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REQUEST: [ leishmaniasis ]
(12 articles match this request)
PMID: 15364993
TITLE: Isoenzymatic Analysis of 712 Strains of Leishmania infantum in the South
of France and Relationship of Enzymatic Polymorphism to Clinical and
Epidemiological Features.
AUTHORS: Francine Pratlong, Jean-Antoine Rioux, Pierre Marty, Françoise
Faraut-Gambarelli, Jacques Dereure, Geneviève Lanotte, Jean-Pierre Dedet
AFFILIATION: Laboratoire de Parasitologie, 163, rue Auguste Broussonet, 34090
Montpellier, France. parasito at univ-montp1.fr
REFERENCE: J Clin Microbiol 2004 Sep 42(9):4077-82
In the south of France, leishmaniasis due to Leishmania infantum occurs
in the following five foci of endemicity (from west to east): Pyrénées
-Orientales, Cévennes, Provence, Côte d'Azur, and Corsica. Between
1981 and 2002, 712 Leishmania strains obtained from humans, dogs, cats,
and sand flies were studied by isoenzyme analysis. In total, seven
zymodemes were identified: MON-1, MON-11, MON-24, MON-29, MON-33, MON-34
, and MON-108. The Pyrénées-Orientales focus is characterized by a
predominance of human cutaneous leishmaniasis and a high enzymatic
polymorphism (five zymodemes). In the other foci, where human visceral
leishmaniasis is predominant, only two zymodemes are present. L.
infantum MON-1 is the parasite most frequently found, in patients both
with and without concomitant human immunodeficiency virus infection. MON
-1 is the only zymodeme present in dogs, which act as the reservoir host
in all of the foci. In Cévennes, where the complete life cycle of
zymodeme MON-1 has been identified, Phlebotomus perniciosus and
Phlebotomus ariasi are vectors. The enzymatic polymorphism is compared
to that of neighboring countries (Spain and Italy). In Pyrénées-
Orientales, small variant zymodemes with electromorphs of heterozygote-
like and homozygotic patterns can be explained by different genetic
hypotheses.
PMID: 15364433
TITLE: Vaccination with a plasmid DNA cocktail encoding the nucleosomal histones
of Leishmania confers protection against murine cutaneous leishmaniosis.
AUTHORS: Salvador Iborra, Manuel Soto, Javier Carrión, Carlos Alonso, Jose M
Requena
AFFILIATION: Centro de BiologÃa Molecular "Severo Ochoa", Universidad Autónoma
de Madrid, Campus de Cantoblanco, Madrid E-28049, Spain.
REFERENCE: Vaccine 2004 Sep 22(29-30):3865-76
Leishmania histones are relevant immunogens for the host immune system
during both Leishmania infection and disease. In the present paper we
have evaluated the prophylactic value of the four Leishmania infantum
histones forming the nucleosomal core in the murine model of cutaneous
leishmaniasis. In a first stage, the immune response elicited by the
intramuscular injection of a mixture of four plasmid DNAs, encoding the
L. infantum histones H2A, H2B, H3 and H4, was determined in BALB/c mice
. It was found that the immunized animals developed a specific Th1
immune response, which was associated with an antigen-specific
production of interferon (IFN-gamma) and a limited humoral response
against histones (dominated by antibodies of the IgG2a isotype).
According to the pure Th1-type immune response elicited by the DNA
vaccination with Leishmania histones, vaccinated mice showed a solid
immunity that efficiently controlled the Leishmania major infection. The
protection in mice vaccinated with histone-DNAs was associated with a
low humoral response against leishmanial antigens, an enhanced IFN-gamma
production and little, if any, IL-4 production. The relative
contribution of both CD8(+) and CD4(+) T cells to the IFN-gamma
production, and the IL-12 dependence were also evaluated. All these data
indicated that DNA vaccination with Leishmania histones genes results
in a specific Th1-like response during L. major infection, and that both
CD4(+) and CD8(+) T cells contribute to the resistance of vaccinated
mice to cutaneous leishmaniasis.
PMID: 15364462
TITLE: Double-blind randomized efficacy field trial of alum precipitated
autoclaved Leishmania major vaccine mixed with BCG against canine visceral
leishmaniasis in Meshkin-Shahr district, I.R. Iran.
AUTHORS: Mehdi Mohebali, Ali Khamesipour, Iraj Mobedi, Zabih Zarei, Reza
Hashemi-Fesharki
AFFILIATION: School of Public Health and Institute of Public Health Research,
Tehran University of Medical Sciences, P.O. Box 14155-6446, Tehran, Iran.
REFERENCE: Vaccine 2004 Sep 22(29-30):4097-100
This study was designed to evaluate the efficacy of a single dose of
aluminum hydroxide (alum) precipitated Leishmania major (Alum-ALM)
vaccine plus BCG against canine visceral leishmaniasis. Three hundred
and forty-seven healthy dogs with no anti-Leishmania antibodies were
double-blind randomly injected intradermally with either 0.1ml of Alum-
ALM (200microg protein) mixed with BCG (182 dogs) or injected with 0.1ml
of normal saline (165 dogs). The results of 16 months follow-up showed
that the vaccine was safe and well-tolerated. Strong seroconversion
using DAT and ELISA techniques at 16 months post-vaccination was
considered as an indication of Leishmania infection. The incidence rate
was 3.7% (6/162) in vaccinated group and 12.0% (17/141) in control group
using DAT technique. The efficacy of the vaccine was calculated to be
69.3%.
