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

Wed Oct 27 21:30:13 BRT 2004

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This is RefScout-Newsletter 44/2004.

REQUEST: [ leishmaniasis ]

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

PMID: 15501518

TITLE: Efficacy of human beta-casein fragment (54-59) and its synthetic analogue
compound 89/215 against Leishmania donovani in hamsters.

AUTHORS: Preeti Sharma, Nasib Singh, Ravendra Garg, Wahajul Haq, Anuradha Dube

AFFILIATION: Division of Parasitology, Central Drug Research Institute, Post Box
No. 173, Lucknow 226001, India.

REFERENCE: Peptides 2004 Nov 25(11):1873-81

The characteristic feature of visceral leishmaniasis (VL) is the 
profound impairment of immune system of the infected host, which 
contributes significantly to the partial success of antileishmanial 
chemotherapy. Since in VL, cure is the combinatorial effect of drug and 
immune status of the host, the rationale approach towards 
antileishmanial chemotherapy would be to potentiate the immune 
functioning of the host to extract desired results. Towards this 
direction several rationally designed analogues of human beta-casein 
fragment (54-59) were evaluated for their ability to stimulate the non-
specific resistance in hamsters against Leishmania donovani infection. 
By virtue of being derived from the food protein casein derivatives may 
be devoid of unwanted side effects associated with the substances of 
microbial origin, e.g. muramyl dipeptide (MDP). Out of this one peptide 
Val-Glu-Gly-Ile-Pro-Tyr (compound 89/215) had been reported to have such
 activity. In this communication, the prophylactic and therapeutic 
efficacy of the peptide along with its natural sequence has been 
evaluated in detail against experimental VL in hamsters. Their use as an
 adjunct to chemotherapy was also explored. Human beta-casein fragment, 
compound 89/215 and MDP were tested in vivo at various dose levels 
wherein compound 89/215 showed superiority over MDP at 3mg/kg x 2 given 
intraperitoneally (i.p.). Compound 89/215 sensitized peritoneal 
macrophages acquired considerable resistance and only 24% of the cells 
were found infected in comparison to control peritoneal macrophages 
where 76.4% of the cells were found infected. Similarly, the efficacy of
 sodium antimony gluconate (SAG) in hamsters pretreated with compound 89
/215 enhanced significantly (P &#60; 0.001). This peptide also exhibited
 considerably good therapeutic efficacy when evaluated either alone or 
in combination with SAG in established infection of L. donovani.

PMID: 15499535

TITLE: Antimony plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating
Factor Applied Topically in Low Doses Enhances Healing of Cutaneous
Leishmaniasis Ulcers: A Randomized, Double-Blind, Placebo-Controlled Study.

AUTHORS: Jussamara B Santos, Amelia Ribeiro de Jesus, Paulo R Machado, Andrea
Magalhaes, Katia Salgado, Edgar M Carvalho, Roque P Almeida

AFFILIATION: Servico de Imunologia, Hospital Universitario Professor Edgard
Santos, Universidade Federal da Bahia, Salvador, Bahia, and Instituto do
Milenio, Instituto de Investigacao em Imunologia, Brazil.

REFERENCE: J Infect Dis 2004 Nov 190(10):1793-6

Cutaneous leishmaniasis (CL) requires 2-6 months to heal. In an effort 
to reduce this healing time, we studied topically applied granulocyte-
macrophage colony-stimulating factor (GM-CSF) as an adjunct to 
antimonial therapy. Ten patients received antimony plus topical GM-CSF, 
and 10 patients received antimony plus placebo (saline). GM-CSF was 
diluted for topical use and was applied 3 times weekly for 3 weeks (1-2 
mu g/cm(2)/lesion). The mean +/- SD healing time was 43 +/- 14 days in 
the GM-CSF group and was 104+/-79 days in the placebo group (P=.043). 
Ten (100%) of 10 patients in the GM-CSF group healed within 60 days, 
compared with 5 (50%) of 10 patients in the placebo group. Two of the 
patients in the placebo group required retreatment with antimony. In 
conclusion, topically applied GM-CSF is effective in the management of 
CL.

PMID: 15501259

TITLE: Ancistroheynine B and two further 7,3'-coupled naphthylisoquinoline
alkaloids from Ancistrocladus heyneanus Wall.

AUTHORS: Gerhard Bringmann, Michael Dreyer, Manuela Michel, Francis S K Tayman,
Reto Brun

AFFILIATION: Institute of Organic Chemistry, University of Wuerzburg, Am
Hubland, D-97074 Wuerzburg, Germany.

REFERENCE: Phytochemistry 2004 Nov 65(21):2903-7

A new axially chiral naphthylisoquinoline alkaloid, ancistroheynine B (7
), has been isolated from the leaves of the Indian liana Ancistrocladus 
heyneanus Wall., along with two known related alkaloids, 
ancistrocladidine (3) and ancistrotanzanine C (6), which are 7,3'-
coupled, too. The structural elucidation was achieved by chemical, 
spectroscopic, and chiroptical methods. Biological activities of 
ancistroheynine B against the pathogens of malaria, leishmaniasis, 
Chagas' disease, and African sleeping sickness were evaluated.

