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heterologous expression of the bifunctional thymidylate synthase-dihydrofolate reductase from leishmania major.the bifunctional thymidylate synthase-dihydrofolate reductase (ts-dhfr) of leishmania major has been cloned and expressed in escherichia coli and saccharomyces cerevisiae. the strategy involved placing the entire 1560-bp coding sequence into a parent cloning plasmid that was designed to permit introduction of unique restriction sites at the 5'- and 3'-ends. in this manner, the entire coding sequence could be easily subcloned into a variety of expression vectors. high levels of ts-dhfr gene expre ...19882841973
dna hybridizations on squash-blotted sandflies to identify both phlebotomus papatasi and infecting leishmania major.epidemiological field studies on leishmaniasis have been hampered by the laborious, and often inefficient, methods used to assess the rates of infection of sandfly vectors (diptera; phlebotominae) by species of the causative disease organisms, protozoal parasites of the genus leishmania (kinetoplastida; trypanosomatidae). we report the rapid and accurate identification of both sandfly vector (phlebotomus (phlebotomus) papatasi (scopoli] and infecting leishmania major yakimov & schokov by dna hyb ...19882856540
aggravation of experimental cutaneous leishmaniasis in mice by administration of interleukin 3.previous studies from our laboratory have shown that some in vitro maintained leishmania major-specific l3t4+ t cells were capable of exacerbating cutaneous leishmaniasis after adoptive transfer to normal syngeneic mice. results presented in this report show that these cells released substantial amounts of interleukin 3 (il 3) and granulocyte-macrophage colony-stimulating factors after specific stimulation in vitro. in order to assess the involvement of such lymphokines in the exacerbation of cu ...19882970970
[isoenzyme analysis of the leishmania major strains isolated from patients with zoonotic cutaneous leishmaniasis in different sections of the endemic territory in the ussr]. 19882971864
leishmania major: analysis of lymphocyte and macrophage cellular phenotypes during infection of susceptible and resistant mice.genetically susceptible balb/c and resistant c57bl/6 mice were infected with leishmania major and the phenotypes of the responding cells in the draining lymph nodes and cutaneous lesions were analyzed. as early as 1 week, significantly increased numbers of l3t4+ cells as compared to lyt-2+ cells were present in balb/c mice lymph nodes (p less than 0.005). increases in l3t4+ and lyt-2+ cells were comparable in c57bl/6 mice, resulting in threefold lower l3t4/lyt-2 ratio than in balb/c mice. t cell ...19883127233
regulation of activated macrophage antimicrobial activities. cooperation of lymphokines for induction of resistance to infection.macrophages treated with the soluble products of ag-stimulated spleen cells from bacillus calmette-guérin-infected c3h/hen mice (lymphokines) (lk] before infection developed the capacity to resist infection with obligately intracellular amastigotes of the protozoan parasite, leishmania major: 40 to 60% fewer cells in lk-treated cultures were infected 2 h after exposure to parasites than cells in medium-treated controls. macrophages treated with lk depleted of ifn-gamma failed to acquire this act ...19883133412
regulation of activated macrophage antimicrobial activities. identification of lymphokines that cooperate with ifn-gamma for induction of resistance to infection.macrophages exposed to lymphokines (lk) before exposure to parasites develop the capacity to resist infection with amastigotes of leishmania major. activity of lk for induction of this activated macrophage effector function is abrogated by depleting the lk of ifn-gamma, yet ifn-gamma is incapable of inducing the activity by itself. to identify the factors in lk that serve as second signals for induction of resistance to infection, we exposed macrophages to the following cytokines available as re ...19883135315
application of recombinant granulocyte-macrophage colony-stimulating factor has a detrimental effect in experimental murine leishmaniasis.the purpose of this study was to evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (rgm-csf) on balb/c mice infected s.c. with the intracellular pathogen leishmania major. daily i.p. application of 1 microgram rgm-csf for 21 days following the infection led to an aggravated course of the disease in most animals. in no case was a therapeutic effect observed. in vitro analysis revealed that the parasite burden was approx. 2- to 7-fold higher in the infected lesion ...19883142778
a family of glycoinositol phospholipids from leishmania major. isolation, characterization, and antigenicity.the glycolipids of the protozoan leishmania major strain lrc-l119 belong to a class of glycoinositol phospholipids (gipl) that show partial structural homology to the phosphatidylinositol-containing glycolipid membrane anchors of several eukaryotic proteins and the lipid moiety of l. major lipophosphoglycan. the gipls were the only glycolipids detected and were purified by octyl-sepharose and thin layer chromatographies. analysis of the native and dephosphorylated glycolipids (gipls 1-6) by gas ...19892910865
cloning of developmentally regulated genes from leishmania major and expression following heat induction.the protozoa leishmania undergo morphological and biochemical transformation from the promastigote to the amastigote form during their life cycle. to characterize this transformation process, we constructed a cdna library for the promastigote stage of leishmania major and used differential cdna hybridization to identify cdna sequences expressed at different abundance in promastigotes or amastigotes of l. major. p100/11e is a single copy gene whose 1600-nucleotide mrna is enriched in promastigote ...19892917999
the developmentally regulated p100/11e gene of leishmania major shows homology to a superfamily of reductase genes.the life cycle transformation of the protozoan parasite leishmania from promastigote to amastigote is accompanied by changes in the level of expression of a number of proteins whose function may be necessary for parasite survival in the sandfly vector or mammalian host. to genetically characterize these proteins, we have cloned and characterized cdna sequences that vary in abundance during the life cycle of leishmania major. one sequence (p100/11e) encodes a poly(a+) rna whose abundance is marke ...19892918000
