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design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase.this paper describes the design, synthesis and evaluation of a series of 2,4-diaminoquinazolines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. compounds were designed by a generating virtual library of compounds and docking them into the enzyme active site. following their synthesis, they were found to be potent and selective inhibitors of leishmanial dihydrofolate reductase. the compounds were also found to have potent activity against trypanosoma brucei rhodesiense, a ...200515755663
role of sulfhydryl groups in band 3 in the inhibition of phosphate transport across erythrocyte membrane in visceral leishmaniasis.membrane destabilization in erythrocytes plays an important role in the premature hemolysis and development of anemia during visceral leishmaniasis (vl). marked degradation of the anion channel protein band 3 is likely to allow modulation of anion flux across the red cell membrane in infected animals. the present study describes the effect of structural modification of band 3 on phosphate transport in vl using (31)p nmr. the result showed progressive decrease in the rate and extent of phosphate ...200515752716
leishmania promastigote membrane antigen-based enzyme-linked immunosorbent assay and immunoblotting for differential diagnosis of indian post-kala-azar dermal leishmaniasis.diagnosis of post-kala-azar dermal leishmaniasis (pkdl), caused by leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. since the disease generally appears very late after the clinical cure of kala-azar in india, it is also difficult to correlate pkdl with a previous exposure to l. donovani. very few attempts have been made so far to diagnose pkdl serologically, and the diagnostic methods vary in their ...200515750095
visceral leishmaniasis in the syrian arab republic: early detection using rk39.leishmaniasis causes significant morbidity and mortality in areas where it is endemic. a seroprevalence survey was conducted in 2 endemic villages in daraa, syrian arab republic, where 80 out of 345 children (23.2%) tested positive for visceral leishmaniasis (vl) using rk39 dipstick test. only 10 cases were symptomatic (12.5%), and 27.5% were positive by elisa test. all the sera (n = 138) obtained from the control village were negative. of the rk39 initially positive cases, 52 had seroconverted ...200315748082
field evaluation of latex agglutination test for detecting urinary antigens in visceral leishmaniasis in sudan.a latex agglutination test to detect urinary antigens for visceral leishmaniasis (vl) was studied. in 204 patients with suspected vl, katex had a sensitivity of 95.2% with good agreement with microscopy smears but poor agreement with 4 different serology tests. it was also positive in 2 confirmed vl cases co-infected with hiv. in all k4tex-positive confirmed cases actively followed up after treatment, the test became negative 1 month after completion of treatment. while ic4tex had a specificity ...200315748081
antimony-resistant leishmania donovaniin eastern sudan: incidence and in vitro correlation.a longitudinal study was done in a leishmaniasis -endemic region in eastern sudan during the period november 2001-february 2003 to determine the incidence of failure of sodium stibogluconate treatment. we studied 820 confirmed visceral leishmaniasis patients. all were treated with sodium stibogluconate, 20 mg/kg body weight for at least 28 days. parasites were isolated from lymph node aspirates from 22 participants identified as relapsed patients. all isolates were typed as leishmania donovaniba ...200315748080
factors affecting variations in exposure to infections by leishmania donovani in eastern sudan.a cross-sectional survey was carried out in gedaref state, eastern sudan to investigate the prevalence of positive leishmanin skin tests and environmental factors related to leishmania donovani infection. a total of 3835 people living in 11 villages in 3 regions were screened. soil types and tree densities were determined in 33 villages inhabited by 44 different tribes. the highest rates of positive skin tests were in rahad region (33.9%), atbara (21.6%) and gedaref (10.6%), with an average of 2 ...200315748079
characterization of a rab5 homologue in trypanosoma cruzi.rab proteins are small gtpases involved in exocytic and endocytic pathways of eukaryotic cells, controlling vesicle docking and fusion. rabs show a remarkable specificity in subcellular localization, so they can be used as molecular markers for studying protein trafficking in trypanosoma cruzi, the causal agent of chagas' disease. rab5 is a component of early endosomes. it has been identified in kinetoplastids such as trypanosoma brucei and leishmania donovani. in this work, we describe the char ...200515737633
ldarl-1 his-tagged recombinant protein: purification by immobilized metal affinity expanded bed adsorption.previously we have cloned three adp-ribosylation factor-like (arl) genes from the parasitic protozoan leishmania donovani: ldarl-3a and 3b, ldarl-1. ldarl-3a was previously purified as an active native form, which was able to bind gtp in vitro. in this paper, we have performed the production and the purification of histidine-tagged (his-tagged) ldarl-1 recombinant protein by immobilized metal affinity chromatography (imac) using expanded bed adsorption (eba) technology. this protein was purified ...200515722039
leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase shp-1.protozoan parasites of the genus leishmania are obligate intracellular parasites of monocytes and macrophages. these pathogens have evolved to invade the mammalian immune system and typically survive for long periods of time. leishmania have developed a variety of remarkable strategies to prevent their elimination by both innate and acquired immune effector mechanisms. one particular strategy of interest involves manipulation of host cell regulatory pathways so as to prevent macrophage activatio ...200515721837
modulation of phagolysosome biogenesis by the lipophosphoglycan of leishmania.promastigotes of the protozoan parasite leishmania are inoculated into the mammalian host by an infected sandfly and are phagocytosed by macrophages. there, they differentiate into amastigotes, which replicate in phagolysosomes. a family of glycoconjugates, the phosphoglycans (pgs), plays an important role in the ability of promastigotes to survive the potentially microbicidal consequences of phagocytosis. lipophosphoglycan (lpg), an abundant promastigote surface glycolipid, has received conside ...200515721836
tuftsin-bearing liposomes as antibiotic carriers in treatment of macrophage infections.tuftsin is a tetrapeptide (thr-lys-pro-arg) that specifically binds monocytes, macrophages, and polymorphonuclear leukocytes and potentiates their natural killer activity against tumors and pathogens. the antimicrobial activity of this peptide is significantly increased by attaching at the c-terminus a fatty acyl residue through the ethylenediamine spacer arm. this activity is further augmented by incorporating the modified tuftsin in the liposomes. the tuftsin-bearing liposomes not only enhance ...200515721387
