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[chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma].leishmaniasis refers to a spectrum of diseases caused by leishmania. clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by leishmania donovani. case report: an 11-year-old thai, living in belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. during a post-chemotherapy bone marrow aplasia, febrile episode with a gener ...199810327996
cationic liposome-encapsulated antisense oligonucleotide mediates efficient killing of intracellular leishmania.antisense oligonucleotides have been considered as inhibitors of growth of intracellular parasites such as leishmania, but only limited inhibition has been observed in vitro. we have encapsulated an antisense oligonucleotide, complementary to the leishmania universal miniexon sequence, in cationic liposomes. low concentrations (4 microm) of encapsulated oligonucleotides specifically reduced the amastigote burden within cultured macrophages by 80%. this result illustrates the importance of effect ...199910333480
phosphoglycosylation of a secreted acid phosphatase from leishmania donovani.the secreted acid phosphatase (sacp) of l.donovani is a heterogeneous glycoprotein that displays a wide array of n- and o-linked glycosylations. the o-linked sugars are of particular interest due to their similarity to the phosphoglycan structures of the major lipophosphoglycan surface antigen and released phosphoglycan (turco et al., 1987; greis et al., 1992). this study describes a structural analysis of the sacp o-linked glycosylations using mass spectroscopy, amino acid sequencing, and enzym ...199910336996
clinical and laboratory study of kala-azar in children in nepal.reports are scanty regarding kala-azar in children in nepal. in this communication we document 20 children diagnosed to have kala-azar who were admitted and treated at b. p. koirala institute of health sciences, dharan, nepal. the children were between 2 and 14 years old. the duration of illness varied between 12 days and 24 months with a majority (65 per cent) of children being ill for less than 6 months. hepatomegaly and splenomegaly were seen in 95 and 90 per cent of cases respectively. splen ...199910341503
down-regulation of marcks-related protein (mrp) in macrophages infected with leishmania.leishmania, a protozoan parasite of macrophages, has been shown to interfere with host cell signal transduction pathways including protein kinase c (pkc)-dependent signaling. myristoylated alanine-rich c kinase substrate (marcks) and marcks-related protein (mrp, macmarcks) are pkc substrates in diverse cell types. marcks and mrp are thought to regulate the actin network and thereby participate in cellular responses involving cytoskeletal rearrangement. because mrp is a major pkc substrate in mac ...199910358020
presence of a vacuolar h+-pyrophosphatase in promastigotes of leishmania donovani and its localization to a different compartment from the vacuolar h+-atpase.inorganic pyrophosphate promoted the acidification of an intracellular compartment in permeabilized promastigotes of leishmania donovani, as measured by acridine orange uptake. the proton gradient generated by pyrophosphate was collapsed by addition of nigericin or nh4cl. pyrophosphate-driven proton translocation was stimulated by potassium ions, and inhibited by naf, the pyrophosphate analogues imidodiphosphate and aminomethylenediphosphonate (amdp), dicyclohexylcarbodiimide, and the thiol reag ...199910359662
leishmania-specific t cells expressing interferon-gamma (ifn-gamma) and il-10 upon activation are expanded in individuals cured of visceral leishmaniasis.peripheral blood mononuclear cells (pbmc) from patients who have recovered from visceral leishmaniasis often respond to leishmania antigens in vitro by production of both il-4, ifn-gamma and il-10. in order to establish the cellular sources of these cytokines, we activated cells from individuals with a history of visceral leishmaniasis with leishmania antigen for 6 days in culture, and identified cytokine production at the single-cell level by flow cytometry. the cytokines were only found in cd3 ...199910361241
in vitro leishmanicidal activity of aurones.a series of aurones with drug-potential for leishmania infections was identified in vitro using both a direct cytotoxicity assay against extracellular promastigotes of leishmania donovani, l. infantum, l. enriettii, and l. major, and a test against intracellular amastigote forms of l. donovani residing within murine macrophages. the most active aurone (6-hydroxy-2-[phenylmethylene]-3(2h)-benzofuranone) had an ec50 of 0.45 microgram/ml in the extra-, and an ec50 of 1.40 micrograms/ml in the intra ...199910364835
characterization of a leishmania donovani gene encoding a protein that closely resembles a type ib topoisomerase.in order to clone the gene encoding a type i dna topoisomerase from leishmania donovani, a pcr-amplified dna fragment obtained with degenerate oligodeoxyribonucleotides was used to screen a genomic library from this parasite. an open reading frame of 1905 bases encoding a putative protein of 635 amino acid residues was isolated. a substantial part of the protein shares a significant degree of homology with the sequence of other known members of the ib topoisomerase family, in a highly conserved ...199910373592
inhibition of succinyl coa synthetase histidine-phosphorylation in trypanosoma brucei by an inhibitor of bacterial two-component systems.recent drug screenings for new antibacterial drugs directed against histidine phospho-relay signalling pathways in bacteria have resulted in compounds which potently inhibit the histidine kinase activity of bacterial two-component systems. the present study demonstrates that one of these compounds, ly266500, is also a potent inhibitor of histidine phosphorylation in the unicellular eukaryotic parasite trypanosoma brucei, both in vitro and in whole cells. in vitro, it inhibits histidine phosphory ...199910376993
effect of acidic ph on heat shock gene expression in leishmania.temperature and ph shifts trigger differential gene expression and stage transformation in leishmania. the parasites encounter dramatic fluctuations in the extra-cellular ph between the mid-gut of the sand fly (ph>8) and the phagolysosomal vacuole of mammalian macrophages (ph<6). the authors examined the effect of ph shifts on heat shock gene expression in leishmania amazonensis and leishmania donovani promastigotes. acidic ph resulted in preferential stability of the hsp83 transcripts at 26 deg ...199910376997
leishmania donovani: cellular and humoral immune responses in indian langur monkeys, presbytis entellus.we have previously reported that disease mimicking human visceral leishmaniasis can be established in presbytis entellus, the indian langur monkey, following a single intravenous challenge of 10(8) leishmania donovani amastigotes. in the present report, infection was assessed in monkeys infected intravenously with a single dose of 10(8) amastigotes (hda group), three weekly doses of 10(7) amastigotes (lda group) and three weekly doses of 5 x 10(7) promastigotes (hdp group). typical clinical infe ...199910379815
