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effect of glycolipids of leishmania parasites on human monocyte activity. inhibition by lipophosphoglycan.lipophosphoglycan (lpg) and glycosyl phosphatidylinositol ag (gpi), are glycolipids present on the membrane of leishmania parasites. both glycolipids have been chemically characterized. lpg is a polysaccharide of repeating phosphorylated units linked to a phosphocarbohydrate core that is anchored to the membrane by lysoalkyl phosphatidylinositol (pi). the gpi are smaller glycolipids with a structure resembling the phosphocarbohydrate core of the lpg. they are anchored to the membrane by alkyl ac ...19902147940
lipophosphoglycan expression and virulence in ricin-resistant variants of leishmania major.lipophosphoglycan (lpg) of leishmania is a polymorphic molecule comprising an alkylglycerol anchor, a conserved oligosaccharide core and a species-specific polymer of oligosaccharide repeats jointed by phosphodiester bonds. this molecule, together with the membrane polypeptide gp63, has been implicated as a parasite receptor for host macrophages. to examine the role of lpg in parasite infectivity glycosylation variants of leishmania major were generated by chemical mutagenesis of a virulent clon ...19902362605
serum resistance of metacyclic stage leishmania major promastigotes is due to release of c5b-9.the mechanism of serum resistance for infective promastigotes of leishmania major was investigated. prior results suggested that the mechanism of resistance was mediated at a step after c3 deposition. equivalent amounts of c3b were deposited on serum-susceptible, noninfective promastigotes harvested from log stage cultures (log) and on c-resistant, infective, metacyclic promastigotes (mp) purified from stationary stage cultures. whereas binding of c9 to log was stable during incubation in serum, ...19902147941
the glycoinositolphospholipid profiles of two leishmania major strains that differ in lipophosphoglycan expression.the glycolipid profiles of two leishmania major strains which differ in their expression of the major glycoconjugate, lipophosphoglycan (lpg), have been compared. all the glycolipids in these strains belong to a class of glycoinositolphospholipids (gipls) which can be metabolically labelled with [3h]inositol and are sensitive to phosphatidylinositol-specific phospholipase c. the major glycolipids in the lpg-producing l. major strain v121 are tetraglycosyl phosphatidylinositol (gipl-1), pentaglyc ...19902157154
tumor necrosis factor-alpha synergizes with ifn-gamma in mediating killing of leishmania major through the induction of nitric oxide.cba mice develop cutaneous lesions when infected with leishmania major. the disease development was significantly reduced by injecting into the lesion a combination of rifn-gamma and rtnf-alpha. the doses of ifn-gamma and tnf-alpha used were suboptimal in that either cytokine alone did not have any effect. the therapeutic effect of ifn-gamma and tnf-alpha in vivo is reflected in their ability to activate macrophages to kill the intracellular parasites in vitro. the macrophage leishmanicidal acti ...19902175327
developmental modification of the lipophosphoglycan from leishmania major promastigotes during metacyclogenesis.lipophosphoglycan was isolated from the dividing, noninfective stage and from the nondividing metacyclic stage of leishmania major promastigotes. the lipophosphoglycans were characterized by sds-page and by chromatographic and quantitative analysis of phosphatidylinositol-specific phospholipase c- and mild acid-generated fragments. the results revealed two stage-specific structural differences: (i) an increase in size of the metacyclic form of the glycoconjugate due to an approximate doubling in ...19902176718
cutaneous leishmaniasis serodiagnosis by immunoperoxidase assay.immunoperoxidase assay was used for the determination of serum-specific anti-leishmanial igg antibodies in 65 patients with cutaneous leishmaniasis (cl), in 5 with visceral leishmaniasis (vl) and in 84 controls. a significant difference was observed between cl and vl sera and the control sera when either leishmania major, l. donovani or l. aethiopica intact promastigotes were used as antigens. cl patients showed similar activity against l. major and l. donovani antigen (titers 4-64 and less than ...19902228558
recurrent de novo appearance of small linear dnas in leishmania major and relationship to extra-chromosomal dnas in other species.we have detected several new chromosome-sized dnas in lines derived from the lt252 isolate of leishmania major. these dnas appeared de novo in two clonal lines undergoing methotrexate (mtx) selection (clone 7-r50, clone 15-r50), in a stably mtx-resistant population reverting from mtx pressure (r1000-11-p55rev), and spontaneously during routine serial passage of the wild-type lt252 line in vitro (lt252+). no association of these new dnas with drug resistance was detected. the new chromosomes were ...19902233897
gene replacement in parasitic protozoa.trypanosomatid protozoa frequently cause severe diseases in humans. many molecules likely to have a role during the infectious cycle have been identified, yet proof of their function is often lacking. we describe studies in leishmania major of homologous gene targeting, a powerful method for testing gene function in other organisms. following introduction of a construct containing dihydrofolate reductase-thymidylate synthase (dhfr-ts) flanking sequences fused to neomycin phosphotransferase, 45% ...19902234081
susceptibility of inbred mice to leishmania major infection: genetic analysis of macrophage activation and innate resistance to disease in individual progeny of p/j (susceptible) and c3h/hen (resistant) mice.we tested the possibility that two phenotypic traits, defective activation of macrophage antileishmanial activities and susceptibility to infection with leishmania major, were controlled by the same gene. we used p/j (susceptible) and c3h/hen (resistant) mice to breed f1, backcross (bx), and f2 mice that were tested individually for both traits, each of which is known to be controlled by a single autosomal gene. we found no correlation between the macrophage defect and cutaneous disease. there w ...19902254035
cyclosporin a treatment converts leishmania donovani-infected c57bl/10 (curing) mice to a noncuring phenotype.cyclosporin a prevents visceralization of leishmania major infection of balb/c mice (n. c. behforouz, c. d. wenger, and b. a. mathison, j. immunol. 136:3067-3075, 1986; w. solbach, k. forberg, e. kammerer, c. bogdan, and m. rollinghoff, j. immunol. 134:702-707, 1986). we report that cyclosporin a exacerbates disseminated leishmaniasis caused by l. donovani in c57bl/10 mice. normal mice challenged with 5 x 10(6) amastigotes intravenously cleared the infection within several months by spontaneous ...19902387638
characterization of leishmania major antigen-liposomes that protect balb/c mice against cutaneous leishmaniasis.leishmania major antigen-liposomes prepared as dehydration-rehydration vesicles (drv) and composed of equimolar amounts of l-alpha-distearoyl phosphatidylcholine and cholesterol confer high-level host-protective immunity against virulent homologous challenge to susceptible balb/c mice. physical and antigenic characterization of these protective liposomes is described. both empty and l. major antigen-drv were multilamellate and heterogeneous in size, ranging from 0.10 to 2.00 microns. although th ...19902401562
