Publications

TitleAbstractYear
Filter
PMID
Filter
in vitro trypanocidal activities of new s-adenosylmethionine decarboxylase inhibitors.a series of novel aromatic derivatives based on the structure of methylglyoxal bis(guanylhydrazone) (mgbg) was examined for in vitro antitrypanosomal activities and cytotoxicities for human cells. one-third of the compounds tested showed trypanocidal activity at concentrations below 0.5 microm after an incubation period of 72 h. structure-activity analysis revealed that bicyclic compounds with homocyclic rings and unmodified termini were the most active compounds. results obtained in three labor ...19968726017
visceral leishmaniasis in a renal transplant recipient: diagnostic and therapeutic problems.visceral leishmaniasis is infrequently reported in renal transplant recipients. a 40-year-old renal transplant recipient developed hepatosplenomegaly and pyrexia of unknown origin 5 months after transplantation. visceral leishmaniasis was confirmed on bone marrow examination. the usual dose of antiparasitic therapy with stibogluconate sodium failed to eradicate leishmania donovani. high-dose conventional therapy with stibogluconate sodium for an extended period of time was successful in the trea ...19968739293
identification of genes mediating lipophosphoglycan biosynthesis by functional complementation of leishmania donovani mutants.a powerful approach for identifying the genes involved in the infectious cycle of pathogens is functional genetic complementation. here, the current status of this technology in leishmania is reviewed, focusing on the genes involved in the biosynthesis of the unique parasite surface glycolipid, lipophosphoglycan (lpg). lpg plays multiple roles in the leishmania infectious cycle, in both the sand fly vector and in establishing successful intracellular parasitism within the vertebrate macrophage. ...19958745922
the bcg/ity/lsh locus: genetic transfer of resistance to infections in c57bl/6j mice transgenic for the nramp1 gly169 allele.the murine bcg/ity/lsh locus determines the susceptibilities of inbred strains to infection with unrelated intracellular parasites, such as mycobacterium bovis, salmonella typhimurium, and leishmania donovani. a candidate for bcg/ity/lsh, designated nramp1, has been recently identified and shown to encode a novel integral membrane protein that is expressed exclusively in professional phagocytes but whose function remains unknown. in inbred strains, the susceptibility to infection is associated w ...19968757814
comparison of three treatment regimens with liposomal amphotericin b (ambisome) for visceral leishmaniasis in india: a randomized dose-finding study.the efficacy and safety of 3 regimens of liposomal amphotericin b (ambisome) in the treatment of indian visceral leishmaniasis were compared in a prospective open randomized trial. thirty parasitologically confirmed patients were randomly divided into 3 equal treatment groups; group 1 received ambisome 2mg/kg on days 1, 2, 3, 4, 5, 6, and 10 (total dose 14 mg/kg); group 2 received ambisome 2 mg/kg on days 1, 2, 3, 4, and 10 (total dose 10 mg/kg); group 3 received the same dosage on 1, 5 and 10 ( ...19968758093
correlation between inhibition of growth and arginine transport of leishmania donovani promastigotes in vitro by diamidines.diamidines are known to possess potent antiprotozoal activity due to their property of binding with dna minor groove. pentamidine or 1,5-bis-(4'-amidinophenoxy)pentane, is the most known aromatic diamidine and is used to treat cases of antimony resistant leishmaniasis. yet, it suffers from limited clinical application due to its adverse and toxic side effects. a set of four structural analogs of pentamidine along with the known antileishmanial diamidines viz., pentamidine, berenil and dibromopro ...19968761349
random amplified polymorphic dna for the differentiation of leishmania donovani isolates from sudan. 19968761592
membrane characterization of amastigote-like forms of leishmania donovani.during in vitro transformation, leishmania donovani promastigotes converted into amastigote-like forms and underwent several changes in membrane parameters. they exhibited significantly increased microviscosity comparable to true amastigotes. activities of several functionally important membrane bound enzymes were also altered, thereby indicating a change in their orientation. peanut agglutinin was found to be specific for agglutination of stationary phase promastigotes whereas wheat-germ agglut ...19968765457
polyarthritis caused by leishmania in a patient with aids. 19968783728
pcr enzyme-linked immunosorbent assay for diagnosis of leishmaniasis in human immunodeficiency virus-infected patients.a pcr enzyme-linked immunosorbent assay (elisa) involving the use of bone marrow aspirates (bma) and blood samples (bs) for the diagnosis of visceral leishmaniasis (vl) in human immunodeficiency virus-infected patients was developed with primers selected from the sequence of the small-subunit rrna gene and compared with direct examination and in vitro cultivation. the pcr was optimized for routine diagnosis: processing of samples with lysis of erythrocytes without isolation of leukocytes, enzyma ...19968784604
synthetic peptide-based enzyme-linked immunosorbent assay for serodiagnosis of visceral leishmaniasis.synthetic peptides, derived from the amino acid sequence of a leishmania donovani clone, were used to develop an enzyme-linked immunosorbent assay (elisa) for detecting antibodies against l. donovani. for this purpose, five peptides were conjugated to a protein carrier, human serum albumin (hsa), by using a heterobifunctional reagent, epsilon-maleimidocaproic acid n-hydroxysuccinimide ester, to obtain a well-defined product. the sensitivity and the specificity of the peptide-specific elisa were ...19968788994
structure and function of the natural-resistance-associated macrophage protein (nramp1), a candidate protein for infectious and autoimmune disease susceptibility.the ability of macrophages to become activated is central to antimicrobial immunity. microbial stimuli can elicit a cascade of gene-inductive events mediating inflammation, elimination of the invading organism and induction of t-cell memory against reinvasion. nramp1, a gene originally identified as ity/lsh/bcg for its role in controlling salmonella typhimurium, leishmania donovani and mycobacterium bovis infections in mice, regulates this cascade. here we examine how the structure of the nramp1 ...19968796889
