[leish-l] Fwd: Articles found by RefScout 06/04/2005 - 14/2005

jeffreyj at usp.br jeffreyj at usp.br
Wed Apr 6 21:27:42 BRT 2005

Jeffrey J. Shaw Ph.D., D.Sc., OBE.,
   Professor Titular, Vice-Chefe do Departmento,
   Gerente "International Leishmania Network©",
   Departmento de Parasitologia,
   Instituto de Ciências Biomédicas,
   Universidade de São Paulo (USP),
   Av. Prof. Lineu Prestes, 1374,
   05508-900 São Paulo, Brazil.				
   Telefone: 55-11-3091-7633 or 55-11-9732-2954
               Fax:  55-11-3091-7417
  Email: jeffreyj at usp.br 

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This is RefScout-Newsletter 14/2005

REQUEST: [ leishmaniasis ]

(12 articles match this request)

PMID: 15804578

TITLE: Melanogenesis and associated cytotoxic reactions: Applications to insect
innate immunity.

AUTHORS: A J Nappi, B M Christensen

AFFILIATION: Department of Animal Health and Biomedical Sciences, University of
Wisconsin-Madison, 1556 Linden Drive, Madison, WI 53706, USA.

REFERENCE: Insect Biochem Mol Biol 2005 May 35(5):443-59

Insects transmit the causative agents for such debilitating diseases as 
malaria, lymphatic filariases, sleeping sickness, Chagas' disease, 
leishmaniasis, river blindness, Dengue, and yellow fever. The 
persistence of these diseases provides testimony to the genetic capacity
 of parasites to evolve strategies that ensure their successful 
development in two genetically diverse host species: insects and mammals
. Current efforts to address the problems posed by insect-borne diseases
 benefit from a growing understanding of insect and mammalian immunity. 
Of considerable interest are recent genomic investigations that show 
several similarities in the innate immune effector responses and 
associated regulatory mechanisms manifested by insects and mammals. One 
notable exception, however, is the nearly universal presence of a brown-
black pigment accompanying cellular innate immunity in insects. This 
response, which is unique to arthropods and certain other invertebrates
, has focused attention on the elements involved in pigment synthesis as
 causing or contributing to the death of the parasite, and has even 
prompted speculation that the enzyme cascade mediating melanogenesis 
constitutes an ill-defined recognition mechanism. Experimental evidence 
defining the role of melanin and its precursors in insect innate 
immunity is severely lacking. A great deal of what is known about 
melanogenesis comes from studies of the process occurring in mammalian 
systems, where the pigment is synthesized by such diverse cells as those
 comprising portions of the skin, hair, inner ear, brain, and retinal 
epithelium. Fortunately, many of the components in the metabolic 
pathways leading to the formation of melanin have been found to be 
common to both insects and mammals. This review examines some of the 
factors that influence enzyme-mediated melanogenic responses, and how 
these responses likely contribute to blood cell-mediated, target-
specific cytotoxicity in immune challenged insects.

PMID: 15796747

TITLE: Genetic variation in the sand fly salivary protein, SP-15, a potential
vaccine candidate against Leishmania major.

AUTHORS: D-E A Elnaiem, C Meneses, M Slotman, G C Lanzaro

AFFILIATION: Department of Entomology, University of California at Davis, Davis,

REFERENCE: Insect Mol Biol 2005 Apr 14(2):145-50

Abstract SP-15 is a sandfly salivary protein that provides strong 
protection against cutaneous leishmaniasis, caused by Leishmania major, 
and has been proposed as a potential vaccine against this disease. To 
investigate possible antigenic variation in this protein, we examined 
genetic polymorphism of SP-15 in 100 Phlebotomus papatasi sandflies, 
from a natural population from Sudan and four laboratory colonies from 
Egypt, Jordan, Israel and Saudi Arabia. We found that although many 
variants of SP-15 may be found in nature, differences among them are 
minimal (mean +/- SD pairwise differences = 1.69 +/- 0.83% for forty 
nucleotide sequences and 3.06 +/- 1.13% for thirty amino acid sequence 
variants). Analysis of proportions of synonymous and non-synonymous 
substitutions indicated that SP-15 is not under diversifying selection. 
Our results suggest that a vaccine based on SP-15 protein should result 
in a uniform immune response.

PMID: 15797810

TITLE: Immunopathogenesis of infection with the visceralizing Leishmania

AUTHORS: Mary E Wilson, Selma M B Jeronimo, Richard D Pearson

AFFILIATION: Departments of Internal Medicine, Microbiology and Epidemiology,
University of Iowa, The VA Medical Center, Iowa City, IA, USA.