evolution of nuclear dna and the occurrence of sequences related to new small chromosomal dnas in the trypanosomatid genus endotrypanum.comparisons of nuclear dna restriction fragment patterns were used to examine the evolutionary relatedness among 17 strains previously identified as endotrypanum, a trypanosomatid parasite of sloths. fragments were obtained with 6 restriction enzymes and analyzed by southern blotting with hybridization probes from three loci. an estimate of the percent nucleotide sequence divergence among strains, delta, was calculated and used to construct molecular evolutionary trees. the 17 isolates fell into ...19902362601
effect of leishmania major on human polymorphonuclear leucocyte function in vitro.the effect of various antigens of leishmania major promastigotes on the function of human polymorphonuclear leucocytes (pmnls) was examined. different concentrations of l. major antigens were incubated with isolated pmnls for various periods and the respiratory burst was assessed by luminol-dependent chemiluminescence. all the leishmania antigens employed inhibited the pmnl respiratory burst by 35-64%. pmnl viability was not affected either by the concentrations or type of the parasite antigen. ...19902374156
leishmania major: inhibition of the chemiluminescent response of human polymorphonuclear leukocytes by promastigotes and their excreted factors.the effect of various leishmanial preparations on the chemiluminescent response (cr) of human polymorphonuclear leukocytes (pmn) was studied. almost no cr was observed with pmn stimulated with either leishmania promastigotes or their excreted factors (efs). promastigotes added to pmn stimulated with phorbol myristate acetate (pma), at a proportion of 20 to 1, respectively inhibited approximately 80-83% of the cr activity. leishmanial promastigotes, whether live or dead, infective or non-infectiv ...19902385444
tumour necrosis factor (tnf alpha) in leishmaniasis. i. tnf alpha mediates host protection against cutaneous leishmaniasis.genetically resistant cba mice developed significantly larger lesions to leishmania major infection when they were injected with rabbit anti-tumour necrosis factor (tnf)-specific antibodies compared to control mice injected with normal rabbit immunoglobulin. balb/c mice recovered from a previous infection following prophylactic sublethal irradiation also developed exacerbated lesions when treated with the anti-tnf antibody. injection of tnf into the lesion of infected cba mice significantly redu ...19902335376
macrophage killing of leishmania parasite in vivo is mediated by nitric oxide from l-arginine.peritoneal macrophages from cba mice incubated with rifn-gamma are effective in killing the protozoal parasite leishmania major in vitro. this leishmanicidal activity can be completely inhibited by l-ng-monomethyl arginine (l-nmma), a specific inhibitor of the l-arginine:nitric oxide (no) pathway. the culture supernatants of macrophage activated by ifn-gamma contain increased levels of no2-, the production of which is inhibited by l-nmma, but not by its d-enantiomer. l. major promastigotes are k ...19902351828
rapid quantitative method for measuring phagocytosis of leishmania promastigotes using a double radiolabelling method.a double radiolabelling method is described for the measurement of phagocytosis of leishmania major promastigotes in cultures of murine resident peritoneal macrophages. l. major promastigotes were radiolabelled during exponential growth in rpmi supplemented with [125i]5-iodo-2-deoxyuridine. they were used to infect sodium [51cr]chromate-labelled macrophages. phagocytosis was evaluated by measuring the radioactivity of the 125iudr-labelled parasites detectable inside 51cr-labelled macrophages by ...19902358689
[the isoenzyme identification and pathogenic characteristics of clones of leishmania major, l. sp. nov. and l. gerbilli].using fonbrune's micromanipulators, 16 freshly obtained leishmania isolates (13 from r. opimus, 1 from p. papatasi, 2 from patients with skin leishmaniasis) have been cloned. 4 out of them were l. major isolates, 5 were l. sp. nov. isolates, 5 were mixed l. major and l. sp. nov. isolates and 1 was l. gerbilli isolate. 316 clones were identified using electrophoresis in polyacrylamide gel by 8 enzymes: pgi, pgm, 6-pgd, mdg, g-6-pgd, me, alat, asat--and tested for pathogenic activity on golden ham ...19902290404
monoclonal antibodies against leishmanial membranes react with specific excreted factors (ef).the interaction was examined between two reagents used for the speciation of leishmania: spent culture-medium excreted factors (ef) and antileishmanial monoclonal antibodies (mca). thirty-three mcas: seven against l. major, five against l. tropica, eight against l. aethiopica, 11 against l. donovani sensu lato and two against all leishmania species were screened by double diffusion for reactions with efs representing seven different sub-serotypes (a1,a2,a4,b1,b2,b3 and a3b2). only five mcas show ...19901701624
changing surface carbohydrate configurations during the growth of leishmania major.surface carbohydrates of leishmanial promastigotes change during their growth cycle. these changes were monitored in a cloned line of leishmania major in 2 media. a freshly isolated virulent strain was also examined. infectivity, surface sugar moieties, and released glycoconjugates (ef) were examined and compared during the growth cycle. when promastigotes of the same clone were grown in different media, their lectin-mediated agglutination profiles were dissimilar, and both quantitative and qual ...19901690797
study of leishmania major-infected macrophages by use of lipophosphoglycan-specific monoclonal antibodies.leishmania major infection of macrophages is followed by a time-dependent appearance of lipophosphoglycan (lpg) that can be detected on the surface of infected cells by monoclonal antibodies. the origin of these lpg epitopes is probably the intracellular amastigote. lpg epitopes could be detected on the amastigote and the infected macrophage by a number of monoclonal antibodies directed to several distinct determinants on the phosphoglycan moiety. the macrophage-expressed lpg may be modified bec ...19901694823
immunoprotective leishmania major synthetic t cell epitopes.using the predictive algorithm of rothbard and taylor (1988. embo j. 7:93) and the primary structure of gp63 (button, l., and m.r. mcmaster. 1988. j. exp. med. 167:724; miller, r.a., s.g. reed, and m. parsons. 1990. mol. biochem. parasitol. 39:267) we have been able to delineate the structures of a number of gp63 t-cell epitopes which stimulate the proliferation of cd4+ cells. one of these synthetic antigens, inoculated subcutaneously with adjuvant, was shown to specifically induce proliferation ...19901695670
rapid shape change and release of ninhydrin-positive substances by leishmania major promastigotes in response to hypo-osmotic stress.leishmania major promastigotes were grown to late-log phase and washed and resuspended in an isosmotic buffer. when osmolality was suddenly decreased by 50%, the cells rapidly became shorter and increased in width. cell volume, calculated assuming a prolate-ellipsoidal shape, increased 1.4 times after 1 min. over the next several minutes, the average length and width returned to control values while the volume returned to baseline, indicating the ability to regulate volume. concomitantly with th ...19902086781