PMID: 15385463

TITLE: Immunization with Leishmania major exogenous antigens protects
susceptible BALB/c mice against challenge infection with L. major.

AUTHORS: Willy K Tonui, J Santiago Mejia, Lisa Hochberg, M Lamine Mbow, Jeffrey
R Ryan, Adeline S T Chan, Samuel K Martin, Richard G Titus

AFFILIATION: Department of Microbiology Immunology and Pathology, Colorado State
University, Fort Collins, Colorado 80523-1619, USA.

REFERENCE: Infect Immun 2004 Oct 72(10):5654-61

The potential of Leishmania major culture-derived soluble exogenous 
antigens (SEAgs) to induce a protective response in susceptible BALB/c 
mice challenged with L. major promastigotes was investigated. Groups of 
BALB/c mice were immunized with L. major SEAgs alone, L. major SEAgs 
coadministered with either alum (aluminum hydroxide gel) or recombinant 
murine interleukin-12 (rmIL-12), L. major SEAgs coadministered with both
 alum and rmIL-12, and L. major SEAgs coadministered with Montanide ISA 
720. Importantly and surprisingly, the greatest and most consistent 
protection against challenge with L. major was seen in mice immunized 
with L. major SEAgs alone, in the absence of any adjuvant. Mice 
immunized with L. major SEAgs had significantly smaller lesions that at 
times contained more than 100-fold fewer parasites. When lymphoid cells 
from L. major SEAg-immunized mice were stimulated with leishmanial 
antigen in vitro, they proliferated and secreted a mixed profile of type
 1 and type 2 cytokines. Finally, analyses with Western blot analyses 
and antibodies against three surface-expressed and secreted molecules of
 L. major (lipophosphoglycan, gp46/M2/PSA-2, and gp63) revealed that two
 of these molecules are present in L. major SEAgs, lipophosphoglycan and
 the molecules that associate with it and gp46/M2/PSA-2.

PMID: 15494841

TITLE: Treatment of cutaneous leishmaniasis by intralesional metronidazole.

AUTHORS: Makram Al-Waiz, Khalifa E Sharquie, Mohammad Al-Assir

AFFILIATION: Department of Dermatology and Venereology, College of Medicine,
University of Baghdad, PO Box 61369, Postal Code 12114, Medical Collection Post
Office, Bab Al-Mua'dham, Baghdad, Iraq. Fax. +964 (1) 4250243. E-mail:
makram552000 at yahoo.com.

REFERENCE: Saudi Med J 2004 Oct 25(10):1512-3

PMID: 15490752

TITLE: About the presence of Phlebotomus sergenti Parrot, 1917 (Diptera:
Psychodidae) in Eastern Sicily, Italy.

AUTHORS: V D'Urso, F Ruta, C Khoury, R Bianchi, J Depaquit, M Maroli

AFFILIATION: Department of animal biology, University of Catania, Italy.

REFERENCE: Parasite 2004 Sep 11(3):279-83

The note reports the data of a three-year sand fly investigation (1997-
99) carried out in Eastern Sicily (Italy) with the aim to study the 
distribution of Phlebotomus sergenti. The survey involved a densely 
inhabited area at the foot of Mount Etna and the area of Iblei mounts. A
 total of 9,095 sand flies, of which 63.4% males, were captured. Five 
species belonging to the genus Phlebotomus (P. perniciosus, P. 
perfiliewi, P. neglectus, P. sergenti and P. papatasi) and one to the 
genus Sergentomyia (S. minuta) were identified. Both the prevalence and 
distribution of the species were different within the two areas studied
. In Mount Etna area, P. perniciosus (77.7%) was the prevalent species 
followed by S. minuta (19.8%), P. sergenti (2.0%), P. neglectus (0.3%) 
and P. papatasi (0.2%). While in Iblei mounts region S. minuta (84.5%) 
showed the highest prevalence, followed by P. perniciosus (14.4%), P. 
perfiliewi (0.9%) and P. neglectus (0.1%). Here, P. sergenti was a very 
rare species (&#60; 0.02). P. sergenti was mostly associated to domestic
 habitats of peri-urban and urban zones located between two and 750 m a.
s.l. The density values of P. sergenti, expressed as number of specimens
/m2 of sticky trap, were between 0.3 and 5.5 with the highest value in 
the hilly collecting sites. The low observed abundance of P. sergenti 
does not allow to draw any prediction on the role that the species could
 play in the transmission of leishmaniasis in Sicily.

PMID: 15325040

TITLE: Sero-epidemiological survey of Neospora caninum infection in dogs in
north-eastern Italy.

