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

[jeffreyj at usp.br]

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    Date: Thu, 5 Aug 2004 00:24:22
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REQUEST: [ leishmaniasis ]

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



PMID: 15271920
 

TITLE: Inbred strains derived from feral mice reveal new pathogenic mechanisms
of experimental leishmaniasis due to Leishmania major.

AUTHORS: Besma E C Babay, Hechmi Louzir, Chahnaz Kebaïer, Samir Boubaker,
Koussay Dellagi, Pierre-André Cazenave

AFFILIATION: Laboratory of Immunology (LAF 301), Institut Pasteur de Tunis, WHO
Collaborating Center for Training and Research on Leishmaniasis, 1002
Tunis-Belvedere, Tunisia.

REFERENCE: Infect Immun 2004 Aug 72(8):4603-11

Two inbred mouse strains, derived from feral founders, are susceptible 
to experimental leishmaniasis due to Leishmania major and support a 
disease of a severity intermediate between those observed in strains 
C57BL/6 and BALB/c. Mice of the MAI strain develop a severe, nonhealing
, but nonfatal disease with no resistance to a secondary parasite 
challenge. The immunological responses showed a TH2 dominance 
characterized by an early peak of interleukin-4 (IL-4) and IL-13. 
However, neutralization of IL-4, which leads to a resistance phenotype 
in BALB/c mice, has no effect on disease progression in MAI mice. Mice 
of strain PWK develop a protracted but self-healing disease, 
characterized by a mixed TH1-plus-TH2 pattern of immune responses in 
which IL-10 plays an aggravating role, and acquire resistance to a 
secondary challenge. These features are close to those observed in human
 cutaneous leishmaniasis due to L. major and make PWK mice a suitable 
model for the human disease.








PMID: 15285729
 

TITLE: The first probable case of platelet transfusion-transmitted visceral
leishmaniasis.

AUTHORS: P Mathur, J C Samantaray

AFFILIATION: Department of Microbiology, All India Institute of Medical
Sciences, New Delhi, India.

REFERENCE: Transfus Med 2004 Aug 14(4):319-21

Summary. Visceral leishmaniasis (VL; kala-azar), a life-threatening 
infection of the mononuclear phagocytic system, is transmitted by the 
bite of infected sand flies. Though peripheral parasitaemia is 
documented for Leishmania spp. causing VL, reports of transfusion-
transmitted infections are rare. A case of probable platelet transfusion
-acquired VL is reported from India and issues related to transfusion 
safety in endemic areas are discussed.




PMID: 15273104
 

TITLE: Novel azasterols as potential agents for treatment of leishmaniasis and
trypanosomiasis.

AUTHORS: Silvia Orenes Lorente, Juliany C F Rodrigues, Carmen Jiménez Jiménez,
Miranda Joyce-Menekse, Carlos Rodrigues, Simon L Croft, Vanessa Yardley, Kate
De Luca-Fradley, Luis M Ruiz-Pérez, Julio Urbina, Wanderley De Souza, Dolores
González Pacanowska, Ian H Gilbert

AFFILIATION: Welsh School of Pharmacy, Cardiff University, Redwood Building,
King Edward VII Avenue, Cardiff, CF10 3XF, United Kingdom. gilbertih at cf.ac.uk

REFERENCE: Antimicrob Agents Chemother 2004 Aug 48(8):2937-50

This paper describes the design and evaluation of novel azasterols as 
potential compounds for the treatment of leishmaniasis and other 
diseases caused by trypanosomatid parasites. Azasterols are a known 
class of (S)-adenosyl-l-methionine: Delta(24)-sterol methyltransferase(
24-SMT) inhibitors in fungi, plants, and some parasitic protozoa. The 
compounds prepared showed activity at micromolar and nanomolar 
concentrations when tested against Leishmania spp. and Trypanosoma spp. 
The enzymatic and sterol composition studies indicated that the most 
active compounds acted by inhibiting 24-SMT. The role of the free 
hydroxyl group at position 3 of the sterol nucleus was also probed. When
 an acetate was attached to the 3beta-OH, the compounds did not inhibit 
the enzyme but had an effect on parasite growth and the levels of 
sterols in the parasite, suggesting that the acetate group was removed 
in the organism. Thus, an acetate group on the 3beta-OH may have 
application as a prodrug. However, there may be an additional mode(s) of
 action for these acetate derivatives. These compounds were shown to 
have ultrastructural effects on Leishmania amazonensis promastigote 
membranes, including the plasma membrane, the mitochondrial membrane, 
and the endoplasmic reticulum. The compounds were also found to be 
active against the bloodstream form (trypomastigotes) of Trypanosoma 
brucei rhodesiense, a causative agent of African trypanosomiasis.




PMID: 15271911
 

TITLE: Intranasal vaccination against cutaneous leishmaniasis with a
particulated leishmanial antigen or DNA encoding LACK.

AUTHORS: Eduardo Fonseca Pinto, Roberta Olmo Pinheiro, Alice Rayol, Vicente
Larraga, Bartira Rossi-Bergmann

AFFILIATION: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal
do Rio de Janeiro, RJ, Brazil.

REFERENCE: Infect Immun 2004 Aug 72(8):4521-7

We have previously demonstrated that oral delivery of a disease-
promoting particulated antigen of Leishmania amazonensis (LaAg) 
partially protects mice against cutaneous leishmaniasis. In the present 
work, we sought to optimize a mucosal vaccine by using the intranasal 
route for delivery of different antigen preparations, including (i) LaAg
, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii
) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two 
intranasal doses of 10 microg of LaAg and were challenged 1 week 
postvaccination with L. amazonensis developed delayed but effective 
control of lesion growth. A diminished parasite burden was accompanied 
by enhancement of both gamma interferon (IFN-gamma) and interleukin-10 
levels in the lesion-draining lymph nodes. The vaccine efficacy improved
 with time. At 4 months postvaccination, when a strong parasite-specific
 TH1-type response was present in vivo, the infection was controlled for
 at least 5 months after challenge. In contrast to the particulated LaAg
, soluble LACK (10 microg/dose) had no effect. Interestingly, LACK DNA (
30 microg/dose), but not empty DNA, promoted rapid and durable 
protective immunity. Parasite growth was effectively controlled, and at 
5 months after challenge LACK-reactive cells in both the mucosal and 
lesion-draining lymph nodes produced high levels of IFN-gamma. These 
results demonstrate for the first time the feasibility of using the 
intranasal route for long-lived memory vaccination against cutaneous 
leishmaniasis with adjuvant-free crude antigens or DNA.




PMID: 15276066
 

TITLE: Phenyl substitution of furamidine markedly potentiates its anti-parasitic
activity against Trypanosoma cruzi and Leishmania amazonensis.

AUTHORS: E M De Souza, A Lansiaux, C Bailly, W D Wilson, Q Hu, D W Boykin, M M
Batista, T C Araújo-Jorge, M N C Soeiro

AFFILIATION: Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ,
Avenida Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, RJ, Brazil.

REFERENCE: Biochem Pharmacol 2004 Aug 68(4):593-600

Furamidine (DB75) and related unfused aromatic diamidines have proven 
useful for the treatment of parasitic infections. These compounds were 
primarily developed to combat infections by Pneumocystis carinii and 
African trypanosomes but they are also active against other parasites. 
Here we have investigated the in vitro effects of DB75 and its phenyl-
substituted analog DB569 on two kinetoplastid haemoflagellates 
Trypanosomatidae: Trypanosoma cruzi and Leishmania (L) amazonensis. The 
phenyl-amidine compound DB569 has equivalent DNA binding properties 
compared to DB75 but it was selected on the basis of its distinct tumor 
cell distribution properties. We found that DB569 is significantly more 
potent than DB75 at reducing the proliferation of the parasites, using 
either isolated parasites in cultures or with cardiomyocyte and 
macrophage host cells. DB569 is effective towards the intracellular 
forms of T. cruzi (IC(50) in the low-micromolar range) and it exhibits 
trypanocidal dose-dependent effects against trypomastigote forms of T. 
cruzi parasites obtained from the Y strain and Dm28c clone, which belong
 to two different biodemes. Fluorescence microscopy experiments 
indicated that both diamidines were mostly localized in the nucleus of 
the mammalian host cells and within the nuclei and kinetoplast of the 
parasites. Electron microscopy studies showed that the treatment of the 
parasites with DB75 and DB569 induces important alterations of the 
parasite nucleus and kinetoplast, at sites where their DNA target is 
localized. Altogether, the data suggest that the phenyl-substituted 
furamidine analogue DB569 is a potential new candidate for the treatment
 of the Chagas' disease and Leishmaniasis.




PMID: 15138256
 

TITLE: Drug uptake and modulation of drug resistance in Leishmania by an
aquaglyceroporin.

AUTHORS: Benjamin Gourbal, Niluefer Sonuc, Hiranmoy Bhattacharjee, Danielle
Legare, Shyam Sundar, Marc Ouellette, Barry P Rosen, Rita Mukhopadhyay

AFFILIATION: Department of Biochemistry and Molecular Biology, School of
Medicine, Wayne State University, Detroit, Michigan 48201, USA.

REFERENCE: J Biol Chem 2004 Jul 279(30):31010-7

Leishmaniasis is a protozoan parasitic disease that affects 12 million 
people worldwide. The first line choice for the treatment of this 
disease is antimonial drugs. In the endemic regions, resistance to this 
class of drugs is a major impediment to treatment. Microbes often become
 resistant to drugs by mutation or down-regulation of uptake systems, 
but the uptake system for the antimonial drugs in Leishmania is unknown
. In other organisms, aquaglyceroporins have been shown to facilitate 
uptake of trivalent metalloids. In this study, we report the 
identification and characterization of aquaglyceroporins from Leishmania
 major (LmAQP1) and Leishmania tarentolae (LtAQP1), respectively. These 
Leishmania proteins have the conserved signature motifs of 
aquaglyceroporins. Transfection of LmAQP1 into three species of 
Leishmania, L. tarentolae, Leishmania infantum, and L. major, produced 
hypersensitivity to both As(III) and Sb(III) in all three strains. 
Increased production of LmAQP1 was detected by immunoblotting. Drug-
resistant parasites with various mutations leading to resistance 
mechanisms became hypersensitive to both metalloids after expression of 
LmAQP1. Increased rates of uptake of As(III) or Sb(III) correlated with 
metalloid sensitivity of the wild type and drug-resistant transfectants
. Transfection of LmAQP1 in a Pentostam-resistant field isolate also 
sensitized the parasite in the macrophage-associated amastigote form. 
One allele of LmAQP1 was disrupted in L. major, and the resulting cells 
became 10-fold more resistant to Sb(III). This is the first report of 
the uptake of a metalloid drug by an aquaglyceroporin in Leishmania, 
suggesting a strategy to reverse resistance in the field.