analyses of surface membrane carbohydrates in parasitic flagellates of the order kinetoplastida using lectins.crithidia fasciculata, leishmania donovani, leishmania major, leishmania mexicana amazonensis, leishmania tropica, leishmania tarentolae, trypanosoma sp. from formosan bats (tb), trypanosoma lewisi, trypanosoma musculi, and different strains of trypanosoma cruzi (tc) were cultivated at 27 degrees c in a liquid culture medium. flagellates harvested from log phase culture were analyzed for their lectin agglutinating characteristics with concanavalin a (con a), peanut agglutinin, ricinus communis a ...19901696387
a case of diffuse cutaneous leishmaniasis due to leishmania major. 19902091348
expression of lpg and gp63 by different developmental stages of leishmania major in the sandfly phlebotomus papatasi.development and forward migration of leishmania parasites in the sandfly gut is accompanied by morphological transformation to highly motile, non-dividing 'metacyclic' forms. previous studies in vitro have demonstrated that this metacyclogenesis is associated with developmentally regulated changes in expression of two major surface glycoconjugates of leishmania, the lipophosphoglycan (lpg) and the glycoprotein protease gp63. studies presented here are the first to examine in situ the changes in ...19902092290
the characterization of leishmania major from phlebotomus papatasi (scopoli) caught in northern sinai, egypt. 19902096507
cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. evidence for a t cell-dependent, interferon gamma-independent mechanism.balb/c mice infected with leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of cd4+ t cells in the draining lymph nodes. the immune response has been further characterized by a lack of ifn-gamma mrna, but increased il-4 mrna in lymphoid tissues, and striking elevation of serum ige. treatment of infected balb/c mice with rifn-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate l. major infectio ...19902104918
synergy between activated leishmania major-specific cd4+ t lymphocytes and bone-marrow-derived cells in the exacerbation of murine cutaneous leishmaniasis.mechanisms of exacerbation of murine cutaneous leishmaniasis mediated by leishmania major-specific cd4+ t lymphocytes were studied. using a limiting dilution assay for the quantification of leishmania parasites, the infected tissues (footpad) of lethally irradiated mice were found to contain tenfold less parasites at four days of infection than the footpads of infected unirradiated animals. injection of bone marrow cells depleted of t cells into irradiated mice at the site of infection led to an ...19901983098
development of a stable leishmania expression vector and application to the study of parasite surface antigen genes.trypanosomatid protozoan parasites cause several important tropical diseases and have been a fertile ground for the discovery of molecular paradigms such as trans-splicing and rna editing. transfection-based methods for the study of these organisms have recently been developed, and we have now designed an expression vector, px, which contains only 2.3 kilobases of leishmania dna and can be stably transfected with high efficiency. genes encoding escherichia coli beta-galactosidase or a leishmania ...19902124701
cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from l-arginine by macrophages and hepatocytes.nitric oxide (no) produced by cytokine-treated macrophages and hepatocytes plays a vital role in protective host responses to infectious pathogens. no inhibits iron-sulfur-dependent enzymes involved in cellular respiration, energy production, and reproduction. synthesis of l-arginine-derived nitrite (no2-), the oxidative end product of no, directly correlates with intracellular killing of leishmania major, an obligate intracellular protozoan parasite of macrophages: the level of no2- production ...19902126524
species- and infective stage-specific monoclonal antibodies to leishmania major produced by an in vitro immunization method.monoclonal antibodies specific to the infective-stage promastigotes of leishmania major are needed for developing rapid diagnostic assays of infected sand flies. an in vitro immunization protocol was applied for the production of monoclonal antibodies using small amounts of l. major. infective-stage promastigotes were isolated from sand flies (phlebotomus papatasi) 7-10 days after infection and used as antigen for immunization. two weeks after a primary immunization, murine splenocytes were remo ...19902087235
oral salmonella typhimurium (aroa-) vaccine expressing a major leishmanial surface protein (gp63) preferentially induces t helper 1 cells and protective immunity against leishmaniasis.the gp63 gene of leishmania major was transformed into the aroa- vaccine strain of salmonella typhimurium (sl3261). the construct (sl3261-gp63), which stably expresses the gp63 ag in vitro, was used to immunize cba mice by the oral route. spleen cells from mice inoculated with sl3261-gp63 developed antibody and proliferative t cell response to l. major. they did not express detectable delayed-type hypersensitivity reactivity. the activated t cells are mainly cd4+ and secrete il-2 and ifn-gamma b ...19902144549
structure of the glycosyl-phosphatidylinositol membrane anchor of the leishmania major promastigote surface protease.in common with many other plasma membrane glycoproteins of eukaryotic origin, the promastigote surface protease (psp) of the protozoan parasite leishmania contains a glycosyl-phosphatidylinositol (gpi) membrane anchor. the gpi anchor of leishmania major psp was purified following proteolysis of the psp and analyzed by two-dimensional 1h-1h nmr, compositional and methylation linkage analyses, chemical and enzymatic modifications, and amino acid sequencing. from these results, the structure of the ...19902145267
[ecoepidemiology of leishmaniasis in syria. 1. leishmania major yakimoff and schokhor (kinetoplastida-trypanosomatidae) infestation of psammomys obesus cretzschmar (rodentia-gerbillidae)].during an epidemiological survey of zoonotic cutaneous leishmaniasis in south-west syria, leishmania major zymodème mon-26 was isolated from a reservoir host, psammomys obesus terraesanctae (rodentia-gerbillidae). the abundance of this rodent, its close contact with infected villages and the high prevalence of the infection (63,1%) indicate that this is the main reservoir host of oriental sore in the semi desert area of this country.19902097930
activated macrophages destroy intracellular leishmania major amastigotes by an l-arginine-dependent killing mechanism.macrophages infected with amastigotes of leishmania major and treated with ifn-gamma in vitro develop potent antimicrobial activities that eliminate the intracellular parasite. this antileishmanial activity was suppressed in a dose dependent fashion by ng-monomethyl-l-arginine (ngmmla), a competitive inhibitor of nitrite, nitrate, nitric oxide and l-citrulline synthesis from l-arginine. excess l-arginine added to infected macrophage cultures reversed the inhibitory effects of ngmmla. addition of ...19902104889
