No subject

20,000 soldiers returning from a yearlong deployment in Iraq with skin 
lesions suspected of being CL were examined by dermatologists. We 
summarized CL diagnoses, laboratory evaluations, and treatments, 
including localized heat therapy (ThermoMed model 1.8; ThermoSurgery 
Technologies, Inc, Phoenix, Ariz), oral fluconazole, cryotherapy, and 
itraconazole. RESULTS: Among 237 soldiers diagnosed with CL, 181 had one
 or more laboratory confirmations, most by Giemsa-stained lesion smears 
and polymerase chain reaction (PCR). PCR was positive for all 122 smear-
positive and 26 biopsy-positive lesions and all 34 smear negative and 
all 3 biopsy-negative cases. Primary outpatient treatments, including 
ThermoMed (n = 26), oral fluconazole (n = 15), cryotherapy (n = 4), and 
itraconazole (n = 2), were safe and tolerable. Treatment failure 
occurred in 2 fluconazole recipients and was suspected in 1 ThermoMed 
and 2 fluconazole recipients. Seventy-two soldiers elected no treatment
. LIMITATION: This was a retrospective study. CONCLUSION: Approximately 
1% of Ft Campbell troops returning from Iraq were diagnosed with CL, 
most by laboratory confirmation. PCR appeared to be the most useful 
diagnostic technique. Among outpatient treatments, ThermoMed and 
cryotherapy had favorable safety and efficacy profiles.




PMID: 15826551
 

TITLE: [Slowly progressing skin ulcers following a stay in Costa Rica]

AUTHORS: María Mateo, Israel Cruz, María D Flores, Rogelio López-Vélez

AFFILIATION: Servicio de Medicina Tropical, Enfermedades Infecciosas,
Microbiología, Hospital Ramón y Cajal, Madrid, Spain. mmateom at terra.es

REFERENCE: Enferm Infecc Microbiol Clin 2005 Apr 23(4):243-4








PMID: 15814284
 

TITLE: European strategies against the parasite transfusion risk.

AUTHORS: H W Reesink

AFFILIATION: Sanquin Blood Bank North-West Region, Sanquin Diagnostic Services,
P.O. Box 9137, NL - 1006 AC Amsterdam, The Netherlands. h.reesink at sanquin.nl

REFERENCE: Transfus Clin Biol 2005 Feb 12(1):1-4

Protozoal infections are endemic in mainly tropical low income countries
, affecting millions of people. Malaria, American trypanosomiasis (
Trypanosoma cruzi/Chagas disease) and protozoal tickborne diseases (e.g
. Babesia) can be efficiently transmitted by transfusion of cellular 
blood components. In non-endemic areas like Europe malaria, Chagas 
disease and Babesia are imported diseases resulting of travelling to 
endemic areas and migration of autochthons from these endemic areas. A 
recent International Forum showed that in Europe, as well as the USA, 
prevention of transfusion-associated protozoal infections depend mainly 
on selection of donors using questionnaires. Most countries divide 
donors at risk for malaria in two groups: individuals who have lived in 
the first 5 years of their life in malaria endemic areas and those who 
are borne and residing in non-endemic areas and visited the endemic area
(s). The first category of donors is rejected for 3 years after their 
last visit to the endemic area, and in one country such donors are 
permanently rejected. In some countries such donors are accepted after 4
 months-3 years, provided a test for malaria is non-reactive. Persons 
from non-endemic areas, who visited the malaria endemic area, are 
rejected for 4-12 months. Some countries reject these donors for 3 years
 or permanently when they resided for more than 6 months in the endemic 
area. The rejection rate of donors for malaria risk in the various 
countries was 0.003-0.43% of all donations. Over the last decade only a 
few cases of TT-malaria were reported in the various countries. In 
several countries donors are questioned for risk of T. cruzi infection. 
In some countries donors are excluded when they (or their mothers) were 
born in South or Central America, if they received a blood transfusion 
in these areas and if they lived in rural areas in these endemic 
countries for more than 4 weeks. In none of the countries donors are 
asked if they had Babesia or Leishmania. At present implemented measures
 to prevent TT-malaria in the European countries are probably highly 
effective. More research is needed to establish the theoretical risk of 
TT-T. cruzi and TT-Leishmania infection in Europe, before preventive 
measures may be considered.