induction of macrophage antiprotozoal activity by monocyte chemotactic and activating factor.to determine if monocyte chemotactic and activating factor (mcaf) induces intracellular antimicrobial activity, human monocyte-derived macrophages were treated with mcaf and challenged with toxoplasma gondii and leishmania donovani. pretreatment with mcaf induced macrophages to inhibit protozoal replication by approximately 50%. these findings suggest a potential host defense role for mcaf in the inflammatory response to intracellular pathogens.19968804977
sinefungin and taxol effects on cell cycle and cytoskeleton of leishmania donovani promastigotes.sinefungin is an antibiotic possessing a strong anti-leishmanial activity. among the most important effects of this molecule on leishmania donovani promastigotes are morphological modifications and a very rapid and effective inhibition of dna synthesis. these cells contain a single dna-rich mitochondrion whose division cycle is coordinated with the nuclear division cycle. we have developed a flow-cytometric procedure based upon mithramycin as fluorochrome that can perform quantitative cell cycle ...19968806432
evidence of a laminin binding protein on the surface of leishmania donovani.both the promastigote and amastigote forms of the intracellular parasite, leishmania donovani bind the basement membrane glycoprotein laminin with high affinity (kd = 3.56 x 10(-9) m and 3.98 x 10(-9) m respectively) with approximately 9000 and approximately 800 sites per cell. bound laminin was identified by direct autoradiography and the binding protein through analysis of the parasite extract by sds-page and immunoblotting. a major component of 67 kda was detected. the same protein was obtain ...19968806598
synergism of il-2-stimulated splenocytes and pentostam enhances the killing of leishmania donovani in vitro.control of infections by the obligate intramacrophage protozoan parasite leishmania donovani is traditionally done with pentavalent antimonial drugs. it was of interest to determine if immunotherapy with il-2-stimulated splenocytes would enhance drug action in an in vitro model system. it is confirmed that nontoxic doses of pentostam decrease infection in a dose-dependent manner in vitro in terms of both the number of amastigotes/100 macrophages and the % of infected macrophages; the curative ef ...19968808645
medium-range restriction maps of five chromosomes of leishmania infantum and localization of size-variable regions.the chromosomes of the human protozoan parasite leishmania exhibit striking size polymorphisms among different strains. to define the structural basis for these variations, we have constructed full-length restriction maps of five chromosomes of 370 to 490 kb in leishmania infantum clone lem1317. rare-cutting sites for the enzymes asei, drai, xbai, sspi, spei, and sfii were mapped by partial and complete digestion of either gel-purified chromosomes or total dna. sixty-eight anonymous dna probes w ...19968812485
identification and overexpression of the a2 amastigote-specific protein in leishmania donovani.leishmania protozoa must adapt rapidly to widely different environments and thus exist as promastigotes in their sandfly host and as amastigotes in their mammalian host. promastigote differentiation into amastigotes is accompanied by both morphological and biological changes. the molecular mechanisms regulating the differentiation and survival of the different life cycle stages are poorly understood. we have therefore undertaken to identify and characterize amastigote-specific genes and their co ...19968813679
structure-function analysis of leishmania lipophosphoglycan. distinct domains that mediate binding and inhibition of endothelial cell function.we have shown that leishmania lipophosphoglycan (lpg) inhibits il-1 beta gene expression in human monocytes. here, we show that lpg can bind in a time-dependent manner and suppress endothelial cell activation, possibly via specific lpg domains. endotoxin (10 ng/ml, 4 h) consistently caused endothelium to increase monocyte adhesion (approximately 20-fold). lpg pretreatment (2 microm, 2 h) completely blocked endotoxin-mediated monocyte adhesion. lpg did not grossly suppress endothelial functions b ...19968816410
characterization of murine lung interstitial macrophages in comparison with alveolar macrophages in vitro.the present study was performed to characterize the immunologic potential of interstitial macrophages (int) in comparison with alveolar macrophages (al). the data showed that al, compared with int, have a more efficient phagocytic potential. in addition, they have a strong microbicidal activity and secrete large amounts of reactive oxygen radicals, nitric oxides, tnf, and ifn on appropriate stimulation. they also exert strong tumoricidal and parasiticidal activities. in contrast, int are more ef ...19968816420
antileishmanial effect of a potent s-adenosylmethionine decarboxylase inhibitor: cgp 40215a.cgp 40215a, specific s-adenosylmethionine decarboxylase (adometdc) inhibitor was found to inhibit the growth of leishmania donovani promastigotes (strain ur6) in a dose-dependent manner with an ic50 of 18 microm. the growth inhibition was reversed with 100 microm of spermidine and spermine. the growth inhibition in vitro by this inhibitor was accompanied by a significant decrease in adometdc activity and spermidine levels. cgp 40215a was more potent than other adometdc inhibitors, berenil or met ...19968817649
leishmania donovani attachment stimulates pkc-mediated oxidative events in bone marrow-derived macrophages.we investigated activation signaling events in bone marrow-derived macrophages after infection with leishmania donovani, an intracellular parasite of macrophages. leishmania donovani infection caused a general suppression of activation parameters like o2- and no production. however, conditions which allow parasite attachment and prevent entry resulted in triggering of o2- and no production and stimulation of o2 consumption. optimal no and o2- production occurred when bone marrow-derived macropha ...19968822807
[visceral leishmaniasis refractory to treatment: the efficacy of amphotericin b]. 19968830578
the roles of phlebotomus martini and p.celiae (diptera: phlebotominae) as vectors of visceral leishmaniasis in the aba roba focus, southern ethiopia.during field studies (december 1988 to april 1990) to determine the vectors of visceral leishmaniasis (kala-azar) in the aba roba (segen valley) focus of southern ethiopia, a total of 40,770 sandflies (diptera: psychodidae: phlebotominae) were collected and identified as six species of phlebotomus and seventeen sergentomyia spp. nine of these species were anthropophilic (four phlebotomus and five sergentomyia spp.), the dominant being phlebotomus (synphlebotomus) martini, p.(s.)celiae and sergen ...19968834743