experimental visceral leishmaniasis in high and low antibody-producer mice (selection iv-a).leishmaniasis is a typical parasite infection whose protective immunity depends on macrophage activation. susceptibility to leishmania donovani infection was compared in h (high antibody responder) and l (low antibody responder) mice from selection iv-a. h mice infected intravenously with 10(7) amastigotes of l. donovani were more susceptible to infection than their l counterparts. this higher susceptibility was characterized by a higher splenic and hepatic parasite burden. an increased splenic ...199910380560
lectin-binding properties of different leishmania species.carbohydrate cell-surface residues on stationary promastigotes of 19 isolates of leishmania were studied with a panel of 27 highly purified lectins, which were specific for n-acetyl-d-glucosamine, d-mannose, l-fucose, d-galactose, n-acetyl-d-galactosamine, and sialic acid. the specificity of the cell-surface carbohydrates was analyzed by agglutination and radioiodinated lectin-binding assays. l. (l.) amazonensis and l. (l.) donovani were agglutinated by 12 and 10 of the 27 lectins used, respecti ...199910382607
immunosuppression in hamsters with progressive visceral leishmaniasis: an evaluation of the role of nitric oxide toward impairment of the lymphoproliferative response.the progressive visceral infection caused in golden hamsters by leishmania donovani amastigotes led to gradual impairment of the proliferative response of their splenic (spmc) or peripheral blood (pbmc) mononuclear cells to in vitro stimulation with leishmanial antigen, with mitogen (concanavalin a), and even with a combination of phorbol myristate acetate (pma) and ionomycin (io). removal of macrophage-like adherent cells from spmc or pbmc of infected animals, however, almost completely restore ...199910382610
diagnostic and prognostic potential of a competitive enzyme-linked immunosorbent assay for leishmaniasis in india.a leishmania donovani species-specific monoclonal antibody (monoclonal antibody d2) was evaluated for its diagnostic and prognostic potential by a competitive enzyme-linked immunosorbent assay (c-elisa) in sera from indian patients with visceral leishmaniasis (vl) and seven patients with post-kala-azar dermal leishmaniasis (pkdl). these results were compared with those obtained by microscopy with giemsa-stained tissue smears and a direct enzyme-linked immunosorbent assay (direct elisa) with crud ...199910391861
crystal structures of adenine phosphoribosyltransferase from leishmania donovani.the enzyme adenine phosphoribosyltransferase (aprt) functions to salvage adenine by converting it to adenosine-5-monophosphate (amp). aprt deficiency in humans is a well characterized inborn error of metabolism, and aprt may contribute to the indispensable nutritional role of purine salvage in protozoan parasites, all of which lack de novo purine biosynthesis. we determined crystal structures for aprt from leishmania donovani in complex with the substrate adenine, the product amp, and sulfate an ...199910393170
h-2m molecules, like mhc class ii molecules, are targeted to parasitophorous vacuoles of leishmania-infected macrophages and internalized by amastigotes of l. amazonensis and l. mexicana.in their amastigote stage, leishmania are obligatory intracellular parasites of mammalian macrophages, residing and multiplying within phagolysosomal compartments called parasitophorous vacuoles (pv). these organelles have properties similar to those described for the mhc class ii compartments of antigen-presenting cells, sites where peptide-class ii molecule complexes are formed before their expression at the cell surface. after infection with leishmania amazonensis or l. mexicana, endocytosis ...199910393812
evidence that the high incidence of treatment failures in indian kala-azar is due to the emergence of antimony-resistant strains of leishmania donovani.the possibility that the high frequency of treatment failures in indian kala-azar might be due to infection with antimony-resistant strains of leishmania donovani has not been experimentally addressed. l. donovani isolates were obtained from splenic aspiration smears of 24 patients in bihar, india, who either did not respond (15) or did respond (9) to 1 or more full courses of treatment with sodium antimony gluconate (sag). a strong correlation (p<.001) between clinical response and sag sensitiv ...199910395884
leishmania: overexpression and comparative structural analysis of the stage-regulated meta 1 gene.the meta 1 gene of leishmania major is upregulated in metacyclic promastigotes and encodes an 11.5-kda protein with no significant similarities to other proteins in the existing databases. in this paper, we characterize the homologous meta 1 genes in l. amazonensis and l. donovani. proteins encoded by this gene in all three species present a high degree of identity. the meta 1 gene cannot be replaced by gene targeting in l. major, suggesting an essential role for the protein, at least in promast ...199910403759
the antileishmanial activity of novel oxygenated chalcones and their mechanism of action.our previous studies have shown that licochalcone a, an oxygenated chalcone, has antileishmanial and antimalarial activities, and alters the ultrastructure and function of the mitochondria of leishmania spp. parasites. the present study was designed to investigate the antileishmanial activity and the mechanism of action of a group of new oxygenated chalcones. the tested oxygenated chalcones inhibited the in-vitro growth of leishmania major promastigotes and leishmania donovani amastigotes. treat ...199910404318
ca2+ and calmodulin-dependent protein phosphatase from leishmania donovani.a protein phosphatase exclusively dependent upon micromolar amounts of ca2+ and calmodulin has been identified and partially purified from leishmania spp. complete obliteration of its activity is observed in the presence of calmodulin antagonists such as trifluoperazine, fluphenazine and calmidazolium. relative insensitivity to okadaic acid and lack of activation in the absence of ca2+ and calmodulin distinguishes this enzyme from pp1, pp2a and pp2c-type protein phosphatases. cross-reactivity of ...199910406035
hypersensitivity reaction over lesions of post-kala-azar dermal leishmaniasis mimicking type 1 reaction in leprosy. 199910407631
relationship of membrane sidedness to the effects of the lipophosphoglycan of leishmania donovani on the fusion of influenza virus.cells expressing the influenza hemagglutinin protein were fused to planar lipid bilayers containing the viral receptor gd1a at ph 5.0. an amphiphile known to alter membrane properties is lipophosphoglycan (lpg). this glycoconjugate was added from aqueous solution to either the cis or the trans monolayer to examine its effects on the fusion process. lpg markedly inhibited the formation of fusion pores when present in the cis monolayer but lpg in the trans monolayer had no effect on the parameters ...199910411653
sequence homology within a minicircle class of the leishmania donovani complex. 199910413058
epidemiology of visceral leishmaniasis in india.kala-azar has re-emerged from near eradication. the annual estimate for the incidence and prevalence of kala-azar cases worldwide is 0.5 million and 2.5 million, respectively. of these, 90% of the confirmed cases occur in india, nepal, bangladesh and sudan. in india, it is a serious problem in bihar, west bengal and eastern uttar pradesh where there is under-reporting of kala-azar and post kala-azar dermal leishmaniasis in women and children 0-9 years of age. untreated cases of kala-azar are ass ...199910416321
