specificity of transfer factor. in vitro lymphoblast transformation of peripheral lymphocytes to leishmania major antigen in the presence of transfer factor.the in vivo and in vitro demonstration of specificity of transfer factor (tf) has so far been hampered by lack of a suitable antigen. the host partiality of leishmania suggested that in the case of leishmania antigen it should be possible to obtain lymphocytes of both donors and recipients of tf which were either sensitized or truly virgin. lymphoblast transformation of normal donor lymphocytes to leishmania major antigen (lma) was therefore measured in the presence of tf prepared from donors wi ...197774087
[virulent properties of leishmania tropica major strains isolated from sandflies in the subzone of the northern deserts].on the territory of the karakalpak assr the infection of sand flies ph. papatasi, ph. caucasicus, ph. andrejevi and ph. monogolensis with the agent l. tropica major ammounts, on the average, to 39.3%. the virulence of 88 investigated strains of leishmania for white mice estimated by their infection and the duration of incubation was found to be different; one half of the strains had high, one third--average, and the other strains--low virulence.1976134342
[distribution characteristics of leishmania tropica major strains of differing virulence in natural and territorial complexes of the murgab eco-area (southeastern turkmenistan)].in september--october of 1973 and 1974 263 specimens of rhombomys opimus were shot in the territory of the murghab stationar. the seeding of the material (a piece of tissue) from all animals into nnn medium was done. 9 strains of l. tropica major were isolated from this material the virulence of which was studied on 2.5--3 months--old golden hamsters, cricetus auratus. differences in the virulence of the isolated strains according to their natural-territorial complexes are shown. these differenc ...1977145568
[characteristics of formation of humoral antibodies in albino mice in experimental infection with leishmania tropica major and leishmania tropica minor]. 1977412046
isolation of leishmania major from mastomys erythroleucus and tatera gambiana in senegal (west africa). 1979534447
isoenzyme characterization of leishmania species from iraq.leishmaniasis in iraq takes both the visceral and cutaneous forms. the causative organisms are identified according to the electrophoretic variation of the enzymes mdh, gpi, 6pgd, pgm and idh. the 37 visceral stocks investigated fall into two groups which differ only with respect to gpi. the six cutaneous stocks were divided into three groups. group 3 represents leishmania major, while groups 4 and 5 refer to l. tropica showing intraspecific variation with regard to 6pgd.1979539855
generalized infection and lack of delayed hypersensitivity in balb/c mice infected with leishmania tropica major.the susceptibility of a few strains of mice to a subcutaneous injection of leishmania tropica major, the causative agent of cutaneous leishmaniasis in humans, was studied. the infection in six strains (cba, akr/j, akr/cu, c57bl/6, a/j, and c3h) remained cutaneous, and the animals recovered within 3 to 4 months. in contast, the infection in balb/c became generalized and killed 1005 of infected animals. intraperitoneal injection of infected liver of balb/c to a/j and syngeneic mice produced a leth ...1979546790
[natural foci of zoonotic cutaneous leishmaniasis in central asia and the problems of the district division of the geographical range of leishmania major]. 1978672776
[factors causing death of mice infected with the culture of leishmania tropica major]. 1977927365
[effect of the dose of leishmania tropica major culture on antibody formation in mice with cutaneous leishmaniasis]. 1977927378
[fate of the promastigotes of leishmania tropica major and l. gymnodactyli in the body of phlebotomus papatasi under conditions of a mixed infection].experimental infection of males and females of phlebotomus papatasi sc. with leishmania tropica major from man and l. gimnodactyli from agama sanguinolenta was carried out in order to obtain mixed infection. sand flies from the laboratory culture were successively infected with promastigotes of each species of leishmania by means of compulsory dose feeding according to alekseev's method. for identification of leishmania cultures isolated from experimentally infected sand flies alder's serologica ...1976940687
[biological properties of promastigotes of leishmania having undergone lyophilization].materials are presented of a comparative study of morphological and cultural properties and virulence of liophylized cultures of leishmania tropica major after their rehydration or after a long passage on the nnn medium. results of investigations of two initial strains and three substrains obtained after the recovery of liophylized cultures have shown that liophylization does not reduce essentially the initial strain virulence. the strains undergone liophylization and passed repeatedly on the nn ...19761026908
ecological causes of predominance of some mammals as reservoirs of leishmania tropica major in turanian deserts. 19751158296
leishmaniasis and the arabian gulf. 19921285153
leishmania major: bacterial contamination of cutaneous lesions in experimental bacterial contamination has been demonstrated in cutaneous leishmaniasis (cl) nodule and in lesions caused by leishmania major in balb/c mice up to 20 days after infection. however, although many phagocytic cells (polymorphonuclear leukocytes and macrophages) were present in the cl lesion, 80% of the lesions showed bacterial contamination that developed within the first 70 days of infection. topical treatment of the lesion with an ointment containing 15% paromomycin and 12% methylbenzethonium ...19921286954