visceral leishmaniasis misdiagnosed as malignant lymphoma.visceral leishmaniasis is a chronic infectious disease caused by a protozoan parasite of the genus leishmania, characterized by intermittent fever, monocytosis, hepatosplenomegaly and hypergammaglobulinemia. this morbid condition is rather difficult to diagnose correctly, especially at its early stage, because it is rarely encountered in japan. recently we treated a case of visceral leishmaniasis in which the patient was misdiagnosed as malignant lymphoma, and went through splenectomy and steroi ...19968835605
isolation of lipophosphoglycans from leishmania donovani amastigotes.leishmania donovani donovani amastigotes, isolated from spleens of infected hamsters or axenically cultured, and promastigotes were comparatively examined for the expression of lipophosphoglycans (lpg). parasites were metabolically labeled with [32p]-phosphate, [3h]galactose, or [3h]mannose. radiolabeled material was extracted with water/ethanol/diethylether/pyridine/nh40h and purified further by gel filtration and hydrophobic column chromatographies. these radiolabeled compounds were identified ...19968837732
[protracted fever, splenomegaly and pancytopenia in a 19-year-old man]. 19968846979
activity of oral atovaquone alone and in combination with antimony in experimental visceral leishmaniasis.balb/c mice with established visceral infection caused by the intracellular protozoan leishmania donovani were treated with oral atovaquone for 7 days. treatment with 100 mg/kg of body weight per day was optimal and halted parasite replication in the liver. in mice treated with atovaquone, the effect of a suboptimal dose of pentavalent antimony was converted from partially leishmanistatic to leishmanicidal. these results demonstrate the in vivo antileishmanial effect of atovaquone and suggest a ...19968851575
activity and mode of action of acridine compounds against leishmania donovani.in the present work, we have assayed both the in vitro and in vivo action of two acridine compounds against leishmania donovani. as part of this effort, we have studied the possible action mechanism of these compounds at the ultrastructural and biochemical levels and in relation to the synthesis of macromolecules. the two acridinones inhibit the in vitro growth of the promastigote forms of l. donovani at the highest concentration assayed (100 micrograms/ml). the in vivo results indicate that bot ...19968851593
drug delivery system: targeting of pentamidines to specific sites using sugar grafted liposomes.different sugar-grafted liposomes were prepared and tested against experimental leishmaniasis in vivo using the classical drug pentamidine isethionate and its methoxy derivative. both the drugs, when encapsulated in sugar-grafted liposomes were found to be more potent in comparison to normal liposome-encapsulated drug or to the free drug. moreover, the mannose-grafted liposomes were adjudged to be the best in lowering of spleen parasite load in comparison with those bearing glucose or galactose. ...19968858467
crystallization of the purine salvage enzyme adenine phosphoribosyltransferase.adenine phosphoribosyltransferase from the protozoan parasite leishmania donovani has been crystallized in the presence of the substrate mg(2+)-alpha-d-5-phosphoribosyl-1-pyrophosphate (prpp) or the product adenosine-5-monophosphate, as well as in the absence of ligand. these crystals belong to the space group p6(1)22 or its enantiomorph p6(5)22, with unit cell dimensions of a = b = 64.0 a, c = 240.5 a, alpha = beta = 90 degrees, and gamma = 120 degrees. the crystals diffract to 1.9 a.19968865346
leishmania infantum: infection of macrophages in vitro with promastigotes.leishmania infantum promastigotes in axenic culture exhibit limited infectivity for mouse peritoneal macrophages (m phi) in vitro using standard culture conditions (37 degrees c; 95% air/5% co2) compared to leishmania donovani promastigotes which induce notable infections. the infectivity of logarithmic (log) and stationary (stat) phase promastigotes of l. infantum was enhanced by the addition of fresh homologous serum, but no amastigotes were observed after 4 days. prolonged infections, includi ...19968875306
transbilayer inhibition of protein kinase c by the lipophosphoglycan from leishmania donovani.lipophosphoglycan (lpg), the predominant molecule on the surface of the parasite leishmania donovani, has previously been shown to be a potent inhibitor of protein kinase c (pkc) isolated from rat brain. the mechanism by which lpg inhibits pkc was further investigated in this study. lpg was found to inhibit the pkc alpha-catalyzed phosphorylation of histone in assays using large unilamellar vesicles composed of 1-palmitoyl, 2-oleoyl phosphatidylserine and 1-palmitoyl, 2-oleoyl phosphatidylcholin ...19968876188
blood, bone marrow and splenic lymphocyte subset profiles in indian visceral leishmaniasis.we examined the lymphocyte subsets in peripheral blood, bone marrow and spleen of 11 patients with acute visceral leishmaniasis (vl) and 9 with chronic vl before and after 8 weeks of antileishmanial therapy. on admission, the cd4 cell count was depressed in the peripheral blood of acute and chronic vl cases as compared to the value in 10 normal control subjects. in contrast, cd4 cell counts were higher in the bone marrow in acute and chronic cases, and in splenic aspirates of chronic cases only, ...19968882198
leishmania donovani possess a nadph-dependent alkylglycerol cleavage enzyme.leishmania parasites possess an abundance of ether-linked hydrocarbons as components of phospholipids and glycosylphosphatidylinositol anchors of glycoproteins and polysaccharides, including important surface molecules such as lipophosphoglycan (lpg) and glycosylinositolphospholipids (gipls). cleavage of the ether bond is an important feature in the turnover pathway of alkylglycerols. in mammals, ether lipid cleavage activity requires a pteridine cofactor (h4 biopterin), suggesting the potential ...19968886025
immunology of murine leishmaniasis. 19968889322
diagnosis of leishmaniasis. 19968889324
relative resistance of promastigotes of a virulent and an avirulent strain of leishmania donovani to hydrogen peroxide.sensitivity of promastigotes of leishmania donovani (dd-8, virulent: ur-6 avirulent strain) to hydrogen peroxide has been studied in vitro conditions. there was a dose-dependent toxic effect of h2o2 on both strains. the promastigotes of dd-8 strain, however, were more resistant compared to ur-6 strain. the cell response was not affected by the forms of h2o2 stress, for instance, single-dose exposure with reagent h2o2 or equivalent amount generated over a period of 1 h. dd-8 promastigotes removed ...19968891670
