[leish-l] Fwd: Articles found by RefScout for your requests

[jeffreyj at usp.br]

----- Forwarded message from info at refscout.com -----
    Date: Wed, 15 Sep 2004 16:05:06
    From: info at refscout.com

New!

Have a look at our new tool, the RefScout‘s PDF-Manager (PDFM)! The RefScout‘s
PDFM will revolutionize your life with PDF files!
 
Simply let your PDF files be organized by the RefScout‘s PDFM in a table and get
direct link to your local copy. In addition, the RefScout‘s PDFM will alert you
each time the NLM PubMed updates information concerning your specific
reference!
Get your free 2 months trial version now at RefScout’s PDF-Manager.



REQUEST: [ leishmaniasis ]

(21 articles match this request)



PMID: 15361245
 

TITLE: The immunopathology of experimental visceral leishmaniasis.

AUTHORS: Paul M Kaye, Mattias Svensson, Manabu Ato, Asher Maroof, Rosalind
Polley, Simona Stager, Soombul Zubairi, Christian R Engwerda

AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, London, UK.

REFERENCE: Immunol Rev 2004 Oct 201():239-53

Summary: Experimental murine infection with the parasites that cause 
human visceral leishmaniasis (VL) results in the establishment of 
infection in the liver, spleen, and bone marrow. In most strains of mice
, parasites are eventually cleared from the liver, and hepatic 
resistance to infection results from a coordinated host response 
involving a broad range of effector and regulatory pathways targeted 
within defined tissue structures called granulomas. In contrast, 
parasites persist in the spleen and bone marrow by mechanisms that are 
less well understood. Parasite persistence is accompanied by the failure
 of granuloma formation and by a variety of pathologic changes, 
including splenomegaly, disruption of lymphoid tissue microarchitecture
, and enhanced hematopoietic activity. Here, we review the salient 
features of these distinct tissue responses and highlight the varied 
roles that cytokines of the tumor necrosis factor family play in 
immunity to this infection. In addition, we also discuss recent studies 
aimed at understanding how splenomegaly affects the survival and 
function of memory cells specific for heterologous antigens, an issue of
 considerable importance for our understanding of the disease-associated
 increase in secondary infections characteristic of human VL.








PMID: 15361244
 

TITLE: Re-examination of the immunosuppressive mechanisms mediating non-cure of
Leishmania infection in mice.

AUTHORS: David Sacks, Charles Anderson

AFFILIATION: Laboratory of Parasitic Diseases, NIAID, Bethesda, MD, USA.

REFERENCE: Immunol Rev 2004 Oct 201():225-38

Summary: The interleukin (IL)-4 driven, polarized T-helper 2 cell (Th2) 
response that controls non-healing infection with Leishmania major in 
BALB/c mice has long been embraced as the underlying principle with 
which to consider the pathogenesis of non-healing and systemic forms of 
leishmaniasis in humans. The inability, however, to reveal a Th2 
polarity associated with non-curing clinical disease has suggested that 
alternative cells and cytokines are involved in susceptibility. In this 
review, various mouse models of non-curing infection with L. major and 
other Leishmania species are re-examined in the context of the 
suppression mediated by IL-10 and regulatory T (Treg) cells. These 
activities are revealed in L. major-infected BALB/c IL-4 knockout (KO) 
and IL-4Ralpha KO mice and especially in non-cure resistant mice that do
 not default to a Th2 pathway as a result of inherent defects in Th1 
differentiation. In contrast to the extreme BALB/c susceptibility 
arising from an aberrant Th2 response, non-cure in resistant mice arises
 from an imbalance in Treg cells that are activated in the context of an
 ongoing Th1 response and whose primary function may be to suppress the 
immunopathology associated with persistent antiparasite responses in 
infected tissues.




PMID: 15361400
 

TITLE: Visceral leishmaniasis resembling systemic lupus erythematosus.

AUTHORS: P V Voulgari, G A Pappas, E N Liberopoulos, M Elisaf, F N Skopouli, A A
Drosos

AFFILIATION: Department of Internal Medicine, Medical School, University of
Ioannina, 45110 Ioannina, Greece. adrosos at cc.uoi.gr

REFERENCE: Ann Rheum Dis 2004 Oct 63(10):1348-9




PMID: 15361229
 

TITLE: Role of the Toll/interleukin-1 receptor signaling pathway in host
resistance and pathogenesis during infection with protozoan parasites.

AUTHORS: Ricardo T Gazzinelli, Catherine Ropert, Marco A Campos

AFFILIATION: Department of Biochemistry and Immunology, Federal University of
Minas Gerais, Belo Horizonte, MG, Brazil.

REFERENCE: Immunol Rev 2004 Oct 201():9-25

Summary: Different studies have illustrated the activation of the innate
 immune system during infection with protozoan parasites. Experiments 
performed in vivo also support the notion that innate immunity has a 
crucial role in resistance as well as pathogenesis observed during 
protozoan infections such as malaria, leishmaniasis, toxoplasmosis, and 
trypanosomiasis. While major advances have been made in the assignment 
of bacterial molecules as Toll-like receptors (TLRs) agonists as well as
 defining the role of the Toll/interleukin-1 receptor (TIR) signaling 
pathway in host resistance to bacterial infection, this research area is
 now emerging in the field of protozoan parasites. In this review, we 
discuss the recent studies describing parasite molecules as TLR agonists
 and those studies indicating the essential role of the TIR-domain 
bearing molecule named myeloid differentiation factor 88 in host 
resistance to infection with protozoan parasites. Together, these 
studies support the hypothesis that the TIR signaling pathway is 
involved in the initial recognition of protozoan parasites by the immune
 system of the vertebrate host, early resistance to infection, 
development of acquired immunity, as well as pathology observed during 
acute infection with this class of pathogens.