interleukin-2, anti-interleukin-2 receptor antibody, and activation of macrophages.macrophages treated with ifn-gamma and il-2 before exposure to parasites develop the ability to resist infection with amastigotes of leishmania major. in this cooperative interaction of cytokines, il-2 can be replaced with any of several mab directed against the beta chain of the il-2 receptor, but not by antibodies to a number of other cell receptors or antigens. thus, antibodies to the il-2 receptor act as agonists of il-2 in the induction of a biologic activity in macrophages, and macrophages ...19902113433
thymidylate synthase-dihydrofolate reductase in protozoa.in protozoa, thymidylate synthase (ts) and dihydrofolate reductase (dhfr) exist on the same polypeptide. the dhfr domain is on the amino terminus, ts is on the carboxy terminus, and the domains are separated by a junction peptide of varying size depending on the source. the native protein is a dimer of two such subunits and is 110-140 kda. most studies of bifunctional ts-dhfr have been performed with the protein from anti-folate resistant strains of leishmania major, which show amplification of ...19902178951
bifunctional thymidylate synthase-dihydrofolate reductase in protozoa.protozoa contain thymidylate synthase (ts) and dihydrofolate reductase (dhfr) on the same polypeptide. in the bifunctional protein, the dhfr domain is on the amino terminus, ts is on the carboxyl terminus, and the two domains are separated by a junction peptide of varying size depending on the source. the native protein is composed of a dimer of two such subunits and is 110-140 kda. most studies of the bifunctional ts-dhfr have been performed with the protein from anti-folate resistant strains o ...19902180768
leishmania major: production of recombinant gp63, its antigenicity and immunogenicity in mice.the mr 63,000 membrane polypeptide (gp63) is one of the leishmania receptors for host macrophages and has been shown to protect mice from infection. the gene encoding gp63, the major mr 63,000 surface glycoprotein of l. major promastigotes, has been expressed as a fusion protein with the enzyme glutathione s- transferase encoded by the parasitic helminth schistosoma japonicum. this fusion protein was recognized by polyclonal antibodies to the native leishmania gp63 polypeptide. the insoluble gp6 ...19902182337
leishmania major: expression and gene structure of the glycoprotein 63 molecule in virulent and avirulent clones and strains.two leishmania membrane glycoconjugates, gp63 and lipophosphoglycan, have been implicated in parasite attachment and uptake into the host macrophage. moreover, recent data suggest that parasite virulence is associated with high expression of gp63. in this study we have surveyed gp63 gene copy number, in addition to the level of expression of gp63 mrna and protein in several leishmania major isolates, as well as virulent and avirulent strains and clones. the highest level of gp63 expression was f ...19902209787
leishmania major and l. donovani: a method for rapid purification of amastigotes. 19902209791
effects of oxygen concentration on the intermediary metabolism of leishmania major promastigotes.leishmania major promastigotes grown in late log phase were incubated with glucose as sole exogenous carbon source in the presence of 5% co2 and the amounts of glucose consumed and of the major products formed--succinate, pyruvate, alanine, acetate, glycerol, and d-lactate--were measured as a function of po2. glucose consumption increased as po2 was lowered to 6% (a positive pasteur effect) and then declined to the same level at 95% n2 as at 95% o2. the production of d-lactate and of glycerol in ...19902108330
genomic variation of trypanosoma cruzi: involvement of multicopy genes.by using improved pulsed field gel conditions, the karyotypes of several strains of the protozoan parasite trypanosoma cruzi were analyzed and compared with those of leishmania major and two other members of the genus trypanosoma. there was no difference in chromosome migration patterns between different life cycle stages of the t. cruzi strains analyzed. however, the sizes and numbers of chromosomal bands varied considerably among t. cruzi strains. this karyotype variation among t. cruzi strain ...19902169461
nuclease mapping and dna sequence analysis of transcripts from the dihydrofolate reductase-thymidylate synthase (r) region of leishmania major.trypanosomatid protozoan parasites utilize a number of nonstandard mechanisms in expressing their genes. to probe these phenomena in a genetically accessible system, we have mapped termini of eight transcripts arising from the amplified r region including the dhfr-ts gene of methotrexate-resistant leishmania major. poly(a)+ rnas transcribed from the dhfr-ts-coding strand exhibit features similar to those observed around other trypanosomatid protein-coding genes. these include close spacing, the ...19902243782
structure of the lipophosphoglycan from leishmania major.the major cell surface glycoconjugate of the parasitic protozoan leishmania major is a heterogeneous lipophosphoglycan. it has a tripartite structure, consisting of a phosphoglycan (mr 5,000-40,000), a variably phosphorylated hexasaccharide glycan core, and a lysoalkylphosphatidylinositol (lysoalkyl-pi) lipid anchor. the structures of the phosphoglycan and the hexasaccharide core were determined by monosaccharide analysis, methylation analysis, fast atom bombardment-mass spectrometry, one- and t ...19902246247
production of tumour necrosis factor during murine cutaneous leishmaniasis.we have assessed the role of tumour necrosis factor-alpha (tnf) during cutaneous leishmaniasis and demonstrated that significant levels of tnf were released by spleen cells from infected mice after in vitro restimulation with leishmania major promastigotes. spleen cells from both genetically resistant and genetically susceptible mice were equally capable of producing tnf. after challenge with bacterial endotoxin, tnf activity could also be demonstrated in the serum of l. major-infected mice and ...19902255560
changes in the shape of leishmania major promastigotes in response to hexoses, proline, and hypo-osmotic stress.leishmania major promastigotes in late-log phase are generally long and slender, and remain so during a 1 h incubation in buffer without exogenous substrate. when glucose, 2-deoxyglucose, fructose, mannose, or proline are added, the cells become shorter and more rounded. the shape change in response to glucose is complete within 20 min and is reversible upon incubating the cells without substrate. galactose, 3-o-methylglucose, 6-deoxyglucose, sucrose, maltose, ribose, glycerol, alanine, glutamat ...19902258829
released glycoconjugate of indigenous leishmania major enhances survival of a foreign l. major in phlebotomus papatasi.the effect of leishmania glycoconjugate in the vector was investigated using phlebotomus papatasi artificially infected with a leishmania major strain that this vector does not transmit in nature. glycoconjugate of the vector-specific strain of l. major was added to the infective meals of some fly groups and the success of infections with or without this substance was compared 4 d later. in the absence of glycoconjugate the parasites survived in 15.6% of the flies, while the addition of 0.5 mg/m ...19902260168