leishmania donovani amastigote component-induced colony-stimulating factor production by macrophages: modulation by morphine.the neuroimmunomodulatory effects of opiates during microbial infections are now well known; however, not much is known during leishmaniasis. here, we report the effects of morphine on purified approximately 12-kda component of leishmania donovani amastigote antigen (ldaa-12)-induced colony-stimulating factor (csf) production by mouse peritoneal macrophages (pms) in vitro. low concentrations (1 x 10(-9) and 1 x 10(-11) m) of morphine significantly (p < 0.05) augmented the production of csfs, whe ...200515716055
interleukin 10 receptor blockade--pentavalent antimony treatment in experimental visceral leishmaniasis.interleukin 10 (il-10), a suppressive th2 cell-type cytokine, promotes disease progression in experimental visceral leishmaniasis. to extend testing the therapeutic effects of applying il-10 receptor (il-10r) blockade with antileishmanial chemotherapy, balb/c mice with established intracellular leishmania donovani infection were injected once with anti-il-10r mab at the time low-dose, daily pentavalent antimony (sb) therapy was initiated. in this treatment model, simultaneous administration of a ...200515716043
leishmania donovani: identification of novel vaccine candidates using human reactive sera and cell lines.leishmaniasis is a complex of diseases caused by protozoan parasites belonging to the genus leishmania. the development of specific resistance against re-infection after cure suggests that a vaccine approach is feasible. various studies in humans and experimental animals strongly suggest that th1 type of cell-mediated immune response is important for protection against the disease. a defined antigen that could elicit a specific t-cell-mediated immune response in the host would be an ideal candid ...200515713447
regulation of k-cl cotransport: from function to genes.this review intends to summarize the vast literature on k-cl cotransport (cot) regulation from a functional and genetic viewpoint. special attention has been given to the signaling pathways involved in the transporter's regulation found in several tissues and cell types, and more specifically, in vascular smooth muscle cells (vsmcs). the number of publications on k-cl cot has been steadily increasing since its discovery at the beginning of the 1980s, with red blood cells (rbcs) from different sp ...200415711773
liposomal amphotericin b and rhugm-csf for treatment of visceral leishmaniasis in aids.in recent years, several reports have emphasized the increasing importance of visceral leishmaniasis as an opportunistic infection among hiv-positive patients in areas where both infections are endemic. major challenges in the treatment of leishmaniasis include widespread resistance to pentavalent antimonial compounds, absence of safe chemotherapeutic agents, and treatment failure and relapses in hiv-leishmania coinfected patients. despite the associated adverse reactions and the need for prolon ...200415711134
n-terminal region of the large subunit of leishmania donovani bisubunit topoisomerase i is involved in dna relaxation and interaction with the smaller subunit.leishmania donovani topoisomerase i is an unusual bisubunit enzyme. we have demonstrated earlier that the large and small subunit could be reconstituted in vitro to show topoisomerase i activity. we extend our biochemical study to evaluate the role of the large subunit in topoisomerase activity. the large subunit (ldtop1l) shows a substantial degree of homology with the core dna binding domain of the topoisomerase ib family. two n-terminal truncation constructs, ldtop1delta39l (lacking amino aci ...200515711017
leishmania donovani amastigote components-induced colony-stimulating factors production.increased hematopoiesis, driven by colony-stimulating factors (csfs), is known to occur in infectious diseases. however, whether leishmania donovani component(s) can directly induce the synthesis and secretion of csfs is not known. we report that l. donovani amastigote antigens soluble in culture medium (ldaa; 0.01-10 mg/kg), injected intravenously in balb/c mice, induced the production of serum csfs; maximum induction (128>16 colonies) occurred at 1 mg/kg. in vitro also, ldaa (0.01-1 mg/ml) ind ...200515710545
first identification of the causative agent of visceral leishmaniasis in djibouti: leishmania donovani.the first identification of the leishmania species responsible for visceral leishmaniasis in djibouti is described. four strains, obtained from three autochthonous cases, were identified by starch-gel electrophoresis and iso-enzyme analysis of 15 enzymatic systems. the strains were found to belong to two newly recognized zymodemes of l. donovani: mon-268 and mon-287.200515701251
cutaneous leishmaniasis in tunisia: results of the iso-enzymatic characterization of 71 strains.three clinico-epidemiological forms of cutaneous leishmaniasis (cl) exist in tunisia: zoonotic cutaneous leishmaniasis (zcl; epidemic in the centre and the south-west); sporadic cutaneous leishmaniasis (scl; found in the north); and chronic cutaneous leishmaniasis (ccl; originally described from tataouine, in the south-east). as few isolates of leishmania from tunisian cases of cl have been typed, isolates were collected, using nnn medium, from 71 such cases. most (59) of the cases investigated ...200515701250
identification and characterization of purine nucleoside transporters from crithidia fasciculata.to initiate a molecular dissection into the mechanism by which purine transport is up-regulated in crithidia, genes encoding nucleoside transporters from crithidia fasciculata were cloned and functionally characterized. sequence analysis revealed cfnt1 and cfnt2 to be members of the equilibrative nucleoside transporter family, and the genes isolated encompassed polypeptides of 497 and 502 amino acids, respectively, each with 11 predicted membrane-spanning domains. heterologous expression of cfnt ...200515694482
the fate of heterologous cd4+ t cells during leishmania donovani infection.little is currently understood about the consequences of chronic parasitic infection for the fate of memory cd4+ t cells that recognize heterologous antigens, e.g. resulting from prior infections or vaccination. here, we address how leishmania donovani infection affected the fate of non-cross-reactive (ova)-specific memory cd4+ t cells. do11 cells were adoptively transferred into naive recipient mice, which were then immunized to generate memory do11 cells. after 6 weeks, mice were infected with ...200515682458