PMID: 15361250
 

TITLE: The development of effector and memory T cells in cutaneous
leishmaniasis: the implications for vaccine development.

AUTHORS: Phillip Scott, David Artis, Jude Uzonna, Colby Zaph

AFFILIATION: Department of Pathobiology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, PA, USA.

REFERENCE: Immunol Rev 2004 Oct 201():318-38

Summary: Leishmania major infections induce the development of a CD4(+) 
T-helper 1 (Th1) response that not only controls the primary infection 
but also results in life-long immunity to reinfection. How that immunity
 is maintained is unknown, although because of the existence of 
infection-induced immunity, there has been an assumption that the 
development of a vaccine against leishmaniasis would be relatively easy
. This has turned out not to be the case. One problem has been the 
finding that a large part of the immunity induced by a primary infection
 depends upon the presence of persistent parasites. Nevertheless, there 
are ample situations where immunologic memory persists without the 
continued presence of antigen, providing the prospect that a non-live 
vaccine for leishmaniasis can be developed. To do so will require an 
understanding of the events involved in the development of an effective 
protective T-cell response and, more importantly, an understanding of 
how to maintain that response. Here, we review work from our laboratory
, describing how Th1 cells develop in L. major-infected mice, the nature
 of the memory T cells that provide protection to reinfection, and how 
that information may be utilized in the development of vaccines.




PMID: 15357212
 

TITLE: The application of gene expression microarray technology to kinetoplastid
research.

AUTHORS: Robert C Duncan, Poonam Salotra, Neena Goyal, Natalia S Akopyants,
Stephen M Beverley, Hira L Nakhasi

AFFILIATION: Division of Emerging and Transfusion Transmitted Diseases, Office
of Blood Research and Review, CBER, FDA, Bethesda, MD, USA.
Duncan at CBER.FDA.GOV

REFERENCE: Curr Mol Med 2004 Sep 4(6):611-21

Protozoan parasites in the order Kinetoplastida cause severe disease 
primarily in tropical and subtropical areas. Vaccines to control these 
diseases have shown some promise, but none are in active clinical use. 
Drug treatments are available for all of the acute infections, but the 
emergence of resistance and an unresponsive chronic phase are current 
problems. Rapid advances in genomic technology open the possibility of 
discovering new genes that can contribute to vaccine initiatives or 
serve as targets for development of new drugs. The DNA microarray is a 
genomic technology, which is being applied to new gene discovery in 
kinetoplastid parasites. Both cDNA and genomic microarrays for 
Leishmania major have identified a number of new genes that are 
expressed in a stage-specific fashion and preliminary results from a L. 
donovani genomic microarray also demonstrated new gene discovery. A 
microarray of Trypanosoma brucei genomic fragments identified new genes 
whose expression differs between the insect borne stage and the human 
infectious stage of the parasite. The next few years, building on this 
foundational work, should witness the most exciting stage as microarrays
 are applied to questions such as the basis of drug resistance, post 
kala azar dermal leishmaniasis, the regulation of differentiation to 
infectious stages, linking coordinately regulated pathways of genes and 
development of genetically defined parasites that may have potential as 
live attenuated vaccines.




PMID: 15357215
 

TITLE: Leishmaniasis: current status of vaccine development.

AUTHORS: Bindu Sukumaran, Rentala Madhubala

AFFILIATION: School of Life Sciences, Jawaharlal Nehru University, New Delhi
110067, India.

REFERENCE: Curr Mol Med 2004 Sep 4(6):667-79

Leishmaniasis, a spectrum of diseases caused by various forms of 
Leishmania has become a major health problem all over the world. 
Vaccination against leishmaniasis has passed through many developmental 
stages beginning with the ancient practice of 'leishmanization'. Due to 
various problems and difficulties associated with traditional vaccines, 
the interest has been shifted to novel approaches of vaccination like 
DNA vaccination, vaccination with live vectors encoding leishmanial 
antigens and finally to designer vaccines. In an effort towards 
developing an anti-leishmanial vaccine, our laboratory has been working 
on various genes present in an amplified locus of Leishmania known as 
the 'LD1 locus'. Two genes, ORFF and BT1 (previously ORFG), are part of 
the multigenic LD1 locus on chromosome 35. BT1 encodes a biopterin 
transporter, while the function of ORFF gene product is unknown. 
Immunization of mice with recombinant ORFF (rORFF) and BT1 proteins, 
individually, or in combination, conferred partial protection against 
challenge with Leishmania donovani. We also tested the protective 
efficacy of ORFF DNA vaccine in BALB/c mice model and found that the 
level of protection was significantly higher than that of ORFF protein. 
Protection conferred by ORFF DNA vaccine correlated with significant 
levels of in vitro splenocyte proliferation and low levels of antigen-
specific antibodies. There was a preferential production of IFN-gamma 
compared to IL-4, which indicated the induction of a protective Th1 
response, by the DNA vaccine. Thus, DNA immunization may offer an 
attractive alternative strategy against leishmaniasis. We present here 
the current status of vaccine development against leishmaniasis.




PMID: 15357216
 

TITLE: Macrophage specific drug delivery in experimental leishmaniasis.