REFERENCE: Microb Pathog 2005 Apr 38(4):147-60

Human leishmaniasis is a spectral disease that includes asymptomatic 
self-resolving infection, localized skin lesions, and progressive 
visceral leishmaniasis. With some overlap, visceral and cutaneous 
leishmaniasis are usually caused by different species of Leishmania. 
This review focuses on host responses to infection with the species that
 cause visceral leishmaniasis, as they contrast with species causing 
localized cutaneous leishmaniasis. Data from experimental models 
document significant differences between host responses to organisms 
causing these diverse syndromes. The visceralizing Leishmania spp. cause
 localized organ-specific immune responses that are important 
determinants of disease outcome. Both the Leishmania species causing 
cutaneous and those causing visceral leishmaniasis require a Type 1 
immune response to undergo cure in mouse models. However, during 
progressive murine infection with the visceralizing Leishmania sp., the 
Type 1 response is suppressed at least in part by TGF-beta and IL-10 
without type 2 cytokine production. This contrasts with the cutaneous 
species L. major, in which a Type 2 response suppresses type 1 cytokines
 and leads to murine disease progression. Population and family studies 
are beginning to elucidate human genetic determinants predisposing to 
different outcomes of Leishmania infection. These studies should 
eventually result in a better understanding of the immunopathogenesis 
and the spectrum of human leishmaniasis.

PMID: 15806230

TITLE: Contribution study of visceral leishmaniasis in Syria.

AUTHORS: Samar Al-Nahhas, Maha Shaaban, Lana Hammoud

AFFILIATION: Professor, Faculty of Sciences, Damascus University, PO Box 10718,
Damascus, Syria. Tel. +963 (11) 3716872. Fax. +963 (11) 3732338. E-mail:
samar at scs-net.org.

REFERENCE: Saudi Med J 2005 Mar 26(3):490-2

PMID: 15682458

TITLE: The fate of heterologous CD4+ T cells during Leishmania donovani

AUTHORS: Rosalind Polley, Soombul Zubairi, Paul M Kaye

AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, London, UK.

REFERENCE: Eur J Immunol 2005 Feb 35(2):498-504

Little is currently understood about the consequences of chronic 
parasitic infection for the fate of memory CD4+ T cells that recognize 
heterologous antigens, e.g. resulting from prior infections or 
vaccination. Here, we address how Leishmania donovani infection affected
 the fate of non-cross-reactive (OVA)-specific memory CD4+ T cells. DO11
 cells were adoptively transferred into naive recipient mice, which were
 then immunized to generate memory DO11 cells. After 6 weeks, mice were 
infected with L. donovani and the fate of DO11 cells was determined. L. 
donovani infection stimulated an approximately threefold expansion in 
the total number of CD4+ T cells and DO11 cells, compared to that 
observed in uninfected mice. DO11 T cells were more actively dividing in
 infected mice, as judged by 5-bromo-2' deoxyuridine labeling, whereas 
their rate of apoptosis in control and infected mice was identical. Both
 CD45RBhiCD44lo naive T cells and to a greater extent CD45RBloCD44hi 
memory DO11 cells increased in number in the spleens of infected mice, 
whereas no changes occurred to DO11 cell number or phenotype in the 
draining lymph nodes. These data indicate that heterologous CD4+ T cells
 may actively divide during chronic infectious diseases, with important 
implications for how chronic infection may impact on heterologous 

PMID: 15657947

TITLE: A critical role for lipophosphoglycan in proinflammatory responses of
dendritic cells to Leishmania mexicana.

AUTHORS: Toni Aebischer, Clare L Bennett, Mattia Pelizzola, Caterina
Vizzardelli, Norman Pavelka, Matteo Urbano, Monica Capozzoli, Alessandra
Luchini, Thomas Ilg, Francesca Granucci, C Clare Blackburn, Paola

AFFILIATION: Max-Planck-Institute for Infection Biology, Department of Molecular
Biology, Berlin, Germany.

REFERENCE: Eur J Immunol 2005 Feb 35(2):476-86

Recognition of pathogen-associated molecular patterns (PAMP) influences 
the response of dendritic cells (DC) and therefore development of innate
 and adaptive immunity. Different forms of Leishmania mexicana have 
distinct effects on DC, with promastigotes and amastigotes being 
activating and apparently neutral, respectively. We investigated whether
 stage-specific differences in surface composition might account for 
these distinct effects. Amastigotes and promastigotes lacking the lpg1 
gene needed for lipophosphoglycan (LPG) biosynthesis could not activate 
DC in vitro. Genome-wide transcriptional profiling of DC infected with 
wild-type or mutant promastigotes or wild-type amastigotes revealed that
 wild-type promastigotes induce an inflammatory signature that is 
lacking in DC exposed to the other parasite forms. The proinflammatory 
response pattern was partly recovered by reconstitution of lpg1 
expression in lpg1-/- parasites, and exposure to purified LPG increased 
the expression of MHC class II and CD86 on DC. Infection with wild-type 
but not lpg1-/- promastigotes increased the number of activated DC in 
draining lymph nodes, and this was correlated with lower early parasite 
burdens in wild-type-infected animals. These in vivo and in vitro 
results suggest an LPG-dependent activation of DC that contributes to 
host defense and agree with the notion that the parasites evolved under 
immune pressure to down-regulate PAMP expression in mammalian hosts.

