[leish-l] Fwd: Articles found by RefScout for your requests
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(19 articles match this request. 1 article matching other requests removed)
PMID: 15350864
TITLE: Successful treatment of cutaneous leishmaniasis with lipid formulations
of amphotericin B in two immunocompromised patients.
AUTHORS: Valdir S Amato, Ana Rabello, Alexandre Rotondo-Silva, Adriana Kono,
Tânia PatrÃcia H Maldonado, Isabel C Alves, Lucile M Floeter-Winter, Vicente
Amato Neto, Maria Aparecida Shikanai-Yasuda
AFFILIATION: Infectious and Parasitic Diseases Clinic, Hospital das ClÃnicas,
Faculdade de Medicina da Universidade de São Paulo, Avenida Dr. Enéas de
Carvalho Aguiar 255, 4 Andar, Sala 4028-ICHC, Cerqueira, CEP number 05403-010,
São Paulo, Brazil.
REFERENCE: Acta Trop 2004 Oct 92(2):127-32
Pentavalent antimonial drugs are habitually the first choice for
treating leishmaniasis, although they possess well-known toxicity and
may present some therapeutic failure. Lipid formulations of amphotericin
B (LFAB) have been increasingly used for treating several types of
leishmaniasis. However, the administration of such lipid formulations
specifically to patients with cutaneous leishmaniasis (CL) is still rare
, including immunocompromised patients to whom standard treatments are
more frequently contraindicated. We describe here two cases of
immunocompromised patients with CL, one of them with AIDS, representing
the first case of AIDS and CL co-infection treated with LFAB described
in the literature. The patient achieved therapeutic success with a total
1.500mg dose of amphotericin B colloidal dispersion. The other had
diabetes mellitus as well as kidney failure and was under dialysis,
having obtained the healing of lesion with a total dose of 600mg of
liposomal amphotericin B. Thus, the authors suggest that LFAB can
represent a safe, efficient and less toxic therapeutic alternative to
pentavalent antimonials, as well as to the so-called second line drugs,
pentamidine and amphotericin B deoxycholate.
PMID: 15336576
TITLE: Leishmania donovani activates nuclear transcription factor-kappaB in
macrophages through reactive oxygen intermediates.
AUTHORS: Vandana Km Singh, Sridevi Balaraman, Poonam Tewary, Rentala Madhubala
AFFILIATION: School of Life Sciences, Jawaharlal Nehru University, New
Delhi-110067, India.
REFERENCE: Biochem Biophys Res Commun 2004 Sep 322(3):1086-95
Interaction of Leishmania donovani with macrophages antagonizes host
defense mechanisms by interfering with a cascade of cell signaling
processes in the macrophages. An early intracellular signaling event
that follows receptor engagement is the activation of transcription
factor NF-kappaB. It has been reported earlier that NF-kappaB-dependent
signaling pathway regulates proinflammatory cytokine release. We
therefore investigated the effect of L. donovani infectivity on this
nuclear transcription factor in macrophage cell line J774A.1. Both L.
donovani and its surface molecule lipophosphoglycan (LPG) resulted in a
dose- and time-dependent activation of NF-kappaB-DNA binding activity in
an electrophoretic mobility shift assay. We also report the involvement
of IkappaB-alpha and IkappaB-beta in the persistent activation of NF-
kappaB by L. donovani. We demonstrate that the NF-kappaB activation was
independent of viability of the parasite. Electrophoretic mobility
supershift assay indicated that the NF-kappaB complex consists of p65
and c-rel subunits. The interaction of parasite with the macrophages and
not the cellular uptake was important for NF-kappaB activation. Both
p38 and ERK mitogen activated protein kinase (MAP) activation appears to
be necessary for NF-kappaB activation by LPG. Preincubation of cells
with antioxidants resulted in inhibition of L. donovani induced NF-
kappaB activation, thereby suggesting a potential role of reactive
oxygen species in L. donovani induced intracellular signaling. The
present data indicate that antioxidants could play an important role in
working out various therapeutic modalities to control leishmaniasis.
PMID: 15335317
TITLE: Recent advances in vaccines for leishmaniasis.
AUTHORS: Jose M Requena, Salvador Iborra, Javier Carrión, Carlos Alonso,
Manuel
Soto
AFFILIATION: Universidad Autónoma de Madrid, Centro de BiologÃa Molecular
'Severo Ochoa', Campus de Cantoblanco, 28049 Madrid, Spain.
jmrequena at cbm.uam.es
REFERENCE: Expert Opin Biol Ther 2004 Sep 4(9):1505-17
The observation that recovery from infection with Leishmania confers
immunity to reinfection suggests that control of leishmaniasis by
vaccination may be possible. However, there are no vaccines available at
present to control any form of leishmaniasis, despite considerable
efforts. Studies of the immunopathogenesis and mechanisms of protective
immunity, mainly derived from animal models of experimental
leishmaniasis, have defined a number of features that should be met by
an effective vaccine. In addition, several antigens have been identified
that may be potential vaccine candidates, and molecular biological
techniques have made them available as recombinant proteins for second-
generation vaccines. Furthermore, molecules present in the saliva of
Leishmania-transmitting vectors have been demonstrated as valuable
candidates for the development of anti-Leishmania vaccines. This review
concentrates on the most promising vaccine candidates and highlights new
approaches for the development of vaccines. Finally, based on present
knowledge, the future prospects for developing an effective vaccine
against the different clinical forms of leishmaniasis are discussed.
