augusta, GA 30912-2100, USA.
REFERENCE: Mol Biochem Parasitol 2004 May 135(1):133-41
Inositol is an essential precursor for the formation of glycosyl-
phosphatidylinositol (GPI)-anchors found in the majority of surface
molecules in trypanosomatids, in addition to its requirement for
phoshatidylinositol signal transduction pathways. In Leishmania donovani
, high-affinity inositol transport is catalyzed by the active myo-
inositol/H+ transporter MIT, which is driven by a proton gradient across
the parasite membrane. We have characterized the substrate specificity
and pharmacology of L. donovani MIT in vitro and in promastigote
cultures. High substrate specificity of myo-inositol transport was shown
in competition studies with 14 different monosaccharides and MIT
function was unaffected by the structurally similar pentose sugars or
hexoses. L-Fucose and D-xylose, both inhibitors of the Na+-dependent
inositol transport system in the human host, did not affect MIT
transport function in the parasite. Competition studies with eight
different inositol isomers revealed that proton bonds between the C-2, C
-3 and C-5 hydroxyl groups of myo-inositol and the transporter protein
played a critical role for substrate recognition, and the C-3 hydroxyl
oxygen appears to act as an electron donor to form an H-bond with a
positive charge of the MIT permease. The cytotoxic inositol analogue 3-
fluoro-myo-inositol was recognized by MIT with similar affinity as myo-
inositol and showed an IC50 value of 42 +/- 8 microM in L. donovani
cultures. Finally, substrate affinities of MIT revealed apparent Km
values of 84 +/- 8 microM for myo-inositol and 5.4 +/- 0.9 nM for H+,
equal pH 8.27 + 0.08, suggesting that the L. donovani myo-inositol/H+
symporter is fully activated at physiological pH in the sandfly midgut
or macrophage phagolysosome. We conclude that Leishmania MIT constitutes
an attractive target for delivery of cytotoxic inositol analogues and
differs significantly from the sodium-coupled myo-inositol transport
system of the human host.
PMID: 15105020
TITLE: DNA microarray analysis of protozoan parasite gene expression: outcomes
correlate with mechanisms of regulation.
AUTHORS: Robert Duncan
AFFILIATION: Division of Emerging and Transfusion Transmitted Diseases, Center
for Biologics Evaluation and Research (CBER), Food and Drug Administration
(FDA), 1401 Rockville Pike, Rockville, MD 20852, USA. duncan at cber.fda.gov
REFERENCE: Trends Parasitol 2004 May 20(5):211-5
PMID: 15147005
TITLE: Is leishmaniasis becoming endemic in Germany?
AUTHORS: T J Naucke, C Schmitt
AFFILIATION: Institute of Medical Parasitology, Bonn University, Bonn, Germany.
TJNaucke at aol.com
REFERENCE: Int J Med Microbiol 2004 Apr 293 Suppl 37():179-81
PMID: 15299845
TITLE: A comparison of two independently determined structures of trypanothione
reductase from Crithidia fasciculata.
AUTHORS: C S Bond
REFERENCE: Acta Crystallogr D Biol Crystallogr 1995 Jul 51(Pt 4):567-74
The enzyme trypanothione reductase (TR) is unique to trypanosomes and
leishmania parasites, the causal agents of several important medical and
veterinary tropical diseases. TR helps regulate the intracellular
reducing environment of the parasite and it has been identified as a
target for developing novel chemotherapeutic agents by structure-aided
drug design. For this purpose it is essential to have confidence in the
structural detail of the molecular target. Two independent studies of
Crithidia fasciculata TR at medium resolution, in different space groups
have afforded an opportunity to assess the reliability of the models.
