[Leish-l] Fwd: Articles found by RefScout 2006/02/15 2006/07

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    Date: Wed, 15 Feb 2006 05:52:21
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REQUEST: [ leishmaniasis ]

(22 articles match this request)



PMID: 16474088
 

TITLE: Leishmania tropica-isolated patient with visceral leishmaniasis in
southern iran.

AUTHORS: Abdolvahab Alborzi, Manoochehr Rasouli, Ahmad Shamsizadeh

AFFILIATION: Prof. Alborzi Clinical Microbiology Research Center, Shiraz
University of Medical Sciences, Shiraz, Iran; Department of Pediatrics, Faculty
of Medicine, Ahwaz University of Medical Sciences, Ahwaz, Iran.

REFERENCE: Am J Trop Med Hyg 2006 Feb 74(2):306-7

Visceral leishmaniasis (VL) is caused by various strains of Leishmania 
donovani, Leishmania infantum, and Leishmania chagasi with different 
geographical distribution. The aim of this study was to identify the 
strains of Leishmania that can cause VL in southern Iran. DNA of 
Leishmania were extracted from the slides of bone marrow aspirates (#42
) and spleen punctures (#22), which were positive for leishman body from
 the patients who were referred to the hospitals affiliated with Shiraz 
University of Medical Sciences. Differences in Leishmania strains were 
determined by size difference of the polymerase chain reaction (PCR) 
amplification as visualized on agarose gel. PCR results and smears had 
100% correlation. The dominant strain of Leishmania was L. infantum (63 
out of the 64 cases), but one case of L. tropica was also detected. VL 
mostly involves children below 2 years of age in Iran, therefore 
infection with L. infantum was expected, but this study is the first 
report of VL that is caused by L. tropica in Iran.








PMID: 16242371
 

TITLE: Infection-induced respiratory burst in BALB/c macrophages kills
Leishmania guyanensis amastigotes through apoptosis: possible involvement in
resistance to cutaneous leishmaniasis.

AUTHORS: Junia Sousa-Franco, Erica Araújo-Mendes, Izaltina Silva-Jardim, Jane
L-Santos, Daniela R Faria, Walderez O Dutra, Maria de Fátima Horta

AFFILIATION: Departamento de Bioquímica e Imunologia, Instituto de Ciências
Biológicas, Universidade Federal de Minas Gerais, C.P. 486, 31270-901 Belo
Horizonte, MG 30161-970, Brazil.

REFERENCE: Microbes Infect 2006 Feb 8(2):390-400

The immune mechanisms that underlie resistance and susceptibility to 
leishmaniasis are not completely understood for all species of 
Leishmania. It is becoming clear that the immune response, the parasite 
elimination by the host and, as a result, the outcome of the disease 
depend both on the host and on the species of the infecting Leishmania. 
Here, we analyzed the outcome of the infection of BALB/c mice with L. 
guyanensis in vivo and in vitro. We showed that BALB/c mice, which are a
 prototype of susceptible host for most species of Leishmania, dying 
from these infections, develop insignificant or no cutaneous lesions and
 eliminate the parasite when infected with promastigotes of L. 
guyanensis. In vitro, we found that thioglycollate-elicited BALB/c 
peritoneal macrophages, which are unable to eliminate L. amazonensis 
without previous activation with cytokines or lipopolysaccharide, can 
kill L. guyanensis amastigotes. This is the first report showing that 
infection of peritoneal macrophages with stationary phase promastigotes 
efficiently triggers innate microbicidal mechanisms that are effective 
in eliminating the amastigotes, without exogenous activation. We 
demonstrated that L. guyanensis amastigotes die inside the macrophages 
through an apoptotic process that is independent of nitric oxide and is 
mediated by reactive oxygen intermediates generated in the host cell 
during infection. This innate killing mechanism of macrophages may 
account for the resistance of BALB/c mice to infection by L. guyanensis.




PMID: 16467337
 

TITLE: Kinetics and diagnostic and prognostic potential of quantitative Western
blot analysis and antigen-specific enzyme-linked immunosorbent assay in
experimental canine leishmaniasis.

AUTHORS: D Talmi-Frank, D Strauss-Ayali, C L Jaffe, G Baneth

AFFILIATION: School of Veterinary Medicine, Hebrew University of Jerusalem, P.O.
Box 12, Rehovot 76100, Israel. baneth at agri.huji.ac.il.

REFERENCE: Clin Vaccine Immunol 2006 Feb 13(2):271-6

Quantitative computerized Western blot analysis of antibody responses 
during experimental canine Leishmania infantum infection distinguished 
between immunodominant and nonimmunodominant protein bands. Six infected
 beagles, positive by both PCR and parasite culture, were monitored over
 75 weeks postinfection and during a 12-week allopurinol treatment 
course. All dogs were symptomatic at the time of treatment. Of 12 
antigenic bands examined, the immunodominant bands (12, 14, 24, 29, 48, 
and 68 kDa) showed significantly increased intensities (P < 0.01) and
 higher frequencies of recognition than the nonimmunodominant bands at 
all time points. Detection of the former bands at 6 weeks postinfection 
preceded seroconversion by enzyme-linked immunosorbent assay (ELISA) 
both on crude Leishmania antigen or the recombinant proteins rK39 and 
HSP70. Reactivity with the 14-, 48-, and 68-kDa bands signified early 
infection, whereas increased reactivity with the 14-, 24-, and 29-kDa 
bands was associated with posttreatment parasite persistence and 
potential unfavorable prognosis. Total lane intensity (TLI) emerged as a
 sensitive marker for early infection and increased as early as 4 weeks 
postinfection. TLI had a significantly higher (P < 0.01) relative 
increase rate than crude Leishmania antigen or HSP70 or rK39 ELISA at 
all time points. These immunodominant antigens and TLI, as determined by
 quantitative Western blotting, will be valuable for early detection and
 treatment evaluation of canine leishmaniasis.




PMID: 16472184
 

TITLE: New formulations and derivatives of amphotericin B for treatment of
leishmaniasis.

AUTHORS: J Golenser, A Domb

AFFILIATION: Departments of 1Parasitology, Faculty of Medicine, The Hebrew
University of Jerusalem, Jerusalem 91120, Israel. golenser at md.huji.ac.il.