anti-protozoal and plasmodial fabi enzyme inhibiting metabolites of scrophularia lepidota roots.the ethanolic root extract of scrophularia lepidota, an endemic plant of the turkish flora, has been investigated for its anti-protozoal and inhibitory effect towards plasmodial enoyl-acp reductase (fabi), a key enzyme of fatty acid biosynthesis in plasmodium falciparum. chromatographic separation of the extract yielded 10 iridoids (1-10), two of which are new, and a known phenylethanoid glycoside (11). the structures of the new compounds were determined as 3,4-dihydro-methylcatalpol (8) and 6-o ...200515680992
antiprotozoal compounds from psorothamnus polydenius.bioactivity-guided fractionation of the methanolic extract of psorothamnus polydenius yielded the new chalcone 2,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), together with six other known compounds, 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (1), dalrubone (3), demethoxymatteucinol (4), eriodictyol (5), and photodalrubone (6a and 6b). this is the first report of chalcones in p. polydenius. the extracts and isolated compounds were tested in vitro for their antiprotozoal activity ...200515679330
leishmanicidal activity of edelfosine, miltefosine and ilmofosine.the anti-proliferative action of three alkyl-lysophospholipid derivatives, edelfosine (et-och), miltefosine (hexadecylphosphocholine), and ilmofosine (bm 14.440) has been studied on the promastigotes and amastigotes of leishmania donovani. the effect of the three drugs has previously been studied, but the action mode was not clearly elucidated. in this study the effect on the intracellular amastigote forms was evaluated by two different methods: the traditional method, counting the amastigotes w ...200515667597
cross-protective efficacy of a prophylactic leishmania donovani dna vaccine against visceral and cutaneous murine leishmaniasis.the fucose-mannose ligand (fml) complex of leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kda nucleoside hydrolase (nh36). in this study, we tested the immune response and protection induced by the purified fml, the recombinant nh36 (rnh36), and nh36 dna vaccines against the agents of visceral (l. chagasi) and cutaneous (l. mexicana) leishmaniasis in balb/c mice. mice developed weak humoral response to the vac ...200515664920
selective targeting of indel-inferred differences in spatial structures of highly homologous proteins.recent findings have shown that the protein elongation factor-1alpha (ef-1alpha) from the eukaryotic pathogen leishmania donovani possesses virulence properties. this was unexpected, since it has greater than 80% sequence identity with its human homologue. given that ef-1alpha is essential for cell survival, in principle, it can be considered an attractive drug target. however, the challenge is to be able to selectively target the protein so as not to affect function of the human homologue. whil ...200515657927
intake of nutrient supplements affects multiplication of leishmania donovani in hamsters.the role of the essential nutrients, vitamins a, b (complex), c and e and iron, as prophylactic as well as supportive therapy in experimental visceral leishmaniasis (vl), was studied in hamsters. prophylactic administration of vitamin c (50, 100 and 250 mg/kg) from day 15 to day 0 (15 doses) significantly reduced the intake of leishmania donovani in hamsters but had no therapeutic effect. in contrast, vitamins a, b complex and e and iron, whether used prophylactically or therapeutically, promote ...200415648691
characterisation of a developmentally regulated amino acid transporter gene from leishmania amazonensis.the metabolism of protozoan parasites of the leishmania genus is strongly based on amino acid consumption, but little is known about amino acid uptake in these organisms. in the present work, we identified a leishmania amazonensis gene (la-pat1) encoding a putative amino acid transporter that belongs to the amino acid/auxin permease family, a group of h(+)/amino acid symporters. this single copy gene is upregulated in amastigotes, the life cycle stage found in the mammalian host. la-pat1 putativ ...200515621448
pulcherrimasaponin, from the leaves of calliandra pulcherrima, as adjuvant for immunization in the murine model of visceral leishmaniasis.a novel triterpenoidal saponin, called pulcherrimasaponin (cp05), isolated from the leaves of calliandra pulcherrima benth. shows remarkable similarities to the previously described potent adjuvant, qs21 saponin (quillaja saponaria molina). on the basis of chemical and physicochemical evidence, its structure was established as [3beta,16alpha,28[2e,6s[2e,6s(2e,6s)]]]-olean-12-en-28-oic acid 3-[[o-alpha-l-arabinopyranosyl-(1-->2)-o-alpha-l-arabinopyranosyl-(1-->6)-2-(acetylamino)-2-deoxy-beta-d-gl ...200515620480
ancistrobenomine a, the first naphthylisoquinoline oxygenated at me-3, and related 5,1'-coupled alkaloids, from the "new" plant species ancistrocladusbenomensis.three new 5,1'-coupled naphthylisoquinoline alkaloids, ancistrobenomine a (1), 6-o-demethylancistrobenomine a (2), and 5'-o-demethylancistrocline (3), have been isolated from the stem bark of a botanically as yet undescribed highland liana ancistrocladus sp., proposed to be named "a. benomensis" according to the region in peninsular malaysia where it has been discovered on the mountain of gunung benom. two of the compounds possess an unprecedented structure with a novel hydroxymethylene group at ...200415620251
screening of new caledonian and vanuatu medicinal plants for antiprotozoal activity.sixty-seven extracts of 30 medicinal plants traditionally used in new caledonia or vanuatu by healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro for their antiprotozoal activity against leishmania donovani, leishmania amazonensis and trypanosoma cruzi. among the selected plants, pagiantha cerifera was the most active against both leishmania species; four extracts were active against promastigotes of leishmania donovani at ec(50) values inferior to 5 microg/m ...200415619580
leishmania inhibits stat1-mediated ifn-gamma signaling in macrophages: increased tyrosine phosphorylation of dominant negative stat1beta by leishmania mexicana.previous studies have demonstrated that leishmania donovani attenuates stat1-mediated signaling in macrophages; however it is not clear whether other species of leishmania, which cause cutaneous disease, also interfere with macrophage ifn-gamma signaling. therefore, we determined the effect of leishmania major and leishmania mexicana infection on stat1-mediated ifn-gamma signaling pathway in j774a.1 and raw264.7 macrophages. we found that both l. major and l. mexicana suppressed ifngammaralpha ( ...200415619518
[alithiasic cholecystitis in association with visceral leishmaniasis in an immunodepressed patient]. 200415615399