sequence analysis and transcriptional activation of heat shock protein 83 of leishmania mexicana amazonensis.changes in environmental temperature regulate the differential expression of genes during leishmania stage differentiation. therefore, molecular analysis of the heat shock proteins (hsps) in these parasites is of interest as a model for thermoregulation of gene expression. sequences of the hsp83 repetitive unit in the genome of leishmania mexicana amazonensis, including both the coding and intergenic regions, are described. the 5' boundary of the message was mapped by s1 analysis, to potential a ...19902270107
expression of t-cell-associated serine proteinase 1 during murine leishmania major infection correlates with susceptibility to disease.the expression of t-cell-associated serine proteinase 1 (mtsp-1) in vivo during leishmania major infection was analyzed in genetically resistant c57bl/6 mice and in genetically susceptible balb/c mice. using a monoclonal antibody as well as an rna probe specific for mtsp-1 to stain tissue sections, we found t cells expressing mtsp-1 in skin lesions and spleens of mice of both strains. in skin lesions, mtsp-1-positive t cells could be detected as early as 3 days after infection. most importantly, ...19911937831
cytokine regulation of murine leishmaniasis: interleukin 4 is not sufficient to mediate progressive disease in resistant c57bl/6 mice.neutralization of interleukin 4 (il-4) at the time of infection with leishmania major allowed susceptible balb/c mice to heal. recombinant il-4, however, had little effect on the course of l. major infection in resistant c57bl/6 mice, nor did coinfection with nippostrongylus brasiliensis, despite marked elevation of endogenous il-4 levels.19911937832
administration of beta-glucan following leishmania major infection suppresses disease progression in mice.the potential of beta-glucan (glucan) to suppress the progression of lesions caused by virulent strains of leishmania major in genetically susceptible balb/c mice when administered post challenge was evaluated. glucan particles (glucanp) prepared from saccharomyces cerevisiae were injected i.v. at 7-day intervals starting 7 days after parasite challenge. four injections gave a more rapid and a higher extent of suppression than 1, 2 or 3 injections. mice receiving only parasites, a glucose soluti ...19912052403
metacyclogenesis of leishmania spp: species-specific in vitro transformation, complement resistance, and cell surface carbohydrate and protein profiles.metacyclic (stationary) and logarithmic (log) forms of promastigotes of leishmania donovani and leishmania major were characterized in several ways. the highly active metacyclic forms were larger with more protein and less carbohydrate. the flagellum increased in length 2.4 times in l. major as compared to 1.8 times in l. donovani. resistance to complement-mediated lysis by normal human serum of in vitro grown leishmania promastigotes was related to the species, the growth phase in culture, and ...19912040953
cytokine interactions in experimental cutaneous leishmaniasis. ii. endogenous tumor necrosis factor-alpha production by macrophages is induced by the synergistic action of interferon (ifn)-gamma and interleukin (il) 4 and accounts for the antiparasitic effect mediated by ifn-gamma and il 4.tumor necrosis factor-alpha (tnf-alpha) strongly activates murine peritoneal macrophages (m phi) for killing of amastigotes from leishmania major in the presence of low amounts of interferon-gamma (ifn-gamma). recently, we found that ifn-gamma and interleukin 4 (il 4) also synergistically enhance the antileishmanial potential of m phi. in this report, evidence is provided that the synergism of ifn-gamma and il 4 is based on the ability of the lymphokines to induce the endogenous production of tn ...19911905642
transmission and scanning em-immunogold labeling of leishmania major lipophosphoglycan in the sandfly phlebotomus papatasi.previous studies using immunostaining and light microscopy demonstrated expression of leishmania major lipophosphoglycan (lpg) on parasites developing in the sandfly gut from 2 days post infection. by days 4 to 7 post infection, there appeared to be large amounts of parasite-free lpg deposited on/in the microvilli and epithelial cells lining the thoracic midgut, while forward migration of parasites and the morphological changes which accompany metacyclogenesis were associated with developmental ...19911935998
biochemical characterization of leishmania major isolated from two egyptian patients.leishmania major, the cause of human zoonotic cutaneous leishmaniasis, is a widely distributed parasite in the old world. here, we report the isoenzyme characterization of two human isolates obtained from egyptians who never travelled abroad. the two isolates were l. major equivalent to zymodene lond i.19912033298
cytokine interactions in experimental cutaneous leishmaniasis.destruction of intracellularly living leishmania major amastigotes is achieved by activated macrophages. in this report, we have investigated the contribution of il-4, tnf-alpha and ifn-gamma to the induction of antileishmanial macrophage activation. it was found that as single lymphokine only ifn-gamma led to amastigote elimination by peritoneal exudate macrophages. neither il-4 nor tnf-alpha or the combination of both cytokines led to antimicrobial activation. when the macrophages were incubat ...19911904708
t-cell responses during infections with leishmania major. 19911904711
[susceptibility to and the characteristics of the course of experimental leishmaniasis in different species of mammals infected with leishmania major, l. turanica and l. gerbilli].40 r. opimus and 69 m. libycus were infected and 59 human subjects were vaccinated in laboratory conditions. 13 cultures of 3 leishmania species and their mixtures were used. r. opimus turned to be sensitive to 3 leishmania species. leishmaniasis developed in the form of infiltrates irrespective of the leishmania species and pathogenic activity. ulceration and visceralization were always absent. differences in the duration of leishmania preservation in r. opimus have been noted. in l. major infe ...19912067472
leishmania-sandfly interactions: an empirical field study.phlebotomus papatasi is the sandfly vector of leishmania major in the jordan valley. the objective of this study was to characterize vector-parasite relations in an active zoonotic focus. seasonality and intensity of promastigote infection rates in female sandflies and the developmental stage of these hosts were established. on 153 trap-nights, 641 female p. papatasi were caught and examined. of these, 48 (7.4%, range 12.9-4.8%) were infected with l. major promastigotes. correlating the number o ...19912010872
identification and characterization of host-protective t-cell epitopes of a major surface glycoprotein (gp63) from leishmania major.by using a series of overlapping synthetic peptides that cover more than 75% of the amino acid sequence of the major surface glycoprotein (gp63) from leishmania major, 11 t-cell epitopes in cba and balb/c mice have been identified. six of the peptides were recognized by t cells of cba mice recovered from l. major infection, while one was recognized by the t cells from balb/c mice recovered from the infection following sublethal doses of gamma-irradiation. lymph node cells from mice immunized wit ...19911997399