PMID: 15347346
TITLE: Cutaneous leishmaniasis in a Kosovan child treated with oral
fluconazole.
AUTHORS: S Baron, S Laube, F Raafat, C Moss
AFFILIATION: Department of Dermatology and Histopathology, Birmingham
Children's
Hospital, Birmingham B4 6NH UK.
REFERENCE: Clin Exp Dermatol 2004 Sep 29(5):546-7
PMID: 15347324
TITLE: The psychological impact of cutaneous leishmaniasis.
AUTHORS: M Yanik, M S Gurel, Z Simsek, M Kati
AFFILIATION: Department of Dermatology, Medical Faculty of Harran University,
Sanliurfa, Turkey.
REFERENCE: Clin Exp Dermatol 2004 Sep 29(5):464-7
Summary A psychiatric disorder would be associated with extensive,
unsightly lesions on exposed body parts. Cutaneous leishmaniasis (CL)
has long been endemic in Sanliurfa and is called 'beauty scar'. The aim
of this study was to determine psychological impact of CL. Patients with
active CL, with CL that had healed with scaring, and healthy controls
were included in this case-control study. The Hospital Anxiety
Depression Scale (HAD), Body Image Satisfaction Scale (BIS), and
Dermatology Quality of Life Scale (DQL) assessments were performed to
determine the psychological effect of CL. The patients with CL had
significantly higher HAD anxiety and depression subscale scores than the
control groups. Patients with CL have decreased body satisfaction and
lower quality of life than those in the control group. It was found that
CL patients with active lesions have the lowest quality of life score
than other groups. CL lesions on exposed body parts such as the face and
hands, active CL for more than 1 year, permanent scar formation, and
social stigmatization cause anxiety, depressive symptoms, decreased body
satisfaction and quality of life in CL patients.
PMID: 15345228
TITLE: Leishmania braziliensis isolates differing at the genome level display
distinctive features in BALB/c mice.
AUTHORS: Camila Indiani De Oliveira, Maria Jania Teixeira, Clarissa Romero
Teixeira, JoÃlson Ramos De Jesus, Andréa Bomura Rosato, João Santa da Silva,
Cláudia Brodskyn, Manoel Barral-Netto, Aldina Barral
AFFILIATION: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua
Waldemar Falcão, 121, Salvador, BA 40295-001, Brazil.
REFERENCE: Microbes Infect 2004 Sep 6(11):977-84
Leishmania braziliensis is the species responsible for the majority of
cases of human cutaneous leishmaniasis in Brazil. In the present study,
L. braziliensis isolates from two different geographic areas in Brazil
were studied by RAPD, using arbitrary primers. We also evaluated other
biological features of these two isolates. We compared (a) the clinical
features they initiate or not once delivered subcutaneously as
stationary-phase promastigotes in the footpad of BALB/c mice; (b) the
parasite load in both the footpad and the draining lymph node; (c) the
cytokines present in the supernatant of cultures of the cell suspensions
from the draining lymph nodes; and (d) the cell types present at the
site of parasite delivery. The results show that the L. braziliensis
strain from Ceará (H3227) is genotypically different from the L.
braziliensis strain from Bahia (BA788). H3227-parasitized mice developed
detectable lesions, whereas BA788-parasitized mice did not. Fifteen
days post parasite inoculation there was an increase in the numbers of
macrophages and lymphocytes in the footpads, whatever the parasite
inoculum. Parasite load at the inoculation site-namely the footpad-did
not differ significantly; in draining lymph nodes, however, it increased
over the period under study. Early after parasite inoculation, the
cells recovered from the draining lymph nodes of BA788-parasitized mice
produced higher levels of IFN-gamma, a feature coupled to a higher
number of NK cells. Later, after the parasite inoculation, there was an
increased content of IL-12p70 and IL-10 in the supernatant of cells
recovered from the lymph nodes of H3227-parasitized mice. This
comparative analysis points out that L. braziliensis isolates differing
in their genomic profiles do establish different parasitic processes in
BALB/c mice.
PMID: 15350508
TITLE: An alternative immunohistochemical method for detecting Leishmania
amastigotes in paraffin-embedded canine tissues.
AUTHORS: Wagner Luiz Tafuri, Renato de Lima Santos Rd, Rosa Maria Esteves
Arantes, Ricardo Gonçalves, Maria Norma De Melo, Marilene Suzan Marques
Michalick, Washington Luiz Tafuri
AFFILIATION: Departamento de Patologia Geral, Instituto de Ciências
Biológicas
(ICB), Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627,
Campus Pampulha, Belo Horizonte, MG/Brasil-CEP 31270-901, Brazil.
REFERENCE: J Immunol Methods 2004 Sep 292(1-2):17-23
Canine visceral leishmaniasis (CVL) is a zoonosis and a chronic systemic
disease of the dog caused by a protozoan by the species Leishmania
infantum in the Old World and Leishmania chagasi in the New World.