AUTHORS: Gioia Capelli, Stefano Nardelli, Antonio Frangipane di Regalbono,
Antonio Scala, Mario Pietrobelli

AFFILIATION: Dipartimento di Scienze Sperimentali Veterinarie, University of
Padua, Italy. gioia.capelli at unipd.it

REFERENCE: Vet Parasitol 2004 Sep 123(3-4):143-8

Risk factors associated with Neospora caninum seroprevalence in north-
eastern Italy in healthy dogs were assessed. Antibodies to N. caninum 
were found in 10.9% of 707 kennel and owned dogs by a commercial 
competitive ELISA (VMRD Inc.). All dogs were negative for Leishmania 
infantum by indirect fluorescent antibody test indicating no cross 
reactivity or association between the two protozoa in this area. 
Seroprevalence association with breed and age of dogs and other factors 
are discussed.

PMID: 15357211

TITLE: New insights into the developmental biology and transmission mechanisms
of Leishmania.

AUTHORS: P A Bates, M E Rogers

AFFILIATION: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3
5QA, UK. pbates at liv.ac.uk

REFERENCE: Curr Mol Med 2004 Sep 4(6):601-9

Leishmania alternates between two main morphological forms in its life 
cycle: intracellular amastigotes in the mammalian host and motile 
promastigotes in the sandfly vector. Several different forms of 
promastigote can be recognised in sandfly infections. The first 
promastigote forms, which are found in the sandfly in the bloodmeal 
phase, are multiplicative procyclic promastigotes. These differentiate 
into nectomonad promastigotes, which are a non-dividing migratory stage 
moving from the posterior to the anterior midgut. When nectomonad 
promastigotes arrive at the anterior midgut they differentiate into 
leptomonad forms, a newly named life cycle stage, which resume 
replication. Leptomonad promastigotes, which are found in the anterior 
midgut, are the developmental precursors of the metacyclic promastigotes
, the mammal-infective stages. Leptomonad forms also produce 
promastigote secretory gel, a substance that plays a key role in 
transmission by forming a physical obstruction in the gut, forcing the 
sandfly to regurgitate metacyclic promastigotes during bloodfeeding.

PMID: 15357214

TITLE: Surface determinants of Leishmania parasites and their role in
infectivity in the mammalian host.

AUTHORS: Thomas Naderer, James E Vince, Malcolm J McConville

AFFILIATION: Department of Biochemistry and Molecular Biology, University of
Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.

REFERENCE: Curr Mol Med 2004 Sep 4(6):649-65

Leishmania are intracellular protozoan parasites that reside primarily 
in host mononuclear phagocytes. Infection of host macrophages is 
initiated by infective promastigote stages and perpetuated by an 
obligate intracellular amastigote stage. Studies undertaken over the 
last decade have shown that the composition of the complex surface 
glycocalyx of these stages (comprising lipophosphoglycan, GPI-anchored 
glycoproteins, proteophosphoglycans and free GPI glycolipids) changes 
dramatically as promastigotes differentiate into amastigotes. Marked 
stage-specific changes also occur in the expression of other plasma 
membrane components, including type-1, polytopic and peripheral membrane
 proteins, reflecting the distinct microbicidal responses and 
nutritional environments encountered by these stages. More recently, a 
number of Leishmania mutants lacking single or multiple surface 
components have been generated. While some of these mutants are less 
virulent than wild type parasites, many of these mutants exhibit only 
mild or no loss of virulence. These studies suggest that, 1) the major 
surface glycocalyx components of the promastigote stage (i.e. LPG, GPI-
anchored proteins) only have a transient or minor role in macrophage 
invasion, 2) that there is considerable functional redundancy in the 
surface glycocalyx and/or loss of some components can be compensated for
 by the acquisition of equivalent host glycolipids, 3) the expression of
 specific nutrient transporters is essential for life in the macrophage 
and 4) the role(s) of some surface components differ markedly in 
different Leishmania species. These mutants will be useful for 
identifying other surface or intracellular components that are required 
for virulence in macrophages.

PMID: 15495722

TITLE: Visceral leishmaniasis in a soldier returning from Operation Enduring
Freedom.

AUTHORS: Eric S Halsey, L Michelle Bryce, Glenn W Wortmann, Peter J Weina,
Jeffrey R Ryan, Caroline C DeWitt

AFFILIATION: Department of Infectious Diseases, Wilford Hall Medical Center,
Lackland Air Force Base, TX 78236, USA.

REFERENCE: Mil Med 2004 Sep 169(9):699-701

This report presents a case of visceral leishmaniasis in a soldier 
returning from Operation Enduring Freedom. During the United States' 
last major military conflict, Operation Desert Storm, the diagnosis of 
multiple cases of visceral leishmaniasis led to policy changes, 
including a temporary ban on troop blood donation. This case 
demonstrates the applicability of recently developed Leishmania 
polymerase chain reaction and serological assays when conventional 
methods of diagnosis, such as tissue microscopy and culture, fail.