activation of phosphotyrosine phosphatase activity attenuates mitogen-activated protein kinase signaling and inhibits c-fos and nitric oxide synthase expression in macrophages infected with leishmania donovani.intracellular protozoan parasites of the genus leishmania antagonize host defense mechanisms by interfering with cell signaling in macrophages. in this report, the impact of leishmania donovani on mitogen-activated protein (map) kinases and nitric oxide synthase (nos) expression in the macrophage cell line raw 264 was investigated. overnight infection of cells with leishmania led to a significant decrease in phorbol-12-myristate-13-acetate (pma)-stimulated map kinase activity and inhibited pma-i ...199910417174
vaccination of swiss albino mice against experimental visceral leishmaniasis with the fml antigen of leishmania donovani.the fml antigen of leishmania donovani in combination with saponin, aluminum hydroxide (al(oh)3) and freund's incomplete adjuvant (fia) was used in vaccines tested in an outbred murine model of visceral leishmaniasis, either through intraperitoneal or subcutaneous routes. the humoral response was significantly higher in the groups treated with fml + saponin or fml + al(oh)3 than in controls, both before and after the infection. animals immunized by the i.p. route developed higher antibody titres ...199910418902
effect of the microtubule stabilising agent taxol on leishmanial protozoan parasites in vitro.taxol, a mitotic spindle toxin, was found to selectively inhibit the proliferation of leishmania donovani in vitro at nanomolar concentrations with an ic50 of 35 nm. concentrations of taxol as high as 50 nm, however, did not affect j774a.1 murine macrophages. taxol (30 nm) also inhibited amastigote multiplication within a j774a.1 macrophage cell line when used in a 10-day experiment. it resulted in the in vitro assembly of l. donovani microtubules in a dose-dependent manner. when promastigotes w ...199910427726
isolation of a taxol-resistant leishmania donovani promastigote mutant that exhibits a multidrug-resistant phenotype.we raised a strain of leishmania donovani in the laboratory that was resistant to 500 nm taxol. the ic50 of the wild-type strain for taxol was 35 nm and that of the taxol-resistant strain (t-500) was 1 microm. the t-500 strain exhibited a mdr phenotype; it was also resistant to other unrelated drugs like vinblastine, adriamycin and the commonly used antimonial drugs pentostam and glucantime. verapamil (20 nm), a calcium channel blocker, was found to reverse the resistance of t-500 to taxol. acqu ...199910427727
intra-species and stage-specific polymorphisms in lipophosphoglycan structure control leishmania donovani-sand fly interactions.the leishmania lipophosphoglycan conveys the ability for the parasites to avoid destruction in diverse host environments. during its life cycle within the sand fly vector, the parasite differentiates from a dividing procyclic promastigote stage that avoids expulsion from the midgut by attaching to the gut wall, to a nondividing metacyclic promastigote stage that is unable to attach to the midgut and migrates to the mouth parts for reinfection of a mammalian host. lipophosphoglycan plays an integ ...199910433687
synergistic effect of interferon-gamma and mannosylated liposome-incorporated doxorubicin in the therapy of experimental visceral leishmaniasis.active targeting of doxorubicin to macrophages was studied by incorporating it in mannose-coated liposomes by use of visceral leishmaniasis in balb/c mice as the model macrophage disease. mannosylated liposomal doxorubicin was more effective than liposomal doxorubicin or free doxorubicin. because leishmaniasis is accompanied by immunosuppression, immunostimulation by interferon (ifn)-gamma was evaluated to act synergistically with mannosylated liposomal doxorubicin therapy. combination chemother ...199910438370
regulation and adaptation of glucose metabolism of the parasitic protist leishmania donovani at the enzyme and mrna levels.adaptation of the glucose metabolism of leishmania donovani promastigotes (insect stage) was investigated by simultaneously measuring metabolic rates, enzyme activities, message levels, and cellular parameters under various conditions. chemostats were used to adapt cells to different growth rates with growth rate-limiting or excess glucose concentrations. l. donovani catabolized glucose to co(2), succinate, acetate, and pyruvate in ratios that depended on growth rate and glucose availability. ra ...199910438756
antimicrobial, antitumor and antileishmania screening of medicinal plants from guinea-bissau.following an ethnobotanical search carried out in guinea-bissau, eighteen extracts derived from sixteen medicinal species were screened for antimicrobial, antitumor and antileishmania activity. significant antitumor activity was found for holarrhena floribunda against kb (squamous carcinoma), sk-mel 28 (melanoma), a 549 (lung carcinoma) and mda-mb 231 (mamma carcinoma) cell lines, with corresponding ic50 values of 7.9, 9.0, 3.4 and 9.9 micrograms/ml. khaya senegalensis and anthostema senegalense ...199910439484
diagnostic pcr with leishmania donovani specificity using sequences from the variable region of kinetoplast minicircle dna.kala azar or visceral leishmaniasis, a parasitic disease caused by leishmania donovani, is presently causing an epidemic in the eastern region of india. diagnosis of kala azar is often complicated. we developed a pair of oligonucleotides suitable as primers from the variable region of a predominant sequence class of minicircles of l. donovani. these primers were used in a nonisotopic polymerase chain reaction and found to be highly specific for the parasites of l. donovani complex. using these p ...199910444321
comparison of different staining procedures for the flow cytometric analysis of u-937 cells infected with different leishmania-species.the human macrophage cell line u-937 infected with different leishmania species, leishmania mexicana amazonensis (lma), leishmania donovani (ld) and leishmania infantum (li), was analyzed by flow cytometry (fcm). leishmania spp. were labeled with different stains prior to the infection of the u-937 cells (bcecf-am, pkh2-gl and syto 17) or after the infection (ao, fitc-conjugated monoclonal antibodies, pi). infected cells were analyzed by flow cytometry, fluorescence microscopy and in parallel mi ...199910445312
serodiagnosis of leishmania donovani infections: assessment of enzyme-linked immunosorbent assays using recombinant l. donovani gene b protein (gbp) and a peptide sequence of l. donovani gbp.the repetitive sequence of leishmania major gene b protein (gbp) has previously been shown to be a useful tool in the diagnosis of cutaneous leishmaniasis (cl). here, we have assessed enzyme-linked immunosorbent assays (elisas) using recombinant l. donovani gbp (rgbp) and a peptide sequence of l. donovani gbp (gbpp) in the diagnosis of l. donovani infections in sudan. the sensitivity of the rgbp elisa in diagnosing visceral leishmaniasis (vl) and post kala-azar dermal leishmaniasis (pkdl) was 92 ...199910450438
