[Leish-l] Fwd: Articles found by RefScout 2006/04/12 2006/15
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This is RefScout-Newsletter 15/2006.
REQUEST: [ leishmaniasis ]
(25 articles match this request)
PMID: 16356518
TITLE: Occurrence of Leishmania infantum cutaneous leishmaniasis in central
Tunisia.
AUTHORS: Moncef Bensaid, Souheila Guerbouj, Fatma Saghrouni, Akila
Fathallah-Mili, Ikram Guizani
AFFILIATION: Laboratoire de Parasitologie, Faculté de Médecine, Sousse,
Tunisia.
REFERENCE: Trans R Soc Trop Med Hyg 2006 Jun 100(6):521-6
Cutaneous leishmaniasis (CL) due to Leishmania infantum occurs
sporadically in Tunisia where its distribution is confined to the
northern parts of the country. However, during the past decade there
have been occasional repeated reports of cases from areas in central
Tunisia, known to be free of CL. Epidemiological, clinical and
parasitological data regarding these patients were collected and
analysed. Data were very suggestive of the sporadic form of CL due to L
. infantum. The parasites contained within the lesions of some of the
patients were characterised by two different previously described PCR
assays, each having different resolutive powers. The first assay, which
amplified complete kDNA minicircles, showed a fragment size
characteristic of the L. donovani complex; whilst the second consisted
of a PCR-RFLP analysis targeting the gp63 coding sequences that
confirmed assignment of the parasites to L. infantum species while
illustrating its differences from the reference isolate. These findings
confirm the aetiology of CL in the concerned areas in central Tunisia
and suggest that L. infantum CL might be more prevalent and widespread
than previously thought, or possibly emerging in these areas.
PMID: 16310236
TITLE: Pool screen PCR for estimating the prevalence of Leishmania infantum
infection in sandflies (Diptera: Nematocera, Phlebotomidae).
AUTHORS: J MartÃn-Sánchez, M Gállego, S Barón, S Castillejo, F
Morillas-Marquez
AFFILIATION: Departamento de ParasitologÃa, Facultad de Farmacia, Universidad
de Granada, Spain.
REFERENCE: Trans R Soc Trop Med Hyg 2006 Jun 100(6):527-32
Prevalence studies of infection in the sandfly vector can be used as an
indicator of a change in the intensity of Leishmania transmission.
However, these studies are difficult to carry out as prevalence in the
vector is usually low and its estimation requires a large number of
sandflies to be dissected. Our objective was to establish whether a L.
infantum-specific PCR-ELISA applied to pools of female sandflies and a
previously described algorithm could be useful tools to study the
prevalence of infection by this parasite in natural vector populations.
We collected sandflies from six collection points in two stable foci of
leishmaniasis in southern (N=3) and north-eastern (N=3) Spain, following
standard procedures. A fraction of the collected females was dissected
and morphologically identified. Another fraction was used for pool
screening. In total, 127 pools of 30 females (3810 specimens) were
studied by PCR-ELISA and 1764 specimens were individually dissected. The
prevalence of infection determined by dissection does not differ from
that determined by pool screen PCR. The results suggest that pool screen
PCR can be of practical use in the epidemiological surveillance of
leishmaniasis in European countries of the western Mediterranean basin,
associated with control interventions or global change.
PMID: 16325874
TITLE: Serological diagnosis of Indian visceral leishmaniasis: direct
agglutination test versus rK39 strip test.
AUTHORS: S Sundar, R K Singh, R Maurya, B Kumar, A Chhabra, V Singh, M Rai
AFFILIATION: Infectious Diseases Research Laboratory, Department of Medicine,
Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005
India.
REFERENCE: Trans R Soc Trop Med Hyg 2006 Jun 100(6):533-7
We evaluated the direct agglutination test (DAT), using freeze-dried (FD
) and aqueous (AQ) antigen, and the rK39 immunochromatographic strip
test in the diagnosis of Indian visceral leishmaniasis (VL). Sera from
508 subjects (150 parasitologically confirmed patients with VL, 100 and
153 healthy controls drawn from non-endemic and endemic regions,
respectively, and 105 patients with other diseases presenting with fever
and/or splenomegaly) were tested. The sensitivity of the tests were as
follows: DAT (FD), 96% (95% CI 91-98); DAT (AQ), 97% (95% CI 93-99);
rK39 strip test, 99% (95% CI 95-100). The specificity of DAT (FD), DAT (
AQ) and rK39 strip tests were 85% (95% CI 81-88), 87% (95% CI 83-91) and
89% (95% CI 86-92), respectively. A significant correlation (high
degree of agreement) was observed between all tests (kappa>0.80). We
conclude that the sensitivity of FD antigen is comparable to that of AQ
antigen. Similarly, the rK39 strip test is as sensitive as the DAT, but
the strip test's greater convenience of use makes it a better tool for
diagnosis of VL in peripheral areas of endemic regions.
PMID: 16586370
TITLE: CD4+CD25+ T Cells in Skin Lesions of Patients with Cutaneous
Leishmaniasis Exhibit Phenotypic and Functional Characteristics of Natural
Regulatory T Cells.
AUTHORS: Ana P Campanelli, Ana M Roselino, Karen A Cavassani, Marcelo S F
Pereira, Renato A Mortara, Claudia I Brodskyn, Heitor S Goncalves, Yasmine
Belkaid, Manoel Barral-Netto, Aldina Barral, Joao S Silva
AFFILIATION: Department of Biochemistry and Immunology, School of Medicine of
Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
REFERENCE: J Infect Dis 2006 May 193(9):1313-22
Endogenous regulatory T (T(reg)) cells are involved in the control of
infections, including Leishmania infection in mice. Leishmania viannia
braziliensis is the main etiologic agent of cutaneous leishmaniasis (CL
) in Brazil, and it is also responsible for the more severe
mucocutaneous form. Here, we investigated the possible involvement of T(
reg) cells in the control of the immune response in human skin lesions
caused by L. viannia braziliensis infection. We show that functional T(
reg) cells can be found in skin lesions of patients with CL. These cells
express phenotypic markers of T(reg) cells--such as CD25, cytotoxic T
lymphocyte-associated antigen 4, Foxp3, and glucocorticoid-induced tumor
necrosis factor receptor--and are able to produce large amounts of
interleukin-10 and transforming growth factor- beta . Furthermore, CD4
(+)CD25(+) T cells derived from the skin lesions of 4 of 6 patients with
CL significantly suppressed in vitro the phytohemagglutinin-induced
proliferative T cell responses of allogeneic peripheral-blood
mononuclear cells (PBMCs) from healthy control subjects at a ratio of 1
T(reg) cell to 10 allogeneic PBMCs. These findings suggest that
functional T(reg) cells accumulate at sites of Leishmania infection in
humans and possibly contribute to the local control of effector T cell
functions.
PMID: 16529708
TITLE: Natural infection of Lutzomyia neivai with Leishmania spp. in
northwestern argentina.
AUTHORS: Elizabeth Córdoba-Lanús, Mercedes Lizarralde De Grosso, José Enrique
Piñero, Basilio Valladares, Oscar Daniel Salomón
AFFILIATION: Instituto Superior de EntomologÃa "Dr. Abraham Willink", Facultad
de Ciencias Naturales, Universidad Nacional de Tucumán, Miguel Lillo 205, 4000
San Miguel de Tucumán, Tucumán, Argentina.
REFERENCE: Acta Trop 2006 Apr 98(1):1-5
The natural infection of Lutzomyia neivai with Leishmania in the endemic
area of American cutaneous leishmaniasis (ACL) in northwestern
Argentina was analyzed by the polymerase chain reaction (PCR)-
hybridization technique. Phlebotominae sand flies were captured in the
provinces of Tucumán and Salta between 1999 and 2003. From a sample of
440 Lu. neivai females analysed for the detection of the Leishmania (
Viannia) and Leishmania (Leishmania) subgenera, 9.1% of the samples
resulted infected with a parasite of the subgenus Viannia and none with
the Leishmania. This is the first report of naturally infected sand
flies in Argentina besides the first report of infected Lu. neivai sensu
strictu. Our results contributed to further incrimination of this
specie as vector of leishmaniasis in the area and the identification of
the main circulating parasite as belonging to the Leishmania (Viannia)
subgenera.