PMID: 15357081
TITLE: Clinical features, epidemiology, and efficacy and safety of intralesional
antimony treatment of cutaneous leishmaniasis: recent experience in Turkey.
AUTHORS: Soner Uzun, Murat Durdu, Gulnaz Culha, Adil M Allahverdiyev, Hamdi R
Memisoglu
AFFILIATION: Department of Dermatology, Cukurova University School of Medicine,
Adana 01330, Turkey. sonuzun at hotmail.com
REFERENCE: J Parasitol 2004 Aug 90(4):853-9
A total of 1,030 patients, 40.2% men and 59.8% women, identified during
the period of October 1998 to November 2002 as having cutaneous
leishmaniasis (CL), were studied; 1,431 lesions were identified in the 1
,030 patients. One lesion was present in 80.7% of the patients. The size
of the lesions (longest axis) was 13.6 mm (standard, 12.1 mm; range 3-
150 mm). Most of the lesions were of the papular type (51.2%), although
several atypical clinical presentations of CL were observed. The
duration of the disease ranged between 1 and 72 mo (mean duration, 10.8
mo). The clinical suspicion of CL was confirmed by the observation of
amastigotes on lesion tissue samples stained by Giemsa. The test was
positive in 851 of 1,030 patients (82.6%). Intralesional meglumine
antimonate solution (85 mg Sb/ml, 0.2-1 ml, depending on the size of the
lesion) weekly until complete cure or up to 20 wk was used for first-
line therapy of 890 patients (86.4%). We found that this regimen of
intralesional Sb has an efficacy of 97.2% with a low relapse rate of 3.9
% and no serious adverse side effects.
PMID: 15357103
TITLE: Molecular characterization of the Leishmania braziliensis L6 ribosomal
protein.
AUTHORS: M C Thomas, E Martinez-Carretero, E Carmelo, A C González, B
Valladares
AFFILIATION: Instituto de Parasitologia y Biomedicina López Neyra, C.S.J.C. Av.
del Conocimiento s/n 18100 Granada, Spain.
REFERENCE: J Parasitol 2004 Aug 90(4):908-13
By screening a Leishmania braziliensis complementary DNA library with a
pool of sera from leishmaniasis patients, the gene coding for L6
ribosomal protein was isolated. The sequence, genomic organization, and
transcription of this gene are described in this article. The sequence
analysis of the L. braziliensis L6 gene shows a single open reading
frame, which codes for a protein of 192 amino acids (aa) with a
hypothetical molecular mass of 20.9 kDa. The protein exhibits
significant sequence similarity to L6 ribosomal proteins from higher
eukaryotes and yeast. Thus, the L. braziliensis L6 protein contains 4
functional motifs, which are located at equivalent positions in other L6
ribosomal proteins described previously. Interestingly, the L6
ribosomal protein from L. braziliensis contains a specific region of 14
aa and a tyrosine kinase motif, which is absent in human and C. elegans
L6 protein. The locus coding the L. braziliensis L6 ribosomal protein is
formed by 2 gene copies arranged in tandem and located in a chromosome
of approximately 0.9. Mb. The genes are actively transcribed as 2
polyadenylated transcripts of approximately 1.15 and 0.85 kb, which
differ in their steady-state level and stability.
PMID: 15372998
TITLE: Case report of leishmaniasis in four cats.
AUTHORS: M G Pennisi, M Venza, S Reale, F Vitale, S Lo Giudice
AFFILIATION: Department of Medical Veterinary Sciences--Faculty of Veterinary
Medicine, University of Messina, Italy. MariaGrazia.Pennisi at unime.it
REFERENCE: Vet Res Commun 2004 Aug 28 Suppl 1():363-6
PMID: 15305319
TITLE: In vitro leishmanicidal activity of some scarce natural products.
AUTHORS: Marii Takahashi, Hiroyuki Fuchino, Setsuko Sekita, Motoyoshi Satake
AFFILIATION: Tsukuba Medicinal Plant Research Station, National Institute of
Health Sciences, Tsukuba, Japan.
REFERENCE: Phytother Res 2004 Jul 18(7):573-8
Leishmanicidal activity of 46 natural products including several fern
and Betula constituents was examined. Several pterosin and atisene
compounds from ferns had high activity. Among the triterpenoids the
carboxyl group was found to be important for activity. In the
diarylheptanoids, the linear-type and the diphenylether-type showed
significant activity, and it was found that the carbonyl group at C-11
is necessary for the activity of biphenyl-types.
PMID: 15234661
TITLE: The Leishmania chagasi proteasome: role in promastigotes growth and
amastigotes survival within murine macrophages.
AUTHORS: Izaltina Silva-Jardim, M Fátima Horta, F Juarez Ramalho-Pinto
AFFILIATION: Departamento de BioquÃmica e Imunologia, Faculdade de Medicina de
Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, CEP
14049-900, Brazil.
REFERENCE: Acta Trop 2004 Jul 91(2):121-30
Proteasomes are multisubunit proteases that exist universally among
eukaryotes. They have multiple proteolytic activities and are believed
to have important roles in regulating cell cycle, selective
intracellular proteolysis, and antigen presentation. Here we have
partially purified Leishmania chagasi proteasome. The L. chagasi
proteasome rich fraction displayed the typical features of eukaryotic
20S proteasome complexes, being active towards peptidyl substrates with
hydrophobic and acidic residues, and sensitive to the proteasome-
specific inhibitor lactacystin. We have shown that lactacystin, or its
active form clasto-lactacystin beta-lactone, but not E-64, blocks the in
vitro growth of L. chagasi promastigotes, demonstrating that the
interference with parasite growth is due to the lack of proteasome
activity. Furthermore, pre-treatment of L. chagasi promastigotes with
lactacystin did not prevent parasite entry in host cells, but markedly
restricted its intracellular survival. These results demonstrate that
intact parasite proteasome function is required for replication of L.
chagasi and for amastigotes survival inside the vertebrate host cell.