Several methods are currently employed for the diagnosis of CVL
including microscopic detection of the parasite in bone marrow and lymph
node aspirates, demonstration of specific antibodies anti-Leishmania in
sera from infected animals, and isolation of the parasite by in vitro
culture or by inoculation of laboratory animals. However, a definitive
diagnosis is based on the actual detection of the parasite, which is
conventionally achieved by examining Giemsa-stained smears or
histopathological sections stained with hematoxylin and eosin. These
methods have a low sensitivity, and therefore, they are often
inconclusive. This is particularly true in canine organs that have a low
level of parasitism such as kidneys, lungs, central nervous system, and
testis, or, in some cases, the skin. The technique for
immunohistochemical detection of leishmanial amastigotes in canine
tissues has been reported previously and has proved to be undoubtedly
efficient for the diagnosis. In this paper, we describe a
straightforward and inexpensive immunohistochemical approach for
Leishmania detection in formalin-fixed paraffin-embedded canine tissues
. Amastigote forms of Leishmania were easily observed within macrophages
in several organs from naturally infected dogs using the streptavidin-
biotin immunohistochemical method with canine hyperimmune serum as the
primary antibody. In addition, the secondary antibody used was not
specific to canine immunoglobulin, characterizing a cross-immune
reaction. Our results indicate that this technique could be a useful
tool for epidemiological, clinical, and histopathological studies.
PMID: 15352720
TITLE: A preliminary approach to the separation of Leishmania cell-surface
antigens.
AUTHORS: Nurten Aksoy, Hatice Ozbilge, Salt Keles, Mehmet Iriadam, Hüjseyin
Vural, Fatih Akcay
AFFILIATION: Department of Biochemistry, Faculty of Medicine, Atatürk
University, Erzurum, Turkey. naksoy at harran.edu.tr
REFERENCE: J Sep Sci 2004 Aug 27(12):1011-6
The purpose of the current study was to characterize Leishmania cell-
surface antigens by two different methods established for the
purification of glycoproteins and proteins, and to point out a useful
approach to define their size and mass heterogeneity. L. tropica
parasites were initially isolated from patients with active cutaneous
leishmaniasis and were then cultured in vitro. The parasite-cell layer
was solubilised with 6 M guanidinium chloride (GuHCl) and subsequently
prepared for the purification procedure. The methods used in this work
were gel filtration chromatography and isopycnic density-gradient
centrifugation. Because of the presence of a substantial amount of non-
specific proteins in the culture medium, these methods were not
effective alone in distinguishing these antigens. However, a good idea
of their N-glycosylated structures could be obtained by using Periodic
acid-Schiffs (PAS) and Con A lectin, and also size and mass
heterogeneity. A combination of these methods effected a clear
separation of the antigens. Amino acid analysis of the purified antigens
was performed to positively identify them as well-known Leishmania cell
-surface antigen gene products. The results confirmed the presence of
more than one cell-surface antigen on the Leishmania parasite and the
combination of gel chromatography and density-gradient centrifugation
could be useful for their isolation.
PMID: 15299234
TITLE: Smouldering focus of kala-azar in Assam.
AUTHORS: Purva Mathur, J C Samantaray, Sunanda Mangraj
REFERENCE: Indian J Med Res 2004 Jul 120(1):56
PMID: 15180401
TITLE: DACTARI: results from the first year.
AUTHORS: P A Manser
REFERENCE: Vet Rec 2004 May 154(20):639
PMID: 15123745
TITLE: The cell surface receptor SLAM controls T cell and macrophage functions.
AUTHORS: Ninghai Wang, Abhay Satoskar, William Faubion, Duncan Howie, Susumu
Okamoto, Stefan Feske, Charles Gullo, Kareem Clarke, Miriam Rodriguez Sosa,
Arlene H Sharpe, Cox Terhorst
AFFILIATION: Division of Immunology, RE-204, Beth Israel Deaconess Medical
Center, Harvard Medical School, 41 Avenue Louis Pasteur, Boston, MA 02215,
USA.
REFERENCE: J Exp Med 2004 May 199(9):1255-64
Signaling lymphocyte activation molecule (SLAM), a glycoprotein
expressed on activated lymphocytes and antigen-presenting cells, has
been shown to be a coregulator of antigen-driven T cell responses and is
one of the two receptors for measles virus. Here we show that T cell
receptor-induced interleukin (IL)-4 secretion by SLAM(-/-) CD4(+) cells
is down-regulated, whereas interferon gamma production by CD4(+) T cells
is only slightly up-regulated. Although SLAM controls production of IL-
12, tumor necrosis factor, and nitric oxide in response to
lipopolysaccharide (LPS) by macrophages, SLAM does not regulate
phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as a
coreceptor that regulates signals transduced by the major LPS receptor
Toll-like receptor 4 on the surface of mouse macrophages. A defective
macrophage function resulted in an inability of SLAM(-/-) C57Bl/6 mice
to remove the parasite Leishmania major. We conclude that the coreceptor
SLAM plays a central role at the interface of acquired and innate
immune responses.
PMID: 14993255
TITLE: MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic
cells is sufficient for control of Leishmania major.