PMID: 16597200
TITLE: Miltefosine: oral treatment of leishmaniasis.
AUTHORS: Jaime Soto, Paula Soto
AFFILIATION: CIBIC, Centro de Investigaciones BioclÃnicas de la Fundación
FADER, Bogotá, Colombia. jaime.soto at medplus.org.co
REFERENCE: Expert Rev Anti Infect Ther 2006 Apr 4(2):177-85
The well-known problems of classic treatment of the leishmaniases with
pentavalent antimony (reduced efficacy), difficulties of administration
and increasing frequency and severity of adverse events have stimulated
the search for new drugs to treat these diseases. Other injectable, oral
and topical drugs have not been consistently effective, especially in
the modern World. Beginning in 1998, Indian researchers conducted
several trials with hexadecylphosphocholine (miltefosine) in patients
with visceral leishmaniasis, and in 1999, clinical studies were
initiated in Colombia for cutaneous disease. More than 2500 patients
have been treated, including patients with diffuse cutaneous
leishmaniasis, mucosal disease and patients coinfected with HIV. Cure
rates between 91 and 100% were reached with a dose of 2.5 mg/kg/day for
28 days, with no difference between treatment-naive and relapsing
patients. Mild gastrointestinal events were present in 35-60% of
patients and 10-20% had mild transaminase and creatinine elevations.
Miltefosine has potent leishmanicidal activity as a consequence of its
interference in parasite metabolic pathways and the induction of
apoptosis. Miltefosine is the first effective and safe oral agent with
the potential to treat all major clinical presentations of leishmaniasis.
PMID: 16597873
TITLE: Comparison of PCR assays for diagnosis of cutaneous leishmaniasis.
AUTHORS: Esther Bensoussan, Abedelmajeed Nasereddin, Flory Jonas, Lionel F
Schnur, Charles L Jaffe
AFFILIATION: Department of Parasitology, P.O. Box 12272, Hebrew
University-Hadassah Medical School, Jerusalem 91120, Israel.
cjaffe at cc.huji.ac.il.
REFERENCE: J Clin Microbiol 2006 Apr 44(4):1435-9
Three PCR assays for diagnosing leishmaniasis were compared and
validated against parasite cultures and microscopic evaluation of
stained tissue smears using 92 specimens from suspected cases of
cutaneous leishmaniasis (CL) in Israel and the West Bank. Samples from
imported and locally acquired disease were examined. The kinetoplast DNA
(kDNA) PCR showed the highest sensitivity (98.7%) of any assay,
correctly diagnosing 77/78 of the confirmed positive samples, followed
by the rRNA gene internal transcribed spacer 1 (ITS1) PCR (71/78
positive, 91.0% sensitivity) and then the spliced leader mini-exon PCR (
42/78 positive, 53.8% sensitivity). Either parasite culture or
microscopy alone detected 62.8% (49/78) or 74.4% (58/78) of the positive
specimens, respectively, while culture and microscopy together improved
overall sensitivity to 83.3% (65/78). Except for the kDNA PCR that had
six false positives, all other assays were 100% specific. Further,
restriction enzyme analysis of the ITS1 PCR product enabled
identification of 74.6% of the positive samples, which included strains
of Leishmania major (50.9%), Leishmania tropica (47.2%), and the
Leishmania braziliensis complex (1.9%). This suggests that a PCR using
kDNA should be used for the diagnosis of CL and that an ITS1 PCR can be
reliably used for the diagnosis of CL when rapid species identification
is needed.
PMID: 16597857
TITLE: Incidence and Time Course of Leishmania infantum Infections Examined by
Parasitological, Serologic, and Nested-PCR Techniques in a Cohort of Naive Dogs
Exposed to Three Consecutive Transmission Seasons.
AUTHORS: Gaetano Oliva, Aldo Scalone, Valentina Foglia Manzillo, Marina
Gramiccia, Annalisa Pagano, Trentina Di Muccio, Luigi Gradoni
AFFILIATION: Unit of Vector-borne Diseases & International Health, MIPI
Department, Istituto Superiore di Sanità , Viale Regina Elena 299, 00161 Rome,
Italy. gradoni at iss.it.
REFERENCE: J Clin Microbiol 2006 Apr 44(4):1318-22
Most experience in the comparison of diagnostic tools for canine
leishmaniasis comes from cross-sectional surveys of dogs of different
ages and breeds and in cases with unknown onset and duration of
leishmaniasis. A longitudinal study was performed on 43 beagle dogs
exposed to three transmission seasons (2002 to 2004) of Mediterranean
leishmaniasis and examined periodically over 32 months through bone
marrow microscopy and nested PCR (n-PCR), lymph node culture, serology (
immunofluorescent-antibody test), and evaluation of clinical parameters
. Starting from January 2003, the highest rate of positives was detected
by n-PCR at all assessments (from 23.3% to 97.3%). Sensitivities of
serologic and parasitological techniques were lower but increased with
time, from 15.8% to 75.0 to 77.8%. Some dogs that tested positive by n-
PCR but negative by other tests ("subpatent infection")
remained so until the end of the study or converted to negative in
subsequent assessments, whereas all dogs with positive serology and/or
microscopy/culture ("asymptomatic patent infection") exhibited
progressive leishmaniasis; 68% of them developed clinical disease (&
quot;symptomatic patent infection") during the study, at 7 (range,
3 to 14) months after being positive to all tests. Postexposure
infection incidences were high and were significantly different between
2002 and 2003 exposures (39.5% and 91.7%, respectively). The time course
of infection was highly variable in each dog, with three patterns being
identified: (i) rapid establishment of a patent condition (0 to 2
months from detection of infection); (ii) a prolonged subpatent
condition (4 to 22 months) before progression; and (iii) a transient
subpatent condition followed by 10 to 21 months of apparent Leishmania-
negative status before progression.
PMID: 16597201
TITLE: Treatment options for visceral leishmaniasis.
AUTHORS: Margriet den Boer, Robert N Davidson
AFFILIATION: Campaign for Access to Essential Medicines, Médecins Sans
Frontières, Rue Lausanne 78 CP 116 CH-1211, Geneva 21, Switzerland.
margriet.den.boer at msf.org
REFERENCE: Expert Rev Anti Infect Ther 2006 Apr 4(2):187-97
This review summarizes the current developments in therapy for visceral
leishmaniasis. With the recent introduction of new drugs, the main
limits in reducing deaths from visceral leishmaniasis are difficulty in
diagnosis in the field and health inequality--patients lack of access to
treatment. No new drugs are currently in the early stages of
development. There are good reasons for the use of combination therapy;
to prevent further development of resistance against the limited
therapeutic options available.
PMID: 16480941
TITLE: Genetic structure of natural populations of the sand fly Lutzomyia
longipalpis (Diptera: Psychodidae) from the Brazilian northeastern region.
AUTHORS: Valdir de Queiroz Balbino, Iliano Vieira Coutinho-Abreu, Ivan Vieira
Sonoda, Márcia Almeida Melo, Paulo Paes de Andrade, José Adail Fonseca de
Castro, José Macário Rebêlo, SÃlvia Maria Santos Carvalho, Marcelo
Ramalho-Ortigão
AFFILIATION: Laboratório de Genética Molecular, Centro de Ciências
Biológicas, Departamento de Genética, Universidade Federal de Pernambuco,
Recife, Pernambuco, Brazil.