PMID: 15498178

TITLE: Leishmaniasis in refugee and local pakistani populations.

AUTHORS: Simon Brooker

AFFILIATION: London School of Hygiene and Tropical Medicine, London, United
Kingdom.

REFERENCE: Emerg Infect Dis 2004 Sep 10(9):1681-4

The epidemiology of anthroponotic cutaneous leishmaniasis was 
investigated in northwest Pakistan. Results suggested similar patterns 
of endemicity in both Afghan refugee and Pakistani populations and 
highlighted risk factors and household clustering of disease.

PMID: 15490751

TITLE: Activity of Lutzomyia pseudolongipalpis and L. longipalpis s.l. (Diptera:
Psychodidae) in Venezuela.

AUTHORS: M D Feliciangeli, J C Arrivillaga, A Bravo, F Arias

AFFILIATION: Universidad de Carabobo, Centro nacional de referencia de
flebÃ³tomos, BIOMED, Maracay, Venezuela. mdora at telcel.net.ve

REFERENCE: Parasite 2004 Sep 11(3):273-8

The nocturnal activity of the phlebotomine sandfly Lutzomyia 
pseudolongipalpis and two populations of L. longipalpis s.l. from 
different American visceral leishmaniasis foci in Venezuela was studied 
using collection bottle rotator traps. The activity of L. 
pseudolongipalpis from Lara State was continuous throughout the night, 
while that of L. longipalpis s.l. from El Layero, GuÃ¡rico State and 
from Santa Ana del Valle, Margarita Island, was greatest before 23:00 h
. The activity of sandflies of both populations and sexes steadily 
decreased thereafter. These different patterns seem to correlate with 
genetic data that indicate the presence in Venezuela of at least two 
sibling species in the L. longipalpis complex. The advantages of the 
bottle rotator trap for this type of study are discussed.

PMID: 15228724

TITLE: Sandflies (Diptera: Psychodidae) in the Bar area of Montenegro
(Yugoslavia). 2. Presence of promastigotes in Phlebotomus neglectus and first
record of P. kandelakii.

AUTHORS: V IvoviÄ‡, J Depaquit, N LÃ©ger, A Urano, B Papadopoulos

AFFILIATION: Laboratory of Clinical Bacteriology, Parasitology, Zoonoses and
Geographical Medicine, Division of Medicine, University of Crete, 71409
Irakleio, Crete, Greece.

REFERENCE: Ann Trop Med Parasitol 2004 Jun 98(4):425-7

PMID: 15482193

TITLE: Progress in the treatment of a neglected infectious disease: visceral
leishmaniasis.

AUTHORS: Henry W Murray

AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, 1300 York Avenue, New York, NY 10021, USA.
hmurray at med.cornell.edu.

REFERENCE: Expert Rev Anti Infect Ther 2004 Apr 2(2):279-92

Visceral leishmaniasis (kala-azar) is a disseminated intracellular 
protozoal infection. Most cases (90%) occur in the rural regions of five
 countries: India, Sudan, Nepal, Bangladesh and Brazil. As with other 
infectious diseases embedded in high-level poverty, developing and/or 
delivering new treatments for visceral leishmaniasis had been painfully 
slow or nonexistent. However, despite persistent unresolved obstacles (e
.g., drug affordability), renewed interest in visceral leishmaniasis and
 numerous successful treatment trials have combined to turn a 
therapeutic corner in the past 5 years, yielding new alternatives to 
conventional pentavalent antimony. Advances include the use of low-cost 
generic pentavalent antimony, rediscovery of amphotericin B, short-
course regimens via lipid formulations of amphotericin B, retesting 
injectible paromyomycin and, of clear-cut importance, identifying 
miltefosine (Impavido, Zentaris) as the first effective oral therapy for
 this neglected disease.

PMID: 15480215

TITLE: Ultrasound of tropical and infectious diseases that affect the scrotum.

AUTHORS: Osmar de Cassio Saito, Nestor de Barros, Maria Cristina Chammas, Ilka
Regina Souza Oliveira, Giovanni Guido Cerri

AFFILIATION: Assistant Doctors, Department of Radiology, School of Medicine,
University of SÃ£o Paulo, SÃ£o Paulo, Brazil. ocsaito at yahoo.com.br

REFERENCE: Ultrasound Q 2004 Mar 20(1):12-8

Ultrasonography of the scrotum permits assessment of testicular and 
extratesticular masses with high sensitivity. It can differentiate a 
variety of conditions involving the scrotum, testicles, and epididymis 
with similar clinical manifestations, including infectious and tropical 
diseases. The authors performed conventional and color Doppler 
ultrasonographic examinations in 76 patients who presented with scrotal 
pain, swelling, and/or tenderness. Their diagnoses included sexually 
transmitted disease (eg, gonorrhea, syphilis, chlamydial infection), 
tuberculosis, mumps, and various tropical diseases (eg, filariasis, 
leishmaniasis, schistosomiasis, paracoccidioidomycosis). The most common
 imaging findings were enlarged hypoechoic testes, hypervascularity, 
small hydroceles, and cutaneous edema. This report reviews these and 
other possible presentations of tropical and infectious diseases 
affecting the scrotum, emphasizing ultrasound findings that facilitate 
diagnosis.