attenuation of mhc class ii expression in macrophages infected with mycobacterium bovis bacillus calmette-guérin involves class ii transactivator and depends on the nramp1 gene.the natural resistance associated macrophage protein 1 (nramp1) gene determines the ability of murine macrophages to control infection with a group of intracellular pathogens, including salmonella typhimurium, leishmania donovani, and mycobacterium bovis bacillus calmette-guérin (bcg). the expression of the resistant allele of the nramp1 gene in murine macrophages is associated with a more efficient expression of several macrophage activation-associated genes, including class ii mhc loci. in thi ...199910453010
possible role of the 34-kilodalton hyaluronic acid-binding protein in visceral leishmaniasis.leishmania donovani, the causative organism of human visceral leishmaniasis, invades host macrophages through its interaction with the cell surface molecules of target cells. the presence of a cell surface protein (mr 34 kda) having specific affinity toward hyaluronan (ha), a major extracellular matrix component, has been previously reported in macrophage cell lines. in order to identify the possible role of this ha-binding protein (habp) in leishmaniasis, initially we demonstrated its overexpre ...199910461949
characterization of tglp-1, a golgi and lysosome-associated, transmembrane glycoprotein of african trypanosomes.purification of endosomal/lysosomal vesicles of trypanosoma brucei brucei bloodstream forms and generation of monoclonal antibodies led to the isolation of antibodies directed against an 85 kda, golgi and endocytic traffic-associated protein termed tglp-1, trypanosoma golgi/lysosome protein-1. preliminary immunoelectron microscopical analysis revealed that the protein is present in, but not restricted to, the limiting membrane of multivesicular lysosomes and is more abundant in bloodstream forms ...199910462522
characterization of intracellular metabolites of axenic amastigotes of leishmania donovani by 1h nmr spectroscopy.the intracellular metabolites of long-term in vitro cultured axenic amastigotes of leishmania donovani (strain dd8) were determined and compared with those of promastigotes and intracellular amastigotes, employing proton nmr spectroscopy. the presence of two new metabolites, i.e. betaine and beta-hydroxybutyrate were reported. betaine was detected in all the three stages being highest in the promastigotes while beta-hydroxybutyrate could be detected only in promastigotes and axenic amastigotes. ...199910465052
expression of hydrophilic surface proteins in infective stages of leishmania donovani. 199910477187
characterization of prenylated protein methyltransferase in leishmania.prenylated protein methyltransferase, an enzyme involved in the post-translational modification of many signalling proteins, has been characterized in a parasitic flagellated protozoan, leishmania donovani. the activity of this enzyme was monitored by the methylation of an artificial substrate, an s-prenylated cysteine analogue, with s-adenosyl-l-[methyl-(3)h]methionine as methyl donor. more than 85% of the methyltransferase activity was associated with membranes. the enzyme methylates n-acetyl- ...199910477261
in vitro antitrypanosomal activity of moringa stenopetala leaves and roots.the leaves and the root extracts of moringa stenopetala were tested in vitro against trypomastigotes of trypanosoma brucei, trypanosoma cruzi and l. donovani amastigotes. the fresh root wood ethanol extract and the dried leaves acetone extract were found to be active against t. brucei with an ed(50) value of 9.2 microg/ml and 10.0 microg/ml respectively. all the other extracts were inactive against all the tested parasite forms.199910479771
dendritic cell (dc)-based anti-infective strategies: dcs engineered to secrete il-12 are a potent vaccine in a murine model of an intracellular infection.infections with intracellular pathogens such as leishmania donovani and mycobacterium tuberculosis pose serious health problems worldwide. effective vaccines for these pathogens are not available. furthermore, despite optimal therapy, disease progression is often seen with several intracellular infections. for these reasons, we initiated studies to develop novel anti-infective vaccine and treatment strategies that couple the potent ag-presenting capacity of dendritic cells (dc) with paracrine de ...199910490989
mycobacterium tuberculosis inhibits ifn-gamma transcriptional responses without inhibiting activation of stat1.ifn-gamma activates macrophages to kill diverse intracellular pathogens, but does not activate human macrophages to kill virulent mycobacterium tuberculosis. we tested the hypothesis that this is due to inhibition of ifn-gamma signaling by m. tuberculosis and found that m. tuberculosis infection of human macrophages blocks several responses to ifn-gamma, including killing of toxoplasma gondii and induction of fcgammari. the inhibitory effect of m. tuberculosis is directed at transcription of ifn ...199910490990
evaluation of the direct agglutination test (dat) using freeze-dried antigen for the detection of anti-leishmania antibodies in stored sera from various patient groups in ethiopia.tests on a panel of 421 serum samples from ethiopia and 11 from europe with the direct agglutination test (dat) and freeze-dried antigen (leishmania donovani 1s) showed that a cut-off titre of 1:200 or 1:400 could be employed. using a cut-off titre of 1:400, 181 (88.3%) of 205 serum samples from visceral leishmaniasis (vl) patients tested positive, as did 5 (13.9%) of 36 sera from patients with localized cutaneous leishmaniasis, 5 (71.4%) sera from 7 patients with diffuse cutaneous leishmaniasis ...199910492758
western blot analysis of humoral immune response to leishmania donovani antigens in patients with post-kala-azar dermal leishmaniasis.sera from 32 indian patients with post-kala-azar dermal leishmaniasis (pkdl) were examined for antibodies by immunoblot analysis using an antigen extract of leishmania donovani. the study revealed that the humoral immune response in pkdl patients was quite distinct compared to that in kala-azar patients. antibodies to 3 antigens of l. donovani (molecular sizes 110, 65 and 38-42 kda) were predominant in a majority (78%) of pkdl patients. the most important finding was the consistent recognition o ...199910492802
role of leishmania donovani and its lipophosphoglycan in cd4+ t-cell activation-induced human immunodeficiency virus replication.chronic immune activation by coinfecting pathogens has been suggested as a cofactor in human immunodeficiency virus (hiv) disease progression, particularly in the setting of developing countries. here, we used in vivo-infected mononuclear cells to examine the role of the protozoan parasite leishmania donovani and its major membrane constituent, lipophosphoglycan (lpg), in mediating cd4+ t-lymphocyte activation-induced hiv replication and cd4+ t-cell death. we found that leishmania antigens upreg ...199910496904
serodiagnosis of leishmaniasis with recombinant orff antigen.the serodiagnostic potential of recombinant orff protein (rorff) from leishmania infantum was assessed by elisa. of 49 sera from confirmed cases of visceral leishmaniasis (vl), all were seropositive using 5 ng of rorff and serum diluted 1:20, while only 38 were positive with 500 ng of soluble antigen (sa) and 44 were positive by a direct agglutination test. there was also a positive correlation between spleen size and level of seropositivity with rorff or sa. the reciprocal endpoint titer with r ...199910497995
