[leish-l] Fwd: Articles found by RefScout 16/03/2005 11/2005
jeffreyj at usp.br
jeffreyj at usp.br
Wed Mar 23 20:53:28 BRT 2005
Date: Wed, 16 Mar 2005 20:17:57
From: info at refscout.com
This is RefScout-Newsletter 11/2005 for user Jeff32630.
REQUEST: [ leishmaniasis ]
(18 articles match this request)
PMID: 15762886
TITLE: Immunostimulatory cellular responses of cured Leishmania-infected
patients and hamsters against the integral membrane proteins and non-membranous
soluble proteins of a recent clinical isolate of Leishmania donovani.
AUTHORS: R Garg, S K Gupta, P Tripathi, S Naik, S Sundar, A Dube
AFFILIATION: Division of Parasitology, Central Drug Research Institute, Lucknow,
India.
REFERENCE: Clin Exp Immunol 2005 Apr 140(1):149-56
Summary Development of an effective immunoprophylactic agent for
visceral leishmaniasis (VL) has become imperative due to the increasing
number of cases of drug resistance and relapse. Live and killed whole
parasites as well as fractionated and recombinant preparations have been
evaluated for vaccine potential. However, a successful vaccine against
the disease has been elusive. Because protective immunity in human and
experimental leishmaniasis is predominantly of the Th1 type, immunogens
with Th1 stimulatory potential would make good vaccine candidates. In
the present study, the integral membrane proteins (IMPs) and non-
membranous soluble proteins (NSPs), purified from promastigotes of a
recent field isolate, Leishmania donovani stain 2001, were evaluated for
their ability to induce cellular responses in cured patients (n = 9),
endemic controls (n = 5) of visceral leishmaniasis (VL) and treated
hamsters (n = 10). IMPs and NSPs induced significant proliferative
responses (SI 6.3 +/- 4.1 and 5.6 +/- 2.3, respectively; P < 0.01)
and IFN-gamma production (356.3 +/- 213.4 and 294.29 +/- 107.6 pg/ml,
respectively) in lymphocytes isolated from cured VL patients.
Significant lymphoproliferative responses against IMPs and NSPs were
also noticed in cured Leishmania animals (SI 7.2 +/- 4.7 & 6.4 +/- 4
.1, respectively; P < 0.01). In addition, significant NO production
in response both IMPs and NSPs was also noticed in macrophages of
hamsters and different cell lines (J774A-1 and THP1). These results
suggest that protective, immunostimulatory molecules are present in the
IMP and NSP fractions, which may be exploited for development of a
subunit vaccine for VL.
PMID: 15763367
TITLE: Efficacy of Desmodium gangeticum extract and its fractions against
experimental visceral leishmaniasis.
AUTHORS: Nasib Singh, Pushpesh Kumar Mishra, Aruna Kapil, Kamal Ram Arya, Rakesh
Maurya, Anuradha Dube
AFFILIATION: Division of Parasitology, Central Drug Research Institute, MG Road,
Post Box No. 173, Lucknow, Uttar Pradesh 226 001, India.
REFERENCE: J Ethnopharmacol 2005 Apr 98(1-2):83-8
Crude ethanolic extract of Indian medicinal plant, Desmodium gangeticum
(A001) and its three fractions-hexane (F002), n-butanol (F003) and
aqueous (F004) were evaluated chemoprophylactically and
chemotherapeutically against experimental visceral leishmaniasis in
hamsters. Ethanolic extract showed 41.2+/-5.3% inhibition of parasite
multiplication when administered at a dose of 250mg/kgx2 on day -7 and +
7 of Leishmania donovani challenge. Its n-butanol fraction exhibited
better efficacy than the ethanolic extract to the tune of 66.7+/-6.1%
inhibition when administered at similar dose schedule. But the other two
fractions failed to exert any action prophylactically. F003 also
imparted significant (P<0.001) non-specific resistance to peritoneal
macrophages against Leishmania infection. F003 also showed moderate
antileishmanial activity when tested against established infection of
Leishmania donovani in hamsters but the rest three fractions failed to
show any significant inhibition of parasite multiplication. These
findings revealed that this plant has potential prophylactic and
therapeutic efficacy against Leishmania infection and warrants detailed
investigations on its possible immunopotentiatory actions.
PMID: 15752716
TITLE: Role of sulfhydryl groups in band 3 in the inhibition of phosphate
transport across erythrocyte membrane in visceral leishmaniasis.
AUTHORS: Sudipa Saha Roy, Gargi Sen, Tuli Biswas
AFFILIATION: Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road,
Kolkata 700 032, India.