PMID: 15270099
 

TITLE: The human cytokine response to Leishmania major early after exposure to
the parasite in vitro.

AUTHORS: Kathleen A Rogers, Richard G Titus

AFFILIATION: Department of Microbiology, Immunology, and Pathology, College of
Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort
Collins, Colorado 80523-1619, USA.

REFERENCE: J Parasitol 2004 Jun 90(3):557-63

Leishmaniasis is caused by the protozoan parasite Leishmania spp. In 
murine leishmaniasis, a T helper cell type-I (Th1) response, 
characterized by the secretion of interferon (IFN)-gamma is necessary 
for clearing the infection. whereas a Th2 response, accompanied by the 
production of interleukin (IL)-5, can exacerbate the disease. Moreover, 
the early cytokine milieu is thought to play an important role in 
determining the outcome of infection. In human leishmaniasis little is 
known about this early cytokine response. Because of this, we cocultured
 human peripheral blood mononuclear cells (PBMC) with Leishmania major 
in vitro and measured the production of IFN-gamma, IL-5, and IL-10. We 
also treated PBMC cultures with various cytokines and neutralizing 
anticytokines. We found that the principal cytokine produced was IFN-
gamma and that its production was regulated by IL-10 and IL-12. In 
contrast, only low levels of Th2 cytokines such as IL-5 were produced. 
Therefore, the Th1-Th2 dichotomy that exists in inbred strains of mice 
does not appear to apply to the response of humans to L. major. Rather, 
Th2 cytokines may play a role in regulating IFN-gamma production.




PMID: 15211001
 

TITLE: Genetic polymorphism within the leishmania donovani complex: correlation
with geographic origin.

AUTHORS: Eva Zemanová, Milan Jirků, Isabel L Mauricio, Michael A Miles, Julius
Lukes

AFFILIATION: Institute of Parasitology, Czech Academy of Sciences, and Faculty
of Biology, University of South Bohemia, Ceske Budejovice, Czech Republic.

REFERENCE: Am J Trop Med Hyg 2004 Jun 70(6):613-7

Random amplified polymorphic DNA (RAPD) was used to detect intraspecific
 diversity for the Leishmania donovani complex. Fifty-two decameric to 
21-meric primers of arbitrary sequence were applied to 15 strains that 
belong to nine zymodemes. Strains belonging to the species L. major and 
L. tropica were used as outgroups. A total of 902 amplicons generated by
 RAPD were scored. Most primers produced species-specific profiles, only
 0.6% amplicons were shared by all species, while 4.3% amplicons were 
common for all 15 strains of the L. donovani complex. Well-supported 
trees have been constructed, which show a rather strong correlation 
between the genetic polymorphism of studied strains and their geographic
 origin. In all obtained trees, L. infantum was paraphyletic. The RAPD 
profiles suggest that MON-30 belongs to L. donovani. Moreover, the 
genetic distance between the L. archibaldi strain and other leishmanias 
does not warrant existence of a separate species.




PMID: 15162428
 

TITLE: Notch1 expression on T cells is not required for CD4+ T helper
differentiation.

AUTHORS: Fabienne Tacchini-Cottier, Cindy Allenbach, Luc A Otten, Freddy Radtke

AFFILIATION: World Health Organization Immunology Research and Training Centre,
and Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Fabienne.Tacchini-Cottier at ib.unil.ch

REFERENCE: Eur J Immunol 2004 Jun 34(6):1588-96

Notch1 proteins are involved in binary cell fate decisions. To determine
 the role of Notch1 in the differentiation of CD4(+) Th1 versus Th2 
cells, we have compared T helper polarization in vitro in naive CD4(+) T
 cells isolated from mice in which the N1 gene is specifically 
inactivated in all mature T cells. Following activation, Notch1-
deficient CD4(+) T cells transcribed and secreted IFN-gamma under Th1 
conditions and IL-4 under Th2 conditions at levels similar to that of 
control CD4(+) T cells. These results show that Notch1 is dispensable 
for the development of Th1 and Th2 phenotypes in vitro. The requirement 
for Notch1 in Th1 differentiation in vivo was analyzed following 
inoculation of Leishmania major in mice with a T cell-specific 
inactivation of the Notch1 gene. Following infection, these mice 
controlled parasite growth at the site of infection and healed their 
lesions. The mice developed a protective Th1 immune response 
characterized by high levels of IFN-gamma mRNA and protein and low 
levels of IL-4 mRNA with no IL-4 protein in their lymph node cells. 
Taken together, these results indicate that Notch1 is not critically 
involved in CD4(+) T helper 1 differentiation and in resolution of 
lesions following infection with L. major.




PMID: 15270002
 

TITLE: Diversity and species composition of sand flies (Diptera: Psychodidae) in
a Venezuelan urban focus of cutaneous leishmaniasis.

AUTHORS: E Rojas, J V Scorza, G Morales, C Morales, R Barazarte, A Torres

AFFILIATION: Universidad de Los Andes, Núcleo Universitario Rafael Rangel,
Avenida Medina Angarita, Frente al Parque Los Ilustres, Trujillo 3102 A,
Venezuela.

REFERENCE: J Am Mosq Control Assoc 2004 Jun 20(2):189-94

The present study examined the spatial and temporal abundance and 
diversity of phlebotomine sand flies in an area of Venezuela that is an 
ancient focus of leishmaniasis. The study was conducted in 6 stations in
 urban localities in Trujillo City, located in northwestern Venezuela (9
 degrees 22' 24" N, 70 degrees 26' 08" W), which is located in a 
mountain range in the Andean ecoregion (altitude = 600-1,010 m). During 
1995-99, entomological surveys were conducted after and before the rainy
 season. Shannon light traps were operated from 1800 to 2000 h in 
peridomestic site trap locations. Twelve species were captured, and 
Lutzomyia youngi, L. ovallesi, L. scorzai, L. gomezi, L. lichyi, and L. 
shannoni occurred at all localities in each year. The abundance of these
 species showed low variation over time but high variation between 
localities. The Sørensen similarity index, used to compare diversity 
between years within each locality, ranged from 0.60 at Carmona to 0.84 
at La Hacienda. Sand fly communities exhibited annual variation in 
species richness and diversity. Variations were affected more by changes
 in species abundance than by changes in species composition. Lutzomyia 
ovallesi, L. lichyi, and L. scorzai had the highest coefficient of 
variation between years (63, 38, and 23%, respectively).




PMID: 15273808
 

TITLE: Anti-leishmanial activity of alkaloidal extract from Aspidosperma
ramiflorum.

AUTHORS: Izabel Cristina Piloto Ferreira, Maria Valdrinez Campana Lonardoni,
Gerzia M C Machado, Leonor L Leon, Lucílio Gobbi Filho, Luís Henrique Bissoli
Pinto, Arildo José Braz de Oliveira

AFFILIATION: Laboratório de Química Farmacêutica e Síntese de Medicamentos,
Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá,
Brasil.

REFERENCE: Mem Inst Oswaldo Cruz 2004 May 99(3):325-7

Infections due to protozoa of the genus Leishmania are a major worldwide
 health problem, with high endemicity in developing countries. The drugs
 of choice for the treatment of leishmaniasis are the pentavalent 
antimonials (SbV), which present renal and cardiac toxicity. Besides, 
the precise chemical structure and mechanism of action of these drugs 
are unknown up to date. In order to find new drugs against leishmaniasis
, we have been studying extracts of Brazilian trees. In the present 
study, we have evaluated the effectiveness of an alkaloid extract of 
Aspidosperma ramiflorum Muell. Arg. (Apocynaceae), against the 
extracellular forms promastigotes of L. (L.) amazonensis and L. (V.) 
braziliensis. The alkaloid extract of A. ramiflorum was much more 
effective against L. (L.) amazonensis (LD50 < 47 microg/ml) than L
. (V.) braziliensis. Based on these in vitro results against L. (L.) 
amazonensis new studies should be made to find the compounds with anti-
leishmanial activity.




PMID: 15273809
 

TITLE: Effect of thiadiazine derivatives on intracellular amastigotes of
Leishmania amazonensis.

AUTHORS: Lianet Monzote Fidalgo, Ana Margarita Montalvo Alvarez, Lisset Fonseca
Geigel, Rolando Pérez Pineiro, Margarita Suárez Navarro, Hortensia Rodríguez
Cabrera

AFFILIATION: Departamento de Parasitología, Instituto de Medicina Tropical
Pedro Kourí, Ciudad de la Habana, Cuba.

REFERENCE: Mem Inst Oswaldo Cruz 2004 May 99(3):329-30

Current therapy for leishmaniasis is not satisfactory. We describe the 
in vitro antiproliferative effects of new thiadiazine derivatives 
against Leishmania amazonensis. The compounds were found to be active 
against the amastigote form of the parasite, inhibiting parasite growing
, from 10 to 89%, at a concentration of 100 ng/ml. This activity 
suggests that thiadiazine derivatives could be considered as potential 
antileishmanial compounds.




PMID: 15273794
 

TITLE: Clinical and immunopathological spectrum of American cutaneous
leishmaniasis with special reference to the disease in Amazonian Brazil: a
review.

AUTHORS: Fernando T Silveira, Ralph Lainson, Carlos E P Corbett

AFFILIATION: Departamento de Parasitologia, Instituto Evandro Chagas, Secretaria
de Vigilância em Saúde, Ministério da Saúde, Belém, PA, 66090-000, Brasil.
fernandotobias at iec.pa.gov.br

REFERENCE: Mem Inst Oswaldo Cruz 2004 May 99(3):239-51

The wide variety of Leishmania species responsible for human American 
cutaneous leishmaniasis combined with the immune mechanisms of the host 
results in a large spectrum of clinical, histopathological, and 
immunopathological manifestations. At the middle of this spectrum are 
the most frequent cases of localized cutaneous leishmaniasis (LCL) 
caused by members of the subgenera Leishmania and Viannia, which respond
 well to conventional therapy. The two pathogenicity extremes of the 
spectrum generally recognized are represented at the hypersensitivity 
pole by mucocutaneous leishmaniasis (MCL) and at the hyposensitivity 
pole by anergic diffuse cutaneous leishmaniasis (ADCL). Following the 
present study on the clinical, histopathological and immunopathological 
features of cutaneous leishmaniasis in Amazonian Brazil, we propose the 
use of the term "borderline disseminated cutaneous leishmaniasis" for 
the disseminated form of the disease, due to parasites of the subgenera 
Leishmania and Viannia, which might be regarded as intermediate between 
LCL and the extreme pathogenicity poles MCL and ADCL.