REFERENCE: Acta Trop 2006 Apr 98(1):15-24
In Latin America, Lutzomyia longipalpis is the principal vector of
Leishmania chagasi, and is associated with the majority of active foci
of visceral leishmaniasis. In spite of the fact that this sand fly is
spread practically throughout the entire Neotropical Region, its
distribution is not uniform due to geographic and environmental barriers
. Geographic isolation coupled with reduced flight abilities may
contribute to the appearance of cryptic species of Lutzomyia longipalpis
, which may differ in their capacity to transmit L. chagasi. In this
work, we describe the genetic structuring patterns based on polymorphism
analysis of 24 RAPD-PCR loci of 7 natural populations of Lutzomyia
longipalpis obtained from Brazil's northeastern region. The estimated
degree of genetic differentiation between populations, based on the
population subdivision index theta(ST) (0.136), suggests a moderate
degree of genetic structuring as a result of geographical isolation and
restricted gene flow. Genetic distances were found to be compatible with
those found between members of a single species, suggesting a taxonomic
uniformity of Lutzomyia longipalpis in the region studied.
PMID: 16513079
TITLE: Leishmania major: Genetic heterogeneity of Iranian isolates by
single-strand conformation polymorphism and sequence analysis of ribosomal DNA
internal transcribed spacer.
AUTHORS: Tashakori Mahnaz, Kuhls Katrin, Al-Jawabreh Amer, Mauricio Isabel,
Schönian Gabriele, Farajnia Safar, Alimohammadian Mohammad Hossein
AFFILIATION: Ali-Ebne Abitaleb Hospital, Rafsanjan University of Medical
Sciences, Rafsanjan, Iran.
REFERENCE: Acta Trop 2006 Apr 98(1):52-8
Protozoan parasites of Leishmania major are the causative agents of
cutaneous leishmaniasis in different parts of Iran. We applied PCR-based
methods to analyze L. major parasites isolated from patients with
active lesions from different geographic areas in Iran in order to
understand DNA polymorphisms within L. major species. Twenty-four
isolates were identified as L. major by RFLP analysis of the ribosomal
internal transcribed spacer 1 (ITS1) amplicons. These isolates were
further studied by single-strand conformation polymorphism (SSCP)
analysis and sequencing of ITS1 and ITS2. Data obtained from SSCP
analysis of the ITS1 and ITS2 loci revealed three and four different
patterns among all studied samples, respectively. Sequencing of ITS1 and
ITS2 confirmed the results of SSCP analysis and showed the potential of
the PCR-SSCP method for assessing genetic heterogeneity within L. major
. Different patterns in ITS1 were due to substitution of one nucleotide
, whereas in ITS2 the changes were defined by variation in the number of
repeats in two polymorphic microsatellites. In total five genotypic
groups LmA, LmB, LmC, LmD and LmE were identified among L. major
isolates. The most frequent genotype, LmA, was detected in isolates
collected from different endemic areas of cutaneous leishmaniasis in
Iran. Genotypes LmC, LmD and LmE were found only in the new focus of CL
in Damghan (Semnan province) and LmB was identified exclusively among
isolates of Kashan focus (Isfahan province). The distribution of genetic
polymorphisms suggests the existence of distinct endemic regions of L.
major in Iran.
PMID: 16529707
TITLE: New administration model of trans-chalcone biodegradable polymers for the
treatment of experimental leishmaniasis.
AUTHORS: Jose Piñero, Rosane M Temporal, Antonio J Silva-Gonçalves, I A
Jiménez, Isabel L Bazzocchi, Alexis Oliva, Antonio Perera, Leonor L Leon,
Basilio Valladares
AFFILIATION: Instituto Universitario de Enfermedades Tropicales y Salud Pública
de Canarias, Universidad de La Laguna, Tenerife, Islas Canarias, Spain.
REFERENCE: Acta Trop 2006 Apr 98(1):59-65
The present study was designed to investigate a new administration model
and the antileishmanial activity of a semi-synthetic chalcone,
benzylideneacetophenone (trans-chalcone). The antileishmanial activity
of this product was first tested in vitro against promastigotes of L.
braziliensis, L. tropica, L. infantum and L. amazonensis. An in vivo
experiment was carried out using subcutaneous administration of trans-
chalcone and implants of synthetic biodegradable polymers, polylactic
acid (PLA) and polylactic/glycolic acid (PLGA). This compound showed
potent inhibitory effects on the growth of all Leishmania strains
examinated. Subcutaneous administration of trans-chalcone at a single
dose of 4mg/kg of body weight reduced lesion development in mice
infected with L. amazonensis. A similar inhibition of the lesion growth
in mice treated with trans-chalcone and pentamidine was observed. PLA
and PGLA implants of trans-chalcone at 4mg/kg were administered to mice
infected with L. amazonensis. PLGA implants induced a highest reduction
in the lesion size (31.25%) than PLA implants (10.75%). Treatment in
vitro with trans-chalcone at IC(50), completely inhibited the
pathogenicity of this parasite in vivo. The development of this model
provides a new practical technique for delivering drugs and can be
useful for experimental leishmaniasis treatment.
PMID: 16455798
TITLE: The wild-derived inbred mouse strain SPRET/Ei is resistant to LPS and
defective in IFN-beta production.
AUTHORS: Tina Mahieu, Jin Mo Park, Hilde Revets, Bastian Pasche, Andreas
Lengeling, Jan Staelens, Andy Wullaert, Ineke Vanlaere, Tino Hochepied, Frans
van Roy, Michael Karin, Claude Libert
AFFILIATION: Department for Molecular Biomedical Research, Flanders
Interuniversity Institute for Biotechnology and Ghent University,
Technologiepark 927, B-9052 Ghent, Belgium.
REFERENCE: Proc Natl Acad Sci U S A 2006 Feb 103(7):2292-7
Although activation of Toll-like receptor 4 (TLR4)-positive cells is
essential for eliminating Gram-negative bacteria, overactivation of
these cells by the TLR4 ligand LPS initiates a systemic inflammatory
reaction and shock. Here we demonstrate that SPRET/Ei mice, derived from
Mus spretus, exhibit a dominant resistance against LPS-induced
lethality. This resistance is mediated by bone marrow-derived cells.
Macrophages from these mice exhibit normal signaling and gene expression
responses that depend on the myeloid differentiation factor 88 adaptor
protein, but they are impaired in IFN-beta production. The defect
appears to be specific for IFN-beta, although the SPRET/Ei IFN-beta
promoter is normal. In vivo IFN-beta induction by LPS or influenza virus
is very low in SPRET/Ei mice, but IFN-beta-treatment restores the
sensitivity to LPS, and IFN type 1 receptor-deficient mice are also
resistant to LPS. Because of the defective induction of IFN-beta, these
mice are completely resistant to Listeria monocytogenes and highly
sensitive to Leishmania major infection. Stimulation of SPRET/Ei
macrophages leads to rapid down-regulation of IFN type 1 receptor mRNA
expression, which is reflected in poor induction of IFN-beta-dependent
genes. This finding indicates that the resistance of SPRET/Ei mice to
LPS is due to disruption of a positive-feedback loop that amplifies IFN-
beta production. In contrast to TLR4-deficient mice, SPRET/Ei mice
resist both LPS and sepsis induced with Klebsiella pneumoniae.
PMID: 16539713
TITLE: Comparative salivary gland transcriptomics of sandfly vectors of visceral
leishmaniasis.
AUTHORS: Jennifer M Anderson, Fabiano Oliveira, Shaden Kamhawi, Ben J Mans,
David Reynoso, Amy E Seitz, Phillip Lawyer, Mark Garfield, Myvan Pham, Jesus G
Valenzuela
AFFILIATION: Laboratory of Malaria and Vector Research, NIAID, NIH, USA.
jenanderson at niaid.nih.gov
REFERENCE: BMC Genomics 2006 7():52
BACKGROUND: Immune responses to sandfly saliva have been shown to
protect animals against Leishmania infection. Yet very little is known
about the molecular characteristics of salivary proteins from different
sandflies, particularly from vectors transmitting visceral leishmaniasis
, the fatal form of the disease. Further knowledge of the repertoire of
these salivary proteins will give us insights into the molecular
evolution of these proteins and will help us select relevant antigens
for the development of a vector based anti-Leishmania vaccine. RESULTS:
Two salivary gland cDNA libraries from female sandflies Phlebotomus
argentipes and P. perniciosus were constructed, sequenced and proteomic
analysis of the salivary proteins was performed. The majority of the
sequenced transcripts from the two cDNA libraries coded for secreted
proteins. In this analysis we identified transcripts coding for protein
families not previously described in sandflies. A comparative sandfly
salivary transcriptome analysis was performed by using these two cDNA
libraries and two other sandfly salivary gland cDNA libraries from P.
ariasi and Lutzomyia longipalpis, also vectors of visceral leishmaniasis
. Full-length secreted proteins from each sandfly library were compared
using a stand-alone version of BLAST, creating formatted protein
databases of each sandfly library. Related groups of proteins from each
sandfly species were combined into defined families of proteins. With
this comparison, we identified families of salivary proteins common
among all of the sandflies studied, proteins to be genus specific and
proteins that appear to be species specific. The common proteins
included apyrase, yellow-related protein, antigen-5, PpSP15 and PpSP32-
related protein, a 33-kDa protein, D7-related protein, a 39- and a 16.1
- kDa protein and an endonuclease-like protein. Some of these families
contained multiple members, including PPSP15-like, yellow proteins and
D7-related proteins suggesting gene expansion in these proteins.