genomic diversity in the leishmania donovani complex.the leishmania donovani complex is considered to be composed of 3 species; l. donovani, l. infantum and l. chagasi, although this classification has been challenged. genotypic relationships within the complex were evaluated at different levels by: binding of the probe lmet9, specific for l. chagasi and old world leishmania spp.; partial sequencing of a constitutive major surface protease single gene (mspc) and random amplification of polymorphic dna (rapd). the old world leishmania spp. and the ...199910503249
hiv viral load and response to antileishmanial chemotherapy in co-infected patients.to investigate whether clearance of leishmania parasites from tissue aspirate smears in patients with hiv and visceral leishmaniasis (vl) co-infection treated with pentavalent antimonials is influenced by initial hiv viral load and to assess the effect of active vl on hiv viral load and replication in vivo.199910513651
leishmaniasis.in 1903, leishman and donovan separately described the protozoan now called leishmania donovani in splenic tissue from patients in india with the life-threatening disease now called visceral leishmaniasis. almost a century later, many features of leishmaniasis and its major syndromes (ie, visceral, cutaneous, and mucosal) have remained the same; but also much has changed. as before, epidemics of this sandfly-borne disease occur periodically in india and elsewhere; but leishmaniasis has also emer ...199910513726
protective efficacy of lambdacyhalothrin-impregnated bednets against phlebotomus orientalis, the vector of visceral leishmaniasis in sudan.field investigations on the sandfly phlebotomus orientalis (diptera: psychodidae), the vector of leishmania donovani causing visceral leishmaniasis (vl) in sudan, were undertaken in two villages (bellow and elgamel) and dinder national park, to determine the protective value of bednets (polyester, 100 denier) impregnated with lambda-cyhalothrin 10 mg a.i./m2 pyrethroid insecticide. after exposure to treated netting for 30 s, p. orientalis females all died within 1 h. when field-tested in acacia ...199910514058
entamoeba histolytica lacks trypanothione metabolism.entamoeba histolytica lacks glutathione reductase activity and the ability to synthesise glutathione de novo. however, a recent report suggested that exogenous glutathione can be taken up and conjugated to spermidine to form trypanothione, a metabolite found so far only in trypanosomatids. given the therapeutic implications of this observation, we have carefully analysed e. histolytica for evidence of trypanothione metabolism. using a sensitive fluorescence-based hplc detection system we could c ...199910514081
leishmania donovani proton translocating p-type adenosine triphosphatases ldh1a and ldh1b: trans-splicing and polyadenylation of transcripts in amastigotes and promastigotes. 199910514086
visceral leishmaniasis in costa rica: first case report.we describe a 15-month-old eutrophic immunocompetent male who presented with fever, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. leishmania amastigotes were identified in spleen and bone marrow specimens. in addition, tissue culture, animal inoculation, and isoenzyme analysis identified the parasite as leishmania donovani infantum or leishmania donovani chagasi. the infant was successfully treated with an antimonial drug. these findings represent the first case of visceral leish ...199910530466
effect of multiple antigenic exposures in the gut on oral tolerance and induction of antibacterial systemic immunity.we have analyzed oral tolerance of microbial antigens in an experimental model in which mice are treated orally with a single small dose of soluble antigen and challenged systemically with the antigen in complete freund's adjuvant. we found that, while oral administration of sonicated extracts of either leishmania major, leishmania donovani, or staphylococcus aureus was tolerogenic, as was administration of the nominal antigen ovalbumin or conalbumin, oral administration of escherichia coli or s ...199910531248
sensitivity and specificity of a rapid immunochromatographic test for diagnosis of visceral leishmaniasis.a rapid immunochromatographic dipstick test has become available for the qualitative detection of total anti-leishmania immunoglobulins using the recombinant k39 antigen. to evaluate the test, 96 serum specimens from patients with a variety of tropical infections were tested. fourteen of the specimens derived from patients with parasitologically confirmed kala-azar, and all were strongly positive for antibodies to leishmania donovani complex using the immunofluorescence test. although all 82 sam ...199910534192
congenital transmission of visceral leishmaniasis (kala azar) from an asymptomatic mother to her child.in this article, we report the case of a 16-month-old german boy who was admitted to the children's hospital of stuttgart with a 4-week history of intermittent fever, decreased appetite, weakness, fatigue, and difficulty sleeping. he was healthy at birth and remained so for the first 15 months of his life. on admission, physical examination showed enlarged cervical, axillary, and inguinal lymph nodes, as well as hepatosplenomegaly. laboratory data revealed pancytopenia, elevated liver function t ...199910545591
polymerase chain reaction-based identification of new world leishmania species complexes by specific kdna probes.here we define a new approach for the detection and characterisation of leishmania complexes by polymerase chain reaction (pcr) and specific hybridisation. the first step consists of pcr amplification of kdna minicircles using general kinetoplastid primers, which generate a polymorphic multi-banding pattern for all leishmania species and other kinetoplastidae. the second step is the identification of the leishmania species complexes by hybridisation of the pcr products with specific kdna probes. ...199910546846
characterization of kinetoplast dna minicircles of an indian isolate of leishmania donovani.characterization of the kinetoplast dna minicircles in a human pathogenic indian isolate of leishmania donovani has not been reported previously. using inverse pcr, we constructed a library of pcr-amplified minicircle variable region from the kinetoplast dna of this isolate. a combination of restriction enzyme digestion and nucleotide sequence analysis revealed five minicircle dna sequence classes within the library, one of which was predominant, representing 75% of the kdna network. another dis ...199910546849
a novel role for 100 kd heat shock proteins in the parasite leishmania donovani.heat shock proteins of the 100 kd family have been known to confer general stress tolerance in yeast and plants. several protozoan parasites possess genes for hsp100 proteins. in leishmania species the protein is expressed under heat stress and during the mammalian stage, the amastigote. we show here that replacement of the clpb gene which encodes hsp100 does not affect thermotolerance or general viability in leishmania donovani insect stages (promastigotes) nor in axenically cultured mammalian ...199910547068