leishmania lipophosphoglycan activates the transcription factor activating protein 1 in j774a.1 macrophages through the extracellular signal-related kinase (erk) and p38 mitogen-activated protein kinase.leishmania donovani is an obligatory intracellular pathogen that resides and multiplies in the phagolysosomes of macrophages. the outcome of this infection depends on the balance between the host ability to activate macrophage killing and the parasite ability to suppress or evade this host immune response. lipophosphoglycan (lpg) glycoconjugate, the surface molecule of the protozoan parasite is a virulence determinant and a major parasite molecule involved in this process. in this study, we exam ...200515610826
mutational analysis of the active-site residues crucial for catalytic activity of adenosine kinase from leishmania donovani.leishmania donovani adenosine kinase (ldadk) plays a pivotal role in scavenging of purines from the host. exploiting interspecies homology and structural co-ordinates of the enzyme from other sources, we generated a model of ldadk that led us to target several amino acid residues (namely gly-62, arg-69, arg-131 and asp-299). replacement of gly-62 with aspartate caused a drastic reduction in catalytic activity, with decreased affinity for either substrate. asp-299 was found to be catalytically in ...200515606359
slc11a1-mediated resistance to salmonella enterica serovar typhimurium and leishmania donovani infections does not require functional inducible nitric oxide synthase or phagocyte oxidase activity.solute carrier family 11a member 1 (slc11a1; formerly natural resistance-associated macrophage protein 1) encodes a late endosomal/lysosomal protein/divalent cation transporter, which regulates iron homeostasis in macrophages. during macrophage activation, slc11a1 exerts pleiotropic effects on gene regulation and function, including generation of nitric oxide (no) via inducible no synthase (inos; encoded by nos2a) and of reactive oxygen intermediates (roi) via the phagocyte oxidase complex. as n ...200415601666
the choice of animal model and reduction.careful choice of the animal model is essential, if research is to be conducted efficiently, by using the minimum number of animals in order to provide the maximum amount of information. inbred strains of rodents provide an excellent way of controlling and investigating genetic variation in characters of interest and in response to experimental treatments. outbred stocks, in which genetic and non-genetic factors are inextricably mixed, are much less suitable, because random and uncontrolled gene ...200415601228
evaluation of a latex agglutination test (katex) for detection of leishmania antigen in urine of patients with hiv-leishmania coinfection: value in diagnosis and post-treatment follow-up.the usefulness of antigen detection in urine as an alternative tool for diagnosis of leishmaniasis and post-treatment follow-up in patients with leishmania-hiv coinfection was evaluated with a latex agglutination test (katex; kalon biological, uk). forty-nine hiv-infected patients with visceral leishmaniasis were included in the study. antigen detection in urine (adu) was positive in 42 of 49 (sensitivity, 85.7%) samples obtained during a primary episode. after treatment, a follow-up study in 23 ...200415599651
infection rates with leishmania donovani and mycobacterium tuberculosis in a village in eastern sudan.leishmania-tuberculosis co-infection is not uncommon in clinical practice in east africa, but little is known about the epidemiology of this problem at population level. a cross-sectional household survey was carried out in an active visceral leishmaniasis (vl) focus in eastern sudan in february 2002.200415598262
stromal cells direct local differentiation of regulatory dendritic cells.cd11c(hi) dendritic cells (dc) play an essential role during the initiation of cell-mediated immunity. recently, cd11c(lo)cd45rb(hi) dc with regulatory properties have been described. however, the origins of regulatory dc are poorly understood. here, we show that spleen-derived stromal cells promote selective development of cd11c(lo)cd45rb(+) il-10-producing regulatory dc from lineage-negative c-kit(+) progenitor cells. these dc have the capacity to suppress t cell responses and induce il-10-pro ...200415589169
identification of novel parasitic cysteine protease inhibitors using virtual screening. 1. the chembridge database.trypanosomiasis, leishmaniasis, and malaria are major parasitic diseases in developing countries. the existing chemotherapy of these diseases suffers from lack of safe and effective drugs and/or the presence of widespread drug resistance. cysteine proteases are exciting novel targets for antiparasitic drug design. virtual screening was performed in an attempt to identify novel druglike nonpeptide inhibitors of parasitic cysteine proteases. the chembridge database consisting of approximately 241 ...200415588096
trypanosomatid flagellum biogenesis: arl-3a is involved in several species.overexpression in leishmania amazonensis promastigotes of the gtpase-deficient small g protein ldarl-3a-q70l specifically provokes the loss of the flagella without affecting cell viability and body size. however, motility is lost and, remarkably, cells do not survive in the insect vector lutzomyia longipalpis gut, leading to interruption of parasite transmission. we report here that overexpression of the same protein in leishmania major, leishmania donovani, and crithidia fasciculata also led to ...200415582509
hemoglobin receptor in leishmania is a hexokinase located in the flagellar pocket.hb endocytosis in leishmania is mediated through a 46-kda protein located in the flagellar pocket. to understand the nature of the hb receptor (hbr), we have purified the 46-kda protein to homogeneity from leishmania promastigote membrane. purified hbr specifically binds hb. the gene for hbr was cloned, and sequence analysis of the full-length hbr gene indicates the presence of hexokinase (hk) signature sequences, atp-binding domain, and pts-ii motif. four lines of evidence indicate that hbr in ...200415579464
distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of leishmania donovani infection.tumor necrosis factor (tnf) is critical for the control of visceral leishmaniasis caused by leishmania donovani. however, the role of the related cytokine lymphotoxin (lt) alpha in this infection is unknown. here we report that c57bl/6 mice deficient in tnf (b6.tnf(-/-)) or lt alpha (b6.lt alpha(-/-)) have increased susceptibility to hepatic l. donovani infection. furthermore, the outcome of infection in bone marrow chimeric mice is dependent on donor hematopoietic cells, indicating that develop ...200415579454
leishmania parasites (kinetoplastida: trypanosomatidae) reversibly inhibit visceral muscle contractions in hemimetabolous and holometabolous insects.female sand flies can acquire protozoan parasites in the genus leishmania when feeding on an infected vertebrate host. the parasites complete a complex growth cycle in the sand fly gut until they are transmitted by bite to another host. recently, a myoinhibitory peptide was isolated from leishmania major promastigotes. this peptide caused significant gut distension and reversible, dose-dependent inhibition of spontaneous hindgut contractions in the enzootic sand fly vector, phlebotomus papatasi. ...200415579321