AUTHORS: Mukul Kumar Basu, Sanchaita Lala

AFFILIATION: Indian Institute of Chemical Biology, 4, Raja SC Mullick Road,
Kolkata-700032, India. biomembrane at iicb.res.in

REFERENCE: Curr Mol Med 2004 Sep 4(6):681-9

Macrophage-specific delivery systems are the subject of much interest 
nowadays, because of the fact that macrophages act as host cells for 
many parasites and bacteria, which give rise to outbreak of so many 
deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. To 
combat these deadly diseases initially macrophage specific liposomal 
delivery system were thought of and tested in vivo against experimental 
leishmaniasis in hamsters using a series of indigenous or synthetic 
antileishmanial compounds and the results were critically discussed. In 
vitro testing was also done against macrophages infected with Leishmania
 donovani, the causative agent for visceral leishmaniasis. The common 
problem of liposome therapy being their larger size, stability and 
storage, non-ionic surfactant vesicles, niosomes were prepared, for 
their different drug distribution and release characteristics compared 
to liposomes. When tested in vivo, the retention capacity of niosomes 
was found to be higher than that of liposomes due to the absence of 
lipid molecules and their smaller size. Thus the therapeutic efficacy of
 certain antileishmanial compounds was found to be better than that in 
the liposomal form. The niosomes, being cheaper, less toxic, 
biodegradable and non-immunogenic, were considered for sometime as 
suitable alternatives to liposomes as drug carriers. Besides the advent 
of other classical drugs carriers(e.g. neoglycoproteins), the biggest 
challenge came from polymeric delivery vehicles, specially the polymeric
 nanoparticles which were made of cost effective biodegradable polymers 
and different natural polymers. Because of very small size and highly 
stable nature, use of nanoparticles as effective drug carriers has been 
explored in experimental leishmaniasis using a series of antileishmanial
 compounds, both of indigenous and synthetic origin. The feasibility of 
application in vivo, when tested for biological as well as for other 
physicochemical parameters, the polymeric nanoparticles have turned out 
to be the best and thus may be projected for effective use in the 
clinics.




PMID: 15357217
 

TITLE: Role of chemokines in Leishmania infection.

AUTHORS: Kaushik Roychoudhury, Syamal Roy

AFFILIATION: Department of Immunology, Indian Institute of Chemical Biology 4,
Raja SC Mullick Road, Kolkata-700 032, India.

REFERENCE: Curr Mol Med 2004 Sep 4(6):691-6

Chemokines are a growing group of chemoattractant cytokines that play 
important roles in physiological as well as pathological processes. 
Their roles in various aspects of pathogenesis and inflammation have 
come to light in the past decade or so. It is becoming increasingly 
clear that chemokines play a major, perhaps decisive role in Leishmania 
infections. In this review, we recapitulate important works linking the 
chemokine system with relation to visceral and cutaneous leishmaniasis 
over the past decade and attemptto put it all together to propose a 
single yet unfinished model to account for all the findings.








PMID: 15357218
 

TITLE: Progress in vaccine research and possible effector mechanisms in visceral
leishmaniasis.

AUTHORS: Rajesh Ravindran, Nahid Ali

AFFILIATION: Infectious Diseases Group, Indian Institute of Chemical Biology,
Calcutta, India.

REFERENCE: Curr Mol Med 2004 Sep 4(6):697-709

Visceral leishmaniasis represents a serious public health concern in 
endemic regions and is rapidly emerging as an opportunistic infection in
 HIV patients. The disease is difficult to diagnose and prevent, and 
available treatment is associated with toxicity and drug resistance. 
Even though significant headway has been made in the development of 
vaccines against cutaneous leishmaniasis, visceral leishmaniasis has 
received limited attention. The fact that a large proportion of the 
people living in endemic areas have self-resolving subclinical infection
 and individuals once recovered are immune to reinfection provides a 
rationale for designing immunoprophylactic strategies against visceral 
leishmaniasis. The primary aim of this paper is to review advances in 
vaccination strategies against visceral leishmaniasis, suggesting 
possible effector mechanism leading to resistance. It also covers the 
role of immunostimulators and gives an account of the adjuvants used 
against visceral leishmaniasis. Vaccine strategies in different 
established experimental models have also been dealt with which can 
provide potential leads for their application in humans. In light of the
 available observations made during the course of studies performed on 
experimental models of visceral leishmaniasis there is increasing 
evidence that a successful approach towards a vaccine involves the 
requirement of Th1 subset of CD4+ cells along with Th2, CD8+, and B 
cells. In this review we present the possible mechanism of interaction 
of these cells and their effector molecules in providing resistance 
against visceral leishmaniasis for the future design of effective 
vaccine against this disease.




PMID: 15357745
 

TITLE: Itraconazole in the treatment of New World mucocutaneous leishmaniasis.

AUTHORS: Manuel Calvopina, Angel G Guevara, Rodrigo X Armijos, Yoshihisa
Hashiguchi, Robert N Davidson, Philip J Cooper

AFFILIATION: Department of Clinical Investigations, Hospital Vozandes, Quito,
Ecuador.

REFERENCE: Int J Dermatol 2004 Sep 43(9):659-63

Abstract Background A well-tolerated oral drug is required for the 
treatment of mucocutaneous leishmaniasis (MCL). Current parenteral 
treatment regimens with pentavalent antimonials are associated with 
marked toxicity and significant rates of relapse. Aim To evaluate the 
efficacy and tolerability of high-dose itraconazole for the treatment of
 MCL. Methods An uncontrolled treatment study was performed in 13 
Ecuadorian patients with MCL. Each patient received a daily dosage of 
400 mg of itraconazole for a minimum of 3 months. Results All 13 
subjects responded to itraconazole during the first month of treatment, 
but by 12 months after treatment the complete resolution of MCL lesions 
was observed in only three (23%) subjects. No adverse effects of 
treatment were reported. Response to treatment was associated with a 
short evolution of the disease and mild to moderate disease severity. 
Conclusion Prolonged and high-dose treatment regimens with itraconazole 
are not effective for the treatment of the majority of patients with MCL.




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: 15355408
 

TITLE: Assessment of nephrotoxicity in patients receiving amphotericin B lipid
complex: a pharmacosurveillance study in Spain.

AUTHORS: J-M Aguado, C Lumbreras, D González-Vidal, 

AFFILIATION: Unidad de Enfermedades Infecciosas, Hospital Universitario '12 de
Octubre', Madrid, Spain.