PMID: 15785061

TITLE: Cutaneous leishmaniasis caused by Leishmania tropica: treatment with oral

AUTHORS: E Laffitte, B Genton, R G Panizzon

REFERENCE: Dermatology 2005  210(3):249-51

PMID: 15715010

TITLE: Detection of Leishmania infantum in canine peripheral blood.

AUTHORS: V Foglia Manzillo, D Piantedosi, L Cortese

AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Sezione Clinica
Medica, Università degli Studi di Napoli Federico II, via F. Delpino 1,80137
Naples, Italy.

REFERENCE: Vet Rec 2005 Jan 156(5):151-2

PMID: 15736529

TITLE: [Visceral leishmaniases]

AUTHORS: Eric Rosenthal, Pierre Marty

AFFILIATION: Service de médecine interne, hôpital de l'Archet, CHU de Nice,
06202 Nice Cedex. rosenthal.e at chu-nice.fr

REFERENCE: Rev Prat 2004 Dec 54(20):2211-6

Visceral leishmaniases (VL), with spreading epidemics in India and Sudan
, and sporadic cases in mediterranean basin, show clinical, 
therapeutical and public health aspects varying according to the 
geographic context. Co-infection of VL with the human immunodeficiency 
virus emerged in southwestern Europe and could occur in a next future in
 India, in Sudan, in Ethiopia or in Brazil. Today, lipid formulations of
 amphotericin B should be the first line drugs in Mediterranean basin. 
Elsewhere, pentavalent antimonials remain the cornerstone of treatment 
in non resistant areas, conventional amphotericin B or miltefosine being
 an alternative in areas of resistance to antimony.


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PMID: 12574369

TITLE: NF-kappa B1 is required for optimal CD4+ Th1 cell development and
resistance to Leishmania major.

AUTHORS: David Artis, Kendra Speirs, Karen Joyce, Michael Goldschmidt, Jorge
Caamaño, Christopher A Hunter, Phillip Scott

AFFILIATION: Department of Pathobiology, School of Veterinary Medicine,
University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.

REFERENCE: J Immunol 2003 Feb 170(4):1995-2003

The NF-kappaB family of transcription factors regulates the expression 
of a wide range of immune response genes involved in immunity to 
pathogens. However, the need for individual family members in regulating
 innate and adaptive immune responses in vivo has yet to be clearly 
defined. We investigated the role of NF-kappaB1 in the induction of 
protective IL-12-dependent Th1 cell responses following infection with 
the intracellular protozoan parasite Leishmania major. Whereas wild-type
 C57BL/6 mice controlled parasite replication, NF-kappaB1 knockout (KO) 
mice were susceptible to infection, developing chronic unresolving 
lesions associated with persistent parasites. There was a profound 
defect in Ag-specific CD4(+) T cell proliferation and IFN-gamma 
production in infected KO mice, although innate responses-including IL-
12 production and control of intracellular parasite replication by 
macrophages-were intact. In vitro polyclonal stimulation of purified 
naive KO T cells revealed an intrinsic defect in CD4(+) T cell 
proliferation associated with reduced IL-2 receptor expression, but 
operating independently of APC function and IL-2 production. Critically
, the frequency of proliferating KO CD4(+) T cells secreting IFN-gamma 
matched that of wild-type cells, suggesting that NF-kappaB1 was not 
required for efficient transcription of the IFN-gamma gene. Taken 
together, these results identify a novel role for NF-kappaB1 in CD4(+) T
 cell proliferation and the development of Th1 cell responses required 
for protective immunity against intracellular pathogens.

PMID: 11970983

TITLE: NF-kappa B2 is required for optimal CD40-induced IL-12 production but
dispensable for Th1 cell Differentiation.

AUTHORS: Kendra Speirs, Jorge Caamano, Michael H Goldschmidt, Christopher A
Hunter, Phillip Scott

AFFILIATION: Department of Pathobiology, University of Pennsylvania,
Philadelphia, PA 19104, USA.