PMID: 15369643
TITLE: Facial and oral aspects of some venereal and tropical diseases.
AUTHORS: Marcia Ramos-E-Silva
AFFILIATION: Dermatology Sector and Post-Graduation Course University Hospital
and School of Medicine Federal University of Rio de Janeiro; Rua Sorocaba, 464
/ 205 22271-110 Rio de Janeiro Brazil; ramos.e.silva at dermato.med.br
REFERENCE: Acta Dermatovenerol Croat 2004 12(3):173-80
Diseases of the tropical areas include some venereal diseases, and they
are still very prevalent in some countries; Brazil is one of them. Very
few cases are originated in large cities, as Rio de Janeiro, but at the
University Hospital of the Federal University of Rio de Janeiro we also
see those patients who come from the interior of the State of Rio de
Janeiro or from other states to seek medical care at better equipped
hospitals for this type of investigation and therapy. Venereal and
tropical dermatoses have many different cutaneous manifestations and may
affect skin in several locations. The face is one of the affected areas
especially when the disease has a predilection for cartilage, oral and/
or nasal mucosa. Alterations observed on the skin of the face and on the
mucosa of the mouth of some tropical diseases, such as leprosy,
leishmaniasis, paracoccidioidomycosis, donovanosis, and syphilis, as
they are observed in Brazil, are presented and discussed in this article
PMID: 15267002
TITLE: A stable focus of canine leishmaniosis in the Bologna Province, Italy.
AUTHORS: E Mollicone, G Battelli, M Gramiccia, M Maroli, R Baldellii
AFFILIATION: Dipartimento di Sanità Pubblica Veterinaria e Patologia Animale,
Alma Mater Studiorum-Università di Bologna, via Tolara di Sopra 50, 40064
Ozzano dell'Emilia (BO), Italy.
REFERENCE: Parassitologia 2003 Jun 45(2):85-8
During an epidemiological survey carried out for two consecutive years (
2001-2002), autochthonous cases of canine leishmaniosis (CanL) were
reported in Communes of the Bologna Province (Emilia-Romagna Region,
northern Italy), involved in the past (1971-1972) in a severe outbreak
of human visceral leishmaniosis (VL). Serological controls, carried out
by immunofluorescence antibody test on a sample of owned dogs, detected
a mean prevalence of 2.5% in the first year in 4 Communes, and of 11.2%
in the second year in only one Commune, where an incidence value of 9.3
% was assessed. The autochthonous origin of the infection was confirmed
in 11 out of 13 positive animals in the first year and in 5 out of 6 new
cases in the second year. In one case the parasitological examinations
led to the isolation of leishmaniae characterized as Leishmania infantum
zymodeme MON 1. Entomological surveys carried out during two sandfly
seasons in one of the areas concerned by the VL outbreak showed the
presence of Phlebotomus perfiliewi and, to a lesser extent, of P
perniciosus, both proven vectors of L. infantum in Italy. The results
obtained seem to suggest the presence of a stable focus of CanL in the
territory involved in the previous VL outbreak of 1971-1972, within
which the infection in the canine population had been assessed only
serologically. Such an epidemiological situation may be seen either as
the persistence of an old focus or as a new imported one.
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PMID: 11269325
TITLE: Non-ulcerative cutaneous lesion in immunodeficient mice with Leishmania
amazonensis infection.
AUTHORS: M Terabe, T Kuramochi, T Hatabu, M Ito, Y Ueyama, K Katakura, S Kawazu,
T Onodera, Y Matsumoto
AFFILIATION: Department of Molecular Immunology, School of Agriculture and Life
Sciences, University of Tokyo, Japan.
REFERENCE: Parasitol Int 1999 Mar 48(1):47-53
Cutaneous leishmaniasis begins as papules or nodules at the site of
promastigote inoculation. The next key pathogenic event in this disease
is the formation of an ulcer at this site. Leishmania infection in
immunodeficient mice, however, showed non-ulcerative cutaneous lesions
suggesting the involvement of the immune system in ulcer formation.
Severe combined immunodeficient (SCID), recombination-activating gene 2
knockout (RAG-2-/-), and immunocompetent mice were inoculated
subcutaneously with cultured L. amazonensis promastigotes. Macroscopic
nodules appeared at the inoculation site within 2 weeks of infection in
all the mice and gradually extended to the surrounding skin tissue.
Although nodules of immunocompetent mice ulcerated within 6 weeks,
immunodeficient mice did not form ulcers even after 25 weeks of
inoculation. These results strongly suggest the importance of functional
T and B cells in ulcer formation of cutaneous leishmaniasis and are
consistent with clinical features of non-ulcerative cutaneous
leishmaniasis in some AIDS patients. The present study also indicates
that the L. amazonensis-infected immunodeficient mouse model might be
suitable for studying the mechanisms of ulcer formation in cutaneous
leishmaniasis.
PMID: 9164958
TITLE: Role of CD4+ T cells in pathogenesis associated with Leishmania
amazonensis infection.
AUTHORS: L Soong, C H Chang, J Sun, B J Longley, N H Ruddle, R A Flavell, D
McMahon-Pratt
AFFILIATION: Department of Epidemiology and Public Health, Yale University
School of Medicine, New Haven, CT 06520, USA.