PMID: 15928579
 

TITLE: Molecular basis of Trypanosoma cruzi and Leishmania interaction with
their host(s): exploitation of immune and defense echanisms by the....

AUTHORS: Ali Ouaissi, Mehdi Ouaissi

AFFILIATION: IRD, Research Unit No.008," The Pathogenesis of Trypanosomatides
",
Montpellier,France.

REFERENCE: Arch Immunol Ther Exp (Warsz) 2005 Mar-Apr 53(2):102-14

A number of features occurring during host-parasite interactions in 
Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and 
Leishmaniasis, caused by a group of kinetoplastid protozoan parasites 
are reminiscent of those observed in cancer diseases. In fact,although 
the cancer is not a single disease, and that T.cruzi and Leishmania are 
sophisticated eukaryotic parasites presenting a high level of genotypic 
variability the growth of the parasites in their host and that of cancer
 cells share at least one common feature, that is their mutual capacity 
for rapid cell division. Surprisingly, the parasitic diseases and 
cancers share some immune evasion strategies. Consideration of these 
immunological alterations must be added to the evaluation of the 
pathogenic processes. The molecular and functional characterization of 
virulence factors and the study of their effect on the arms of the 
immune system have greatly improved understanding of the regulation of 
immune effectors functions. The purpose of this review is to analyze 
some of the current data related to the regulatory components or 
processes originating from the parasite that control or interfere with 
host cell physiology. Attempts are also made to delineate some 
similarities between the immune evasion strategies that parasites and 
tumors employ. The elucidation of the mode of action of parasite 
virulence factors toward the host cell allow not only provide us with a 
more comprehensive view of the host-parasite relationships but may also 
represent a step forward in efforts aimed to identify new target 
molecules for therapeutic intervention.




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

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to license agreement with the NLM.

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


PMID: 15789648
 

TITLE: Efficacy of the treatment of dogs with leishmaniosis with a combination
of metronidazole and spiramycin.

AUTHORS: M G Pennisi, M De Majo, M Masucci, D Britti, F Vitale, R Del Maso

AFFILIATION: Dipartimento di Scienze Mediche Veterinarie, Università degli
Studi di Messina, Messina, Italy.

REFERENCE: Vet Rec 2005 Mar 156(11):346-9

Twenty-seven dogs infected naturally with Leishmania infantum were used 
in a randomised controlled trial to compare the clinical and 
parasitological efficacy of an oral treatment with a combination of 
metronidazole and spiramycin (13 dogs) with the efficacy of conventional
 treatment with meglumine antimonate and allopurinol (14 dogs) as 
controls. In the test group one dog had to be withdrawn from the 
treatment because it developed pemphigus foliaceus; 10 of the dogs were 
clinically responsive but none was cured parasitologically. In the 
control group four dogs were withdrawn from the treatment because of 
side effects; eight of the dogs were clinically responsive but none was 
cured parasitologically. The control group showed signs of improvement 
after an average of 30 days, whereas the test group did not show signs 
of improvement until after an average of 45 days.




REQUEST: [ leishmania ]

(20 articles match this request. 8 articles matching other requests removed)



PMID: 15876538
 

TITLE: Studies on quinones. Part 39: Synthesis and leishmanicidal activity of
acylchloroquinones and hydroquinones.

AUTHORS: Jaime A Valderrama, Carlos Zamorano, M Florencia González, Eric
Prina,
Alain Fournet

AFFILIATION: Facultad de Química, Pontificia Universidad Católica de Chile,
Casilla 306, Santiago 22, Chile.