REFERENCE: Mini Rev Med Chem 2006 Feb 6(2):153-62

The clinical treatment of leishmaniasis is based on a limited number of 
drugs, which are associated with adverse effects and have already 
induced resistance. Amphotericin B (AmB), a polyene antibiotic produced 
by Streptomyces sp, is the only anti-leishmanial drug which has not 
induced clinical resistance since its discovery in 1956. The limiting 
factor in the use of AmB is its toxic effects, mainly nephrotoxicity. 
The maximal dose of AmB for human use is 1.5 mg/kg which sometimes is 
not sufficient for cure. The mode of action of AmB is associated with 
its toxicity: it selectively binds to parasite membrane ergosterol but 
also, to a lesser extent, to human cholesterol. Apart from this 
mechanism, AmB has immunomodulatory effects, some of them are 
deleterious. Reduction of the toxic effects by using lipid formulations 
allows the infusion of higher doses of AmB. Unfortunately, these 
formulations are relatively expensive and therefore out of reach for 
patients in need, in the endemic areas. All the existing formulations 
are given parenterally, which has obvious disadvantages; most important 
is the need for hospitalization or multiple visits in the clinic. The 
current efforts to improve AmB are directed at the production of AmB 
aggregates in liquid solutions, encapsulation with lipid components, and
 solubilization by binding to soluble polymers. The expected improved 
treatment resulting from use of the new formulations is based on better 
pharmacokinetics, reduced toxicity originating from slow release, 
targeting to the infected organ and an altered pattern of immune 
responses (related to AmB). Of particular importance are the attempts to
 produce derivatives for oral treatment, which will decrease costs of 
hospitalization and improve applicability for children and the elderly 
population.




PMID: 16386855
 

TITLE: The pathogenesis of post kala-azar dermal leishmaniasis from the field to
the molecule: Does ultraviolet light (UVB) radiation play a role?

AUTHORS: A Ismail, E A G Khalil, A M Musa, I M El Hassan, M E Ibrahim, T G
Theander, A M El Hassan

AFFILIATION: Department of Clinical Pathology and Immunology, Faculty of
Medicine, Institute of Endemic Diseases, University of Khartoum, Medical
Sciences Campus, Qasr Street, Khartoum, Sudan.

REFERENCE: Med Hypotheses 2006  66(5):993-9

Post kala-azar dermal leishmaniasis (PKDL) is a dermatosis caused by 
persistence of Leishmania donovani parasites in the skin following 
apparently successful treatment of visceral leishmaniasis. The 
distribution of PKDL lesions in Sudanese patients often mirrors the 
clothing habits of those affected. It is most severe in or confined to 
the sun-exposed parts of the skin. It is well established that 
elimination of Leishmania parasites requires activation of parasitised 
macrophages by a Th1 immune response and that the latter is depressed by
 ultraviolet light (UVB). In this paper, we hypothesized that UVB light 
might be a key player in the pathogenesis of PKDL. This paper links 
observations made in the field with immunological data that are 
compatible with this hypothesis. We therefore investigated patients with
 PKDL immunologically for a possible role of UVB exposure in the 
pathogenesis of this condition. We marshal evidence that the changes in 
the tissues are compatible with the effects of UVB light and it is 
probable that UVB appears to be a key factor in the pathogenesis of PKDL
. Immunopathologically the lesions were characterized by an influx of 
various inflammatory cells. The number of CD1a (Langerhans' cells) was 
decreased, they lost their dendrites, their HLA-DR and B7-1 expression 
was down regulated while B7-2 was expressed. Others have shown that 
Langerhans' cells with these features result from UVB exposure and that 
such cells are unable to present antigen to Th1 cells while retaining 
the capacity to present antigen to Th2 cells. Various cytokines known to
 be induced by UVB radiation could be demonstrated in PKDL lesions. Of 
these IL-10, TGF-beta, IL-12, IL-4 and TNF-alpha were found in different
 quantities. The Th-1 cytokine IFN-gamma was constantly present. The 
tissue origin of the Th-1 cells in PKDL is unknown. We believe that the 
antagonistic action of the different cytokines is the cause of the 
inflammation and chronicity of PKDL.




PMID: 16369039
 

TITLE: Immunization with persistent attenuated Delta lpg2 Leishmania major
parasites requires adjuvant to provide protective immunity in C57BL/6 mice.

AUTHORS: Chahnaz Kébaïer, Jude E Uzonna, Stephen M Beverley, Phillip Scott

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

REFERENCE: Infect Immun 2006 Jan 74(1):777-80

Leishmania major parasites lacking the GDP-mannose transporter, termed 
Deltalpg2 parasites, fail to induce disease in mice but persist long-
term. We previously found that Deltalpg2 organisms protect BALB/c mice 
from virulent L. major challenge. In contrast, we report here that 
Deltalpg2 parasites induce protective immunity in C57BL/6 mice only when
 administered with CpG-containing oligodeoxynucleotides, indicating that
 parasite persistence alone is not sufficient to maintain protective 
immunity to L. major.




PMID: 16460490
 

TITLE: Liver biopsy in the diagnosis of visceral leishmaniasis.

AUTHORS: Reha Artan, Aygen Yilmaz, Mustafa Akçam, Nazif Hikmet Aksoy

AFFILIATION: Departments of Pediatric Gastroenterology, Hepatology and
Nutrition, Akdeniz University School of Medicine, Antalya, Turkey.

REFERENCE: J Gastroenterol Hepatol 2006 Jan 21(1):299-302

Aim: To determine whether liver biopsy might be useful in the diagnosis 
of visceral leishmaniasis when bone marrow examination and serologic 
tests are inconclusive. Methods: Over a 10-year period, liver biopsy was
 performed in five children with suspected visceral leishmaniasis when 
indirect hemagglutination tests and bone marrow aspirations were not 
diagnostic. Results: Leishmania amastigotes were seen in Kupffer cells 
in all patients. The accompanying liver histopathological findings were 
ischemic necrosis in two children, macrovesicular steatosis in two 
children, portal inflammatory inflammation in two children, and 
piecemeal necrosis in one child. During the study period, 32 additional 
pediatric visceral leishmaniasis cases were diagnosed by bone marrow 
examination. Conclusion: Liver biopsy can be recommended for diagnosing 
suspected visceral leishmaniasis in children when serology and bone 
marrow aspiration are inconclusive.




PMID: 16319783
 

TITLE: Characterization of cell cultures derived from Lutzomyia spinicrassa
(Diptera: Psychodidae) and their susceptibility to infection with Leishmania
(Viannia) braziliensis.

AUTHORS: Angela Cristina Zapata Lesmes, Estrella Cárdenas Castro, Felio Bello

AFFILIATION: Entomology, Cell Biology, and Genetics Laboratory, Universidad de
La Salle, Bogotá, Colombia.