REFERENCE: Clin Microbiol Infect 2004 Sep 10(9):785-90

Abstract This study assessed the risk of haematological, renal and 
hepatic toxicity associated with amphotericin B lipid complex (ABLC; 
Abelcet) in a multicentre, open-label, non-comparative study of 93 
patients from 17 different hospitals who received ABLC because of proven
 or suspected systemic fungal infection or leishmaniasis. Most (66%) 
patients had onco-haematological diseases. Optimum treatment with ABLC 
comprised a slow (2-h) infusion dose of 5 mg/kg/day for a minimum period
 of 14 days. Biochemical and haematological parameters were measured pre
-, during and post-treatment. In the overall patient group, the mean 
serum creatinine concentration was similar pre- and post-study (1.00
 +/- 1.14 mg/dL vs. 1.20 +/- 1.19 mg/dL; p > 0.05). There were no 
significant changes pre- and post-treatment in concentrations of 
haemoglobin, potassium, transaminases and bilirubin. There was no 
significant correlation between the dose administered and the 
concentrations of serum creatinine (Spearmann 0.22). There was no 
greater nephrotoxicity in the patients with previous renal failure, or 
in those who had received amphotericin B previously. There were serious 
adverse events in five patients, but other alternative causes that could
 explain these events were present in three of these patients. Fevers or
 chills were experienced by 23% of the patients during the ABLC infusion
, but only in one case did this necessitate the suspension of treatment
. It was concluded that ABLC is a drug with low nephrotoxicity, even 
when administered to patients with pre-existing renal insufficiency. 
Adverse events were generally slight or moderate, and were managed 
easily with appropriate pre-medication.




PMID: 15252045
 

TITLE: Dual Action of Antimonial Drugs on Thiol Redox Metabolism in the Human
Pathogen Leishmania donovani.

AUTHORS: Susan Wyllie, Mark L Cunningham, Alan H Fairlamb

AFFILIATION: Division of Biological Chemistry and Molecular Biology, Wellcome
Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH,
Scotland.

REFERENCE: J Biol Chem 2004 Sep 279(38):39925-32

Despite extensive use of antimonial compounds in the treatment of 
leishmaniasis, their mode of action remains uncertain. Here we show that
 trivalent antimony (Sb(III)) interferes with trypanothione metabolism 
in drug-sensitive Leishmania parasites by two inherently distinct 
mechanisms. First, Sb(III) decreases thiol buffering capacity by 
inducing rapid efflux of intracellular trypanothione and glutathione in 
approximately equimolar amounts. Second, Sb(III) inhibits trypanothione 
reductase in intact cells resulting in accumulation of the disulfide 
forms of trypanothione and glutathione. These two mechanisms combine to 
profoundly compromise the thiol redox potential in both amastigote and 
promastigote stages of the life cycle. Furthermore, we demonstrate that 
sodium stibogluconate, a pentavalent antimonial used clinically for the 
treatment for leishmaniasis, induces similar effects on thiol redox 
metabolism in axenically cultured amastigotes. These observations 
suggest ways in which current antimony therapies could be improved, 
overcoming the growing problem of antimony resistance.




PMID: 15361111
 

TITLE: Anti-leishmanial activity of a new formulation of amphotericin B.

AUTHORS: M A Dea-Ayuela, S Rama-Iñiguez, J A Sánchez-Brunete, J J Torrado, J M
Alunda, F Bolás-Fernández

AFFILIATION: Departamento de Parasitología, Universidad Complutense, Madrid,
Spain.

REFERENCE: Trop Med Int Health 2004 Sep 9(9):981-90

Summary The effectiveness of albumin microspheres loaded with 
amphotericin B was tested in an in vivo model of visceral leishmaniasis 
using the golden hamster. Free and encapsulated amphotericin B was 
tested at the dose of 1 mg/kg given by the intracardiac route on days 25
, 26 and 27 post-infection (p.i.) to treat animals previously infected 
with 10(7) stationary promastigotes by the intracardiac route. 
Encapsulated amphotericin was highly effective against infection causing
 a reduction of 88.8% and 87.2% in the early stage of infection (day 32 
p.i.) and of 66.7% and 54% in a later stage of infection (day 135 p.i.) 
in liver and spleen parasite load respectively, compared with untreated 
animals, whereas free amphotericin was inactive. Lymphocyte 
proliferation was restored together with an increase in CD4(+) subsets 
in animals treated with encapsulated amphotericin B, but not in those 
treated with the non-encapsulated compound. Antibody responses did not 
increase after treatment with encapsulated amphotericin B with antibody 
levels remaining at base levels for most animals in contrast to those of
 untreated or treated with free amphotericin, where in most animals the 
antibody levels sharply increased. This new formulation could be a more 
economical alternative to liposomes for the treatment of visceral 
leishmaniasis with amphotericin B.




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: 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: 15354854
 

TITLE: Cutaneous leishmaniasis in red kangaroos.

AUTHORS: K Rose

REFERENCE: Aust Vet J 2004 Jul 82(7):440




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

 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.

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


PMID: 12000658
 

TITLE: Humoral and cellular immune responses to glucose regulated protein 78 --
a novel Leishmania donovani antigen.

