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influence of heat shock, drugs, and radiation on karyotype of leishmania major.leishmaniasis is one of the important tropical diseases in the world. although it is not prevalent in korea, imported cases have been recorded. the karyotype of leishmania sp. has been observed to be variable by localities or by strains, but the karyotype of a strain is known to be stable. this study was performed to observe if the karyotype of a leishmania sp. would be changed under some stressful conditions. the karyotype, analyzed by pulsed field gradient gel electrophoresis, was not grossly ...19938241087
recombinant leishmania surface glycoprotein gp63 is secreted in the baculovirus expression system as a latent metalloproteinase.a gene encoding the leishmania surface metalloproteinase, gp63, was modified using the polymerase chain reaction to obtain effective secretion of recombinant gp63 (regp63) in the baculovirus insect cell expression system. the coding region for the n-terminal signal peptide (sp) of gp63 was modified to resemble the sp for the gp67 envelope protein from the budded virus form of autographa californica nuclear polyhedrosis virus. to prevent processing at the c-terminus with a glycosyl phosphatidylin ...19938244034
a trypanosomal cchc-type zinc finger protein which binds the conserved universal sequence of kinetoplast dna minicircles: isolation and analysis of the complete cdna from crithidia fasciculata.replication of the kinetoplast dna minicircle light strand initiates at a highly conserved 12-nucleotide sequence, termed the universal minicircle sequence. a crithidia fasciculata single-stranded dna-binding protein interacts specifically with the guanine-rich heavy strand of this origin-associated sequence (y. tzfati, h. abeliovich, i. kapeller, and j. shlomai, proc. natl. acad. sci. usa 89:6891-6895, 1992). using the universal minicircle sequence heavy-strand probe to screen a c. fasciculata ...19938246992
leishmanin and tuberculin sensitivity in leishmaniasis in the sudan, with special reference to kala-azar.the application of leishmanin and tuberculin skin tests was studied in patients with leishmaniasis in the sudan. 35 cases of active kala-azar and 3 relapse cases were leishmanin negative. 81% of patients treated for kala-azar showed a positive reaction after 6 months. 17 of 29 patients with post kala-azar dermal leishmaniasis (pkdl) were leishmanin positive. 2 of 16 patients with kala-azar tested with tuberculin were positive; one was diagnosed as tuberculosis. in 7 initially tuberculin negative ...19938249072
epidemiology of cutaneous leishmaniasis at a focus monitored by the multinational force and observers in the northeastern sinai desert of egypt.a longitudinal epidemiologic study of cutaneous leishmaniasis (cl) transmission was conducted between july 1989 and june 1991 in a 1,200-km2 sector of the northeastern sinai desert monitored by the multinational force and observers (mfo), an international peace keeping mission between egypt and israel. the occurrence of human cases, sand fly density, rodent collection, and isolations of leishmania confirmed only one of four surveyed locations as a significant focus of cl transmission. phlebotomu ...19938250099
antiparasitic effects of nitric oxide in an in vitro murine model of chlamydia trachomatis infection and an in vivo murine model of leishmania major infection. 19948251567
interactions between leishmania major and macrophages. 19948251585
leishmania: immunochemical comparison of the secretory (extracellular) acid phosphatases from various species.promastigotes of all leishmania species, except most leishmania major stocks, synthesize and secrete extracellular soluble acid phosphatases [sacp(s)] which are capable of dephosphorylating a wide range of substrates and, consequently, of modifying the parasite environment. to assess their antigenic/structural relatedness, the sacp(s) from various species were compared immunochemically using both a monospecific rabbit antiserum and several monoclonal antibodies made against the purified promasti ...19938253156
heterogeneity of cysteine proteinases in leishmania braziliensis and leishmania major.sodium dodecyl sulfate-polyacrylamide gel electrophoresis (sds-page) with acrylamide copolymerized with gelatin (substrate-sds-page) was used to compare promastigote proteinases from two leishmania species (l. braziliensis and l. major-like). substrate-sds-page resolved at least 6 distinct proteinase activities with relative molecular masses between 20 and 65 kda. the profile of proteinase activity was the same for both species, although qualitative differences were observed. l. major-like expre ...19938257917
reversion to virulence in leishmania major correlates with expression of surface lipophosphoglycan.an attenuated clone of leishmania major was produced by chemical mutagenesis with n-methyl-n'-nitro-n-nitrosoguanidine and was biochemically characterized to determine the reason(s) for its loss of virulence. we found that the degree of virulence of l. major did not correlate with either the level of expression of promastigote surface protease (psp) or with the enzymatic activity of the molecule. in contrast, the levels of lipophosphoglycan (lpg) expressed by the attenuated clone were found to b ...19938264725
effective immunization against cutaneous leishmaniasis with recombinant bacille calmette-guérin expressing the leishmania surface proteinase gp63.leishmania parasites cause a spectrum of diseases that afflict the populations of 86 countries in the world. the parasites can survive within the lysosomal compartments of the host's macrophages, unless those macrophages are appropriately activated. despite the fact that protective immunity can be induced by vaccination with crude parasite preparations, little progress has been made toward a defined vaccine for humans. in this study the gene encoding the leishmania surface proteinase gp63 was cl ...19938265576
evaluation of the efficacy of iran leishmanin and comparison with leishmanins from wellcome (uk) and roma (italy) in cured cutaneous leishmaniasis patients. 19938266406
[disseminated cutaneous leishmaniasis in a case of an immunodepressed woman].the authors report a case of leishmania major leishmaniasis which occurred in a female kidney transplant recipient. in contrast with visceral leishmaniasis, disseminated cutaneous leishmaniasis seems to be exceptional in immunodepressed patients.19938279793
interleukin-2 suppresses activated macrophage intracellular killing activity by inducing macrophages to secrete tgf-beta.phorbol myristate acetate (pma) treatment of an el-4 thymoma cell line (el-4farrar) induced secretion of a factor that inhibited intracellular killing of leishmania major amastigotes by activated macrophages. analysis of the cytokines produced by el-4 cells after pma stimulation identified interleukin-2 (il-2, 2500 u/ml), il-4 (1280 u/ml), interferon-gamma (ifn-gamma; 100 u/ml), and granulocyte-macrophage colony-stimulating factor (gm-csf; 50 u/ml). neither tumor necrosis factor nor transforming ...19948283143