conservation of low-copy gene loci in old world leishmanias identifies mechanisms of parasite evolution and diagnostic markers.genome plasticity has been hypothesized to be a driving force behind parasite speciation. we have evaluated divergence in single and low-copy genes in terms of locus organization, chromosomal localization and gene expression in leishmania infantum, l. major, l. tropica and three widely divergent geographic isolates of l. donovani. seventeen genes of low to moderate copy number (1-4 copies/haploid genome) were analyzed to identify restriction fragment length polymorphisms (rflps) providing herita ...19968892303
isolation and characterization of leishmania donovani calreticulin gene and its conservation of the rna binding activity.calreticulin has been implicated in multiple cell functions. recently, we have shown that both human and simian calreticulin are rna binding proteins and that their binding activity is due to phosphorylation. to demonstrate that the rna binding property of calreticulin is an intrinsic part of this multi-functional molecule and is evolutionarily conserved, we isolated and characterized the calreticulin gene from the unicellular parasite, leishmania donovani. amino acid sequence homology between h ...19968892305
molecular characterization of the kinetoplastid membrane protein-11 from african trypanosomes.the kinetoplastid membrane protein-11 molecule was purified from trypanosoma brucei rhodesiense and an internal peptide sequence was obtained. this sequence information was used with cosmid library screening and polymerase chain reaction amplifications of both genomic dna and cdna to obtain the entire dna sequence of the encoding gene and the corresponding translated amino acid sequence of 92 residues. the sequence showed 18% divergence from the corresponding molecule of the related kinetoplasti ...19968892307
digestive leishmaniasis in acquired immunodeficiency syndrome: a light and electron microscopic study of two cases.an increased incidence of visceral leishmaniasis in patients infected with the human immunodeficiency virus (hiv) is observed in areas in which both infectious diseases are endemic. intensive worldwide traveling has also resulted recently in an increasing number of leishmanial and hiv coinfections in nonendemic areas. we describe the clinical, light microscopic, and ultrastructural features of two cases of imported, hiv-related, visceral leishmaniasis involving the alimentary tract, including th ...19968902832
leishmania donovani: metabolite mapping of promastigotes using proton nuclear magnetic resonance spectroscopy.proton nuclear magnetic resonance spectroscopy was used for studying the intracellular metabolite profile of promastigotes of leishmania donovani. the major intracellular metabolites observed in the promastigotes were acetate, alanine, succinate, glycine, alpha-glycerophosphorylcholine, acetoacetate, arginine and ethanol. a comparative study of the intracellular metabolite profile of promastigotes of different strains of l. donovani showed that, all the major intracellular metabolites were prese ...19968905621
the outcome of the parasitic process initiated by leishmania infantum in laboratory mice: a tissue-dependent pattern controlled by the lsh and mhc loci.human visceral leishmaniasis is mainly due to intracellular protozoan parasites of the leishmania donovani complex, i.e., l. donovani and l. infantum (or l. chagasi). a mouse model has been established to monitor 1) the parasitic process initiated by l. infantum in three tissues they invade, and 2) parameters of the acquired immune response they trigger. mice congenic at the lsh locus and mice of inbred strains differing at the mhc locus have been inoculated by the i.v. route with l. infantum. t ...19968906832
antileishmanial activity of rac-1-dodecyl-2-octanamido-2-deoxy-glycerophosphocholine, a new dialkylglycerophosphocholine, in vitro. 19968915134
pentavalent antimony-mannan conjugate therapy of experimental visceral leishmaniasis.pentavalent antimony-mannan (sb[v]-mannan) was 10-fold more potent than sodium stibogluconate in a murine model of visceral leishmaniasis. liver antimony concentrations were six-fold higher after sb[v]-mannan therapy compared with a dose of sodium stibogluconate that was equipotent in reducing liver parasite burdens. murine toxicity of sb[v]-mannan was variable, with a 50% lethal dose (ld50) for one preparation that was well above the concentration that killed 90% of the parasites, and for anoth ...19968916804
an m(r) 145,000 low-density lipoprotein (ldl)-binding protein is conserved throughout the kinetoplastida order.in view of the importance of the low-density lipoprotein (ldl)-receptor in trypanosoma brucei, we have examined whether other bloodstream trypanosomes of medical and veterinary importance (t.b. rhodesiense, t. equiperdum, t. vivax, t. congolense), but also related parasites developing in mammalian (leishmania donovani) and non-mammalian hosts (crithidia luciliae and phytomonas sp. isolated from euphorbia), would possess an ldl-receptor of their own. (1) all these parasites specifically accumulat ...19968919994
in vitro activity and biochemical effectiveness of new organometallic complexes of osmium(iii) against leishmania donovani and trypanosoma cruzi.in the present paper, the in vitro activities of 10 osmium(iii) complexes with [osiii(l)] degrees structure against promastigote forms of leishmania donovani and epimastigote forms of trypanosoma cruzi haven been assayed. the complexes osiii-2,4dinitroimidazole dithiocarbamate, osiii-4-nitroimidazole dithiocarbamate, osiii-benznidazole dithiocarbamate and osiii-2-amino-6-br-benzothiazole dithiocarbamate induced high percentages of growth inhibition in the parasites. the four compounds showed mod ...19968931894
an in vivo analysis of cytokine production during leishmania donovani infection in scid mice.leishmania donovani, the causative agent of visceral leishmaniasis, fails to induce nk cell activation in scid mice. in order to further our understanding of the host response to l. donovani, we analysed cytokine mrna accumulation and tnf alpha protein synthesis in the liver of scid and balb/c mice infected with this parasite. scid mice infected with l. donovani exhibited very little proinflammatory response, as measured by cytokine mrna accumulation and tnf alpha protein expression, supporting ...19968932769
creation of homozygous mutants of leishmania donovani with single targeting constructs.homozygous null mutants of the hypoxanthine-guanine phosphoribosyltransferase (hgprt) and adenine phosphoribosyltransferase (aprt) loci were created in leishmania donovani in which both alleles were eliminated using only a single targeting construct. functional heterozygotes were first generated by homologous recombination after transfection with vectors containing 5'- and 3'-flanking regions of either the hgprt or the aprt gene circumscribing drug resistance markers. homozygous null mutants wer ...19968940067