REFERENCE: Arch Biochem Biophys 2005 Apr 436(1):121-7
Membrane destabilization in erythrocytes plays an important role in the
premature hemolysis and development of anemia during visceral
leishmaniasis (VL). Marked degradation of the anion channel protein band
3 is likely to allow modulation of anion flux across the red cell
membrane in infected animals. The present study describes the effect of
structural modification of band 3 on phosphate transport in VL using (31
)P NMR. The result showed progressive decrease in the rate and extent of
phosphate transport during the post-infection period. Interdependence
between the intracellular ionic levels seems to be a determining factor
in the regulation of anion transport across the erythrocyte membrane in
control and infected conditions. Infection-induced alteration in band 3
made the active sites of transport more susceptible to binding with
amino reactive agents. Inhibition of transport by oxidation of band 3
and subsequent reversal by reduction using dithiothreitol suggests the
contribution of sulfhydryl group in the regulation of anion exchange
across the membrane. Quantitation of sulfhydryl groups in the anion
channel protein showed the inhibition to be closely related to the
decrease of sulfhydryl groups in the infected hamsters. Downregulation
of phosphate transport during leishmanial infection may be ascribed to
the sulfhydryl modification of band 3 resulting in the impaired
functioning of this protein under the diseased condition.
PMID: 15755663
TITLE: Design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors
of trypanosomal and leishmanial dihydrofolate reductase.
AUTHORS: Soghra Khabnadideh, Didier Pez, Alexander Musso, Reto Brun, Luis M Ruiz
Pérez, Dolores González-Pacanowska, Ian H Gilbert
AFFILIATION: Welsh School of Pharmacy, Cardiff University, Redwood Building,
King Edward VII Avenue, Cardiff, CF10 3XF, UK; Department of Pharmacy,
University of Shiraz, Shiraz, Iran.
REFERENCE: Bioorg Med Chem 2005 Apr 13(7):2637-49
This paper describes the design, synthesis and evaluation of a series of
2,4-diaminoquinazolines as inhibitors of leishmanial and trypanosomal
dihydrofolate reductase. Compounds were designed by a generating virtual
library of compounds and docking them into the enzyme active site.
Following their synthesis, they were found to be potent and selective
inhibitors of leishmanial dihydrofolate reductase. The compounds were
also found to have potent activity against Trypanosoma brucei
rhodesiense, a causative organism of African trypanosomiasis and also
against Trypanosoma cruzi, the causative organism of Chagas disease.
There was significantly lower activity against Leishmania donovani, one
of the causative organisms of leishmaniasis.
PMID: 15755418
TITLE: Leishmania chagasi/infantum: further investigations on Leishmania
tropisms in atypical cutaneous and visceral leishmaniasis foci in Central
America.
AUTHORS: M Campos-Ponce, C Ponce, E Ponce, R D C Maingon
AFFILIATION: Faculty of Earth and Life Sciences, Institute of Health Sciences,
Free University of Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The
Netherlands.
REFERENCE: Exp Parasitol 2005 Apr 109(4):209-19
In Central America, apparently genetically identical Leishmania chagasi/
infantum parasites cause cutaneous (CL) and visceral leishmaniasis (VL
), the latter being more frequent in young children. The present study
investigated if there were pathology-related differences in virulence
between Honduran CL and VL strains using Mediterranean L. infantum
strains as a reference. Macrophage infectivity and serum sensitivity,
properties thought to be associated with virulence, were similar between
CL and VL strains from both regions. Attention focused on the genome
organisation of genes for two candidate virulence factors: Leishmania
mitogen activated protein kinase (LMPK) and cysteine proteinase b (Cpb
). Interestingly, the Mediterranean strains exhibited restriction enzyme
polymorphisms associated with tropism for both LMPK and Cpb genes
whereas no differences were observed for the Honduran strains. We also
report relative genetic homogeneity of the Honduran strains as compared
to the Mediterranean strains and discuss it in terms of the probable
origin for the Central American L. chagasi/infantum.
PMID: 15753208
TITLE: A role for IgG immune complexes during infection with the intracellular
pathogen Leishmania.
AUTHORS: Suzanne A Miles, Sean M Conrad, Renata G Alves, Selma M B Jeronimo,
David M Mosser
AFFILIATION: Department of Cell Biology and Molecular Genetics, University of
Maryland, College Park, MD 20742.
REFERENCE: J Exp Med 2005 Mar 201(5):747-54
We examined the role of immunoglobulin (Ig)G antibodies in mediating
host defense to the intracellular parasite, Leishmania. We show that IgG
not only fails to provide protection against this intracellular
pathogen, but it actually contributes to disease progression. The J(H)
strain of BALB/c mice, which lack IgG because they have a targeted
deletion in the Ig heavy chain (J) locus, were more resistant to
infection with Leishmania major than were normal BALB/c mice. However,
the passive administration of anti-Leishmania IgG caused J(H) mice to
develop large lesions containing high numbers of parasites. Antibody
administration correlated with an increase in interleukin (IL) 10
production in lesions, and blocking the murine IL-10 receptor prevented
antibody-mediated disease exacerbation. In human patients with active
visceral leishmaniasis, high IgG levels are predictive of disease.
Patients with ongoing disease had high IgG antibody titers and no
delayed-type hypersensitivity (DTH) responses to Leishmania antigens.
This pattern was reversed upon disease resolution after treatment,
resulting in a decrease in total IgG, which was accompanied by a
progressive increase in DTH responsiveness. We conclude that IgG can
cause a novel form of immune enhancement due to its ability to induce IL
-10 production from macrophages.