characterization of a leishmania antigen associated with cytoplasmic vesicles resembling endosomal-like structure.in the present study we have used antibodies to leishmania major promastigote antigens which were eluted from a glutathione-agarose column (lmgbp) and could identify several parasite components among different leishmania species by using immunoprecipitation and western blot techniques. the results also showed that some of lmgbp are present among the molecules released into the culture medium. moreover, immunofluorescence assays clearly demonstrated that lmgbp are expressed by intracellular amast ...19938295789
selective expansion of activated v delta 4+ cells during experimental infection of mice with leishmania major.previous work from this laboratory has revealed that infection of mice with leishmania major leads to an expansion of gamma delta+ t cells in the spleen. further examination of the gamma delta+ t cells expanding in infected mice has shown that the majority of these cells in the spleen, lymph nodes, blood and liver expressed the v delta 4 gene segment. cell cycle analysis, using propidium iodide incorporation, demonstrated that while only 1% of alpha beta+ t cells in the spleen were in either s + ...19948299701
mortality of leishmania major in phlebotomus papatasi caused by plant feeding of the sand flies.the plant feeding of phlebotomus papatasi and the effects of plant diets on the leishmania major infections were investigated. plant-fed flies had small free particles and membranous shreds in their gut that were stained by calcofluor as cellulosic plant tissues. they were found in 34.0% of the female and 14.3% of the male sand flies following feeding on the caper plant (capparis spinosa). no plant residues were found in 54 females that had been fed on plant-derived honeydew secretions of aphis ...19948304569
interferon-gamma and interleukin-4 in human leishmania donovani infections.clinical and immunological similarities between leishmania donovani infections in humans and l. major infections in mice suggest that some of the pathophysiological mechanisms are the same in the two conditions. both infections can result either in a fatal systemic disease or in a self-limiting infection with few and mild symptoms. in the murine model the outcome of the infection is critically related to the cytokines produced by t lymphocytes activated by leishmanial antigens. activation of the ...19938314285
molecular cloning and expression of a leishmania major gene encoding a single-stranded dna-binding protein containing nine "cchc" zinc finger motifs.the genes encoding gp63, the major surface glycoprotein of the protozoan parasite leishmania, are highly conserved across diverse species of leishmania both within the protein coding region and in the immediate 5'-untranslated region. located between the 3' trans-spliced leader acceptor site and the translational initiation codon of the gp63 gene is an area of conserved hexanucleotide direct repeats (ctcgcc) which vary in number according to species. to determine whether these repeats represent ...19938314766
expression of a mitochondrial stress protein in the protozoan parasite leishmania major.the dna sequence has been determined of a gene from leishmania major that shares sequence identity with members of the eukaryotic heat shock protein (hsp) 70 gene family. the deduced open reading frame for translation shares a number of features common to hsp70 stress proteins, including conserved amino acids implicated in atp binding and a putative calmodulin-binding site. in addition, the protein has an n-terminal sequence characteristic of a mitochondrial targeting signal. specific antibodies ...19938314893
[the virulence and cytochemical properties of leishmania major during long-term cultivation].it has been shown that morphogenesis of leishmania major in each culture passage is characterised by the depletion of rna and increase in its dispersion degree, by the change of the nadp-h-diaphorese, peroxidase and janus green-b-oxidative activity in the promastigotes. cytochemical peculiarities of invasive metacyclic promastigotes are an extreme depletion of rna, its disperse form, a low activity of oxidative enzymes. this properties may manifest the pre-adaptation of leishmania promastigotes ...19938321558
langerhans cells transport leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific t cells.murine epidermal langerhans cells (lc) have been shown to internalize leishmania major, a cause of human cutaneous leishmaniasis, and to stimulate a vigorous parasite-specific t cell response. the present study emphasizes the critical role of lc in leishmaniasis by documenting directly that lc have the ability to transport l. major from the skin to the draining lymph node (ln). this was revealed by irreversible labeling of lc with a fluorescent cell linker and in vivo tracking. in contrast, no m ...19938325337
interleukin-4 but not gamma interferon production correlates with the severity of murine cutaneous leishmaniasis.for murine cutaneous leishmaniasis, data to date suggest a correlation between the presence of gamma interferon (ifn-gamma) and resistance in c57bl/6 mice and the presence of interleukin-4 (il-4) and disease in balb/c mice. in this study, 13 inbred strains of mice covering the range of susceptibility to disease were infected with leishmania major to determine whether the subsequent expression of ifn-gamma or il-4 is a reliable indicator of cure or progressive disease. the presence of il-4 and if ...19938335376
gamma interferon response in secondary leishmania major infection: role of cd8+ t cells.cd8+ t cells have been shown to contribute to the rapid resolution of secondary lesions developing in immune mice challenged with leishmania major. in the present study, we assessed directly the participation of specific cd8+ t cells in the memory response induced in immune mice by reinfection. lymphocyte populations from reinfected immune mice exhibit marked secondary gamma interferon (ifn-gamma) responses. the participation of ifn-gamma-producing cd8+ t cells in the memory response elicited by ...19938359894
interleukin-7 enhances antimicrobial activity against leishmania major in murine macrophages.recently, it has been shown that interleukin-7 (il-7) is able to induce secretion of cytokines and tumoricidal activity by human monocytes. this study shows that treatment of murine macrophages infected with leishmania major with il-7 without any other stimulus reduced the percentage of infected cells, as well as the parasite burden per cell, in a dose-dependent manner to a limited degree (45% reduction of the number of amastigotes per 100 macrophages). simultaneous treatment of macrophages with ...19938359927