leishmania major: histopathological responses before and after topical treatment in experimental animals.the cellular response in the cutaneous leishmaniasis lesion (cl), of balb/c mice treated topically with an ointment composed of 15% paromomycin and 12% methylbenzethonium chloride (pr-ointment) was studied. in the infected, untreated control group, the lesion showed progressive necrosis with an increase in the number of parasites, macrophages, lymphocytes, and polymorphonuclear cells over a period of 18 weeks. in the pr ointment-treated group, complete healing of the lesion was observed 4 weeks ...19892924878
genes encoding the major surface glycoprotein in leishmania are tandemly linked at a single chromosomal locus and are constitutively transcribed.the major surface glycoprotein of leishmania, gp63, is encoded by a small multi-gene family of tandemly linked genes which map to a single chromosome. for leishmania major, there are five 3.1 kilobasepair (kb) direct repeat units which include a 1.8-kb open reading frame and a 1.3-kb intergenic or spacer region. in addition, there is a single gene copy linked as a direct repeat but separated from the tandem array of gp63 genes by about 8 kb. the restriction enzyme map of the repeat unit is highl ...19892927448
l3t4+ t cells promoting susceptibility to murine cutaneous leishmaniasis express the surface marker ly-24 (pgp-1).in a murine model of cutaneous leishmaniasis, the importance of t cell-dependent immunity has been documented by the susceptibility to parasite infection of athymic nude mice of both genetically resistant and genetically susceptible strains. t lymphocytes from uninfected mice have the capacity to promote resistance to leishmania major infection in nude recipients, whereas t cells from mice chronically infected with l. major not only fail to mediate protection, but totally abrogate the host-prote ...19892467816
the immunochemical structure and surface arrangement of leishmania donovani lipophosphoglycan determined using monoclonal antibodies.using intact leishmania donovani promastigotes or purified l. donovani lipophosphoglycan (lpg) as immunogens, we have derived four lpg-specific monoclonal antibodies (mabs). two of these mabs recognize an epitope consisting of the repeating phosphorylated galactose beta-1,4-mannose disaccharide portion of the molecule and cross-reacted with lpg from leishmania major. these mabs bound to the surface of living promastigotes of both species. the two other mabs bound to the phosphosaccharide core st ...19892475775
wild-type and drug-resistant leishmania major hydrolyze methotrexate to n-10-methyl-4-deoxy-4-aminopteroate without accumulation of methotrexate polyglutamates.we have examined the metabolism of the folate analog methotrexate (mtx) in the human parasite leishmania major. these cells readily hydrolyzed mtx to n-10-methyl-4-deoxy-4-aminopteroate (mapa), such that following a 24-h incubation in 1 microm [3h]mtx approximately 30% of the cell-associated radioactivity was mapa. mapa also accumulated in the culture medium, exceeding the concentration of mtx after 24 h. neither 7-hydroxy-methotrexate nor mtx polyglutamates were observed in cells or medium, eve ...19892476435
transcriptional mapping of the amplified region encoding the dihydrofolate reductase-thymidylate synthase of leishmania major reveals a high density of transcripts, including overlapping and antisense rnas.we have examined the transcriptional organization of the r region of the protozoan parasite leishmania major. this region encodes the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (dhfr-ts) and is frequently amplified as a 30-kilobase (kb) extrachromosomal circular dna in methotrexate-resistant lines. northern (rna) blot analysis shows that the r region encodes at least 10 stable cytoplasmic polysomal poly(a)+ rnas, ranging in size from 1.7 to 13 kb and including the 3.2-kb dh ...19892476667
phosphocholine epitopes on helminth and protozoal parasites and their presence in the circulation of infected human patients.antigens containing phosphocholine (pc) circulate in the blood during chronic filarial infection. because of the wide occurrence of such pc epitopes, we examined their specificity by evaluating 10 common parasites of humans for the presence of pc epitopes, and sera from patients infected with these parasites for circulating antigens containing pc. immunoblot analysis of extracts from various parasites using an anti-pc monoclonal antibody (ca101) demonstrated the presence of pc epitopes on the pr ...19892482559
hepatic microsomal protein and cytochrome p-450 in balb/c mice infected with leishmania.the effects of infection of mice with leishmania major on liver microsomal protein and cytochrome p-450 were examined. the levels of hepatic microsomal protein and cytochrome p-450 were monitored at 6, 7, 9 and 12 weeks post-infection. the results indicated that the amount of hepatic microsomal protein and cytochrome p-450 were unchanged throughout the course of infection with l. major, despite the high degree of parasite proliferation in kupffer cells and marked reduction in phagocytosis. the c ...19892491220
inhibition of interferon gamma-induced macrophage microbicidal activity against leishmania major by liposomes: inhibition is dependent upon composition of phospholipid headgroups and fatty acids.multilamellar liposomes of phosphatidylcholine and phosphatidylserine at a 7:3 molar ratio significantly inhibited activation of murine resident peritoneal macrophages by recombinant murine interferon-gamma for cytotoxicity against amastigotes of the protozoan parasite leishmania major; other macrophage effector functions, such as particle phagocytosis or tumoricidal activity, were unaffected. this inhibition was not due to direct toxic effects of liposomes against parasite or macrophage, was fu ...19892495252