axenic cultivation of amastigotes of leishmania donovani and leishmania major and their infectivity.two clones of promastigotes, one of leishmania donovani and one of l. major, and an uncloned stock of l. major were axenically transformed to heat-shock amastigotes, at 35 and 37 degrees c, respectively. of the four different culture media tested, a relatively cheap, liquid medium, rblm, was found to be the best, both for the transformation of the promastigotes and the serial, axenic cultivation of the amastigotes. in an experiment of 30 days duration, serial cultivation, in an atmosphere with 5 ...19921288430
[leishmania major mon-117, an agent of cutaneous leishmaniasis in mauritania].the causative agent of cutaneous leishmaniasis in mauritania is identified for the first time as leishmania major mon-117, a new zymodeme closely related to mon-26. the authors point out the need to study this previously unknown focus.19921290377
ecoepidemiology of leishmaniases in syria. 3. leishmania major infection in psammomys obesus provides clues to life history of the rodent and possible control measures.collections of psammomys obesus from near damascus, syria in may 1990 and november 1991 contained animals of all ages. both series had a high prevalence of leishmania major infection. lesions were small in november and large in may. assuming the two collections were representative of typical years, it is inferred that the breeding season is between october and may: there is high winter mortality of animals born early in the breeding season, but high survival of their parents, and there is high m ...19921301732
experimental chemotherapy of leishmaniasis with adenosine analogue formycin a, in combination with inhibitor of nucleoside transport, nitrobenzylthioinosinate.a single dose of the adenosine analogue formycin a (foa) (20 mg/kg), combined with nitrobenzyl mercaptopurine ribonucleoside 5'-monophosphate (nbmpr-p) (10 mg/kg), a prodrug of nitrobenzylthioinosine (nbmpr), was effective in reducing the size of the foot pad lesions from 7.4 +/- 0.2 to 3.9 +/- 0.2 of syrian golden hamsters infected with leishmania major. there was a statistical difference (p < 0.01) in the size of the foot pad by the fifth day between the infected groups that received treatment ...19921306154
cellular responses of vervet monkeys (cercopithecus aethiops) experimentally infected with leishmania major. 19921307757
thymidine kinase as a negative selectable marker in leishmania major. 19921315415
soluble tnf and membrane tnf expressed on cd4+ t lymphocytes differ in their ability to activate macrophage antileishmanial our studies of host defense against the intracellular parasite leishmania major, we obtained evidence for a novel mechanism of macrophage activation for antimicrobial defense that involves direct cell contact between cd4+ t lymphocytes and leishmania-infected macrophages. the mechanism is distinctive as it does not involve secretion of lymphokines but is apparently mediated by the membrane-anchored form of tumor necrosis factor (mtnf; approximately 50-60 kd) present on the surface of the effe ...19921347312
immunobiology of experimental leishmaniasis.self-cure versus uncontrolled disease progression in experimental murine cutaneous leishmaniasis depends upon a delicate interplay among various activated cells of the host's immune system. susceptibility or resistance to infection with leishmania major is correlated with the ability of different inbred strains of mice to produce the characteristic spectra of lymphokines upon infection. appropriate experimental interventions now allow the modulation of these responses, providing the possibility ...19921349724
thymopentin reduces the susceptibility of aged mice to cutaneous leishmaniasis by modulating cd4 t-cell subsets.balb/c mice are highly susceptible to leishmania major infection. the susceptibility increases progressively with the age of the mice. aged mice produce progressively lower levels of interleukin-2 (il-2) and interferon-gamma (ifn-gamma) but higher levels of il-4 compared to younger mice. thymopentin, a pentapeptide with thymopoietin activity, dramatically increases the resistance to leishmania major infection in aged mice. the thymopentin-treated mice produce enhanced levels of il-2 and ifn-gamm ...19921356094
immunology of leishmaniasis.resolution of leishmanial infections requires the expansion of specific type 1 t helper cells that secrete or express on their membrane lymphokines capable of activating macrophages that contain these parasites to a microbicidal state. specific cd8+ t cells, which are triggered during infection, also appear to play a role in protective immunity, possibly through their ability to secrete interferon-gamma. in the mouse model of infection with leishmania major, the expansion of specific type 2 t he ...19921356346
changes in the precursor frequencies of il-4 and ifn-gamma secreting cd4+ cells correlate with resolution of lesions in murine cutaneous leishmaniasis.limiting dilution analysis was used to estimate the frequency of clonogenic ag-specific cd4+ t lymphocytes in draining lymph nodes of mice over the course of infection with leishmania major, and to measure the production of il-2, il-3, il-4, ifn-gamma, and tnf by the resultant clones. infection of both genetically susceptible balb/c ("non-healer") and resistant c57bl/6 ("healer") mice resulted in at least a fourfold increase in the frequency (to about 0.3%) and at least a 10-fold increase in the ...19921357029