CONCLUSION: This comprehensive analysis allows us the identification of
genus- specific proteins, species-specific proteins and, more
importantly, proteins common among these different sandflies. These
results give us insights into the repertoire of salivary proteins that
are potential candidates for a vector-based vaccine.
PMID: 16599172
TITLE: Laboratory estimation of degree-day developmental requirements of
Phlebotomus papatasi (Diptera: Psychodidae).
AUTHORS: Ozge Erisoz Kasap, Bulent Alten
AFFILIATION: Department of Biology, Faculty ofScience, Ecology Section, EBAL
Laboratories, Hacettepe University, 06800, Ankara-Turkey.
REFERENCE: J Vector Ecol 2005 Dec 30(2):328-33
Cutaneous leishmaniasis is one of the most important vector-borne
endemic diseases in Turkey. The main objective of this study was to
evaluate the influence of temperature on the developmental rates of one
important vector of leishmaniasis, Phlebotomus papatasi (Scopoli, 1786
) (Diptera: Psychodidae). Eggs from laboratory-reared colonies of
Phlebotomus papatasi were exposed to six constant temperature regimes
from 15 to 32 degrees C with a daylength of 14 h and relative humidity
of 65-75%. No adult emergence was observed at 15 degrees C. Complete egg
to adult development ranged from 27.89 +/- 1.88 days at 32 degrees C to
246.43 +/- 13.83 days at 18 degrees C. The developmental zero values
were estimated to vary from 11.6 degrees C to 20.25 degrees C depending
on life stages, and egg to adult development required 440.55 DD above 20
.25 degrees C.
PMID: 16599035
TITLE: Clinicopathological features of childhood visceral leishmaniasis in Azad
Jammu & Kashmir Pakistan.
AUTHORS: Chauhdry Altaf, Parvez Ahmed, Tanveer Ashraf, Masood Anwar, Irfan
Ahmed
AFFILIATION: Combined Military Hospital, Muzaffarabad, AJK.
altaf444 at hotmail.com
REFERENCE: J Ayub Med Coll Abbottabad 2005 Oct-Dec 17(4):48-50
BACKGROUND: In Pakistan visceral leishmaniasis (VL) is endemic in Azad
Jammu & Kashmir. Northern Areas and Northwest Frontier Province; the
areas which lack adequate diagnostic facilities. This study describes
the clinical and laboratory features in 61 cases of childhood VL.
METHODS: All the children below 12 years of age who were managed as
indoor cases from 1st Jan 1999 to 31st Dec 1999 were included in this
study. The diagnosis of VL was established by demonstration of
leishmania parasites in bone marrow aspiration. The demographic
information, physical signs at presentations and results of complete
blood picture and formol gel test were recorded. RESULTS: Median age of
the patients was 18 months. Eighty four percent children were
malnourished. Mean duration of fever before diagnosis was 45 days.
Hepatosplenomegaly was present in all cases with mean enlargement of
spleen and liver 6.8 and 3.2 cm respectively. Mean haemoglobin level.
WBC and platelet counts were 6.7 g/dl, 4.8 x 109 /l and 70 x 109 /l
respectively. Absolute neutrophil count was <1.5 x 109 /l in 61%
cases. Mean reticulocyte count was 6.2%. There was significant negative
correlation (p= 0.014) between haemoglobin level and spleen size. Formol
gel test was positive in all cases. Mean hospital stay to established
diagnosis was 8.6 days. CONCLUSION: The clinical and laboratory features
of childhood VL in Azad Jammu and Kashmir are similar to Mediterranean
type of disease caused by leishmania infantum. Cytopenia with high or
normal reticulocyte count provides a useful clue to diagnosis in a
febrile patient with hepatosplenomegally in an endemic area.
PMID: 16599036
TITLE: Clinical presentation and management of visceral leishmaniasis.
AUTHORS: Zardad Muhammad Tanoli, Manzoor Elahi Rai, Abdus Salam Khan Gandapur
AFFILIATION: Department of Paediatrics, Women Medical College, Abbottabad.
REFERENCE: J Ayub Med Coll Abbottabad 2005 Oct-Dec 17(4):51-3
BACKGROUND: Febrile illnesses like malaria, typhoid, and tuberculosis
are the commonest problems in our area, but visceral leishmaniasis (VL)
is also one of the diseases presenting with fever in this part of the
country. This study was conducted to evaluate its clinical spectrum and
way of management. METHODS: This study was conducted in Paediatric
Department of Women and Children Hospital and Ayub Teaching Hospital,
Abbottabad from October 1985 to August 1999 during which 70 cases of VL
were diagnosed and managed. RESULTS: All patients were below 10 years of
age and were from Hazara division. Majority of them were from two
specific localities, one in Abbottabad District (43%) and the other in
Mansehra District (14%). Common clinical features were Fever 99%,
Splenomegaly (99%), Anaemia (96%), Hepatomegaly (86%), distension of
abdomen (47%) and bleeding diathesis 14%. Haemoglobin was below 7.9 gm
in 82.86%, white cell count was below 4000/mm3 in 42.85%, Platelet count
was below 100000/mm3 in 67.14% and ESR was >50 mm at the end of first
hour in 86% of the patients. All the patients showed Leishmania Donovani
bodies in the bone marrow smears except one, where tap was dry and then
trephine biopsy was performed to confirm the diagnosis. In 67 cases
amastigote form was found and only in 3 patients the promastigotes were
found. Fifty two patients had received meglumine antimoniate (glucantime
) and 18 received sodium stibogluconate (pentostam) along with
supportive therapy. Mortality was 11.43%. CONCLUSIONS: The disease is
gradually spreading southwards in the country. Children below 5 years
are mainly affected. Bone marrow examination is the most reliable and
simple method of diagnosis. A high index of suspicion must he kept in
mind for all febrile cases coming from Hazara division, Northern areas,
Azad Kashmir.
PMID: 16312564
TITLE: Side effects of treatment with antimony salts.
AUTHORS: R Malta, M Affronti, S Di Rosa, L Vassallo, M Renda, G Trifirò, M E
Rubino, G B Rini
AFFILIATION: Department of Internal Medicine, Unversity of Palermo, Italy.
REFERENCE: J Chemother 1989 Jul 1(4 Suppl):628-9
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The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
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PMID: 15470021
TITLE: Localization of marginal zone macrophages is regulated by C-C chemokine
ligands 21/19.
AUTHORS: Manabu Ato, Hideki Nakano, Terutaka Kakiuchi, Paul M Kaye
AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, UK.
REFERENCE: J Immunol 2004 Oct 173(8):4815-20
The marginal zone (MZ) of the spleen is an important site for the
capture of blood-borne pathogens and a gateway for lymphocytes entering
the white pulp. We have recently reported that Leishmania donovani
infection results in a remarkably selective loss of MZ macrophages (MZM
) from the MZ. To understand the basis of this observation, we have
investigated how MZM maintain their anatomical distribution in the
steady state in uninfected mice. We now report that plt/plt mice, which
lack functional CCL19 and CCL21, have significantly reduced numbers of
MZM compared with normal C57BL/6 (B6) mice. Similarly, in B6.CD45.1-->
plt/plt chimeras, donor-derived MZM were rare compared with the number
observed in reciprocal plt/plt-->B6.CD45.1 chimeras. Moreover, we show
that administration of pertussis toxin, an inhibitor of chemokine
receptor signaling, to B6 mice results in exit of MZM from the MZ, that
MZM can migrate in response to CCL19 and CCL21 in vitro, and that MZM
colocalize with CD31+CCL21+ endothelial cells. Collectively, these data
indicate that CCL21 and, to a lesser extent, CCL19 play significant
roles in the distinctive localization of MZM within the splenic MZ.