REFERENCE: Med Sci Monit 2005 Dec 11(12):BR457-64

BACKGROUND: The sand fly Lutzomyia spinicrassa (Morales, Osorno-Mesa, 
Osorno & de Hoyos, 1969) is a vector of Leishmania (Viannia) 
braziliensis, an etiological agent of cutaneous leishmaniasis in 
Colombia. The present article describes, for the first time, the 
morphological, karyotypical, and isozymatic characteristics of cell 
cultures derived from L. Spinicrassa embryonic tissues as well as the 
interaction of L. Braziliensis with these cell cultures. MATERIAL/
METHODS: L. Spinicrassa embryonated eggs and neonate larvae were taken 
for tissue explants. These were seeded in Grace, L-15, Grace/L-15, MM/
VP12, and MK/VP12 culture media. The pH range in these media was 6.7 to 
6.9 and the cultures were incubated at 28 degrees C. The MHOM/CO/86/
CL250 strain of L. Braziliensis was used for experimental infection of 
cell cultures of L. Spinicrassa. RESULTS: Cell growth was achieved in L-
15 medium and a confluent monolayer was obtained 180 days after the 
embryonated eggs were explanted. The cell morphology of the primary cell
 cultures was initially heterogeneous, but in the confluent monolayer of
 these cell cultures and in the subcultures the predominant cell types 
were later fibroblast-like and epithelial-like. Cultured cells were 
predominantly diploid (2n=8); however, significant percentages of 
aneuploids were also recorded. The cell culture isozyme patterns of L. 
Spinicrassa coincided with pupae samples from the same species. 
Promastigote forms of L. Braziliensis could invade cells and transform 
into amastigote-like forms inside them. CONCLUSIONS: The characteristics
 of cell cultures derived from L. Spinicrassa embryonic tissues were 
determined. These cultures emerge as a new model to study the life-cycle
 of L. Braziliensis.




PMID: 16465730
 

TITLE: Lutzomyia longipalpis peritrophic matrix: formation, structure, and
chemical composition.

AUTHORS: N F C Secundino, I Eger-Mangrich, E M Braga, M M Santoro, P F P
Pimenta

AFFILIATION: Laboratory of Medical Entomology Centro de Pesquisas René Rachou,
Fundação Oswaldo Cruz, Minas Gerais, Brazil.

REFERENCE: J Med Entomol 2005 Nov 42(6):928-38

Sandflies are vectors of several pathogens, constituting serious health 
problems. Lutzomyia longipalpis (Lutz & Neiva, 1912) is the main 
vector of Leishmania chagasi, agent of visceral leishmaniasis. They 
synthesize a thick bag-like structure that surrounds the bloodmeal, 
named peritrophic matrix (PM). One of the major roles of PM in blood-fed
 insects includes protection against ingested pathogens by providing a 
defensive barrier to their development. We used traditional and modern 
morphological methods as well as biochemical and immunolabeling tools to
 define details of the PM structure of the Lu. longipalpis sandfly, 
including composition, synthesis, and degradation. The kinetics of PM 
formation and degradation was found to be related to the ingestion and 
time of digestion of the bloodmeal. The midgut changes its size and 
morphology after the blood ingestion and during the course of digestion
. A striking morphological modification takes place in the midgut 
epithelium after the stretching caused by the bloodmeal, revealing a 
population of cells that was not observed in the unfed midgut. The 
transmission and scanning electron microscopies were used to reveal 
several morphological aspects of PM formation. The PM looks thicker and 
well formed 24 h after the bloodmeal. Presence of chitin in the PM was 
demonstrated by immunolabeling with an alpha-chitin monoclonal antibody
. SDS-polyacrylamide gel electrophoresis showed at least five protein 
bands with molecular masses of 38.7-135 kDa, induced by the protein-free
 diet. Mouse polyclonal antiserum was produced against PMs induced by 
protein-free meal and used in Western blotting, which revealed at least 
three associated proteins.




PMID: 16465739
 

TITLE: Nocturnal activity rhythms of Lutzomyia intermedia and Lutzomyia whitmani
(Diptera: Psychodidae) in a transmission area of American cutaneous
leishmaniasis in Rio de Janeiro State, Brazil.

AUTHORS: Nataly A Souza, Cláudia A Andrade-Coelho, Alexandre A Peixoto,
Elizabeth F Rangel

AFFILIATION: Departments of Entomology and Biochemistry and Molecular Biology,
Instituto Oswaldo Cruz, FIOCRUZ, Manguinhos, Rio de Janeiro, Brazil.

REFERENCE: J Med Entomol 2005 Nov 42(6):986-92

The phlebotomine sand flies Lutzomyia (Nyssomyia) intermedia (Lutz &amp
; Neiva) and Lutzomyia (Nyssomyia) whitmani (Coutinho & Antunes) are
 important vectors of Leishmania (Vianna) braziliensis, the etiological 
agent of American cutaneous leishmaniasis. In some areas, both species 
occur in sympatry, and their relative roles as vectors in these areas 
are not clear. We studied the nocturnal activity and biting rhythms of 
both species in Posse, a locality in Rio de Janeiro State, Brazil. Our 
results show differences between the activity patterns of Lu. intermedia
 and Lu. whitmani that might be epidemiologically important. Although 
the activity profiles vary between seasons and microhabitats (
peridomestic versus forest), the two species show marked differences in 
their tendencies to bite humans in the early morning (0400-0600 hours), 
with Lu. whitmani showing higher feeding rates than Lu. intermedia.








PMID: 16465797
 

TITLE: [Medecine and health in the Tropics. Leishmaniasis]

AUTHORS: E Philippon, C Gramond, C Chouc

REFERENCE: Med Trop (Mars) 2005 Nov 65(5):419-20




PMID: 16465821
 

TITLE: [Management of cutaneous leishmaniasis in adults and children]

AUTHORS: P Minodier, G Noël, P Blanc, M Uters, K Retornaz, J M Garnier

AFFILIATION: Unite des urgences pédiatriques, CHU Nord, Chemin des Bourrely,
13915 Marseille, France. philippe.minodier at ap-hm.fr

REFERENCE: Med Trop (Mars) 2005 Nov 65(5):487-95

Cutaneous leishmaniasis can present a variety of clinical features and 
courses. The causative Leishmania species is an important prognostic 
factor in immunocompetent patients. Local treatment modalities including
 topical paromomycin, cryotherapy, localized controlled heat, carbon 
dioxide laser therapy, or intralesional meglumine antimoniate can be 
effective against Leishmania major or Leishmania tropica. Oral 
fluconazole may be a second-line treatment. Parenteral antimonials are 
useful for persistent or recurrent Old World leishmaniasis. For New 
World leishmaniasis, parenteral antimonials represent the first-line 
treatment in all forms except those caused by Leishmania guyanensis in 
which pentamidine is preferable. Liposomal amphotericin B appears to be 
effective for treatment of cutaneous leishmaniasis but further study 
will be needed. Results using oral Miltefosine are promising against 
Indian kala-azar (Leishmania donovani) but disappointing against South 
American leishmaniasis.




PMID: 16209934
 

TITLE: Serological screening for Leishmania infantum in asymptomatic blood
donors living in an endemic area (Sicily, Italy).

AUTHORS: Claudia Colomba, Laura Saporito, Valentina Frasca Polara, Teresa
Barone, Antonino Corrao, Lucina Titone

AFFILIATION: Istituto di Patologia Infettiva e Virologia, Università di
Palermo, piazza Montalto 8, 90134 Palermo, Italy. claudia.colomba at libero.it

REFERENCE: Transfus Apher Sci 2005 Nov 33(3):311-4

The purpose of our study was to assess whether Leishmania infantum 
parasitemia occurs in asymptomatic Leishmania-seropositive subjects. 
Samples from 500 blood donors were tested using an enzyme-linked 
immunosorbent assay (ELISA). Anti-Leishmania antibodies were not found 
in any sample. Our findings suggest that the risk of L. infantum 
transmission by blood transfusion in Sicily is very low.