AUTHORS: Maria P Lemos, Fatima Esquivel, Phillip Scott, Terri M Laufer
AFFILIATION: Department of Medicine, University of Pennsylvania, Philadelphia
19104, USA.
REFERENCE: J Exp Med 2004 Mar 199(5):725-30
Control of the intracellular protozoan, Leishmania major, requires major
histocompatibility complex class II (MHC II)-dependent antigen
presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC
II-positive macrophages are a primary target of infection and a crucial
effector cell controlling parasite growth, yet their function as antigen
-presenting cells remains controversial. Similarly, infected Langerhans
cells (LCs) can prime interferon (IFN)gamma-producing Th1 CD4+ T cells,
but whether they are required for Th1 responses is unknown. We explored
the antigen-presenting cell requirement during primary L. major
infection using a mouse model in which MHC II, I-Abeta(b), expression is
restricted to CD11b+ and CD8alpha+ dendritic cells (DCs). Importantly,
B cells, macrophages, and LCs are all MHC II-negative in these mice. We
demonstrate that antigen presentation by these DC subsets is sufficient
to control a subcutaneous L. major infection. CD4+ T cells undergo
complete Th1 differentiation with parasite-specific secretion of
IFNgamma. Macrophages produce inducible nitric oxide synthase,
accumulate at infected sites, and control parasite numbers in the
absence of MHC II expression. Therefore, CD11b+ and CD8alpha+ DCs are
not only key initiators of the primary response but also provide all the
necessary cognate interactions for CD4+ T cell Th1 effectors to control
this protozoan infection.
PMID: 15334262
TITLE: [Clinical and epidemiological aspects of visceral leishmaniasis in
children up to 15 years of age in Alagoas, Brasil]
AUTHORS: Célia Maria Silva Pedrosa, Eliana Maria Mauricio da Rocha
AFFILIATION: Departamento de ClÃnica Médica, Centro de Ciências da Saúde,
Universidade Federal de Alagoas, Maceió, AL, Brasil. leishmania at ig.com.br
REFERENCE: Rev Soc Bras Med Trop 2004 Jul-Aug 37(4):300-4
In order to investigate epidemiological and clinical characteristics of
visceral leishmaniasis in children up to 15 years old, a prospective
study was carried out in Alagoas, Brasil from 1981 to 1995. Of the 530
diagnosed cases, predominantly from the rural area of Alagoas State, 58
% were male and 42% female, being 55.3% children under 5 years old. The
most frequently observed clinical manifestations were:
hepatosplenomegaly, fever and parlor. The average size of the liver and
the spleen of patients with shorter time of disease (<30 days) were
smaller than those presenting sickness for a extended time (>or= 360
days). No matter the length of disease there was reduction of the liver
and the spleen after treatment. However, the reduction of the spleen was
higher in those patients with less time of sickness. With relation to
liver that difference was not observed.
PMID: 15334263
TITLE: [Visceral leishmaniasis among Indians of the State of Roraima, Brazil:
clinical and epidemiologic aspects of the cases observed from 1989 to 1993]
AUTHORS: Jorge Augusto O Guerra, Marcus LuÃz B Barros, Nelson Ferreira Fé,
Marcus Vinitius F Guerra, Eloy Castellon, Marcilene Gomes Paes, Italo A
Sherlock
AFFILIATION: Fundação de Medicina Tropical do Amazona, Manaus, AM.
jguerra at horizon.com.br
REFERENCE: Rev Soc Bras Med Trop 2004 Jul-Aug 37(4):305-11
A description of the epidemiological profile of visceral leishmaniasis
among Indians in the State of Roraima, Brazil, was based on the clinical
characteristics of human and dog disease, ecological aspects of the
area where the cases occurred and entomologic investigations performed
from 1989 to 1993. The 82 human cases were reported in six out of eight
Counties that existed then in the state; there was a 69.5% predominance
of male cases among those registered and a greater (52.4%) occurrence of
the disease in children from zero to ten years old. The rate of natural
infection was 10.3% out of 3,773 dogs examined in 74 different
locations. Lutzomyia longipalpis was found in 31 areas with greater
prevalence of the disease. The human and animal cases as well as the
vectors were concentrated in areas where mountains and arable soil
predominate, typical locations for the occurrence of American visceral
leishmaniasis.
PMID: 14693119
TITLE: Histological and immunohistochemical study of clinically normal skin of
Leishmania infantum-infected dogs.
AUTHORS: L Solano-Gallego, H Fernández-Bellon, P Morell, D Fondevila, J
Alberola, A Ramis, L Ferrer
AFFILIATION: Departament de Farmacologia, Terapèutica i ToxicologÃa,
Universitat Autònoma de Barcelona 08193, Bellaterra, Barcelona, Spain.
REFERENCE: J Comp Pathol 2004 Jan 130(1):7-12
Skin lesions are the most usual manifestation of canine leishmaniosis.