PMID: 15034061
 

TITLE: Macrophage interactions with neutrophils regulate Leishmania major
infection.

AUTHORS: Flávia L Ribeiro-Gomes, Ana C Otero, Nitza A Gomes, Maria Carolina A
Moniz-De-Souza, Lea Cysne-Finkelstein, Andrea C Arnholdt, Vera L Calich, Sergio
G Coutinho, Marcela F Lopes, George A DosReis

AFFILIATION: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal
do Rio de Janeiro, Rio de Janeiro, Brazil.

REFERENCE: J Immunol 2004 Apr 172(7):4454-62

Macrophages are host cells for the pathogenic parasite Leishmania major
. Neutrophils die and are ingested by macrophages in the tissues. We 
investigated the role of macrophage interactions with inflammatory 
neutrophils in control of L. major infection. Coculture of dead exudate 
neutrophils exacerbated parasite growth in infected macrophages from 
susceptible BALB, but killed intracellular L. major in resistant B6 mice
. Coinjection of dead neutrophils amplified L. major replication in vivo
 in BALB, but prevented parasite growth in B6 mice. Neutrophil depletion
 reduced parasite load in infected BALB, but exacerbated infection in B6
 mice. Exacerbated growth of L. major required PGE(2) and TGF-beta 
production by macrophages, while parasite killing depended on neutrophil
 elastase and TNF-alpha production. These results indicate that 
macrophage interactions with dead neutrophils play a previously 
unrecognized role in host responses to L. major infection.




PMID: 15034056
 

TITLE: Subpopulations of mouse blood monocytes differ in maturation stage and
inflammatory response.

AUTHORS: Cord Sunderkötter, Tatjana Nikolic, Marilyn J Dillon, Nico Van
Rooijen, Martin Stehling, Douglas A Drevets, Pieter J M Leenen

AFFILIATION: Institute of Experimental Dermatology and Department of
Dermatology, University of Münster, Münster, Germany.

REFERENCE: J Immunol 2004 Apr 172(7):4410-7

Blood monocytes are well-characterized precursors for macrophages and 
dendritic cells. Subsets of human monocytes with differential 
representation in various disease states are well known. In contrast, 
mouse monocyte subsets have been characterized minimally. In this study 
we identify three subpopulations of mouse monocytes that can be 
distinguished by differential expression of Ly-6C, CD43, CD11c, MBR, and
 CD62L. The subsets share the characteristics of extensive phagocytosis
, similar expression of M-CSF receptor (CD115), and development into 
macrophages upon M-CSF stimulation. By eliminating blood monocytes with 
dichloromethylene-bisphosphonate-loaded liposomes and monitoring their 
repopulation, we showed a developmental relationship between the subsets
. Monocytes were maximally depleted 18 h after liposome application and 
subsequently reappeared in the circulation. These cells were exclusively
 of the Ly-6C(high) subset, resembling bone marrow monocytes. Serial 
flow cytometric analyses of newly released Ly-6C(high) monocytes showed 
that Ly-6C expression on these cells was down-regulated while in 
circulation. Under inflammatory conditions elicited either by acute 
infection with Listeria monocytogenes or chronic infection with 
Leishmania major, there was a significant increase in immature Ly-6C(
high) monocytes, resembling the inflammatory left shift of granulocytes
. In addition, acute peritoneal inflammation recruited preferentially Ly
-6C(med-high) monocytes. Taken together, these data identify distinct 
subpopulations of mouse blood monocytes that differ in maturation stage 
and capacity to become recruited to inflammatory sites.




PMID: 15067040
 

TITLE: Cutting edge: early IL-4 production governs the requirement for
IL-27-WSX-1 signaling in the development of protective Th1 cytokine responses
following Leishmania major infection.

AUTHORS: David Artis, Leanne M Johnson, Karen Joyce, Christiaan Saris, Alejandro
Villarino, Christopher A Hunter, Phillip Scott

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

REFERENCE: J Immunol 2004 Apr 172(8):4672-5

There are conflicting reports on the requirements for the IL-27-WSX-1 
pathway in the development of Th type 1 responses and resistance to 
intracellular pathogens; although early IFN-gamma production and 
resistance to Leishmania major are impaired in the absence of WSX-1 
signaling, WSX-1(-/-) mice generate robust IFN-gamma responses and 
control infection with other intracellular protozoan pathogens. In this 
report, we resolve these conflicting observations and demonstrate that, 
in the absence of IL-4, WSX-1 is not required for early IFN-gamma 
production and control of L. major. Thus, the requirement for WSX-1 
signaling in Th type 1 cell differentiation is restricted to conditions 
in which IL-4 is produced.




PMID: 15279623
 

TITLE: Th1 and Th2 immunological profile induced by cysteine proteinase in
murine leishmaniasis.

AUTHORS: C R Alves, T C Benévolo-De-Andrade, J L Alves, C Pirmez

AFFILIATION: Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo
Cruz-FIOCRUZ, Manguinhos, Rio de Janeiro, Brazil.

REFERENCE: Parasite Immunol 2004 Mar 26(3):127-35

SUMMARY This study evaluated the immune response to three synthetic 
peptides (pI, VMVEQVICFD; pII, VGGGLCFE; pIII, PYFLGSIMNTCHYT) from the 
COOH-terminal region of Leishmania amazonensis cysteine proteinases, in 
BALB/c- and CBA-infected mice with this parasite. Only BALB/c mice, 
previously inoculated with pI, showed a distinct exacerbation of the 
lesion. Blastogenesis assays were performed with lymph node cells from 
the group of mice infected with L. amazonensis, but not inoculated with 
the peptides, and we detected lymphoproliferative responses in BALB/c 
and CBA mice with a 5.0xand 2.5xstimulation index, respectively. Cell 
phenotypes were evaluated and in both mouse strains CD8(+)cells 
proliferated more extensively than CD4(+)cells. INF-gamma and nitric 
oxide were detected only in supernatants obtained from CBA mouse lymph 
node cell cultures, whereas IL-4 was detected in supernatant cultures 
from both strains of mice. Our results indicate a preferential 
stimulation of CD8(+)T-cell subsets by the pI cysteine proteinase 
peptide and the induction of both Th1 and Th2 phenotypes during L. 
amazonensis infections in both BALB/c and CBA mice. We suggest that the 
pI peptide from the COOH-terminal region of the cysteine proteinase 
induces immune responses different from those elicited by the whole 
molecule.




PMID: 14963556
 

TITLE: [Data on hospital infection, external causes of death, and visceral
leishmaniose in the state of São Paulo, Brazil]

AUTHORS: , , , 

REFERENCE: Rev Saude Publica 2004 Feb 38(1):141-4








PMID: 15286825
 

TITLE: Azithromycin in the treatment of mucosal leishmaniasis.

AUTHORS: Mario León Silva-Vergara, Luciana de Almeida Silva Ld, Frederico
Ricardo Zago Maneira, Achilles Gustavo da Silva, Aluízio Prata

AFFILIATION: Departamento de Clínica Médica, Faculdade de Medicina do
Triângulo Mineiro, Uberaba, MG, Brasil.

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: 15275077
 

TITLE: Leishmania vaccines: Old and New.

AUTHORS: E Handman

AFFILIATION: The Walter and Eliza Hall Institute of Medical Research, Victoria
3050, Australia. Tel: +61 3 9345 2555, Fax: +61 3 9347 0852.

REFERENCE: Parasitol Today 1997 Jun 13(6):236-8

The approach to the development of a Leishmania vaccine has undergone a 
revolution since its early beginnings with the ancient practice of 
leishmazation: the inoculation of infectious parasites from an active 
lesion in order to produce a self-healing lesion in a healthy individual
. Controlled infection has been followed by injection of killed 
parasites and has now progressed to subunit and naked DNA vaccines. 
Emanuela Handman here discusses the current studies and the future 
prospects for a Leishmania vaccine with a focus on cutaneous 
leishmaniasis. Unfortunately, what J.F. Williams said about antiparasite
 vaccines in 1987 (Ref. 1) is still true in 1997: 'the reasons for 
optimism are less evident than the reasons for enthusiasm'.




PMID: 15275128
 

TITLE: A simple method for quantifying Leishmania in tissues of infected
animals.

AUTHORS: H C Lima, J A Bleyenberg, R G Titus

AFFILIATION: Department of Pathology, College of Veterinary Medicine and
Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1671 USA
Tel: +1 970 491 4964, Fax: +1 970 491 0603.

REFERENCE: Parasitol Today 1997 Feb 13(2):82

In experimental animals infected with Leishmania major, the size of 
cutaneous lesions of the parasite often does not correlate with the 
number of parasites within the lesion. Indeed, cutaneous lesions can 
heal, but still contain parasites. Thus, the ability to determine 
parasite burden in infected animals becomes important, especially when 
assessing vaccines that are intended to induce sterilizing immunity. 
Here, Hermenio Lima, Julie Bleyenberg and Richard Titus describe a 
simple technique for enumerating Leishmania in infected tissue. It is 
hoped that this technique will allow all researchers working with 
Leishmania (especially those in countries where leishmaniasis is endemic
) to determine parasite burden easily in infected animals.




PMID: 15275127
 

TITLE: Modulating ongoing Th2-cell responses in experimental leishmaniasis.

AUTHORS: G S Nabors

AFFILIATION: Division of Immunology, Department of Research. Pasteur Merieux
Connaught. Route 611. PO Box 187. Swiftwater, PA 18370, USA. Tel: +1 717 839
4689, Fax: +1 717 839 0619.

REFERENCE: Parasitol Today 1997 Feb 13(2):80-2

Dramatically polarized T helper (Th)-cell responses are seen in 
experimental murine infections with Leishmania major. Resistant mice 
develop a Th1-cell type response and heal the primary lesion, while 
susceptible mice develop non-protective Th2-cell responses, and the 
disease eventually proves fatal. Deservedly, much effort has gone into 
determining factors that influence the development of these T-cell 
subsets early in infection; however, little is known about how the 
polarity of established responses can be permanently modified. In this 
article, Gary Nabors reviews his findings on modifying ongoing Th2-cell 
responses in susceptible mice, and discusses therapies that have proven 
effective involving reducing the level of infection using a conventional
 antileishmanial drug, combined with agents that push the response 
towards the Th1 pole.