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PMID: 14742526
 

TITLE: Myd88-dependent in vivo maturation of splenic dendritic cells induced by
Leishmania donovani and other Leishmania species.

AUTHORS: Carl De Trez, Maryse Brait, Oberdan Leo, Tony Aebischer, Fabiola
Aguilar Torrentera, Yves Carlier, Eric Muraille

AFFILIATION: Laboratory of Animal Physiology, Institut de Biologie et de
Médecine Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium.

REFERENCE: Infect Immun 2004 Feb 72(2):824-32

The usual agent of visceral leishmaniasis in the Old World is Leishmania
 donovani, which typically produces systemic diseases in humans and mice
. L. donovani has developed efficient strategies to infect and persist 
in macrophages from spleen and liver. Dendritic cells (DC) are sentinels
 of the immune system. Following recognition of evolutionary conserved 
microbial products, DC undergo a maturation process and activate antigen
-specific naïve T cells. In the present report we provide new insights 
into how DC detect Leishmania in vivo. We demonstrate that in both C57BL
/6 and BALB/c mice, systemic injection of L. donovani induced the 
migration of splenic DC from marginal zones to T-cell areas. During 
migration, DC upregulated the expression of major histocompatibility 
complex II and costimulatory receptors (such as CD40, CD80, and CD86). 
Leishmania-induced maturation requires live parasites and is not 
restricted to L. donovani, as L. braziliensis, L. major, and L. mexicana
 induced a similar process. Using a green fluorescent protein-expressing
 parasite, we demonstrate that DC undergoing maturation in vivo display 
no parasite internalization. We also show that L. donovani-induced DC 
maturation was partially abolished in MyD88-deficient mice. Taken 
together, our data suggest that Leishmania-induced DC maturation results
 from direct recognition of Leishmania by DC, and not from DC infection
, and that MyD88-dependent receptors are implicated in this process.




PMID: 14638820
 

TITLE: High levels of susceptibility and T helper 2 response in MyD88-deficient
mice infected with Leishmania major are interleukin-4 dependent.

AUTHORS: Andrea Debus, Joachim Gläsner, Martin Röllinghoff, André Gessner

AFFILIATION: Institut für Klinische Mikrobiologie, Immunologie und Hygiene der
Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

REFERENCE: Infect Immun 2003 Dec 71(12):7215-8

Myeloid differentiation protein 88 (MyD88) is a general adaptor for the 
signaling cascade through receptors of the Toll/IL-1R family. When 
infected with Leishmania major parasites, MyD88-deficient mice displayed
 a dramatically enhanced parasite burden in their tissues similar to 
that found in susceptible BALB/c mice. In contrast, MyD88 knockout mice 
did not develop ulcerating lesions despite a lack of interleukin-12 (IL-
12) production and a predominant T helper 2 cell response. Blockade of 
IL-4 produced early (day 1) after infection restored a protective T 
helper 1 response in MyD88 knockout mice.




PMID: 14515266
 

TITLE: MyD88 is essential for clearance of Leishmania major: possible role for
lipophosphoglycan and Toll-like receptor 2 signaling.

AUTHORS: Michael J de Veer, Joan M Curtis, Tracey M Baldwin, Joseph A DiDonato,
Adrienne Sexton, Malcolm J McConville, Emanuela Handman, Louis Schofield

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

REFERENCE: Eur J Immunol 2003 Oct 33(10):2822-31

Leishmania major is an obligate intracellular eukaryotic pathogen of 
mononuclear phagocytes. Invasive promastigotes gain entry into target 
cells by receptor-mediated phagocytosis, transform into non-motile 
amastigotes and establish in the phagolysosome. 
Glycosylphosphatidylinositol-anchored lipophosphoglycan (LPG) is a 
virulence factor and a major parasite molecule involved in this process
. We observed that mice lacking the Toll-like receptor (TLR) pathway 
adaptor protein MyD88 were more susceptible to infection with L. major 
than wild-type C57BL/6 mice, demonstrating a central role for this 
innate immune recognition pathway in control of infection, and 
suggesting that L. major possesses a ligand for TLR. We sought to 
identify parasite molecules capable of activating the protective Toll 
pathway, and found that purified Leishmania LPG, but not other surface 
glycolipids, activate innate immune signaling pathways via TLR2. 
Activation of cytokine synthesis by LPG required the presence of the 
lipid anchor and a functional MyD88 adaptor protein. LPG also induced 
the expression of negative regulatory pathways mediated by members of 
thesuppressors of cytokine signaling family SOCS-1 and SOCS-3. Thus, the
 Toll pathway is required for resistance to L. major and LPG is a 
defined TLR agonist from this important human pathogen.




PMID: 12682257
 

TITLE: Genetically resistant mice lacking MyD88-adapter protein display a high
susceptibility to Leishmania major infection associated with a polarized Th2
response.

AUTHORS: Eric Muraille, Carl De Trez, Maryse Brait, Patrick De Baetselier,
Oberdan Leo, Yves Carlier

AFFILIATION: Laboratory of Parasitology, Université Libre de Bruxelles, Erasme,
Belgium.

REFERENCE: J Immunol 2003 Apr 170(8):4237-41

Host resistance to the intracellular protozoan Leishmania major is 
highly dependent on IL-12 production by APCs. Genetically resistant 
C57BL/6 mice develop IL-12-mediated Th1 immune response dominated by IFN
-gamma and exhibit only small cutaneous lesions that resolve 
spontaneously. In contrast, because of several genetic differences, BALB
/c mice develop an IL-4-mediated Th2 immune response and a chronic 
mutilating disease. Myeloid differentiation marker 88 (MyD88) is an 
adaptator protein that links the IL-1/Toll-like receptor family to IL-1R
-associated protein kinase. Toll-like receptors recognize pathogen 
associated molecular patterns and are crucially implicated in the 
induction of IL-12 secretion by APC. The role of MyD88 protein in the 
development of protective immune response against parasites is largely 
unknown. Following inoculation of L. major, MyD88(-/-) C57BL/6 mice 
presented large footpad lesions containing numerous infected cells and 
frequent mutilations. In response to soluble Leishmania Ag, cells from 
lesion-draining lymph node showed a typical Th2 profile, similar to 
infected BALB/c mice. IL-12p40 plasma level collapses in infected MyD88
(-/-) mice compared with infected wild-type C57BL/6 mice. Importantly, 
administration of exogenous IL-12 rescues L. major-infected MyD88(-/-) 
mice, demonstrating that the susceptibility of these mice is a direct 
consequence of IL-12 deficiency. In conclusion, MyD88-dependent pathways
 appear essential for the development of the protective IL-12-mediated 
Th1 response against the Leishmania major parasite. In absence of MyD88 
protein, infected mice develop a nonprotective Th2 response.