REFERENCE: J Immunol 2002 May 168(9):4406-13

NF-kappa B is a ubiquitously expressed transcription factor involved in 
the regulation of innate and adaptive immunity. As part of studies to 
define the role of various NF-kappa B family members in Th cell 
development and maintenance, we infected NF-kappa B2(-/-) and control 
mice with Leishmania major and followed disease progression. NF-kappa B2
(-/-) mice on a normally resistant background develop chronic nonhealing
 lesions associated with uncontrolled parasite replication and a failure
 to develop an IFN-gamma response. We show that there are no intrinsic 
defects in Th cell differentiation in the absence of NF-kappa B2. Indeed
, NF-kappa B2(-/-) T cells are able to develop a Th1 phenotype and 
protect recombination-activating gene(-/-) mice from progressive 
cutaneous leishmaniasis. We demonstrate instead that the susceptibility 
of NF-kappa B2(-/-) mice to L. major is the result of an IL-12 
deficiency, and we provide evidence for a specific impairment in CD40-
induced IL-12 production by macrophages lacking this transcription 

PMID: 15424995

TITLE: Visceral leishmaniasis.


REFERENCE: U S Armed Forces Med J 1950 Jun 1(6):661-4

REQUEST: [ leishmania ]

(18 articles match this request. 5 articles matching other requests removed)

PMID: 15804377

TITLE: Flow cytometric assessment of Leishmania spp metacyclic differentiation:
Validation by morphological features and specific markers.

AUTHORS: Elvira M Saraiva, Lucia H Pinto-da-Silva, João Luiz M Wanderley,
Adriana C Bonomo, Marcello A Barcinski, Maria Elisabete C Moreira

AFFILIATION: Instituto de Microbiologia, Universidade Federal do Rio de Janeiro,
Rio de Janeiro, Brazil.

REFERENCE: Exp Parasitol 2005 May 110(1):39-47

Characterization of infective metacyclic promastigotes of Leishmania spp
 can be an essential step in several experimental protocols. Metacyclic 
forms of all Leishmania species display a typical morphology with short
, narrow cell body, and an elongated flagellum. This feature suggests 
that metacyclics can be distinguished from procyclic forms by non-
fluorimetric flow cytometric parameters thus enabling the follow-up of 
their appearance and acquisition of specific properties, during 
metacyclogenesis in in vitro cultures. Here we describe the flow 
cytometric parameters of stage-specific promastigotes of Leishmania 
major, Leishmania donovani, Leishmania amazonensis, and Leishmania 
braziliensis. Our findings were validated by optical microscopy 
morphology and specific procyclic labeling with FITC-peanut agglutinin. 
Furthermore, we show that parasite's distribution in the plot during 
differentiation in culture is not species specific and that the 
parasites displaying low forward-angle light scatter (FSC(low)) are 
three times more infective than the FSC(high) ones. The method here 
described can be applied to the identification of metacyclics of 
different Leishmania spp within the whole stationary population.

PMID: 15797809

TITLE: Exploiting calnexin expression on phagosomes to isolate Leishmania
parasitophorous vacuoles.

AUTHORS: Peter E Kima, Waltraud Dunn

AFFILIATION: Department of Microbiology and Cell Science, University of Florida,
Building 981, Box 110700, Gainesville, FL 32611, USA.

REFERENCE: Microb Pathog 2005 Apr 38(4):139-45

We have developed a simple scheme for the isolation of parasitophorous 
vacuoles (PVs) that harbor Leishmania parasites. This scheme exploits 
the observation that PVs display endoplasmic reticulum molecules, 
including the transmembrane protein calnexin. The presence of calnexin 
at the surface of the PVs distinguishes them from late endosomal 
vesicles of comparable density. As a result, PVs can be isolated by 
calnexin affinity selection from an enriched PV fraction obtained by 
sucrose density fractionation.

PMID: 15784607

TITLE: Leishmania major modulates chemokine and chemokine receptor expression by
dendritic cells and affects their migratory capacity.

AUTHORS: Mario Steigerwald, Heidrun Moll

AFFILIATION: Institut für Molekulare Infektionsbiologie, Universität
Würzburg, Röntgenring 11, 97070 Würzburg, Germany.

REFERENCE: Infect Immun 2005 Apr 73(4):2564-7

Dendritic cells (DC) both produce and respond to chemokines. We examined
 the profiles of chemokines and chemokine receptors expressed by DC and 
their chemotactic response after interaction with Leishmania major. 
Expression of the chemokine receptors CCR2 and CCR5 by DC and their 
responsiveness to the respective ligands, CCL2 and CCL3, were 
downregulated, while the level of CCR7 and the DC response to its ligand
 CCL21 were enhanced. These parasite-induced alterations were observed 
with DC from L. major-resistant and -susceptible mice. In contrast, 
expression of the chemokine CXCL10 was elicited only in DC from L. major
-resistant mice.

PMID: 15784551

TITLE: Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania
mexicana lesions.

AUTHORS: Laurence U Buxbaum, Phillip Scott

AFFILIATION: Department of Pathobiology, University of Pennsylvania School of
Veterinary Medicine, 216 ROS, 3800 Spruce Street, Philadelphia, PA 19104, USA.