PMID: 15275239
 

TITLE: Glomerulopathy associated with parasitic infections.

AUTHORS: M L Van Velthuysen

AFFILIATION: Department of Pathology, University of Rotterdam, PO Box 1738, 3000
DR Rotterdam, The Netherlands.

REFERENCE: Parasitol Today 1996 Mar 12(3):102-7

Numerous infectious diseases, among them several parasitic infectious, 
have been shown to be associated with glomerular disease, although the 
exact pathogenetic mechanisms have not yet been elucidated. In this 
article, Marie-Louise van Velthuysen reviews the work published on 
glomerulopathy associated with the most important parasitic infections, 
ie. malaria, schistosomiasis, leishmaniasis and irypanosomiasis.




PMID: 15275398
 

TITLE: The ins and outs of editing RNA in kinetoplastids.

AUTHORS: S D Seiwert

REFERENCE: Parasitol Today 1995 Oct 11(10):362-8

Over 30 million people in tropical regions suffer from Chagas disease, 
African sleeping sickness or leishmaniasis. The causative agents of 
these diseases, flagellated protozoa collectively known as 
kinetoplastids, represent an ancient lineage of eukaryotes. These 
unusual organisms carry out a large number of unique biochemical 
processes, one striking example being the sequence editing of 
mitochondrial messenger RNAs. In this review, Scott Seiwert focuses on 
recent studies that examine the reaction mechanism, molecular machinery 
and evolutionary history of this unusual RNA processing reaction.




PMID: 15275334
 

TITLE: Immunobiology of experimental cutaneous leishmaniasis.

AUTHORS: G Milon, G Del Giudice, J A Louis

REFERENCE: Parasitol Today 1995 Jul 11(7):244-7

The study of the murine model of infection with Leishmania major is 
providing important insights into the understanding of the complex 
interactions between the host and intracellular pathogens. Using this 
model system, basic research is actively leading to the identification 
of host factors promoting or circumventing the development of immunity 
to L. major. Here, Geneviève Milon, Giuseppe Del Giudice and Jacques A
. Louis review recent results related to the characterization of 
immunological host factors determining resistance and susceptibility to 
this parasite, and try to identify areas where further research is 
required for a better understanding of the complex events triggered by 
intracellular parasites within their hosts. Extrapolation to the human 
leishmaniases of the rapid advances made in this murine model of 
infection, should pave the way to the rational design of future 
immunoprophylactic and immunotherapeutic measures.




PMID: 15275504
 

TITLE: Medicinal plants in the fight against leishmaniasis.

AUTHORS: M M Iwu, J E Jackson, B G Schuster

AFFILIATION: Division of Experimental Therapeutics, Walter Reed Army Institute
of Research, Washington, DC 20307-5100, USA.

REFERENCE: Parasitol Today 1994  10(2):65-8

Despite the tremendous progress mode in the understanding o f the 
molecular biology of Leishmania and the clinical possibilities presented
 by some experimental chemotherapeutic agents, no new drugs have been 
developed for the treatment of leishmaniasis since the introduction of 
the pentovalent antimoniols more than 50 years ago. As reviewed here by 
Maurice M. Iwu, Joan E. Jackson and Brion G. Schuster, recognition of 
the current extensive use of herbal therapy in Leishmania-endemic 
regions has renewed interest in evaluation of plant remedies used in 
traditional medicine as sources of potential antileishmanials.




PMID: 15275519
 

TITLE: Maximum likelihood for parasitologists.

AUTHORS: B G Williams, C Dye

AFFILIATION: Brian Williams and Christopher Dye are at the London School o f
Hygiene and Tropical Medicine, Keppel Street, London, UK WC I E 7HT.

REFERENCE: Parasitol Today 1994  10(12):489-93

In quantitative biology, observed data are fitted to a model that 
captures the essence of the system under investigation in order to 
obtain estimates of the parameters of the model, as well as their 
standard errors and interactions. The fitting is best done by the method
 of maximum likelihood, though least-squares fits are often used as an 
approximation because the calculations are perceived to be simpler. Here
 Brian Williams and Chris Dye argue that the method of maximum 
likelihood is generally preferable to least squares giving the best 
estimates of the parameters for data with any given error distribution, 
and the calculations are no more difficult than for least-squares 
fitting. They offer a relatively simple explanation of the methods and 
describe its implementation using examples from leishmaniasis 
epidemiology.




PMID: 15275568
 

TITLE: Visceral leishmaniasis in Rio de Janeiro.

AUTHORS: M C Marzochi, K B Marzochi, R W Carvalho

AFFILIATION: Escola Nacional de Saúde Pública, Fundacão Oswaldo Cruz, FIOCRUZ
CP 926, 21041-010, Rio de Janeiro, RJ, Brazil.

REFERENCE: Parasitol Today 1994  10(1):37-40

Visceral leishmoniosis has recently become established in the peri-urban
 areas of the city of Rio de Janeiro. Mauro Marzochi, Keyla Marzochi and
 Raimundo Carvalho here discuss its incidence, and consider the factors 
involved in its establishment and propagation, as well as environmental
, human, social, economic and historical factors.




PMID: 15275563
 

TITLE: Recurrent cutaneous leishmaniasis: A role for persistent parasites?

AUTHORS: T Aebischer

AFFILIATION: Walter and Eliza Hall Institute of Medical Research, PO Royal
Melbourne Hospital, Melbourne, Victoria 3050, Australia.

REFERENCE: Parasitol Today 1994  10(1):25-8

Leishmaniosis is, with increasing frequency, reported as an 
opportunistic infection of immunosuppressed individuals. Re-activation 
of persistent parasites may be responsible for the disease in a number 
of these patients. Here, Toni Aebischer reviews some of the evidence for
 the implication of persistent Leishmania infections in recurrent 
disease with the emphasis on cutaneous leishmoniasis in humans and in 
the mouse model. The data suggest that parasite persistence is a common 
feature in Leishmania infections. The availability of on excellent 
laboratory model provides on opportunity to study this phenomenon in 
detail. The findings of these analyses are likely to be important for 
the identification of people at risk of developing recurrent disease and
 for the assessment of new therapies for relapsing leishmaniasis and 
might also have implications for the design of a future anti-Leishmania 
vaccine.




PMID: 15275441
 

TITLE: Leishmania infantum Tropism: Strain genotype or host immune status?

AUTHORS: L Gradoni, M Gramiccia

AFFILIATION: Luigi Gradoni and Marina Gromiccia are at the Laboratorio di
Parossitologia, Istituto Superiore di Sanitá Viale Regina Elena 299, 00161
Rome, Italy.

REFERENCE: Parasitol Today 1994  10(7):264-7

In apparently immunocompetent patients, Leishmania infantum provokes a 
spectrum of disease, ranging from simple skin lesion to severe visceral 
leishmaniasis, that is determined mainly by the protozoan genotype. In 
HIV-positive individuals, leishmanial infection results almost 
exclusively in visceral disease. In this review, Luigi Grodoni and 
Marina Gromiccia discuss the role o f the intrinsic virulence of L. 
infantum strains and the immune condition of the host, and focus on 
recently described mechanisms of immunological control of leishmanial 
infection.




PMID: 15275451
 

TITLE: Blood monocytes: Differing effector role in experimental visceral versus
cutaneous leishmaniasis.

AUTHORS: H W Murray

AFFILIATION: Henry Murray is at the Division of Infectious Diseases, Cornell
University Medical College, New York, NY 10021, USA.

REFERENCE: Parasitol Today 1994  10(6):220-3

Irrespective of the tissue infected or the strain involved, all 
Leishmania species selectively parasitize and replicate within the 
resident tissue macrophage. Henry Murray here discusses the role of a 
second mononuclear phagocyte, the blood monocyte, which is also 
attracted to leishmanial lesions, but which appears to play quite 
different roles in experimental visceral versus cutaneous infection: in 
visceral disease, the monocyte is a critical host defense effector cell
, in cutaneous disease, it may, paradoxically, serve to perpetuate 
intracellular infection.




PMID: 15275471
 

TITLE: Interleukin 12 and the regulation of CD4(+) T-cell subset responses
during murine Leishmaniasis.

AUTHORS: F P Heinzel

AFFILIATION: Frederick Heinzel is at the Division of Geographic Medicine, Case
Western Reserve University School of Medicine and the VA Medical Center,
Cleveland, OH 44106, USA.

REFERENCE: Parasitol Today 1994  10(5):190-2

Interleukin 12 is unique among cytokines in that it is capable of 
protecting genetically susceptible mice against progressive infection 
with Leishmania major. Because of the probable causal relationships 
between CD4(+) T-cell differentiation, cytokine production and disease 
outcome, this cytokine may prove useful as a component of cytokine-bosed
 therapies and Thl-selective vaccines, as discussed here by Frederick 
Heinzel.




PMID: 15275487
 

TITLE: Leishmaniasis and AIDS co-infection: The Spanish example.

AUTHORS: J Alvar

AFFILIATION: Laboratorio de Referencia de Leishmaniasis, Centro National de
Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

REFERENCE: Parasitol Today 1994  10(4):160-3

There are an estimated 300 instances of Leishmania/HIV co-infection, of 
which 200 have occurred in Spain. Jorge Alvar here asks: is there an 
epidemiological or immunological basis for this high proportion?




PMID: 15275583
 

TITLE: Clinical presentations of Leishmania braziliensis braziliensis.

AUTHORS: P D Marsden

AFFILIATION: Nucleo de Medicina Tropical Universidade de Brasilia Brasilia - DF
70910, Brazil.

REFERENCE: Parasitol Today 1985 Nov 1(5):129-33

Leishmania braziliensis braziliensis (Lbb) is probably the most serious
, leishmanial infection of the New World. Although epidemiological 
information is incomplete, its distribution is believed to extend from 
Belize in Central America to northern Argentina, involving all countries
 east of the Andes. Lbb causes a variety of clinical lesions and is one 
of the most difficult forms of leishmaniasis to treat. We still do not 
know how many patients suffer from mucosal disease requiring treatment. 
In this review of 10 years field experience in an endemic area of Brazil
, Philip Marsden shows that parasitologists have much to contribute, 
especially in improving diagnostic methods, developing better animal 
models, and providing new drugs suitable for routine treatment on a 
large-scale.