The aim of this study was to investigate the histological pattern and
parasite load in clinically normal skin of Leishmania-infected dogs. Two
groups of Leishmania-infected dogs were studied. Group A consisted of
15 symptomless animals which, although seronegative or only mildly
seropositive, gave a positive polymerase chain reaction (PCR) for
Leishmania in the skin. Group B consisted of 20 clinically affected dogs
which were highly seropositive and PCR-positive. Biopsies of normal
skin from all dogs were processed for routine histology and Leishmania
immunohistochemistry. The study demonstrated microscopical lesions and
the presence of parasites in the skin from dogs of group B, but not
group A. The results cast doubt on the relevance of infected but
symptomless dogs in the epidemiology of canine leishmaniosis. In
contrast, however, the clinically normal skin of sick dogs harbours the
parasite and probably plays a role in the transmission of leishmaniosis.
PMID: 15339122
TITLE: Characterization of Leishmania parasites isolated from provinces of the
Islamic Republic of Iran.
AUTHORS: H Motazedian, B Noamanpoor, S Ardehali
AFFILIATION: Department of Parasitology and Mycology, Shiraz University of
Medical Sciences, Shiraz, Islamic Republic of Iran.
REFERENCE: East Mediterr Health J 2002 Mar-May 8(2-3):338-44
Leishmania parasites isolated in the Islamic of Iran were studied by a
random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR).
Of 82 isolates, 80 were from cutaneous lesions, 1 from a human throat
lesion and 1 from a dog. Of these, 42 isolates were L. tropica, 36 were
L. major and 2 were L. infantum. There were 2 unidentified isolates (
from the throat lesion and a cutaneous lesion) and these demonstrated 52
% and 48% similarity with L. tropica and L. infantum. Both L. tropica
and L. major were isolated from four provinces indicating a recent
change in the epidemiology of cutaneous leishmaniasis. L. tropica was
isolated from three provinces; L. major from one province. L. infantum
was isolated from a human cutaneous lesion and from a dog in Bushehr
province.
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PMID: 12189207
TITLE: Dysregulated T helper cell differentiation in the absence of interferon
regulatory factor 4.
AUTHORS: Michael Lohoff, Hans-Willi Mittrücker, Stefan Prechtl, Susi Bischof,
Frank Sommer, Sonja Kock, David A Ferrick, Gordon S Duncan, Andre Gessner, Tak
W Mak
AFFILIATION: Institut für Medizinische Mikrobiologie, Pilgrimstein 2, 35037
Marburg, Germany.
REFERENCE: Proc Natl Acad Sci U S A 2002 Sep 99(18):11808-12
Certain IFN regulatory factor (IRF) transcription factors indirectly
influence T helper (Th) cell differentiation by regulating the
production of IL-12. Here, we show that IRF4 directly regulates Th cell
differentiation in vitro and in vivo during murine leishmaniasis. In the
absence of IRF4, IL-12-induced Th1 cell differentiation was compromised
, while IL-4 failed to induce Th2 cell differentiation. Instead, IL-4
tended to induce Th1 cells, defined by production of IFN-gamma and TNF.
Although early IL-4 signaling was normal in IRF4(-/-) Th cells, the
protein GATA-3, a transcription factor critical for Th2 development, was
not up-regulated following IL-4 treatment. Retroviral overexpression of
GATA-3 rescued Th2 differentiation. Therefore, IRF4 deficiency
manifests itself as severely dysregulated Th cell differentiation.
PMID: 8731290
TITLE: Current concepts on the transmission of bacteria and parasites by blood
components.
AUTHORS: S Wendel Neto
AFFILIATION: Hospital Sirio-Libanês Blood Bank, São Paulo, Brazil.
REFERENCE: Sao Paulo Med J 1995 Nov-Dec 113(6):1036-52
Several bacterial and parasite transfusion-transmitted diseases have
been described in the medical literature. This review deals with the
main bacterial (Syphilis, Lyme disease, Gram positive and Gram negative
agents), parasite (Chagas disease, malaria, leishmaniasis, toxoplasmosis
and babesiosis) and rickettsial diseases that are carried by blood
products. Preventional aspects (e.g. storage, screening tests, use of
leukocyte-depleted components), diagnosis, geographical distribution and
the incidence of these transfusional hazards are also discussed.
REQUEST: [ leishmania ]
(19 articles match this request. 8 articles matching other requests removed)
PMID: 15336561
TITLE: TcRRMs and Tcp28 genes are intercalated and differentially expressed in
Trypanosoma cruzi life cycle.
AUTHORS: Giselle Guimarães Gomes, Turán Peter Urményi, Edson Rondinelli,
Noreen Williams, Rosane Silva
AFFILIATION: Instituto de BiofÃsica Carlos Chagas Filho, Universidade Federal
do Rio de Janeiro, Brazil.
REFERENCE: Biochem Biophys Res Commun 2004 Sep 322(3):985-92
The identification and characterization of RNA binding proteins in
Trypanosoma cruzi are particularly relevant as they play key roles in
the regulatory mechanisms of gene expression. In this work, we have
identified coding sequences for the proteins, named TcRRM1 and TcRRM2,
in the EST database generated by the T. cruzi genomic initiative. TcRRM1
and TcRRM2 contain two RNA binding domains (RRM) and are very similar
to two Trypanosoma brucei RNA binding proteins previously reported,
Tbp34 and Tbp37, and to a not yet annotated ORF in Leishmania major
genome project. The T. cruzi RRM genes are organized in tandem,
alternating with copies of Tcp28, a gene of unknown function. However,
TcRRM transcript accumulation is higher in the spheromastigote stage,
while Tcp28 transcripts accumulate more in the trypomastigote stage
suggesting developmental regulation.