AUTHORS: Anja T R Jensen, Ahmed Ismail, Ameera Gaafar, Ahmed M El Hassan, Thor G
Theander

AFFILIATION: Centre for Medical Parasitology, Institute for Medical Microbiology
and Immunology, University of Copenhagen, Denmark. parasite at biobase.dk

REFERENCE: Trop Med Int Health 2002 May 7(5):471-6

The recently cloned glucose regulated protein 78 (GRP78) of Leishmania 
donovani has been suggested as a new and promising Leishmania vaccine 
candidate. We assessed antibody and T-cell reactivity to GRP78 in an 
enzyme-linked immunosorbent assay (ELISA) and in lymphoproliferative 
assays. Serological evaluation of plasma samples obtained in Sudan 
revealed that 89% of patients with visceral leishmaniasis (VL), 78% with
 post kala-azar dermal leishmaniasis (PKDL), and 85% with cutaneous 
leishmaniasis (CL) had antibody reactivity to this Leishmania antigen. 
Plasma from healthy Sudanese individuals living in an area endemic for 
malaria but free of leishmaniasis and plasma from healthy Danes was 
negative in the assay. GRP78 antibody was detected in 10% and 5% of 
plasma samples from Sudanese and Ghanaian malaria patients, respectively
, whereas 35% of plasma samples from otherwise healthy Sudanese 
individuals with a positive leishmanin skin test showed antibody 
reactivity to recombinant GRP78 (rGRP78). In lymphoproliferative assays
, 9 of 13 isolates of peripheral blood mononuclear cells (PBMC) from 
individuals previously infected with L. donovani and one of three 
individuals previously infected with L. major showed a response to 
rGRP78, whereas PBMC isolates from Danish control individuals did not 
respond. These findings, in addition to our previous observations in 
experimental CL (Jensen et al. 2001), confirm GRP78 as a possible 
vaccine antigen.




PMID: 12019027
 

TITLE: In vitro susceptibility to pentavalent antimony in Leishmania infantum
strains is not modified during in vitro or in vivo passages but is modified
after host treatment with meglumine antimoniate.

AUTHORS: Jaume Carrió, Montserrat Portús

AFFILIATION: Laboratory of Parasitology, Departament de Microbiologia i
Parasitologia Sanità ries, Facultat de Farmà cia, Universitat de Barcelona,
08028 Barcelona, Spain. jcarrio at farmacia.far.ub.es

REFERENCE: BMC Pharmacol 2002 May 2(1):11

BACKGROUND: Leishmaniasis is a common parasitic disease in Southern 
Europe, caused by Leishmania infantum. The failures of current treatment
 with pentavalent antimonials are partially attributable to the 
emergence of antimony-resistant Leishmania strains. This study analyses 
the in vitro susceptibility to pentavalent antimony of intracellular 
amastigotes from a range of L. infantum strains, derived from the same 
infected animal, during in vitro and in vivo passages and after host 
treatment with meglumine antimoniate. RESULTS: SbV-IC50 values for 
strains from two distinct isolates from the same host and one stock 
after two years of culture in NNN medium and posterior passage to 
hamster were similar (5.0 +/- 0.2; 4.9 +/- 0.2 and 4.4 +/- 0.1 mgSbV/L, 
respectively). In contrast, a significant difference (P < 0.01, t 
test) was observed between the mean SbV-IC50 values in the stocks 
obtained before and after treatment of hosts with meglumine antimoniate
 (4.7 +/- 0.4 mgSbV/L vs. 7.7 +/- 1.5 mgSbV/L). Drug-resistance after 
drug pressure in experimentally infected dogs increased over repeated 
drug administration (6.4 +/- 0.5 mgSbV/L after first treatment vs. 8.6
 +/- 1.4 mgSbV/L after the second) (P < 0.01, t test). CONCLUSIONS: 
These results confirm previous observations on strains from Leishmania/
HIV co-infected patients and indicate the effect of the increasing use 
of antimony derivatives for treatment of canine leishmaniasis in endemic
 areas on the emergence of Leishmania antimony-resistant strains.




PMID: 9820738
 

TITLE: Host susceptibility factors to cutaneous leishmaniasis.

AUTHORS: D E Jones, M M Elloso, P Scott

AFFILIATION: Department of Pathobiology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
jonesdou at mail.med. upenn.edu

REFERENCE: Front Biosci 1998 Nov 3():D1171-80

The host-pathogen relationship is the focus of many different studies 
which use a variety of disease models and different pathogens. 
Immunological studies in the mouse using the intracellular parasite 
Leishmania have helped define several aspects of host-pathogen 
interactions. Resistance to Leishmania is dependent on the development 
of CD4+ Th1 cells which promote an effective cell mediated immune 
response. Production of the cytokine IFN-gamma during this immune 
response activates macrophages enabling them to kill the parasite and 
control the infection. In contrast, susceptibility to this parasite is 
characterized by a Th2 response which produces predominantly IL-4. This 
cytokine promotes high antibody titers directed towards the parasite but
 does not activate macrophages for parasite killing. This host response 
results in high parasite numbers and a progressive increase in lesion 
size. The mouse model of leishmaniasis has been extremely useful in 
gaining an understanding of the immunological factors important in 
determining T cell commitment into Th1 or Th2 populations during an in 
vivo immune response.




REQUEST: [ leishmania ]

(27 articles match this request. 13 articles matching other requests removed)



PMID: 15361232
 

TITLE: New lessons from old pathogens: what parasitic infections have taught us
about the role of nuclear factor-kappaB in the regulation of immunity.

AUTHORS: Nicola J Mason, David Artis, Christopher A Hunter

AFFILIATION: Department of Pathobiology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, PA, USA.

REFERENCE: Immunol Rev 2004 Oct 201():48-56

Summary: The nuclear factor-kappaB (NF-kappaB) family of transcription 
factors is activated by many infectious and inflammatory stimuli. This 
family regulates the expression of multiple genes, whose products 
include cytokines, chemokines, adhesion molecules, and antiapoptotic 
factors that are important components of the innate and adaptive immune 
response. A prominent role of NF-kappaB transcription factors in 
resistance to a variety of infectious diseases was revealed by studies 
with mice that lack individual family members. However, little is known 
about the basis for these effects or about the role of individual family
 members during a coordinated immune response to infection. Diverse 
parasites such as Toxoplasma gondii, Leishmania major, and Trichuris 
muris provide a unique opportunity to understand the role of the NF-
kappaB system in the development of innate and adaptive immunity to 
these infections. The basis for resistance and susceptibility to these 
parasites is well understood, and studies using these experimental 
systems have provided unique insights into the role of NF-kappaB in the 
regulation of T-helper 1 cell (Th1) and Th2 type responses. It has 
become clear that NF-kappaB family members have cell lineage-specific 
functions and that their relative importance varies with type of 
infection as well as route of pathogen entry. Thus, studies with models 
of parasitic infection have revealed that individual NF-kappaB family 
members perform distinct, nonoverlapping, and biologically significant 
functions in the regulation of immunity and inflammation.