REQUEST: [ leishmania ]

(67 articles match this request. 30 articles matching other requests removed)



PMID: 15279966
 

TITLE: Genetic complementation of Leishmania deficient in PSA (GP46) restores
their resistance to lysis by complement.

AUTHORS: Leslie M Lincoln, Masayo Ozaki, John E Donelson, Jeffrey K Beetham

AFFILIATION: Departments of Entomology and Veterinary Pathology, Iowa State
University, Ames, IA 50011, USA.

REFERENCE: Mol Biochem Parasitol 2004 Sep 137(1):185-9




PMID: 15279954
 

TITLE: A survey of Leishmania braziliensis genome by shotgun sequencing.

AUTHORS: Eliane C Laurentino, Jeronimo C Ruiz, Gholam Fazelinia, Peter J Myler,
Wim Degrave, Marcelo Alves-Ferreira, José Marcos C Ribeiro, Angela K Cruz

AFFILIATION: Departamento de Biologia Celular e Molecular e Bioagentes
Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brasil.

REFERENCE: Mol Biochem Parasitol 2004 Sep 137(1):81-6

We have carried out a survey of the genome of Leishmania (Viannia) 
braziliensis by shotgun sequencing. Approximately 15% of the haploid 
genome of the parasite (5.15Mb of genomic sequence) was obtained. A 
large number of known and putative genes, predicted to be involved in 
several cellular processes, were identified. Some genomic features were 
investigated, such as the general G + C content, which was found to be 
lower than L. major (57% versus 63%). BlastN searches revealed that 60.2
% of the clusterized GSS sequences displayed similarity to L. major 
genomic sequences, while a BlastX search showed that 45.3% of the thus 
obtained predicted protein sequences showed similarity to annotated 
proteins of L. major. Further comparison of the degree of conservation 
between L. major and L. braziliensis revealed that coding regions are 
much more conserved than non-coding ones. The shotgun sequence analysis 
of Leishmania braziliensis appears to be an efficient and suitable 
strategy contributing to the search for vaccines and novel drug targets
. The sequence data described in this paper have been submitted to the 
dbGSS database under the following accession numbers ( to; to; to; to; 
to; to; to; to; to; to ). All data including sequences are also 
available at ().








PMID: 15271907
 

TITLE: Characterization of an I-E-restricted, gp63-specific, CD4-T-cell clone
from Leishmania major-resistant C3H mice that secretes type 2 cytokines and
exacerbates infection with L. major.

AUTHORS: Cynthia M Theodos, Robin V Morris, Jeanette V Bishop, Jeremy D Jones, W
Robert McMaster, Richard G Titus

AFFILIATION: Biogen, Inc., Cambridge, Massachusetts 02142, USA.

REFERENCE: Infect Immun 2004 Aug 72(8):4486-93

A T-cell clone (designated KLmB-3) was derived from resistant C3H mice 2
 weeks after infection with Leishmania major. KLmB-3 was a CD4-T-cell 
clone that utilized the V beta 8.1 T-cell receptor. When adoptively 
transferred to naive C3H mice, KLmB-3 unexpectedly exacerbated infection
 with L. major (it increased the cutaneous lesion size and the parasite 
burden within the lesion). The ability of KLmB-3 to exacerbate disease 
correlated with its ability to produce the type 2-associated cytokines 
interleukin-4 (IL-4), IL-5, IL-10, and transforming growth factor beta. 
Interestingly, KLmB-3 was specific for an epitope in the amino-terminal 
end of the L. major surface gp63 zinc metalloproteinase (leishmanolysin
) that has been shown to be capable of inducing a protective immune 
response. Moreover, KLmB-3 was activated when this epitope was presented
 in the context of H-2 I-E rather than H-2 I-A.




PMID: 15273109
 

TITLE: Role of positional hydrophobicity in the leishmanicidal activity of
magainin 2.

AUTHORS: Esther Guerrero, José María Saugar, Katsumi Matsuzaki, Luis Rivas

AFFILIATION: Centro de Investigaciones Biológicas (CSIC), c/Ramiro de Maeztu,
9, E-28040, Madrid, Spain. luis_rivas at cib.csic.es

REFERENCE: Antimicrob Agents Chemother 2004 Aug 48(8):2980-6

The emergence of membrane-active antimicrobial peptides as new 
alternatives against pathogens with multiantibiotic resistance requires 
the design of better analogues. Among the different physicochemical 
parameters involved in the optimization of linear antimicrobial peptides
, positional hydrophobicity has recently been incorporated. This takes 
into consideration the concept of the topological distribution of 
hydrophobic residues throughout the sequence rather than the classical 
concept of hydrophobicity as a global parameter of the peptide, 
calculated as the summation of the individual hydrophobicities of the 
residues. In order to assess the contribution of this parameter to the 
leishmanicidal mechanisms of magainin 2 analogues, the activities of two
 of these analogues, MG-H1 (GIKKFLHIIWKFIKAFVGEIMNS) and MG-H2 (
IIKKFLHSIWKFGKAFVGEIMNI), which have similar charges, amino acid 
compositions, and hydrophobicities but different positional 
hydrophobicities, against Leishmania donovani promastigotes were assayed
 (T. Tachi, R. F. Epand, R. M. Epand, and K. Matsuzaki, Biochemistry 41:
10723-10731, 2002). The activities were compared with that of the 
parental peptide, F5W-magainin 2 (GIGKWLHSAKKFGKAFVGEIMNS). The three 
peptides were active at micromolar concentrations, in the order MG-H2 > 
MG-H1 > F5W-magainin 2. These activities differ from their hemolytic and
 bactericidal activities. The results demonstrate that positional 
hydrophobicity, which reflects the presence of short stretches of 
sequences rich in hydrophobic amino acids, plays an important role in 
the activities of leishmanicidal peptides.




PMID: 15273114
 

TITLE: Possible Mechanism of Miltefosine-Mediated Death of Leishmania donovani.

AUTHORS: Navin K Verma, Chinmoy S Dey

AFFILIATION: Department of Biotechnology, NIPER, Sector 67, S.A.S. Nagar, Punjab
160 062, India. csdey at niper.ac.in

REFERENCE: Antimicrob Agents Chemother 2004 Aug 48(8):3010-5

Miltefosine causes leishmanial death, but the possible mechanism(s) of 
action is not known. The mode of action of miltefosine was investigated 
in vitro in Leishmania donovani promastigotes as well as in extra- and 
intracellular amastigotes. Here, we demonstrate that miltefosine induces
 apoptosis-like death in L. donovani based on observed phenomena such as
 nuclear DNA condensation, DNA fragmentation with accompanying ladder 
formation, and in situ labeling of DNA fragments by the terminal 
deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling 
method. Understanding of miltefosine-mediated death will facilitate the 
design of new therapeutic strategies against Leishmania parasites.




PMID: 15273118
 

TITLE: Inhibitors of Leishmania mexicana CRK3 Cyclin-Dependent Kinase: Chemical
Library Screen and Antileishmanial Activity.

AUTHORS: Karen M Grant, Morag H Dunion, Vanessa Yardley, Alexios-Leandros
Skaltsounis, Doris Marko, Gerhard Eisenbrand, Simon L Croft, Laurent Meijer,
Jeremy C Mottram

AFFILIATION: Wellcome Centre for Molecular Parasitology, University of Glasgow,
Anderson College, 56 Dumbarton Rd., Glasgow G11 6NU, United Kingdom.
k.grant at vet.gla.ac.uk

REFERENCE: Antimicrob Agents Chemother 2004 Aug 48(8):3033-42

The CRK3 cyclin-dependent kinase of Leishmania has been shown by genetic
 manipulation of the parasite to be essential for proliferation. We 
present data which demonstrate that chemical inhibition of CRK3 impairs 
the parasite's viability within macrophages, thus further validating 
CRK3 as a potential drug target. A microtiter plate-based histone H1 
kinase assay was developed to screen CRK3 against a chemical library 
enriched for protein kinase inhibitors. Twenty-seven potent CRK3 
inhibitors were discovered and screened against Leishmania donovani 
amastigotes in vitro. Sixteen of the CRK3 inhibitors displayed 
antileishmanial activity, with a 50% effective dose (ED(50)) of less 
than 10 microM. These compounds fell into four chemical classes: the 2,6
,9-trisubstituted purines, including the C-2-alkynylated purines; the 
indirubins; the paullones; and derivatives of the nonspecific kinase 
inhibitor staurosporine. The paullones and staurosporine derivatives 
were toxic to macrophages. The 2,6,9-trisubstituted purines inhibited 
CRK3 in vitro, with 50% inhibitory concentrations ranging from high 
nanomolar to low micromolar concentrations. The most potent inhibitors 
of CRK3 (compounds 98/516 and 97/344) belonged to the indirubin class; 
the 50% inhibitory concentrations for these inhibitors were 16 and 47 nM
, respectively, and the ED(50)s for these inhibitors were 5.8 and 7.6 
microM, respectively. In culture, the indirubins caused growth arrest, a
 change in DNA content, and aberrant cell types, all consistent with the
 intracellular inhibition of a cyclin-dependent kinase and disruption of
 cell cycle control. Thus, use of chemical inhibitors supports genetic 
studies to confirm CRK3 as a validated drug target in Leishmania and 
provides pharmacophores for further drug development.




PMID: 15271903
 

TITLE: CD4+ Th1 cells induced by dendritic cell-based immunotherapy in mice
chronically infected with Leishmania amazonensis do not promote healing.

AUTHORS: Yannick F Vanloubbeeck, Amanda E Ramer, Fei Jie, Douglas E Jones

AFFILIATION: Department of Veterinary Pathology, College of Veterinary Medicine,
Iowa State University, Ames, IA 50011-1250, USA.