PMID: 15329410
TITLE: A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in
Leishmania major.
AUTHORS: Tim J Vickers, Neil Greig, Alan H Fairlamb
AFFILIATION: Division of Biological Chemistry and Molecular Microbiology,
Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, DD1
5EH Dundee, Scotland.
REFERENCE: Proc Natl Acad Sci U S A 2004 Sep 101(36):13186-91
Glyoxalase I forms part of the glyoxalase pathway that detoxifies
reactive aldehydes such as methylglyoxal, using the spontaneously formed
glutathione hemithioacetal as substrate. All known eukaryotic enzymes
contain zinc as their metal cofactor, whereas the Escherichia coli
glyoxalase I contains nickel. Database mining and sequence analysis
identified putative glyoxalase I genes in the eukaryotic human parasites
Leishmania major, Leishmania infantum, and Trypanosoma cruzi, with
highest similarity to the cyanobacterial enzymes. Characterization of
recombinant L. major glyoxalase I showed it to be unique among the
eukaryotic enzymes in sharing the dependence of the E. coli enzyme on
nickel. The parasite enzyme showed little activity with glutathione
hemithioacetal substrates but was 200-fold more active with
hemithioacetals formed from the unique trypanosomatid thiol
trypanothione. L. major glyoxalase I also was insensitive to glutathione
derivatives that are potent inhibitors of all other characterized
glyoxalase I enzymes. This substrate specificity is distinct from that
of the human enzyme and is reflected in the modification in the L. major
sequence of a region of the human protein that interacts with the
glycyl-carboxyl moiety of glutathione, a group that is conjugated to
spermidine in trypanothione. This trypanothione-dependent glyoxalase I
is therefore an attractive focus for additional biochemical and genetic
investigation as a possible target for rational drug design.
PMID: 15336424
TITLE: Characterisation of a new Leishmania META gene and genomic analysis of
the META cluster.
AUTHORS: Camila S Ramos, Fernando A L Franco, Deborah F Smith, Silvia R B
Uliana
AFFILIATION: Department of Parasitology, Institute of Biomedical Sciences,
Universidade de São Paulo, São Paulo 05508-900 SP, Brazil.
REFERENCE: FEMS Microbiol Lett 2004 Sep 238(1):213-9
The META1 gene of Leishmania is upregulated in metacyclic promastigotes
and encodes a 12 kDa virulence-related protein, conserved in all
Leishmania species analysed. In this study, the genomic region adjacent
to the Leishmania amazonensis META1 gene was characterised and compared
to the Leishmania major META1 locus as well as to syntenic loci
identified in Trypanosoma brucei and Trypanosoma cruzi. Three new genes
expressed with increased abundance of steady state mRNA in L.
amazonensis promastigotes were identified, two of which are upregulated
in stationary phase promastigotes, sharing the pattern of expression
previously described for the META1 mRNA. One of these new genes, named
META2, encodes a polypeptide of 444 amino acid residues with a
repetitive structure showing three repeats of the META domain (defined
as a small domain family found in the Leishmania META1 protein and in
bacterial proteins hypothetically secreted and/or implicated in motility
) and a carboxyl-terminal region similar to several putative calpain-
like proteins of Trypanosoma and Leishmania.
PMID: 15202932
TITLE: Incomplete glycosylation and defective intracellular targeting of mutant
solute carrier family 11 member 1 (Slc11a1).
AUTHORS: Jacqueline K White, Abigail Stewart, Jean-Francois Popoff, Shona
Wilson, Jenefer M Blackwell
AFFILIATION: Cambridge Institute for Medical Research, University of Cambridge
School of Clinical Medicine, Wellcome Trust/MRC Building, Addenbrooke's
Hospital, Hills Road, Cambridge CB2 2XY, U.K.
REFERENCE: Biochem J 2004 Sep 382(Pt 3):811-9
Solute carrier family 11 member 1 (Slc11a1, formerly Nramp1) is a highly
glycosylated, 12 transmembrane domain protein expressed in macrophages
. It resides in the membrane of late endosomes and lysosomes, where it
functions as a bivalent cation transporter. Mice susceptible to
infection by various intracellular pathogens including Leishmania
donovani and Salmonella typhimurium carry a glycine to aspartic acid
substitution at position 169 (G169D, Gly(169)-->Asp), within
transmembrane domain 4 of Slc11a1. To investigate the molecular
pathogenesis of infectious disease susceptibility, we compared the
behaviour of heterologously and endogenously expressed wild-type and
mutant Slc11a1 by immunofluorescence, immunoelectron microscopy and
Western-blot analysis. We found occasional late endosome/lysosome
staining of mutant protein using immunoelectron microscopy, but most of
the mutant Slc11a1 was retained within the ER (endoplasmic reticulum).
Using glycosylation as a marker for protein maturation in two
independent heterologous expression systems, we found that most mutant
Slc11a1 existed as an ER-dependent, partially glycosylated intermediate
species. Correct endosomal targeting of wild-type Slc11a1 continued
despite disruption of N-glycosylation sites, indicating that
glycosylation did not influence folding or sorting. We propose that the
G169D mutation causes localized misfolding of Slc11a1, resulting in its
retention in the ER and manifestation of the loss of function phenotype.