serodiagnosis of cutaneous leishmaniasis: assessment of an enzyme-linked immunosorbent assay using a peptide sequence from gene b protein.an enzyme-linked immunosorbent assay (elisa) using a 28 amino acid sequence of the repetitive element of gene b protein (gbp) from leishmania major was developed for serodiagnosis of cutaneous leishmaniasis (cl). the assay was compared to elisas using crude amastigote and promastigote antigens from l. donovani and the major surface glycoprotein (gp63) from either l. donovani or l. major as a solid-phase ligand. the sensitivity of the assays was tested in 33 patients suffering from cl caused by l ...19968940979
antigenic components of partially purified antigens of leishmania donovani infantum recognized by sera from dogs with asymptomatic or active visceral leishmaniasis.the antigenic components of a semipurified fraction of leishmania donovani infantum were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis using 14 serum samples from dogs with symptomatic visceral leishmaniasis and 11 serum samples from apparently healthy dogs collected in an area endemic for canine visceral leishmaniasis (cvl). it was found that these antigens were composed of many polypeptides, among which seven components recognized by symptoma ...19968940982
hepatic extracellular matrix in balb/c mice infected with leishmania donovani.the development of the extracellular matrix (ecm) in the liver of the balb/c mouse infected with leishmania donovani was observed by histology, immunocytochemistry and electron microscopy at 1, 2, 4, 8, 14 and 20 weeks after infection. collagen iii and proteoglycan were detected in granulomas and in the portal spaces from 4 to 20 weeks after infection. laminin was not detected in granulomas but was observed in the basement membrane of new small blood vessels in the granulation tissue around the ...19968943737
enhancement of leishmanicidal activity of human macrophages against leishmania major and leishmania donovani infection using recombinant human granulocyte macrophage colony stimulating factor.the in vitro effect of recombinant human granulocyte macrophage colony stimulating factor (rh-gmcsf) on the leishmanicidal activity and superoxide anion productivity of macrophages derived from human blood monocytes (mos) were investigated. mos treated with 25, 125, or 250 u/ml of rh-gmcsf for 72 h prior to infection with leishmania parasites, manifested significant dose-dependent increase in its leishmanicidal activities against leishmania major and leishmania donovani parasites. the percentage ...19968946701
effect of leishmania donovani antigens on superoxide anion generation by mice polymorph in vitro.the present study was planned to study the effect of priming of balb/c mice peritoneal polymorphs (pmnls) by viable, heat killed and formaline fixed promastigotes of l. donovani and soluble extract of proteins of l. donovani promastigotes on their capacity to produce toxic oxygen radicals (tor). tor production was measured by superoxide dismutase (sod), inhibitable cytochrome c reduction and nitroblue tetrazolium reduction tests. no significant stimulation or inhibition in sod inhibitable cytoch ...19968952177
[detection of leishmania in bone marrow using an automatic hemoculture system]. 19968962897
delivery of human interferon-gamma via gene transfer in vitro: prolonged expression and induction of macrophage antimicrobial activity.daily parenteral administration of exogenous interferon-gamma (ifn-gamma) induces or accelerates recovery in experimental and human infections. to develop an alternative delivery system, a replication-defective recombinant adenovirus expressing human ifn-gamma was constructed. the complete coding region of ifn-gamma was amplified by rt-pcr and inserted into an adenovirus cloning vector under the control of a human cytomegalovirus promoter. recombinant adenovirus containing the ifn-gamma minigene ...19968974003
vaccine efficacy of salmonella strains expressing glycoprotein 63 with different promoters.the development of salmonella vaccine vectors has been hindered by both the requirement for multiple doses to induce immune responses and a lack of plasmid stability. direct comparisons of different promoter systems with the same antigen are necessary to address these important issues. we have previously described an aroa- arod- deletion mutant of salmonella typhimurium (gid101) which expresses the gene encoding the leishmania major promastigote surface glycoprotein gp63 (gid101). while this con ...19978975908
functional properties of murine macrophages promoted by nerve growth factor.the stimulating effect of nerve growth factor (ngf) on phagocytosis, parasite killing, and interleukin-1beta (il-1beta) production of murine peritoneal macrophages was assessed. in the presence of various doses of ngf, macrophages showed the increased phagocytosis of both nonspecific hydrophilic microspheres and sheep red blood cells (srbc) opsonized with anti-srbc antibodies (ab) or complement in a dose-dependent manner. ngf also enhanced killing of leishmania donovani promastigotes by macropha ...19968977255
effects of steroidal allenic phosphonic acid derivatives on the parasitic protists leishmania donovani, leishmania mexicana mexicana, and pneumocystis carinii carinii.several pathogenic fungi and protozoa are known to have sterols distinct from those of their mammalian hosts. of particular interest as targets for drug development are the biosyntheses of the sterols of important parasites such as the kinetoplastid flagellates and the aids-associated opportunistic protist pneumocystis carinii. these pathogens synthesize sterols with an alkyl group at c-24, and some have a double bond at c-22 of the side chain. humans and other mammalian hosts are incapable of c ...19978980773
characterization of alpha-difluoromethylornithine resistant leishmania donovani and its susceptibility to other inhibitors of the polyamine biosynthetic pathway.the promastigote form of leishmania donovani is sensitive to growth inhibition by dl-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, exhibiting an ic50 of 125 microm. exposure of a wild type cell population to gradually increasing concentrations of dl-alpha-difluoromethylornithine resulted in the selection of a strain of leishmania, which was capable of proliferating in 5 mm dfmo with an ic50 value of 10 mm. this resistant strain showed increased ornithine de ...19968981555
amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized inhibitor of topoisomerase i from leishmania donovani.a meoh extract of swertia chirata found to inhibit the catalytic activity of topoisomerase i of leishmania donovani was subjected to fractionation to yield three secoiridoid glycosides: amarogentin (1), amaroswerin (2), and sweroside (3). amarogentin is a potent inhibitor of type i dna topoisomerase from leishmania and exerts its effect by interaction with the enzyme, preventing binary complex formation.19968984149