the comparative fine structure and surface glycoconjugate expression of three life stages of leishmania major.the cellular ultrastructure and surface glycoconjugate expression of three life stages of leishmania major were compared. noninfective logarithmic phase promastigotes (lp) are immature cells bearing a thin cell coat, short flagellum, small and empty flagellar pocket, and a loose cytoplasm filled with profiles of er and large golgi complex. lp also contain subpopulations of maturing cells containing less er and golgi and synthesizing cytoplasmic granules of different size, number, and electron-de ...19912009923
monoclonal antibodies that react with leishmania (viannia) naiffi.monoclonal antibodies were raised against leishmania (viannia) naiffi, which recently has been characterized as a new species. balb/c mice were immunized with membrane-enriched fractions of a mixture of l. (v.) naiffi isolates. subsequent fusion of immunized splenocytes with ns-1 myeloma cells resulted in the production of 5 mabs (n1-n5). screening by elisa and indirect immunofluorescence against an extensive cross-panel of leishmania strains revealed that n3 was species-specific and could thus ...19911919913
activation of human t lymphocytes by leishmania lipophosphoglycan.this study describes leishmania antigen-induced activation of lymphocytes isolated from kenyan donors, previously treated for visceral leishmaniasis, and from danish and kenyan controls. peripheral blood mononuclear cells (pbmc) from cured kala-azar patients proliferated and produced interferon-gamma in vitro in response to lipophosphoglycan (lpg) isolated from leishmania major. the proliferative response was mainly due to activation of cd2-positive t cells. pbmc from controls did not respond to ...19911902000
establishment of resistance to leishmania major infection in susceptible balb/c mice requires parasite-specific cd8+ t cells.although cd4+ t cells are generally accepted to be responsible for the determination of resistance to infection in experimental murine cutaneous leishmaniasis, a contribution of cd8+ lymphocytes to immunity can be demonstrated under certain well-defined conditions. normally highly susceptible balb/c mice can be rendered resistant to infection with leishmania major promastigotes by a single injection of monoclonal anti-cd4 antibodies at the beginning of infection. mice treated in such a way can h ...19911909563
simultaneous transient expression assays of the trypanosomatid parasite leishmania using beta-galactosidase and beta-glucuronidase as reporter enzymes.we describe a transient transfection protocol for cultured leishmania major promastigotes, utilizing escherichia coli genes encoding beta-galactosidase and beta-glucuronidase inserted into an expression vector derived from the dihydrofolate reductase-thymidylate synthase locus. less than 0.1 pg of either reporter enzyme can be detected with a simple fluorimetric assay, and transfection of 10 micrograms of either reporter construct yields activities at least 100-fold over background. simultaneous ...19911908808
role of tumor necrosis factor in macrophage leishmanicidal activity in vitro and resistance to cutaneous leishmaniasis in vivo.recombinant human tumor necrosis factor (tnf) and purified murine tnf were both able to activate macrophages to destroy intracellular leishmania major in vitro. in addition, parasitizing macrophages with l. major markedly increased the ability of the cells to produce tnf. finally, when mice were vaccinated with an avirulent form of l. major, the animals produced large amounts of tnf but no gamma interferon in response to infection with virulent l. major. treating these mice with a neutralizing a ...19911906844
modification of gp63 genes from diverse species of leishmania for expression of recombinant protein at high levels in escherichia coli.toward the future development of a defined subunit vaccine against leishmaniasis is, high levels of recombinant gp63 for diverse species of leishmania were produced in escherichia coli. several features of leishmania gp63 genes were simultaneously modified with the polymerase chain reaction (pcr) using either cloned genes or total genomic dna from leishmania as template dna for the pcr amplification reactions. the pcr products included only the coding region for the predicted mature form of gp63 ...19911711153
stable dna transfection of a wide range of trypanosomatids.we have shown that the leishmania major transfection vector pr-neo (or derivatives thereof) can be introduced and stably maintained in four species complexes of pathogenic leishmania (l. tropica, l. mexicana, l. donovani, l. braziliensis), and the genera endotrypanum and crithidia; transfection of trypanosoma cruzi or trypanosoma brucei was not successful. quantitative plating assays showed that the transfection efficiencies were high in l. major and leishmania amazonensis (5x10(-5)/cell) and ab ...19911906580
a possible novel pathway of regulation by murine t helper type-2 (th2) cells of a th1 cell activity via the modulation of the induction of nitric oxide synthase on macrophages.murine peritoneal macrophages activated with interferon (ifn)-gamma and lipopolysaccharide (lps) produce high levels of nitric oxide (no) and are efficient in killing the intracellular protozoan parasites leishmania major in vitro. earlier studies have shown that no, whose synthesis in murine macrophages is catalyzed by an inducible enzyme no synthase, plays a major effector role in the host resistance against microbial infection. we now shown that both the no synthesis and the leishmanicidal ac ...19911717284
production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by cd4+ lymphocytes in vivo during healing and progressive murine leishmaniasis.the expression of interleukin (il) 2, il-4, il-10, and interferon gamma (ifn-gamma) by lymphocyte subsets was examined during infection of resistant c57bl/6 and susceptible balb/c mice with the protozoan parasite leishmania major. cd4+ and cd8+ t lymphocytes and b lymphocytes were isolated from the lymph nodes draining infectious lesions, and their rna was examined for lymphokine transcripts. distinct patterns of cd4+ cell cytokine expression were apparent: c57bl/6 cd4+ cells contained ifn-gamma ...19911908085
structure and antigenicity of the lipophosphoglycan from leishmania major amastigotes.the lipophosphoglycan (lpg) of the intracellular amastigote form of the protozoan parasite leishmania major is chemically distinct from the lpg on the surface of the extracellular promastigote form. amastigote lpg is composed of the monosaccharides galactose, glucose, mannose, glucosamine and inositol in the molar ratio 51:30:24:1:1; arabinose is absent. the lipid anchor comprises four alkylglycerols, with alkyl chain lengths 24:0, 22:0, 20:0 and 26:0 in the molar ratio 68:18:8:6. phosphate is p ...19911820201
reduced numbers of cd4+ suppressor cells with subsequent expansion of cd8+ protective t cells as an explanation for the paradoxical state of enhanced resistance to leishmania in t-cell deficient balb/c mice.compared to their normal, t-cell competent counterparts, balb/c mice that have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells (txb) were found to be resistant to leishmania major. even though txb mice possess less than 30% of the normal number of t cells in their lymphoid organs, they generated a protective immune response that prevented the progressive multiplication of the parasite in the primary cutaneous lesion and its dissemination to distant visceral site ...19911826673