the structure of leishmania major amastigote lipophosphoglycan.intracellular amastigotes of leishmania major produce 6 x 10(4) copies/cell of a lipophosphoglycan (lpg) that is structurally distinct from the lpg produced by the extracellular promastigote form of l. major, leishmania donovani, and leishmania mexicana (reviewed by mcconville, m. j. (1991) cell biol. int. rep. 15, 779-798). l. major amastigote lpg is composed of a lysoalkyl phosphatidylinositol lipid anchor that links via a diphosphorylated hexasaccharide core to a phosphoglycan (6-100 kda). th ...19938360147
life cycle of leishmania major (kinetoplastida: trypanosomatidae) in the neotropical sand fly lutzomyia longipalpis (diptera: psychodidae).the development of leishmania major yakimoff & schokhor in the new world sand fly lutzomyia longipalpis (lutz & neiva) was examined by light and electron microscopy. in this unnatural host, parasites differentiated into 10 typical morphological forms, multiplied at three sites, migrated anteriorly and established in the foregut, and attached to gut surfaces. in the blood meal, amastigotes divided and transformed into two successive dividing, stumpy promastigote stages. elongate nectomonad promas ...19938360894
interleukin-4 and interleukin-10 synergize to inhibit cell-mediated immunity in vivo.the lack of cell-mediated (th1-like) immunity that is often associated with strong humoral immune responses is thought to be due in part to the inhibition of th1 effector function by the th2-derived cytokine interleukin-10 (il-10). this hypothesis, however, is based entirely on results from in vitro studies, wherein il-10 has been shown to inhibit th1 cytokine synthesis. in this study we have compared the regulatory effects of both il-4 and il-10 on the development of a more complex th1 effector ...19938370402
natural killer cells participate in the early defense against leishmania major infection in mice.in this study the role of natural killer (nk) cells in the course of experimental leishmania major infection was investigated. nk cells in genetically resistant c57bl/6 mice were depleted by in vivo administration of anti-asialo-gm1 or anti-nk1.1 antibodies. a marked exacerbation of the infection was found in the nk-depleted mice within the first two weeks of infection. both the local tissue swelling and the number of parasites in the lesions were significantly higher than in normal animals. lym ...19938370404
identification and genetic comparison of leishmanial parasites causing viscerotropic and cutaneous disease in soldiers returning from operation desert storm.six leishmania major and seven l. tropica parasites were isolated and identified from participants in operation desert shield/storm. a complete enzyme analysis (21 enzymes) revealed that there was enzyme polymorphism among the isolates of each species group. any one desert storm l. major isolate could differ from any other for 1-3 enzymes, and any l. tropica isolate could differ from any one other for up to eight enzymes. enzyme polymorphism data from other l. major and l. tropica isolates from ...19938372957
effects of sinefungin on growth and sterol composition of leishmania promastigotes.the s-adenosylmethionine analogue sinefungin was tested in vitro against promastigotes of various strains of leishmania. the ic50 values for the leishmania mexicana, leishmania major, and leishmania donovani strains used were of the order of 10 ng/ml but the leishmania amazonensis strain tested was more resistant to the drug, the ic50 value being 6 micrograms/ml. sterol profiles, in which 24-alkyl (c28) sterols predominated, were relatively unaffected by sinefungin. incorporation of label derive ...19938375483
leishmania major in meriones sacramenti thomas 1922 in nakhel, north sinai, egypt.leishmania major is a protozoal parasite of desert and savanna rodents, the vectors being mainly phlebotomus (phlebotomus) papatasi and very closely related species. man in an incidental host, in whom usually it causes zoonotic cutaneous leishmaniasis. in this paper, spot light survey was carried out in nakhel to identify the role of animal reservoir(s) where a sudden outbreak occurred in nakhel center. the trapped rodents were m. musculus, meriones sacramenti and gerbillus pyramidum. three isol ...19938376854
leishmania major infection in balb/c mice: protection or exacerbation by treatment with different doses of bcg.the effect of live bacillus calmette-guérin (bcg), administered intraperitoneally to balb/c mice, upon the development of lesions induced by subcutaneous infection with leishmania major was examined. lesions in mice given 10(7) bcg colony-forming units (cfu) 9 days before challenge with l. major were less severe and contained significantly fewer parasites than those of similarly infected control mice not given bcg. this effect of treatment with high doses of bcg upon the development of leishmani ...19938378590
experimental cutaneous leishmaniasis: langerhans cells internalize leishmania major and induce an antigen-specific t-cell response. 19938379429
plasticity in chromosome number and testing of essential genes in leishmania by targeting.we attempted to generate homozygous dhfr-ts (dihydrofolate reductase-thymidylate synthase) knockouts in virulent leishmania major, an asexual diploid protozoan parasite. transfection of a neo (neomycin phosphotransferase) targeting fragment yielded heterozygous replacement lines with high efficiency. however, second transfections with a hyg (hygromycin b phosphotransferase) targeting fragment in the presence of metabolites shown to rescue homozygous knockouts in attenuated leishmania did not yie ...19938381972
unusually extensive disease caused by leishmania major parasites.simple cutaneous leishmaniasis (cl), which is endemic in several areas of israel, is usually caused by leishmania major. cl, which is caused by replication of parasites within dermal macrophages, is self-limited and almost always confined to the skin. we recently encountered two cases of cl in which skin defenses were breached and lesions appeared in subcutaneous locations. in one case, abnormal cell-mediated immune function was detected. the purpose of this article is to present these data and ...19938382568
sequence of a leishmania major gene encoding an ubiquitin fusion protein.a gene encoding an ubiquitin-tail protein fusion was isolated from the parasitic protozoan, leishmania major, and sequenced. the l. major tail protein shares 97, 96, 67, 62, 62 and 61% sequence identity with the tail proteins of trypanosoma brucei, trypanosoma cruzi, yeast, dictyostelium discoideum, human, and arabidopsis thaliana, respectively. the putative 'zinc finger' nucleic acid-binding domain found in all ubiquitin 'tail' or 'extension' proteins described is also conserved in the l. major ...19938396548
resistance of mice to experimental leishmaniasis is associated with more rapid appearance of mature macrophages in vitro and in vivo.resistance to murine leishmaniasis has been related to the propagation of specific th cell subsets (th1 and th2). this study shows that there are differences between resistant and susceptible mice in the initial myelomonocytic infiltrate, which precede the specific t cell response. after subcutaneous injection of 2 x 10(7) leishmania major into footpads of resistant c57bl/6 and susceptible balb/c mice we performed immunohistochemical studies on the infiltrate. two days after infection the percen ...19938409447