PMID: 15752175
TITLE: Micro-geographical variation among male populations of the sandfly,
Lutzomyia (Nyssomyia) intermedia, from an endemic area of American cutaneous
leishmaniasis in the state of Rio de Janeiro, Brazil.
AUTHORS: C R V Meneses, E Cupolillo, F Monteiro, E F Rangel
AFFILIATION: Departamento de Entomologia, Instituto Oswaldo Cruz, Rio de
Janeiro, Brazil.
REFERENCE: Med Vet Entomol 2005 Mar 19(1):38-47
Abstract. The genetic relationships among male Lutzomyia (Nyssomyia)
intermedia (Lutz & Neiva) (Diptera: Psychodidae) from three
populations from the same endemic area of American cutaneous
leishmaniasis (ACL) in the state of Rio de Janeiro, Brazil, were
compared. The sandflies were collected in three ecologically different
habitats: domestic, extra-domestic and sylvatic over a total range of
800 m. Three molecular markers were employed to assess population
variation. Based on MLEE markers, it could not be concluded that the
three populations do not belong to the same gene pool (F(st) = 0.005).
No within-population departure from Hardy-Weinberg equilibrium was
detected (P < 0.05) and they presented the same level of gene
variation. The number of migrants (Nm) indicated that at least 50
individuals per generation migrated between the three habitats. RAPD-PCR
markers revealed that, except for the primer five, all were polymorphic
. Phenetic analysis of the genotypes showed the presence of two
principal clusters corresponding to: (1) domestic plus extra-domestic
and (2) sylvatic. Unique genotypes were observed in each population. The
sylvatic population was the most polymorphic, showing the largest
number of genotypes and low level of similarity between them. Three
mtDNA gene markers were studied by SSCP analysis. The most frequent
haplotype for each marker ranged in frequency from 60 to 87% and
individuals with unique haplotypes varied from 1 to 5%. Interestingly,
the SSCP analysis showed a low level of polymorphism within populations
. The disagreement between the different molecular markers observed and
the hypothesis that L. intermedia could be participating in the
transmission cycle of Leishmania (Viannia) braziliensis in environments
ranging from the interior of human dwellings to the forest, are
discussed.
PMID: 15757166
TITLE: Nonhealing skin lesions in a sailor and a journalist returning from
Iraq.
AUTHORS: Emil P Lesho, Glenn Wortmann, Ronald Neafie, Naomi Aronson
AFFILIATION: Walter Reed Army Medical Center, Washington, DC, USA.
REFERENCE: Cleve Clin J Med 2005 Feb 72(2):93-4, 96, 98-9 passim
US health care providers who are not familiar with cutaneous
leishmaniasis may now begin to encounter more patients with this
challenging entity as military personnel return from rotations in Iraq
or Afghanistan. Diagnosis requires a skin scraping, aspiration, or
biopsy, followed by examination by an experienced microscopist or
pathologist. Demonstration of the parasite DNA by PCR or culture in
special media can also be used to confirm the diagnosis. Sodium
stibogluconate is the mainstay of therapy, but other options for
selected cases include topical thermal or cryotherapy treatment and oral
triazole compounds. Assistance is available through the CDC and, for
Department of Defense beneficiaries, certain military facilities.
PMID: 15751739
TITLE: Recent advances in antileishmanial drug development.
AUTHORS: Antony J Davis, Lukasz Kedzierski
AFFILIATION: Division of Infection and Immunity, The Walter and Eliza Hall
Institute of Medical Research, 1G Royal Parade, Parkville 3050, Victoria,
Australia.
REFERENCE: Curr Opin Investig Drugs 2005 Feb 6(2):163-9
Leishmania are protozoan parasites responsible for a spectrum of
diseases collectively known as leishmaniasis. The disease is a
significant health problem in many regions of the world and emerges as a
serious co-infection in HIV-positive individuals. Current treatment of
the disease is based on a limited number of chemotherapeutic agents
which are rapidly becoming ineffective, and are characterized by high
toxicity and cost. This review focuses on recent advances in
antileishmanial drug development and improvements to current treatment
options. Novel approaches currently used to identify leishmanicidal
compounds as diverse as antimicrobial peptides and natural plant
extracts are described in this review.
PMID: 15753470
TITLE: Cutaneous Leishmaniasis in Naturally Infected Dogs is Associated with a T
Helper-2-biased Immune Response.
AUTHORS: C Brachelente, N Müller, M G Doherr, U Sattler, M Welle
AFFILIATION: Institute for Animal Pathology, Vetsuisse Faculty, University of
Berne, Postfach, Länggassstrasse 122, Bern CH-3001 (Switzerland).
monika.welle at itpa.unibe.ch.