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

 The following references are revised files and are brought to you in accordance
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PMID: 11323694

TITLE: SAP controls T cell responses to virus and terminal differentiation of
TH2 cells.

AUTHORS: C Wu, K B Nguyen, G C Pien, N Wang, C Gullo, D Howie, M R Sosa, M J
Edwards, P Borrow, A R Satoskar, A H Sharpe, C A Biron, C Terhorst

AFFILIATION: Division of Immunology, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA 02215, USA.

REFERENCE: Nat Immunol 2001 May 2(5):410-4

SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)-
associated protein (SAP), is altered in patients with X-linked 
lymphoproliferative disease (XLP), a primary immunodeficiency. SAP-
deficient mice infected with lymphocytic choriomeningitis virus had 
greatly increased numbers of CD8+ and CD4+ interferon-gamma-producing 
spleen and liver cells compared to wild-type mice. The immune responses 
of SAP-deficient mice to infection with Leishmania major together with 
in vitro studies showed that activated SAP-deficient T cells had an 
impaired ability to differentiate into T helper 2 cells. The aberrant 
immune responses in SAP-deficient mice show that SAP controls several 
distinct key T cell signal transduction pathways, which explains in part
 the complexity of the XLP phenotypes.

PMID: 4908372

TITLE: Effects of interferon inducers on the intracellular growth of the
protozoan parasite, Leishmania donovani.

AUTHORS: R Herman, S Baron

REFERENCE: Nature 1970 Apr 226(5241):168-70

REQUEST: [ leishmania ]

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

PMID: 15388875

TITLE: Cap-binding activity of an eIF4E homolog from Leishmania.

AUTHORS: Yael Yoffe, Joanna Zuberek, Magdalena Lewdorowicz, Ziv Zeira, Chen
Keasar, Irit Orr-Dahan, Marzena Jankowska-Anyszka, Janusz Stepinski, Edward
Darzynkiewicz, Michal Shapira

AFFILIATION: Department of Life Sciences, Ben-Gurion University of the Negev,
P.O.B. 653, Beer Sheva 84105, Israel. shapiram at bgu.ac.il.

REFERENCE: RNA 2004 Nov 10(11):1764-75

All eukaryotic mRNAs possess a 5'-cap (m(7)GpppN) that is recognized by 
a family of cap-binding proteins. These participate in various processes
, such as RNA transport and stabilization, as well as in assembly of the
 translation initiation complex. The 5'-cap of trypanosomatids is 
complex; in addition to 7-methyl guanosine, it includes unique 
modifications on the first four transcribed nucleotides, and is thus 
denoted cap-4. Here we analyze a cap-binding protein of Leishmania, in 
an attempt to understand the structural features that promote its 
binding to this unusual cap. LeishIF4E-1, a homolog of eIF4E, contains 
the conserved cap-binding pocket, similar to its mouse counterpart. The 
mouse eIF4E has a higher K(as) for all cap analogs tested, as compared 
with LeishIF4E-1. However, whereas the mouse eIF4E shows a fivefold 
higher affinity for m(7)GTP than for a chemically synthesized cap-4 
structure, LeishIF4E-1 shows similar affinities for both ligands. A 
sequence alignment shows that LeishIF4E-1 lacks the region that 
parallels the C terminus in the murine eIF4E. Truncation of this region 
in the mouse protein reduces the difference that is observed between its
 binding to m(7)GTP and cap-4, prior to this deletion. We hypothesize 
that variations in the structure of LeishIF4E-1, possibly also the 
absence of a region that is homologous to the C terminus of the mouse 
protein, promote its ability to interact with the cap-4 structure. 
LeishIF4E-1 is distributed in the cytoplasm, but its function is not 
clear yet, because it cannot substitute the mammalian eIF4E in a rabbit 
reticulocyte in vitro translation system.

PMID: 15500921

TITLE: Shotgun optical mapping of the entire Leishmania major Friedlin genome.

AUTHORS: Shiguo Zhou, Andrew Kile, Erika Kvikstad, Mike Bechner, Jessica
Severin, Dan Forrest, Rod Runnheim, Chris Churas, Thomas S Anantharaman, Peter
Myler, Christy Vogt, Al Ivens, Kenneth Stuart, David C Schwartz

AFFILIATION: Laboratory for Molecular and Computational Genomics, UW
Biotechnology Center, University of Wisconsin-Madison, 425 Henry Mall, Madison,
WI 53706, USA; Department of Chemistry, Laboratory of Genetics, University of
Wisconsin-Madison, Madison, WI 53706, USA.