role of t cell subsets during the recall of immunologic memory to leishmania major.the contributions of different t cell subpopulations to the maintenance of immunity during secondary leishmania major infections were analyzed in healed, resistant animals by depletion of t cell subsets in vivo. the strong delayed-type hypersensitivity mounted in immune genetically resistant mice upon challenge with viable promastigotes was mediated by both cd4+ and cd8+ t cells. each t cell subpopulation alone contributes, although to a different extent, to the resolution of secondary lesions; ...19921359969
lessons from leishmania: a model for investigations of cd4+ subset differentiation.infection of inbred mice with leishmania major remains the best model of human infection with visceralizing leishmania that cause kala-azar. immunologic investigations have correlated the outcome of disease with expansion of different subsets of cd4+ cells, designated th1 and th2. although the capacity of fixed effector th1 and th2 populations to mediate the diverse outcomes of disease through the release of soluble cytokines, particularly ifn-gamma and il-4, has been demonstrated, the mechanism ...19921365527
identification of a macrophage-binding determinant on lipophosphoglycan from leishmania major promastigotes.leishmania are obligatory intracellular parasites in mammalian macrophages that gain entry by receptor-mediated phagocytosis. their major cell surface glycoconjugate, lipophosphoglycan (lpg), has been implicated in this process. a monoclonal antibody specific for leishmania major lpg (wic 79.3), which has been shown to block promastigote attachment to macrophages, was used to identify a macrophage-binding determinant of lpg. wic 79.3 bound exclusively to the phosphorylated repeats of lpg and not ...19921370357
genomic organisation and expression of a differentially-regulated gene family from leishmania major.we have isolated and characterised a differentially-regulated gene family in the protozoan parasite leishmania major. the family contains 5 genes linked within a 10kb region of the genome: three of the genes are closely related in dna sequence, the other two have only limited homology. post-transcriptional control of the differential expression pattern is suggested by detection of precursor rna molecules containing intergenic sequences and evidence that mature mrna molecules contain a 35nt splic ...19921371863
short amino acid sequences derived from c1q receptor (c1q-r) show homology with the alpha chains of fibronectin and vitronectin receptors and collagen type iv.the human c1q receptor (c1q-r) is a 65-70-kd, highly acidic, hydrophobic glycoprotein that is expressed on a wide variety of cell surfaces. although the c1q-r itself appears to bind preferentially to c1q, the region of the ligand to which c1q-r binds is the primary binding site for several other molecules, including fibronectin, laminin, and c1q inhibitor (chondroitin 4-sulfate proteoglycan) as well as the complement c1r2c1s2 tetramer. in order to further characterize the c1q-r molecule with reg ...19921377218
[the identification of marker strains of leishmania major, l. turanica and l. gerbilli by the polymer chain reaction with a universal primer].the leningrad nuclear physics institute, academy of science of the ussr, and martsinovskiÄ­ institute of medical parasitology and tropical medicine, ussr ministry of health, developed polymerase chain reaction (pcr) technique with universal primer 3-2 for leishmania identification. the primers were patented in the ussr (patent no 4757254, 1989). reference strains of three leishmania species were identified: l. major--mrho/su/59/neal p; l. gerbilli--mrho/cn/60/gerbilli; l. turanica--mrho/su/80/cl ...19921380631
developmental modification of lipophosphoglycan during the differentiation of leishmania major promastigotes to an infectious stage.protozoan parasites of the genus leishmania produce the novel surface glycoconjugate, lipophosphoglycan (lpg), which is required for parasite infectivity. in this study we show that lpg structure is modified during the differentiation of l. major promastigotes from a less infectious form in logarithmic growth phase to a highly infectious 'metacyclic' form during stationary growth phase. in both stages, the lpgs comprise linear chains of phosphorylated oligosaccharide repeat units which are ancho ...19921396559
chronic cutaneous leishmaniasis: leishmania parasites in blood.two patients with chronic cutaneous leishmaniasis had positive blood cultures. the diagnosis was established by the clinical picture, skin biopsy, and culture for leishmania major and tropica.19921428447
topical treatment of old world cutaneous leishmaniasis caused by leishmania major: a double-blind control study.a controlled study of the efficacy of topical paromomycin sulfate (pr) and methylbenzethonium chloride (mbcl) in cutaneous leishmaniasis (cl) has not yet been performed.19921430361