ifn-gamma produced in vivo during the first two days is critical for resolution of murine leishmania major infections.resolution of murine infection with leishmania major is dependent upon the presence of ifn-gamma during the first week of infection. to more precisely determine the period during which ifn-gamma is critical, we infected footpads of resistant c3h/hen mice with amastigotes of l. major and treated these mice with neutralizing monoclonal ab (mab) specific for ifn-gamma on successive days. mice treated with anti-ifn-gamma mab on or before day 2 had significantly enlarged lesions, and increased parasi ...19938412622
[the virulence, metacyclogenesis and respiratory enzymes of leishmania isolated in culture from laboratory animals].it has been shown that an increase of virulence of leishmania major, l. tropica, l. braziliensis as a result of passing through animals and its decrease during the cultivation are accompanied by certain changes of biochemical characteristics of these promastigotes. in the former case the activity of nadp-h-diaphorase and peroxidase of promastigotes and their ability to be transformed into final (invasional) metacyclic forms increase and in the latter case these characteristics decrease. the leve ...19938414649
identification of truncated forms of lipophosphoglycan in mutant cloned lines of leishmania major that are deficient in mature lipophosphoglycan. 19938415552
influence of leishmania infection on blood-meal digestion in the sandflies phlebotomus papatasi and p. langeroni.the presence of amastigote-initiated infections of leishmania major parasites caused a significant suppression in alkaline protease, trypsin and aminopeptidase activity during the first 30 h after ingestion of the infected bloodmeal in phlebotomus papatasi, the natural vector of l. major. protease levels were significantly higher in infected flies after 72 h than in the control group, where digestion had ceased. evidence for the suppression of protease activity in infected p. langeroni, a sympat ...19938415565
reconstitution of c.b-17 scid mice with balb/c t cells initiates a t helper type-1 response and renders them capable of healing leishmania major infection.c.b-17 scid mice, which were found to be very susceptible to infection with leishmania major, were reconstituted with various doses of t cells, t plus b cells or unfractionated spleen cells from nonhealer balb/c mice. all reconstitution protocols, except for the transfer of very high numbers of balb/c spleen cells, led to a spontaneously healing infection and resistance to reinfection, rather than the lethal, nonhealing infection typical of balb/c mice. these healing responses were associated wi ...19938419179
a role for gamma delta + t cells during experimental infection of mice with leishmania major.to assess the importance of gamma delta + t lymphocyte responses in experimental murine cutaneous leishmaniasis, the expression of gamma delta + tcr on the surface of lymphocytes in spleen and draining lymph nodes of mice infected with leishmania major was examined. in both susceptible balb/c and resistant cba/j mice, an increase in gamma delta + t cells was observed after s.c. infection. whereas in chronically infected balb/c mice, these cells can represent up to 35% of the cd3+ cells in the sp ...19938419488
parasitism of epidermal langerhans cells in experimental cutaneous leishmaniasis with leishmania major.murine epidermal langerhans cells (lc) have been demonstrated to stimulate a vigorous t cell response to leishmania major, a cause of human cutaneous leishmaniasis. it was therefore of interest to analyze whether lc can take up viable parasites. epidermal cells were obtained from mouse ear skin for incubation with l. major and subsequent detection of intracellular parasites by cytochemistry. freshly isolated lc, but not cultured lc, phagocytosed l. major and the uptake was inhibited by antibodie ...19938421175
identification of two distinct cysteine proteinase genes of leishmania pifanoi axenic amastigotes using the polymerase chain reaction.a developmentally regulated cysteine proteinase associated with an unique lysosomal organelle, the megasome, has been described for the intracellular amastigotes of the leishmania mexicana complex; this proteinase appears to be important in the survival of the parasite. degenerate primers encoding the active sites residues have been used to amplify cysteine proteinase cdna sequences from axenically cultured amastigotes of leishmania pifanoi, a member of the l. mexicana complex. based on sequence ...19938426606
leishmania donovani-reactive th1- and th2-like t-cell clones from individuals who have recovered from visceral leishmaniasis.infections in humans by leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (vl), or in a self-limiting asymptomatic infection. in murine models of the infection employing leishmania major, the course of the disease can be directed into a vl-like syndrome by interleukin-4 (il-4)-producing th2 cells, or cure may result by th1 cells secreting gamma interferon (ifn-gamma). the present study examined the potential of human t cells to generate th1 or th2 responses to l ...19938432588
interleukin-4 transgenic mice of resistant background are susceptible to leishmania major infection.the outcome of cutaneous leishmaniasis is dependent on the balance of th1 and th2 cells. in the murine model, th1 cells are host-protective whereas the th2 cells are disease-promoting. however, the in vivo role of interleukin-4 (il-4), a signature product of th2 cells, is uncertain. we compared the course of leishmania major infection in the genetically resistant 129/sv mice and the mutant 129/sv mice transgenic for the murine il-4 gene under the control of the immunoglobulin heavy chain enhance ...19938436188
leishmania major interferes with antigen presentation by infected macrophages.impairment of the ag-presenting capacity of macrophages harboring intracellular leishmania might represent one of the several mechanisms by which these parasites can evade host-protective t cell responses. thus, the present study was designed to investigate the ability of macrophages, parasitized with leishmania major, to present ag to relevant t cell hybridomas. results show that bone marrow-derived macrophages from balb/c mice, after infection with l. major, have a greatly reduced capacity to ...19938436821
vaccine development against cutaneous leishmaniasis. subcutaneous administration of radioattenuated parasites protects cba mice against virulent leishmania major challenge.experiments described in this paper were aimed at determining whether subcutaneous inoculation of live, avirulent leishmania major would protect mice against infection by the virulent parasite. to this effect, promastigotes or amastigotes of a highly virulent strain of l. major (mrho/ir/76), used in human trials of leishmanization, and which induces non-healing skin lesions in both cba and balb/c mice, were rendered non-pathogenic by gamma irradiation. a dose of 150 krad was required to abrogate ...19938446467