elevated plasma levels of interferon (ifn)-gamma, ifn-gamma inducing cytokines, and ifn-gamma inducible cxc chemokines in visceral leishmaniasis.interferon (ifn)- gamma plays an important role during immune responses against leishmaniasis. production of ifn-gamma is regulated by interleukin (il)-12, il-18, and il-15. interferon-gamma-inducible protein (ip)-10 and monokine induced by ifn-gamma (mig) are cxc chemokines, the production of which, at least in part, is ifn-gamma dependent. a follow-up study of individuals infected with leishmania donovani was undertaken in an area of ethiopia endemic for visceral leishmaniasis (vl). plasma lev ...200415569785
sudanese mucosal leishmaniasis: isolation of a parasite within the leishmania donovani complex that differs genotypically from l. donovani causing classical visceral leishmaniasis.mucosal leishmaniasis, which is a sporadic disease in the sudan, was shown by isoenzyme characterization and pcr to be caused by leishmania donovani. however, it was not clear if the parasite was exactly the same strain as that causing visceral leishmaniasis (vl), or of a different strain. we utilized a new generation of molecular dna markers, minisatellites and kinetoplast dna, for rapid characterization of the parasite. the results show that the genotypes of some of the parasites causing vl ar ...200515567136
inhibition of leishmania donovani promastigote dna topoisomerase i and human monocyte dna topoisomerases i and ii by antimonial drugs and classical antitopoisomerase agents.we have compared the inhibitor sensitivities of dna topoisomerase i (topi) from leishmania donovani promastigotes and tops i and ii of human monocytes using pentavalent and trivalent antimonials (sbv, sbiii) and classical top inhibitors. bis-benzimidazoles (hoechst-33258 and -33342) were potent inhibitors of both parasite and human topi, but hoechst-33342 was markedly less cytotoxic to promastigotes than to monocytes in vitro. leishmania donovani was also considerably less sensitive than monocyt ...200415562618
crystallographic and nmr studies of antiinfective tricyclic guanidine alkaloids from the sponge monanchora unguifera.three tricyclic guanidine alkaloids, including 1,8a;8b,3a-didehydro-8beta-hydroxyptilocaulin (1), 1,8a;8b,3a-didehydro-8alpha-hydroxyptilocaulin (2) and mirabilin b (3), were identified from the marine sponge monanchora unguifera. 1,8a;8b,3a-didehydro-8alpha-hydroxyptilocaulin (2) is a new stereoisomer of 1, the structure of which was elucidated by spectroscopic analysis, comparison of its spectral data with those of 1, and confirmed by x-ray analysis. compounds 1 and 2 co-crystallized in an unu ...200415556763
overexpression in escherichia coli and purification of pteridine reductase (ptr1) from a clinical isolate of leishmania donovani.pteridine reductase 1 (ptr1) is part of a novel metabolic pathway in leishmania associated with folate metabolism. its main function is to salvage pterins but a second one is to reduce folates. the novelty and possible uniqueness of the pathway in which ptr1 is involved opens the possibility of developing specific inhibitors, which in combination with dihydrofolate reductase inhibitors could be highly effective against leishmania. in order to increase our understanding of this putative important ...200415555938
a new pcr-elisa for diagnosis of visceral leishmaniasis in blood of hiv-negative subjects.the pcr-elisa represents a promising advance for diagnosis of visceral leishmaniasis (vl) in blood samples. however, the method has been validated mostly with hiv-positive patients who are known to have high levels of parasitaemia. we developed a new pcr-elisa assay for specific detection of leishmania in patients' blood and validated it in nepalese subjects with clinically suspected vl, almost all of whom were hiv-negative. for blood samples, pcr-elisa was more sensitive (83.9%) than convention ...200515550258
reconstitution of gdp-mannose transport activity with purified leishmania lpg2 protein in liposomes.activated nucleotide sugars required for the synthesis of glycoconjugates within the secretory pathway of eukaryotes are provided by the action of nucleotide sugar transporters (nsts). typically, nsts are studied in microsomal preparations from wild-type or mutant lines; however, in this setting it can be difficult to assess nst properties because of the presence of glycosyltransferases and other interfering activities. here we have engineered leishmania donovani to express high levels of an act ...200515542612
efficacy of trypan: a diminazene based drug as antileishmanial agent.trypan, a diamidine based drug, was tested as an antileishmanial agent. duplicate cultures of both leishmania major and leishmania donovani promastigotes in m199 medium and trypan at various concentrations were tested. the cultures were incubated at 25 degrees c and parasites counted at 48 h interval, and the data generated was used to establish growth inhibition curves. drug-free cultures were included to serve as control. in the in vivo study, a total of 40 balb/c mice were divided into five g ...200415533297
antibodies directed against o-acetylated sialoglycoconjugates accelerate complement activation in leishmania donovani promastigotes.an enhanced presence of 9-o-acetylated sialoglycoconjugates (9-o-acsgs) triggers the alternate pathway (ap) in indian visceral leishmaniasis (vl). antibodies directed against these epitopes are present in high titers. the biological relevance of these antibodies, with regard to activation of the classical pathway (cp), was investigated.200415529267
quantification of leishmania infantum dna by a real-time pcr assay with high sensitivity.a real-time pcr was developed to quantify leishmania infantum kinetoplast dna and optimized to reach a sensitivity of 0.0125 parasites/ml of blood. in order to analyze the incidence of heterogeneity and number of minicircles, we performed comparative pcr by using the leishmania dna polymerase gene as a reporter. assays performed in both promastigote and amastigote stages showed variations among different l. infantum and leishmania donovani strains and the stability of the minicircle numbers for ...200415528722
contribution of electron and confocal microscopy in the study of leishmania-macrophage interactions.promastigotes of the protozoan parasite genus leishmania are inoculated into a mammalian host when an infected sand fly takes a bloodmeal. following their opsonization by complement, promastigotes are phagocytosed by macrophages. there, promastigotes differentiate into amastigotes, the form of the parasite that replicates in the phagolysosomal compartments of host macrophages. although the mechanisms by which promastigotes survive the microbicidal consequence of phagocytosis remain, for the most ...200415525438