REFERENCE: Infect Immun 2004 Aug 72(8):4455-63

The susceptibility of mice to Leishmania amazonensis infection is 
thought to result from an inability to develop a Th1 response. Our data 
show that the low levels of gamma interferon (IFN-gamma) produced by the
 draining lymph node (DLN) cells of chronically infected mice could be 
enhanced in vitro and in vivo with L. amazonensis antigen-pulsed bone 
marrow-derived dendritic cells (BM-DC) and the Th1-promoting cytokine 
interleukin-12 (IL-12). Given intralesionally to chronically infected 
mice, this treatment induced the upregulation of mRNA levels for IFN-
gamma, the transcription factor T-box expressed in T cells, and IL-12 
receptor beta 2 in CD4(+) T cells from the DLN and an increase in 
parasite-specific immunoglobulin G2a in the serum. However, this Th1 
response was not associated with healing, and the antigen-specific 
enhancement of IFN-gamma production remained impaired in the DLN. 
However, addition of IL-12 to the in vitro recall response was able to 
recover this defect, suggesting that antigen-presenting cell-derived IL-
12 production may be limited in infected mice. This was supported by the
 fact that L. amazonensis amastigotes limited the production of IL-12p40
 from BM-DC in vitro. Altogether, our data indicate that the immune 
response of mice chronically infected with L. amazonensis can be 
enhanced towards a Th1 phenotype but that the presence of Th1 CD4(+) T 
cells does not promote healing. This suggests that the phenotype of the 
CD4(+) T cells may not always be indicative of protection to L. 
amazonensis infection. Furthermore, our data support growing evidence 
that antigen-presenting cell function, such as IL-12 production, may 
limit the immune response in L. amazonensis-infected mice.




PMID: 15190060
 

TITLE: Differential Protein Expression Analysis of Leishmania major Reveals
Novel Roles for Methionine Adenosyltransferase and S-Adenosylmethionine in
Methotrexate Resistance.

AUTHORS: Jolyne Drummelsmith, Isabelle Girard, Nathalie Trudel, Marc Ouellette

AFFILIATION: Infectious Diseases Research Centre, Laval University, Quebec City,
Quebec G1V 4G2, Canada.

REFERENCE: J Biol Chem 2004 Aug 279(32):33273-80

Leishmania is a trypanosomatid parasite causing serious disease and 
displaying resistance to various drugs. Here, we present comparative 
proteomic analyses of Leishmania major parasites that have been either 
shocked with or selected in vitro for high level resistance to the model
 antifolate drug methotrexate. Numerous differentially expressed 
proteins were identified by these experiments. Some were associated with
 the stress response, whereas others were found to be overexpressed due 
to genetic linkage to primary resistance mediators present on DNA 
amplicons. Several proteins not previously associated with resistance 
were also identified. The role of one of these, methionine 
adenosyltransferase, was confirmed by gene transfection and metabolite 
analysis. After a single exposure to low levels of methotrexate, L. 
major methionine adenosyltransferase transfectants could grow at high 
concentrations of the drug. Methotrexate resistance was also correlated 
to increased cellular S-adenosylmethionine levels. The folate and S-
adenosylmethionine regeneration pathways are intimately connected, which
 may provide a basis for this novel resistance phenotype. This thorough 
comparative proteomic analysis highlights the variety of responses 
required for drug resistance to be achieved.




PMID: 15271962
 

TITLE: DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination
biases towards T helper 1 responses and enhances protection against Leishmania
major infection in mice.

AUTHORS: Uta G Lange, Pietro Mastroeni, Jenefer M Blackwell, Carmel B Stober

AFFILIATION: Cambridge Institute for Medical Research, and Department of
Medicine, School of Clinical Medicine, University of Cambridge, United
Kingdom.

REFERENCE: Infect Immun 2004 Aug 72(8):4924-8

Successful resolution of infections by intracellular pathogens requires 
gamma interferon (IFN-gamma). DNA vaccines promote T helper 1 (Th1) 
responses by triggering interleukin-12 (IL-12) release by dendritic 
cells (DC) through Toll-like receptor 9 (TLR9). In humans TLR9 is 
restricted to plasmacytoid DC. Here we show that DNA-Salmonella enterica
 serovar Typhimurium primer-booster vaccination, which provides 
alternative ligands to bind TLR4 on myeloid DC, strongly biases towards 
Th1 responses compared to vaccination with DNA alone. This results in 
higher immunoglobulin G2a (IgG2a) responses compared to IgG1 responses, 
higher IFN-gamma responses compared to IL-10 CD4(+)-T-cell responses, 
and enhanced protection against Leishmania major infection in 
susceptible BALB/c mice.




PMID: 15271961
 

TITLE: Involvement of the chemokine RANTES (CCL5) in resistance to experimental
infection with Leishmania major.

AUTHORS: Helton da Costa Santiago, Carolina Ferreira Oliveira, Luciana Santiago,
Fernanda Oliveira Ferraz, Daniele da Glória de Souza, Luiz Antônio Rodrigues
de-Freitas, Luís Carlos Crocco Afonso, Mauro Martins Teixeira, Ricardo Tostes
Gazzinelli, Leda Quercia Vieira

AFFILIATION: Departamento de Bioquímica e Imunologia, Instituto de Ciências
Biológicas, Universidade Federal de Minas Gerais, Brazil.

REFERENCE: Infect Immun 2004 Aug 72(8):4918-23

The expression and putative role of chemokines during infection with 
Leishmania major in mice were investigated. CCL5 expression correlates 
with resistance, and blockade of CCL5 rendered mice more susceptible to 
infection. CCL5 is part of the cascade of events leading to efficient 
parasite control in L. major infection.




PMID: 15140885
 

TITLE: Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii.

AUTHORS: Kshitiz Chaudhary, John A Darling, Leah M Fohl, William J Sullivan,
Robert G K Donald, Elmer R Pfefferkorn, Buddy Ullman, David S Roos

AFFILIATION: Department of Biology, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, USA.

REFERENCE: J Biol Chem 2004 Jul 279(30):31221-7

We have exploited a variety of molecular genetic, biochemical, and 
genomic techniques to investigate the roles of purine salvage enzymes in
 the protozoan parasite Toxoplasma gondii. The ability to generate 
defined genetic knockouts and target transgenes to specific loci 
demonstrates that T. gondii uses two (and only two) pathways for purine 
salvage, defined by the enzymes hypoxanthine-xanthine-guanine 
phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK). Both 
HXGPRT and AK are single-copy genes, and either one can be deleted, 
indicating that either one of these pathways is sufficient to meet 
parasite purine requirements. Fitness defects suggest both pathways are 
important for the parasite, however, and that the salvage of adenosine 
is more important than salvage of hypoxanthine and other purine 
nucleobases. HXGPRT and AK cannot be deleted simultaneously unless one 
of these enzymes is provided in trans, indicating that alternative 
routes of functionally significant purine salvage are lacking. Despite 
previous reports to the contrary, we found no evidence of adenine 
phosphoribosyltransferase (APRT) activity when parasites were propagated
 in APRT-deficient host cells, and no APRT ortholog is evident in the T
. gondii genome. Expression of Leishmania donovani APRT in transgenic T
. gondii parasites yielded low levels of activity but did not permit 
genetic deletion of both HXGPRT and AK. A detailed comparative genomic 
study of the purine salvage pathway in various apicomplexan species 
highlights important differences among these parasites.




PMID: 15270094
 

TITLE: Effect of hypoxia on macrophage infection by Leishmania amazonensis.

AUTHORS: Marcelle Carolina Colhone, Wagner Welber Arrais-Silva, Claudia Picoli,
Selma Giorgio

AFFILIATION: Departamento de Parasitologia, Instituto de Biologia, Universidade
Estadual de Campinas, CxP 6109, 13087-970 Campinas, SP, Brazil.

REFERENCE: J Parasitol 2004 Jun 90(3):510-5

In the present study, we compared the effect of 5% oxygen tension (
hypoxia) with a normal tension of 21% oxygen (normoxia) on macrophage 
infection by the protozoan parasite Leishmania amazonensis. Macrophages 
from different sources (human cell line U937, murine cell line J774, and
 murine peritoneal macrophages) exposed to hypoxia showed a reduction of
 the percentage of infected cells and the number of intracellular 
parasites per cell. Observations on the kinetics of infection indicated 
that hypoxia did not depress L. amazonensis phagocytosis but induced 
macrophages to reduce intracellular parasitism. Furthermore, hypoxia did
 not act synergistically with gamma-interferon and bacterial 
lipopolysaccharides in macrophages to induce killing of parasites. 
Experiments also indicated no correlation between nitric oxide 
production and control of infection in macrophages under hypoxic 
condition. Thus, we have provided the first evidence that hypoxia, which
 occurs in various pathological conditions, can alter macrophage 
susceptibility to a parasitic infection.




PMID: 15273802
 

TITLE: Leishmania braziliensis: partial control of experimental infection by
interleukin-12 p40 deficient mice.

AUTHORS: Sebastião Martins de Souza-Neto, Cláudia Martins Carneiro, Leda
Quercia Vieira, Luís Carlos Crocco Afonso

AFFILIATION: Departamento de Ciências Biológicas, Instituto de Ciências
Exatas e Biológicas.

REFERENCE: Mem Inst Oswaldo Cruz 2004 May 99(3):289-94

Resistance to infection by Leishmania major has been associated with the
 development of a Th1 type response that is dependent on the presence of
 interleukin 12 (IL-12). In this work the involvement of this cytokine 
in the response to infection by L. braziliensis, a less virulent species
 in the mouse model, was evaluated. Our results show that while 
interferon (IFN<FONT FACE="Symbol">-g</FONT>) deficient (-/-) 
mice inoculated L. braziliensis develop severe uncontrolled lesions, 
chronic lesions that remained under control up to 12 weeks of infection 
were observed in IL-12p40 -/- mice. IL 12p40 -/- mice had fewer 
parasites in their lesions than IFN<FONT FACE="Symbol">-g</FONT
>-/- mice. Lymph node cells from IL-12p40 -/- were capable of producing 
low but consistent levels of IFN<FONT FACE="Symbol">-g</FONT> 
suggestive of its involvement in parasite control. Furthermore, as 
opposed to previous reports on L. major-infected animals, no switch to a
 Th2 response was observed in IL-12p40 -/- infected with L. braziliensis.




PMID: 15286399
 

TITLE: Involvement of Leishmania donovani major surface glycoprotein gp63 in
promastigote multiplication.

AUTHORS: Sanjeev Pandey, Phuljhuri Chakraborti, Rakhi Sharma, Santu
Bandyopadhyay, Dwijen Sarkar, Samit Adhya

AFFILIATION: Indian Institute of Chemical Biology, 4 Raja SC Mullick Road,
Kolkata 700 032, India. sadhya at iicb.res.in

REFERENCE: J Biosci 2004 Mar 29(1):15-22

The major surface glycoprotein gp63 of the kinetoplastid protozoal 
parasite Leishmania is implicated as a ligand mediating uptake of the 
parasite into, and survival within, the host macrophage. By expressing 
gp63 antisense RNA from an episomal vector in L. donovani promastigotes
, gp63-deficient transfectants were obtained. Reduction of the gp63 
level resulted in increased generation times, altered cell morphology, 
accumulation of cells in the G2/M phase of the cell cycle, and increased
 numbers of binucleate cells with one or two kinetoplasts. Growth was 
stimulated, and the number of binucleate cells reduced, by addition to 
the culture of a bacterially expressed fusion protein containing the 
fibronectin-like SRYD motif and the zinc-binding (metalloprotease) 
domain of gp63. These observations support an additional role of gp63 in
 promastigote multiplication; the fibronectin-like properties of gp63 
may be important in this process




PMID: 15275047
 

TITLE: LD1 amplifications in Leishmania.