REFERENCE: Vet Pathol 2005 Feb 42(2):166-75
Skin lesions are a frequent manifestation of Leishmania infantum
infections in Mediterranean countries. This study demonstrates by real-
time reverse transcriptase-polymerase chain reaction the local cytokine
response in skin biopsies from Leishmania-infected dogs (n = 10). As
controls, we investigated skin biopsies from healthy (n = 10) and
fleabite hypersensitive dogs (n = 10). We established a quantitative PCR
to determine the parasite burden in biopsies. The objective was to
elucidate whether a correlation exists between parasite number,
histologic response, and T helper-1 (TH1)/T helper-2 (TH2) cytokine
expression in lesional skin of naturally infected dogs. In Leishmania-
infected dogs, interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-
alpha) and interferon-gamma (IFN-gamma) messenger RNA production was
significantly higher than controls. Furthermore, dogs with a high
Leishmania burden had a significantly higher IL-4 expression, whereas no
difference was noted with regard to expression of other cytokines. By
comparing the pattern of inflammation and cytokine expression, a clear
trend became evident in that levels of IL-4, TNF-alpha, and IFN-gamma
were elevated in biopsies with a periadnexal nodular pattern and in
biopsies where the severity of the periadnexal infiltrate was equal to
the perivascular to interstitial infiltrate. Expression of IL-4, IL-13,
and TNF-alpha was slightly increased in biopsies where plasma cells
prevailed on lymphocytes, whereas expression of IFN-gamma was moderately
higher when lymphocytes were predominating. In summary, the present
study demonstrates that the local immune response in naturally occurring
leishmaniasis includes TH1 as well as TH2 cytokine subsets. Furthermore
, respective data suggest that increased expression of the TH2-type
cytokine IL-4 is associated with both severe clinical signs and a high
parasite burden in the skin lesions.
PMID: 15664963
TITLE: Distinct Leishmania braziliensis isolates induce different paces of
chemokine expression patterns.
AUTHORS: Maria Jania Teixeira, Juliana Dumet Fernandes, Clarissa Romero
Teixeira, Bruno Bezerril Andrade, Margarida Lima Pompeu, João Santana da
Silva, Cláudia Ida Brodskyn, Manoel Barral-Netto, Aldina Barral
AFFILIATION: Centro de Pesquisas Gonçalo Moniz-Fiocruz-BA, 121 Rua Waldemar
Falcão, Salvador, Bahia, Brazil 40295-001.
REFERENCE: Infect Immun 2005 Feb 73(2):1191-5
Inflammatory events during Leishmania braziliensis infection in mice
were investigated. Large lesions were directly correlated with the
inflammatory reaction but not with parasite burden. Different L.
braziliensis strains induce different paces of chemokine expression
patterns, leading to diverse cell recruitment and differential
inflammatory responses.
PMID: 15589800
TITLE: First detection of Leishmania major in peridomestic Phlebotomus papatasi
from Isfahan province, Iran: comparison of nested PCR of nuclear ITS ribosomal
DNA and semi-nested PCR of minicircle kinetoplast DNA.
AUTHORS: P Parvizi, I Mauricio, A M Aransay, M A Miles, P D Ready
AFFILIATION: Molecular Systematics Laboratory, Department of Entomology, Natural
History Museum, Cromwell Road, London SW7 5BD, UK.
REFERENCE: Acta Trop 2005 Jan 93(1):75-83
Two PCR methods were compared for their sensitivity in detecting
cultured Leishmania major, before being used to estimate infection rates
in female sandflies (Phlebotomus papatasi) collected from peridomestic
animal shelters and the nearby burrows of the gerbil reservoir hosts,
Rhombomys opimus, in Isfahan province, central Iran. A semi-nested PCR
was used to amplify a fragment of minicircle kinetoplast (k) DNA with a
length and sequence diagnostic for L. major, and a nested PCR was
developed to amplify a fragment containing the internal transcribed
spacers of the ribosomal RNA genes (ITS-rDNA) with a sequence diagnostic
for L. major. The semi-nested PCR was less sensitive than the nested
PCR when using DNA extracted from cultured promastigotes of L. major,
but it was more sensitive for detecting L. major in wild-caught
sandflies. At the edges of two Isfahan villages, infection rates were
significantly higher in P.papatasi collected outside gerbil burrows (14/
28) compared with those from peridomestic animal shelters (2/21). This
is the first record of L. major detected in P.papatasi from peridomestic
sites in Isfahan province.
PMID: 15757817
TITLE: Comparison of topical paromomycin sulfate (twice/day) with intralesional
meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L.
major.
AUTHORS: Babak Shazad, Babak Abbaszadeh, Ali Khamesipour
AFFILIATION: Internal Medicine Department, School of Medicine, Iran University
of Medical Sciences, Tehran, Iran.
REFERENCE: Eur J Dermatol 2005 Mar-Apr 15(2):85-7
This is an open study to compare the cure rate of cutaneous
leishmaniasis caused by L. major and treated with either paromomycin
sulfate or intralesional injection of meglumine antimoniate. Sixty
parasitologically proven cases with 1-3 lesions were included and
divided randomly into two equal groups; one group received 1 ml of
meglumine antimonate intradermally every other day for 20 days, the
other group received the ointment containing 15% parmomycin sulfate in
urea twice daily for 20 days. The patients were clinically evaluated at
1 and 6 weeks after treatment was completed. The results of clinical
evaluation at 1 week after treatment completed showed a cure rate of 18
out of 27 (66%) in the meglumine antimonate injected group and 20 out of
29 (68%) in the paromomycin sulfate treated group. The chi square test
was used to compare the cure rate between the two groups and showed no
significant difference (p = 0.85).