REFERENCE: Bioorg Med Chem 2005 Jul 13(13):4153-9

Acylhydroquinone-based compounds are attractive targets for the design 
of new leishmanicidal drugs. We have previously described sesquiterpene 
quinones and hydroquinones series, which exhibit different degree of 
potency against Leishmania amazonensis. The present study details the 
preparation of acylchloroquinones and hydroquinones possessing 
lipophilic substituents and examines their in vitro activity against 
intracellular L. amazonensis amastigotes. The quinone or hydroquinone 
nucleus is essential for the activity of the members of the series. The 
lipophilicity of the cycloaliphatic systems in these members seems to 
attenuate the cytotoxical effect and increases the selectivity of those 
compounds containing the norbornene system.




PMID: 15923618
 

TITLE: Trypanosome Telomeres Are Protected by a Homologue of Mammalian TRF2.

AUTHORS: Bibo Li, Amin Espinal, George A M Cross

AFFILIATION: Laboratory of Molecular Parasitology, The Rockefeller University,
1230 York Avenue, New York, NY 10021. gamc at mail.rockefeller.edu.

REFERENCE: Mol Cell Biol 2005 Jun 25(12):5011-21

Putative TTAGGG repeat-binding factor (TRF) homologues in the genomes of
 Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major were 
identified. They have significant sequence similarity to higher 
eukaryotic TRFs in their C-terminal DNA-binding myb domains but only 
weak similarity in their N-terminal domains. T. brucei TRF (tbTRF) is 
essential and was shown to bind to duplex TTAGGG repeats. The RNA 
interference-mediated knockdown of tbTRF arrested bloodstream cells at G
(2)/M and procyclic cells partly at S phase. Functionally, tbTRF 
resembles mammalian TRF2 more than TRF1, as knockdown diminished 
telomere single-stranded G-overhang signals. This suggests that tbTRF, 
like vertebrate TRF2, is essential for telomere end protection, and this
 also supports the hypothesis that TRF rather than Rap1 is the more 
ancient DNA-binding component of the telomere protein complex. 
Identification of the first T. brucei telomere DNA-binding protein and 
characterization of its function provide a new route to explore the 
roles of telomeres in pathogenesis of this organism. This work also 
establishes T. brucei as an attractive model for telomere biology.




PMID: 15923379
 

TITLE: Structure-function analysis of yeast tRNA ligase.

AUTHORS: Li Kai Wang, Stewart Shuman

AFFILIATION: Molecular Biology Program, Sloan-Kettering Institute, New York, NY
10021, USA. s-shuman at ski.mskcc.org.

REFERENCE: RNA 2005 Jun 11(6):966-75

Trl 1 is an essential 827-amino-acid enzyme that executes the end-
healing and end-sealing steps of tRNA splicing in Saccharomyces 
cerevisiae. Trl1 consists of two catalytic domains-an N-terminal 
adenylyltransferase/ligase component (amino acids 1-388) and a C-
terminal 5'-kinase/cyclic phosphodiesterase component (amino acids 389-
827)-that can function in tRNA splicing in vivo when expressed as 
separate polypeptides. Sedimentation analysis indicates that the ligase 
and kinase/CPD domains are monomeric proteins that do not form a stable 
complex in trans. To understand the structural requirements for the RNA 
ligase component, we performed a mutational analysis of amino acids that
 are conserved in Trl1 homologs from other fungi. Alanine scanning 
identified 23 new residues as essential for Trl1-(1-388) activity in 
vivo. Structure-activity relationships at these positions, and four 
essential residues defined previously, were clarified by introducing 50 
different conservative substitutions. Lethal mutations of Lys114, Glu184
, Glu266, and Lys284 abolished Trl1 adenylyltransferase activity in 
vitro. The essential elements embrace (1) putative equivalents of 
nucleotidyltransferase motifs I, Ia, III, IV, and V found in DNA ligases
, T4 RNA ligase 2, and mRNA capping enzymes; (2) an N-terminal segment 
shared with the T4 RNA ligase 1 subfamily only; and (3) a constellation 
of conserved residues specific to fungal tRNA splicing enzymes. We 
identify yeastlike tRNA ligases in the proteomes of Leishmania and 
Trypanosoma. These findings recommend tRNA ligase as a target for 
antifungal and antiprotozoal drug discovery.