pure protein from leishmania donovani protects mice against both cutaneous and visceral leishmaniasis.a protein purified from leishmania donovani promastigotes, dp72, was shown to partially protect balb/c mice against a challenge by this parasite. immunized mice infected i.v. with 10(7) l. donovani promastigotes showed a 0, 60, and 78% reduction in liver parasite burden compared with the control mice at each time point examined after challenge, 1, 20, and 108 days, respectively. western blotting demonstrated that the sera from the immune mice, which reacted specifically with dp72 in lysates of l ...19938450215
th1 and th2 cell antigen receptors in experimental leishmaniasis.the complexity and chronicity of parasitic infections have obscured the identification of biologically relevant antigens. analysis of the t cell receptor repertoire used by mice infected with leishmania major revealed the expansion of a restricted population of cd4+ cells. these cells expressed the v alpha 8-j alpha ta72, v beta 4 heterodimer in both progressive infection and protective immunity and across several major histocompatibility haplotypes. thus, the same immunodominant parasite epitop ...19938451641
comparison of receptors required for entry of leishmania major amastigotes into macrophages.we investigated the mechanisms of entry of amastigotes of leishmania major from two different sources into macrophages by comparing their use of the fc receptor (fcr), complement receptor type 3 (cr3), and mannose-fucose receptor (mfr). amastigotes were obtained from balb/c mice and scid mice. fcr involvement was examined by opsonizing l. major with parasite-specific immunoglobulin g (igg). antiparasite igg did not alter the uptake of amastigotes from balb/c mice since these amastigotes had anti ...19938454363
expression of lipophosphoglycan, high-molecular weight phosphoglycan and glycoprotein 63 in promastigotes and amastigotes of leishmania mexicana.the abundant surface glycoconjugate of leishmania promastigotes, lipophosphoglycan (lpg), forms a blue-colored complex (lambda max = 649 nm) with the cationic dye stains-all, which can be quantitated densitometrically on polyacrylamide gels of cell lysates. promastigotes of leishmania mexicana, leishmania major and leishmania donovani yield values of 1-3 x 10(6) lpg molecules cell-1. in amastigotes the lpg content is down-regulated below the detection limit (< 10(3) molecules cell-1) in l. mexic ...19938459823
leishmania differentiation in natural and unnatural sand fly hosts.leishmania differentiation in the gut of phlebotomine sand flies was evaluated based on five light and electron microscopic studies of natural (leishmania panamensis/lutzomyia gomezi, leishmania chagasi/lutzomyia longipalpis) and unnatural (leishmania mexicana/lutzomyia abonnenci, leishmania panamensis/phlebotomus papatasi, leishmania major/lutzomyia longipalpis) life cycles. in the bloodmeal, transformation of amastigotes into stumpy promastigotes occurred before or during division. further div ...19938461893
phlebotomus (phlebotomus) duboscqi (diptera: phlebotominae), naturally infected with leishmania major in southern ethiopia.in a survey of leishmania infections in phlebotomine sandflies in visceral leishmaniasis focus at aba roba, segen valley, southern ethiopia, phlebotomus duboscqi was found naturally infected with l. major (zymodeme mon-74). this is the first isolation of l. major from a vector sandfly in ethiopia, from an area where human and/or rodent infections with l. major are, so far, unknown.19938465376
il-2 is necessary for the progression of leishmaniasis in susceptible murine hosts.balb/c mice are highly susceptible to disseminated infection with the intracellular protozoa leishmania major. progression of disease requires in vivo expansion of th2 cd4+ lymphocytes and is reversed by treatment with anti-il-4 monoclonal antibody. inasmuch as il-2 may be necessary for both the production of il-4 and differentiation of th2 cells, the possible contribution of il-2 to progressive infection was examined. four weekly injections of anti-il-2 mab (s4b6) cured more than 80% of balb/c ...19938473741
characterization of a surface metalloprotease from herpetomonas samuelpessoai and comparison with leishmania major promastigote surface protease.the monogenetic kinetoplastid protozoan parasite herpetomonas samuelpessoai expresses a surface-exposed metalloprotease. comparable to the leishmania promastigote surface protease, or psp, the protease of herpetomonas is active at the surface of fixed and live organisms, and both enzymes display an identical cleavage specificity toward a nonapeptide substrate. the protease was enriched 440 times by partition into triton x-114 followed by 2 steps of anion exchange chromatography. the 56-kda enzym ...19938479451
effects of qinghaosu (artemisinin) and its derivatives on experimental cutaneous leishmaniasis.we have investigated the effect of qinghaosu (qhs, artemisinin) and its derivatives on leishmania major replication in vitro and on the disease development in mice infected with l. major. artemisinin is effective against promastigotes in vitro, with an ed50 (50% effective dose) at 7.5 x 10(-7) m. both artemisinin and artemether are leishmanicidal for amastigotes in infected murine macrophages in vitro, with ed50 at 3 x 10(-5) m and 3 x 10(-6) m respectively. these compounds have no effect on the ...19938479804
[in vitro study of leishmanicidal agents with drug carriers].antileishmanial chemotherapy is hampered by the location of parasites within lysosomal vacuoles of the macrophages which restricts the bioavailability of many potential antileishmanial compounds. in this study, the effectiveness of pentamidine targeted to the infected cells by a linkage to a colloidal drug carrier, methacrylate polymer nanoparticles was explored. in the same way, polyisoalkylcyanoacrylate nanospheres which have, in vitro, trypanolytic properties were also tested. the study was p ...19938494298
induction of macrophage parasiticidal activity by staphylococcus aureus and exotoxins through the nitric oxide synthesis pathway.murine peritoneal macrophages stimulated in vitro with killed gram-positive bacteria staphylococcus aureus or its membrane components in the presence of interferon-gamma (ifn-gamma) expressed high levels of nitric oxide (no) synthase and produced large amounts of no in a dose-dependent manner. this is not due to the contamination by gram-negative endotoxin because the stimulatory activity was not affected by the addition of polymyxin b. the expression of the no synthase and the synthesis of no b ...19938495974