PMID: 15761608
TITLE: Subclinical form of the American visceral leishmaniasis.
AUTHORS: Mônica Elinor Alves Gama, Jackson MaurÃcio Lopes Costa, Cláudia
Maria Castro Gomes, Carlos Eduardo Pereira Corbett
AFFILIATION: Departamento de Medicina III (Pediatria).
REFERENCE: Mem Inst Oswaldo Cruz 2004 Dec 99(8):889-93
The subclinical form of visceral leishmaniasis (VL) shows nonspecific
clinical manifestations, with difficulties being frequently met in its
clinical characterization and diagnostic confirmation. Thus, the
objective of the present study was to define the clinical-laboratory
profile of this clinical form. A cohort study was conducted in the state
of Maranhao, Brazil, from January/1998 to December/2000, with monthly
follow-up of 784 children aged 0-5 years. Based on the clinical-
laboratory parameters reported in the literature, four categories were
established, with the children being classified (according to their
clinical-evolutive behavior) as asymptomatic (N = 144), as having the
subclinical form (N = 33) or the acute form (N = 12) or as subjects &
quot;without VL" (N = 595). Multiple discriminant analysis
demonstrated that the combination of fever, hepatomegaly,
hyperglobulinemia, and increased blood sedimentation rate (BSR) can
predict the subclinical form of VL as long as it is not associated with
splenomegaly or leukopenia. Subjects with the subclinical form did not
show prolonged or intermittent evolution or progression to the acute
form of VL. Subclinical cases have a profile differing from the
remaining clinical forms of VL, being best characterized by the
combination of fever, hepatomegaly, hyperglobulinemia, and increased BSR.
PMID: 15761593
TITLE: Study on phlebotomine sand fly (Diptera: Psychodidae) fauna in Belo
Horizonte, state of Minas Gerais, Brazil.
AUTHORS: Carina Margonari de Souza, Jose Eduardo Pessanha, Ricardo Andrade
Barata, Erika Michalsky Monteiro, Daniela Carmargos Costa, Edelberto Santos
Dias
AFFILIATION: Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, MG,
30190-002, Brasil.
REFERENCE: Mem Inst Oswaldo Cruz 2004 Dec 99(8):795-803
A study on the phlebotomine sand fly fauna in Belo Horizonte city, state
of Minas Gerais, Brazil, was carried out. From April 2001 to March 2003
, monthly systematic collections were performed in three houses from
each of the nine regions of the city, using CDC light traps for four
consecutive days. The traps were set into the houses and in peridomestic
areas totaling 54 traps. A number of 3871 sand fly specimens of the
genera Lutzomyia and Brumptomyia were collected. Sixty eight percent of
the specimens were L. longipalpis and 16% L. whitmani, insect vectors of
visceral and American cutaneous leishmaniasis, respectively.
Environmental factors such as temperature, humidity, and frequency of
precipitation suggest that the number of insects increases after rainy
periods. During the same period mentioned above, seasonal captures were
carried out in parks and green areas of Belo Horizonte, using Shannon
trap. A total of 579 phlebotomine sand flies were collected from which
398 (68.7%) were females with the predominance of L. whitmani and L.
monticola. Those specimens were used for natural infection examination,
by polymerase chain reaction. No Leishmania DNA was present in any of
the specimens tested.
PMID: 15683040
TITLE: [Comparative attempts for the establishment and optimisation of a PCR on
Leishmania for the purpose of diagnosis]
AUTHORS: Ursula Fürnkranz, Julia Walochnik, Felix Grimm, Peter Deplazes, Horst
Aspöck
AFFILIATION: Abteilung für Medizinische Parasitologie, Klinisches Institut für
Hygiene und Medizinische Mikrobiologie der Medizinischen Universität Wien,
Wien, Osterreich.
REFERENCE: Wien Klin Wochenschr 2004 116 Suppl 4():30-4
Leishmania spp. are the causative agents of visceral, cutaneous and
mucocutaneous leishmaniosis with several taxa ("species") of
the genus Leishmania being involved in human disease. As diagnostics
based on microscopical detection of the parasites or on serological
tests are often unsatisfactory, also molecular biological methods,
particularly the polymerase chain reaction (PCR), have been employed for
the detection of Leishmania spp. in the past years. The aim of the
present study was to compare different PCR-protocols and optimise them
for our needs, placing emphasis on the improvement of DNA isolation. PCR
was performed with whole cell DNA isolated from cultures, as well as
from simulated blood samples and clinical samples. Three different
methods for the isolation of DNA from blood samples and two different
PCR-protocols, one amplifying a fragment of the 18S rDNA and one for the
amplification of the whole kDNA-circle, were applied and compared. No
significant difference in sensitivity was detected between the different
PCR-protocols, however, it was shown that the highest yield of DNA was
achieved with a DNA isolation protocol based on urea.
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PMID: 15596060
TITLE: Expression of hypoxia-inducible factor-1alpha in the cutaneous lesions of
BALB/c mice infected with Leishmania amazonensis.