carbon dioxide abolishes the reverse pasteur effect in leishmania major promastigotes.the products released by leishmania major promastigotes incubated with [1-13c]glucose as sole exogenous carbon source were identified using nuclear magnetic resonance (nmr). under aerobic (95% o2/5% co2) conditions, acetate, succinate, and small amounts of pyruvate, d-lactate, and glycerol were released in addition to co2. under anaerobic (95% n2/5% co2) conditions, the relative amounts of products formed changed and alanine was also released. the changes in the rates of glucose consumption and ...19892498656
administration of monoclonal anti-ifn-gamma antibodies in vivo abrogates natural resistance of c3h/hen mice to infection with leishmania major.c3h/hen mice that are naturally resistant to cutaneous disease and systemic infections with the protozoan parasite, leishmania major, were treated at the time of infection, and weekly thereafter, with mouse anti-rat ifn-gamma mab or an irrelevant antibody of similar isotype. anti-ifn-gamma-treated mice developed cutaneous lesions; parasites spread to the regional lymph nodes and then metastasized to spleens and livers. the course of disease in these animals was similar to that of genetically sus ...19892499629
immunity to experimental infection with leishmania major: generation of protective l3t4+ t cell clones recognizing antigen(s) associated with live parasites.exacerbation and resolution of lesions induced by leishmania major promastigotes are, at least in part, the result of the activity of distinct parasite-specific l3t4+ t lymphocytes. the present report describes l. major-specific cloned l3t4+ t lymphocytes capable of transferring substantial protective immunity to normal highly susceptible balb/c mice. the two protective t cell clones analyzed appear to recognize antigen associated only with live l. major parasites. therefore, the pattern of anti ...19892500348
macrophage activation by interferon-gamma from host-protective t cells is inhibited by interleukin (il)3 and il4 produced by disease-promoting t cells in leishmaniasis.balb/c mice are highly susceptible to leishmania major infection. they develop a progressive fatal disseminating disease even with a minimum infecting dose. however, these mice are able to contain the disease if they are exposed to sublethal gamma-irradiation shortly before infection. earlier studies demonstrated that cd4+ t cells from mice which had recovered from infection (tr) can adoptively transfer resistance. in contrast, cd4+ cells from mice with progressive disease (ts) not only failed t ...19892503386
enhancement of macrophage il-1 production by leishmania major infection in vitro and its inhibition by ifn-gamma.peritoneal cells from highly susceptible balb/c mice were infected with leishmania major and cultured for various times in vitro. the culture supernatants contained significant levels of il-1 which were consistently higher than those in the cell cultures stimulated with an optimal concentration of lps. this finding extends to a macrophage cell line, p388d1, and peritoneal exudate cells stimulated with starch in vivo. however, the level of il-1 produced was significantly reduced when the cells we ...19892506273
reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. evidence for expansion of distinct helper t cell subsets.we purified poly(a)+ mrna from the spleen and lymph nodes at designated times after infection with leishmania major in genetically susceptible balb/c and resistant c57bl/6 mice. the steady-state levels of il-2, ifn-gamma, il-4, and il-1 beta mrna were determined using northern hybridizations. il-2 mrna levels in the infected organs of balb/c and c57bl/6 mice were comparable after infection, but ifn-gamma and il-4 mrna levels were reciprocally expressed. levels of ifn-gamma mrna in c57bl/6 draini ...19892521244
elimination of cd4+ suppressor t cells from susceptible balb/c mice releases cd8+ t lymphocytes to mediate protective immunity against leishmania.this study examined the capacity of balb/c mice that had been depleted of t cell subpopulations to generate a protective immune response to leishmania major. thymectomized mice were depleted of either l3t4+ (cd4+) t lymphocytes, ly2+ (cd8+) t lymphocytes, or both, by treatment with appropriate mabs. it was found that susceptible mice were rendered resistant to leishmania by an intravenous infusion of anti-l3t4 mab. these mice generated an immune response that destroyed the parasite in the primar ...19892523955
structural analysis of glycosyl-phosphatidylinositol antigens of leishmania major.three glycosyl-phosphatidylinositol glycolipids recognized by antibodies from patients with cutaneous leishmaniasis were extracted from leishmania major promastigotes by hexane:isopropanol and then purified by thin layer chromatography and lh-20 gel chromatography. structural analysis was carried out using chemical analyses, fast atom bombardment mass spectrometry, and 1h nmr. the major structures deduced can be summarized as follows: (formula: see text) where n = 0, 1, 2; r1 = (ch2)23-ch3; r2 = ...19892525125
cr1, the c3b receptor, mediates binding of infective leishmania major metacyclic promastigotes to human macrophages.the role of complement receptors on monocyte derived human macrophages in phagocytosis of infective (mp) and noninfective (lp) developmental stages of leishmania major promastigotes was studied. we compared binding of these specific developmental stages to mo after preincubation in fresh or heat-inactivated serum. although lp do not require fresh serum for attachment, mp were dependent on serum c opsonization for entry. inhibition of cr1 substantially abolished binding of the infective mp. in co ...19892525590
[effect of the irrigation and reclamation transformation of the karshi steppe on burrow sandflies of the genus phlebotomus--vectors of the causative agent of zoonotic cutaneous leishmaniasis].studies of land irrigation effect on phlebotomus sandflies, carriers of leishmania major (a zoonotic cutaneous leishmaniasis causative agent)--were performed for 15 field work periods, from 1967 to 1981, at 18 sites in various natural areas of the karshi steppe (uzbek ssr). over 43500 sandfly specimen were caught and identified. regularities in sandfly number changes, first of all, that of ph. papatasi, after irrigation were determined, with respect to various proximity of great gerbils' settlem ...19892528673