REFERENCE: J Immunol 1997 Jun 158(11):5374-83
Most inbred strains of mice are susceptible to Leishmania amazonensis
infection. We have examined the mechanism(s) underlying this generalized
susceptibility using mice deficient in T cell development or in the
expression of either MHC class I or class II. In contrast to wild-type
C57BL/6 (B6) mice that uniformly developed large ulcerating lesions,
mice lacking functional CD4+ T cells (due to targeted disruption of
genes for either MHC class II trans-activator or I-A beta) showed no
signs of lesion development for up to 12 to 14 wk postinfection and
contained significantly lower numbers of parasites in lesions. Similarly
, both B6 nude and RAG2 -/- mice failed to develop lesions. However,
RAG2 -/- mice reconstituted with naive wild-type CD4+ T cells and beta2m
-/- mice did develop lesions. Lesions of MHC class II -/- mice
contained minimal numbers of CD8+ T cells, a marked reduction of
monocytes/macrophages, and evident extracellular parasites. The
inability to mount an inflammatory response in MHC class II -/- mice
correlated with the failure to produce lymphokines that lead to the
recruitment of monocytes/granulocytes. These results demonstrate that
CD4+ T cells are the primary lymphocyte subset that mediates cellular
infiltration, lesion pathology, and therefore, susceptibility to L.
amazonensis infection. The disease-promoting CD4+ T cells in L.
amazonensis-infected mice have the characteristics of Th1 cells. The
striking differences in the course of infection between MHC class II
-/- mice infected with L. amazonensis and Leishmania major suggest that
these parasites may have adapted different strategies regarding the CD4
-dependent immune response.
REQUEST: [ leishmania ]
(22 articles match this request. 7 articles matching other requests removed)
PMID: 15368281
TITLE: Frontline: Self-peptides that bind with low affinity to the
diabetes-associated I-A(g7) molecule readily induce T cell tolerance in
non-obese diabetic mice.
AUTHORS: Walter G Ferlin, Evelyne Mougneau, Stéphanie Hugues, Heiner Appel,
Mei-Huei Jang, Julie Cazareth, Lucie Beaudoin, Corinne Schricke, Agnès Lehuen,
Kai W Wucherpfennig, Nicolas Glaichenhaus
AFFILIATION: INSERM E0344, Université de Nice-Sophia Antipolis, Valbonne,
France.
REFERENCE: Eur J Immunol 2004 Oct 34(10):2656
Although non-obese diabetic (NOD) mice spontaneously develop T cell
autoimmunity, it is not clear whether this phenomenon results from a
defect in tolerance to self-Ag. Furthermore, as autoimmunity has been
postulated to result from T cell responses directed toward self-peptides
that bind with low affinity to NOD I-A(g7) MHC class II molecules, it
is important to determine whether the expression of such peptides
induces tolerance. We have constructed NOD transgenic (Tg) mice
expressing the Leishmania antigen receptor for C kinase (LACK) Ag in
either the thymus or pancreatic beta cells. We identified LACK peptides
that were the targets of T cells in LACK-immunized NOD mice while
binding to I-A(g7) with low affinity. While CD4(+) T cells from NOD mice
secreted IFN-gamma, IL-4, IL-5 and IL-10 in response to LACK, those
from LACK-expressing Tg mice secreted reduced levels of cytokines.
Experiments using peptide/MHC multimers showed that LACK-expressing Tg
mice exhibited self-reactive CD4(+) T cells with impaired proliferation
capabilities. Hence, even self-peptides that bind to I-A(g7) with low
affinity can induce tolerance in NOD mice. This result is important in
light of the commonly held hypothesis that T cells reacting to peptides
that bind to MHC with low affinity escape tolerance induction and cause
autoimmunity.
PMID: 15371479
TITLE: Identification of the most abundant secreted proteins from the salivary
glands of the sand fly Lutzomyia longipalpis, vector of Leishmania chagasi.
AUTHORS: Jesus G Valenzuela, Mark Garfield, Edgar D Rowton, Van M Pham
AFFILIATION: Vector Molecular Biology Unit, Laboratory of Malaria and Vector
Research, NIAID, National Institutes of Health, 12735 Twinbrook Parkway, Room
2E-22C, Rockville, MD 20852, USA.
REFERENCE: J Exp Biol 2004 Oct 207(Pt 21):3717-29
Using massive cDNA sequencing, proteomics and customized computational
biology approaches, we have isolated and identified the most abundant
secreted proteins from the salivary glands of the sand fly Lutzomyia
longipalpis. Out of 550 randomly isolated clones from a full-length
salivary gland cDNA library, we found 143 clusters or families of
related proteins. Out of these 143 families, 35 were predicted to be
secreted proteins. We confirmed, by Edman degradation of Lu. longipalpis
salivary proteins, the presence of 17 proteins from this group. Full-
length sequence for 35 cDNA messages for secretory proteins is reported
, including an RGD-containing peptide, three members of the yellow-
related family of proteins, maxadilan, a PpSP15-related protein, six
members of a family of putative anticoagulants, an antigen 5-related
protein, a D7-related protein, a cDNA belonging to the Cimex apyrase
family of proteins, a protein homologous to a silk protein with amino
acid repeats resembling extracellular matrix proteins, a 5'-nucleotidase
, a peptidase, a palmitoyl-hydrolase, an endonuclease, nine novel
peptides and four different groups of proteins with no homologies to any
protein deposited in accessible databases. Sixteen of these proteins
appear to be unique to sand flies. With this approach, we have tripled
the number of isolated secretory proteins from this sand fly. Because of
the relationship between the vertebrate host immune response to
salivary proteins and protection to parasite infection, these proteins
are promising markers for vector exposure and attractive targets for
vaccine development to control Leishmania chagasi infection.