REFERENCE: Mol Biochem Parasitol 2004 Nov 138(1):97-106

Leishmania is a group of protozoan parasites which causes a broad 
spectrum of diseases resulting in widespread human suffering and death, 
as well as economic loss from the infection of some domestic animals and
 wildlife. To further understand the fundamental genomic architecture of
 this parasite, and to accelerate the on-going sequencing project, a 
whole-genome XbaI restriction map was constructed using the optical 
mapping system. This map supplemented traditional physical maps that 
were generated by fingerprinting and hybridization of cosmid and P1 
clone libraries. Thirty-six optical map contigs were constructed for the
 corresponding known 36 chromosomes of the Leishmania major Friedlin 
genome. The chromosome sizes ranged from 326.9 to 2821.3kb, with a total
 genome size of 34.7Mb; the average XbaI restriction fragment was 25.3kb
, and ranged from 15.7 to 77.8kb on a per chromosomes basis. Comparison 
between the optical maps and the in silico maps of sequence drawn from 
completed, nearly finished, or large sequence contigs showed that 
optical maps served several useful functions within the path to create 
finished sequence by: guiding aspects of the sequence assembly, 
identifying misassemblies, detection of cosmid or PAC clones 
misplacements to chromosomes, and validation of sequence stemming from 
varying degrees of finishing. Our results also showed the potential use 
of optical maps as a means to detect and characterize map segmental 
duplication within genomes.

PMID: 15491584

TITLE: Blocked stomodeal valve of the insect vector: similar mechanism of
transmission in two trypanosomatid models.

AUTHORS: P Volf, M Hajmova, J Sadlova, J Votypka

AFFILIATION: Department of Parasitology, Charles University, Prague, Vinicna 7,
128 44 Prague 2, Czech Republic.

REFERENCE: Int J Parasitol 2004 Oct 34(11):1221-7

The regurgitation of metacyclic stages from the sand fly cardia is 
thought to be the prevailing mechanism of Leishmania transmission. This 
regurgitation may result through damage of the stomodeal valve and its 
mechanical block by the parasites. We found this phenomenon in three 
sand fly-Leishmania models and also in avian trypanosomes transmitted by
 Culex mosquitoes. Phlebotomus duboscqi, Phlebotomus papatasi, Lutzomyia
 longipalpis, and Culex pipiens were membrane-fed on blood containing 
Leishmania major, Leishmania chagasi (syn. infantum) and an unidentified
 avian Trypanosoma from Trypanosoma corvi clade, respectively. Females 
with the late-stage infections were processed for the optical and 
transmission electron microscopy. Localization of the parasites and 
changes to the stomodeal valve were in some aspects similar in all 
vector-parasite pairs studied: (i) a large plug of flagellates was 
observed in cardia region, (ii) parasites were attached to the chitin 
lining of the stomodeal valve by the formation of zonal hemidesmosome-
like plaques. Leishmania promastigotes were found both attached to the 
valve as well as unattached in the lumen of midgut. The stomodeal valve 
of infected sand flies was opened, its chitin lining was destroyed and 
the unique filamentous structures on the apical end of cylindrical cells
 were degraded. In the Culex-Trypanosoma model, the whole population of 
epimastigotes was found in close contact with the chitin lining, and 
degenerative changes of the valve were less pronounced. We suggest that 
the phenomenon involving a blocked valve facilitating the regurgitation 
of parasites into the vertebrate host may occur generally in 
heteroxenous trypanosomatids transmitted by the bite of nematoceran 
Diptera.

PMID: 15350130

TITLE: Entropy effects on protein hinges: the reaction catalyzed by
triosephosphate isomerase.

AUTHORS: Jingyi Xiang, Ju-yeon Jung, Nicole S Sampson

AFFILIATION: Department of Chemistry, State University of New York, Stony Brook,
New York 11794-3400, USA.

REFERENCE: Biochemistry 2004 Sep 43(36):11436-45

Many proteins utilize segmental motions to catalyze a specific reaction
. The Omega loop of triosephosphate isomerase (TIM) is important for 
preventing the loss of the reactive enediol(ate) intermediate. The loop 
opens and closes even in the absence of the ligand, and the loop itself 
does not change conformation during movement. The conformational changes
 are localized to two hinges at the loop termini. Glycine is never 
observed in native TIM hinge sequences. In this paper, the hypothesis 
that limited access to conformational space is a requirement for protein
 hinges involved in catalysis was tested. The N-terminal hinge was 
mutated to P166/V167G/W168G (PGG), and the C-terminal hinge was mutated 
to K174G/T175G/A176G (GGG) in chicken TIM. The single-hinge mutants PGG 
and GGG had k(cat) values 200-fold lower than that of the wild type and 
K(m) values 10-fold higher. The k(cat) of double-hinge mutant P166/V167G
/W168G/K174G/T175G/A176G was reduced 2500-fold; the K(m) was 10-fold 
higher. A combination of primary kinetic isotope effect measurements, 
isothermal calorimetric measurements, and (31)P NMR spectroscopic 
titration with the inhibitor 2-phosphoglycolate revealed that the 
mutants have a different ligand-binding mode than that of the wild-type 
enzyme. The predominant conformations of the mutants even in the 
presence of the inhibitor are loop-open conformations. In conclusion, 
mutation of the hinge residues to glycine resulted in the sampling of 
many more hinge conformations with the consequence that the population 
of the active-closed conformation is reduced. This reduced population 
results in a reduced catalytic activity.