changes in orthophosphate, pyrophosphate and long-chain polyphosphate levels in leishmania major promastigotes incubated with and without glucose.the intracellular levels of orthophosphate (pi), pyrophosphate (ppi) and short- and long-chain polyphosphate (poly p) were measured in leishmania major promastigotes incubated in a phosphate-free medium. in the absence of exogenous substrate, the levels of both pi and ppi increased during a 1 h incubation. the increase in both pi and ppi was prevented when glucose was present, but glycerol prevented the rise in pi only. a rise in pi and ppi was also seen in cells incubated in the absence of exog ...19892543817
evidence for a phosphatidylinositol anchor in glycolipid antigens of leishmania major.the structure of the membrane anchor of three leishmania major surface antigenic glycolipids was analyzed. phosphatidylinositol-specific phospholipase c treatment and nitrous acid deamination indicated the presence of a phosphatidylinositol anchor linked to the glycan through a non-n-acetylated hexosamine. an ester linkage on the c-2 of glycerol was revealed by phospholipase a2 hydrolysis. this fatty acyl substitution was not found on the phosphatidylinositol anchor of the leishmania lipophospho ...19892550007
lymphokine mediated microbicidal activity of peritoneal macrophages from leishmania donovani infected and drug treated balb/c mice.the resident peritoneal macrophages from untreated mice develop potent microbicidal activity against amastigotes of leishmania major and leishmania donovani after in vitro exposure to lymphokines (lk) from mitogen stimulated spleen cells. however, to the best of our knowledge, the response of l. donovani infected peritoneal macrophages from already infected/treated animals to lk has not been investigated. therefore in the present study, the effect of lk on infected macrophages from balb/c mice f ...19892554031
a kinetoplast dna probe diagnostic for leishmania major: sequence homologies between regions of leishmania minicircles.a restriction fragment from a cloned kinetoplast minicircle dna has been shown to be diagnostic for leishmania major. this 402-bp taqi fragment has been used routinely (as a radiolabelled probe) to detect 10(4) parasites in simple dot blots, both experimentally and in epidemiological surveys. it positively identified all stocks of l. major tested (including all six known zymodemes) and showed very low homology to kinetoplast dna (kdna) and chromosomal dna of leishmania infantum and leishmania tr ...19892558320
coexistence of antigen-specific th1 and th2 cells in genetically susceptible balb/c mice infected with leishmania major.cd4-positive t cell clones with specificity for the protozoan parasite leishmania major (l. major) of both the protective th1 and the disease-exacerbating th2 subtype were isolated from a diseased l. major-infected mouse of the susceptible balb/c strain. in addition, th2 cells were isolated from the lesion-draining lymph nodes of an animal clinically healed nine months after sublethal irradiation and subsequent infection. our data support the notion that the differential outcome of the disease i ...19892575598
the psa-2 glycoprotein complex of leishmania major is a glycosylphosphatidylinositol-linked promastigote surface antigen.polyclonal rabbit antiserum to the triton x-114 phase material of leishmania major, which comprises the surface and internal integral membrane proteins of the parasite, was used to screen a lambda gt11 genomic expression library. a recombinant clone producing a mr 123,000 beta-galactosidase fusion protein was isolated. antibodies affinity-purified on this fusion protein recognized a complex of three surface-oriented proteins of promastigotes of l. major of mr 94,000, 90,000, and 80,000 that we h ...19892592773
transfection of leishmania enriettii and expression of chloramphenicol acetyltransferase gene.we report a transient expression transfection system in leishmania enriettii. a hybrid gene containing an intergenic region of the alpha-tubulin cluster and the bacterial chloramphenicol acetyltransferase (cat; ec 2.3.1.28) gene is expressed after transfection of l. enriettii with the hybrid plasmid. the expression of the cat gene is dependent on the presence of sequences from the alpha-tubulin gene. the hybrid gene is also active in leishmania braziliensis and leishmania major.19892594753
studies on the topical treatment of experimental cutaneous leishmaniasis: the therapeutic effect of methyl benzethonium chloride and the aminoglycosides, gentamicin and paromomycin.balb/c mice infected with either leishmania major or leishmania mexicana were treated twice a day for 10 days with an ointment containing 15% gentamicin or paromomycin, with or without 12% methylbenzethonium chloride (mbcl). it was found that topical application of either paromomycin or mbcl cured the parasite lesion, and that combined treatment with the two compounds had an additive effect. however, after four days' therapy there was a severe inflammatory response at the treatment site, and in ...19892604461
characterization of the promastigote surface protease of leishmania as a membrane-bound zinc endopeptidase.the effects of a variety of inhibitors suggested that the promastigote surface protease (psp) of leishmania might be a zinc metalloprotease. to investigate this possibility, we conducted atomic emission and absorption spectroscopic analyses, which show that psp contains 1 atom of zinc per 63-kda monomer. further studies showed that the enzyme can be biosynthetically labeled with 65zncl2. the comparison of the amino acid sequence of leishmania major psp with nine other zinc metalloproteinases rev ...19892608099
delayed-type hypersensitivity and lymphocyte proliferation in response to leishmania major infection in a group of children in jericho.the cellular response to leishmania major was evaluated in vitro with a lymphocyte proliferation microtest, performed on 100 microliters of whole blood obtained by finger prick. the maximum time and optimum conditions for storage of fresh blood before testing were determined, and the ability of the assay to evaluate cellular immunity to leishmania was compared to that of the classical montenegro skin test. a positive correlation between the diameter of the skin induration and the stimulation ind ...19892609368