AUTHORS: Wagner W Arrais-Silva, Valdemar A Paffaro, Aureo T Yamada, Selma
Giorgio
AFFILIATION: Departamento de Parasitologia, Instituto de Biologia, Universidade
Estadual de Campinas, 13083-970, Campinas, São Paulo, Brazil.
REFERENCE: Exp Mol Pathol 2005 Feb 78(1):49-54
The hypoxia-inducible factor-1alpha (HIF-1alpha) is expressed in
response to hypoxia and has been recently demonstrated in a variety of
cells such as tumor cells and tumor-associated macrophages. Several
characteristics of leishmanial lesions in humans and in animal models,
such as microcirculation impairment, metabolic demand for leukocyte
infiltration into infected tissue, parasite proliferation, and secondary
bacterial infection, are strong indications of a hypoxic
microenvironment in the lesions. We evaluated HIF-1alpha expression in
the cutaneous lesions of BALB/c mice during Leishmania amazonensis
infection. Immunohistochemical analyses of the lesions demonstrated,
only in the later stages of infection when the lesion size is maximal
and parasite burden is enormous and massive numbers of recruited
macrophages and ulcers are observed, positive HIF-1alpha-infected cells
throughout the lesions. HIF-1alpha is expressed mainly in the cytoplasm
and around parasites inside the parasitophorous vacuoles of macrophages
. This is the first evidence that macrophages in the microenvironment of
lesions caused by a parasite produce a hypoxia-inducible factor.
PMID: 14662870
TITLE: Basal chromatin modification at the IL-4 gene in helper T cells.
AUTHORS: Jane L Grogan, Zhi-En Wang, Sarah Stanley, Brian Harmon, Gaby G Loots,
Edward M Rubin, Richard M Locksley
AFFILIATION: Howard Hughes Medical Institute, Department of Medicine and
Microbiology/Immunology, University of California, San Francisco, CA 94143-
0654, USA.
REFERENCE: J Immunol 2003 Dec 171(12):6672-9
Chromatin immunoprecipitations in naive CD4, but not CD8, T cells,
demonstrated association of the IL-4 promoter with acetylated histone.
Histone modifications and rapid IL-4 transcription were absent in
conserved noncoding sequence 1 (CNS-1)(-/-) cells lacking an 8-kb-
distant enhancer in the IL-4/IL-13 intergenic region, but also in CD4
(-/-) and Itk(-/-) cells, which have similar Th2 deficiencies. Histones
associated with the IL-13 promoter were not similarly acetylated in
naive T cells, but became acetylated in differentiated Th2 cells.
Conversely, Th1 differentiation induced histone methylation at the type
2 cytokine locus. Like CD4(-/-) and Itk(-/-) mice, CNS-1(-/-) BALB/c
mice were highly resistant to the Th2-inducing protozoan, Leishmania
major. CNS-1 deficiency led to failure of IL-4 gene repositioning to
heterochromatin after Th1 polarization, possibly related to the presence
of reiterative Ikaros binding sites in the intergenic element.
Hyperacetylation of nonexpressed genes may serve to mark lineage-
specific loci for rapid expression and further modification.
REQUEST: [ leishmania ]
(17 articles match this request. 11 articles matching other requests removed)
PMID: 15760660
TITLE: Characterization and developmental gene regulation of a large gene family
encoding amastin surface proteins in Leishmania spp.
AUTHORS: Annie Rochette, François McNicoll, Joanne Girard, Marie Breton, Eric
Leblanc, Michel G Bergeron, Barbara Papadopoulou
AFFILIATION: Infectious Diseases Research Center, RC-709, CHUL Research Center
and Department of Medical Biology, Faculty of Medicine, Laval University, 2705
Laurier Blvd., Ste-Foy (QC), Que., Canada G1V 4G2.
REFERENCE: Mol Biochem Parasitol 2005 Apr 140(2):205-20
The ability of Leishmania amastigotes to survive within the drastic
environmental changes encountered in the phagolysosomes of mammalian
macrophages is heavily dependent on the developmental regulation of a
variety of genes. The identification of genes that are expressed
preferentially in the mammalian stage of the parasite should increase
our understanding of the molecular mechanisms regulating stage-specific
gene expression and of the determinants that control its intracellular
survival and contribute to its pathogenesis. We report here detailed
sequence characterization and structural organization of the amastin
gene family in Leishmania major and Leishmania infantum and the study of
their developmental gene regulation throughout the parasite's life
cycle. Amastin surface proteins represent the largest developmentally
regulated gene family reported so far in Leishmania comprising up to 45
members. All the members of the amastin gene family in both Leishmania
and Trypanosoma species share a similar structural organization and
contain a highly conserved 11 amino acid extracellular domain, which is
unique to amastin proteins. The majority of the amastin gene homologs
are specifically expressed in the amastigote stage of the parasite.
Three distinct RNA elements were identified in the 3'-untranslated
regions (3'UTR) of the amastin transcripts. The majority of these
transcripts contain a conserved 450nt cis-acting 3'UTR element shown
previously to regulate stage-specific gene expression at the level of
translation, which suggests that several amastin homologs may be
regulated by a similar mechanism of translational control inside the
macrophage. These findings further highlight the unique features of gene
expression control in Leishmania.