Deficiency of CCL19 and CCL21, as also previously observed in mice
infected with L. donovani, may thus account for the selective loss of
MZM seen during this infection.
PMID: 15074875
TITLE: Leishmania donovani complex: genotyping with the ribosomal internal
transcribed spacer and the mini-exon.
AUTHORS: I L Mauricio, J R Stothard, M A Miles
AFFILIATION: Pathogen Molecular Biology Unit, Department of Infectious and
Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel
Street, London WC1E 7HT, UK. isabel.mauricio at lshtm.ac.uk
REFERENCE: Parasitology 2004 Mar 128(Pt 3):263-7
Intergenic region typing by restriction analysis of the ribosomal
internal transcribed spacer (ITS) and mini-exon provide diagnostic
markers for some Leishmania. Here, we evaluate restriction analysis of
these targets for genotyping and phylogenetic analysis within the
Leishmania donovani complex (agents of visceral leishmaniasis). Each
method was useful for genotyping of both L. donovani complex strains and
Old World Leishmania species. The targets produced less robust groups
than gp63 intergenic regions, but support the need for re-evaluation of
the taxonomy of the L. donovani complex.
PMID: 12595483
TITLE: Interleukin-12 regulates chemokine gene expression during the early
immune response to Leishmania major.
AUTHORS: Colby Zaph, Phillip Scott
AFFILIATION: Department of Pathobiology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
REFERENCE: Infect Immun 2003 Mar 71(3):1587-9
Following infection with Leishmania major, the chemokines XCL1, CXCL10,
and CCL2 were preferentially expressed in draining lymph nodes of
resistant mice. Neutralization of interleukin 12 (IL-12) or gamma
interferon in resistant mice resulted in decreased chemokine expression
, while administration of IL-12 to susceptible mice resulted in an
increase in the level of chemokine gene expression.
PMID: 12436111
TITLE: Defective CCR7 expression on dendritic cells contributes to the
development of visceral leishmaniasis.
AUTHORS: Manabu Ato, Simona Stäger, Christian R Engwerda, Paul M Kaye
AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
REFERENCE: Nat Immunol 2002 Dec 3(12):1185-91
Interaction between dendritic cells (DCs) and T cells is essential for
the generation of cell-mediated immunity. Here we show that DCs from
mice with chronic Leishmania donovani infection fail to migrate from the
marginal zone to the periarteriolar region of the spleen. Stromal cells
were fewer, which was associated with loss of CCL21 and CCL19
expression. The residual stromal cells and endothelium produced
sufficient CCL21 to direct the migration of DCs transferred from naïve
mice. However, DCs from infected mice had impaired migration both in na
ïve recipients and in vitro, in response to CCL21 and CCL19. Defective
localization was attributable to tumor necrosis factor-alpha-dependent,
interleukin 10-mediated inhibition of CCR7 expression. Effective
immunotherapy was achieved with CCR7-expressing DCs, without the need to
identify protective Leishmania antigens. Thus defective DC migration
plays a major role in the pathogenesis of this disease and the
immunosuppression is mediated, at least in part, through the spatial
segregation of DCs and T cells.
PMID: 12399206
TITLE: Evaluation of the murine immune response to Leishmania meta 1 antigen
delivered as recombinant protein or DNA vaccine.
AUTHORS: Carlos Henrique Cardoso Serezani, Amanda Richards Franco, Mariana Wajc,
Jenicer K Umada Yokoyama-Yasunaka, Gerhard Wunderlich, Monamaris Marques Borges,
Silvia Reni Bortolin Uliana
AFFILIATION: Departamento de Parasitologia, Instituto de Ciências Biomédicas,
Universidade de São Paulo, Av Prof Lineu Prestes, 1374, São Paulo, CEP
05508-900 Brazil.
REFERENCE: Vaccine 2002 Nov 20(31-32):3755-63
The meta 1 gene of Leishmania is conserved across the genus and encodes
a protein upregulated in metacyclic promastigotes. Meta 1 constitutive
overexpressing mutants show increased virulence to mice. In this paper,
both meta 1 recombinant protein and plasmids bearing the meta 1 gene
were tested for their antigenicity and potential for inducing protective
immunity in mice. Vaccination with the recombinant protein induced a
predominant Th2-type of response and did not result in protection upon
challenge with live parasites. Surprisingly, the expected reversal to a
CD4(+) Th1-type of response upon genetic immunisation by the
intramuscular route was not observed. Instead, vaccination with either
the meta 1 gene alone or in fusion with the monocyte chemotactic protein
(MCP)-3 cDNA induced a Th2-type of response that correlated with lack
of protection against infection.
PMID: 7698752
TITLE: Genetic and physical mapping of 2q35 in the region of the NRAMP and IL8R
genes: identification of a polymorphic repeat in exon 2 of NRAMP.
AUTHORS: J K White, M A Shaw, C H Barton, D P Cerretti, H Williams, B A Mock, N
P Carter, C S Peacock, J M Blackwell
AFFILIATION: University of Cambridge Clinical School, Department of Medicine,
Addenbrooke's Hospital, United Kingdom.
REFERENCE: Genomics 1994 Nov 24(2):295-302
Recent interest has focused on the region of conserved synteny between
mouse chromosome 1 and human 2q33-q37, particularly over the region
encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate
Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster
. In this paper, identification of a restriction fragment length
polymorphism in the IL8RB gene in 35 pedigrees previously typed for
markers in the 2q33-q37 interval provided evidence (lod scores > 3) for
linkage between IL8RB and the 2q34-q35 markers FN1, TNP1, VIL1, and DES
. Physical mapping, using yeast artificial chromosomes isolated with
VIL1, confirmed that IL8RA, IL8RB, and the IL8RB pseudogene map within
the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5' LSH
to 3' VIL1 representing approximately 3-fold that observed in the mouse
. Partial sequencing of NRAMP confirmed the presence of the N-terminal
proline/serine-rich putative SH3 binding domain in exon 2 of the human
gene. Further analysis of Brazilian leprosy and visceral leishmaniasis
pedigrees identified a rare second allele varying in a 9-nucleotide
repeat motif of the exon 2 sequence but segregating independently of the
disease phenotype.
PMID: 6649998
TITLE: [Spread of infectious agents through refuse by domestic, community and
field parasites with special reference to human health]
AUTHORS: A Mayr
REFERENCE: Zentralbl Bakteriol Mikrobiol Hyg [B] 1983 Sep 178(1-2):53-60
The accumulation of refuse in urban and agricultural areas provides
parasitic vermin with new feeding sources and also creates for them
partly entirely new biotopes. Vermin transmit both mechanically and
biologically the most varied species of pathogens to man, domestic
animals and work animals. With respect to the spread of pathogens by
vermin via the refuse route, we must distinguish between vermin
infesting either the human body, the houses, communities or our
environment. Among the human vermin and house species, cockroaches,
house gnats and house flies are the most important genera for the spread
of pathogens via refuse. Cockroaches transmit bacteria (e.g. Salmonella
), viruses (e.g. enterovirus, rota and corona viruses), fungi (e.g.
Trichophyton and Candida) and worm eggs (e.g. Ascaris lumbricoides).