novel motifs in amino acid permease genes from leishmania.eight amino acid permease genes from the protozoan parasite leishmania donovani (aaplds) were cloned, sequenced, and shown to be expressed in promastigotes. seven of these belong to the amino acid transporter-1 and one to the amino acid polyamino-choline superfamilies. using these sequences as well as known and characterized amino acid permease genes from all kingdoms, a training set was established and used to search for motifs, using the meme motif discovery tool. this study revealed two motif ...200415522240
in vivo selection for leishmania donovani miniexon genes that increase virulence in leishmania major.different species of leishmania are responsible for the diverse pathologies associated with leishmaniasis including leishmania donovani which results in fatal visceral infection and leishmania major which causes non-fatal cutaneous infection. in an attempt to identify genotypic differences between these related old world leishmania species which contribute to their distinct phenotypic characteristics, we have introduced a l. donovani cosmid library into l. major to select for l. donovani sequenc ...200415522086
leishmania donovani is the only cause of visceral leishmaniasis in east africa; previous descriptions of l. infantum and "l. archibaldi" from this region are a consequence of convergent evolution in the isoenzyme data.isoenzyme-based studies have identified 3 taxa/species/'phylogenetic complexes' as agents of visceral leishmaniasis in sudan: l. donovani, l. infantum and "l. archibaldi". however, these observations remain controversial. a new chitinase gene phylogeny was constructed in which stocks of all 3 putative species isolated in sudan formed a monophyletic clade. in order to construct a more robust classification of the l. donovani complex, a panel of 16 microsatellite markers was used to describe 39 st ...200415521628
adjunct effect of immunostimulating hexapeptide analogous to human beta-casein fragment (54-59) to sodium stibogluconate against experimental visceral leishmaniasis.visceral leishmaniasis (vl) is a major public health problem in many tropical countries of the world. the available chemotherapeutics require parenteral administration and have other limitations like cost, toxicity, variable efficacy or restricted supplies. there is no effective treatment for immunosuppressed patients with leishmaniasis- hiv co-infection. hence, new therapies, that are effective when treatment with the currently available drugs fails, must be developed. one of the major strategi ...200415518175
short report: fluorescent leishmania: application to anti-leishmanial drug testing.classic techniques for detecting the susceptibility of leishmania to different drugs are time-consuming, laborious, and require the use of macrophages. the use of flow cytometry for monitoring leishmania susceptibility to drugs is beginning to be implemented. using green fluorescent protein (gfp), we have improved and simplified the screening procedure. we introduced a gfp marker into field strains of leishmania causing kala-azar (visceral leishmaniasis) and explored the suitability of transgeni ...200415516633
[treatment of acanthamoeba keratitis: possibilities, problems, and new approaches].acanthamoeba keratitis is a corneal disease associated predominantly with contact lens wear. the occurrence of acanthamoeba keratitis has been rising since 1990 in correlation to the growing number of contact lens wearers. to date approximately 2000 cases have been published around the world. due to the complicated diagnostics, the elaborate treatment and the usually bad compliance of the patients, acanthamoeba keratitis unfortunately very often takes a serious progression, which may lead to ser ...200315508774
antimicrobial and antileishmanial activities of hypocrellins a and b.hypocrellins a and b were evaluated for in vitro antimicrobial and antileishmanial activities. hypocrellin a exhibited promising activity against candida albicans and moderate activity against staphylococcus aureus, methicillin-resistant s. aureus, pseudomonas aeruginosa, and mycobacterium intracellulare. hypocrellin b showed weak antimicrobial activities. hypocrellin a exhibited potent antileishmanial activity, while hypocrellin b was only moderately active. these results of promising antifunga ...200415504880
second-site suppression of a nonfunctional mutation within the leishmania donovani inosine-guanosine transporter.ldnt2 is a member of the equilibrative nucleoside transporter family, which possesses several conserved residues located mainly within transmembrane domains. one of these residues, asp(389) within ldnt2, was shown previously to be critical for transporter function without affecting ligand affinity or plasma membrane targeting. to further delineate the role of asp(389) in ldnt2 function, second-site suppressors of the ldnt2-d389n null mutation were selected in yeast deficient in purine nucleoside ...200515501825
efficacy of human beta-casein fragment (54-59) and its synthetic analogue compound 89/215 against leishmania donovani in hamsters.the characteristic feature of visceral leishmaniasis (vl) is the profound impairment of immune system of the infected host, which contributes significantly to the partial success of antileishmanial chemotherapy. since in vl, cure is the combinatorial effect of drug and immune status of the host, the rationale approach towards antileishmanial chemotherapy would be to potentiate the immune functioning of the host to extract desired results. towards this direction several rationally designed analog ...200415501518
[chromosomal localization of the kmp-11 genes in the kp1(+) and kp1(-) strains of trypanosoma rangeli].genes encoding for the kmp-11 protein were localized on the chromosomes of trypanosoma rangeli. these genes were located in two chromosomes of 3,100 and 3,400 kb in the kp1(-) strain whereas in the kp1(+) h14 and choachí strains, the genes are located in a chromosome of 1,600 kb. the choachí strain presents an additional band of 1,400 kb. in the shubacbarina and munanta strains of trypanosoma cruzi, the kmp-11 genes are located on a chromosomal band of 1,490 kb. therefore, the chromosomal locali ...200415495600
visceral leishmaniasis: a trip to the greek islands is not always idyllic.although cutaneous leishmaniasis is occasionally seen in australia in overseas travellers and migrants, visceral leishmaniasis has been reported rarely and only in people who were immunocompromised. we describe an 18-year-old immunocompetent man who presented with pancytopenia and a 2-week history of fever and lethargy a year after visiting the greek islands. visceral leishmaniasis was diagnosed after a bone marrow biopsy showed protozoa, and the patient responded well to treatment with liposoma ...200415487964