protective effect of isoprinosine in genetically susceptible balb/c mice infected with leishmania major.the effects of an immunopotentiating drug inosine pranobex (isoprinosine) were investigated in an experimental cutaneous leishmaniasis model. the highly susceptible balb/c mice treated orally with isoprinosine developed significantly delayed onset of disease when infected with leishmania major compared to untreated mice. the drug itself is not toxic to the parasite up to millimolar levels in vitro. the increase in resistance to l. major infection is accompanied by a marked decrease in the cd4+/c ...19911718853
concurrent infection with leishmania donovani and leishmania major in a kenyan patient: clinical description and parasite characterization.leishmania isolates aspirated a few months apart from the spleen of an indigenous adult male kala-azar patient from baringo district, kenya, were biochemically characterized and compared. the patient lived within a dual focus of l. donovani kalazar and l. major cutaneous leishmaniasis. a primary leishmania isolate from splenic aspirates was cryopreserved (nlb-294). the patient was treated with sodium stibogluconate for kala-azar and discharged. three months later, he had clinical relapse and ret ...19911928563
differential production of th1- and th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis.recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of cd4+ t cell subsets in determining the outcome of infectious disease. in leishmania major infections, cure vs progressive disease correlates with the expansion of th1-like or th2-like cd4+ populations, respectively. we have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by l. donovani. splenic lymphocy ...19911901883
characterization of a membrane antigen of leishmania amazonensis that stimulates human immune responses.to investigate human immune responses to defined leishmania ag we have begun to characterize biochemically and immunologically, an abundant 42-kda surface ag of leishmania amazonensis, a causative agent of human leishmaniasis. we have shown that this ag, la gp42, is expressed on the surface of l. amazonensis promastigotes, being anchored to the membrane by a glycosyl-phosphatidylinositol moiety. as demonstrated by lectin blotting studies, la gp42 is glycosylated, binding both con a and wheat ger ...19911824776
expression of a stage-specific lipophosphoglycan in leishmania major amastigotes.amastigotes of leishmania major were isolated from infected mice and radiolabeled for 2 h with [3h]galactose. an acidic [3h]glycoconjugate was extracted from a dilipidated residue fraction with the solvent water/ethanol/diethylether/pyridine/nh4oh (15:15:5:1:0.017). the radioactivity labeled glycoconjugate was found to possess the following characteristics that were similar to the lipophosphoglycan extractable from promastigotes: (i) migrated as a broad band upon electrophoresis on sds polyacryl ...19911646960
induction of th1 and th2 cd4+ subsets during murine leishmania major infection. 19911829257
studies on the leishmaniases in the sudan. 2. clinical and parasitological studies on cutaneous leishmaniasis.in the omdurman hospital for tropical diseases, sudan, from 6 october to 1 december 1986, 736 patients with cutaneous leishmaniasis (cl) were studied. the duration of the lesions varied from a few days to 4 months, usually (56%) 1-3 months. multiple lesions ranging from one to 50 (mean = 4) were present in 80% of cases. ulcerative lesions were found in 44%, nodulo-ulcerative in 31%, nodular in 31% and others, including infiltrated, fungating and warty lesions, in 5% of patients. the lower limbs ...19911661450
a search for cells carrying the gamma/delta t cell receptor in mice infected with leishmania major. 19911833155
leishmanial protein kinases phosphorylate components of the complement system.externally oriented protein kinases are present on the plasma membrane of the human parasite, leishmania. since activation of complement plays an important role in the survival of these parasites, we examined the ability of protein kinases from leishmania major to phosphorylate components of the human complement system. the leishmanial protein kinase-1 (lpk-1) isolated from promastigotes of l. major was able to phosphorylate purified human c3, c5 and c9. only the alpha-chain of c3 and c5 was pho ...19911756717
variants of a leishmania surface antigen derived from a multigenic family.the promastigote surface antigen-2 (psa-2) complex comprises a group of immunogenic surface antigens linked to the surface of the leishmania major promastigote with glycosylphosphatidylinositol anchors. the l. major genome contains at least 14 psa-2 genes on a 950-kilobase chromosome and comprising approximately 20% of the length of this chromosome. the sequence of three independent, but incomplete, psa-2 cdnas and one genomic fragment encoding a complete psa-2 coding sequence were compared. psa ...19911761547
changes in intracellular levels of fructose 2,6-bisphosphate and several glycolytic intermediates in leishmania major promastigotes as a function of po2.leishmania major promastigotes were grown to late log phase, washed and resuspended in hanks' balanced salt solution, and incubated with glucose at various po2s in the presence of 5% co2. samples were taken at times from 0-40 min and assayed for fructose 2,6-bisphosphate (fru(2,6)p2), glucose-6-phosphate (g6p), fructose-6-phosphate (f6p), phospho(enol)pyruvate (pep), and atp. at 95% o2 atp remained constant throughout the incubation. it did not decrease significantly at 10% o2, but decreased by ...19911944414
cyclosporine-induced autoimmunity and immune hyperreactivity.cyclosporine (cs) is a potent immunosuppressive agent which under some circumstances paradoxically augments dth responses, aggravates some autoimmune diseases, and induces specific forms of autoimmunity. the enhancement of dth and other immune responses is closely related to the timing of cs administration relative to immunization. cs inhibits il-2 production (and several other lymphokines) at a pretranscriptional level, but does not usually prevent the antigen-specific priming of t cells, such ...19911954315
production of interferon gamma in cultures of whole blood obtained in the course of and after healing of cutaneous leishmaniasis.whole-blood cultures from individuals with cutaneous leishmaniasis due to leishmania major, tested under field conditions, showed a good correlation between the production of interferon-gamma and total blood lymphocyte proliferation (tlp), assayed by response to specific leishmania antigen. a group of patients, re-tested on several occasions, converted to positive in both parameters of cell mediated immunity (cmi) at the same time. it is suggested that the tlp assay and the production of interfe ...19911796880