[the serological examination of the population for leishmaniasis and the detection of leishmania in rodents in the republic of guinea].a serological study on leishmaniasis in human population of guinea revealed the percentage of seropositive persons varying in different parts of the country from 0.84 to 4.76 (according to c-elisa) and from 1.0 to 5.1 (according to ifat). the majority of sera positively reacting in c-elisa with the antigen of leishmania major in dilutions of 1:800 and higher were received from kundara district (northwestern part of the country), and with the antigen of l. donovani sensu lato from sigiri and kank ...19921435540
dynamics and size polymorphisms of minichromosomes in leishmania major lv-561 cloned lines.various lines and cloned lines of leishmania major of varying degrees of virulence in balb/c mice possessed size polymorphic multicopy minichromosomes related to previously described ld1/cd1 and 715-class dnas of leishmania. the minichromosomes were not necessary for virulence. two of these dnas (m180 and m210), coexisting in a single cloned line, showed remarkable dynamics in terms of loss or gain when followed through multiple transfers during in vitro culture and in vivo passage in balb/c mic ...19921435877
cutaneous leishmaniasis: review of 59 cases seen at the national institutes of health.fifty-nine cases of cutaneous leishmaniasis seen at the national institutes of health in bethesda, maryland, are reviewed. the group of patients involved was unique in that the majority were american civilians, their disease was acquired in many different endemic areas of the world, and their illnesses represented all points on the clinical spectrum of cutaneous disease. the majority of american patients acquired leishmaniasis while engaging in activities related to their occupations. cutaneous ...19921457663
effects of long-term in vitro cultivation on the virulence of cloned lines of leishmania major promastigotes.the virulences of several clones from a single leishmania major strain were studied in balb/c mice. clones showed the same pattern of infectivity and virulence two months after cloning as the parental population. after prolonged in vitro culture, however, it was apparent that two types of virulent clones existed: although the level of virulence remained stable in some clones, in others, such as c-11, it progressively decreased, as in the parental population. the progressive loss in virulence in ...19921463354
role of t cells in immunity to the intracellular pathogen, leishmania major. 19921485362
leishmania major and leishmania donovani: effect of lpg-containing and lpg-deficient strains on monocyte chemotaxis and chemiluminescence.lipophosphoglycan (lpg) is a major glycolipid present on the membrane of leishmania promastigotes and amastigotes. we have previously shown that preincubation of peripheral blood monocytes with purified lpg inhibits il-1 production, chemotactic locomotion, and luminol-dependent chemiluminescence (ldcl). in the present study we tested the effect of lpg present on live parasites on monocyte activity. for this purpose, we used two mutant strains deficient in lpg and two lpg-containing strains. one ...19921493876
differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice.sites of cutaneous infection with leishmania major in genetically susceptible (balb/c) and resistant (c57b1/6) mice were investigated for the early inflammatory response (6 h to 12 days) by electron microscopy combined with enzyme-histochemical methods. susceptible balb/c mice spontaneously recruited only polymorphonuclear leukocytes (pmns) at the site of infection. infiltrating mononuclear phagocytes (and eosinophils) were first observed at day 1 in a ratio equal to the influx of pmns (about 40 ...19921506767
ifn-gamma and delayed-type hypersensitivity are associated with cutaneous leishmaniasis in vervet monkeys following secondary rechallenge with leishmania major.ifn-gamma levels and delayed-type hypersensitivity (dth) responses were evaluated in vervet monkeys, following secondary infection with leishmania major (l. major). the animals had previously been vaccinated with leishmanial antigen, exposed to a primary infection and allowed to self-cure. supernatants of peripheral blood mononuclear cell (pbmc) cultures, stimulated with either l. major antigen or concanavalin a (con a), were examined for the presence of ifn-gamma in a double sandwich enzyme-lin ...19921514049
mechanisms of resistance to leishmania aethiopica. i. interferon-gamma in combination with a cytokine (not tumor necrosis factor-alpha) is required, but cannot act alone in the inhibition of intracellular forms of l. aethiopica in thp1 cells.following exposure to promastigotes of various leishmania species, mononuclear cells from non-exposed as well as potentially exposed individuals produced a cytokine response which inhibited intracellular forms of leishmania aethiopica in a permissive monocytic cell line (thp1). interferon-gamma (ifn-gamma), was one of the cytokines responsible for this anti-leishmanial effect. ifn-gamma was necessary for inhibition but could not act on its own inhibiting l. aethiopica. tumor necrosis factor-alph ...19921516623
leishmania major: differential regulation of the surface metalloprotease in amastigote and promastigote stages.during its life cycle, the protozoan parasite leishmania major alternates from an intracellular amastigote form in the mammalian host to a flagellated promastigote form in the insect vector. the expression of the surface metalloprotease (psp) during differentiation in vitro was investigated by western and northern blots, by immunoprecipitation of cells metabolically labeled with [35s]methionine or labeled at the surface with radioactive iodine, and by quantification of the proteolytic activity i ...19921516667