We summarize the important methodological details of each analysis and
present a comparison of the geometry, thermal parameters and three-
dimensional structure of the models. Particular attention has been paid
to the disulfide substrate-binding site which is the area of most
interest with respect to enzyme inhibition. The comparison has shown
that the structures agree closely with Calpha atoms superposing with an
r.m.s. of less than 0.5 A. The consistency of the models gives a high
level of confidence that they are suitable for computer-aided drug
design. The conformation of many side chains in the active site, in
particular the catalytic residues, are well conserved in both structures
. However, the comparison indicates a difference in the conformation of
Trp21 and Met113 which together form a hydrophobic patch on the rim of
the active-site cleft and interact with the spermidine moiety of the
substrate. Consideration of the electron-density maps together with the
structural comparison indicates that there is some conformational
flexibility in this region of the active site. This heterogeneity may be
used in the recognition of the substrate by the enzyme and should be
considered when mapping out the size, shape and chemical properties of
the active site.
PMID: 15299452
TITLE: Structure of trypanothione reductase from Crithidia fasciculata at 2.6 A
resolution; enzyme-NADP interactions at 2.8 A resolution.
AUTHORS: S Bailey
REFERENCE: Acta Crystallogr D Biol Crystallogr 1994 Mar 50(Pt 2):139-54
Trypanothione reductase is an FAD-dependent disulfide oxidoreductase
which catalyses the reduction of trypanothione using NADPH as co-factor
. The enzyme is unique to protozoan parasites from the genera
Trypanosoma and Leishmania and is an important target for the design of
improved antitrypanocidal drugs. We present details of the structure of
trypanothione reductase from Crithidia fasciculata solved by molecular
replacement, using human glutathione reductase as a search model, and
refined to an R factor of 16.1% with data between 8.0 and 2.6 A
resolution. The model comprises two subunits (one containing 487
residues, the other 486), an FAD prosthetic group, plus 392 solvent
molecules. The last four C-terminal residues are not seen in either
subunit and the density is poor for the N-terminal residue of subunit B
. The model has a root-mean-square deviation from ideality of 0.016 A
for bond lengths and 3.2 degrees for bond angles. Each subunit was
independently refined in the latter stages of the analysis but the
subunits remain similar as indicated by the root-mean-square deviation
of 0.35 A for C(alpha) atoms. Trypanothione reductase has 36% sequence
identity with human glutathione reductase and the root-mean-square
deviation between the 462 C(alpha) atoms in the secondary structural
units common to the two proteins is 1.1 A. However, there are large
differences in the loop regions and significant shifts in the
orientation of the four domains within each subunit. Domain II, which
binds the dinucleotide co-factor, and domain IV, which forms the
interface between the two subunits, are both rotated by approximately 5
degrees with respect to domain I, which binds the FAD moiety, when
compared with glutathione reductase. Crystals of trypanothione reductase
have been soaked in the dinucleotide co-factor NADPH and N(1)-
glutathionylspermidine disulfide substrate and the structure of the
resulting complex determined at 2.8 A resolution. Strong density is
observed for the adenosine end of the co-factor which forms many charged
interactions with the protein though the density for the nicotinamide
moiety is more diffuse. The mode of binding indicates that NADP is bound
to the enzyme in a similar conformation to that observed with human
glutathione reductase.
********************************************************************************************************************
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PMID: 9310377
TITLE: Molecular cloning of the hamster CMP-sialic acid transporter.
AUTHORS: M Eckhardt, R Gerardy-Schahn
AFFILIATION: Institut für Medizinische Mikrobiologie, Medizinische Hochschule
Hannover, Germany.
REFERENCE: Eur J Biochem 1997 Aug 248(1):187-92
Chinese hamster ovary (CHO) glycosylation mutants of the Lec2
complementation group are unable to express sialylated glycoproteins and
glycolipids due to a defect in the Golgi CMP-sialic acid transporter (
CMP-Sia-Tr). Using an expression cloning strategy, we isolated a cDNA
encoding the hamster CMP-Sia-Tr which complements the Lec2 phenotype.