the failure of traditionally used desert plants to act against cutaneous leishmaniasis in experimental animals.several desert plants that are traditionally used by the bedouin community as folkloristic treatment for skin diseases were examined for their efficacy against cutaneous leishmaniasis (cl) in balb/c mice. water and chloroform extracts made from these plants were incorporated into cetomacrogol and soft white paraffin respectively and some were supplemented with dmso. these preparations were applied twice daily for up to 30 days to cl lesions caused by leishmania major. none of the extracts tested ...19911809242
reconstitution of leishmania immunity in severe combined immunodeficient mice using th1- and th2-like cell lines.leishmania major disseminates in genetically susceptible balb/c mice to cause fatal disease. progressive infection has been linked to the failure of parasite-specific th1, ifn-gamma-producing, cd4+ t lymphocytes to expand and direct macrophage activation and control of intracellular parasitism. in contrast, th2 cd4+ cell expansion accompanies disease progression. immunomodulation using cd4 cell depletion at the time of infection results in control of infection and th1 cd4+ cell expansion. a th1- ...19911831830
ifn-gamma modulates the early development of th1 and th2 responses in a murine model of cutaneous leishmaniasis.resistance to leishmania major in mice is associated with the generation of distinct cd4+ th subsets, termed th1 and th2. to define the factors contributing to the genesis of these th cells, we first investigated when these subsets developed following l. major infection. lymph node (ln) cells collected 3 days after infection of balb/c mice secreted il-4 and il-5 in vitro, but little ifn-gamma, whereas ln cells from a resistant strain, c3h/hen, secreted ifn-gamma and no il-4 or il-5. cytokine pro ...19911833466
comparison on the performance of leishmania major-like and leishmania braziliensis braziliensis as antigen for new world leishmaniasis igg-immunofluorescence test.the performance of an antigen of l. major-like promastigotes for the serological diagnosis of mucocutaneous leishmaniasis in the igg-immunofluorescent test was compared to that of an antigen of l.braziliensis braziliensis. each antigen was used to test two hundred and twenty-four sera of etiologies such as mucocutaneous leishmaniasis, deep mycoses, toxoplasmosis, malaria. chagas' disease, visceral leishmaniasis, anti-nuclear factor, schistosomiasis, rheumatoid factor and normal controls. agreeme ...19911844982
effect of hyper-osmotic stress on alanine content of leishmania major promastigotes.earlier studies showed that leishmania major promastigotes are sensitive to osmotic conditions. a reduction in osmolality caused the cells to shorten and to rapidly release most of their large internal pool of alanine. in this study some effects of hyper-osmotic stress were examined. an increase in osmolality of the culture medium from 308 to 625 mosm/kg caused only a small decrease in growth rate. when cells grown in the usual culture medium (308 mosm/kg) were washed, resuspended in iso-osmotic ...19911997677
leishmania major and meriones crassus in north sinai governorate, egypt.zoonotic cutaneous leishmaniasis (zcl.) now seems to be more than was once thought in north sinai. in the present study, meriones crassus (23) and m. sacramenti (10) were collected from limited foci of human cl. leishmania major (four strains) were isolated from m. crassus as indicated enzymologically by the cellulose acetate electrophoresis of nine different enzymes (mdh, 6 pgd, gd, pk, pgm, nh, gpi, me and sod). the four strains were equivalent to zymodeme lon 1 (three strains) and lon 2 (one ...19911875065
[the characteristics of the epidemic activation of a natural focus of zoonotic cutaneous leishmaniasis in places with a sympatric dissemination of leishmania major, l. turanica and l. gerbilli].in 1975-1978 and in 1985-1988 studies of species composition and number of phlebotomus, r. opimus infestation with l. major, l. turanica and l. gerbilli as well as epidemic activity of the natural foci were performed in the karshi steppe in uzbekistan. typical areas have been compared in the desert, oasis and desert land irrigated for cotton growing. a correlation has been established between the epidemic activity of the natural focus and the nature of epizootic development in r. opimus and spec ...19911837582
analysis of enhancing effect of sand fly saliva on leishmania infection in mice.salivary gland lysates of the sand fly lutzomyia longipalpis markedly enhance the course of infection with leishmania major in mice. here we examine various parameters of this phenomenon. the exacerbative effect of l. longipalpis salivary gland lysates occurred in five different mouse strains; however, the character of the effect varied from one strain to another. consistent exacerbation of infection was achieved with as little as 1/10 of a gland. the exacerbative effect applied to more than one ...19912019430
resistance to leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages.inbred strains of mice differ considerably in their innate resistance to leishmanial infection. balb/c mice are highly susceptible to cutaneous leishmaniasis caused by leishmania major, whereas cba mice are resistant. we now show that this resistance correlates with the ability of macrophages to synthesize nitric oxide (no) following activation with interferon-gamma or tumor necrosis factor alpha. furthermore, the larger amounts of no generated by resistant macrophages are related to higher leve ...19911721024
tnf-alpha reverses the disease-exacerbating effect of subcutaneous immunization against murine cutaneous leishmaniasis.earlier studies have demonstrated that mice injected subcutaneously or intramuscularly with leishmanial antigens develop significantly exacerbated disease compared with unimmunized controls when challenged with the cutaneous protozoan parasites leishmania major. we report here that this disease enhancement can be prevented, and protective immunity induced, by the incorporation of recombinant tumour necrosis factor (tnf-alpha) in the immunizing inoculum. this effect of tnf-alpha is dose-dependent ...19911748478
t-cell reactivity to purified lipophosphoglycan from leishmania major: a model for analysis of the cellular immune response to microbial carbohydrates.the major macromolecule on the surface of leishmania major promastigotes is a lipophosphoglycan (lpg). this glycoconjugate plays a key role in determining infectivity and survival of parasites in the mammalian host cell. in addition, l. major lpg is able to induce a host-protective immune response. in this article, we summarise the evidence for recognition of highly purified lpg by t cells and we discuss the potential mechanisms of t-cell stimulation by this non-protein antigen.19912049034
a test for genetic exchange in mixed infections of leishmania major in the sand fly phlebotomus papatasi.we tested if genetic exchange was observable between two strains of leishmania major (trypanosomatidae) during mixed infection of the sand fly phlebotomus papatasi. previous studies suggested that genetic exchange may occur in natural populations of leishmania at a low frequency, but experimental crosses examining small numbers of progeny (less than 60) did not reveal hybrid parasites. accordingly, a strategy was devised to increase the number of progeny that could be screened by 100-fold. clona ...19911880760
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