PMID: 15364110
TITLE: Vaccination with Leishmania soluble antigen and immunostimulatory
oligodeoxynucleotides induces specific immunity and protection against
Leishmania donovani infection.
AUTHORS: Poonam Tewary, Jayesh Mehta, Bindu Sukumaran, Rentala Madhubala
AFFILIATION: School of Life Sciences, Jawaharlal Nehru University, New Delhi
110067, India.
REFERENCE: FEMS Immunol Med Microbiol 2004 Oct 42(2):241-8
In this report, we investigated the effect of ODN containing
immunostimulatory CG motifs as adjuvant with soluble antigen (SA) from
Leishmania donovani. BALB/c mice were vaccinated with the soluble
antigen with or without CpG-ODN as adjuvant and then challenged with L.
donovani metacyclic promastigotes. CpG-ODN alone resulted in partial
protection against challenge with L. donovani. Immunization of mice with
SA and CpG-ODN showed enhanced reduction in parasite load (
approximately 60%) when compared to SA ( approximately 40%) immunized
mice. Immunization with SA by itself resulted in a mixed Th1/Th2
response whereas co-administration of SA with CpG-ODN resulted in a
strong Th1 promoting isotype as they together promoted production of
immunoglobulin G2a. Leishmania-specific Th1 cytokine response was
induced by co-administering CpG-ODN and SA as they together promoted
production of IFN-gamma and IL-12. In the present study, we demonstrate
that immunostimulatory phosphorothioate-modified ODN are promising
immune enhancers for vaccination against visceral leishmaniaisis.
PMID: 15362872
TITLE: Isomerase-Independent Chaperone Function of Cyclophilin Ensures
Aggregation Prevention of Adenosine Kinase Both in vitro and under in vivo
Conditions.
AUTHORS: Anutosh Chakraborty, Banibrata Sen, Rupak Datta, Alok K Datta
AFFILIATION: Division of Infectious Diseases, Leishmania Group, Indian Institute
of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700 032, India.
REFERENCE: Biochemistry 2004 Sep 43(37):11862-72
Using inactive aggregates of adenosine kinase (AdK) from Leishmania
donovani as the model substrate, we recently demonstrated that a
cyclophilin (LdCyP) from the same source in an isomerase-independent
fashion reactivated the enzyme in vitro by disaggregating its inactive
oligomers [Chakraborty et al. (2002) J. Biol. Chem. 277, 47451-47460].
Besides disrupting preformed aggregates, LdCyP also prevents
reaggregation of the newly formed active protein that is generated after
productive refolding from its urea-denatured state. To investigate
possible physiological implications of such phenomena, a unique
expression system that simultaneously induces both AdK and LdCyP in
naturally AdK-deficient Escherichia coli, was developed. Both in vitro
and in vivo experiments revealed that oligomerization is an inherent
property of this particular enzyme. In vivo protein cross-linking
studies, activity determination analysis and Ado phosphorylation
experiments carried out in cells coexpressing both the proteins
unequivocally demonstrated that, similar to the phenomena observed in
vitro, aggregates of the enzyme formed in vivo are able to interact with
both LdCyP and its N-terminal truncated form (N(22)(-)(88)DEL LdCyP) in
a crowded intracellular environment, resulting in aggregation
prevention and reactivation of the enzyme. Our results indicate that the
isomerase-independent chaperone function of LdCyP, detected in vitro,
participates in vivo as well to keep aggregation-prone proteins in a
monomeric state. Furthermore, analogous to yeast/bacterial two-hybrid
systems, development of this simple coexpression system may help in the
confirmation of interaction of two proteins under simulated in vivo
conditions.
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: 15372110
TITLE: A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced
IL-12 production and Th cell differentiation.
AUTHORS: Kenji Sugimoto, Mutsuhiro Ohata, Jun Miyoshi, Hiroyoshi Ishizaki,
Naotake Tsuboi, Akio Masuda, Yasunobu Yoshikai, Masaya Takamoto, Kazuo Sugane,
Seiichi Matsuo, Yasuhiro Shimada, Tetsuya Matsuguchi
AFFILIATION: Division of Host Defense, Center for Neural Disease and Cancer,
and.
REFERENCE: J Clin Invest 2004 Sep 114(6):857-66
A serine/threonine protein kinase, Cot/Tpl2, is indispensable for
extracellular signal-regulated kinase (ERK) activation and production of
TNF-alpha and PGE(2) in LPS-stimulated macrophages. We show here that
Cot/Tpl2 is also activated by other Toll-like receptor (TLR) ligands.
Bacterial DNA rich in the dinucleotide CG (CpG-DNA), unlike LPS or
synthetic lipopeptide, activated ERK in a Cot/Tpl2-independent manner.
Peritoneal macrophages and bone marrow-derived DCs from Cot/Tpl2(-/-)
mice produced significantly more IL-12 in response to CpG-DNA than those
from WT mice. Enhanced IL-12 production in Cot/Tpl2(-/-) macrophages is
, at least partly, regulated at the transcriptional level, and the
elevated IL-12 mRNA level in Cot/Tpl2(-/-) macrophages is accompanied by
decreased amounts of IL-12 repressors, such as c-musculoaponeurotic
fibrosarcoma (c-Maf) and GATA sequence in the IL-12 promoter-binding
protein (GA-12-binding protein; GAP-12) in the nucleus. Consistently,
Cot/Tpl2(-/-) mice showed Th1-skewed antigen-specific immune responses
upon OVA immunization and Leishmania major infection in vivo. These
results indicate that Cot/Tpl2 is an important negative regulator of Th1
-type adaptive immunity, that it achieves this regulation by inhibiting
IL-12 production from accessory cells, and that it might be a potential
target molecule in CpG-DNA-guided vaccination.