REFERENCE: Infect Immun 2005 Apr 73(4):2101-8

Infection of C57BL/6 (B6) mice with Leishmania mexicana is associated 
with a minimal immune response and chronic disease. Here we show that B6
 interleukin 10-/- (IL-10-/-) mice resolve their lesions and exhibit 
increased gamma interferon (IFN-gamma), nitric oxide production, and 
delayed-type hypersensitivity. This enhanced resistance was dependent 
upon IL-12p40, since treatment of L. mexicana-infected IL-10-/- mice 
with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-
opsonized L. mexicana induced IL-10 production by B6 macrophages in 
vitro, implicating antibody binding to Fc receptors as a mechanism 
involved in IL-10 production in this infection. Furthermore, B6 FcRgamma
-/- mice resolve L. mexicana lesions, and lymph node cells from these 
mice produced less IL-10 and more IFN-gamma than cells from infected 
wild-type mice. These data demonstrate that removal of IL-10 or FcgammaR
 leads to resolution of L. mexicana disease and support a model in which
 ligation of FcgammaR by L. mexicana-bound immunoglobulin G promotes IL-
10 production, leading to chronic disease.

PMID: 15788098

TITLE: Heterologous expression of the filarial nematode alt gene products
reveals their potential to inhibit immune function.

AUTHORS: Natalia Gomez-Escobar, Clare Bennett, Lidia Prieto-Lafuente, Toni
Aebischer, Clare C Blackburn, Rick M Maizels

AFFILIATION: Institute of Immunology and Infection Research, University of
Edinburgh, UK. r.maizels at ed.ac.uk.

REFERENCE: BMC Biol 2005 Mar 3(1):8

BACKGROUND: Parasites exploit sophisticated strategies to evade host 
immunity that require both adaptation of existing genes and evolution of
 new gene families. We have addressed this question by testing the 
immunological function of novel genes from helminth parasites, in which 
conventional transgenesis is not yet possible. We investigated two such 
novel genes from Brugia malayi termed abundant larval transcript (alt), 
expression of which reaches ~5% of total transcript at the time 
parasites enter the human host. RESULTS: To test the hypothesis that ALT
 proteins modulate host immunity, we adopted an alternative transfection
 strategy to express these products in the protozoan parasite Leishmania
 mexicana. We then followed the course of infection in vitro in 
macrophages and in vivo in mice. Expression of ALT proteins, but not a 
truncated mutant, conferred greater infectivity of macrophages in vitro
, reaching 3-fold higher parasite densities. alt-transfected parasites 
also caused accelerated disease in vivo, and fewer mice were able to 
clear infection of organisms expressing ALT. alt-transfected parasites 
were more resistant to IFN-gamma-induced killing by macrophages. 
Expression profiling of macrophages infected with transgenic L. mexicana
 revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, 
both associated with the Th2-type response observed in in vivo filarial 
infection. CONCLUSION: Leishmania transfection is a tractable and 
informative approach to determining immunological functions of single 
genes from heterologous organisms. In the case of the filarial ALT 
proteins, our data suggest that they may participate in the Th2 bias 
observed in the response to parasite infection by modulating cytokine-
induced signalling within immune system cells.

PMID: 15725130

TITLE: A simple method allowing DIC imaging in conjunction with confocal

AUTHORS: S H Cody, S D Xiang, M J Layton, E Handman, M H C Lam, J E Layton, E C
Nice, J K Heath

AFFILIATION: Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne
Hospital, Victoria 3050, Australia. stephen.cody at ludwig.edu.au

REFERENCE: J Microsc 2005 Mar 217(Pt 3):265-74

Current optical methods to collect Nomarski differential interference 
contrast (DIC) or phase images with a transmitted light detector (TLD) 
in conjunction with confocal laser scanning microscopy (CLSM) can be 
technically challenging and inefficient. We describe for the first time 
a simple method that combines the use of the commercial product QPm (
Iatia, Melbourne Australia) with brightfield images collected with the 
TLD of a CLSM, generating DIC, phase, Zernike phase, dark-field or 
Hoffman modulation contrast images. The brightfield images may be 
collected at the same time as the confocal images. This method also 
allows the calculation of contrast-enhanced images from archival data. 
The technique described here allows for the creation of contrast-
enhanced images such as DIC or phase, without compromising the intensity
 or quality of confocal images collected simultaneously. Provided the 
confocal microscope is equipped with a motorized z-drive and a TLD, no 
hardware or optical modifications are required. The contrast-enhanced 
images are calculated with software using the quantitative phase-
amplitude microscopy technique (Barone-Nugent et al., 2002). This 
technique, being far simpler during image collection, allows the 
microscopist to concentrate on their confocal imaging and experimental 
procedures. Unlike conventional DIC, this technique may be used to 
calculate DIC images when cells are imaged through plastic, and without 
the use of expensive strain-free objective lenses.