PMID: 15361243
 

TITLE: Does the Leishmania major paradigm of pathogenesis and protection hold
for New World cutaneous leishmaniases or the visceral disease?

AUTHORS: Diane McMahon-Pratt, James Alexander

AFFILIATION: Department of Epidemiology & Public Health, Yale University
School of Medicine, New Haven, CT, USA.

REFERENCE: Immunol Rev 2004 Oct 201():206-24

Summary: Parasitic protozoa of the genus Leishmania have provided a 
useful perspective for immunologists in terms of host defense mechanisms
 critical for the resolution of infection caused by intracellular 
pathogens. These organisms, which normally reside in a late endosomal, 
major histocompatibility complex (MHC) class II(+) compartment within 
host macrophages cells, require CD4(+) T-cell responses for the control 
of disease. The paradigm for the CD4(+) T-helper 1 (Th1)/Th2 dichotomy 
is largely based on the curing/non-curing responses, respectively, to 
Leishmania major infection. However, this genus of parasitic protozoa is
 evolutionarily diverse, with the cutaneous disease-causing organisms of
 the Old World (L. major) and New World (Leishmania mexicana/ Leishmania
 amazonensis) having diverged 40-80 million years ago. Further 
adaptations to survive within the visceral organs (for Leishmania 
donovani, Leishmania chagasi, and Leishmania infantum) must have been 
required. Consequently, significant differences in host-parasite 
interactions have evolved. Different virulence factors have been 
identified for distinct Leishmania species, and there are profound 
differences in the immune mechanisms that mediate susceptibility/
resistance to infection and in the pathology associated with disease. 
These variations not only point to interesting features of the host-
pathogen interaction and immunobiology of this genus of parasitic 
protozoa, but also have important implications for immunotherapy and 
vaccine development.




PMID: 15356347
 

TITLE: Leashing leishmania.

AUTHORS: R John Davenport

REFERENCE: Sci Aging Knowledge Environ 2004 Sep 2004(36):NF82

Most of the people who die from flu each winter are older than 65. But a
 new study suggests that sometimes age bolsters, rather than cripples, 
the immune system. In at least one strain of mice, geriatric rodents 
resist a parasitic skin infection better than youngsters do. The finding
 highlights the convoluted changes that time imparts on the immune 
system, although researchers don't yet know how the finding relates to 
human health.




PMID: 15357210
 

TITLE: cAMP signalling in the kinetoplastid protozoa.

AUTHORS: T Seebeck, R Schaub, A Johner

AFFILIATION: Institute of Cell Biology, University of Bern, Baltzerstrasse 4,
CH-3012 Bern, Switzerland. thomas.seebeck at izb.unibe.ch

REFERENCE: Curr Mol Med 2004 Sep 4(6):585-99

Several species of kinetoplastid protozoa cause major human infectious 
diseases. Trypanosoma cruzi is responsible for the fatal Chagas disease 
in large parts of South America, the various species of Leishmania cause
 a number of different human diseases with millions of patients world-
wide, and the African trypanosome Trypanosoma brucei is the agent of 
human sleeping sickness, a disastrously re-emerging epidemic of fatal 
infections in Sub-Saharan Africa. Chemotherapy of all of these 
infections is in a very unsatisfactory state. cAMP signalling pathways 
in humans have provided interesting drug targets for a number of 
clinical conditions, from asthma to impotency. Similarly, cAMP 
signalling in kinetoplastids might offer useful targets for the 
development of novel antiparasitic drugs, which makes their exploration 
an urgent need. Current knowledge suggests that cAMP signalling proceeds
 along very similar pathways in all kinetoplastid pathogens (T. cruzi, 
the Leishmanias and T. brucei). Their adenylyl cyclases are structurally
 very different from the human enzymes and appear to function as enzyme-
linked cell surface receptors. They might represent the major sensory 
apparatus of the kinetoplastids, guiding much of their environmental 
sensing and host/parasite interaction. The cAMP-specific 
phosphodiesterases of the kinetoplastids are rather similar to those of 
human cells and might function in similar ways. Essentially nothing is 
known on downstream effectors of cAMP in the kinetoplastids. Homologues 
of protein kinase A and its regulatory subunits have been identified, 
but their biochemical properties seem to be disctinct from that of 
mammalian protein kinase A.




PMID: 15357211
 

TITLE: New insights into the developmental biology and transmission mechanisms
of Leishmania.

AUTHORS: P A Bates, M E Rogers

AFFILIATION: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3
5QA, UK. pbates at liv.ac.uk

REFERENCE: Curr Mol Med 2004 Sep 4(6):601-9

Leishmania alternates between two main morphological forms in its life 
cycle: intracellular amastigotes in the mammalian host and motile 
promastigotes in the sandfly vector. Several different forms of 
promastigote can be recognised in sandfly infections. The first 
promastigote forms, which are found in the sandfly in the bloodmeal 
phase, are multiplicative procyclic promastigotes. These differentiate 
into nectomonad promastigotes, which are a non-dividing migratory stage 
moving from the posterior to the anterior midgut. When nectomonad 
promastigotes arrive at the anterior midgut they differentiate into 
leptomonad forms, a newly named life cycle stage, which resume 
replication. Leptomonad promastigotes, which are found in the anterior 
midgut, are the developmental precursors of the metacyclic promastigotes
, the mammal-infective stages. Leptomonad forms also produce 
promastigote secretory gel, a substance that plays a key role in 
transmission by forming a physical obstruction in the gut, forcing the 
sandfly to regurgitate metacyclic promastigotes during bloodfeeding.