The deduced amino acid sequence of the cloned cDNA shows 95% identity to
the recently cloned murine CMP-Sia-Tr. The expression of a hamster CMP-
Sia-Tr fusion protein with an N-terminal MDYKDDDDK (FLAG) sequence
revealed Golgi localisation of the transporter. Amino acid sequence
comparison revealed strong similarity (44.6% identity and 19.3%
similarity) of CMP-Sia-Tr to the recently cloned human UDP-galactose
transporter (UDP-Gal-Tr). In contrast, sequence similarities to the
yeast UDP-N-acetylglucosamine transporter (UDP-GlcNAc-Tr) and the GDP-
mannose transporter (GDP-Man-Tr) of Leishmania donovani are restricted
to a region encoding the two most C-terminally located transmembrane
helices. A computer-based structural analysis of CMP-Sia-Tr proposes an
eight transmembrane helix model with the N- and C-termini located on the
cytosolic side of the Golgi membrane.
REQUEST: [ sand fly ]
(1 article matches this request)
PMID: 15297516
TITLE: Population Genetic Analysis of Bartonella bacilliformis Isolates from
Areas of Peru Where Carrion's Disease Is Endemic and Epidemic.
AUTHORS: Tina M Hambuch, Scott A Handley, Barbara Ellis, Judith Chamberlin,
Sofia Romero, Russell Regnery
AFFILIATION: Poxvirus Section, Division of Viral and Rickettsial Diseases, NCID,
CDC, 1600 Clifton Rd. NE, MS G-13, Atlanta, GA 30333. Rregnery at cdc.gov
REFERENCE: J Clin Microbiol 2004 Aug 42(8):3675-80
Carrion's disease is caused by infection with the alpha-proteobacterium
Bartonella bacilliformis. Distribution of the disease is considered
coincident with the distribution of its known vector, the sand fly
Lutzomyia verrucarum. Recent epidemics of B. bacilliformis infections
associated with atypical symptomatology in nonendemic regions have
raised questions regarding the historic and present distribution of this
bacterium and the scope of disease that infection causes. Phylogenetic
relationships and genomic diversity of 18 B. bacilliformis isolates (10
isolates from a region where Carrion's disease is epidemic, Cuzco, Peru
, and 8 isolates from a region where Carrion's disease is endemic, Caraz
, Peru) were assessed using genomic data generated by infrequent
restriction site PCR and gene sequence analysis of the flagellin gltA
and ialB genes. A population genetic analysis of the genomic diversity
suggests that what was once considered an epidemic region of Peru did
not result from the recent introduction of B. bacilliformis.
REQUEST: [ sandfly ]
(2 articles match this request. 1 article matching other requests removed)
PMID: 15066251
TITLE: [Meningitis by Toscana virus in Spain: description of 17 cases]
AUTHORS: José MarÃa Navarro, Concepción Fernández-Roldán, Mercedes
Pérez-Ruiz, Sara Sanbonmatsu, Manuel de la Rosa, M Paz Sánchez-Seco
AFFILIATION: Servicio de MicrobiologÃa. Hospital Universitario Virgen de las
Nieves. Granada. España. josem.navarro.sspa at juntadeandalucia.es
REFERENCE: Med Clin (Barc) 2004 Mar 122(11):420-2
BACKGROUND AND OBJECTIVE: We aimed to analyze the clinical and
epidemiological data from the first series of patients with meningitis
by Toscana virus in Spain. PATIENTS AND METHOD: We analyzed a total of
724 cerebrospinal fluid (CSF) samples from patients with suspicion of
aseptic meningitis for virus isolation in cell culture. The clinical
records of patients in whom Toscana virus was isolated were analyzed.
RESULTS: Toscana virus was isolated in CSF in 17 patients (7% of all
viral isolates). The first case was diagnosed in June 1988 and the last
one in August 2002. The mean age was 27 years (range: 10-64 years). Most
patients were based in rural area (n = 11, 64.7%). Most common symptoms
were headache (holocranial or focal) present in all patients and
moderate fever observed in 76.5% of them with a mean duration of 48 h (
range: 18 h-5 days). Nuchal rigidity was present in 9 patients (53%).
All cases were seen between June and October, and predominantly in
August (53%). The outcome was favorable in all cases, and the mean time
of duration of the disease was 7 days (range: 3-10 days). CONCLUSIONS:
Toscana virus must be taken into account among those agents responsible
of lymphocytic meningitis in Spain.
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