PMID: 7601889
 

TITLE: Case in point. Cutaneous leishmaniasis.

AUTHORS: J J Olivero

AFFILIATION: Department of Internal Medicine, Baylor College of Medicine,
Houston, USA.

REFERENCE: Hosp Pract (Minneap) 1995 Jul 30(7):16




PMID: 3242280
 

TITLE: [Cutaneous leishmaniasis in the light of personal observations with
regard to its diagnosis and treatment in tropical countries]

AUTHORS: A Kotłowski

REFERENCE: Wiad Parazytol 1988  34(4-6):509-14




PMID: 3242300
 

TITLE: [Cutaneous leishmaniasis among the cases of the Institute of Infectious
and Parasitic Diseases, Medical Academy, in Warsaw]

AUTHORS: Z Dziubek, A Horban, H Zarnowska, J Powałowska, M Baka, M Olszyńska

REFERENCE: Wiad Parazytol 1988  34(4-6):663-4








PMID: 3687006
 

TITLE: [Genetic control of the host's immune processes in parasitic diseases]

AUTHORS: E Siński, J Behnke

REFERENCE: Wiad Parazytol 1987  33(2):133-46




PMID: 6806987
 

TITLE: [Serological diagnosis of amebiasis and diagnosis of exotic protozoan
infection]

AUTHORS: P Myjak

REFERENCE: Wiad Parazytol 1980  26(4-5):399-406




REQUEST: [ leishmania ]

(32 articles match this request. 14 articles matching other requests removed)



PMID: 16467468
 

TITLE: Retention and loss of amino Acid biosynthetic pathways based on analysis
of whole-genome sequences.

AUTHORS: Samuel H Payne, William F Loomis

AFFILIATION: Bioinformatics Program, Division of Biological Sciences, University
of California San Diego, MC 0368, 9500 Gilman Dr., La Jolla, CA 92093.
spayne at ucsd.edu.

REFERENCE: Eukaryot Cell 2006 Feb 5(2):272-6

Plants and fungi can synthesize each of the 20 amino acids by using 
biosynthetic pathways inherited from their bacterial ancestors. However
, the ability to synthesize nine amino acids (Phe, Trp, Ile, Leu, Val, 
Lys, His, Thr, and Met) was lost in a wide variety of eukaryotes that 
evolved the ability to feed on other organisms. Since the biosynthetic 
pathways and their respective enzymes are well characterized, orthologs 
can be recognized in whole genomes to understand when in evolution 
pathways were lost. The pattern of pathway loss and retention was 
analyzed in the complete genomes of three early-diverging protist 
parasites, the amoeba Dictyostelium, and six animals. The nine pathways 
were lost independently in animals, Dictyostelium, Leishmania, 
Plasmodium, and Cryptosporidium. Seven additional pathways appear to 
have been lost in one or another parasite, demonstrating that they are 
dispensable in a nutrition-rich environment. Our predictions of pathways
 retained and pathways lost based on computational analyses of whole 
genomes are validated by minimal-medium studies with mammals, fish, 
worms, and Dictyostelium. The apparent selective advantages of retaining
 biosynthetic capabilities for amino acids available in the diet are 
considered.




PMID: 16369915
 

TITLE: RNA interference reveals a role for TLR2 and TLR3 in the recognition of
Leishmania donovani promastigotes by interferon-gamma-primed macrophages.

AUTHORS: Jean-Frédéric Flandin, Frédéric Chano, Albert Descoteaux

AFFILIATION: INRS- Institut Armand-Frappier and Centre for host-parasite
interactions, Laval QC, Canada.

REFERENCE: Eur J Immunol 2006 Feb 36(2):411-20

Leishmania donovani promastigotes evade the induction of a 
proinflammatory response during their invasion of naive macrophages. 
However, their entry into IFN-gamma-primed macrophages is accompanied by
 the secretion of nitric oxide (NO) and proinflammatory cytokines. In 
the present study, we addressed the hypothesis that priming with IFN-
gamma induces the expression of a receptor that enables mouse 
macrophages to recognize L. donovani promastigotes. We observed that in 
IFN-gamma-primed macrophages, L. donovani promastigotes stimulated 
Interleukin-1 receptor-associated kinase-1 (IRAK-1) activity. We next 
showed that Toll-like receptor (TLR)3 is barely detectable in naive 
macrophages but is expressed in IFN-gamma-treated macrophages. Silencing
 of TLR3, TLR2, IRAK-1 and myeloid differentiation factor 88 (MyD88) 
expression by RNA interference revealed that both TLR are involved in 
the secretion of NO and TNF-alpha induced by L. donovani promastigotes. 
Using L. donovani mutants, we showed that TLR2-mediated responses are 
dependent on Galbeta1,4Manalpha-PO(4)-containing phosphoglycans, whereas
 TLR3-mediated responses are independent of these glycoconjugates. 
Furthermore, our data indicate a participation of TLR2 and TLR3 in the 
phagocytosis of L. donovani promastigotes and a role for TLR3 in the 
leishmanicidal activity of the IFN-gamma-primed macrophages. 
Collectively, our data are consistent with a model where recognition of 
L. donovani promastigotes depends on the macrophage activation status 
and requires the expression of TLR3.




PMID: 16316982
 

TITLE: Distinct Genes Encode Type II Topoisomerases for the Nucleus and
Mitochondrion in the Protozoan Parasite Trypanosoma brucei.

AUTHORS: Tomasz Kulikowicz, Theresa A Shapiro

AFFILIATION: Division of Clinical Pharmacology, Departments of Medicine and of
Pharmacology and Molecular Sciences, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21205.

REFERENCE: J Biol Chem 2006 Feb 281(6):3048-56

Topoisomerases are essential for orderly nucleic acid metabolism and 
cell survival and are proven targets for clinically useful antimicrobial
 and anticancer drugs. Interest in the topologically intricate 
mitochondrial DNA (kinetoplast or kDNA) of Trypanosoma brucei brucei and
 related kinetoplastid protozoan parasites has led to many reports of 
type II topoisomerases that participate in kDNA metabolism (we term the 
T. brucei brucei gene TbTOP2mt). We have now identified and 
characterized two new genes for type II topoisomerases in T. brucei 
brucei, termed TbTOP2alpha and TbTOP2beta. Phylogenetically, they share 
a common node with other nuclear topoisomerases, clearly distinct from a
 clade that includes the previously reported kinetoplastid genes, all of
 which are homologs of TbTOP2mt. Southern blot analysis reveals the new 
genes are single copy and positioned approximately 1.7 kb apart. Cognate
 mRNAs are expressed in African trypanosomes, but only a single message 
is detected in Leishmania or Crithidia. TbTOP2alpha encodes an ATP-
dependent topoisomerase that appears as a single approximately 170-kDa 
band on immunoblots and localizes to the nucleus; RNA interference leads
 to pleomorphic nuclear (but not kDNA) abnormalities and early growth 
arrest. The role of TbTOP2beta is unclear. Although transcribed in 
trypanosomes, TbTOP2beta is not detected by beta-specific antiserum, and
 RNAi silencing results in no obvious phenotype. These studies indicate 
that African trypanosomes and related kinetoplastid human pathogens are 
unusual in having independent topoisomerase II genes to service their 
nuclear and mitochondrial genomes, and they highlight TbTOP2alpha as a 
promising target for the development of much-needed new therapies.