induction of macrophage killing of leishmania donovani by human cd4+ t cell clones.immunity in leishmaniasis is mediated by t cells, but protective responses in humans have not been fully defined. in this study, the functional activity of cd4+ t cell clones derived from an immune individual was investigated to identify potentially protective responses. the t cells proliferated and produced interferon-gamma (ifn-gamma) in response to a soluble leishmania donovani antigen extract and live amastigotes. there was considerable variation in the anti-leishmanial activity of the t cel ...19968987180
antigenic differences between axenic amastigotes & promastigotes of leishmania donovani.the axenic amastigotes of an indian strain of l. donovani have been generated from the promastigote form at 37 degrees c in rpmi-1640 medium, ph 6.0 +/- 0.5, supplemented with 10 per cent heat inactivated foetal calf serum and these are being maintained through serial subculturing under the same conditions. the present study was carried out to differentiate axenic amastigote from the promastigote stage on the basis of their antigenic constitution and also to look for any immunoreactive antigen(s ...19968996935
uptake and release of 2-aminoisobutyrate by leishmania donovani: culture-age dependent effects of osmolality and of protein kinase inhibitors.the rate of uptake of 2-aminoisobutyrate (aib), a non-metabolizable analogue of alanine, by leishmania donovani was investigated as a function of culture age and osmolality in the presence of protein kinase inhibitors and of glucose, glutamate or proline. hyperosmolality inhibited aib uptake by cells of both growth stages, but to a greater extent for log than for stationary cells. staurosporine, a protein kinase c inhibitor, had no effect on aib uptake by cells of either culture age, but it redu ...19969004489
cloning of a trypanosomatid gene coding for an ornithine decarboxylase that is metabolically unstable even though it lacks the c-terminal degradation domain.mammalian ornithine decarboxylase (odc) is among the most labile of cellular proteins, with a half-life of usually less than an hour. like other short-lived proteins odc is degraded by the 26s proteasome. its degradation is not triggered by ubiquitination, but is stimulated by the binding of an inducible protein, antizyme. truncations and mutations in the c terminus of mammalian odc have been shown to prevent the rapid turnover of the enzyme, demonstrating the presence of a degradation signal in ...19979012793
golgi gdp-mannose uptake requires leishmania lpg2. a member of a eukaryotic family of putative nucleotide-sugar transporters.the synthesis of glycoconjugates within the secretory pathway of eukaryotes requires the provision of lumenal nucleotide-sugar substrates. this is particularly important for eukaryotic microbes such as leishmania because they must synthesize considerable amounts of extracellular and cell surface glycoconjugates that play significant roles in the infectious cycle. here we used properly oriented sealed microsomes to characterize lumenal uptake of gdp-man in leishmania donovani. in this system, gdp ...19979013638
dual inhibition of dna topoisomerases of leishmania donovani by novel indolyl quinolines.omoindolyl)]ty of biologically active compounds contain indole and quinoline nuclei. a one step synthesis of some novel indolyl quinoline analogs e.g. 2-(2"-dichloro-acetamidobenzyl)-3-(3'-indolyl)-quinoline [1], 2-(2"-dichloroacetamido-5"-bromobenzyl)-3'-[3'-(5'-bromoindolyl ] -6-bromo quinoline [2], and 2-(2"-acetamido benzyl)-3-(3'-indolyl)-quinoline [3] has been developed under friedel-crafts acylation conditions. the compounds inhibit the relaxation and decatenation reactions catalysed by ...19979020039
the activities of four anticancer alkyllysophospholipids against leishmania donovani, trypanosoma cruzi and trypanosoma brucei.the in-vitro activities of four anticancer alkyllysophospholipids, et-18-och3 (edelfosine), hexadecylphosphocholine (miltefosine), ilmofosine and sri 62-834, were determined with ed50 values for leishmania donovani and trypanosoma cruzi amastigotes between 0.2 and 5.0 microm and for trypanosoma brucei trypomastigotes between 7.0 and 50.8 microm. in balb/c mice miltefosine and ilmofosine were the most active compounds with ed50 values of 2.9 and 14.5 mg/kg x 5 doses against l. donovani and a supp ...19969023651
cloning of genes and expression and antigenicity analysis of the leishmania infantum kmp-11 protein. 19979024210
migration of leishmania donovani amastigotes in the cerebrospinal fluid.a 10-year-old boy had been suffering from kala-azar (visceral leishmaniasis) for two and a half years. he failed to respond to all known anti-leishmanial treatment regimens. even the drastic step of splenectomy failed to cure him. in november 1991, he presented with symptoms of meningitis. a diagnostic lumbar puncture revealed leishmanial amastigotes in his cerebrospinal fluid. the patient was finally cured with a course of amphotericin b, a drug known to cross the blood-brain barrier.19969025693
effects of osmotic stress on metabolism, shape, and amino acid content of leishmania.an acute decrease in osmolality causes a rapid change in the shape of the parasitic protozoan leishmania donovani as determined by light microscopy and by flow cytometry. incubation of the cells is an isotonic buffer supplemented with glucose. 2-deoxyglucose (2-dg), alanine, or proline also causes a shape change, presumably due to the swelling caused by the water that accompanies these substrates as they are actively transported into the cells. hypo-osmolality also causes a rapid release of alan ...19969026223
heterologous protection by leishmania donovani for leishmania major infections in the vervet monkey model of the disease.the study was aimed at analyzing immunological cross-reactivity between leishmania major and leishmania donovani and possible cross-protection between the two parasite species in the vervet monkey model of the disease. nine vervet monkeys (cercopithecus aethiops) from the institute animal colony were sued in the study. five of the animals had been previously infected with l. donovani but had remained asymptomatic while the other four animals were naive and comprised the control group. immunologi ...19979030661