PMID: 15193556
TITLE: Virulence and disease in leishmaniasis: what is relevant for the
patient?
AUTHORS: Luis Rivas, Javier Moreno, Carmen Cañavate, Jorge Alvar
AFFILIATION: Centro de Investigaciones Biológicas, Consejo Superior de
Investigaciones CientÃficas (CSIC), Ramiro de Maeztu 9, 28040-Madrid, Spain.
REFERENCE: Trends Parasitol 2004 Jul 20(7):297-301
PMID: 15193564
TITLE: Leishmaniasis in Israel and the Palestinian Authority.
AUTHORS: Charles L Jaffe, Gad Baneth, Ziad A Abdeen, Yosef Schlein, Alon
Warburg
AFFILIATION: Department of Parasitology, Kuvin Centre for the Study of
Infectious and Tropical Diseases, Hebrew University-Hadassah Medical School, PO
Box 12272, Jerusalem 91220, Israel.
REFERENCE: Trends Parasitol 2004 Jul 20(7):328-32
PMID: 15193411
TITLE: Protective vaccination against murine visceral leishmaniasis using
aldehyde-containing Quillaja saponaria sapogenins.
AUTHORS: C B Palatnik de Sousa, W R Santos, C P Casas, E Paraguai de Souza, L W
Tinoco, B P da Silva, M Palatnik, J P Parente
AFFILIATION: Instituto de Microbiologia, Prof. Paulo de Góes, Universidade
Federal do Rio de Janeiro (UFRJ), CCS, Cidade Universitária, Ilha do Fundão,
CP 68040, CEP 21941-590, Rio de Janeiro, RJ, Brazil. clarisaps at infolink.com.br
REFERENCE: Vaccine 2004 Jun 22(19):2470-9
The presence of aldehyde groups at C-23 and C-24 of the triterpen
aglycon moiety was disclosed in 1H NMR spectra of both the Riedel de
Haen saponin (R) (delta 9.336) and Quillaja saponaria QuilA saponin (
delta 9.348). The sign of the C-28 acylated linked moiety (delta 176)
was present in both saponins, while the delta 171 at C-28 (carboxy group
) corresponding to the deacylated saponin, was only detected in the
QuilA preparation, indicating 50% of hydrolysis of the ester moiety,
probably due to the storage in aqueous solution. The normoterpen moiety
was present in both saponins (signals at delta 14-18).The chemical
removal of saponin glicidic moieties gave rise to their sapogenin
fractions. Their 1H NMR spectra showed the presence of two signals (
delta 9.226 and 9.236) for sapogenin R and two signals (delta 9.338 and
9.352) for the QuilA sapogenin. The intensity of the signals suggested
two conformational isomers of sapogenin R in the ratio 53% of equatorial
aldehyde group to 47% of axial aldehyde group, and two conformational
isomers of QuilA sapogenin in the ratio 76% of equatorial aldehyde group
to 24% of axial aldehyde group. The chemical treatment abolished the
saponin slight in vivo toxicity, reduced their hemolytic potential, did
not affect their aldehyde contents, but gave rise to an enriched axial
aldehyde-containing sapogenin R with enhanced potential on antibody
humoral response (anti-IgM, IgG, IgG1, IgG2a, IgG2b and IgG3) and to an
enriched equatorial aldehyde-containing QuilA-sapogenin that induced a
mainly cellular specific immune response (increased intradermal response
to leishmanial antigen and IFNgamma sera levels) and effective
protection against murine infection by L. donovani (77% reduction in
liver parasitic load). Our results suggest that the Riedel de Haen
saponin is probably a Quillaja saponaria saponin.
PMID: 15338471
TITLE: Protein kinase A activity is associated with metacyclogenesis in
Leishmania amazonensis.
AUTHORS: Marcelo Genestra, Léa Cysne-Finkelstein, Leonor Leon
AFFILIATION: Department of Immunology, Oswaldo Cruz Institute, Rio de Janeiro,
RJ, Brazil.
REFERENCE: Cell Biochem Funct 2004 Sep-Oct 22(5):315-20
Because of the importance of cell signalling processes in proliferation
and differentiation, the adenylate cyclase pathway was studied,
specifically the protein kinase A (PKA) in Leishmania amazonensis. The
PKAs of soluble (SF) and enriched membrane fractions (MF) from infective
/non-infective promastigotes and axenic amastigotes were assayed. In
order to purify the PKA molecule, fractions were chromatographed on DEAE
-cellulose columns and the phosphorylative activity was evaluated using
[gamma(32)P]-ATP as the phosphate source. These experiments were
performed in the presence of cyclic adenosine monophosphate (cAMP) and
an inhibitor of PKA. Our data demonstrated that the PKA activity was
significantly higher (about two times) in SF from promastigotes with a
high concentration of metacyclic forms, when compared with the non-
infective promastigotes, suggesting an association of this activity and
the metacyclogenesis process. A discrete phosphorylative activity in
axenic amastigotes was observed. As the adenylate cyclase/cAMP pathway
would be involved in the parasite-host interiorization, the PKA activity
may constitute a good intracellular target for studies of
leishmanicidal drugs. Copyright 2004 John Wiley & Sons, Ltd.