PMID: 15372990
TITLE: Haemostatic disorders in dogs naturally infected by Leishmania infantum.
AUTHORS: M Corona, P Ciaramella, A Pelagalli, L Cortese, M E Pero, D Santoro, P
Lombardi
AFFILIATION: Department of Veterinary Clinical Science--Section of Internal
Medicine, University of Naples, Italy.
REFERENCE: Vet Res Commun 2004 Aug 28 Suppl 1():331-4
PMID: 15368649
TITLE: Anthranoid compounds with antiprotozoal activity from Vismia orientalis.
AUTHORS: Zakaria H Mbwambo, Sandra Apers, Mainen J Moshi, Modest C Kapingu,
Sabine Van Miert, Magda Claeys, Reto Brun, Paul Cos, Luc Pieters, Arnold
Vlietinck
AFFILIATION: Institute of Traditional Medicine, Muhimbili University College of
Health Sciences, Dar es Salaam, Tanzania. zmbwambo at muchs.ac.tz
REFERENCE: Planta Med 2004 Aug 70(8):706-10
A phytochemical investigation of the 80% ethanolic extract of stem bark
of Vismia orientalis Engl. (Guttiferae or Clusiaceae), a plant used in
traditional medicine in Tanzania, resulted in the isolation and
spectroscopic characterisation of 3-geranyloxy-6-methyl-1,8-
dihydroxyanthraquinone, emodin, vismione D and bianthrone A1. Vismione D
exhibited a broad range of antiprotozoal activities against Trypanosoma
brucei rhodesiense and T. cruzi (IC50 < 10 micrograms/mL),
Leishmania donovani (IC50 0.37 micrograms/mL) and Plasmodium falciparum
strain K1 (IC50 1.0 microgram/mL). However, it was also slightly
cytotoxic against human L6 cells (IC50 4.1 micrograms/mL). Emodin showed
antileishmanial activity (IC50 2.0 micrograms/mL), while its IC50
against L6 cells was 20.3 micrograms/mL. Other antiprotozoal activities
observed for emodin against both Trypanosoma species and P. falciparum,
for bianthrone A1 against T. b. rhodesiense and P. falciparum, and for 3
-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone against T. b.
rhodesiense, L. donovani and P. falciparum were in the range of 10 to 50
micrograms/mL. None of the compounds showed antibacterial or antiviral
(including also HIV) activity.
PMID: 15372989
TITLE: Plasma thrombomodulin levels in dogs naturally infected with Leishmania
infantum.
AUTHORS: P Ciaramella, L Cortese, M Corona, R Ambrosio, A Di Loria, A
Persechino
AFFILIATION: Department of Veterinary Clinical Science--Section of Internal
Medicine--University of Naples Federico II, via Delpino, 1--80137 Naples,
Italy. paociara at unina.it
REFERENCE: Vet Res Commun 2004 Aug 28 Suppl 1():327-30
PMID: 15234664
TITLE: Comparison of the effectiveness of two topical paromomycin treatments
versus meglumine antimoniate for New World cutaneous leishmaniasis.
AUTHORS: Rodrigo X Armijos, M Margaret Weigel, Manuel Calvopiña, Manuel
Mancheno, Roberto Rodriguez
AFFILIATION: Health Sciences Program, College of Health Sciences, Room 705, 1101
North Campbell Street, The University of Texas at El Paso, El Paso, TX
79902-0581, USA.
REFERENCE: Acta Trop 2004 Jul 91(2):153-60
The randomized, controlled study compared the therapeutic efficacy and
safety of two paromomycin-containing topical preparations with the gold
treatment standard, meglumine antimoniate, and with each other in 120
Ecuadorian patients with ulcerated lesions. The two paromomycin
treatment comparisons were double-blinded. Group 1 (n = 14) received 15
% paromomycin plus 12% methylbenzonium chloride (PR-MBCL) dissolved in a
soft white paraffin base, applied twice daily for 30 days. Group 2 (n
= 40) was also treated for 30 days with 15% paromomycin plus 10% urea (
PR-U) dissolved in the same paraffin base. Group 3 (n = 40) received
20mg/kg/day of IM meglumine antimoniate (MA) for 10 days as per
Ecuadorian Ministry of Public Health recommendations at the time of the
study. The 10-day treatment was completed by 90% of the MA group
compared to 72.5% of the PR-MBCL (X2 = 4.0, P = 0.045) and 75% of the PM
-U (X2 = 3.1, P > 0.05) groups whose treatment regime lasted 20 days
longer than the MA treatment. Post-treatment lesion burning, redness,
inflammation, and soreness were more common in the two paromomycin
groups compared to MA group (P < 0.05). The frequency of treatment-
related side effects in the two paromomycin groups was similar. Six
weeks after the start of treatment, 80.6% of MA subjects were clinically
cured compared to 48.3% in the PR-MBCL (X2 = 6.1, P = 0.014) and 40% in
the PM-U groups (X2 = 12.6, P = 0.002). By 12 weeks, the proportion of
clinically cured subjects in the MA (91.7%) compared to PM-MBCL (79.3%)
or PM-U (70%) groups was not significantly different (P > 0.05). MA-
treated subjects clinically cured by 12 weeks had a faster mean healing
time (29.5 +/- 12.2 days) compared to those in the PM-MBCL (versus 43.1
+/- 14.4 days, t = -3.7, P = 0.001) or PR-U groups (43.5 +/- 17 days; t
= -3.2, P = 0.002). During the 48-week post-treatment follow-up period
, infection reactivation was observed in 15.2% of the MA subjects
compared to 17.4% in the PM-MBCL and 10.5% PM-U of subjects diagnosed as
clinically healed by 12 weeks (P > 0.05). The results suggest that
although the time required for the clinical healing of ulcerated lesions
takes longer, topical paromomycin may be an acceptable therapeutic
alternative in endemic areas where meglumine antimoniate is not
available, is too costly or medically contraindicated.