House flies and house gnats take up all infection carriers from refuse
and transmit the pathogens, as a rule, purely mechanically. Rats and
mice are the most important species among community vermin. These
rodents act both as mechanical and biological vehicles of infectious
diseases. A case in point is lymphocytic chorio-meningitis and three
different types of hemorrhagic fever in man. Among the vermin infesting
our environment, the diptera are the most important carriers. Gnats,
especially, often act as intermediate hosts (biological transmission)
and, as a result, represent an inexhaustible reservoir of pathogen
transmitters. More than 50 diseases caused by arbovirus in man and
animal are known. Beside the viruses, the field diptera transmit
bacteria (e.g. Rickettsiosis) and protozoa (e.g. Leishmaniasis,
Trypanosomiasis).(ABSTRACT TRUNCATED AT 250 WORDS)
REQUEST: [ leishmania ]
(30 articles match this request. 18 articles matching other requests removed)
PMID: 16530278
TITLE: Identification of developmentally-regulated proteins in Leishmania
panamensis by proteome profiling of promastigotes and axenic amastigotes.
AUTHORS: John Walker, Juan-José Vasquez, Maria Adelaida Gomez, Jolyne
Drummelsmith, Richard Burchmore, Isabelle Girard, Marc Ouellette
AFFILIATION: Centro Internacional de Entrenamiento e Investigaciones Medicas
(CIDEIM), Avenida 1 Norte No. 3-03, Cali, Colombia.
REFERENCE: Mol Biochem Parasitol 2006 May 147(1):64-73
We have employed proteomics to identify proteins upregulated in the
amastigote life-stage of Leishmaniapanamensis, using axenically-
differentiated forms as models of authentic intracellular parasites.
Resolution of the soluble proteomes of axenic amastigotes and
promastigotes by two-dimensional electrophoresis (2DE) in the neutral pI
range (5-7) revealed equivalent numbers of protein spots in both life-
stages (644-682 using Coomassie Blue and 851-863 by silver staining).
Although representing a relatively low proportion (8.1-10.8%) of the
predicted 8000 gene products of Leishmania, these proteome maps enabled
the reproducible detection of 75 differentially-regulated protein spots
in amastigotes, comprising 24 spots "uniquely" expressed in
this life-stage and 51 over-expressed by 1.2-5.7-fold compared to
promastigotes. Of the 11 amastigote-specific spots analysed by mass
spectrometry (MS), 5 yielded peptide sequences with no orthologues in
Leishmania major, and the remaining 6 were identified as 7 distinct
proteins (some of which were truncated isoforms) representing several
functional classes: carbohydrate/energy metabolism (fructose 1,6-
bisphosphate aldolase, glucose 6-phosphate dehydrogenase, pyruvate
dehydrogenase), stress response (heat shock protein [HSP] 83), cell
membrane/cytoskeleton (beta-tubulin), amino acid metabolism (cysteine
synthase) and cell-cycle (ran-binding protein). Four additional over-
expressed spots were tentatively identified as HSPs 60 and 70 and HSP 70
-related proteins -1 and -4 by positional analogy with these landmark
proteins in the Leishmania guyanensis proteome. Our data demonstrate the
feasibility of proteomics as an approach to identify novel
developmentally-regulated proteins linked to Leishmania differentiation
and intracellular survival, while simultaneously pinpointing therapeutic
targets. In particular, the amastigote-specific expression of cysteine
synthase underlines the importance of de novo cysteine synthesis both as
a potential parasite virulence factor and as a major metabolic
difference from mammalian host cells.
PMID: 16603532
TITLE: In primary human monocyte-derived macrophages exposed to Human
immunodeficiency virus type 1, does the increased intracellular growth of
Leishmania infantum rely on its enhanced uptake?
AUTHORS: Chenqi Zhao, Sandra Thibault, Nadine Messier, Marc Ouellette, Barbara
Papadopoulou, Michel J Tremblay
AFFILIATION: Research Center in Infectious Diseases, CHUL Research Center, and
Faculty of Medicine, Laval University, RC709, 2705 Laurier Blvd, Québec, QC
G1V 4G2, Canada.
REFERENCE: J Gen Virol 2006 May 87(Pt 5):1295-302
Concurrent uncontrolled development of human immunodeficiency virus type
1 (HIV-1) and Leishmania spp. is regarded as an emerging pathogenic
combination in countries where human beings are exposed to these two
micro-organisms. The present study was aimed at exploring whether HIV-1
development within a culture of human monocyte-derived macrophages (MDMs
) affected the further development of luciferase-encoding Leishmania
infantum using the luciferase activity as a readout assay. It was
demonstrated that, in cultures of HIV-1-loaded MDMs exposed to axenic
amastigotes, the luciferase activity was higher than in HIV-1-free MDMs
. As a preliminary approach to deciphering the possible mechanism
through which HIV-1 can affect Leishmania infantum, attention was
focused on the very early processes that could underlie this increased
luciferase activity. Using GFP-labelled parasites, it was possible to
establish that, in HIV-1-infected MDMs, the percentage of GFP-expressing
MDMs was higher (10-20 %) than in cell cultures not exposed to HIV-1 (5
%). Two-colour immunofluorescence staining suggested that HIV-1
indirectly affects the uptake of parasites inside MDMs. Thus, the
observed phenomenon seems to be linked with a higher uptake of parasites
within MDMs. Taken together, the data reported here may contribute to
our understanding of disseminated Leishmania infection in HIV-1-infected
individuals.
PMID: 16585577
TITLE: In vivo recognition of ovalbumin expressed by transgenic leishmania is
determined by its subcellular localization.
AUTHORS: Sara Prickett, Peter M Gray, Sara L Colpitts, Phillip Scott, Paul M
Kaye, Deborah F Smith
AFFILIATION: Wellcome Trust Laboratories for Molecular Parasitology, Centre for
Molecular Microbiology and Infection, Imperial College, London, United
Kingdom;
REFERENCE: J Immunol 2006 Apr 176(8):4826-33
The importance of the site of Ag localization within microbial pathogens
for the effective generation of CD8(+) T cells has been studied
extensively, generally supporting the view that Ag secretion within
infected target cells is required for optimal MHC class I-restricted Ag
presentation. In contrast, relatively little is known about the
importance of pathogen Ag localization for the activation of MHC class
II-restricted CD4(+) T cells, despite their clear importance for host
protection. We have used the N-terminal targeting sequence of Leishmania
major hydrophilic acylated surface protein B to generate stable
transgenic lines expressing physiologically relevant levels of full-
length OVA on the surface of metacyclic promastigotes and amastigotes.
In addition, we have mutated the hydrophilic acylated surface protein B
N-terminal acylation sequence to generate control transgenic lines in
which OVA expression is restricted to the parasite cytosol. In vitro,
splenic dendritic cells are able to present membrane-localized, but not
cytosolic, OVA to OVA-specific DO.11 T cells. Strikingly and
unexpectedly, surface localization of OVA is also a strict requirement
for recognition by OVA-specific T cells (DO.11 and OT-II) and for the
development of OVA-specific Ab responses in vivo. However, recognition
of cytosolic OVA could be observed with increasing doses of infection.
These data suggest that, even under in vivo conditions, where varied
pathways of Ag processing are likely to operate, the site of Leishmania
Ag localization is an important determinant of immunogenicity and hence
an important factor when considering the likely candidacy of vaccine Ags
for inducing CD4(+) T cell-dependent immunity.
PMID: 16569701
TITLE: Virulence of Leishmania major in macrophages and mice requires the
gluconeogenic enzyme fructose-1,6-bisphosphatase.
AUTHORS: Thomas Naderer, Miriam A Ellis, M Fleur Sernee, David P De Souza, Joan
Curtis, Emanuela Handman, Malcolm J McConville
AFFILIATION: *Department of Biochemistry and Molecular Biology, Bio21 Molecular
Science and Biotechnology Institute, University of Melbourne, Parkville,
Victoria 3010, Australia.