immunological analysis of the zinc-binding peptides of surface metalloproteinase (gp63) of leishmania major.the surface metalloproteinase, gp63, is highly conserved and immunogenic. a peptide spanning the zinc-binding region of the molecule is immunogenic and can induce protective immunity in mice against leishmania major infection. we report here that the minimum length of the immunogenic peptide in this region is a heptapeptide, vvthema, corresponding to residues 161-167. optimal immunogenicity is conferred by a decapeptide, lvtvvthema, corresponding to residues 158 to 167, where h and e are consens ...19938495977
coupling of poly(a) site selection and trans-splicing in leishmania.intergenic regions of polycistronic pre-mrnas of trypanosomatid protozoans are the sites of two processing reactions: polyadenylation of the upstream gene and trans-splicing of the capped miniexon to the downstream gene. their close proximity and the lack of consensus motifs at poly(a) sites led us to test whether poly(a) site selection is governed by the location of the downstream splice acceptor in the dhfr-ts locus of leishmania major. whenever the position of the downstream splice site was a ...19938504937
leishmania major: respiratory burst response of infected murine macrophages treated with paromomycin.the effect of paromomycin sulfate (pr) on the respiratory burst response (rb) of c3h/hej mouse peritoneal macrophages infected with leishmania major, lrc-l137, was studied in vitro. giemsa staining and acridine orange staining combined with nitro blue tetrazolium (nbt) reduction reaction were used to determine parasite survival and rb response at the level of individual cells. rb response was detected in only 18% of the infected macrophages compared with 60% of the control, uninfected cells. onl ...19938513874
immune responses associated with susceptibility of c57bl/10 mice to leishmania amazonensis.leishmaniae are protozoans which, depending upon both the host and parasite species, can cause either a healing or nonhealing infection. while c57bl/10 mice are able to heal following infection with leishmania major, they fail to heal following infection with leishmania amazonensis. in order to address the role of th1 and th2 cell responses in the outcome of these infections in c57bl/10 mice, gamma interferon (ifn-gamma) and interleukin-4 (il-4) production was assessed. while cells from l. major ...19938514400
leishmania antigens presented by gm-csf-derived macrophages protect susceptible mice against challenge with leishmania major.leishmania major, a causative agent of leishmaniasis, in humans is also capable of infecting mice. several strains of mice, including the balb/c strain, are unable to mount appropriate t cell responses to the parasite and develop a fatal, disseminated infection. we present evidence that injection of granulocyte-macrophage-csf derived bone marrow macrophages (gmm phi), previously incubated with l. major antigens, into balb/c mice before infection, induced a th1-dominated response and subsequent h ...19938515072
herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans.leishmaniasis is a major tropical disease for which current chemotherapies, pentavalent antimonials, are inadequate and cause severe side effects. it has been reported that trifluralin, a microtubule-disrupting herbicide, is inhibitory to leishmania amazonensis. in this study, the in vitro effect of trifluralin on different species of trypanosomatid protozoans was determined. in addition to l. amazonensis, trifluralin is effective against leishmania major and leishmania tropica, which cause cuta ...19938516314
molecular karyotype characterization of leishmania panamensis, leishmania mexicana, and leishmania major-like parasites: agents of cutaneous leishmaniasis in ecuador.molecular karyotypes of leishmania isolates from patients with cutaneous leishmaniasis in ecuador were analyzed by pulsed-field gel electrophoresis (pfge) and southern blot hybridization. the dna karyotypes of l. major-like parasites were similar between two human isolates from a lowland coastal and a highland andean region, but were apparently different from those of eleven world health organization reference strains including l. major. the smallest chromosome of 240 kilobases in l. major-like ...19938517490
9-anilinoacridines as potential antileishmanial agents.a number of 1'-substituted 9-anilinoacridines were evaluated for their activities against promastigote and amastigote forms of leishmania major and for their toxicities to human jurkat leukemia cells. several compounds possessing 1'-nh-alkyl substituents produced more than 80% growth inhibition of macrophage-infected l. major amastigotes at or below a concentration of 1 microm. 1'-hexylamino-9-anilinoacridine (compound 14) was the least toxic compound to human jurkat cells, while it retained str ...19938517726
leishmania major and toxoplasma gondii have opposite effects on cytokine synthesis by macrophages. 19948524067
concomitant natural infection with l. donovani and l. major: a case report from iraq.this is a case report of kala-azar with cutaneous leishmaniasis. upon admission, the patient had fever, hepatosplenomegaly and an ulcer on her cheek. the patient responded to pentostam. isoenzyme studies of parasite isolates from the bone marrow and from the cutaneous lesion revealed that these were l. donovani and l. major, respectively. this is the first report in iraq of a proven concomitant infection with two species of leishmania parasites.19958525713
processing and presentation of protein and parasite-derived antigens by 4f7+ dendritic cells. 19958526063
dendritic cells seclude leishmania parasites that persist in cured mice--a role in the maintenance of t-cell memory? 19958526129
[spontaneous course of lesions of leishmania major cutaneous leishmaniasis in tunisia].the evolution of zoonotic cutaneous leishmaniasis (zcl) caused by l. major, was usually described with crosssectional studies of patients under anti-leishmanial drugs. this work aimed to describe the clinical and parasitological status by a follow-up study of patients with zcl and treated with a placebo.19958526421
leishmania major mon-26 isolated from naturally infected phlebotomus papatasi (diptera: psychodidae) in isfahan province, iran.in a survey of leishmania infections in phlebotomine sandflies in one of the most important focus of zoonotic cutaneous leishmaniasis (zcl) at borkhar, a rural district north of the city of isfahan, central iran, phlebotomus (phlebotomus) papatasi scopoli from gerbil and jird burrows were naturally infected with leishmania major zymodeme mon-26. this is the first isolation and characterization of l. major from p. papatasi in iran, from an area where human and rodent infections with l. major have ...19958533663