PMID: 15761661
TITLE: Acute chagas' disease presenting with a suprasellar mass and
panhypopituitarism.
AUTHORS: Hoon-Ji Helen Choi, Marcia Cornford, Lina Wang, Julie Sun, Theodore C
Friedman
AFFILIATION: Department of Endocrinology, Metabolism, and Molecular Medicine,
Charles Drew University of Medicine & Science, 1731 East 120th Street, Los
Angeles, CA 90059, USA.
REFERENCE: Pituitary 2005 Apr 7(2):111-4
Although intrinsic pituitary lesions are the most common cause of
hypopituitarism, suprasellar masses can produce similar symptoms. The
differential diagnosis of a suprasellar mass includes cystic lesions,
tumors, granulomatous disease, and infection. The etiology is not always
obvious, and despite extensive work-up, may remain elusive. A 28-year-
old Mexican man presented with complaints of headache and weakness for
two weeks duration. He became increasingly lethargic and an MRI revealed
a two centimeter suprasellar mass. Testing of the hypothalamic-
pituitary axis suggested panhypopituitarism. He was prescribed treatment
with hydrocortisone, DDAVP, and levothyroxine. Open craniotomy and
biopsy of the hypothalamus revealed marked inflammation with plasma
cells, histiocytes, and small lymphocytes. Light microscopy revealed
macrophage-contained leishmania-like organisms although results were not
immediately available. Pathological data was consistent with acute
infection by Trypanasoma cruzi. Despite supportive efforts, the patient
expired two months after presentation.This case illustrates the
difficulty of diagnosing and the potential rapid mortality of a
suprasellar mass. Because of the wide consideration of etiologies, a
tissue diagnosis is needed. However, as this case illustrates, a
definitive tissue diagnosis is not always possible, even following
biopsy during open craniotomy.
PMID: 15755914
TITLE: Cryptic paraflagellar rod in endosymbiont-containing kinetoplastid
protozoa.
AUTHORS: Catarina Gadelha, Bill Wickstead, Wanderley de Souza, Keith Gull,
Narcisa Cunha-E-Silva
AFFILIATION: Sir William Dunn School of Pathology, University of Oxford, South
Parks Road, Oxford OX1 3RE, United Kingdom. catarina.gadelha at path.ox.ac.uk.
REFERENCE: Eukaryot Cell 2005 Mar 4(3):516-25
Cilia and flagella are central to many biological processes in a diverse
range of organisms. The kinetoplastid protozoa are very appealing
models for the study of flagellar function, particularly in the light of
the availability of extensive trypanosomatid genome information. In
addition to the highly conserved 9 + 2 axoneme, the kinetoplastid
flagellum contains a characteristic paraflagellar rod structure (PFR).
The PFR is necessary for full motility and provides support for
metabolic regulators that may influence flagellar beating. However,
there is an intriguing puzzle: one clade of endosymbiont-containing
kinetoplastids apparently lack a PFR yet are as motile as species that
possess a PFR and are able to attach to the invertebrate host epithelia
. We investigated how these organisms are able to locomote despite the
apparent lack of PFR. Here we have identified a PFR1 gene in the
endosymbiont-bearing trypanosome Crithidia deanei. This gene is
expressed in C. deanei and is able to partially complement a pfr1 null
mutation in Leishmania mexicana cells, demonstrating that the encoded
protein is functional. Careful reexamination of C. deanei flagellar
ultrastructure revealed a greatly reduced PFR missed by many previous
analyses. This affirms the PFR as a canonical organelle of
kinetoplastids. Moreover, although PFR proteins have been conserved in
evolution, primary sequence differences contribute to particular PFR
morphotypes characteristic of different kinetoplastid species.
PMID: 15755918
TITLE: Intracellular Glycosylphosphatidylinositols Accumulate on Endosomes:
Toxicity of Alpha-Toxin to Leishmania major.
AUTHORS: Zhifeng Zheng, Rodney K Tweten, Kojo Mensa-Wilmot
AFFILIATION: Department of Cellular Biology, The University of Georgia, 724
Biological Sciences, Athens, GA 30602. mensawil at cb.uga.edu.
REFERENCE: Eukaryot Cell 2005 Mar 4(3):556-66
Glycosylphosphatidylinositols (GPIs) are ubiquitous glycolipids in
eukaryotes. In the protozoan Leishmania major, GPIs occur "free&
quot; or covalently linked to proteins (e.g., gp63) and polysaccharides
. While some free GPIs are detected on the plasma membrane, specific
sites where GPIs accumulate intracellularly are unknown in most cells,
although the glycolipids are synthesized within the secretory system.
Herein, we describe a protocol for identifying intracellular sites of
GPI accumulation by using alpha-toxin (from Clostridium septicum). Alpha
-toxin bound to gp63 and GPIs from L. major. Intracellular binding sites
for alpha-toxin were determined in immunofluorescence assays after
removal of GPI-anchored macromolecules (e.g., gp63) from the plasma
membrane of fixed cells by using detergent. Endosomes were a major site
for GPI accretion in L. major. GPI-less gp63 was detected at the
endoplasmic reticulum. In studies with live parasites, alpha-toxin
killed L. major with a 50% lethal concentration of 0.77 nM.