immunochemotherapy for leishmania donovani infection in golden hamsters: combinatorial action of poly iclc plus l-arginine and sodium stibogluconate (stibanate).we demonstrate that golden hamsters infected with leishmania donovani amastigotes develop the capacity to eliminate intracellular pathogens on treatment with low-dose standard antileishmanial sodium stibogluconate (stibanate) in combination with polyinosinic-polycytidilic acid stabilized with polylysine and carboxymethycellulose (poly iclc), a potent inducer of interferon (ifn) and immune enhancer, plus l-arginine. data suggest that low doses of both stibanate and poly iclc plus l-arginine provi ...199910547149
characterization of the leishmania donovani ribosomal rna promoter.the rrna genes of leishmania donovani are organized on chromosome 27 as tandem repeats of approximately 12.5-kb units that each contain a promoter, the subunit rrnas, and approximately 39 copies of a 64-bp species-specific sequence. the transcription initiation site was mapped to 1020 bp upstream of the 18s rrna gene by rnase protection and primer extension. a 349-bp sequence between the 64-bp repeats and the 18s rrna gene appears to contain a promoter, since it directs a 60-fold increase in luc ...199910551363
role of protein kinase c-alpha in the control of infection by intracellular pathogens in macrophages.the protein kinase c (pkc) family regulates macrophage function involved in host defense against infection. in this study, we investigated the role of macrophage pkc-alpha in the uptake and subsequent fate of leishmania donovani promastigotes and legionella pneumophila infections. to this end, we used clones of the murine macrophage cell line raw 264.7 overexpressing a dominant-negative (dn) mutant of pkc-alpha. while phagocytosis of l. donovani promastigotes was not affected by dn pkc-alpha ove ...199910553077
defects in the generation of ifn-gamma are overcome to control infection with leishmania donovani in cc chemokine receptor (ccr) 5-, macrophage inflammatory protein-1 alpha-, or ccr2-deficient mice.we investigated the immune responses in mice lacking ccr2, ccr5, or macrophage inflammatory protein-1 alpha (mip-1 alpha), a ligand for ccr5, in two situations: following t cell stimulation or after challenge with leishmania donovani, an intracellular microbe whose control is dependent on a th1 immune response. mice deficient in ccr5, mip-1 alpha, or ccr2 had reduced ifn-gamma responses following ligation of the tcr. reduced ifn-gamma responses following pma and ionomycin were also observed in c ...199910553079
leishmania-induced increases in activation of macrophage shp-1 tyrosine phosphatase are associated with impaired ifn-gamma-triggered jak2 activation.leishmania-induced macrophage (mphi) dysfunctions have been correlated with altered signaling events. recent findings from our laboratory suggest that modulation of host protein tyrosine phosphatase (ptp) following leishmania infection could lead to these mphi defects. to address this issue, mphi ptp activity and ifn-gamma-inducible signaling events were evaluated in leishmania donovani (ld)-infected cells. we observed that ld promastigotes can rapidly trigger host ptp activity simultaneously wi ...199910556830
molecular characterization of a leishmania donovanii cdna clone with similarity to human 20s proteasome a-type subunit.using plasma from patients infected or previously infected with leishmania donovanii, we isolated a l. donovanii cdna clone with similarity to the proteasome a-type subunit from humans and other eukaryotes. the cdna clone, designated lepa, was dna sequenced and northern blot analysis of l. donovanii poly(a(+))mrna indicated the isolation of a full length cdna clone with a transcript size of 1.9 kb. the expressed recombinant lepa fusion protein induced proliferation of peripheral blood mononuclea ...200010564720
increased natural killer activity does not prevent progression of experimental kala-azar.kala-azar is the visceral form of leishmaniasis and it is caused by intracellular parasites from the complex leishmania donovani. golden hamster (mesocricetus auratus) infected with leishmania donovani develop a disease very similar to human kala-azar. there is conspicuous hipergammaglobulinaemia and their t cells do not respond to stimulation with parasite antigens. we used this experimental model to evaluate the natural killer (nk) activity during the initial phase of the disease. outbred hams ...199910564913
xanthine phosphoribosyltransferase from leishmania donovani. molecular cloning, biochemical characterization, and genetic analysis.xanthine phosphoribosyltransferase (xprt) from leishmania donovani is a unique enzyme that lacks a mammalian counterpart and is, therefore, a potential target for antiparasitic therapy. to investigate the enzyme at the molecular and biochemical level, a cdna encoding the l. donovani xprt was isolated by functional complementation of a purine auxotroph of escherichia coli that also harbors deficiencies in the prokaryotic phosphoribosyltransferase (prt) activities. the cdna was then used to isolat ...199910567419
differential decline in leishmania membrane antigen-specific immunoglobulin g (igg), igm, ige, and igg subclass antibodies in indian kala-azar patients after chemotherapy.pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin g (igg) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. using leishmanial membrane antigenic extracts, we investigated the relative levels of specific igg, igm, iga, ige, and igg s ...199910569788
c-reactive protein binds to phosphorylated carbohydrates.c-reactive protein (crp) is a major acute phase protein in man. in order to more fully understand the physiological role of this serum protein, we have demonstrated high avidity binding for a defined chemically synthesized carbo-hydrate ligand which represents the repeating disaccharide of lipophosphoglycan, the major surface glycoconjugate of the unicellular parasite leishmania donovani. increasing the number of phosphorylated disaccharides in a molecule from one up to seven did not increase th ...200010570224
glycoconjugates in leishmania infectivity.leishmaniasis is a major health problem to humans and is caused by one of the world's major pathogens, the leishmania parasite. these protozoa have the remarkable ability to avoid destruction in hostile environments they encounter throughout their life cycle. that leishmania parasites have adapted to not only survive, but to proliferate largely is due to the protection conferred by unique glycoconjugates that are either on the parasites' cell surface or secreted. most of these specialized molecu ...199910571023
the fatty acid and monosaccharide compositions of three neutral and three phosphorylated glycolipids isolated from leishmania donovani promastigotes grown in a chemically defined medium.several lipids and macromolecular lipoconjugates of leishmania spp. have now been well characterized; however, the glycolipids of l. donovani have not been thoroughly examined. in the present study, 3 neutral and 3 phosphorylated glycolipids were detected in promastigote forms of the organism grown in a chemically defined medium. the fatty acid and sugar compositions of these glycolipids, isolated and purified by adsorption column chromatography and thin-layer chromatographic procedures, were id ...199910577709