il-4 induces a th2 response in leishmania major-infected mice.the infection of mice with leishmania major can cause either a fatal disseminated disease or a localized healing disease, depending on the genetic background of the mice. a strong correlation has been shown between disease outcome and the nature of the t cell response, with healer strains developing a th1-like response and nonhealer strains a th2-like response. the treatment of nonhealer balb/c mice with a single dose of an anti-il-4 antibody, given at the time of infection with l. major, allowe ...19921531351
identification of the defect in lipophosphoglycan biosynthesis in a non-pathogenic strain of leishmania major.the major macromolecule on the surface of the protozoan parasite, leishmania major, is a complex lipophosphoglycan (lpg), which is anchored to the plasma membrane by an inositol-containing phospholipid. a defect in lpg biosynthesis is thought to be responsible for the avirulence of the l. major strain lrc l119 in mice. in order to identify the nature of this defect we have characterized two truncated forms of lpg, which are accumulated in this strain, by one- and two-dimensional 500-mhz 1h nmr s ...19921532574
catalase inhibits nitric oxide synthesis and the killing of intracellular leishmania major in murine macrophages.mouse peritoneal macrophages activated with interferon-gamma (ifn-gamma) and lipopolysaccharide produce substantial amounts of nitric oxide (no), which correlates with the elimination of the intracellular protozoan parasite leishmania major. both the production of no and the leishmanicidal function of the activated macrophages can be significantly inhibited by catalase in a dose- and time-dependent manner. these results could not be interpreted by the reduction of h2o2 by catalase since the remo ...19921537380
loss of the gp46/m-2 surface membrane glycoprotein gene family in the leishmania braziliensis complex.immunization with the gp46/m-2 membrane glycoprotein of leishmania amazonensis has been shown to induce a protective immune response against infection. we have surveyed a variety of trypanosomatid species and genera for the presence and expression of this gene family, information that will be relevant to future vaccine studies against leishmaniasis. molecular karyotype analysis revealed the presence of gp46/m-2 genes in all members of the leishmania mexicana complex, leishmania major, leishmania ...19921542309
structure of leishmania mexicana lipophosphoglycan.lipophosphoglycan (lpg) was isolated from the culture supernatant of leishmania mexicana promastigotes and its structure elucidated by a combination of 1h nmr, fast atom bombardment mass spectrometry, methylation analysis, and chemical and enzymatic modifications. it consists of the repeating phosphorylated oligosaccharides po4-6gal beta 1-4man alpha 1- and po4-6[glc beta 1-3]gal beta 1-4man alpha 1-, which are linked together in linear chains by phosphodiester linkages. each chain of repeat uni ...19921551890
effect of fibronectin and interferon-gamma on the uptake of leishmania major and leishmania infantum promastigotes by u937 cells.uptake of leishmania major and leishmania infantum promastigotes by u937 cells was determined by microscopic observation and by using radiolabelled parasites. with both species we observed an increase in uptake after parasite pretreatments with fibronectin, and a decrease in uptake after cell pretreatment with interferon-gamma (ifn gamma). when both pretreatments were performed, the uptake was significantly decreased only in l. infantum experiments. these findings may be of some importance in th ...19921556959
cytokine control of leishmania infection in the balb/c mouse: enhancement and inhibition of parasite growth by local administration of il-2 or il-4 is species and time dependent.the therapeutic potential of locally injected interleukin-2 (il-2) or interleukin-4 (il-4) was studied in the footpads of leishmania mexicana or leishmania major infected balb/c mice. the disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. il-2 (0.5 microgram/dose) or il-4 (0.1 microgram/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions ...19921557229
identification and isolation of the leishmania transferrin a previous report, we have presented several lines of evidence, derived from widely different methodologies, suggesting that leishmania has specific receptors for transferrin with a kd similar to the mammalian transferrin receptor. this paper describes the identification, purification, and biochemical characterization of leishmania transferrin receptor. the leishmania transferrin receptor, detected on intact parasites by immunoperoxidase staining, was first identified by sodium dodecyl sulfat ...19921577747
two successive years studies on phlebotomus papatasi in north sinai governorate, doubt, zoonotic cutaneous leishmaniasis (zcl) is increasing in north sinai governorate. the causative agent, l. major was identified as well as two animal reservoir hosts, gerbillus pyramidum and meriones crassus. this paper was intended to study the seasonal abundance and the sex ratio of the suspected insect, phlebotomus papatasi as well as to search for natural infected in wild caught females. the c.d.c. miniature light traps were used for adult collections, dissection was used for demonst ...19921578184