PMID: 15357214
 

TITLE: Surface determinants of Leishmania parasites and their role in
infectivity in the mammalian host.

AUTHORS: Thomas Naderer, James E Vince, Malcolm J McConville

AFFILIATION: Department of Biochemistry and Molecular Biology, University of
Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.

REFERENCE: Curr Mol Med 2004 Sep 4(6):649-65

Leishmania are intracellular protozoan parasites that reside primarily 
in host mononuclear phagocytes. Infection of host macrophages is 
initiated by infective promastigote stages and perpetuated by an 
obligate intracellular amastigote stage. Studies undertaken over the 
last decade have shown that the composition of the complex surface 
glycocalyx of these stages (comprising lipophosphoglycan, GPI-anchored 
glycoproteins, proteophosphoglycans and free GPI glycolipids) changes 
dramatically as promastigotes differentiate into amastigotes. Marked 
stage-specific changes also occur in the expression of other plasma 
membrane components, including type-1, polytopic and peripheral membrane
 proteins, reflecting the distinct microbicidal responses and 
nutritional environments encountered by these stages. More recently, a 
number of Leishmania mutants lacking single or multiple surface 
components have been generated. While some of these mutants are less 
virulent than wild type parasites, many of these mutants exhibit only 
mild or no loss of virulence. These studies suggest that, 1) the major 
surface glycocalyx components of the promastigote stage (i.e. LPG, GPI-
anchored proteins) only have a transient or minor role in macrophage 
invasion, 2) that there is considerable functional redundancy in the 
surface glycocalyx and/or loss of some components can be compensated for
 by the acquisition of equivalent host glycolipids, 3) the expression of
 specific nutrient transporters is essential for life in the macrophage 
and 4) the role(s) of some surface components differ markedly in 
different Leishmania species. These mutants will be useful for 
identifying other surface or intracellular components that are required 
for virulence in macrophages.




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 Biofísica 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: 15355348
 

TITLE: Differences in substrate specificities between cysteine protease CPB
isoforms of Leishmania mexicana are mediated by a few amino acid changes.

AUTHORS: Maria A Juliano, Darren R Brooks, Paul M Selzer, Hector L Pandolfo,
Wagner A S Judice, Luiz Juliano, Morten Meldal, Sanya J Sanderson, Jeremy C
Mottram, Graham H Coombs

AFFILIATION: Department of Biophysics, Escola Paulista de Medicina, Universidade
Federal de São Paulo, Brazil.

REFERENCE: Eur J Biochem 2004 Sep 271(18):3704-14

The CPB genes of the protozoan parasite Leishmania mexicana encode stage
-regulated cathepsin L-like cysteine proteases that are important 
virulence factors and are in a tandem array of 19 genes. In this study, 
we have compared the substrate preferences of two CPB isoforms, CPB2.8 
and CPB3, and a H84Y mutant of the latter enzyme, to analyse the roles 
played by the few amino acid differences between the isoenzymes in 
determining substrate specificity. CPB3 differs from CPB2.8 at just 
three residues (N60D, D61N and D64S) in the mature domain. The H84Y 
mutation mimics an additional change present in another isoenzyme, CPB18
. The active recombinant CPB isoenzymes and mutant were produced using 
Escherichia coli and the S(1)-S(3) and S(1)'-S(3)' subsite specificities
 determined using a series of fluorogenic peptide derivatives in which 
substitutions were made on positions P(3) to P(3)' by natural amino 
acids. Carboxydipeptidase activities of CPB3 and H84Y were also observed
 using the peptide Abz-FRAK(Dnp)-OH and some of its analogues. The 
kinetic parameters of hydrolysis by CPB3, H84Y and CPB2.8 of the 
synthetic substrates indicates that the specificity of S(3) to S(3)' 
subsites is influenced greatly by the modifications at amino acids 60, 
61, 64 and 84. Particularly noteworthy was the large preference for Pro 
in the P(2)' position for the hydrolytic activity of CPB3, which may be 
relevant to a role in the activation mechanism of the L. mexicana CPBs.




PMID: 15361310
 

TITLE: Activity of dihydroartemisinin against Leishmania donovani both in vitro
and vivo.

AUTHORS: Ying Ma, Dian-Mei Lu, Xiao-Jun Lu, Lin Liao, Xiao-Su Hu

AFFILIATION: Department of Parasitology, School of Preclinical and Forensic
Medicine, Sichuan University, Chengdu 610041, China.

REFERENCE: Chin Med J (Engl) 2004 Aug 117(8):1271-3




PMID: 15358142
 

TITLE: Post genomic analysis of permeases from the amino acid/auxin family in
protozoan parasites.

AUTHORS: León A Bouvier, Ariel M Silber, Camila Galvão Lopes, Gaspar E Canepa,
Mariana R Miranda, Renata R Tonelli, Walter Colli, Maria Júlia M Alves,
Claudio A Pereira

AFFILIATION: Laboratorio de Biología Molecular de Trypanosoma cruzi (LBMTC),
Instituto de Investigaciones Médicas Alfredo Lanari, Consejo Nacional de
Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos
Aires, Argentina.

REFERENCE: Biochem Biophys Res Commun 2004 Aug 321(3):547-56

The "amino acid/auxin permeases" is probably the most represented family
 of transporters in the Trypanosoma cruzi genome. Using a high-
throughput searching routine and preliminary data from the T. cruzi 
genome project, more than 15,000 sequences were iteratively assembled 
into contigs, and 60 open reading frames corresponding to different 
putative amino acid transporters, clustered in 12 groups, were detected 
and characterized in silico. T. cruzi genomic organization of such 
sequences showed that these putative amino acid transporter genes are in
 an unusually large number and arranged in repeat clusters comprising 
about 0.2% of the genome. These data suggest that the family has evolved
 following tandem duplication events and constitutes a novel family of 
variable proteins in protozoan organisms. The mRNA expression of the 
predicted genes was demonstrated in infective and non-infective parasite
 forms. Orthologous sequences were also identified in other unicellular 
parasites such as Leishmania spp., Plasmodium spp., and Trypanosoma 
brucei.