AUTHORS: M Segovia, G Ortiz

AFFILIATION: Departamento de Genética y Microbiología, Facultad de Medicina,
Universidad de Murcia, Spain. Tel: +34 68 256 900, Fax: +34 68 363 963.

REFERENCE: Parasitol Today 1997 Sep 13(9):342-8

The genome of Leishmania is quite plastic. Chromosomal rearrangements 
and DNA amplifications are common events in all the species of the genus
. Gene amplification occurs both as a mechanism of drug resistance and 
in the absence of drug pressure. The best known spontaneous 
amplification in Leishmania is the so-called LD1 family of amplicons. In
 the past few years there have been great advances in our knowledge of 
LD1 elements; here, Manuel Segovia and Ginés Ortiz review all the 
available data.




PMID: 15275161
 

TITLE: The Trypanosoma cruzi genome initiative.

AUTHORS: The Trypanosoma CruziGenome Consortium

REFERENCE: Parasitol Today 1997 Jan 13(1):16-22

An initiative was launched in 1994 by the Special Programme for Research
 and Training in Tropical Diseases (TDR) of the WHO to analyse the 
genomes of the parasites Filaria, Schistosoma, Leishmania, Trypanosoma 
brucei and Trypanosoma cruzi. Five networks were established through 
wide publicity, holding meetings of key laboratories and developing 
proposals which were then reviewed by the Steering Committee of 
Strategic Research for financial support. The aim of the Programme was 
to use the platform of these networks to: (1) train scientists from 
tropical disease-endemic countries; (2) transfer technology and share 
material and expertise, thereby reducing costs and increasing efficiency
; and (3) provide an information system that is accessible globally as 
soon as the results become available. The initial target was to produce 
a low-resolution genome map for each of the parasites, but it soon 
became evident that by using rapidly developing technologies, it might 
be feasible to complete DNA-sequence analysis for some of the parasites 
in the next decade, as discussed here by Alberto Carlos Frasch and 
colleagues, with particular focus on the T. cruzi genome initiative.




PMID: 15275279
 

TITLE: Exploitation of the complement system by Leishmania promastigotes.

AUTHORS: A Brittingham, D M Mosser

AFFILIATION: Department of Microbiology and Immunology, Temple University School
of Medicine, Philadelphia, PA 19140, USA.

REFERENCE: Parasitol Today 1996 Nov 12(11):444-7

Complement has long been acknowledged as an important component of host 
defense to extracellular pathogens. David Mosser and Andrew Brittingham 
here describe how Leishmania spp, intracellular pathogens of mononuclear
 phagocytes, exploit the opsonic and chemotactic effects of complement 
to initiate infection in the mammalian host.




PMID: 15275299
 

TITLE: Viable Leishmania infantum in urine and semen in experimentally infected
dogs.

AUTHORS: C Riera, J E Valladares

AFFILIATION: Department de Microbiologia i Parasitologia Santà nes Unitat de
Parasitologia Facultat de Farmà cia Universitat de Barcelona Avda. Joan XXIII,
s/n 08028 Barcelona, Spain.

REFERENCE: Parasitol Today 1996 Oct 12(10):412




PMID: 15275202
 

TITLE: Topoisomerases in kinetoplastids.

AUTHORS: C Burri, A L Bodley, T A Shapiro

AFFILIATION: Department of Medicine, Johns Hopkins University School of
Medicine, 301 Hunterian Building, 725 North Wolfe Street, Baltimore, MD
21205-2185, USA. Tel: +1 410 955 1888, Fax: +1 410 955 2634.

REFERENCE: Parasitol Today 1996 Jun 12(6):226-31

Topoisomerases are enzymes that mediate topological changes in DNA that 
are essential for nucleic acid biosynthesis and for cell survival. The 
kinetoplastid protozoa, which include pathogenic trypanosomes and 
Leishmania, have yielded an interesting variety of purified 
topoisomerase activities as well as several topoisomerase genes. In 
these parasites, topoisomerases are involved in the metabolism of both 
nuclear and mitochondrial (kinetoplast) DNA. In this review, Christian 
Burri, Armette Bodley and Theresa Shapiro summarize what is known about 
topoisomerases in kinetoplastids, and consider the intriguing 
possibility that these enzymes may act as valuable antiparasite drug 
targets.




PMID: 15275256
 

TITLE: The role of Ca(2+) in the process of cell invasion by intracellular
parasites.

AUTHORS: R Docampo, S N Moreno

AFFILIATION: Department of Veterinary Pathobiology, University of Illinois at
Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61801, USA. Tel: +1 217
333 3845, FAX: +1 217 244 7421.

REFERENCE: Parasitol Today 1996 Feb 12(2):61-5

In order to replicate, many parasites must invade host cells. Changes in
 the intracellular Ca(2+) concentration ([Ca(2+)](i)) of different 
parasites and tissue culture cells during their interaction have been 
studied. An increase in cytosolic Ca(2+) in Trypanosoma cruzi 
trypomastigotes occurs after association of the parasites with host 
cells. Ca(2+) mobilization in the host cells also takes place upon 
contact with T. cruzi trypomastigotes, Leishmania donovani amastigotes 
or Plasmodium falciparum merozoites. When Ca(2+) transients are 
prevented by intracellular Ca(2+) chelators, a decrease in parasite 
association to host cells is observed. This reveals the importance of [
Ca(2+)](i) in the process of parasite-host cell interaction, as 
discussed here by Roberto Docampo and Silvia Moreno.




PMID: 15275381
 

TITLE: Trypanosomatid shuttle vectors: new tools for the functional dissection
of parasite genomes.

AUTHORS: J M Kelly

AFFILIATION: Department of Medical Parasitology. London School of Hygiene and
Tropical Medicine, Keppel Street, London, UK WCIE 7HT.

REFERENCE: Parasitol Today 1995 Dec 11(12):447-51

In the past five years, gene-transfer systems have been established for 
each of the medically important trypanosomatids: Leishmania sp, 
Trypanosoma brucei and T. cruzi. Transformation can be mediated by 
integration, which occurs exclusively by homologous recombination, or by
 episomal shuttle vectors. In this article, John Kelly will focus on 
recent progress in the development and applications of trypanosomatid 
shuttle vectors, ie. vectors which are maintained extrachromosomally and
 which are capable of autonomous replication in both trypanosomatid and 
bacterial hosts.








PMID: 15275406
 

TITLE: Leishmania major infection: the overture.

AUTHORS: W Solbach, T Laskay

REFERENCE: Parasitol Today 1995 Oct 11(10):394-7

Local infection of mice with Leishmania major results in either healing 
or death depending on the preferential action of Th1 or Th2 T helper 
cells, respectively. Although the parasite-induced T-cell responses and 
their consequences for the disease are well understood, relatively 
little is known about the initial events that kindle the adaptive immune
 response. Werner Salbach and Tamás Laskay here discuss how differences
 in parasites spreading from the site of infection to different immune 
organs during the first 10-24 hours and, in consequence, the 'where and 
when' of the first encounter of Leishmania with the cells of the immune 
system may well be the starting point for the development of resistance 
or susceptibility.




PMID: 15275312
 

TITLE: The lipophosphoglycan-associated molecules of Leishmania.

AUTHORS: P A Bates

AFFILIATION: Paul Bates is at the Division of Molecular Biology and Immunology,
Liverpool School of Tropical Medicine, Pembroke Place, UK L3 5QA. Tel: +44 151
708 9393, Fax: +44 151 708 9007LiverpoolUK.

REFERENCE: Parasitol Today 1995 Sep 11(9):317-8




PMID: 15275337
 

TITLE: Co-stimulatory activity of Leishmania-infected macrophages: Reply.

AUTHORS: P Kaye

AFFILIATION: Immunology and Cell Biology Unit Department of Medical Parasitology
London School of Hygiene and Tropical Medicine Keppel Street London, UK WC1E
7HT.

REFERENCE: Parasitol Today 1995 Jul 11(7):254




PMID: 15275333
 

TITLE: Co-stimulatory activity of Leishmania-infected macrophages.

AUTHORS: J C Antoine

REFERENCE: Parasitol Today 1995 Jul 11(7):242-3




PMID: 15275340
 

TITLE: Leishmania, LPG and the Sandfly connection.

AUTHORS: R L Jacobson

REFERENCE: Parasitol Today 1995 Jun 11(6):203-4




PMID: 15275534
 

TITLE: Plant microtubule inhibitors against trypanosomatids.

AUTHORS: M M Chan, D Fong

AFFILIATION: Department of Biological Sciences, Rutgers, The State University of
New Jersey, Piscataway, NJ 08855-1059, USA.

REFERENCE: Parasitol Today 1994  10(11):448-51

Trypanosomatid protozoa are etiologic agents of several prevalent 
tropical diseases. Tubulins constitute 10% of the total proteins of 
these organisms. In addition, they are conserved within the 
Trypanosomatidae family but are different from that of the mammalian 
hosts. Since current chemotherapy has severe side effects, new compounds
 are urgently needed. The microtubular system provides a target for 
selective chemotherapy. Plant microtubule inhibitors, trifluralin and 
its analogues, inhibits Leishmania and Trypanosoma brucei, and Marion 
Chan and Dunne Fong here discuss the biosafety and potential for 
development of drug resistance to these compounds.




PMID: 15275436
 

TITLE: cdc2-related protein kinases and cell cycle control in trypanosomatids.

AUTHORS: J C Mottram

AFFILIATION: Wellcome Unit of Molecular Parasitology, Institute of Genetics,
University of Glasgow, Church Street, Glasgow, UK GII 5JS.