efficacy of the triazole sch 56592 against leishmania amazonensis and leishmania donovani in experimental murine cutaneous and visceral leishmaniases.current therapy for leishmaniasis is unsatisfactory. efficacious and safe oral therapy would be ideal. we examined the efficacy of sch 56592, an investigational triazole antifungal agent, against cutaneous infection with leishmania amazonensis and visceral infection with leishmania donovani in balb/c mice. mice were infected in the ear pinna and tail with l. amazonensis promastigotes and were treated with oral sch 56592 or intraperitoneal amphotericin b for 21 days. at doses of 60 and 30 mg/kg/d ...199910582881
diagnostic pcr with leishmania donovani specificity. 199910588774
the leishmania donovani ld1 locus gene orfg encodes a biopterin transporter (bt1).we have previously described two genes, orff and orfg, from the ld1 locus near one telomere of chromosome 35, which are frequently amplified in leishmania isolates. in leishmania donovani lsb-51.1, gene conversion of the rrna gene locus on chromosome 27 with these two genes resulted in their over-expression, because of their transcription by the rna polymerase i-mediated rrna promoter. the predicted orfg protein has substantial sequence homology to the esag10 gene product from the trypanosoma br ...199910589984
substrate depletion upregulates uptake of myo-inositol, glucose and adenosine in leishmania.leishmania flagellates undergo a digenetic life cycle in the gut of the sandfly insect vector and in macrophage phagolysosomes of the mammalian host. this involves vast changes of the environment to which the parasite has to adapt, including temperature, ph and concentration of nutrients between different types of meals of the insect vector or within the enclosed intracellular environment of the phagolysosome. the regulation of transporters for important organic substrates in leishmania donovani ...199910589986
evaluation of the in-vivo activity and toxicity of amarogentin, an antileishmanial agent, in both liposomal and niosomal forms.the antileishmanial property of amarogentin, a secoiridoid glycoside isolated from the indian medicinal plant swertia chirata, was examined in a hamster model of experimental leishmaniasis. the therapeutic efficacy of amarogentin was evaluated in free and two different vesicular forms, liposomes and niosomes. the amarogentin in both liposomal and niosomal forms was found to be a more active leishmanicidal agent than the free amarogentin; and the niosomal form was found to be more efficacious tha ...199910590280
dermatofibroma parasitized by leishmania in hiv infection: a new morphologic expression of dermal kala azar in an immunodepressed patient.visceral leishmaniasis is a protozoan infection that may complicate the course of patients with human immunodeficiency virus (hiv). dermatofibroma is a cutaneous fibrohistiocytic lesion considered neoplastic by some authors and inflammatory by others. eruptive dermatofibromas have been described in patients with hiv infection or with other altered immunity situations. we present the case of a 32-year-old, hiv-positive man with visceral leishmaniasis who complained of the appearance of a cutaneou ...199910599943
characterization of the glucosyltransferases that assemble the side chains of the indian leishmania donovani lipophosphoglycan.the life cycle of leishmania parasites within its sand fly vector involves the development of extracellular promastigotes from a noninfective, "procyclic" stage into an infective, "metacyclic" stage that is adapted for transmission in the fly and survival in the mammalian host. lipophosphoglycan (lpg), the predominant surface glycoconjugate in both procyclic and metacyclic stages, is a critical virulence determinant. lpg is a multidomain molecule; the structural polymorphisms among species lie i ...199910600177
leishmania donovani: characterization and expression of orff, a gene amplified from the ldi locus.the ld1 locus is a 27.5-kb region of chromosome 35 that is conserved among all species of leishmania and is amplified in several different isolates. here, we report the genomic distribution of orff, a gene from the ld1 region, and its expression at the rna and protein levels in two indian isolates of leishmania donovani. in both of these isolates, orff was present as a single copy on chromosome 35. densitometric analysis of orff mrna abundance revealed relative abundance of 0.2 and 1.0 in ag83 a ...199910600448
roles of endogenous gamma interferon and macrophage microbicidal mechanisms in host response to chemotherapy in experimental visceral leishmaniasis.in experimental visceral leishmaniasis, in which the tissue macrophage is the target, in vivo responsiveness to conventional chemotherapy (pentavalent antimony [sb]) requires a t-cell-dependent mechanism. to determine if this mechanism involves gamma interferon (ifn-gamma)-induced activation and/or specific ifn-gamma-regulated macrophage leishmanicidal mechanisms (generation of reactive nitrogen or oxygen intermediates, we treated gene-deficient mice infected with leishmania donovani. in ifn-gam ...200010603400
combined liposomal immuno- and chemotherapy of visceral leishmaniasis.visceral leishmaniasis is a tropical disease caused by leishmania donovani, an obligate intracellular parasite. host cells of these parasites are macrophages. the conventional therapy of visceral leishmaniasis uses pentavalent antimony (pentostam). to minimize the undesired side effects of antimony and to possibly reduce the therapeutical dose of antimony it was combined with interferon gamma (ifn gamma) and encapsulated both in multilamellar vesicles for treatment of murine visceral leishmanias ...199910604050
leishmania donovani invasion of the blood in a child with dermal leishmaniasis.cutaneous leishmaniasis is highly endemic in eastern mediterranean countries. the causative organisms are leishmania tropica or leishmania major but, further west, variants of leishmania infantum frequently cause cutaneous leishmaniasis. we report a young girl from beirut with an acute cutaneous leishmaniasis in whom the causative organism was cultured from both the skin lesion and the blood in the absence of any signs or symptoms typical of systemic involvement. the parasite was found to have a ...199910605522
leishmania major proteophosphoglycan is expressed by amastigotes and has an immunomodulatory effect on macrophage function.proteophosphoglycan (ppg) is a newly described mucin-like glycoprotein found on the surface of leishmania major promastigotes and secreted in the culture supernatant. we show here that antigenically similar ppgs are present in several leishmania species. ppg could also be detected on the surface of amastigotes and in small, parasite-free vesicles in infected macrophages. because of the similarity of its carbohydrate chains to lipophosphoglycan, a parasite receptor for host macrophages, ppg was t ...199910611735
stimulation of nonspecific resistance by thymopentin and its analogs against leishmania donovani infection in hamsters.thymopentin and its analogs have been synthesized by the solution phase method of peptide synthesis and evaluated for their prophylactic efficacy against l. donovani infection in hamsters. thymopentin and some of the analogs were found to stimulate nonspecific resistance of the host against leishmania donovani infection in hamsters.199910612455