PMID: 15363945
TITLE: The modelling of mononuclear phagocyte-connective tissue adhesion in
vitro: application to disclose a specific inhibitory effect of Leishmania
infection.
AUTHORS: Djalma G F Carvalhal, Aryon Barbosa, Micely D'El-Rei Hermida, Jorge
Clarencio, Nathanael F Pinheiro, Patricia S T Veras, Washington L C Dos-Santos
AFFILIATION: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua
Waldemar Falcão 121, 40295-001 Salvador, BA, Brazil.
REFERENCE: Exp Parasitol 2004 Jul-Aug 107(3-4):189-99
In this work, we have developed an adhesion assay to study interactions
between mononuclear phagocytes and connective tissue in vitro and show
its potential use to study diseases caused by intracellular
microorganisms. The assay reproduces most of the characteristics of
macrophage adhesion to connective tissue in vivo, such as: preferential
adhesion to inflamed connective tissue, divalent cation and integrin
dependence, and up-regulation upon cell activation. The phagocyte
adhesion to connective tissue was inhibited by infection with Leishmania
(58+/-22%, [Formula: see text] ) and was not affected by infection with
Mycobacterium or by endocytosis of latex beads. Manganese partially
reverted the loss in adherence produced by Leishmania infection,
indicating that the mechanisms regulating the function of integrins are
affected by cell infection with Leishmania. This assay might be a useful
tool for the study of the mechanisms by which mononuclear phagocytes
play a role in the immune-inflammatory response and in the development
of lesions. Index Descriptors and Abbreviations: Adhesion assay; Cell
adhesion; Macrophage adhesion; J774 cells; Leishmania amazonensis;
Leishmania braziliensis; Leishmania chagasi; Mycobacterium fortuitum;
Promastigotes; ANOVA, analysis of variance; CD, cluster designation for
classification of cell markers; CS-1, connecting segment 1 of
fibronectin; EDTA, ethylenediaminetetracetic acid; FACS, fluorescence
activated cell sorting; FBS, fetal bovine serum; HBSS, Hanks' balanced
salt solution; LFA-1, leukocyte activation antigen 1 (beta2-integrin,
CD11a/CD18); LPS, lypopolysaccharide; Mac-1, beta2-integrin named after
macrophages (CD11b/CD18); PBS, phosphate-buffered saline; RGD, peptide
containing RGD sequence; RPMI, Roswell Park Memorial Institute-1640 (
tissue culture medium); SNK, Student-Newman-Keuls test; VCAM-1, vascular
cell adhesion molecule 1
PMID: 15363943
TITLE: Leishmania (Leishmania) amazonensis: purification and characterization of
a promastigote serine protease.
AUTHORS: Raquel Elisa Da Silva-Lopez, Salvatore Giovanni-De-Simone
AFFILIATION: Laboratório de BioquÃmica de ProteÃnas e PeptÃdeos,
Departamento de BioquÃmica e Biologia Molecular, Instituto Oswaldo Cruz,
FIOCRUZ, Av. Brasil 4365, 21045-900, Rio de Janeiro, RJ, Brazil.
REFERENCE: Exp Parasitol 2004 Jul-Aug 107(3-4):173-82
Pathogenic protozoan proteases play crucial roles in the host-parasite
interaction, and its characterization contributes to the understanding
of protozoan disease mechanisms. A Leishmania amazonensis promastigote
protease was purified 36-fold, using aprotinin-agarose affinity
chromatography and gel filtration high performance liquid chromatography
, yielding a total recovery of 49%. The molecular mass of active enzyme
obtained from native gel filtration HPLC and SDS-PAGE under conditions
of reduction and non-reduction was 68kDa, suggesting that the enzyme may
exist as a monomer. The protease isoelectric point (pI) was around 4.45
and, as demonstrated by deglycosylation assay, it did not have any
carbohydrate content. The optimal pH and temperature of the enzyme were
8.0 and 28 degrees C, respectively, determined using alpha-N-rho-tosyl-l
-arginyl-methyl ester (l-TAME) as substrate. Assays of thermal stability
indicated that 50% of the enzymatic activity was preserved after 4min
of pre-treatment at 42 degrees C and after 24h of pre-treatment at 37
degrees C, both in the absence of substrate. Hemoglobin, bovine serum
albumin (BSA), ovalbumin, and both gelatin and peptide substrates
containing arginine in ester bound were hydrolyzed by 68kDa protease.
The insulin beta-chain was also hydrolyzed by the protease, and four
peptidic bonds (L(11)-V(12), E(13)-A(14), L(15)-Y(16), and Y(16)-L(17))
were susceptible to the 68-kDa protease action. Inhibition studies
suggested that the enzyme belonged to a serine protease class inhibited
by calcium ions and activated by manganese ions. These findings
demonstrate that the L. amazonensis 68-kDa serine protease differs from
those of other protozoan parasites.