extrachromosomal genetic complementation of surface metalloproteinase (gp63)-deficient leishmania increases their binding to macrophages.a major surface glycoprotein of 63 kda (gp63) has been previously identified biochemically and genetically as a zinc proteinase conserved in pathogenic leishmania spp. the functional significance of this proteinase was analyzed by genetic approaches. a 15-kilobase dna with a tunicamycin-resistance gene from leishmania amazonensis was ligated in two different orientations into pbluescript containing a gp63 gene from leishmania major. these plasmid constructs were used to transfect a variant of l. ...19921594604
murine epidermal langerhans cells are potent stimulators of an antigen-specific t cell response to leishmania major, the cause of cutaneous leishmaniasis.cutaneous leishmaniasis is initiated by the bite of an infected sandfly and inoculation of leishmania major parasites into the mammalian skin. macrophages are known to play a central role in the course of infection because they are the prime host cells and function as antigen-presenting cells (apc) for induction of the cell-mediated immune response. however, in addition to macrophages in the dermis, the skin contains epidermal langerhans cells (lc) which can present antigen (ag) to t cells. ther ...19921601029
the effect of tunicamycin on the protease activity of gp63 from leishmania major.the protease activity of gp63 from l. major was studied in relation to tunicamycin induced n-deglycosylation. it was found that after tunicamycin treatment, a n-deglycosylated product of gp63 with protease activity is present at the cell surface of leishmania promastigote.19921608400
genes selectively expressed in the infectious (metacyclic) stage of leishmania major promastigotes encode a potential basic-zipper structural motif.complementary dna clones representing transcripts selectively expressed in the non-dividing, infective (metacyclic) stage of leishmania major promastigotes (mp) were identified by differential and subtractive screening. the majority of the selected clones hybridized on northern blots to a set of transcripts highly expressed by mp, but to a much lower extent in proliferating and stationary-phase attenuated promastigotes. stationary, but not log-phase cultures, of each of 5 l. major strains showin ...19921620162
the ser-arg-tyr-asp region of the major surface glycoprotein of leishmania mimics the arg-gly-asp-ser cell attachment region of fibronectin.the major surface glycoprotein of leishmania, gp63, a fibronectin-like molecule, plays a key role in parasite-macrophage interaction. binding of gp63 to macrophage receptors is inhibited by arg-gly-asp-ser (rgds)-containing synthetic peptides of fibronectin and by antibodies to these peptides. however, gp63 lacks an rgds tetrapeptide. we sought to identify the region of gp63 that antigenically and functionally mimics the rgds-containing region of fibronectin. we thus synthesized on polyethylene ...19921629196
establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to leishmania major.cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. balb/c mice "innately susceptible" to leishmania major produce antibodies after substantial infection. in the present study, "susceptible" mice injected with ...19921636090
nucleoside transporters in leishmania major: diversity in adenosine transporter expression or function in different strains.cytotoxic nucleoside derivatives may become useful in the treatment of parasitic infections. as part of our drug development studies, the effect of a number of nucleosides (100 microm) on the cellular transport of 3h-adenosine and 3h-inosine (each at 1 microm) in promastigotes from four leishmania major strains was investigated. when 3h-inosine was used as permeant, all strains exhibited essentially the same inhibition profile, with unlabeled inosine, guanosine, formycin b, and 3'-deoxyinosine b ...19921636887
[isolation of leishmania major in phlebotomus papatasi in biskra (algeria). the end of an ecoepidemiological saga].out of 1,167 females of sandflies dissected, one specimen of phlebotomus papatasi captured at a transmission site near biskra, a well known algerian focus of zoonotic cutaneous leishmaniasis, was found naturally infected with leishmania major zymodeme mon-25. this supports classical observations of sergent and al. p. papatasi as vector in this focus in 1921.19921642393
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
evaluation of different assay techniques to assess the interaction between leishmania major and l. infantum promastigotes and u937 cells.adherence of leishmania major and l. infantum promastigotes to u937 cells was determined by microscopic observation or by using radiolabelled parasites. with both methods l. infantum showed a greater adherence. aspecific attachment to plastic was greater for l. major. the possible implications of these findings in connection with disease pathogenesis are briefly discussed.19911648163
double targeted gene replacement for creating null mutants.we have used double gene targeting to create homozygous gene replacements in the protozoan parasite leishmania major, an asexual diploid. this method uses two independent selectable markers in successive rounds of gene targeting to replace both alleles of an endogenous gene. we developed an improved hygromycin b-resistance cassette encoding hygromycin phosphotransferase (hyg) for use as a selectable marker for leishmania. hyg-containing vectors functioned equivalently to those containing the neo ...19911651496