PMID: 15890467
 

TITLE: Antileishmanial and antifungal activities of xanthanolides isolated from
Xanthium macrocarpum.

AUTHORS: Marie Lavault, Anne Landreau, Gérald Larcher, Jean-Philippe Bouchara,
Fabrice Pagniez, Patrice Le Pape, Pascal Richomme

AFFILIATION: SONAS UPRES-EA 921, UFR des Sciences Pharmaceutiques et
Ingéniérie de la santé, 16 Bd Daviers, Angers, France.

REFERENCE: Fitoterapia 2005 Jun 76(3-4):363-6

Seven xanthanolides, xanthinosin, xanthatin, 4-hydroxyxanthinosin, 
xanthinin, 4-epiisoxanthanol, 4-epixanthanol, 2-hydroxyxanthinosin and 4
-oxobedfordia acid, were isolated from the fruits of Xanthium 
macrocarpum. A valuation of the antifungal activity of these 
xanthanolides against Candida albicans, Candida glabrata and Aspergillus
 fumigatus and of their antileishmanial activity against Leishmania 
infantum and Leishmania mexicana is presented.




PMID: 15905034
 

TITLE: Periodic administration of allopurinol is not effective for the
prevention of canine leishmaniosis (Leishmania infantum) in the endemic areas.

AUTHORS: Manolis N Saridomichelakis, Mathios E Mylonakis, Leonidas S Leontides,
Charalambos Billinis, Alexander F Koutinas, Apostolos D Galatos, Pagona
Gouletsou, Anastasia Diakou, Vassilios I Kontos

AFFILIATION: Clinic of Companion Animal Medicine, School of Veterinary
Medicine,
Aristotle University of Thessaloniki, 11 Stavrou Voutyra str., GR-54627
Thessaloniki, Greece.

REFERENCE: Vet Parasitol 2005 Jun 130(3-4):199-205

A total of 95 clinically healthy and seronegative for Leishmania 
infantum dogs, residing an area highly endemic for canine leishmaniosis
 (CL) and living an outdoor life-style, were split into positive and 
negative groups, and then were randomly assigned to receive allopurinol
 (n=51; 20mg/kg once daily), or placebo (n=44) for 1 week per month, 
from April to November. Forty per cent (38/95) of these dogs were not 
reexamined and retested at the end of the trial for reasons unrelated to
 CL. None of the remaining 57 dogs exhibited the symptomatic form of the
 disease at the end of the 1-year follow-up period. Of the 15 
allopurinol-treated dogs that were non-infected (negative PCR and tissue
 smear microscopy) at the beginning of the trial, 6 (40% P=0.03) became 
PCR-positive, of which 3 became also seropositive, at the end of the 
observation period. In contrast, only 1 of 7 (14.3%) placebo-treated non
-infected dogs became PCR positive at the same time point. Of the 19 
allopurinol-treated dogs that were infected (PCR-positive) at the 
beginning of the trial, 18 (94.7%) remained PCR-positive and one (5.3%) 
seroconverted, at the end of the observation period. Of the 16 initially
 infected and placebo-treated dogs, 14 (87.5%) remained PCR positive, of
 which one (6.7%) also turned positive by tissue smear microscopy. 
Therefore, it is concluded that the use of allopurinol, at the daily 
dose of 20mg/kg, for 1 week per month, during the period of sandfly 
activity, does not prevent the infection of non-infected dogs by L. 
infantum, and, also, does not help in the elimination of the parasite 
from dogs with asymptomatic infections.




PMID: 15852008
 

TITLE: Transforming growth factor-beta controls T helper type 1 cell
development
through regulation of natural killer cell interferon-gamma.