evaluation of the direct agglutination test based on freeze-dried leishmania donovani promastigotes for the serodiagnosis of visceral leishmaniasis in sudanese patients.the direct agglutination test (dat) based on freeze-dried (fd) leishmania donovani antigen was evaluated for the serodiagnosis of kala-azar in a rural setting in eastern sudan. the performance of the fd-dat was compared with standard liquid antigen (lq) by testing serum samples and blood samples collected on filter paper of microscopically and pcr-confirmed vl patients, apparently healthy endemic controls and patients with other relevant infectious diseases for the region. in the present study, ...200415482407
ldarf1 in trafficking and structural maintenance of the trans-golgi cisternal network in the protozoan pathogen leishmania donovani.adenosine diphosphate ribosylation factors (arfs) are small guanosine-5'-triphosphatases that are essential in vesicular trafficking and in the maintenance of the golgi network. in this report, we identified a homolog of the mammalian arf1 in the human pathogenic protozoan parasite, leishmania donovani (ld). ld arf1 is a 549 bp gene encoding a 183-amino acid deduced protein of approximately 20 kda. we demonstrated by southern blot analysis that there are at least two copies of arf1 in the ld gen ...200415479452
macrophages, pathology and parasite persistence in experimental visceral leishmaniasis.many infectious diseases are associated with parasite persistence, often restricted to certain tissue sites, yet the determinants of such persistence are poorly understood. infection with the protozoan parasite leishmania donovani has proved a useful experimental tool to address how immune responses can be differentially effective in clearing parasites from different tissues and, conversely, it might also provide a good model for understanding the basis of parasite persistence. this article revi ...200415471704
localization of marginal zone macrophages is regulated by c-c chemokine ligands 21/19.the marginal zone (mz) of the spleen is an important site for the capture of blood-borne pathogens and a gateway for lymphocytes entering the white pulp. we have recently reported that leishmania donovani infection results in a remarkably selective loss of mz macrophages (mzm) from the mz. to understand the basis of this observation, we have investigated how mzm maintain their anatomical distribution in the steady state in uninfected mice. we now report that plt/plt mice, which lack functional c ...200415470021
a subset of liver nk t cells is activated during leishmania donovani infection by cd1d-bound lipophosphoglycan.natural killer (nk) t cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. despite the immunogenicity of microbial lipoglycans and their promiscuous binding to cd1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. in the current work, we show increased susceptibility of nk t cell-deficient cd1d(-/-) mice to leishmania donovani infection and leishmania-in ...200415466622
glucose and proline transport in kinetoplastids.the parasitic protozoa belonging to the kinetoplastids can use both sugars and amino acids as carbon and energy sources. in this review, benno ter kuile discusses nutrient acquisition and utilization and how the metabolic strategies reflect the environment encountered in host and vector. recent genetic and physiological evidence suggests that facilitated diffusion may be the primary uptake mechanism for glucose, and possibly for proline as well, even though there is biochemical and genetic evide ...199315463755
intermediary metabolism of leishmania.in the course of their existence, parasites develop several metabolic pathways that differ significantly from those of their hosts. despite the fairly close evolutionary kinship between leishmania donovani and trypanosoma brucei, the forms that live in the insect vectors have evolved different strategies for the disposition of available food resources. in this brief review, joseph blum will focus on the data available from studies on leishmania spp and will largely ignore the information availab ...199315463727
rapid characterization of recombinant lambdagt11 clones expressing parasite antigens.recombinant dna techniques allow any parasite gene to be isolated, propagated and analysed in great detail. the techniques are now well known and widely used in research on parasite diagnosis, vaccine development and identification of chemotherapeutic targets. there are difficulties, for example in analysing carbohydrate antigens, and in selecting which genes merit the intensive investigation required. in this article john kelly and mark blaxter discuss two simple procedures that allow recombina ...198715462876
therapeutic potential of new pt(ii) and ru(iii) triazole-pyrimidine complexes against leishmania donovani.we have already established an in vitro culture system using murine macrophages infected with leishmania donovani in which the time course of parasite growth is determined quantitatively. we adopted this system for the screening of three triazole-pyrimidine derivatives that would ideally prove to be effective against l. donovani with no toxicity to the host cell. amphotericin b deoxycholate was used as the standard drug and gave a ic50 value of 3.89 microg/ml. the three triazole-pyrimidine compo ...200515452362
studies on protozoa. part ii: the golden hamster (cricetus auratus) and cotton rat (sigmodon hispidus) as experimental hosts for leishmania donovani. 195015443044
the rate of disappearance of leishmania donovani from the spleen of the infected golden hamster following a single injection of a pentavalent antimonial. 195015425728
studies on protozoa; the metabolism of leishman-donovan bodies and flagellates of leishmania donovani. 194915395877
purification, characterization of o-acetylated sialoglycoconjugates-specific igm, and development of an enzyme-linked immunosorbent assay for diagnosis and follow-up of indian visceral leishmaniasis patients.the surface expression of 9-o-acetylated sialic acid (9-oacsa) is elevated on hematopoietic cells and erythrocytes of visceral leishmaniasis (vl) patients. in this study, we show that vl patients contain elevated levels of igm antibodies directed against 9-o-acetylated sialoglycoconjugates (9-oacsg). these antibodies were affinity purified with bovine submaxillary protein as the affinity matrix containing the terminal epitope, 9-oacsaalpha2-6galnac. they also bound to 9-oacsgs on hematopoietic c ...200415380274
anthranoid compounds with antiprotozoal activity from vismia orientalis.a phytochemical investigation of the 80% ethanolic extract of stem bark of vismia orientalis engl. (guttiferae or clusiaceae), a plant used in traditional medicine in tanzania, resulted in the isolation and spectroscopic characterisation of 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone, emodin, vismione d and bianthrone a1. vismione d exhibited a broad range of antiprotozoal activities against trypanosoma brucei rhodesiense and t. cruzi (ic50 < 10 micrograms/ml), leishmania donovani (ic50 0.3 ...200415368649