functional identification of a leishmania gene related to the peroxin 2 gene reveals common ancestry of glycosomes and peroxisomes.glycosomes are membrane-bounded microbody organelles that compartmentalize glycolysis as well as other important metabolic processes in trypanosomatids. the compartmentalization of these enzymatic reactions is hypothesized to play a crucial role in parasite physiology. although the metabolic role of glycosomes differs substantially from that of the peroxisomes that are found in other eukaryotes, similarities in signals targeting proteins to these organelles suggest that glycosomes and peroxisome ...19979032236
suppressor activity in leishmania donovani-infected hamster serum: reversion by delipidated bovine serum albumin and role in cell cycle events.visceral leishmaniasis, caused by leishmania donovani, is a chronic disease with a high mortality rate. this protozoan induces a serious dysfunction of the immune system characterized by suppression of the cellular response to parasite antigens. we provide evidence for the involvement of lipids in the immunological alterations of experimental leishmaniasis. sera obtained from 60-day-infected hamsters present increased triglyceride levels. inhibition of cell proliferation was observed when spleno ...19969033811
comparative studies on ifat, elisa & dat for serodiagnosis of visceral leishmaniasis in bangladesh.the purpose of the study was to estimate the specificity and sensitivity of different serological methods for the diagnosis of visceral leishmaniasis in bangladesh. blood samples from 155 suspected kala-azar patients together with 80 sick subjects and 50 healthy subjects from the endemic areas were collected. out of the 155 suspected kala-azar patients, bone marrow were collected from 126 patients. all bone marrow samples were examined by direct microscopy. 92 bone marrow samples were also exami ...19969037842
biochemical alterations in paromomycin-treated leishmania donovani promastigotes.paromomycin is used for the treatment of leishmaniasis in humans, but little is known about its mechanism of action. investigating the effect of this antibiotic on promastigotes of leishmania donovani, we showed that inhibition of the multiplication of these parasites could be related to its effect on rna synthesis and to modifications of membranous polar lipids and membrane fluidity, leading to altered membrane permeability.19979039704
visceral leishmaniasis without fever in a kidney transplant recipient. 19979041551
a c-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the escherichia coli ubie gene.strains of escherichia coli with mutations in the ubie gene are not able to catalyze the carbon methylation reaction in the biosynthesis of ubiquinone (coenzyme q) and menaquinone (vitamin k2), essential isoprenoid quinone components of the respiratory electron transport chain. this gene has been mapped to 86 min on the chromosome, a region where the nucleic acid sequence has recently been determined. to identify the ubie gene, we evaluated the amino acid sequences encoded by open reading frames ...19979045837
function of metal-ion homeostasis in the cell division cycle, mitochondrial protein processing, sensitivity to mycobacterial infection and brain function.a novel saccharomyces cerevisiae mutant, unable to grow in the presence of 12.5 mmol l-1 egta, was isolated. the phenotype of the mutant is caused by a single amino acid change (gly149 to arg) in the essential yeast cell division cycle gene cdc1. the mutant could be suppressed by overexpression of the smf1 gene, which codes for a plasma membrane mn2+ transporter. we observed that the yeast smf1 gene shares homology with the mouse nramp gene. nramp (bcg) was cloned as a gene responsible for mouse ...19979050240
protection of mice against visceral leishmaniasis by immunization with promastigote antigen incorporated in liposomes.leishmanial antigens (lag) were used as a vaccine against leishmania donovani, the causative agent of visceral leishmaniasis. balb/c mice, immunized intraperitoneally with 20 micrograms of the antigen in phosphate-buffered saline (pbs) or entrapped in liposomes, were infected intravenously with 2 x 10(7) l. donovani promastigotes. mice immunized with pbs and empty liposomes showed similar levels of parasite burdens in the liver and spleen. injection of the antigen alone or entrapped in liposomes ...19979057699
oronasal leishmaniasis caused by a parasite with an unusual isoenzyme profile.a 45-year-old sudanese man from western sudan presented with oronasal leishmaniasis of three years duration. he had no history of previous kala-azar or cutaneous leishmaniasis. the parasite isolated from the oral mucosa was characterized by isoenzymes using 12 enzymes and by polymerase chain reaction amplification of kinetoplast dna using species-specific primers. the specific primers gave products indistinguishable from those of the leishmania donovani complex. however, the isoenzyme profile sh ...19979063369
the plasma-membrane ca2+-atpase of leishmania donovani is an extrusion pump for ca2+.controlled exposure of leishmania donovani promastigotes to hypotonic shock results in the formation of deflagellated unsealed ghosts of original polarity that largely retain the pellicular microtubular structure associated with plasma membrane of the parasite. gentle shearing followed by suspension of the purified membrane in appropriate isotonic buffer containing mg2+ (4mm) results in the formation of sealed everted vesicles. the presence of mg2+ (4 mm) appears to be essential for efficient se ...19979078270
leishmania donovanib - knocking the door. 19959081956
ketoconazole in antimonial unresponsive cases of kala-azar. 19959081966
[postkala-azar dermal leishmaniasis]. 19979082890
the conserved serine-tyrosine dipeptide in leishmania donovani hypoxanthine-guanine phosphoribosyltransferase is essential for catalytic activity.crystal structures of hypoxanthine-guanine phosphoribosyltransferase (hgprt) proteins have implied that the translocation of a flexible loop containing a highly conserved ser-tyr dipeptide is necessary for the protection of the proposed oxocarbonium ion transition state of the enzyme (eads, j. c., scapin, g. t., xu, y., grubmeyer. c., and sacchettini, j. c. (1994) cell 78, 325-334; schumacher, m. a., carter, d., roos, d. s., ullman, b., and brennan, r. g. (1996) nature struct. biol. 3, 881-887). ...19979083019
effects of pentamidine on polyamine level and biosynthesis in wild-type, pentamidine-treated, and pentamidine-resistant leishmania.polyamine biosynthesis was studied in wild-type promastigotes of leishmania donovani and leishmania amazonensis treated with pentamidine and in the parasites resistant to this drug. treatment of wild-type clones with low pentamidine concentrations for 24 hr provoked a strong decrease in arginine, ornithine, and putrescine pools, while the level of intracellular spermidine remained unchanged. in these cells, the activity of the enzyme ornithine decarboxylase was found to be decreased. compared to ...19979085924