AUTHORS: Yasmina Laouar, Fayyaz S Sutterwala, Leonid Gorelik, Richard A Flavell

AFFILIATION: Section of Immunobiology, Yale University School of Medicine, New
Haven, Connecticut 06520, USA.

REFERENCE: Nat Immunol 2005 Jun 6(6):600-7

Interferon-gamma and interleukin 12 produced by the innate arm of the 
immune system are important regulators of T helper type 1 (T(H)1) cell 
development, but signals that negatively regulate their expression 
remain controversial. Here we show that transforming growth factor-beta
 (TGF-beta) controlled T(H)1 differentiation through the regulation of 
interferon-gamma produced by natural killer (NK) cells. Blockade of TGF-
beta signaling in NK cells caused the accumulation of a large pool of NK
 cells secreting copious interferon-gamma, responsible for T(H)1 
differentiation and protection from leishmania infection. In contrast, 
blockade of TGF-beta signaling in dendritic cells did not affect 
dendritic cell homeostasis or interleukin 12 production, thus indicating
 a previously undescribed demarcation of the function of TGF-beta in NK 
cells versus dendritic cells.




PMID: 15917541
 

TITLE: Effects of acyl versus aminoacyl conjugation on the properties of
antimicrobial peptides.

AUTHORS: Inna S Radzishevsky, Shahar Rotem, Fadia Zaknoon, Leonid Gaidukov,
Arie
Dagan, Amram Mor

AFFILIATION: Laboratory of Antimicrobial Investigation, Department of
Biotechnology & Food Engineering, Technion-Israel Institute of Technology,
Haifa, Israel.

REFERENCE: Antimicrob Agents Chemother 2005 Jun 49(6):2412-20

To investigate the importance of increased hydrophobicity at the amino 
end of antimicrobial peptides, a dermaseptin derivative was used as a 
template for a systematic acylation study. Through a gradual increase of
 the acyl moiety chain length, hydrophobicity was monitored and further 
modulated by acyl conversion to aminoacyl. The chain lengths of the acyl
 derivatives correlated with a gradual increase in the peptide's global 
hydrophobicity and stabilization of its helical structure. The effect on
 cytolytic properties, however, fluctuated for different cells. Whereas 
acylation gradually enhanced hemolysis of human red blood cells and 
antiprotozoan activity against Leishmania major, bacteria displayed a 
more complex behavior. The gram-positive organism Staphylococcus aureus 
was most sensitive to intermediate acyl chains, while longer acyls 
gradually led to a total loss of activity. All acyl derivatives were 
detrimental to activity against Escherichia coli, namely, but not solely
, because of peptide aggregation. Although aminoacyl derivatives behaved
 essentially similarly to the nonaminated acyls, they displayed reduced 
hydrophobicity, and consequently, the long-chain acyls enhanced activity
 against all microorganisms (e.g., by up to 12-fold for the aminolauryl 
derivative) but were significantly less hemolytic than their acyl 
counterparts. Acylation also enhanced bactericidal kinetics and peptide 
resistance to plasma proteases. The similarities and differences upon 
acylation of MSI-78 and LL37 are presented and discussed. Overall, the 
data suggest an approach that can be used to enhance the potencies of 
acylated short antimicrobial peptides by preventing hydrophobic 
interactions that lead to self-assembly in solution and, thus, to 
inefficacy against cell wall-containing target cells.








PMID: 15908413
 

TITLE: Recombinant cysteine proteinase from Leishmania (Leishmania) chagasi
implicated in human and dog T-cell responses.

AUTHORS: Paulo Henrique da Costa Pinheiro, Suzana de Souza Dias, Kelsen Dantas
Eulálio, Ivete L Mendonça, Simone Katz, Clara Lúcia Barbiéri

AFFILIATION: Division of Parasitology, Universidade Federal de São Paulo,
Escola Paulista de Medicina, Rua Botucatu, 862-6o andar, São Paulo, SP, Brazil
04023-062.

