[leish-l] Fwd: Articles found by RefScout for your requests

jeffreyj at usp.br jeffreyj at usp.br
Fri Aug 13 21:19:41 BRT 2004





----- Forwarded message from info at refscout.com -----
    Date: Wed, 11 Aug 2004 12:34:09
    From: info at refscout.com
Reply-To: info at refscout.com
 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 Ødum, 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: Luís 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 Luís, 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, Aluízio Prata

AFFILIATION: Departamento de Clínica 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, Letícia 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.




********************************************************************************************************************

 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.

********************************************************************************************************************


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 María Navarro, Concepción Fernández-Roldán, Mercedes
Pérez-Ruiz, Sara Sanbonmatsu, Manuel de la Rosa, M Paz Sánchez-Seco

AFFILIATION: Servicio de Microbiología. 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.















You receive this email because you requested RefScout®'s literature
update.
If you would like to change or add requests, please go to your user
profile.

If you can't read our newsletter, please resend newsletter back to us to
info at refscout.com, including information
about your operating system and mail client software you use, and we will do
our
best to solve the problem.

If you would like to be removed from RefScout®'s literature service, please
press the
remove button.



DISCLAIMER







----- End forwarded message -----




More information about the Leish-l mailing list