PMID: 16239118
 

TITLE: NKT cells mediate organ-specific resistance against Leishmania major
infection.

AUTHORS: Jochen Mattner, Norbert Donhauser, Gabriele Werner-Felmayer, Christian
Bogdan

AFFILIATION: Institute of Clinical Microbiology, Immunology and Hygiene,
University of Erlangen-Nuremberg, Germany; University of Chicago, Department of
Pathology, USA.

REFERENCE: Microbes Infect 2006 Feb 8(2):354-62

Whereas the acquired T cell-mediated protection against intracellular 
pathogens such as Leishmania major has been well studied in the past, 
the cells and mechanisms involved in their innate control are still 
poorly understood. Here, we investigated the role of natural killer T (
NKT) cells in a high dose L. major mouse infection model. In vitro, L. 
major only weakly stimulated NKT cells and antagonized their response to
 the prototypic NKT cell ligand alpha-galactosylceramide, indicating 
that L. major partially escapes the activation of NKT cells. NKT cell 
deficiency as analyzed by subcutaneous infection of Jalpha281(-/-) mice
 (lacking invariant CD1d-restricted NKT cells) and CD1(-/-) mice (
lacking all CD1d-restricted NKT cells) led to a transient increase in 
skin lesions, but did not impair the clinical cure of the infection, NK 
cell cytotoxicity, the production of IFN-gamma, the expression of 
inducible nitric oxide synthase, and the control of the parasites in the
 lymph node. In the spleen, however, NKT cells were required for NK cell
 cytotoxicity and early IFN-gamma production, they lowered the parasite 
burden, and exerted bystander effects on Leishmania antigen-specific T 
cell responses, most notably after systemic infection. Thus, NKT cells 
fulfill organ-specific protective functions during infection with L. 
major, but are not essential for parasite control.




PMID: 16368097
 

TITLE: Characterization of LST-R533: Uncovering a novel repetitive element in
Leishmania.

AUTHORS: André L Pedrosa, Andrea M Silva, Jeronimo C Ruiz, Angela K Cruz

AFFILIATION: Departamento de Ciências Biológicas, Universidade Federal do
Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

REFERENCE: Int J Parasitol 2006 Feb 36(2):211-7

We have previously isolated and sequenced a novel repetitive element, 
now named LST-R533, which is present in four different regions of one 
extremity of Leishmania major chromosome 20. The repeats are polymorphic
 in size, ranging from 367 to 533bp and contain an internal 81bp 
sequence with highly conserved segments (14-81bp long) dispersed 
throughout the parasite's genome. These sequences were not found in 
coding regions of any predicted gene in L. major Friedlin genome, but 
are part of untranslated regions of some Leishmania transcripts. 
Analysis of the 81bp sequence revealed significant degrees of identity 
with retrotransposons described in several other organisms. The presence
 of the sequence in other species from genus Leishmania was determined 
by Southern hybridisation and DNA sequencing. This analysis indicated 
the conservation of the 81-nucleotide element in all the Leishmania 
species evaluated. No sequences corresponding to LST-R533 or the 81bp 
element were found on either Trypanosoma brucei or Trypanosoma cruzi 
databanks.




PMID: 16307745
 

TITLE: Microsatellite analysis reveals genetic structure of Leishmania tropica.

AUTHORS: Jan M Schwenkenbecher, Thierry Wirth, Lionel F Schnur, Charles L Jaffe,
Henk Schallig, Amer Al-Jawabreh, Omar Hamarsheh, Kifaya Azmi, Francine Pratlong,
Gabriele Schönian

AFFILIATION: Institute of Microbiology and Hygiene, Humboldt University,
Charité Campus Mitte, Dorotheenstr. 96, D-10117 Berlin, Germany.

REFERENCE: Int J Parasitol 2006 Feb 36(2):237-46

The current rapid spread of leishmaniases caused by Leishmania tropica 
and the complexity of its clinical spectrum call for this parasite's 
epidemiological and evolutionary investigation. Evaluation of its 
population structure by isoenzyme electrophoresis and previous molecular
 biological analysis has proved difficult. In this study, we used 21 
microsatellite loci to type 117 strains from different African and Asian
 locations. Eighty-one different genotypes were found. A genetic 
bottleneck supported by a gradient in the number of alleles and 
consistent with the geographical structure of the Middle East suggests 
an African origin of this species. A Bayesian approach identified 10 
genetic clusters that correlated predominantly with geographical origin
. The strains in the 'Asia' cluster form a very heterogeneous sub-
population, with a varied but inter-related genotype that is 
geographically very widely dispersed and consistent with anthroponotic 
transmission of the parasite. The other nine clusters were more 
homogenous. The propagation of L. tropica appears to be predominantly 
clonal. In Africa and the Middle East, anthroponotic and zoonotic 
systems of distribution may contribute to the development of overlapping
, genetically distinct populations of L. tropica.




PMID: 16472181
 

TITLE: Functional cloning as a means to identify leishmania genes involved in
drug resistance.

AUTHORS: Joachim Clos, Kohelia Choudhury

AFFILIATION: Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht
Street 74, D-20359 Hamburg, FRG, Germany. clos at bni-hamburg.de.

REFERENCE: Mini Rev Med Chem 2006 Feb 6(2):123-9

Resistance to anti-leishmanial drugs is a mounting problem in high-
endemicity regions of South Asia and, potentially, in the context of HIV
-Leishmania coinfections in Southern Europe. The molecular basis for 
clinical drug resistance is still largely unknown. It is important, 
however, to identify all relevant drug resistance markers for further 
drug development and for epidemiological surveys. An elegant and 
powerful method to identify such drug resistance markers without bias is
 functional cloning, using cosmid-based genomic DNA libraries. This 
review discusses the merits and caveats of this approach.




PMID: 16369458
 

TITLE: Macrophage may responses to androgen via its receptor.