PMID: 15225981

TITLE: Leishmaniasis: current situation and new perspectives.

AUTHORS: P Desjeux

AFFILIATION: Department of Control, Prevention and Elimination (CDS/CPE),
Cluster of Communicable Diseases, World Health Organization (WHO), Avenue
Appia, 1211 Geneva 27, Switzerland. desjeuxp at who.int

REFERENCE: Comp Immunol Microbiol Infect Dis 2004 Sep 27(5):305-18

Leishmaniasis represents a complex of diseases with an important 
clinical and epidemiological diversity. Visceral leishmaniasis (VL) is 
of higher priority than cutaneous leishmaniasis (CL) as it is a fatal 
disease in the absence of treatment. Anthroponotic VL foci are of 
special concern as they are at the origin of frequent and deathly 
epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 
countries, 350 million people at risk, 500,000 new cases of VL per year
, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is 
concentrated on few countries which allows clear geographic priorities. 
Leishmaniasis is still an important public health problem due to not 
only environmental risk factors such as massive migrations, urbanisation
, deforestation, new irrigation schemes, but also to individual risk 
factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part
 of those diseases which still requires improved control tools. 
Consequently WHO/TDR research for leishmaniasis has been more and more 
focusing on the development of new tools such as diagnostic tests, drugs
 and vaccines. The ongoing effort has already produced significant 
results. The newly available control tools should allow a scaling up of 
control activities in priority areas. In anthroponotic foci, the 
feasibility of getting a strong impact on mortality, morbidity and 
transmission, is high.

PMID: 15357218

TITLE: Progress in vaccine research and possible effector mechanisms in visceral
leishmaniasis.

AUTHORS: Rajesh Ravindran, Nahid Ali

AFFILIATION: Infectious Diseases Group, Indian Institute of Chemical Biology,
Calcutta, India.

REFERENCE: Curr Mol Med 2004 Sep 4(6):697-709

Visceral leishmaniasis represents a serious public health concern in 
endemic regions and is rapidly emerging as an opportunistic infection in
 HIV patients. The disease is difficult to diagnose and prevent, and 
available treatment is associated with toxicity and drug resistance. 
Even though significant headway has been made in the development of 
vaccines against cutaneous leishmaniasis, visceral leishmaniasis has 
received limited attention. The fact that a large proportion of the 
people living in endemic areas have self-resolving subclinical infection
 and individuals once recovered are immune to reinfection provides a 
rationale for designing immunoprophylactic strategies against visceral 
leishmaniasis. The primary aim of this paper is to review advances in 
vaccination strategies against visceral leishmaniasis, suggesting 
possible effector mechanism leading to resistance. It also covers the 
role of immunostimulators and gives an account of the adjuvants used 
against visceral leishmaniasis. Vaccine strategies in different 
established experimental models have also been dealt with which can 
provide potential leads for their application in humans. In light of the
 available observations made during the course of studies performed on 
experimental models of visceral leishmaniasis there is increasing 
evidence that a successful approach towards a vaccine involves the 
requirement of Th1 subset of CD4+ cells along with Th2, CD8+, and B 
cells. In this review we present the possible mechanism of interaction 
of these cells and their effector molecules in providing resistance 
against visceral leishmaniasis for the future design of effective 
vaccine against this disease.

PMID: 15491550

TITLE: Leishmania (Viannia): genetic analysis of cutaneous and mucosal strains
isolated from the same patient.

AUTHORS: Patricia Cuervo, Elisa Cupolillo, Nedia Nehme, Vivian Hernandez, Nancy
Saravia, Octavio Fernandes

AFFILIATION: Department of Tropical Medicine, Oswaldo Cruz Institute, FIOCRUZ,
Rio de Janeiro, Brazil; International Center of Training and Medical Research,
CIDEIM, Cali, Colombia.