PMID: 15796010

TITLE: Identification of the first pyrimidine nucleobase transporter in
Leishmania: similarities with the Trypanosoma brucei U1 transporter and
antileishmanial activity of uracil analogues.

AUTHORS: I G Papageorgiou, L Yakob, M I Al Salabi, G Diallinas, K P Soteriadou,
H P De Koning

AFFILIATION: Department of Biochemistry, Hellenic Pasteur Institute, 115 21
Athens, Greece.

REFERENCE: Parasitology 2005 Mar 130(Pt 3):275-83

While purine transport has been widely studied in protozoa, almost 
nothing is known about their capacity to salvage pyrimidines. Here, we 
report a Leishmania major transporter with high affinity for uracil (Km=
0.32+/-0.07 microM) which we designated LmU1. This transporter displayed
 a high degree of specificity, as it had virtually no affinity for 
cytosine, thymine or purine nucleobases, nor did it transport pyrimidine
 nucleosides. Highest affinity was for 5-fluorouracil. The results show 
that the permeant binding site of LmU1 interacts strongly with the keto 
groups of uracil, as shown by a low affinity for 2-thio- and 4-
thiouracil. LmU1 appears to further bind uracil through a weak hydrogen 
bond with N(1)H of the pyrimidine ring in addition to a stronger H-bond 
with N(3)H. Substrate binding and selectivity were strikingly similar to
 that of the U1 transporter in the related kinetoplastid Trypanosoma 
brucei. Uracil analogues likely to be transported by LmU1 were also 
screened for antileishmanial activity, with 5-fluorouracil displaying 
strong activity against promastigotes and intracellular amastigotes. 
Overall, the results show that, like purine nucleobase transport, 
pyrimidine nucleobase transport function is very similar in L. major and
 T. brucei insect forms.

PMID: 15781861

TITLE: Functional complementation of Trypanosoma brucei RNA in vitro editing
with recombinant RNA ligase.

AUTHORS: Guanghan Gao, Agda M Simpson, Xuedong Kang, Kestrel Rogers, Martina
Nebohacova, Feng Li, Larry Simpson

AFFILIATION: Department of Microbiology, Immunology, and Molecular Genetics and
Howard Hughes Medical Institute, University of California, Los Angeles, CA

REFERENCE: Proc Natl Acad Sci U S A 2005 Mar 102(13):4712-7

The approximately 20S RNA ligase-containing complex (L-complex) in 
trypanosomatid mitochondria interacts by means of RNA linkers with at 
least two other multiprotein complexes to mediate the editing of 
mitochondrial cryptogene transcripts. The L-complex contains 
approximately 16 proteins, including the two RNA-editing ligases (RELs
), REL1 and REL2. Leishmania tarentolae REL1 and REL2 and Trypanosoma 
brucei REL1 were expressed as enzymatically active tandem affinity 
purification-tagged proteins in a Baculovirus system. When these 
proteins were added to mitochondrial lysates from T. brucei procyclic 
cells that were depleted of the cognate endogenous ligase by RNA 
interference down-regulation of expression, the added proteins were 
integrated into the L-complex, and, in the case of REL1, there was a 
complementation of in vitro-precleaved U-insertion and U-deletion 
editing activities of the 20S L-complex. Integration of the recombinant 
proteins did not occur or occurred at a very low level with noncognate 
ligase-depleted L-complex or with wild-type L-complex. A C-terminal 
region of the T. brucei recombinant REL1 downstream of the catalytic 
domain was identified as being involved in integration into the L-
complex. The ability to perform functional complementation in vitro 
provides a powerful tool for molecular dissection of the editing 

PMID: 15799523

TITLE: Isolation of a myoinhibitory peptide from Leishmania major
(Kinetoplastida: Trypanosomatidae) and its function in the vector sand fly
Phlebotomus papatasi (Diptera: Psychodidae).

AUTHORS: Rajeev Vaidyanathan

AFFILIATION: Department of Parasitology, Hebrew University of Jerusalem,
Hadassah Medical School, Ein Kerem, Jerusalem 91120, Israel.