incrimination of phlebotomus papatasi as vector of leishmania major in the southern jordan valley.the status of sandflies as vectors of cutaneous leishmaniasis in the southern jordan valley was investigated during 1992. sandflies were collected from domestic habitats and from burrows of psammomys obesus. of 686 phlebotomus papatasi females collected from burrows, fourteen harboured promastigotes in their guts. on the other hand, none of 1446 p.papatasi females collected from domestic habitats were found infected. the highest infection rate (5.5%) was recorded in november at the end of the sa ...19958541595
pregnancy impairs resistance of c57bl/6 mice to leishmania major infection and causes decreased antigen-specific ifn-gamma response and increased production of t helper 2 cytokines.resolution of cutaneous leishmaniasis in infected mice is associated with a polarized th1 immune response by the host, whereas maternal immune responses during pregnancy appear to be biased toward humoral (th2) and away from cell-mediated (th1) responses. the objective of this study was to evaluate whether the putative th2 bias in pregnant c57bl/6 mice would impair their normal ability to mount a curative th1 response against leishmania major infection. pregnant c57bl/6 mice developed larger cut ...19968543816
t helper 1 response against leishmania major in pregnant c57bl/6 mice increases implantation failure and fetal resorptions. correlation with increased ifn-gamma and tnf and reduced il-10 production by placental cells.maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. the th1 cytokines ifn-gamma and il-2 can cause fetal loss, whereas the th2 cytokine il-10 is protective. however, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a th1 response, whereas a th2 response exacerbates the disease. we therefore asked whether the curative th1 response against leishmania major ...19968543817
inhibition of hiv-1-induced syncytia formation and infectivity by lipophosphoglycan from leishmania.in hiv-1 infection, the appearance of syncytia-inducing (si) isolates is associated with a more rapid decline of cd4+ cells and progression to aids. agents that inhibit either virus infection or syncytia formation have the potential to be therapeutically useful. lipophosphoglycan (lpg), the major glycoconjugate of leishmania, was recently shown to be a potent nonspecific inhibitor of viral membrane fusion. in this study, lpg demonstrated a dose-dependent inhibition of hiv-1-induced syncytia form ...19958548328
lack of inducible nitric oxide synthase activity in t cell clones and t lymphocytes from naive and leishmania major-infected mice.nitric oxide (no) generated by the inducible isoform of nitric oxide synthase (inos) is implicated in a number of immunological processes including killing of intracellular parasites, suppression of t cell proliferation, production of cytokines and destruction of tissue in autoimmune diseases. considering that cytokine-activated mouse macrophages, fibroblasts and endothelial cells are potent producers of no, we investigated whether t cells, as central participants in immune responses, can also b ...19958566005
in susceptible mice, leishmania major induce very rapid interleukin-4 production by cd4+ t cells which are nk1.1-.susceptibility of balb/c mice to infection with leishmania major is associated with a t helper type 2 (th2) response. since interleukin-4 (il-4) is critically required early for th2 cell development, the kinetics of il-4 mrna expression was compared in susceptible and resistant mice during the first days of infection. in contrast to resistant mice, susceptible mice exhibited a peak of il-4 mrna in their spleens 90 min after i.v. injection of parasites and in lymph nodes 16 h after s.c. injection ...19958566015
characterization of the immunological memory state generated in mice susceptible to leishmania major following exposure to low doses of l. major and resulting in resistance to a normally pathogenic challenge.balb/c mice are susceptible to a high-dose infection of the protozoan leishmania major, which induces a parasite-specific antibody, th2-like response, exclusive of a significant and protective cell-mediated th1 component. we have shown, in contrast, that infection with a low number of parasites induces cell-mediated immunity exclusive of antibody production, and results in resistance to substantial subsequent high-dose infection. low-dose exposure thus constitutes effective vaccination. in the p ...19968566074
effect of il-7 treatment on leishmania major-infected balb.xid mice: enhanced lymphopoiesis with sustained lack of b1 cells and clinical aggravation of disease.the xid immunodeficiency was characterized by a total lack of b1 cells and reduced numbers and functions of b2 cells. in balb.xid mice, this defect results in an reduced susceptibility against infections with parasites such as trypanosoma cruzi and leishmania major. since il-7 acts on the b cell compartment by stimulation of pre-b cell proliferation, we analyzed the effect of recombinant il-7 on l. major infection in balb.xid mice. after application of a single dose of il-7 simultaneously with t ...19958580086
leishmania susceptibility puzzle gets another twist. 19968584928
genetic susceptibility to leishmania: il-12 responsiveness in th1 cell development.the genetic background of t lymphocytes influences development of the t helper (th) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as leishmania major. with an in vitro model system, a difference in maintenance of responsiveness of t cells to interleukin-12 (il-12) was detected between balb/c and b10.d2 mice. although naive t cells from both strains initially responded to il-12, balb/c t cells lost il-12 responsiveness after stimulation wit ...19968584935
susceptibility to leishmania major infection in interleukin-4-deficient mice.interleukin-4 (il-4), a pleiotropic cytokine, is a major regulator of the immune system and is considered crucial for the development of t helper cell type 2 (th2) responses. the susceptibility of balb/c mice to infection with leishmania major has been associated with a polarized th2 response and an inability to down-modulate il-4 production. the role of il-4 in vivo was examined directly by disrupting the il-4 gene in balb/c embryonic stem cells. despite the absence of il-4, the genetically pur ...19968584936
the gene b protein localises to the surface of leishmania major parasites in the absence of metacyclic stage lipophosphoglycan.the stage specific gene b protein (gbp) of leishmania major localises to the surface of infective metacyclic parasites, where it associates with the developmentally regulated surface glycoconjugate, lipophosphoglycan (lpg). this association has been proposed to aid maintenance of gbp on the parasite surface. in this paper, we show that the abundance of gbp on the extracellular metacyclic cell surface is in the order of 100,000 copies per cell. this level of expression is comparable to that seen ...19958586648
ex vivo evidence for pge2 and ltb4 involvement in cutaneous leishmaniasis: relation with infection status and cytokine production.ex vivo culture of spleen cells from balb/c mice infected with 2 x 10(6) leishmania major (l. major) promastigotes were cultured with concanavalina (cona) or leishmanial antigen (l. ag) and tested for prostaglandin e2 (pge2) and for leukotriene b4 (ltb4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. the data were compared with those obtained in balb/c mice protected against l. major by sublethal irradiation ...19968587796