vaccination with leishmania soluble antigen and immunostimulatory oligodeoxynucleotides induces specific immunity and protection against leishmania donovani infection.in this report, we investigated the effect of odn containing immunostimulatory cg motifs as adjuvant with soluble antigen (sa) from leishmania donovani. balb/c mice were vaccinated with the soluble antigen with or without cpg-odn as adjuvant and then challenged with l. donovani metacyclic promastigotes. cpg-odn alone resulted in partial protection against challenge with l. donovani. immunization of mice with sa and cpg-odn showed enhanced reduction in parasite load ( approximately 60%) when comp ...200415364110
isomerase-independent chaperone function of cyclophilin ensures aggregation prevention of adenosine kinase both in vitro and under in vivo conditions.using inactive aggregates of adenosine kinase (adk) from leishmania donovani as the model substrate, we recently demonstrated that a cyclophilin (ldcyp) from the same source in an isomerase-independent fashion reactivated the enzyme in vitro by disaggregating its inactive oligomers [chakraborty et al. (2002) j. biol. chem. 277, 47451-47460]. besides disrupting preformed aggregates, ldcyp also prevents reaggregation of the newly formed active protein that is generated after productive refolding f ...200415362872
activity of dihydroartemisinin against leishmania donovani both in vitro and vivo. 200415361310
the immunopathology of experimental visceral leishmaniasis.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 ...200415361245
does the leishmania major paradigm of pathogenesis and protection hold for new world cutaneous leishmaniases or the visceral disease?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 ...200415361243
progress in vaccine research and possible effector mechanisms in visceral leishmaniasis.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 ...200415357218
macrophage specific drug delivery in experimental leishmaniasis.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 ...200415357216
leishmaniasis: current status of vaccine development.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 fin ...200415357215
camptothecin-induced imbalance in intracellular cation homeostasis regulates programmed cell death in unicellular hemoflagellate leishmania donovani.leishmania, a unicellular trypanosomatid protozoan parasite, causes a wide range of human diseases ranging from the localized self-healing cutaneous lesions to fatal visceral leishmaniasis. however, it undergoes a process of programmed cell death during treatment with the topoisomerase i poison camptothecin (cpt). the present study shows that cpt-induced formation of reactive oxygen species increases the level of cytosolic calcium through the release of calcium ions from intracellular stores as ...200415355995
leishmania donovani activates nuclear transcription factor-kappab in macrophages through reactive oxygen intermediates.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 ...200415336576
seroepidemiological study of visceral leishmaniasis among humans and animal reservoirs in bushehr province, islamic republic of iran.using direct agglutination tests, a survey of visceral leishmaniasis was carried out among children and adults from 13 villages and from nomadic tribes in bushehr province during 1998-99. of the 1496 plasma samples, the overall seropositive rate (titres > or = 1:3200) was 3.4%. almost all cases (94.1%) were in children under 10 years old. eighteen patients were diagnosed with kala azar; fever and splenomegaly were the predominant signs and symptoms. parasitology and serology examinations of loca ...200115332732
combination therapy using sodium antimony gluconate in stearylamine-bearing liposomes against established and chronic leishmania donovani infection in balb/c mice.in this work we report the activity seen with combination therapy using sodium antimony gluconate in liposomes composed of egg phosphatidyl choline and stearylamine for elimination of leishmania donovani parasites from the liver and spleen of balb/c mice with established and chronic infections.200415328135
inhibiting activities of the secondary metabolites of phlomis brunneogaleata against parasitic protozoa and plasmodial enoyl-acp reductase, a crucial enzyme in fatty acid biosynthesis.anti-plasmodial activity-guided fractionation of phlomis brunneogaleata (lamiaceae) led to the isolation of two new metabolites, the iridoid glycoside, brunneogaleatoside and a new pyrrolidinium derivative (2 s,4 r)-2-carboxy-4-( e)- p-coumaroyloxy-1,1-dimethylpyrrolidinium inner salt [(2 s,4 r)-1,1-dimethyl-4-( e)- p-coumaroyloxyproline inner salt]. moreover, a known iridoid glycoside, ipolamiide, six known phenylethanoid glycosides, verbascoside, isoverbascoside, forsythoside b, echinacoside, ...200415326547
dynamics of cd62l/cd45rb cd4+ and cd8+ lymphocyte subsets in hepatic and splenic tissues during murine visceral leishmaniasis.this study aimed to characterise, for the first time, the dynamics of cd4+ and cd8+ lymphocyte cd62l/cd45rb subsets, during visceral leishmaniasis. memory/activated status of hepatic and splenic t cells was compared in mice strains with "cure" and "non-cure" phenotypes to leishmania infantum infection. in both mice strains, a correlation between the dynamics of the memory cd4+ and cd8+ t cells (cd62llow/cd45rblow) subsets in the liver and the pre-activated phenotype of lymphocytes (cd62llow/cd45 ...200415325799
impact of a co-factor on the dynamics of leishmania donovani infection: does hiv infection encourage the recurrence of visceral leishmaniasis following post-kala-azar dermal leishmaniasis? 200415324473
modulation of the leishmania donovani peroxin 5 quaternary structure by peroxisomal targeting signal 1 ligands.the import of proteins containing the peroxisomal targeting signal 1 (pts1) into the leishmania glycosome is dependent on the docking of the pts1-loaded ldpex5 cytosolic receptor with ldpex14 on the glycosome surface. here we show that, in the absence of pts1, ldpex5 is a tetramer that is stabilized by two distinct interaction domains; the first is a coiled-coil motif encompassing residues 277 to 310, whereas the second domain is localized to residues 1 to 202. by using microcalorimetry, surface ...200415314146
disseminated intravascular coagulation as an unusual presentation of kala-azar: report of two cases.kala-azar (visceral leishmaniasis) is a common problem in various well-defined areas of india. it is characterized by fever of long duration, enlarged liver and spleen, anaemia and leucopoenia. bleeding is an uncommon manifestation of kala-azar. we report 2 cases, in which disseminated intravascular coagulation was an unusual complication.200415307590
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