REFERENCE: Infect Immun 2005 Jun 73(6):3787-9

High in vitro lymphoproliferative responses were induced in humans and 
dogs by a recombinant Leishmania (Leishmania) chagasi cysteine 
proteinase, with secretion of IFN-gamma in asymptomatic subjects or of 
IFN-gamma, interleukin 4 (IL-4), and IL-10 in oligosymptomatic subjects
. In contrast, responses of symptomatic patients and dogs were lower, 
with production of IL-4 and IL-10.




PMID: 15933773
 

TITLE: Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay.

AUTHORS: J L M Wanderley, A Benjamin, F Real, A Bonomo, M E C Moreira, M A
Barcinski

REFERENCE: Braz J Med Biol Res 2005 Jun 38(6):807-12

Apoptosis is the most common phenotype observed when cells die through 
programmed cell death. The morphologic and biochemical changes that 
characterize apoptotic cells depend on the activation of a diverse set 
of genes. Apoptosis is essential for multicellular organisms since their
 development and homeostasis are dependent on extensive cell renewal. In
 fact, there is strong evidence for the correlation between the 
emergence of multicellular organisms and apoptosis during evolution. On 
the other hand, no obvious advantages can be envisaged for unicellular 
organisms to carry the complex machinery required for programmed cell 
death. However, accumulating evidence shows that free-living and 
parasitic protozoa as well as yeasts display apoptotic markers. This 
phenomenon has been related to altruistic behavior, when a subpopulation
 of protozoa or yeasts dies by apoptosis, with clear benefits for the 
entire population. Recently, phosphatidylserine (PS) exposure and its 
recognition by a specific receptor (PSR) were implicated in the 
infectivity of amastigote forms of Leishmania, an obligatory vertebrate 
intramacrophagic parasite, showing for the first time that unicellular 
organisms use apoptotic features for the establishment and/or 
maintenance of infection. Here we focus on PS exposure in the outer 
leaflet of the plasma membrane - an early hallmark of apoptosis - and 
how it modulates the inflammatory activity of phagocytic cells. We also 
discuss the possible mechanisms by which PS exposure can define 
Leishmania survival inside host cells and the evolutionary implications 
of apoptosis at the unicellular level.




PMID: 15927005
 

TITLE: Leishmania donovani Amastigotes Mobilize Organic and Inorganic Osmolytes
During Regulatory Volume Decrease.

AUTHORS: Ann Lefurgey, Melissa Gannon, Joseph Blum, Peter Ingram

AFFILIATION: Durham Veterans Affairs Medical Center, Duke University Medical
Center, Durham, North Carolina, 27705.

REFERENCE: J Eukaryot Microbiol 2005 May-Jun 52(3):277-89

The protozoan parasite Leishmania donovani encounters large fluctuations
 in osmolality as it cycles between its insect vector and human host. 
The flagellated promastigote exhibits regulatory volume responses 
involving organic and inorganic osmolytes, but little is known about 
volume regulation in the clinically relevant amastigote that multiplies 
within the parasitophorous vacuoles of mammalian host cells. Using a 
combination of morphological, X-ray microanalytical, and biochemical 
approaches we determined that non-motile amastigotes respond to 
hypotonic stress with (1) an amino acid and l-alanine-mediated 
regulatory volume decrease, and (2) a parallel release of Na(+), K(+), P
 (presumably as negatively charged phosphates), and subsequently Cl(-) 
from cytoplasm and the cell as a whole. In addition P, Zn(2+), and 
subsequently Ca(2+) increase in acidocalcisomes as Cl(-) content 
declines in this compartment. This evidence is the first to document 
subcellular translocation of, and thus a potential role for, zinc in 
volume regulatory responses. These coordinated changes in organic and 
inorganic osmolytes demonstrate that amastigote subcellular compartments
, particularly acidocalcisomes, function in maintaining ionic 
homeostasis in the response of Leishmania amastigotes to hypo-osmotic 
stress.