the role of phosphoglycans in leishmania-sand fly interactions.leishmania promastigotes synthesize an abundance of phosphoglycans, either attached to the cell surface through phosphatidylinositol anchors (lipophosphoglycan, lpg) or secreted as protein-containing glycoconjugates. these phosphoglycans are thought to promote the survival of the parasite within both its vertebrate and invertebrate hosts. the relative contributions of different phosphoglycan-containing molecules in leishmania-sand fly interactions were tested by using mutants specifically defici ...200010618431
leishmania mini-exon genes for molecular epidemiology of leishmaniasis in china and ecuador.the mini-exon gene is unique and is tandemly repeated in the leishmania genome. the transcribed region is highly conserved, but the non-transcribed spacer region is distinct in length and in sequence among different leishmania species. the usefulness of pcr amplification of the leishmania mini-exon gene was examined for molecular epidemiology of visceral and cutaneous leishmaniasis. we previously described a pcr method for amplification of the mini-exon gene and obtained positive amplification i ...199810622637
leishmanicidal activity of aurones.this is the first report on aurones as a new class of natural products with leishmanicidal activity. a series of aurones with drug-potential for leishmania infections was identified in vitro using both a direct cytotoxicity test against extracellular promastigotes of leishmania donovani, l. infantum, l. enriettii, and l. major, and a test against intracellular amastigote l. donovani residing within murine macrophages. the compounds proved to be active at concentrations in the microgram range bet ...199810622641
immunopathology of post kala-azar dermal leishmaniasis (pkdl): t-cell phenotypes and cytokine profile.in sudan, post kala-azar dermal leishmaniasis (pkdl) caused by leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). in most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. this study examined the immunological response in lesions of pkdl patients by immunohistochemistry and compared the findings with results obtained using peripheral blood mononuclear cells (pbmcs). in all lesions, parasites or parasite ...199910629566
leishmania donovani: development and characterisation of a kinetoplast dna probe and its use in the detection of parasites.the polymerase chain reaction is used increasingly widely for the diagnosis of both cutaneous and visceral leishmaniasis and for the identification of asymptomatic carriers in the population in endemic disease areas. the use of complex-specific hybridisation probes in conjunction with the polymerase chain reaction increases the specificity as well as the sensitivity of the diagnostic procedure as it discriminates between different infecting leishmania species. a minicircle kinetoplast dna probe, ...200010631076
leishmania donovani parasites interact with gamma/delta+ human peripheral blood t cells and induce susceptibility to nk cell-mediated lysis.we recently reported that leishmania donovani infect the human t-cell line in vitro. to examine whether primary human t cells could be infected by this parasite, a direct interaction of the peripheral blood t cells with l. donovani was examined. the percentage of gamma/delta+ t cells was markedly increased when in vitro generated normal human t-cell blasts were cultured with l. donovani amastigotes. about 30% of the gamma/delta+ t cells in the parasite exposed t-cell blasts expressed parasite an ...199910636768
new trichothecenes isolated from holarrhena floribunda.bioassay-guided fractionation of an extract of holarrhena floribunda stem, has led to the isolation of the new trichothecenes, 8-dihydrotrichothecinol a (1), loukacinol a (2), and loukacinol b (3), and the known compounds, trichothecolone (4), trichothecin (5), trichothecinol a (6), rosenonolactone (7), 6beta-hydroxyrosenonolactone (8), and rosololactone (9). the structures were determined by spectral and chemical methods, and absolute configurations were established by a modified horeau's metho ...200010650079
targeting of piperine intercalated in mannose-coated liposomes in experimental leishmaniasis.the leishmanicidal property of piperine intercalated in liposomes and in mannose-coated liposomes was tested in experimental visceral leishmaniasis in hamsters. mannose-coated liposomal piperine eliminated intracellular amastigotes of leishmania donovani in splenic macrophages much more efficiently than did the liposomal piperine or free piperine. at a dose equivalent to 6 mg/kg body wt every 4th day for a total of 4 doses in 12 days, the mannose-coated liposomal piperine was found to reduce spl ...199910650726
organ-specific immune responses associated with infectious disease.the immune response to infection can vary markedly in different organs of the same animal. in some organs, the infection can resolve with subsequent immunity to re-infection, whereas in other organs, pathogens can persist. here, christian engwerda and paul kaye highlight the importance of defining organ-specific immune mechanisms for developing strategies that deal effectively with infectious diseases and their associated pathologies.200010652464
the humoral immune response to the kinetoplastid membrane protein-11 in patients with american leishmaniasis and chagas disease: prevalence of igg subclasses and mapping of epitopes.the kinetoplastid membrane protein-11 (kmp-11) is a major target of the humoral immune response during leishmania-infections. the majority of sera from visceral leishmaniasis, mucocutaneous leishmaniasis and even some cutaneous leishmaniasis patients contain detectable igg antibodies against kmp-11. we also provide evidence that this protein may act as a potent antigen in t. cruzi infections, since most chagas sera show immunological cross-reactivity. therefore, kmp-11 cannot be used as a specif ...199910656675
molecular characterization of kmp11 from trypanosoma cruzi: a cytoskeleton-associated protein regulated at the translational level.kinetoplasmid membrane protein-11 (kmp11) is present in a wide range of trypanosomatids. in the present paper, we show that the t. cruzi kmp11 gene is organized in a cluster formed by four gene units arranged in a head-to-tail tandem manner located on a chromosome of about 1900 kb. northern blot analyses indicated that the steady-state level of mature kmp11 transcripts of 0.52 kb is high and similar in the three forms of the parasite. the kmp11 mrnas have a half-life of about 16 h whose steady-s ...200010668791
visceral leishmanicidal activity of hexadecylphosphocholine (miltefosine) in mice deficient in t cells and activated macrophage microbicidal mechanisms.hexadecylphosphocholine (miltefosine), a membrane-active alkylphospholipid, may be the first effective oral agent for visceral leishmaniasis, an intracellular protozoal infection of tissue macrophages. in vitro, miltefosine stimulates t cells and macrophages to respond to and secrete activating cytokines, including interferon (ifn)-gamma, and enhances macrophage production of microbicidal reactive nitrogen and oxygen intermediates (rnis and rois, respectively). to determine whether these effects ...200010669380
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