antileishmanial activities of 2,4-diaminoquinazoline putative dihydrofolate reductase inhibitors.2,4-diaminoquinazoline analogs of folate were assessed as antileishmanial agents and as dihydrofolate reductase inhibitors. against leishmania major in human macrophages in vitro, two compounds with tertiary amines attached directly to the quinazoline ring were remarkably active. the 50% effective doses were in the picogram per milliliter range (12 to 91 pg/ml), and the in vitro therapeutic indices were approximately 10(5). these compounds were 1,000 times more active on an absolute basis and ha ...19892610496
course of infection and humoral response to leishmania major in inbred meriones unguiculatus.numerous species of meriones have been incriminated as natural reservoir hosts of leishmania major in mongolia, soviet asia, afghanistan, the middle east, and north africa. however, little is known about the immunological response or course of infection in these small rodents. in this study, 40 commercially obtained inbred meriones unguiculatus were divided into equal groups and injected in the right hind footpad with various doses of l. major promastigotes or with medium only. at regular interv ...19892614604
effect of leishmania major on luminol-dependent chemiluminescence of human whole blood phagocytosis.the aim of this study is to examine the effect of l. major on human whole blood phagocytosis. the phagocytosis was activated by phorbol myristate acetate (pma) or opsonized zymosan. various types of leishmania antigens were tested on luminol-dependent chemiluminescence. in pma-activated whole blood phagocytosis group, promastigotes and infected medium significantly (p less than 0.001) depressed the maximum peak of chemiluminescence to 5.77 +/- 1.6 and 5.65 +/- 0.45 mv respectively, compared to 9 ...19892617033
surface reaction of leishmania. iv. variation in the surface membrane carbohydrates of different strains of leishmania major.eleven strains of leishmania major were characterized by enzyme electrophoresis, excreted factor serotyping and lectin specificity determination. nine of the 12 enzyme mobilities were identical for all the strains. variation was seen in 6pgd, nh and ak. seven serological entities were recognized, including a non-ef producing strain. a panel of six lectins and sugar inhibitors was used to determine surface membrane carbohydrate configurations, which displayed considerable variation.19892619362
effects of anaerobiosis on adenine nucleotide levels and the release of atp by leishmania major promastigotes.1. leishmania major promastigotes showed a large decrease in atp and increases in adp and amp contents after 4 min of anaerobiosis. 2. when adp was added to intact promastigotes, it was completely metabolized, apparently by its conversion to adenosine extracellularly followed by adenosine uptake, further metabolism intracellularly, and release of hypoxanthine. under anaerobic conditions, adenosine uptake was strongly inhibited and adp degradation was stopped at adenosine. 3. under both aerobic a ...19892620489
[presence of leishmania major mon-26 in mali].the arabo-african zymodem mon-26 was identified for the first time in an autochtonous patient from mali. l. major has been previously identified in this country but it was in european patient and it was zymodem mon-25.19892624380
t-cell responses and immunity to experimental infection with leishmania major. 19892653376
experiences with vaccines against cutaneous leishmaniasis: of men and mice.the need for a vaccine(s) against cutaneous leishmaniasis and the populations at risk for whom such vaccines should be developed are briefly discussed. the current human vaccine studies are reviewed, as are some experimental mouse studies with emphasis on leishmania major infection relevant to vaccine development. based on the information available from the mouse model and those data which are being sought in human studies, the benign nature of the cutaneous disease, the ease with which l. major ...19892657601
anti-leishmanial antibodies during natural infection of psammomys obesus and meriones shawi (rodentia, gerbillinae) by leishmania major.sera from 77 rodents (psammomys obesus: 64; meriones (m.) shawi: 10; m. libycus: 3) trapped in a focus of zoonotic cutaneous leishmaniasis (zcl) (leishmania (l.) major) were examined for the presence of anti-leishmanial antibodies by the indirect fluorscence antibody technique (ifat) (l. major antigens) using homologous antiglobulins and/or anti-rattus conjugates. sera from 21 animals were positive with titres that ranged from 1: 20 up to 1: 640. the investigation revealed that a good correlatio ...19892658879
interactions of plasmodium berghei sporozoites and murine kupffer cells in vitro.malaria sporozoites must leave the bloodstream and cross a layer of sinusoidal lining cells in order to infect hepatocytes and undergo exoerythrocytic schizogony. to determine whether kupffer cells (kc) derived from this layer interact with sporozoites, murine kc were isolated from perfused livers of balb/cj mice and incubated in vitro with plasmodium berghei sporozoites. isolated kc had characteristic macrophage surface ag and were phagocytic, ingesting both latex particles and leishmania major ...19892668413
amastigote stage-specific monoclonal antibodies against leishmania major.monoclonal antibodies were produced against gamma-irradiated amastigotes of leishmania major. five antibodies (t16 through t20) were selected which reacted in enzyme-linked immunoassays with the intracellular stage of the parasite. these antibodies did not react with promastigotes of l. major or leishmania donovani. one of the monoclonal antibodies (t16) reacted with amastigotes of leishmania mexicana amazonensis and l. donovani. western blotting (immunoblotting) and immunoprecipitation of [35s] ...19892680982
analysis of the cellular parameters of the immune responses contributing to resistance and susceptibility of mice to infection with the intracellular parasite, leishmania major.although the course of infection induced by l.major in mice is influenced by several factors, including the parasite virulence, the macrophage permissiveness to this parasite and response to t cell-produced lymphokines, this review has been restricted to summarizing, the recent data concerning the t-cell responses generated during infection and their effect on the disease process. experimental evidence strongly suggests that t-cell responses play a fundamental role in resistance and susceptibili ...19892691392