AUTHORS: Kazem Ahmadi, Alan B McCruden

AFFILIATION: Department of Immunology, Faculty of Medicine and Research Centre
of Molecular Biology, Baqiyatallah Medical Science University, Tehran, I.R.
Iran. K.ahmadi at bmsu.ac.ir

REFERENCE: Med Sci Monit 2006 Jan 12(1):BR15-20

BACKGROUND: Sex hormones have profound effects on immune responses and 
may influence the disease which caused by intracellular parasite(
Leishmania) and bacterial (tuberculosis)and also autoimmune disease such
 as rheumatoid arthritis (RA). It has also been demonstrated that 5alpha
-Dihydrotestosterone (5alpha-DHT) modulate nitric oxide and cytokine 
release by macrophages. These effects seem to be exerted by specific 
receptors for androgen in macrophages. MATERIAL/METHODS: Protein 
secretion: The effect of 5alpha-DHT on protein secretion by peritoneal 
macrophages of NZB\BALBc mice was investigated using radiolabelled 
protein secretion following SDS-PAGE and Fluorography. Binding assay: 
Androgen binding was also investigated using an autoradiography method. 
Peritoneal macrophages were treated with [3H]- 5alpha-DHT and incubated 
for 2 h before smearing on to microscope slides. Slides were air dried, 
dipped in Kodak NTB photographic emulsion, sealed in light proof boxes 
and left at 4 degrees C for 6 weeks. RESULTS: The results showed that 
protein secretion by macrophages changed under 5alpha-DHT treatment. 
Analysis of the data according to quantitation of [(3)H]-5alphaDHT 
binding receptors in fixed-slide mounted cells, identified a high 
specific androgen binding at physiological concentration. The receptors 
had a relatively high affinity for the 5alpha-DHT, So that binding 
affinity was not inhibited in the presence of 100-fold excess of non 
labelled 17-beta Estradiol. CONCLUSIONS: These results suggest that the 
immunosuppressive action exerted by androgen is at least partially 
achieved through a direct influence on macrophages.








PMID: 16451193
 

TITLE: Insights into the role of gp63-like proteins in lower trypanosomatids.

AUTHORS: Claudia Masini d'Avila-Levy, Felipe de Almeida Dias, Ana Cristina
Nogueira de Melo, Juliana Lopes Martins, Angela Hampshire De Carvalho Santos
Lopes, André Luis Souza Dos Santos, Alane Beatriz Vermelho, Marta Helena
Branquinha

AFFILIATION: Departamento de Microbiologia Geral, Instituto de Microbiologia
Prof. Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do
Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

REFERENCE: FEMS Microbiol Lett 2006 Jan 254(1):149-56

Any actual understanding of trypanosomatids in general requires a 
comprehensive analysis of the less-specialized species as thorough as 
our knowledge of the more specialized Leishmania and Trypanosoma. In 
this context, we have shown by antibody cross-reactivity that purified 
extracellular metallopeptidases from Phytomonas françai, Crithidia 
deanei (cured strain) and Crithidia guilhermei share common epitopes 
with the leishmanial gp63. Flow cytometry and fluorescence microscopy 
analyses indicated the presence of gp63-like molecules on the cell 
surface of these lower trypanosomatids. Binding assays with explanted 
guts of Aedes aegypti incubated with purified gp63 and the pretreatment 
of trypanosomatids with anti-gp63 antibodies indicated that the gp63-
like molecules are involved in the adhesive process of these 
trypanosomatids to the A. aegypti gut wall. In addition, our results 
indicate for the first time that the gp63-like molecule binds to a 
polypeptide of 50 kDa on the A. aegypti gut epithelium extract.




PMID: 16369038
 

TITLE: Adoptive immunotherapy against experimental visceral leishmaniasis with
CD8+ T cells requires the presence of cognate antigen.

AUTHORS: Rosalind Polley, Simona Stager, Sara Prickett, Asher Maroof, Soombul
Zubairi, Deborah F Smith, Paul M Kaye

AFFILIATION: Immunology and Infection Unit, Dept. of Biology, University of
York, P.O. Box 373, York YO10 5YW, United Kingdom.

REFERENCE: Infect Immun 2006 Jan 74(1):773-6

CD8+ T cells have a protective role in experimental visceral 
leishmaniasis. However, the observation that inflammatory cytokines 
induce bystander activation of CD8+ T cells questions the need for 
antigen-dependent effector function. Here, we demonstrate that 
successful adoptive immunotherapy with CD8+ T cells is strictly 
dependent upon the presence of cognate antigen.




PMID: 16472522
 

TITLE: A serological study of exposure to arthropod-borne pathogens in dogs from
northeastern Spain.

AUTHORS: Laia Solano-Gallego, Joan Llull, Montsant Osso, Barbara Hegarty, Edward
Breitschwerdt

AFFILIATION: Department of Clinical Sciences, College of Veterinary Medicine,
North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606,
North Carolina, USA.

REFERENCE: Vet Res 2006 Mar-Apr 37(2):231-44

There is limited information regarding the prevalence of many vector 
borne pathogens in Europe and especially in Spanish dogs. We 
investigated 206 sick and 260 clinically healthy dogs from three 
different regions in northeastern Spain for antibodies to Rickettsia 
conorii (Rc), Ehrlichia canis (Ec), Anaplasma phagocytophilum (Ap), 
Bartonella henselae (Bh), Bartonella vinsonii subsp. berkhoffii (Bvb), 
Leishmania infantum (Li) and Borrelia burgdorferi (Bb) and for antigen 
of Dirofilaria immitis (Di). Total prevalences were the following: Rc (
56.4%), Li (30%), Ec (16.7%), Bh (16.8%), Ap (11.5%), Bvb (1.07%), Di (0
.6%) and Bb (0.6%). Seroprevalences for Rc, Ec, Ap, Bh, and Bvb and Bb 
and Di antigens were similar among the three different study sites. The 
Ec seroprevalence, as determined by Snap 3DX, was statistically lower in
 dogs from Mallorca (0%) than Tarragona (16%) and Barcelona (5%) (P &lt
; 0.0001). Detection of Rc antibodies was associated with seroreactivity
 to Ec and Ap antigens (P = 0.018 and P = 0.002, respectively). IFA Ec 
antibodies were associated with Ap seroreactivity (P < 0.0001). There
 was no association between the clinical status, sex, time of the year 
when samples were collected, life-style or exposure to fleas or ticks 
and a positive test result for Ec, Bh, Bvb, or Bb antibodies or Di 
antigens. Li seroreactivity was associated with illness and living 
outdoors (P < 0.0001, P = 0.029; respectively), Rc seroreactivity 
with the male gender (P = 0.028) and Ap seroreactivity with living 
outdoors (P = 0.045). This study indicates that exposure to Rc, Li, Ec 
or related Ehrlichia spp., Bh and Ap or a related spp., is common 
whereas Di, Bb and Bvb is uncommon among dogs from the Mediterranean 
basin. We also provide serological data that suggests the existence of a
 novel Ehrlichia species on Mallorca island.




PMID: 16244984
 

TITLE: Feline leishmaniasis and ehrlichiosis: serological investigation in
Abruzzo region.

AUTHORS: S Vita, D Santori, I Aguzzi, E Petrotta, A Luciani

AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Università degli
Studi di Teramo, Viale Crispi 212, I-64100, Teramo, Italy. boari at unite.it

REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():319-21




PMID: 16244972
 

TITLE: Pancreatitis associated with N-methyl-glucamine therapy in a dog with
leishmaniasis.