PMID: 15358255
 

TITLE: Cysteine peptidases as virulence factors of Leishmania.

AUTHORS: Jeremy C Mottram, Graham H Coombs, James Alexander

AFFILIATION: Wellcome Centre for Molecular Parasitology, University of Glasgow,
Glasgow G12 8QQ, UK.

REFERENCE: Curr Opin Microbiol 2004 Aug 7(4):375-81

Leishmania mexicana amastigotes are particularly rich in cysteine 
peptidases (CPs), which play important roles in facilitating the 
survival and growth of the parasites in mammals. The importance of the 
CPs as virulence factors and their potential as drug targets and vaccine
 candidates has been investigated extensively. Recent years, however, 
have heralded advances in our knowledge and understanding of leishmanial
 CPs on two fronts. Firstly, genome analysis has revealed the great 
diversity of CPs, and, secondly, the ways in which the most widely 
studied CPs, designated CPB, influence the interaction between parasite 
and mammalian host have been elucidated. These topics are the focus of 
this review.




PMID: 15354357
 

TITLE: The Selenophosphate synthetase gene from Leishmania major.

AUTHORS: P Cyril Jayakumar, Vijay V Musande, Yogesh S Shouche, Milind S Patole

AFFILIATION: National Centrefor Cell Science, University of Pune Campus, Ganesh
Khind, Pune 411007, India.

REFERENCE: DNA Seq 2004 Feb 15(1):66-70

Selenophosphate synthetase coding sequence was cloned from Leishmania 
major by RT-PCR amplification. The DNA sequence was found to have an 
open reading frame encoding protein with 398 amino acids and does not 
have in-frame UGA codon. The deduced amino acid sequence indicates that 
it has cysteine residue instead of selenocysteine at the active site of 
enzyme. Amino acid sequence alignment of Selenophosphate synthetase from
 parasite with the human enzyme showed approximately 45% homology. The 
sequences also indicated presence of conserved amino acid residues and 
motifs that are present in mammalian Selenophosphate synthetase. 
Southern analysis done with restriction enzyme digested genomic DNA and 
pulse filed separated chromosome suggests that L. major genome contain a
 single copy of Selenophosphate synthetase sequence. Expression analysis
 by Northern analysis and RT-PCR indicated Selenophosphate synthetase 
mRNA is present in promastigote and amastigote stages of parasite.




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

 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.

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


PMID: 11420107
 

TITLE: Identification and characterisation of a RAD51 gene from Leishmania
major.

AUTHORS: P G McKean, J K Keen, D F Smith, F E Benson

AFFILIATION: Department of Biochemistry, Imperial College of Science, Technology
and Medicine, South Kensington, SW7 2AZ, London, UK. paul.g.mckean at man.ac.uk

REFERENCE: Mol Biochem Parasitol 2001 Jul 115(2):209-16

The RAD51 gene is a homologue of Escherichia coli recA which plays a 
central role in homologous recombination and DNA repair. This paper 
describes the identification of the RAD51 gene from the trypanosomatid 
parasite Leishmania major. The LmRAD51 gene codes for a 377 amino acid 
polypeptide with a predicted molecular mass of 41259 Da that is highly 
homologous to the Rad51 family of proteins. Recombinant L. major Rad51 
protein (LmRad51) was over-expressed in a bacterial expression system, 
purified to homogeneity and shown to bind DNA and exhibit DNA-stimulated
 ATPase activity, consistent with previously reported biochemical 
characteristics of Rad51 protein. Although LmRad51 expression is below 
the level of detection in exponentially growing cultures of Leishmania, 
high levels of LmRad51 mRNA and protein expression can be detected 
following exposure to the DNA-damaging agent phleomycin. LmRAD51 is one 
of the first examples of a DNA damage-inducible gene to be characterised
 in Leishmania, and will be invaluable in studying the contribution of 
homologous recombination to Leishmania virulence.




PMID: 3516722
 

TITLE: The occurrence and distribution of alpha-hydroxy-acid dehydrogenase in
some members of the order Kinetoplastida.

AUTHORS: M B Taylor, W E Gutteridge

REFERENCE: FEBS Lett 1986 Apr 199(2):237-41

LDH-X is the isoenzyme of lactate dehydrogenase found in mammalian 
spermatozoa, occurring in cytosolic and mitochondrial locations. 
Gossypol strongly inhibits it, and the spermicidal action of this 
compound is attributed to the disruption of a reducing shuttle. The 
flagellated protozoan, Trypanosoma cruzi, contains an enzyme activity 
similar to LDH-X, called alpha-hydroxy-acid dehydrogenase, which is here
 shown to possess cytosolic and glycosomal components. The glycosome is 
a microbody-like organelle containing the early glycolytic enzymes. We 
postulate that the inhibition of replication of T. cruzi by gossypol 
derives from interference with glycosomal reducing shuttles. T. lewisi 
resembles T. cruzi in this respect.




REQUEST: [ sand fly ]

(0 articles match this request)



REQUEST: [ sandfly ]

(1 article matches this request. 1 article matching other requests removed)














You receive this email because you requested RefScout®'s literature
update.
If you would like to change or add requests, please go to your user
profile.

If you can't read our newsletter, please resend newsletter back to us to
info at refscout.com, including information
about your operating system and mail client software you use, and we will do
our
best to solve the problem.

If you would like to be removed from RefScout®'s literature service, please
press the
remove button.



DISCLAIMER







----- End forwarded message -----