REFERENCE: Parasitol Today 1994  10(7):253-7

The molecular mechanisms that control the cell cycle have been studied 
extensively in yeast and higher eukaryotes. Investigations have centred 
on the cyclin-dependent kinase family of serine/threonine protein 
kinases, the best characterized of which is cdc2, a key regulatory 
element in the control of mitosis. Cell cycle control plays an important
 role in trypanosomes and Leishmania, not only in cellular proliferation
, but also in the developmental system that controls the transfer of the
 parasite between hosts. In this review, Jeremy Mottram compares the 
family of trypanosome cdc2-related kinases with that of yeast and the 
higher eukaryotes.




PMID: 15275484
 

TITLE: The existence of lipophosphoglycanlike molecules in Trichomonads.

AUTHORS: B N Singh

AFFILIATION: Bibhuti N. Singh is at the Department of Microbiology and
Immunology, SUNY Health Science Center, Syracuse, NY 13210, USA.

REFERENCE: Parasitol Today 1994  10(4):152-4

The trichomonods, Trichomonas vaginalis and Tritrichomonas foetus, 
appear to express novel lipophosphoglycon (LPG) like glycoconjugates on 
their cell surface, which are structurally distinct from Leishmania LPGs
'. In this article, Bibhuti Singh discusses the structural and cellular 
aspects o f these molecules, and speculates on their biological 
significance.




PMID: 15275492
 

TITLE: Intermediary metabolism of Trypanosoma cruzi.

AUTHORS: J A Urbina

AFFILIATION: Laboratorio de Química Biológica, Centro de Bioquimico y
Biofísica, Instituto Venezolono de Investigaciones Cientí ficas, Apartodo
21827, Caracas 1020A, Venezuela.

REFERENCE: Parasitol Today 1994  10(3):107-10

In this article, Julio Urbino discusses the characteristics o f the 
intermediary metabolism of Trypanosoma cruzi (the causative agent o f 
Chagas disease), which are responsible for the unusual capacity of this 
parasite to use carbohydrates or amino acids as carbon and energy 
sources without drastic changes in its catabolic enzyme levels(1-3). 
Many, but not all, o f the metabolic capabilities of this organism are 
shared with Leishmania and the procyclic form o f the African 
trypanosomes, and the reviewer presents a metabolic model which is also 
consistent with the information available on these other parasites(2,4).




PMID: 15275518
 

TITLE: Parasites and T helper cell development: Some insights.

AUTHORS: S L Reiner

AFFILIATION: Steven Reiner was at the Department of Medicine at the University
of California in San Francisco, CA 94143, USA.

REFERENCE: Parasitol Today 1994  10(12):485-8

Five years after the initial observations implicating the T helper (Th)-
cell dichotomy ( [Formula: see text] ) as the point in the 
immunoregulation of murine infection with Leishmania major, 
investigation has shifted to the factors that govern the differentiation
 of a specific immune response from its pre-immune of undifferentiated 
state. In this article, Steven Reiner focuses on the most recent 
advances concerning the lineage commitment of mature Th-cell populations
, showing how new techniques [such as polymerase chain reaction (PCR) 
and transgenic mice] have allowed for a more-careful dissection of the 
early evolution of an immune response.




PMID: 15275612
 

TITLE: T-lymphocytes recognise Leishmania glycoconjugates.

AUTHORS: G F Mitchell, E Handman

AFFILIATION: Walter and Eliza Hall Institute of Medical Research, Melbourne,
Victoria 3050, Australia.

REFERENCE: Parasitol Today 1985 Aug 1(2):61-3




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

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

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


PMID: 12744545
 

TITLE: Primer on medical genomics. Part VII: The evolving concept of the gene.

AUTHORS: Eric D Wieben

AFFILIATION: Department of Biochemistry and Molecular Biology, Mayo Clinic,
Rochester, Minn 55905, USA.

REFERENCE: Mayo Clin Proc 2003 May 78(5):580-7

The draft sequence of the human genome was reported 2 years ago, and the
 task of filling gaps and polishing the sequence is nearing completion. 
However, despite this remarkable achievement, there is still no 
definitive assessment of the number of genes contained in the human 
genome. In part, this uncertainty reflects our growing understanding of 
the complexity and diversity of gene structure. Examples of complex gene
 structure are considered in the context of a discussion about the 
evolution of our understanding of gene structure and function.




PMID: 11260462
 

TITLE: An essential dimeric membrane protein of trypanosome glycosomes.

AUTHORS: A Maier, P Lorenz, F Voncken, C Clayton

AFFILIATION: Zentrum für Molekulare Biologie (ZMBH), Im Neuenheimer Feld 282,
D-69120 Heidelberg, Germany.

REFERENCE: Mol Microbiol 2001 Mar 39(6):1443-51

Kinetoplastid parasites compartmentalize the first seven enzymes of 
glycolysis in a peroxisome-like microbody, the glycosome. Genes encoding
 the most abundant protein of the glycosomal membrane, GIM5, have been 
cloned and the protein characterized. Two genes, GIM5A and GIM5B, encode
 26 kDa proteins. Although many microbody membrane proteins are 
conserved in evolution, the only homologues of GIM5 in the available 
databases are from the closely related kinetoplastids Trypanosoma cruzi 
and Leishmania. The N- and C-termini are conserved between the two genes
, and between species, and are oriented towards the cytosol. They are 
separated by a short loop that is located between two transmembrane 
domains and shows almost no sequence conservation. This suggests that 
the N- and C-terminal domains are more important for function. GIM5 
forms dimers in vivo. Overexpression of GIM5B inhibits growth, whereas 
depletion of GIM5 to below 10% of wild-type levels is very rapidly 
lethal. This novel organellar membrane protein is therefore essential 
for bloodstream trypanosome survival.




PMID: 10564812
 

TITLE: Cloning of a Leishmania major gene encoding for an antigen with extensive
homology to ribosomal protein S3a.

AUTHORS: K Zemzoumi, E Guilvard, D Sereno, A Preto, M Benlemlih, A C Da Silva, J
L Lemesre, A Ouaissi

AFFILIATION: CJF-INSERM n degrees 96-04, Centre IRD, 911 Av. Agropolis, BP 5045,
34032, Montpellier, France.

REFERENCE: Gene 1999 Nov 240(1):57-65

Following purification by affinity chromatography, a Leishmania major S-
hexylglutathione- binding protein of molecular mass 66kDa was isolated. 
The immune serum against the parasite 66kDa polypeptide when used to 
screen a L. major cDNA library could identify clones encoding for the 
human v-fos transformation effector homologue, namely ribosomal protein 
S3a, and thus was named LmS3a-related protein (LmS3arp). A 1027bp cDNA 
fragment was found to contain the entire parasite gene encoding for a 
highly basic protein of 30kDa calculated molecular mass sharing homology
 to various ribosomal S3a proteins from different species. Using 
computer methods for a multiple alignment and sequence motif search, we 
found that LmS3arp shares a sequence homology to class theta glutathione
 S-transferase mainly in a segment containing critical residues involved
 in glutathione binding. These new findings are discussed in the light 
of recent published data showing multiple function(s) of the ribosomal 
proteins S3a.




PMID: 10481179
 

TITLE: Unravelling the kinetoplastid paraflagellar rod.

AUTHORS: J A Maga, J H LeBowitz

AFFILIATION: Dept of Biochemistry, Purdue University, West Lafayette, IN 47907,
USA.

REFERENCE: Trends Cell Biol 1999 Oct 9(10):409-13

Researchers who study human pathogens are often interested in unique and
 essential aspects of the biology of the pathogen. Recent progress has 
been made in understanding such a target in kinetoplastid parasites. The
 paraflagellar rod is a unique cytoskeletal structure that plays a key 
role in the life-cycle of these fascinating organisms. This review 
discusses the protein components and structure of the paraflagellar rod 
and its function in cell motility.




PMID: 10023079
 

TITLE: Kinetoplast DNA minicircles of Leishmania donovani express a protein
product.

AUTHORS: N Singh, A K Rastogi

AFFILIATION: Division of Biochemistry, Central Drug Research Institute, Lucknow,
India. root at cscdri.ren.nic.in

REFERENCE: Biochim Biophys Acta 1999 Feb 1444(2):263-8

We describe an unprecedented finding of an open reading frame present in
 the variable region in one of the minicircle sequence classes of a 
human pathogenic strain of Leishmania donovani (MHOM/IN/90/RMRI 68) 
which is transcribed and translated. The encoded protein showed 
homologies to known transport proteins.




REQUEST: [ sand fly ]

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



PMID: 15264620
 

TITLE: Evaluation of 1-octen-3-ol and carbon dioxide as attractants for
Phlebotomus papatasi (Diptera: Psychodidae) in southern Egypt.

AUTHORS: Gregory M Beavers, Hanafi A Hanafi, Elizabeth A Dykstra

AFFILIATION: Vector Biology Research Program, U.S. Naval Medical Research Unit
Number Three, PSC 452, Box 5000, FPO, AE 09835-0007.

REFERENCE: J Am Mosq Control Assoc 2004 Jun 20(2):130-3

The effectiveness of 1-octen-3-ol (octenol) as an attractant for 
collecting medically important psychodids has never been reported. This 
study evaluated the effects of carbon dioxide (CO2) and octenol released
 at 2 rates, individually and in combination, as attractants for adult 
sand flies in a small village in southern Egypt. Four sand fly species 
were collected: Phlebotomus papatasi, P. sergenti, Sergentomyia 
palestinensis, and S. schwetzi. Only P. papatasi was collected in 
numbers sufficient to allow statistical analysis. This study reaffirms 
that CO2 is an effective attractant for female P. papatasi and also 
demonstrates that neither male nor female P. papatasi respond to octenol
 alone. Additionally, no synergistic attractancy for either females or 
males was observed when CO2 and octenol were combined.




REQUEST: [ sandfly ]

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



PMID: 15281455
 

TITLE: [Ultrastructural study on pharyngeal armatures of seven species of
sandflies in china by scanning electron microscopy]

AUTHORS: Dong-xing Guo, Chang-fa Jin, Yu-mei Hong, Bing Ni, Zhong-dong Qiao

AFFILIATION: School of Preclinical and Forensic Medicine, Sichuan University,
Chengdu, 610041, China.

REFERENCE: Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2004 Apr
22(2):101-2

OBJECTIVE: To observe the ultrastructure of pharyngeal armature of 7 
species of sandflies in China. METHODS: The pharyngeal armatures of 
various sandflies were studied by scanning electron microscopy. RESULTS
: The pharyngeal armature of sandfly consisted of pointed-teeth with 
various shape, number and arrangement among different species. 
CONCLUSION: Such differences may provide the morphological proof for 
identification of species.















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