REFERENCE: Proc Natl Acad Sci U S A 2006 Apr 103(14):5502-7
Leishmania are protozoan parasites that replicate within mature
phagolysosomes of mammalian macrophages. To define the biochemical
composition of the phagosome and carbon source requirements of
intracellular stages of L. major, we investigated the role and
requirement for the gluconeogenic enzyme fructose-1,6-bisphosphatase (
FBP). L. major FBP was constitutively expressed in both extracellular
and intracellular stages and was primarily targeted to glycosomes,
modified peroxisomes that also contain glycolytic enzymes. A L. major
FBP-null mutant was unable to grow in the absence of hexose, and
suspension in glycerol-containing medium resulted in rapid depletion of
internal carbohydrate reserves. L. major Deltafbp promastigotes were
internalized by macrophages and differentiated into amastigotes but were
unable to replicate in the macrophage phagolysosome. Similarly, the
mutant persisted in mice but failed to generate normal lesions. The data
suggest that Leishmania amastigotes reside in a glucose-poor phagosome
and depend heavily on nonglucose carbon sources. Feeding experiments
with [(13)C]fatty acids showed that fatty acids are poor gluconeogenic
substrates, indicating that amino acids are the major carbon source in
vivo. The need for amino acids may have forced Leishmania spp. to adapt
to life in the mature phagolysosome.
PMID: 16586484
TITLE: Leishmaniosis-A report about the microvascular and cellular architecture
of the infected spleen in Canis familiaris.
AUTHORS: G Alexandre-Pires, D Pais, M Correia, J A Esperança Pina
AFFILIATION: Faculty of Veterinary Medicine (Anatomy), Rua Prof. Cid dos Santos,
1300-477 Lisbon, Portugal.
REFERENCE: Microsc Res Tech 2006 Apr 69(4):227-35
Leishmaniosis is an anthropozoonosis caused by an intracellular
protozoan parasite that causes a wide spectrum of diseases in humans and
dogs worldwide. In the Mediterranean basin, Portugal, Central and South
America, and in the Middle East, visceral leishmaniosis is caused by
Leishmania infantum. In these areas, dogs are believed to be the natural
reservoirs of this parasite. In the case of visceral leishmaniosis, the
spleen is one of the several hematopoietic and immunocompetent organs
involved. Since this viscera is a blood filter, the authors investigated
the expression of the morphological and microvascular environment and
modifications of the spleen cell population related to immunological
responses to this parasitic condition. The tools used to perform this
study were scanning electronic microscopy of intact tissue and corrosion
casts, transmission electronic microscopy, histology and
immunohistochemistry. The results reveal three important modifications
concerning the spleen's microvascular architecture when compared with
its normal pattern, independently of the serological titer obtained with
indirect immunofluorescence. (1) A marked scarcity of the sinusoidal
system sheet that surrounds the central artery/arteriole of the white
pulp; (2) A huge development of pulp venules and veins; (3) The presence
of a surprising development of reticular fibers. The authors postulate
that independent of the virulence of the parasite involved and the type
of immunity prevalent in a particular host, the spleen develops blood
dynamic conditions that permit reduction in the speed of blood flow so
that cells involved in immunological processes can proliferate and
differentiate, and also contributes to trapping lymphocytes within the
area through the differentiation of characteristics that resemble those
of HEV endothelial cells. Microsc. Res. Tech. 69:227-235, 2006. (c) 2006
Wiley-Liss, Inc.
PMID: 16479587
TITLE: HFIP-induced structures and assemblies of the peptides from the
transmembrane domain 4 of membrane protein Nramp1.
AUTHORS: Rong Xue, Shuo Wang, Chunyu Wang, Tao Zhu, Fei Li, Hongzhe Sun
AFFILIATION: Key Laboratory for Supramolecular Structure and Materials of
Ministry of Education, Jilin University, 2699 Qianjin Avenue, Changchun 130012,
People's Republic of China.
REFERENCE: Biopolymers 2006 84(3):329-39
Membrane protein Nramp1 (natural resistance-associated macrophage
protein 1) is a pH-dependent divalent metal cation transporter that
regulates macrophage activation in infectious and autoimmune diseases. A
naturally occurring glycine to aspartic acid substitution at position
169 (G169D) within the transmembrane domain 4 (TM4) of Nramp1 makes mice
susceptible to Leishmania donovani, Salmonella typhimurium, and
Mycobacterium bovis. Here we present a structural and self-assembling
study on two synthetic 24-residue peptides, corresponding to TM4 of
mouse Nramp1 and its G169D mutant, respectively, in 1,1,1,3,3,3-
hexafluoroisopropanol-d(2) (HFIP-d(2)) aqueous solution by nuclear
magnetic resonance (NMR) spectroscopy. The results show that amphipathic
alpha-helical structures are formed from residue Ile173 to Tyr187 for
the wild-type peptide and from Trp168 to Tyr187 for the G169D mutant,
respectively. The segment of the N-terminus from Leu167 to Leu172 is
poorly structured for the wild-type peptide, whereas it is well defined
for the G169D mutant. Both peptides aggregate to form a tetramer and the
monomeric peptides in peptide bundles are structurally and
orientationally similar. The intermolecular interactions in assemblies
could be stronger in the C-terminal regions related to residues Phe180-
Leu184 than those in the central helical segments for both peptides. The
G169D mutation may change the size of the opening on the termini of
assembly. (c) 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84:
329-339, 2006This article was originally published online as an accepted
preprint. The "Published Online" date corresponds to the
preprint version. You can request a copy of the preprint by emailing the
Biopolymers editorial office at biopolymers at wiley.com.
PMID: 16594576
TITLE: Effects of allopurinol treatment on the progression of chronic nephritis
in Canine leishmaniosis (Leishmania infantum).
AUTHORS: K Plevraki, A F Koutinas, H Kaldrymidou, N Roumpies, L G Papazoglou, M
N Saridomichelakis, I Savvas, L Leondides
AFFILIATION: Clinic of Companion Animal Medicine, School of Veterinary Medicine,
Aristotle University of Thessaloniki, Greece. kplevraki at hotmail.com
REFERENCE: J Vet Intern Med 2006 Mar-Apr 20(2):228-33
Forty dogs with canine leishmaniosis (CL) participated in this study,
which was designed to investigate the effect of allopurinol on the
progression of the renal lesions associated with this disease. The
animals were allocated into 5 groups. Group A dogs (n = 12) had neither
proteinuria nor renal insufficiency, group B dogs (n= 10) had
asymptomatic proteinuria, and group C dogs (n = 8) were proteinuric and
azotemic. Two more groups, CA and CB, comprising 5 dogs each, served as
controls for groups A and B, respectively. Group A, B, and C dogs
received allopurinol PO (10 mg/kg q12h) for 6 months, whereas group CA
and CB dogs were placebo-treated. Serum biochemistry profile, urinalysis
, urine protein/creatinine ratio, and glomerular filtration rate (GFR)
measurements were carried out at the beginning of the study, the 3rd
month, and the 6th month, whereas renal biopsies were carried out only
at the beginning and the end of the trial. Membranoproliferative
glomerulonephritis was the most common cause of chronic renal failure.
Mesangioproliferative and tubulointerstitial nephritis were detected
even in group A and CA dogs. Allopurinol not only lowered proteinuria in
group B dogs but also prevented the deterioration of GFR and improved
the tubulointerstitial, but not the glomerular, lesions in both group A
and group B dogs. Further, it resolved the azotemia in 5 of the 8 dogs
admitted with 2nd stage chronic renal failure (group C). Consequently,
treatment with allopurinol is advisable in CL cases with asymptomatic
proteinuria or 1st-2nd stage chronic renal failure.
PMID: 16522215
TITLE: Cyclic nucleotide specific phosphodiesterases of Leishmania major.
AUTHORS: Andrea Johner, Stefan Kunz, Markus Linder, Yasmin Shakur, Thomas
Seebeck
AFFILIATION: Institute for Cell Biology, University of Bern, Baltzerstrasse 4,
CH-3012 Bern, Switzerland. thomas.seebeck at izb.unibe.ch.