PMID: 15926996
 

TITLE: Infection with Leishmania infantum Inhibits Actinomycin D-Induced
Apoptosis of Human Monocytic Cell Line U-937.

AUTHORS: Sabrina Lisi, Margherita Sisto, Angela Acquafredda, Rosa Spinelli,
Mariaangela Schiavone, Vincenzo Mitolo, Olga Brandonisio, Mariaantonietta
Panaro

AFFILIATION: Department of Human Anatomy and Histology, University of Bari,
I-70124 Bari, Italy.

REFERENCE: J Eukaryot Microbiol 2005 May-Jun 52(3):211-7

Modulation of host cell apoptosis has been observed in many bacterial, 
protozoal, and viral infections. The aim of this work was to investigate
 the effect of viscerotropic Leishmania (L.) infantum infection on 
actinomycin D-induced apoptosis of the human monocytic cell line U-937. 
Cells were infected with L. infantum promastigotes or treated with the 
surface molecule lipophosphoglycan (LPG) or with parasite-free 
supernatant of Leishmania culture medium and submitted to action of 
actinomycin D as the apoptosis-inducing agent. Actinomycin D-induced 
apoptosis in U-937 cells was inhibited in the presence of both viable L
. infantum promastigotes and soluble factors contained in Leishmania 
culture medium or purified LPG. Leishmania infantum affected the 
survival of U-937 cells via a mechanism involving inhibition of caspase-
3 activation. Furthermore, protein kinase C delta (PKC delta) cleavage 
was increased in actinomycin D-treated U-937 cells and was inhibited by 
the addition of LPG. Thus, inhibition of the PKC-mediated pathways by 
LPG can be implicated in the enhanced survival of the parasites. These 
results support the claim that promastigotes of L. infantum, as well as 
its surface molecule, LPG, which is in part released in the culture 
medium, inhibit macrophage apoptosis, thus allowing intracellular 
parasite survival and replication.




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

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

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


PMID: 11544261
 

TITLE: Expression of a mutant form of Leishmania donovani centrin reduces the
growth of the parasite.

AUTHORS: A Selvapandiyan, R Duncan, A Debrabant, S Bertholet, G Sreenivas, N S
Negi, P Salotra, H L Nakhasi

AFFILIATION: Laboratory of Bacterial, Parasitic, and Unconventional Agents,
Division of Emerging and Transfusion Transmitted Disease, Center for Biologics
Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
20892, USA.

REFERENCE: J Biol Chem 2001 Nov 276(46):43253-61

Leishmania donovani, a protozoan parasite, causes visceral disease in 
humans. To identify genes that control growth, we have isolated for the 
first time in the order Kinetoplastida a gene encoding for centrin from 
L. donovani. Centrin is a calcium-binding cytoskeletal protein essential
 for centrosome duplication or segregation. Protein sequence similarity 
and immunoreactivity confirmed that Leishmania centrin is a homolog of 
human centrin 2. Immunofluorescence analysis localized the protein in 
the basal body. Calcium binding analysis revealed that its C-terminal Ca
(2+) binding domain binds 16-fold more calcium than the N-terminal 
domain. Electrophoretic mobility shift of centrin treated with EGTA and 
abrogation of the shift in its mutants lacking a Ca(2+) binding site 
suggest that Ca(2+) binding to these regions may have a role in the 
protein conformation. The levels of centrin mRNA and protein were high 
during the exponential growth of the parasite in culture and declined to
 a low level in the stationary phase. Expression of N-terminal-deleted 
centrin in the parasite significantly reduces its growth rate, and it 
was found that significantly more cells are arrested in the G(2)/M stage
 than in control cells. These studies indicate that centrin may have a 
functional role in Leishmania growth.




REQUEST: [ sand fly ]

(1 article matches this request. 1 article matching other requests removed)



REQUEST: [ sandfly ]

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



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

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

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


PMID: 15708593
 

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

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

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

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

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















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