evidence of genetic recombination in the genus leishmania there has been no convincing demonstration of genetic exchange, and it has been proposed that reproduction is clonal. however, preliminary characterization of two strains of leishmania isolated from wild animals in a zoonotic focus of cutaneous leishmaniasis in the eastern province of saudi arabia, has suggested that they may represent hybrids of leishmania major and leishmania arabica. evidence presented here strongly supports this hypothesis. isoenzyme analysis and mole ...19911656255
studies on the leishmaniases in the sudan. 2. clinical and parasitological studies on cutaneous 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
extracellular dephosphorylation in the parasite, leishmania major.leishmania major promastigotes were analyzed for the presence of protein phosphatase activity in intact cells and membrane-enriched fractions. parasite phosphoproteins, phosphorylated in live cells with [gamma-32p]adenosine 5'-triphosphate (atp) and an endogenous leishmanial ectokinase, were dephosphorylated by endogenous protein phosphatase-like activity in intact cells and a membrane-rich fractions. an alkaline phosphatase-like activity was also identified using the artificial substrate, p-nit ...19911668866
exacerbation of experimental murine cutaneous leishmaniasis with cd4+ leishmania major-specific t cell lines or clones which secrete interferon-gamma and mediate parasite-specific delayed-type hypersensitivity.leishmania major-specific t cell lines were derived from mice sensitized to the parasite. the cells were of the cd4+ t cell lineage and, upon adoptive transfer, were found to be capable of inducing parasite-specific delayed-type hypersensitivity. adoptive transfer of these l. major-specific t cells to syngeneic recipients which were either normal, t cell deficient or b cell and antibody deficient led to exacerbation of infection upon subsequent challenge with l. major. this suggested that host t ...19911672641
effects of osmotic pressure on the oxidative metabolism of leishmania major promastigotes.leishmania major promastigotes were washed and resuspended in an iso-osmotic buffer. the rate of oxidation of 14c-labeled substrates was then measured as a function of osmolality. an acute decrease in osmolality (achieved by adding h2o to the cell suspension) caused an increase in the rates of 14co2 production from [6-14c]glucose and, to a lesser extent, from [1,(3)-14c]glycerol. an acute increase in osmolality (achieved by adding nacl, kcl, or mannitol) strongly inhibited the rates of 14co2 pro ...19911679134
mycobacterial heat-shock proteins as carrier molecules.we have previously shown that the priming of mice with live mycobacterium tuberculosis var. bovis (bacillus calmette-guérin, bcg) and immunization with the repetitive malaria synthetic peptide (nanp)40 conjugated to purified protein derivative (ppd), led to the induction of high and long-lasting titers of anti-peptide igg antibodies, overcoming the requirement of adjuvants and the genetic restriction of the antibody response to the peptide (lussow et al., proc. natl. acad. sci. usa 1990. 87:2960 ...19911680693
interferon-gamma inhibits the efficacy of interleukin 1 to generate a th2-cell biased immune response induced by leishmania major.splenic adherent cells from l. major-infected resistant and susceptible mice were restimulated in vitro and analyzed for the expression of il-1 activity. three weeks or later after infection, cells from parasite infected susceptible balb/c mice produced substantially more il-1 activity than those from non-infected controls or from l. major-infected resistant c57bl/6 animals. more than 95% of the il-1 bioactivity was mediated by il-1 alpha, as determined by blocking experiments with an anti-il-1 ...19911680802
heavy metal resistance: a new role for p-glycoproteins in leishmania.p-glycoproteins are responsible for multidrug resistance in tumor cell lines and are thought to have a physiologic role in exporting cellular metabolites. we now report that a p-glycoprotein gene in the h region of the trypanosomatid protozoan leishmania confers resistance to heavy metals when present in multiple copies. the leishmania h region is frequently amplified in drug-resistant lines and is associated with metal resistance. leishmania expression vectors were used to introduce multiple co ...19911680861
antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on cd4+ t lymphocyte plasma our studies of host defense to the intracellular protozoan leishmania major, we uncovered a novel mechanism of antileishmanial defense that involves direct cell contact between effector cd4+ lymphocytes and leishmania-infected macrophages. the mechanism is distinctive because it does not involve lymphokine secretion and induces no cytotoxic effects in the host cells; its expression is antigen-specific and genetically restricted. we now demonstrate that these effector cd4+ cells display tumor ...19911680956
chitinase secreted by leishmania functions in the sandfly vector.leishmania major parasites ingested with host blood by the sandfly phlebotomus papatasi multiply confined within the peritrophic membrane. this membrane consists of a chitin framework and a protein carbohydrate matrix and it is secreted around the food by the insect midgut. histological sections of infected flies show lysis of the chitin layer in the anterior region of the peritrophic membrane that permits the essential forward migration of a concentrated mass of parasites. both the location and ...19911682935