REFERENCE: BMC Microbiol 2006 6():25
ABSTRACT : BACKGROUND : Leishmania represent a complex of important
human pathogens that belong to the systematic order of the
kinetoplastida. They are transmitted between their human and mammalian
hosts by different bloodsucking sandfly vectors. In their hosts, the
Leishmania undergo several differentiation steps, and their coordination
and optimization crucially depend on numerous interactions between the
parasites and the physiological environment presented by the fly and
human hosts. Little is still known about the signalling networks
involved in these functions. In an attempt to better understand the role
of cyclic nucleotide signalling in Leishmania differentiation and host-
parasite interaction, we here present an initial study on the cyclic
nucleotide-specific phosphodiesterases of Leishmania major. RESULTS :
This paper presents the identification of three class I cyclic-
nucleotide-specific phosphodiesterases (PDEs) from L. major, PDEs whose
catalytic domains exhibit considerable sequence conservation with, among
other, all eleven human PDE families. In contrast to other protozoa
such as Dictyostelium, or fungi such as Saccharomyces cerevisiae,
Candida ssp or Neurospora, no genes for class II PDEs were found in the
Leishmania genomes. LmjPDEA contains a class I catalytic domain at the C
-terminus of the polypeptide, with no other discernible functional
domains elsewhere. LmjPDEB1 and LmjPDEB2 are coded for by closely
related, tandemly linked genes on chromosome 15. Both PDEs contain two
GAF domains in their N-terminal region, and their almost identical
catalytic domains are located at the C-terminus of the polypeptide.
LmjPDEA, LmjPDEB1 and LmjPDEB2 were further characterized by functional
complementation in a PDE-deficient S. cerevisiae strain. All three
enzymes conferred complementation, demonstrating that all three can
hydrolyze cAMP. Recombinant LmjPDEB1 and LmjPDEB2 were shown to be cAMP-
specific, with Km values in the low micromolar range. Several PDE
inhibitors were found to be active against these PDEs in vitro, and to
inhibit cell proliferation. CONCLUSION : The genome of L. major contains
only PDE genes that are predicted to code for class I PDEs, and none
for class II PDEs. This is more similar to what is found in higher
eukaryotes than it is to the situation in Dictyostelium or the fungi
that concomitantly express class I and class II PDEs. Functional
complementation demonstrated that LmjPDEA, LmjPDEB1 and LmjPDEB2 are
capable of hydrolyzing cAMP. In vitro studies with recombinant LmjPDEB1
and LmjPDEB2 confirmed this, and they demonstrated that both are
completely cAMP-specific. Both enzymes are inhibited by several
commercially available PDE inhibitors. The observation that these
inhibitors also interfere with cell growth in culture indicates that
inhibition of the PDEs is fatal for the cell, suggesting an important
role of cAMP signalling for the maintenance of cellular integrity and
proliferation.
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The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
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PMID: 15996670
TITLE: Identification of a DNA fragment that increases mitotic stability of
episomal linear DNAs in Leishmania major.
AUTHORS: Liane Casagrande, Jeronimo C Ruiz, Stephen M Beverley, Angela K Cruz
AFFILIATION: Departamento de Biologia Celular e Molecular e Bioagentes
Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
REFERENCE: Int J Parasitol 2005 Aug 35(9):973-80
The centromere is a specialized region of eukaryotic chromosomes, the
site of kinetochore formation, spindle attachment and regulation of
chromosome segregation during mitotic and meiotic cell divisions. To
identify sequences which increase mitotic stability and/or act as
potential centromeres in Leishmania major, we first generated libraries
of Leishmania linear artificial chromosomes (LACs) bearing 30 kb inserts
of randomly selected genomic DNAs. These were introduced into parasites
, and then their stability was assessed following a period of 10
passages of growth in the absence of selective pressure. Approximately
80% of the 108 transfectants tested lost their LACs promptly and only 20
% of the recombinants were retained; of these six showed strong but
partial stability (maintained in 30-46% of cells). Mapping and
sequencing of one clone (cSC10), which confers the highest degree of
maintenance, revealed the presence of a sequence that was found within
another stable episome, and which is dispersed in the genome of L. major
. The implications of these data to the possible mechanisms of
chromosomal maintenance are discussed.
PMID: 12067410
TITLE: Rac2-deficient mice display perturbed T-cell distribution and chemotaxis,
but only minor abnormalities in T(H)1 responses.
AUTHORS: Ben A Croker, Emanuela Handman, John D Hayball, Tracey M Baldwin,
Valentina Voigt, Leonie A Cluse, Feng-Chun Yang, David A Williams, Andrew W
Roberts
AFFILIATION: Divisions of Cancer, Walter and Eliza Hall Institute of Medical
Research, Royal Melbourne Hospital, Parkville, Victoria, South Australia.
REFERENCE: Immunol Cell Biol 2002 Jun 80(3):231-40
The haematopoietic-specific RhoGTPase, Rac2, has been indirectly
implicated in T-lymphocyte development and function, and as a pivotal
regulator of T Helper 1 (T(H)1) responses. In other haematopoietic cells
it regulates cytoskeletal rearrangement downstream of extracellular
signals. Here we demonstrate that Rac2 deficiency results in an abnormal
distribution of T lymphocytes in vivo and defects in T-lymphocyte
migration and filamentous actin generation in response to
chemoattractants in vitro. To investigate the requirement for Rac2 in
IFN-gamma production and TH1 responses in vivo, Rac2-deficient mice were
challenged with Leishmania major and immunized with ovalbumin-
expressing cytomegalovirus.Despite a minor skewing towards a T(H)2
phenotype, Rac2-deficient mice displayed no increased susceptibility to
L. major infection. Cytotoxic T-lymphocyte responses to cytomegalovirus
and ovalbumin were also normal. Although Rac2 is required for normal T-
lymphocyte migration, its role in the generation of T(H)1 responses to
infection in vivo is largely redundant.
PMID: 10461166
TITLE: Genetic manipulation of kinetoplastida.
AUTHORS: C E Clayton
AFFILIATION: Zentrum für Molekulare Biologie (ZMBH), Im Neuenheimer Feld 282,
Postfach 106249, D-69120 Heidelberg, Germany. cclayton at zmbh.uni-heidelberg.de
REFERENCE: Parasitol Today 1999 Sep 15(9):372-8
During the 1980s, many kinetoplastid genes were cloned and their
function inferred from homology with genes from other organisms,
location of the corresponding proteins or expression in heterologous
systems. Up until 1990, before the availability of DNA transfection
methodology, we could not analyze the function of kinetoplastid genes
within the organisms themselves. Since then, it has become possible to
create and complement mutants, to overexpress foreign proteins in the
parasites, to knock out genes and even to switch off essential functions
. However, these methods are not equally applicable in all parasites.
Here, Christine Clayton highlights the differences and similarities
between the most commonly used model organisms, and assesses the
relative advantages of different approaches and parasites for different
types of investigation.
PMID: 10489462
TITLE: Crystallization of recombinant Leishmania major pteridine reductase 1
(PTR1).
AUTHORS: D G Gourley, J Luba, L W Hardy, S M Beverley, W N Hunter
AFFILIATION: The Wellcome Trust Building, Department of Biochemistry, University
of Dundee, Dundee DD1 5EH, Scotland.
REFERENCE: Acta Crystallogr D Biol Crystallogr 1999 Sep 55(Pt 9):1608-10
The enzyme pteridine reductase (PTR1) has recently been discovered in
the protozoan parasite Leishmania and validated as a target for
therapeutic intervention. PTR1 is responsible for the salvage of
pteridines and also contributes to antifolate drug resistance.
Structural analysis, in combination with ongoing biochemical
characterization will assist the elucidation of the structure-activity
relationships of this important enzyme and support a structure-based
approach to discover novel inhibitors. Recombinant L. major PTR1 has
been purified from an Escherichia coli expression system and used in
crystallization experiments. Orthorhombic crystals have been obtained
and data to 2.8 A has been measured. The space group is P2(1)2(1)2 or P2
(1)2(1)2(1) with unit-cell dimensions of a = 103.9, b = 134.7, c = 96.2
A. One homotetramer, of molecular mass approximately 120 kDa, probably
constitutes the asymmetric unit and gives a Matthews coefficient, V(m),
of 2.8 A(3) Da(-1) and 56% solvent volume. Self-rotation function
calculations show a single well defined non-crystallographic twofold
axis with features that might represent additional elements of non-
crystallographic symmetry. The detail of exactly what constitutes the
asymmetric unit will be resolved by structure determination.
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