PMID: 15589796
TITLE: Positive Montenegro skin test among patients with sporotrichosis in Rio
De Janeiro.
AUTHORS: Mônica Bastos de Lima Barros, Armando Schubach, Antônio Carlos
Francesconi-do-Valle, Maria Clara Gutierrez-Galhardo, Tânia Maria Pacheco
Schubach, Fátima Conceição-Silva, Mariza de Matos Salgueiro, Eliame
Mouta-Confort, Rosani Santos Reis, Maria de Fátima Madeira, Tullia Cuzzi,
Leonardo Pereira Quintella, JanaÃna Pinho da Silva Passos, Maria José
Conceição, Mauro Célio de Almeida Marzochi
AFFILIATION: Instituto de Pesquisa ClÃnica Evandro Chagas (IPEC), Fundação
Oswaldo Cruz (Fiocruz), Av. Brasil 4365, Manguinhos, Rio de Janeiro CEP
21045-900, Brazil. monica at ipec.fiocruz.br
REFERENCE: Acta Trop 2005 Jan 93(1):41-7
We studied 52 patients with sporotrichosis confirmed by isolation of
Sporothrix schenckii and reactivity to the Montenegro skin test (MST)
during an ongoing outbreak of this mycosis in Rio de Janeiro. The
objective was to emphasize the importance of parasitological
confirmation and the possibility of incorrect diagnosis based on the
lesion's appearance, epidemiological information, and immunological
tests. The antigen used for the MST was conserved in either thimerosal 1
:10,000 (group 1) or 0.4% phenol (group 2). Nineteen patients (39%) in
group 1 and seven (12%) in group 2 presented an induration>or=10 mm (p&
lt;0.001). Sera from three patients (6.7%) reacted to indirect
immunofluorescence (IIF) for leishmaniasis, while sera from 10 patients
(22.2%) reacted to enzyme-linked immunosorbent assay (ELISA). Fifteen
patients (28.8%) presented up to two lesions, with a predominance of
ulcers. Forty-four patients (84.6%) were treated with itraconazole. In
the differential diagnosis between sporotrichosis and cutaneous
leishmaniasis, the possibility of co-infection, allergy to the reagent
diluent, and cross-reactions should be further investigated, especially
in regions with limited laboratory facilities.
PMID: 15620251
TITLE: Ancistrobenomine a, the first naphthylisoquinoline oxygenated at Me-3,
and related 5,1'-coupled alkaloids, from the "new" plant species
ancistrocladusbenomensis.
AUTHORS: Gerhard Bringmann, Michael Dreyer, Heiko Rischer, Kristina Wolf, Hamid
A Hadi, Reto Brun, Harald Meimberg, Günther Heubl
AFFILIATION: Institut für Organische Chemie der Universität Würzburg, Am
Hubland, D-97074 Würzburg, Germany. bringman at chemie.uni-wuerzburg.de
REFERENCE: J Nat Prod 2004 Dec 67(12):2058-62
Three new 5,1'-coupled naphthylisoquinoline alkaloids, ancistrobenomine
A (1), 6-O-demethylancistrobenomine A (2), and 5'-O-
demethylancistrocline (3), have been isolated from the stem bark of a
botanically as yet undescribed highland liana Ancistrocladus sp.,
proposed to be named "A. benomensis" according to the region
in Peninsular Malaysia where it has been discovered on the mountain of
Gunung Benom. Two of the compounds possess an unprecedented structure
with a novel hydroxymethylene group at C-3 of the fully dehydrogenated
isoquinoline moiety. The structural elucidation was achieved by chemical
, spectroscopic, and chiroptical methods. As typical of the so-called
Ancistrocladaceae type, all of the compounds isolated bear an oxygen at
C-6. Biological activities of these alkaloids against different
protozoic pathogens are described.
REQUEST: [ sand fly ]
(1 article matches this request. 1 article matching other requests removed)
REQUEST: [ sandfly ]
(2 articles match this request. 1 article matching other requests removed)
PMID: 15751918
TITLE: Seroprevalence of three emerging arboviral infections in Kuwaiti
nationals.
AUTHORS: A S Pacsa, U C Chaturvedi, A S Mustafa
AFFILIATION: Department of Microbiology, Faculty of Medicine, University of
Kuwait, Kuwait.
REFERENCE: East Mediterr Health J 2003 May 9(3):266-73
Diseases caused by dengue, sandfly fever and hanta viruses pose a major
health risk in many countries. We determined the threat of these
arboviral infections through a serologic using enzyme linked
immunosorbent assay (ELISA) based tests. Hantavirus-specific antibodies
were also detected using immunofluorescence. Of 499 samples tested for
dengue virus IgG antibodies l4% were as positive for dengue positive by
all the ELISA tests. Among the 42 showing strong IgG reactivity, only 1
was positive for dengue virus IgM antibodies. All samples tested for IgG
antibodies to sandfly fever virus were negative. Hantavirus antibodies
were detected in 11% of the 46 samples from high-risk individuals. The
low prevalences suggest that at present these infections are not a
serious problem in Kuwait.
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