REFERENCE: J Med Entomol 2005 Mar 42(2):142-52

Protozoan parasites in the genus Leishmania are ingested by sand flies 
with blood and multiply in the gut until they are transmitted to a 
vertebrate host when the sand fly blood feeds again. Infections of the 
enzootic vector Phlebotomus papatasi Scopoli result in distended midguts
 with no spontaneous gut contractions. Using a P. papatasi hindgut 
contraction bioassay, a paralytic factor sensitive to trypsin, 
chymotrypsin, proteinase-K, and heating at 56 degrees C was detected in 
crude lysates of Leishmania major promastigotes. Application of parasite
 lysate to isolated hindguts resulted in reversible, dose-dependent 
inhibition of spontaneous contractions. Mean volume of isolated midguts 
and hindguts increased by 50-60% after application of L. major lysate. L
. major paralytic factor was purified 10(4)-fold over the total protein 
preparation and yielded a hydrophobic 12-kDa peptide. Myoinhibitory 
activity eluted as a single peak in reverse phase-high-pressure liquid 
chromatography. Tandem mass spectrometry resulted in 15 amino acid 
sequences, three of them sharing 45-73% homology with short hypothetical
 gene products of undefined function from Pseudomonas, Halobacterium, 
and Drosophila. This unique protozoan peptide mimics the function of 
endogenous insect neuropeptides that control visceral muscle 
contractions. By this novel mechanism, parasites persist in the expanded
, relaxed midgut after blood meal and peritrophic matrix digestion. This
 allows time for development and migration of infective forms, 
facilitating sand fly vector competence and parasite transmission.

PMID: 15557260

TITLE: Structural and functional analysis of the gpsA gene product of
Archaeoglobus fulgidus: a glycerol-3-phosphate dehydrogenase with an unusual
NADP+ preference.

AUTHORS: Shin-Ichi Sakasegawa, Christoph H Hagemeier, Rudolf K Thauer, Lars-O
Essen, Seigo Shima

AFFILIATION: Max-Planck-Institut für terrestrische Mikrobiologie and
Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps Universität,
Marburg, Germany.

REFERENCE: Protein Sci 2004 Dec 13(12):3161-71

NAD(+)-dependent glycerol-3-phosphate dehydrogenase (G3PDH) is generally
 absent in archaea, because archaea, unlike eukaryotes and eubacteria, 
utilize glycerol-1-phosphate instead of glycerol-3-phosphate for the 
biosynthesis of membrane lipids. Surprisingly, the genome of the 
hyperthermophilic archaeon Archaeoglobus fulgidus comprises a G3PDH 
ortholog, gpsA, most likely due to horizontal gene transfer from a 
eubacterial organism. Biochemical characterization proved G3PDH-like 
activity of the recombinant gpsA gene product. However, unlike other 
G3PDHs, the up to 85 degrees C thermostable A. fulgidus G3PDH exerted a 
15-fold preference for NADPH over NADH. The A. fulgidus G3PDH bears the 
hallmarks of adaptation to halotolerance and thermophilicity, because 
its 1.7-A crystal structure showed a high surface density for negative 
charges and 10 additional intramolecular salt bridges compared to a 
mesophilic G3PDH structure. Whereas all amino acid residues required for
 dihydroxyacetone phosphate binding and reductive catalysis are highly 
conserved, the binding site for the adenine moiety of the NAD(P) 
cosubstrate shows a structural variation that reflects the observed 
NADPH preference, for example, by a putative salt bridge between R49 and
 the 2'-phosphate.

PMID: 15615399

TITLE: [Alithiasic cholecystitis in association with visceral leishmaniasis in
an immunodepressed patient]

AUTHORS: T Coton, P Kraemer, F Simon, J J Morand, J J Depina, T Lonjon, P

REFERENCE: Med Trop (Mars) 2004  64(4):407-8


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


PMID: 15550118

TITLE: Novel adjuvant based on a proteoliposome-derived cochleate structure
containing native lipopolysaccharide as a pathogen-associated molecular

AUTHORS: Oliver Pérez, Gustavo Bracho, Miriam Lastre, Nestor Mora, Judith del
Campo, Danay Gil, Caridad Zayas, Reinaldo Acevedo, Domingo González, José A
López, Carlos Taboada, Cameron Turtle, Rosa L Solis

AFFILIATION: Immunology Department, Finlay Institute, Havana, Cuba.
oliverp at finlay.edu.cu

REFERENCE: Immunol Cell Biol 2004 Dec 82(6):603-10

Proteoliposomes (PL) from Neisseria meningitidis B have been widely used
 as a core antigen for antimeningococcal vaccination. PL contain major 
outer membrane proteins, LPS and phospholipids, and they induce a strong
 Th1 immune response, but they have low stability in solution. Attending
 to the need for new vaccine adjuvants, we developed a highly stable 
cochleate structure (CS) from PL using a technology that allows easy 
incorporation of new antigens. We explored the ability of PLCS to 
activate the immune system and its possible application as an adjuvant 
for parenteral and mucosal routes. Our results showed that PLCS were 
able to upregulate the expression of MHC class II and costimulatory 
molecules on human dendritic cells, as well as being able to stimulate 
the production of soluble mediators of a Th1 response, such as IL-12 and
 nitric oxide. High levels of anti-PL IgG were detected in serum after i
.m. or mucosal (oral and nasal) administration, but also anti-PL 
secretory IgA was produced in saliva following nasal delivery. The 
immune response polarization to a Th1 pattern was confirmed by the 
induction of IgG2a antibodies, positive delayed type hypersensitivity 
reactions, and IFN-gamma production by splenocytes from immunized mice. 
The adjuvant potential was explored using PLCS containing ovalbumin (Ova
). PLCS-Ova was able to elicit a substantial increase in anti-Ova IgG 
compared with Ova alone. In addition, a significant reduction in lesion 
size was observed in mice immunized with Leishmania major antigens in 
PLCS after challenge with virulent protozoa, suggesting at least partial
 modulation of the Th2 environment induced by this parasite. In 
conclusion, our results support the use of PLCS as a potent Th1 adjuvant
 for parenteral and mucosal vaccines.