REFERENCE: Exp Parasitol 2004 Sep-Oct 108(1-2):59-66

Ten pairs of Leishmania (Viannia) strains isolated from mucosal and 
cutaneous lesions of the same patient were analyzed genotypically in 
order to determine whether populations that had metastasized to mucosal 
sites differed from those in the cutaneous lesion. The strains were 
previously characterized by multi locus enzyme electrophoresis and/or 
monoclonal antibodies reactivity, and, for this study, only isolates 
from the same patient which were identified as the same species were 
employed. PCR-RFLP of internal transcribed spacer (ITS) rDNA, random 
amplified polymorphic DNA (RAPD), and schizodeme analyses were conducted
. All genotyping methods revealed microheterogeneity between cutaneous 
and mucosal isolates from the same patient. The PCR-RFLP of the ITS rDNA
 and RAPD analysis were numerically analyzed through similarity 
coefficients and dendrograms were generated. All phenograms clustered 
cutaneous and mucosal strains of the same patient in one branch with a 
high degree of similarity, and phenetic analysis matched between them. 
Schizodeme analysis revealed differences between strains that composed 
some pairs. Genetic analyses indicate that some populations that 
metastasize to mucosal sites are distinguishable from the population in 
cutaneous lesions, however, other approaches will be required to 
associate genetic polymorphisms with the cutaneous or mucosal phenotype 
of strains.

PMID: 15202852

TITLE: Nerve involvement in Indian post kala-azar dermal leishmaniasis.

AUTHORS: Sujay Khandpur, M Ramam, Vinod K Sharma, Poonam Salotra, Manoj K Singh,
Amit Malhotra

REFERENCE: Acta Derm Venereol 2004  84(3):245-6

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

 The following references are revised files and are brought to you in accordance
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********************************************************************************************************************

PMID: 15311940

TITLE: CYP51 from Trypanosoma brucei is obtusifoliol-specific.

AUTHORS: Galina I Lepesheva, W David Nes, Wenxu Zhou, George C Hill, Michael R
Waterman

AFFILIATION: Department of Biochemistry, Vanderbilt University School of
Medicine, Nashville, Tennessee 37232-0146, USA.
galina.i.lepesheva at vanderbilt.edu

REFERENCE: Biochemistry 2004 Aug 43(33):10789-99

New isoforms of CYP51 (sterol 14alpha-demethylase), an essential enzyme 
in sterol biosynthesis and primary target of azole antimycotic drugs, 
are found in pathogenic protists, Trypanosoma brucei(TB), T. vivax, T. 
cruzi, and Leishmania major. The sequences share approximately 80% amino
 acid identity and are approximately 25% identical to sterol 14alpha-
demethylases from other biological kingdoms. Differences of residues 
conserved throughout the rest of the CYP51 family that align with the BC
-loop and helices F and G of CYP51 from Mycobacterium tuberculosis (MT
)) imply possible alterations in the topology of the active site cavity 
of the protozoan enzymes. CYP51 and cytochrome P450 reductase (CPR) from
 TB were cloned, expressed in Escherichia coli, and purified. The P450 
has normal spectral features (including absolute absorbance, carbon 
monoxide, and ligand binding spectra), is efficiently reduced by TB and 
rat CPR but demonstrates altered specificity in comparison with human 
CYP51 toward three tested azole inhibitors, and contrary to the human, 
Candida albicans, and MT isoforms, reveals profound substrate preference
 toward obtusifoliol (turnover 5.6 min(-1)). It weakly interacts with 
the other known CYP51 substrates; slow lanosterol conversion 
predominantly produces the 14alpha-carboxyaldehyde intermediate. 
Although obtusifoliol specificity is typical for plant isoforms of CYP51
, the set of sterol biosynthetic enzymes in the protozoan genomes 
together with available information about sterol composition of 
kinetoplastid cells suggest that the substrate preference of TBCYP51 may
 reflect a novel sterol biosynthetic pathway in Trypanosomatidae.

PMID: 12788347

TITLE: Structure-activity relationships of antileishmanial and antimalarial
chalcones.

AUTHORS: Mei Liu, Prapon Wilairat, Simon L Croft, Agnes Lay-Choo Tan, Mei-Lin
Go

AFFILIATION: Department of Pharmacy, National University of Singapore, 18
Science Drive 4, Singapore 117543, Singapore.

REFERENCE: Bioorg Med Chem 2003 Jul 11(13):2729-38

A series of oxygenated chalcones which have been evaluated earlier for 
antimalarial activity (Plasmodium falciparum K1) were tested for 
antileishmanial activity against Leishmania donovani amastigotes. A 
comparison of structure-activity relationships reveal that different 
physicochemical and structural requirements exist for these two 
activities. Antileishmanial activity is associated with less lipophilic 
chalcones, in particular those with 4'-hydroxyl-substituted B rings and 
hetero/polyaromatic A rings. In contrast, chalcones with good 
antimalarial activity have alkoxylated B rings and electron-deficient A 
rings. Visualization of the steric and electrostatic fields generated 
from comparative molecular field analysis (CoMFA) indicate that the ring
 A of chalcones make a more significant contribution to antileishmanial 
activity while both rings A and B are important for antimalarial 
activity. Despite different requirements, two alkoxylated chalcones (8, 
19) were identified which combined good antimalarial and antileishmanial
 activities.

PMID: 4908583

TITLE: Changes in leptomonads of Leishmania tropica grown in media containing
immune serum.

AUTHORS: G Wertheim, A Roner, B Montilio

REFERENCE: Nature 1970 Apr 226(5242):267-9

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