genetics and molecular pathogenesis of legionella pneumophila, an intracellular parasite of macrophages.in addition to providing a powerful approach for identifying bacterial factors required for full infectivity and disease production, genetic analysis of legionella pathogenesis should also lend critical insight into the biology of the macrophage and into the pathogenesis of other intracellular parasites. the interaction between l. pneumophila and the macrophage exhibits many features found in a wide variety of prokaryotic and eukaryotic intracellular human pathogens. for example, binding to comp ...19892696860
the histopathological picture of concomitant infection with leishmania major and toxoplasma gondii in albino mice.zoonotic cutaneous leishmaniasis caused by l. major and toxoplasmosis caused by t. gondii are prevalent among man and animals in several localities in egypt particularly in the nile delta and sinai. double infection may take place. in this paper, it was intended to study the concomitant infection in albino mice. the results showed that the clinical and histopathological pictures differ in concomitant infection from that shown by infection with either parasite alone. therefore leishmaniasis and t ...19892708848
structural alterations of chromosome 2 in leishmania major as evidence for diploidy, including spontaneous amplification of the mini-exon array.we have utilized pulsed field electrophoresis to characterize several karyotypic alterations in leishmania major. promastigotes of the lt252 line contain three small chromosomes, of 300, 350 and 385 kb. quantitative densitometry of ethidium bromide-stained gels suggest that these chromosomes are present in equal levels (2:2:2). two derivatives of this line, one appearing spontaneously (lt252 delta) and one obtained following selection with methotrexate (11-mtxr20), exhibit altered levels of thes ...19892710169
biochemical characteristics of the metacyclic forms of leishmania major and l. mexicana mexicana.metacyclic forms of leishmania major and putative metacyclics of l. mexicana mexicana were found to occur in abundance in stationary phase cultures. these forms have been compared in several ways with promastigotes from mid-log phase cultures and, in the case of l. m. mexicana, amastigotes. metacyclics are smaller, contain less protein and appear more active than other promastigotes. both forms of promastigote respire at a high rate in the absence of exogenous substrate. the free amino-acid cont ...19892717219
peripheral neural involvement in cutaneous leishmaniasis. a pathologic study of human and experimental animal lesions.peripheral neural involvement in cutaneous leishmaniasis has recently been recognized. a man presented with several tender hyperesthetic skin nodules. histopathologic examination confirmed the diagnosis of cutaneous leishmaniasis. of most interest was the presence of a striking lymphohistocytic inflammatory infiltrate around and within cutaneous nerves in addition to demonstrable leishmania organisms in the perineural space. this observation led to a detailed histopathologic evaluation of leishm ...19892722338
dissemination in cutaneous leishmaniasis. 3. lymph node involvement.in a study of zoonotic cutaneous leishmaniasis (cl) due to leishmania major in an endemic focus in saudi arabia, lymph node enlargement was observed in 66 of 643 patients (10.26%). the epitrochlear lymph nodes were most commonly involved (68%), but cervical (11%), axillary (15%), and inguinal (18%) lymph nodes were also involved. in eight patients (12%), two lymph node areas were involved. the affected lymph nodes were typically solitary, firm, mobile, nontender, only moderately enlarged, and ap ...19892722339
characterization of integral membrane proteins of leishmania major by triton x-114 fractionation and analysis of vaccination effects in mice.the total integral membrane proteins of promastigotes of leishmania major were extracted by using the triton x-114 phase separation technique and were characterized by immunoprecipitation, western blotting (immunoblotting), and lectin chromatography. of the 40 or more proteins which partitioned into the detergent phase, only about 10 proteins could be surface radioiodinated on live promastigotes, suggesting their surface orientation. the abundance of the gp58-63 antigen varied markedly between t ...19892731987
cell surface nanoanatomy of leishmania major as revealed by fracture-flip. a surface meshwork of 44 nm fusiform filaments identifies infective developmental stage promastigotes.fracture-flip (anderson-forsman and pinto da silva, j. cell sci. 90, 531-541; 1988) was used to reveal the nanoanatomy of the surface of leishmania major promastigotes. over the cell surface of infective metacyclic promastigotes we identify a meshwork of 44 nm long, fusiform filaments. these filaments are not seen in noninfective stages of the parasite. replica-staining immunocytochemistry with monoclonal antibody against infective metacyclic lipophosphoglycan shows a uniform distribution of pro ...19892743996
the influence of temperature and serum deprivation on the synthesis of heat-shock proteins and alpha and beta tubulin in promastigotes of leishmania major.we have examined changes in the relative synthesis of individual proteins in promastigotes of leishmania major subjected to decreasing serum levels in vitro. we observed increases in the relative synthesis of the putative heat-shock proteins of 82 and 70 kda and of proteins of 79 and 41 kda but decreases in the synthesis of proteins of 38 and 28 kda. the relative synthesis of alpha-tubulin increased, whereas that of beta-tubulin decreased, in promastigotes subjected to decreased serum concentrat ...19892761570