PMID: 15102766

TITLE: Leishmania major amastigotes induce p50/c-Rel NF-kappa B transcription
factor in human macrophages: involvement in cytokine synthesis.

AUTHORS: Lamia Guizani-Tabbane, Khadija Ben-Aissa, Meriam Belghith, Atfa Sassi,
Koussay Dellagi

AFFILIATION: Laboratory of Immunology, Vaccinology and Molecular Genetics (WHO
Collaborating Center for Research and Training in Leishmaniasis), Institut
Pasteur de Tunis, 1002 Tunis-Belvedere, Tunisia. lamia.guizani at Pasteur.rns.tn

REFERENCE: Infect Immun 2004 May 72(5):2582-9

Invasion of a host by pathogens is frequently associated with activation
 of nuclear factor kappa B (NF-kappaB), which is implicated in various 
aspects of immune function required for resistance to infection. However
, pathogens may also subdue these mechanisms to secure their survival. 
Here we describe the effect of Leishmania major infection on NF-kappaB 
transcription factor activation in both promonocytic human cell line 
U937 and fresh human monocytes. Infection by L. major amastigotes 
blocked nuclear translocation of a phorbol-12 myristate-13 acetate (PMA
)-induced p50/p65 NF-kappaB complex in PMA-treated differentiated U937 
cells and triggered expression of p50- and c-Rel-containing complexes in
 both U937 cells and fresh human monocytes. These p50/c-Rel complexes, 
triggered by direct cell-parasite interactions, were detectable within 
30 min after the interaction and were transcriptionally active. The NF-
kappaB inhibitor caffeic acid phenethyl ester inhibited production of 
both tumor necrosis factor alpha and interleukin-10 (IL-10) induced by 
Leishmania amastigotes in differentiated U937 cells. Similar results for
 IL-10 induction were observed with amastigote-infected human monocytes
. Our results indicate that L. major amastigotes activate NF-kappaB by 
specifically inducing p50- and c-Rel-containing complexes which are 
likely involved in the regulation of cytokine synthesis.

REQUEST: [ sand fly ]

(2 articles match this request. 2 articles matching other requests removed)

REQUEST: [ sandfly ]

(2 articles match this request. 1 article matching other requests removed)

PMID: 15708593

TITLE: Development of a mouse model for the study of Toscana virus

AUTHORS: Maria Grazia Cusi, Gianni Gori Savellini, Chiara Terrosi, Giuseppa Di
Genova, Marcello Valassina, Melissa Valentini, Sabrina Bartolommei, Clelia

AFFILIATION: Department of Molecular Biology, Virology Section, University of
Siena, Policlinico Le Scotte, V.le Bracci, Building V, 53100 Siena, Italy.
cusi at unisi.it

REFERENCE: Virology 2005 Mar 333(1):66-73

Toscana virus (TOSV) has recently been recognized as an emerging virus 
transmitted by phlebotomus vectors, responsible for acute neurological 
diseases in Mediterranean countries. In our study, we demonstrated that 
adult Balb/c mice were susceptible to TOSV when infected intracerebrally
 (i.c.) or subcutaneously (s.c.) with a neuroadapted strain of the virus
. We have shown that by performing serial passages of a wild type human 
isolate of TOSV in mouse brains, selection occurs for a highly virulent 
variant which replicates efficiently in the central nervous system (CNS
) of i.c.-injected mice, causing acute encephalitis and death. 
Immunohistochemical analysis and TUNEL assay of post-mortem organs 
showed that TOSV replication was highly restricted to neurons in which 
it induced apoptotic death; however, virus antigen-positivity was also 
observed in the spleen and lymph nodes. In s.c.-injected mice, virus was
 detectable in the spleen and lymph nodes, whereas only few meningeal 
cells and neurons were affected, allowing for the mouse survival the 
infection. The presence of TOSV in spleen and lymph node cells in both s
.c.- and i.c.-treated mice suggests their possible involvement in the 
diffusion of the infection. This animal model may be helpful for the 
development of prophylactic measures against TOSV infections.

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