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PMID: 15249594
TITLE: Enhanced TCR-induced apoptosis in interferon regulatory factor
4-deficient CD4(+) Th cells.
AUTHORS: Michael Lohoff, Hans-Willi Mittrücker, Anne Brüstle, Frank Sommer,
Bärbel Casper, Magda Huber, David A Ferrick, Gordon S Duncan, Tak W Mak
AFFILIATION: Advanced Medical Discovery Institute, 620 University Ave, Suite
706, Toronto, Ontario, Canada M5G 2C1.
REFERENCE: J Exp Med 2004 Jul 200(2):247-53
Transcription factors of the interferon regulatory factor (IRF) family
contribute to the regulation of cell proliferation and apoptosis. Here,
we show that CD4(+) T helper (Th) cells lacking IRF4 (IRF4(-/-)) are
highly sensitive to apoptosis. After infection of IRF4(-/-) mice with
the protozoan parasite Leishmania major, the lesion-draining lymph nodes
developed the prototypic lymphadenopathy of wild-type mice after 4 wk,
but demonstrated almost total loss of cellularity and enhanced apoptosis
after 7 wk. In vitro, activation of IRF4(-/-) CD4(+) Th cells led to
greatly increased apoptosis compared with wild-type cells. Coculture of
IRF4(-/-) and IRF4(+/+) CD4(+) cells did not increase survival of IRF4
(-/-) CD4(+) cells, indicating that the enhanced rate of IRF4(-/-) Th
cell apoptosis was neither transferable nor due to lack of a cytokine.
Enhanced CD4(+) cell apoptosis was also observed after anti-CD95 mAb
treatment, despite normal CD95 expression. Removal of endogenous
cytokines, notably interleukin (IL)-4, led to increased and equally high
levels of IRF4(-/-) and IRF4(+/+) cell apoptosis, whereas the
protective activity of exogenous IL-4 was reduced in IRF4(-/-) CD4(+)
cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is
central in protecting CD4(+) cells against proapoptotic stimuli.
PMID: 14592970
TITLE: Rab5-mediated endosome-endosome fusion regulates hemoglobin endocytosis
in Leishmania donovani.
AUTHORS: Sudha B Singh, Ruchi Tandon, Ganga Krishnamurthy, Rajagopal Vikram,
Nimisha Sharma, Sandip K Basu, Amitabha Mukhopadhyay
AFFILIATION: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi
110067, India.
REFERENCE: EMBO J 2003 Nov 22(21):5712-22
To understand the trafficking of endocytosed hemoglobin (Hb) in
Leishmania, we investigated the characteristics of in vitro fusion
between endosomes containing biotinylated Hb (BHb) and avidin-
horseradish peroxidase (AHRP). We showed that early endosome fusion in
Leishmania is temperature and cytosol dependent and is inhibited by ATP
depletion, ATPgammaS, GTPgammaS and N-ethylmaleimide treatment. The Rab5
homolog from Leishmania donovani, LdRab5, was cloned and expressed. Our
results showed that homotypic fusion between the early endosomes in
Leishmania is Rab5 dependent. Early endosomes containing BHb fused
efficiently with late endosomes in a process regulated by Rab7, whereas
no fusion between early and late endosomes was detected using fluid
phase markers. Pre-treatment of early endosomes containing BHb with
monoclonal antibody specific for the C-terminus of the Hb receptor (HbR
) or the addition of the C-terminal cytoplasmic fragment of the HbR
specifically inhibited the fusion with late endosomes, suggesting that
signal(s) mediated through the HbR cytoplasmic tail promotes the fusion
of early endosomes containing Hb with late endosomes.
PMID: 11166387
TITLE: Tetracycline regulated gene expression in Leishmania donovani.
AUTHORS: S Yan, P J Myler, K Stuart
AFFILIATION: Seattle Biomedical Research Institute, 4 Nickerson Street,
Seattle,
WA 98109-1651, USA.
REFERENCE: Mol Biochem Parasitol 2001 Jan 112(1):61-9
The prokaryotic tetracycline-responsive repressor/operator system has
proven to be useful for studying the function of essential genes and the
expression of toxic gene products in a number of organisms, including
Trypanosoma brucei. We report here the adaptation of this system for use
in Leishmania. The inducible promoter construct contains a bleomycin
resistance-luciferase fusion (BLE-LUC) gene driven by an rRNA promoter
with two copies of the TetO sequence inserted two nucleotides upstream
of the transcriptional start site. This construct showed regulation of
BLE-LUC expression by two orders of magnitude when targeted into the
rDNA locus in the reverse orientation relative to transcription of the
rRNA genes in a Leishmania donovani cell line expressing TETR. The
luciferase expression level in the absence of tetracycline was
approximately 50-fold lower than that in the tubulin locus (where it is
transcribed by pol II), while the expression level in the presence of
tetracycline was approximately five-fold higher than that from the
tubulin locus. There was no linear relationship between the level of
TETR expression and the regulation, and changing of positions of
operator did not increase regulation.
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