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
an antigenically distinct lipophosphoglycan on amastigotes of leishmania major.we show that lipophosphoglycan (lpg) on the surface of amastigotes of leishmania major is antigenically and biochemically distinct from promastigote lpg. a rabbit antiserum raised against the amastigote integral membrane fraction detected lpg spanning the region of mr 55,000-100,000 on western blots of the amastigote integral membrane fraction, but did not recognize the promastigote integral membrane fraction. wic 79.3, a monoclonal antibody which recognizes l. major metacyclic promastigote lpg, ...19911710036
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
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
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
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
cutaneous leishmaniasis acquired during military service in the middle east.cutaneous leishmaniasis is endemic in much of the middle east. personnel from more than 55 nations are currently participating in middle east peacekeeping and military activities.19921739291
effects of hypoxia and acute osmotic stress on intermediary metabolism in leishmania promastigotes.this study further explores the effects of hypoxia and acute osmotic stress on intermediary metabolism of leishmania major and leishmania donovani. late log phase promastigotes were washed and incubated with glucose as the sole exogenous carbon source, and rates of glucose consumption and product formation were measured as a function of osmotic strength (610, 305, and 167 mosm kg-1) and po2 (95, 10, and 0% o2) in the presence of 5% co2. very mild hypoxia dramatically altered flux through the pat ...19921741010
leishmania major: resistance of promastigotes to paromomycin, and susceptibility of amastigotes to paromomycin-methylbenzethonium chloride ointment.cutaneous lesions caused by leishmania major in balb/c mice were cured completely when treated topically with an ointment comprising 15% paromomycin sulphate and 1-2% methylbenzethonium chloride ointment in soft white paraffin twice daily for 10 days. no parasites were detected in tissue smears or in cultures from treated cutaneous lesions. re-developing lesions, considered to be resulting from the migration of parasites from internal organs, showed almost the same response to topical treatment. ...19911746981
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
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
heterogeneity of the genes encoding the major surface glycoprotein of leishmania donovani.the major surface glycoprotein of leishmania (gp63) is present on all known species of leishmania and likely plays an integral role during the infection of macrophages in the mammalian host. to identify regions of gp63 which may be of functional significance, the nucleotide sequence of a gene encoding gp63 of leishmania donovani was determined and compared to the sequences reported for gp63 genes of leishmania major and leishmania chagasi. the gp63 nucleotide and predicted protein sequence was h ...19911762629
molecular karyotype and chromosomal localization of genes encoding two major surface glycoproteins, gp63 and gp46/m2, hsp70, and beta-tubulin in cloned strains of several leishmania species.the molecular karyotypes of several leishmania isolates (leishmania amazonensis, leishmania braziliensis, leishmania guyanensis, leishmania panamensis, leishmania donovani, leishmania major, leishmania aethiopica, leishmania tropica, leishmania enriettii) have been analyzed by clamped homogeneous electric field (chef) gel electrophoresis. the chromosomal localization of genes encoding 2 major surface glycoproteins, gp63 and gp46/m2, heat shock protein 70 (hsp70), and beta-tubulin was determined ...19911779988
isolation and characterization of leishmania major from phlebotomus papatasi and military personnel in north sinai, egypt. 19911780981
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
enhanced antiparasitic activity of lipophilic tetracyclines: role of was previously noted that the inhibitory activities of lipophilic tetracyclines against the growth of giardia lamblia in vitro were up to 40-fold greater than those of nonlipophilic tetracyclines (50% inhibitory concentration [ic50] = 1.8 to 71 micrograms/ml) (t. d. edlind, antimicrob. agents chemother. 33:2144-2145, 1989). we have now extended this observation to trichomonas vaginalis (ic50 = 2.9 to 200 micrograms/ml), entaoeba histolytica (ic50 = 3.8 to 36 micrograms/ml), and leishmania maj ...19911803991
[human cutaneous leishmaniasis caused by leishmania major mon-26 in the region of damascus (syria)].in response to an epidemic of oriental sore around damascus, an ecological and epidemiological survey was carried out in the village of dmeir, 40 km ne of damascus. parasites isolated from six cases from dmeir, and two other cases from syria were identified as leishmania major, zymodeme mon-26. this zymodeme is known as the agent of zoonotic cutaneous leishmaniasis from the sub-saharian sahel to the near and middle east. this is the first report of l. major in syria. in a group of 234 school chi ...19911807849
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
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
characterization of a membrane antigen of leishmania amazonensis that stimulates human immune 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
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