effects of thiastearic acids on growth and on dihydrosterculic acid and other phospholipid fatty acyl groups of leishmania promastigotes.thiastearic acid positional isomers (8, 9, 10, 11) were examined for their ability to inhibit population growth and the biosynthesis of a phosphatidylethanolamine cyclopropane fatty acyl group, cis-9,10-methyleneoctadecanoic acid (dihydrosterculic acid), by promastigotes of leishmania species. thiastearic acids are candidate chemotherapeutic agents, since cyclopropane fatty acids are not formed by vertebrate cells. 8- and 10-thiastearic acids strongly inhibited the growth of strains containing t ...19892761573
a family of heat shock protein 70-related genes are expressed in the promastigotes of leishmania major.we describe the isolation and characterisation of two novel genes of the parasitic protozoan leishmania major that are related by nucleotide sequence homology to eukaryotic genes encoding 70 kd. heat shock proteins. the transcription of neither gene is heat-inducible but both are constituitively-expressed throughout the promastigote stage of the parasite life cycle. a third gene shows differential expression between non-infective and infective promastigote stages in the absence of any temperatur ...19892762121
multiple drug resistance and conservative amplification of the h region in leishmania major.amplification of the h region has been previously observed in methotrexate (mtx)-resistant strains of leishmania major and in unselected laboratory stocks of l. tarentolae. we now show that selection of l. major with the structurally unrelated drugs primaquine or terbinafine generated resistant lines exhibiting h region amplification and 23- and 12-fold cross-resistance to mtx, respectively. these and other drug-resistant lines bearing h region amplification also exhibited weak cross-resistance ...19892768255
sequence of a cdna for the nd1 gene from leishmania major: potential uridine addition in the polyadenosine tail. 19892770790
a role for lyt-2+ t cells in resistance to cutaneous leishmaniasis in immunized mice.the role of lyt-2+ t cells in immunologic resistance to cutaneous leishmaniasis was analyzed by comparing infection patterns in resistant c57bl/6 mice and susceptible balb/c mice induced to heal their infections after sub-lethal irradiation or i.v. immunization, with similar mice treated in vivo with anti-lyt-2 antibodies. administration of anti-lyt-2 mab resulted in a dramatic reduction in the number of lymphoid cells expressing the lyt-2+ phenotype. such treatment led to enhanced disease in bo ...19892784148
effect of cd4 monoclonal antibody in vivo on lesion development, delayed-type hypersensitivity and interleukin 3 production in experimental murine cutaneous leishmaniasis.highly susceptible balb/c mice subjected to adult thymectomy followed by prolonged (15 weeks), twice-weekly injections of a low dose (100 micrograms) of cd4 monoclonal antibody (moab) develop resistance to otherwise uniformly fatal and disseminating leishmania major infection. in contrast, similar treatment with cd8 moab has no effect on the course of l. major infection. cd4 moab administered after the lesion establishment also has no effect. mice which become resistant following cd4 moab treatm ...19892784747
vaccination against murine cutaneous leishmaniasis by using leishmania major antigen/liposomes. optimization and assessment of the requirement for intravenous immunization.efficacy of vaccination against cutaneous leishmaniasis in highly susceptible balb/c mice was assessed comparatively by using radiation-attenuated promastigotes and colloidal ag mixtures generated from a mixed leishmania major (lv39) isolate (slv39) and from a virulent cloned line (svj2) derived from the jericho 2 l. major isolate. dehydration-rehydration vesicle (drv) liposomes were used as adjuvants. in optimization experiments phospholipid composition of drv was varied, and the distearoyl der ...19892786033
the induction of protective immunity to leishmania major in the balb/c mouse by interleukin 4 treatment.the ability of interleukin 4 (il4), administered subcutaneously around the cutaneous lesion in the form of hydrophilic gels, to affect the development of established leishmania major infections in the balb/c mouse was studied. il4 had a therapeutic effect on l. major lesion growth compared with control mice, causing not only resolution of the parasite lesions over a period of 10 weeks but also rendering animals resistant to reinfection. adoptive transfer of splenic t cells, obtained from il4-tre ...19892786473
distinct il-3 activation profile induced by intravenous versus subcutaneous routes of immunization.lymphoid cells from mice immunized i.v. or s.c. with leishmania major antigens were analyzed for their capacity to produce lymphokines when stimulated with specific antigens in vitro. spleen cells from balb/c mice immunized by the s.c. route produced significantly higher levels of il-3 and il-3 mrna than those from mice immunized by the i.v. route. the differential production of il-3 was maintained at a wide range of antigen concentrations tested in vitro and for different culturing times. t cel ...19892788514
evidence of t-cell recognition in mice of a purified lipophosphoglycan from leishmania major.we have previously reported that a leishmania major lipophosphoglycan (lpg), given with killed corynebacterium parvum as an adjuvant, can vaccinate mice against cutaneous leishmaniasis. in order to analyze whether t cells are able to recognize this important parasite antigen, we have studied both humoral and cellular immune responses to l. major lpg that had been isolated from promastigotes by sequential solvent extraction and hydrophobic chromatography. the data show that immunization of mice w ...19892807527
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
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
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
leishmania major: nature of immunity induced by immunization with a mutagenized avirulent clone of the parasite in mice.a chemically mutagenized avirulent form of leishmania major was used to immunize balb/c and c57b1/6 mice against challenge with virulent l. major. immunity was elicited when the avirulent parasite was injected intravenously or intraperitoneally, but not subcutaneously. in fact, the latter route of immunization sometimes resulted in exacerbation of a subsequent infection with virulent l. major. mice immunized with avirulent l. major developed upon challenge with virulent l. major cutaneous lesion ...19901972362