the antileishmanial agent licochalcone a interferes with the function of parasite mitochondria.our previous studies have shown that licochalcone a, an oxygenated chalcone, has antileishmanial (m. chen, s.b. christensen, j. blom, e. lemmich, l. nadelmann, k. fich, t.g. theander, and a. kharazmi, antimicrob, agents chemother. 37:2550-2556, 1993; m. chen, s.b. christensen, t.g. theander, and a. khrazmi, antimicrob. agents chemother. 38:1339-1344, 1994) and antimalarial (m. chen, t.g. theander, s.b. christensen, l. hviid, l. zhai, and a. kaharazmi, antimicrob. agents chemother. 38:1470-1475, ...19958593012
sudanese mucosal leishmaniasis: epidemiology, clinical features, diagnosis, immune responses and treatment.the epidemiology, clinical features, pathology, immune responses, diagnosis and treatment of 14 patients with mucosal leishmaniasis in the sudan are described. the condition occurred mainly in adult males, particularly in certain closely related tribes from the western sudan. it affected the mucosa of the upper respiratory tract and/or the oral mucosa and sometimes followed treated kala azar. the parasites were sometimes confined to the mucosa, sometimes spread to the lymph nodes, and rarely inf ...19958594683
broad spectrum antibiotic activity of the skin-pyy.neuropeptide y (npy) and polypeptide yy (pyy) are two ubiquitous neuropeptides, found in brain and intestines, respectively, where they exert important regulatory functions. in this study, a new member of the yy family recently isolated from amphibian skin, skin-pyy (spyy), is reported to inhibit irreversibly the proliferation of a broad spectrum of pathogenic microorganisms. npy and pyy are shown to be endowed with the same activity. their potency is similar to that of other antibacterial pepti ...19968601432
successful chemotherapy in experimental leishmaniasis is influenced by the polarity of the t cell response before treatment.little is known about the influence of host factors on successful chemotherapy in leishmaniasis. although successfully treated patients will convert from a delayed-type hypersensitivity (dth)-negative to a dth-positive state, the importance of the immune status of the host before treatment remains largely unexplored. in experimental murine cutaneous leishmaniasis, it was found that increased polarization towards a th2 cytokine profile before the onset of drug therapy leads to an increased freque ...19968603980
the chemotactic effect of phlebotomus duboscqi (diptera: psychodidae) salivary gland lysates to murine monocytes.the possibility that salivary gland lysates of phlebotomus duboscqi are able to attract vertebrate monocytes was investigated. in vitro studies showed that salivary gland lysates of p. duboscqi, the vector of leishmania major in kenya, are chemotactic to mouse peritoneal monocytes. this attraction of monocytes by vector salivary gland lysates may form part of the mechanisms through which sandfly saliva ensures successful parasitization of macrophages in a susceptible host by leishmania parasites ...19958610544
structural studies on a lipoarabinogalactan of crithidia fasciculata.the monosaccharide d-arabinopyranose has only been found in glycoconjugates of the trypanasomatid parasites leishmania major, endotrypanum schaudinni and crithidia fasciculata. the donor molecule for the relevant arabinosyltransferases is known to be gdp-alpha-d-arap in l. major and c. fasciculata, and the latter organism is being used to study the biosynthesis of gdp-alpha-d-arap. in this study, we describe the structure of the terminal product of arabinose metabolism in c. fasciculata, namely ...19968611182
leishmania major: infection of human monocytes induces expression of il-8 and mcaf.leishmania major, the causative agent of cutaneous leishmaniasis, is an intracellular parasite of monocytic cells. leishmania lesions are characterized by recruitment of neutrophils, eosinophils, and blood monocytes. to clarify the mechanism of this cellular influx we examined the expression of il-8 and mcaf, cytokines chemotactic for neutrophils and monocytes, respectively, in human monocytes infected by l. major. supernatants of monocytes infected with l. major had chemotactic activity for neu ...19968617327
the genomic organization of the hsp83 gene locus is conserved in three leishmania species. 19968617351
protective role of cd40 in leishmania major infection at two distinct phases of cell-mediated immunity.cd40-deficient mice are susceptible to leishmania major infection while their wild-type littermates can resolve the infection. upon stimulation with l. major antigens, draining lymph node t cells of the mutant mice and the susceptible mice, balb/c, secrete comparable amounts of il-4. the mutant mice produce less ifn gamma than wild-type mice. the expression of il-12 p40 mrna was significantly lower in l. major antigen-stimulated cells of mutant mice than those of wild-type or balb/c mice. in nor ...19968624817
cd40 ligand is required for protective cell-mediated immunity to leishmania major.the cd40-cd40 ligand (cd40l) signaling process is a pivotal component of multiple immunoregulatory pathways. although the role that cd40l plays in humoral immune responses is fairly well defined, its function(s) in cell-mediated responses in vivo has not been established. we investigated this issue by assessing the course of leishmania major infection in cd40l knockout (cd40lko) mice that were generated on a resistant background. in response to parasite challenge, cd40lko mice developed ulcerati ...19968624818
animal reservoirs of leishmaniasis in marigat, baringo district, kenya.a total of 1128 rodents belonging to seven genera were examined for leishmanial parasites over a period of sixteen months. parasites were isolated from 36 (12.5%) tatera robusta, 3 (0.5%) arvicanthis niloticus, and 2 (0.8%) mastomys natalensis. all isolates were characterised by isoenzyme analysis using nine enzymes. the enzymes examined were: malate dehydrogenase (mdh), phosphoglucomutase (pgm), glucose phosphate isomerase (gpi), isocitrate dehydrogenase (icd), nucleoside hydrolase (nh), glucos ...19968625862
murine epidermal langerhans cells do not express inducible nitric oxide synthase.in leishmania-infected macrophages (m phi), the formation of reactive nitrogen intermediates by the inducible isoform of nitric oxide synthase (inos) is critical for the killing of the intracellular parasites. we have recently shown that, in addition to m phi, epidermal langerhans cells (lc) can phagocytose leishmania major, but they do not allow parasite replication. therefore, we analyzed whether lc and m phi display the same leishmanicidal effector mechanism. unlike m phi, stimulation of unse ...19968625969
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