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
********************************************************************************************************************
PMID: 12682728
TITLE: Characterization of the human autoimmune response to the major C-terminal
epitope of the ribosomal P proteins.
AUTHORS: M Mahler, K Kessenbrock, J Raats, R Williams, M J Fritzler, M
Blüthner
AFFILIATION: Pharmacia Diagnostics, Munzingerstrasse 7, 79111 Freiburg, Germany.
m.mahler.job at web.de
REFERENCE: J Mol Med 2003 Mar 81(3):194-204
Autoantibodies to the ribosomal phospho (-P) proteins P0, P1, and P2,
collectively referred to as Rib-P, are specifically found in 10-40% of
patients with systemic lupus erythematosus (SLE). These antibodies are
believed to be correlated with lupus nephritis, hepatitis, and central
nervous system involvement. The major immunoreactive epitope of these
ribosomal antigens has been localized to the carboxy terminus, which is
a highly conserved domain of all three proteins and contains two
phosphorylated serine residues. The phosphorylated amino acids of the P
proteins are known not to be critical epitope determinants. Furthermore
, epitope-mapping studies have shown that the major epitope is located
within the last 11 C-terminal amino acids. Using peptide arrays we
identified more precisely this shared epitope as the six C-terminal
amino acids GFGLFD and elucidated the molecular recognition events of
anti-Rib-P antibodies at the amino acid level. We identified Phe(111)
and Phe(114) of Rib-P2 as the key residues for the interaction, with
further contributions of Gly-112 and Asp-115. This amino acid stretch is
also present in proteins of several pathogenic micro-organisms such as
Trypanosoma cruzi, Brugia malayi, Pseudomonas aeruginosa, Candida
albicans, several Leishmania species, and Bartonella henselae. Using
newly developed ELISA systems with a C-terminal peptide (C22) and the
recombinant proteins (P0, P1, and P2) as antigens we found a high
specificity of anti-Rib-P antibodies for SLE and demonstrated positive
correlations with anti-U1-C, anti-Sm-B/B' and anti-D and anti-dsDNA
antibodies. The sensitivity and specificity in the peptide (C22) based
assay varied between 12.8%/100% and 23.4%/96.7% for SLE, depending on
the assigned cutoff. In contrast to other studies, we found no
significant correlation of anti-Rib-P reactivity with central nervous
system manifestations or renal involvement in SLE patients. We conclude
that the epitope motif GFGLFD in the C-termini of the ribosomal P
proteins is the key determinant of anti-Rib-P antibodies, and that the
C22 peptide and the recombinant proteins can be used equally well for
the detection of anti-Rib-P antibodies. The role of the major Rib-P
epitope in the development of anti-ribosomal P antibodies and in the
pathogenesis of SLE remains a subject of further investigation.
PMID: 9476797
TITLE: Identification of a transcription factor like protein at the TOR locus in
Leishmania mexicana amazonensis.
AUTHORS: S Detke
AFFILIATION: University of North Dakota School of Medicine, Department of
Biochemistry and Molecular Biology, Grand Forks 58202, USA.
sdetke at mail.med.und.nodak.edu
REFERENCE: Mol Biochem Parasitol 1997 Dec 90(2):505-11
The TOR gene (TOxic nucleoside Resistance gene) was mapped to a 2.3 kb
fragment on the amplified DNA from tubercidin resistant Leishmania (TUB
). This DNA fragment conferred upon wild type cells resistance to
tubercidin, inosine dialdehyde, formycin A and B and allopurinol
riboside and a reduced ability to accumulate purine nucleobases and
nucleosides. These properties were characteristic of the parental TUB
cells which carried the intact amplified DNA and have been hypothesized
to be caused by a reduction in the activity of the multiple purine
transporters within this organism. The TOR gene was found to be
partially homologous to the rodent and human Oct-6/SCIP/Tst-1 gene. It
lacked, however, the POU specific domain of this class of transcription
factors and contained only the first two helices of the POU homeodomain
. This truncated homeodomain was not required to confer resistance upon
wild type cells to toxic nucleosides, suggesting that TOR was not a
repressor with independent DNA binding capability.
PMID: 8619813
TITLE: Cloning and characterization of a ribosomal P protein from Taenia solium,
the aetiological agent of human cysticercosis.
AUTHORS: B H Kalinna, D P McManus
AFFILIATION: Molecular Parasitology Unit, Queensland Institute of Medical
Research, Bancroft Centre, Brisbane, Australia. berndK at qimr.edu.au
REFERENCE: Biochem Biophys Res Commun 1996 Feb 219(1):231-7
A cDNA encoding the complete open reading frame of the Taenia solium
acidic ribosomal phosphoprotein P2 has been cloned. The 417 bp cDNA (
arpP2) was isolated from a T. solium cDNA expression library by PCR
using P protein specific pimers. The ORF encodes a protein of 121 amino
acids exhibiting 40-55% identity to mammalian, fungal, insect, and
parasite P2 proteins. The inferred molecular mass of the protein is 12,
592 Daltons, similar to that reported for other ribosomal P2 proteins.
After subcloning and expression, the recombinant protein was purified by
affinity chromatography under non-denaturing conditions and was shown
to have a molecular mass of 15 kDa which is equivalent to the expected
size of the full length recombinant fusion protein, comprising the 12.5
kDa arpP2 plus an additional 2 kDa for the N-terminal fusion peptide
incorporating the six histidine residues required for purification.
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