AUTHORS: G Aste, M Di Tommaso, J M Steiner, D A Williams, A Boari

AFFILIATION: Department of Veterinary Clinical Sciences, Section of Internal
Medicine, Faculty of Veterinary Medicine, University of Teramo, 64100, Teramo,
Italy. gaste at unite.it

REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():269-72




PMID: 16244980
 

TITLE: Real-time PCR in dogs treated for leishmaniasis with allopurinol.

AUTHORS: M G Pennisi, S Reale, S Lo Giudice, M Masucci, S Caracappa, M Vitale, F
Vitale

AFFILIATION: Department of Veterinary Medical Science, Faculty of Veterinary
Medicine, University of Messina, Polo Universitario dell'Annunziata, 98168,
Messina, Italy. MariaGrazia.Pennisi at unime.it

REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():301-3




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

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PMID: 12270723
 

TITLE: Leishmania major activates IL-1 alpha expression in macrophages through a
MyD88-dependent pathway.

AUTHORS: Thomas R Hawn, Adrian Ozinsky, David M Underhill, Frederick S Buckner,
Shizuo Akira, Alan Aderem

AFFILIATION: Division of Infectious Diseases, Department of Medicine, University
of Washington, Seattle, WA 98195, USA.

REFERENCE: Microbes Infect 2002 Jul 4(8):763-71

Leishmania species present unusual challenges to the immune system with 
their capacity to downregulate inflammatory responses as well as their 
ability to live within macrophages. Although toll-like receptor (TLR) 
pathways have been implicated in the recognition of several classes of 
pro-inflammatory microbes, it is not known if pathogens with anti-
inflammatory properties activate the host response through this family 
of proteins. In this study, Leishmania major stimulation of cytokine 
promoter-luciferase reporter constructs was examined in transfected 
macrophages to detect early signs of cellular activation. L. major 
selectively activated the promoter region of IL-1 alpha, but not IL-6, 
IL-8, IL-10, or an NF-kappa B reporter. IL-1 alpha mRNA expression was 
also stimulated by L. major, although at lower levels than 
lipopolysacharide-stimulated macrophages. No IL-1 alpha protein was 
detectable in stimulated cell lysates or culture supernatants. 
Transfection of macrophages with a dominant-negative version of myeloid 
differentiation factor 88 (MyD88), an adaptor protein which interacts 
with TLRs, inhibited activation of the IL-1 alpha promoter. Furthermore
, stimulation of IL-1 alpha RNA expression by L. major was inhibited in 
peritoneal macrophages from MyD88-/- as compared to MyD88+/+ mice. These
 observations indicate that L. major stimulates IL-1 alpha promoter 
activity and mRNA expression in macrophages through MyD88-dependent 
pathways. However, additional anti-inflammatory pathways must also be 
activated which downregulate transcription and ultimately inhibit 
translation of the IL-1 alpha protein. Examination of promoter 
activation is a powerful tool for understanding the early events in 
macrophage activation for anti-inflammatory pathogens such as Leishmania
 that have mechanisms to downregulate transcription and translation.




PMID: 7638963
 

TITLE: [Contemporary strategies and methods of modeling antiparasitic drugs]

AUTHORS: K Boczoń

AFFILIATION: Katedra i Zakład Biologii i Parazytologii Lekarskiej AM, Poznań.

REFERENCE: Wiad Parazytol 1995  41(1):43-52

Contemporary methods of directed chemotherapy are based on multi-step 
procedures, which require co-ordinated activities of interdisciplinary 
teams of biochemists, pharmacologists, geneticists, crystallographers as
 well as computer scientists. Biochemists select the proper target, such
 as an enzyme, throughout screening of the biochemical influence of 
compounds-potential drugs on this target. For further research they use 
targets with very low inhibition constants (> 10(-6) M). Determination 
of the relation between therapeutic activity of the compound and 
modelling of its chemical structure constitutes an important part of the
 procedure. The most important part of the procedure is the recognition 
of the primary structure of the target. The two following pathways allow
 to do that: 1. isolation of DNA and gDNA or cDNA-started cloning of a 
gene responsible for production of the target protein and then its 
sequencing. 2. purification and crystallization of the target protein 
and further computer-aided processing of crystallographic data in order 
to determine the primary structure. Computational chemistry (C/C) 
methods are the basic part of the procedure of molecular modelling (M/M
) of a target molecule and its interactions with a molecule of the 
future drug. Data obtained using a technology which engages the C/C and 
M/M methods not only allow to determine the aminoacid sequence of the 
target protein in question (e.g. a unique parasite enzyme); they also 
enable to further speculate on its secondary and tertiary structures. 
Such structure includes specified number of repeated motifs of alpha-
helixes, beta-sheets and loops or turns. Particularly, the "barrel&
quot; structure is very common in numerous enzymes. Two following 
examples of research on target-antiparasitic drug interactions is 
presented. They are the interaction between phosphoglicerate kinase in 
Leishmania and drug suramin and malic enzyme of Trichinella and drug 
closantel. New promising targets for new anti-protozoan drugs (protozoa 
of Trypanosoma species) include e.g. microbody translocation signal in 
kinetosom proteins (SKL) or protein blocking the transport of proteins 
to glycosomes-metabolic centres in Trypanosoma (repetitive groups of 
QRLQ). Recently, scientists from Arris Pharmaceutical (San Francisco) 
have considered, employing new data, up to 100 to fully characterize the
 surface structure of a molecule, using the systems of artificial 
intelligence.




PMID: 7571630
 

TITLE: [Viruses of parasitic protozoa]

AUTHORS: W Kasprzak, A C Majewska

AFFILIATION: Katedra Biologii i Parazytologii Lekarskiej AM, Poznań.

REFERENCE: Wiad Parazytol 1995  41(2):131-7

The authors present the actual review on several publications concerning
 the molecular characterizations of the viruses found in parasitic 
protozoa such as Giardia, Trichomonas, Leishmania and Entamoeba 
histolytica. All of the RNA viruses observed in parasitic protozoa 
showed several similarities and did not considerably differ from the 
viruses found in simple eukaryotic cells; they closely correspond to 
dsRNA viruses of yeast. The supposition that the protozoan symbionts 
detected in laboratories transfer to their hosts in natural conditions 
seemed to be rational, though, there are no evidences that these 
symbionts are potential pathogens. However, the opinion reiterates that 
intestinal protozoa (e.g. Entamoeba histolytica) may serve as vectors 
for HIV or cofactors of HIV infection. The authors point out that 
irrespective of the potential role of viruses as vectors in the 
transfection system for parasitic protozoa, the observed viral system 
constitutes an unusual experimental system to solve the problems of gene
 expression.




PMID: 14346886
 

TITLE: [THE SPECIFICITY OF TOXOPLASMA GONDII, TRICHOMONAS VAGINALIS AND
LEISHMANIA TROPICA ANTIGENS IN THE COMPLEMENT FIXATION TEST.]

AUTHORS: D KOZLOWSKA

REFERENCE: Wiad Parazytol 1964  10():390-1




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