resistance to murine cutaneous leishmaniasis is mediated by th1 cells, but disease-promoting cd4+ cells are different from th2 cells.a limiting dilution system has been used for quantitative analysis of antigen-reactive t cells producing interleukin (il)2, il4 and interferon (ifn)-gamma in the course of murine infection with leishmania major. the precursor frequencies of cd4+ cells with the potential for production of ifn-gamma, which has been associated with th1 cells, are much higher in resistant than in susceptible mice, whereas the reverse is found for cd4+ cells secreting il4 which have been classified as th2 cells. our ...19901976523
immunization of susceptible hosts with a soluble antigen fraction from leishmania major leads to aggravation of murine leishmaniasis mediated by cd4+ t cells.this study was performed in order to define leishmania major antigens that function as disease-modulating immunogens in susceptible balb/c mice. a soluble leishmanial antigen preparation (s-sla) derived from highly infective stationary-phase l. major parasites was fractionated by preparative gel electrophoresis. in vitro, the low molecular mass fraction (less than 31 kda) of s-sla fraction d (fr d) was found to be a potent stimulator of l. major-specific th1 and th2 helper cell clones. in vivo, ...19901980108
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
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
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
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
[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
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
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
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
tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of leishmania major amastigotes.we have previously shown that during an infection with leishmania major, susceptible balb/c mice, as opposed to mice of a resistant strain (c57bl/6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor-alpha (tnf-alpha) which is known to be a potent macrophage (m phi) stimulator in other parasitic diseases. in the present study we investigated whether tnf-alpha activates m phi for killing of l. major parasites. in the absence of interferon-gamma (ifn-gamma ...19902113475
il-2. a cofactor for induction of activated macrophage resistance to infection.macrophages cultured with il-2 and ifn-gamma before exposure to microorganisms developed the ability to resist infection with the obligate intracellular parasite, leishmania major. the induction of this macrophage effector response was maximal by 6 to 8 h after lymphokine addition, and was independent of lymphokine treatment sequence. activation of macrophages for resistance to infection was the result of the direct action of il-2 and ifn-gamma on macrophages: the effector reaction was demonstra ...19902115543
patterns of cytokine secretion in murine leishmaniasis: correlation with disease progression or resolution.susceptibility or resistance to infection with leishmania major correlates with the ability of mice to produce characteristic panels of lymphokines in response to the parasite. to investigate the role of antigen-presenting cells in this phenomenon, we developed a model system which used congenic (h-2d) susceptible and resistant mice. l. major-specific t cells were isolated from infected balb/c and b10.d2 mice, and the cells were restimulated in vitro on syngenic or congenic antigen-presenting ce ...19902123823
leishmania major amastigotes initiate the l-arginine-dependent killing mechanism in ifn-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha.macrophages exposed to ifn-gamma and infected with amastigotes of leishmania major develop the capacity to eliminate the intracellular pathogen. this antimicrobial activity of activated macrophages correlates with the initiation of nitrogen oxidation of l-arginine, yet other reports suggest that two signals are required for induction of this biochemical pathway for effector activity. in the present studies, macrophages treated with up to 100 u/ml ifn-gamma, or 100 ng lps, or 10(7) amastigotes pr ...19902124240
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
leishmania infecting man and wild animals in saudi arabia. 8. the influence of prior infection with leishmania arabica on challenge with l. major in man.a clinical trial is described of an attempt to protect against leishmania major by prior vaccination with live l. arabica. after a single, previously leishmanin-negative, adult male volunteer was bitten by 8 phlebotomus papatasi infected with l. arabica, no infected lesions were observed. he remained leishmanin-negative and his lymphocytes reacted weakly to antigens of l. arabica or l. major. subsequently he and 3 other leishmanin-negative adult male volunteers were vaccinated with cultures cont ...19902126153
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
effects of culture age and hexoses on fatty acid oxidation by leishmania major.the effect of culture age on the rate of oxidation of short-, medium, and long-chain fatty acids by leishmania major promastigotes was investigated. promastigotes from 5-day stationary phase cultures oxidized several saturated fatty acids about 3-to-4-fold faster than cells from late log phase cultures, but [10-14c]oleate was oxidized 9-fold faster. the increase in rate of oxidation was partially reversed within 5 h and almost completely reversed within 30 h after resuspending cells from a 5-day ...19902128337
structures of the glycoinositolphospholipids from leishmania major. a family of novel galactofuranose-containing glycolipids.structures of the major glycolipids isolated from the protozoan parasite leishmania major (strains v121 and lrc-l119), were elucidated by fast atom bombardment-mass spectrometry, two-dimensional proton nmr, methylation analysis, exoglycosidase digestions and mild acid hydrolysis. these glycolipids belong to a family of glycoinositolphospholipids (gipls), which contain 4-6 saccharide residues linked to alkylacylphosphatidylinositol (alkylacyl-pi) or lyso alkyl-pi. the general structure of the elu ...19902139661
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
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