molecular and biochemical studies on the hypoxanthine-guanine phosphoribosyltransferases of the pathogenic haemoflagellates.all genera of protozoan parasites are auxotrophic for purines, and thus, purine acquisition from the host is a nutritional necessity for the survival and growth of these pathogens. many of these parasites, including trypanosoma brucei, trypanosoma cruzi and leishmania spp., access host purines by phosphoribosylating purine bases via purine phosphoribosyltransferase (prt) enzymes. the trypanosomatid hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzyme has been implicated as a critical en ...19979088991
rapd for the differentiation of leishmania. 19979093642
destruction of follicular dendritic cells during chronic visceral leishmaniasis.follicular dendritic cells (fdcs) play a pivotal role in the germinal center (gc) response and in the development and regulation of b lymphocytes. pathologic changes in gcs and a loss of fdcs have previously been noted in various viral infections, notably hiv-1. however, such changes have not been formally described in a chronic parasitic infection. in balb/c mice infected with leishmania donovani, parasites persist in the spleen for long periods, with associated splenomegaly. to examine the fat ...19979103448
intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-gamma gene-disrupted mice.despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-gamma (ifn-gamma) gene knockout (gko) mice infected with leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. this late-developing ifn-gamma-independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-alpha (tnf-alpha): l. donovani infection induced tnf-alpha mrna expression in parasitized gko livers and neutralization of tnf-alpha reve ...19979104810
duodenal leishmaniasis diagnosed by biopsy in two hiv-positive patients.we describe two cases of duodenal leishmaniasis in patients with human immunodeficiency virus (hiv) infection, diagnosed by light and electron microscopy. the patients presented nonspecific signs and symptoms, blood cultures were sterile, and serological tests for leishmania spp. were negative. endoscopy showed normal-appearing mucosa in one patient and possible peptic duodenitis in the other patient. in these patients, the parasite was only detected in a duodenal biopsy specimen. in view of the ...19979112272
behavior of visceral leishmania donovani in an experimentally induced t helper cell 2 (th2)-associated response model.although implicated in the clinical expression of human visceral leishmaniasis, a disease-exacerbating t helper cell 2 (th2)-associated immune response involving interleukin-4 (il-4) and/ or il-10 is not readily detectable in experimental visceral infection. to overcome this obstacle to analyzing visceral leishmania donovani in this relevant immunopathogenetic environment, we sought a model in which a th2 response induces noncuring infection. four initial approaches were tested primarily in balb ...19979120392
osteomyelitis and arthrosynovitis associated with leishmania donovani infection in a dog.a 10-month-old male maremma shepherd dog was presented with chronic diarrhoea, moderate polyuria/polydipsia, lethargy, dysorexia and stiffness. pain was elicited in the distal parts of all four limbs. radiographs of the limbs showed increased endomedullary radiopacity and lysis, with thick periosteal proliferations at the metadiaphyseal areas of each radius-ulna and tibia and of the distal metacarpus on one side. polyclonal hypergammaglobulinaemia was documented and a similar electrophoretic pro ...19979121132
epitope cleavage by leishmania endopeptidase(s) limits the efficiency of the exogenous pathway of major histocompatibility complex class i-associated antigen presentation.the activation of cd8+ t cell responses is commonplace during infection with a number of nonviral pathogens. consequently, there has been much interest in the pathways of presentation of such exogenous antigens for major histocompatibility complex class i-restricted recognition. we had previously shown that leishmania promastigotes transfected with the ovalbumin (ova) gene could efficiently target ova to the parasitophorous vacuole (pv), with subsequent recognition by class ii-restricted t cells ...19979130657
pleural and peritoneal leishmaniasis in an aids patient.the case of an aids patient who developed pleuritis and peritonitis in the course of relapsing visceral leishmaniasis is reported. visceral leishmaniasis, considered an opportunistic infection in patients infected with the human immunodeficiency virus (hiv) who live in endemic areas, has a chronic relapsing course. typical manifestations such as fever, hepatosplenomegaly, lymphadenopathy, weight loss, or pancytopenia are not specific in advanced hiv infection. atypical clinical presentations are ...19979131331
antileishmanial action of organometallic complexes of pt(ii) and rh(i).the three organometallic complexes [(cis-ptii (ddh) (2,5-dihidroxibenzensulfonic)2, rhi(co)2cl(2-aminobenzothiazole) and rhi(co)2cl(5-cl-2-methilbenzothiazole)] used in this study had been previously found to have a high in vitro activity against promastigote and amastigote like forms of leishmania donovani. here, the cytotoxic effect of these new organometallic complexes on the j-774 macrophages were studied. only the rhi(co)2cl(2-aminobenzothiazole) complex induced substantial toxicity in the ...19969137749
use of polymerase chain reaction-based single strand conformational polymorphism and denaturing gradient gel electrophoresis methods for detection of sequence variation of ribosomal dna of trypanosoma cruzi.polymerase chain reaction (pcr) was used to amplify the v1 region of the small sub-unit (18s) ribosomal dna gene from representative strains of trypanosoma cruzi. in order to screen for sequence variation, amplification products were subsequently analysed by single strand conformational polymorphism (sscp) and denaturing gradient gel electrophoresis (dgge) techniques. sscp could not detect sequence variation within t. cruzi, although electrophoretic profiles were clearly distinct from both leish ...19979138037
the isolation of leishmania donovani mon-18, from an aids patient in portugal: possible needle transmission.the spread of hiv infection into leishmaniasis endemic areas has increased the incidence of immunosupressed patients with kalaazar in portugal. the dermotropic zymodeme mon-24 of leishmania infantum has been already isolated from a portuguese aids patient, as in some other mediterranean countries. in this paper we report the isolation of l. donovani mon-18 from a drug addicted portuguese patient with clinical visceral leishmaniasis and aids, that suggests a mechanically transmitted infection by ...19949140504
Displaying items 1701 - 1800 of 5301