Publications

the comparative fine structure and surface glycoconjugate expression of three life stages of leishmania major.	the cellular ultrastructure and surface glycoconjugate expression of three life stages of leishmania major were compared. noninfective logarithmic phase promastigotes (lp) are immature cells bearing a thin cell coat, short flagellum, small and empty flagellar pocket, and a loose cytoplasm filled with profiles of er and large golgi complex. lp also contain subpopulations of maturing cells containing less er and golgi and synthesizing cytoplasmic granules of different size, number, and electron-de ...	1991	2009923
leishmania-sandfly interactions: an empirical field study.	phlebotomus papatasi is the sandfly vector of leishmania major in the jordan valley. the objective of this study was to characterize vector-parasite relations in an active zoonotic focus. seasonality and intensity of promastigote infection rates in female sandflies and the developmental stage of these hosts were established. on 153 trap-nights, 641 female p. papatasi were caught and examined. of these, 48 (7.4%, range 12.9-4.8%) were infected with l. major promastigotes. correlating the number o ...	1991	2010872
analysis of enhancing effect of sand fly saliva on leishmania infection in mice.	salivary gland lysates of the sand fly lutzomyia longipalpis markedly enhance the course of infection with leishmania major in mice. here we examine various parameters of this phenomenon. the exacerbative effect of l. longipalpis salivary gland lysates occurred in five different mouse strains; however, the character of the effect varied from one strain to another. consistent exacerbation of infection was achieved with as little as 1/10 of a gland. the exacerbative effect applied to more than one ...	1991	2019430
biochemical characterization of leishmania major isolated from two egyptian patients.	leishmania major, the cause of human zoonotic cutaneous leishmaniasis, is a widely distributed parasite in the old world. here, we report the isoenzyme characterization of two human isolates obtained from egyptians who never travelled abroad. the two isolates were l. major equivalent to zymodene lond i.	1991	2033298
metacyclogenesis of leishmania spp: species-specific in vitro transformation, complement resistance, and cell surface carbohydrate and protein profiles.	metacyclic (stationary) and logarithmic (log) forms of promastigotes of leishmania donovani and leishmania major were characterized in several ways. the highly active metacyclic forms were larger with more protein and less carbohydrate. the flagellum increased in length 2.4 times in l. major as compared to 1.8 times in l. donovani. resistance to complement-mediated lysis by normal human serum of in vitro grown leishmania promastigotes was related to the species, the growth phase in culture, and ...	1991	2040953
t-cell reactivity to purified lipophosphoglycan from leishmania major: a model for analysis of the cellular immune response to microbial carbohydrates.	the major macromolecule on the surface of leishmania major promastigotes is a lipophosphoglycan (lpg). this glycoconjugate plays a key role in determining infectivity and survival of parasites in the mammalian host cell. in addition, l. major lpg is able to induce a host-protective immune response. in this article, we summarise the evidence for recognition of highly purified lpg by t cells and we discuss the potential mechanisms of t-cell stimulation by this non-protein antigen.	1991	2049034
administration of beta-glucan following leishmania major infection suppresses disease progression in mice.	the potential of beta-glucan (glucan) to suppress the progression of lesions caused by virulent strains of leishmania major in genetically susceptible balb/c mice when administered post challenge was evaluated. glucan particles (glucanp) prepared from saccharomyces cerevisiae were injected i.v. at 7-day intervals starting 7 days after parasite challenge. four injections gave a more rapid and a higher extent of suppression than 1, 2 or 3 injections. mice receiving only parasites, a glucose soluti ...	1991	2052403
[susceptibility to and the characteristics of the course of experimental leishmaniasis in different species of mammals infected with leishmania major, l. turanica and l. gerbilli].	40 r. opimus and 69 m. libycus were infected and 59 human subjects were vaccinated in laboratory conditions. 13 cultures of 3 leishmania species and their mixtures were used. r. opimus turned to be sensitive to 3 leishmania species. leishmaniasis developed in the form of infiltrates irrespective of the leishmania species and pathogenic activity. ulceration and visceralization were always absent. differences in the duration of leishmania preservation in r. opimus have been noted. in l. major infe ...	1991	2067472
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, ...	1991	1710036
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 ...	1991	1711153
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 ...	1991	1717284
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 ...	1991	1718853
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 ...	1991	1721024
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 ...	1991	1646960
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.	1991	1648163
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 ...	1991	1651496
evidence of genetic recombination in leishmania.	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 ...	1991	1656255
studies on the leishmaniases in the sudan. 2. clinical and parasitological studies on cutaneous leishmaniasis.	in the omdurman hospital for tropical diseases, sudan, from 6 october to 1 december 1986, 736 patients with cutaneous leishmaniasis (cl) were studied. the duration of the lesions varied from a few days to 4 months, usually (56%) 1-3 months. multiple lesions ranging from one to 50 (mean = 4) were present in 80% of cases. ulcerative lesions were found in 44%, nodulo-ulcerative in 31%, nodular in 31% and others, including infiltrated, fungating and warty lesions, in 5% of patients. the lower limbs ...	1991	1661450
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 ...	1991	1668866
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 ...	1991	1672641
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 ...	1991	1679134
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 ...	1991	1680693
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 ...	1991	1680802
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 ...	1991	1680861
antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on cd4+ t lymphocyte plasma membrane.	in 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 ...	1991	1680956
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 ...	1991	1682935
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.	1992	1739291
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 ...	1992	1741010
leishmaniasis and the arabian gulf.		1992	1285153
leishmania major: bacterial contamination of cutaneous lesions in experimental animals.	no 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 ...	1992	1286954
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 ...	1992	1288430
[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.	1992	1290377
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 ...	1992	1301732
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 ...	1992	1306154
cellular responses of vervet monkeys (cercopithecus aethiops) experimentally infected with leishmania major.		1992	1307757
thymidine kinase as a negative selectable marker in leishmania major.		1992	1315415
soluble tnf and membrane tnf expressed on cd4+ t lymphocytes differ in their ability to activate macrophage antileishmanial defense.	in 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 ...	1992	1347312
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 ...	1992	1349724
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 ...	1992	1356094
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 ...	1992	1356346
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 ...	1992	1357029
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; ...	1992	1359969
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 ...	1992	1365527
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 ...	1992	1370357
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 ...	1992	1371863
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 ...	1992	1377218
[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 martsinovskiĭ 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 ...	1992	1380631
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 ...	1992	1396559
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.	1992	1428447
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.	1992	1430361
[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 ...	1992	1435540
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 ...	1992	1435877
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 ...	1992	1457663
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 ...	1992	1463354
role of t cells in immunity to the intracellular pathogen, leishmania major.		1992	1485362
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 ...	1992	1493876
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 ...	1992	1506767
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 ...	1992	1514049
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 ...	1992	1516623
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 ...	1992	1516667
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 ...	1992	1531351
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 ...	1992	1532574
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 ...	1992	1537380
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 ...	1992	1542309
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 ...	1992	1551890
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 ...	1992	1556959
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 ...	1992	1557229
identification and isolation of the leishmania transferrin receptor.	in 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 ...	1992	1577747
two successive years studies on phlebotomus papatasi in north sinai governorate, egypt.	no 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 ...	1992	1578184
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. ...	1992	1594604
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 ...	1992	1601029
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.	1992	1608400
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 ...	1992	1620162
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 ...	1992	1629196
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 ...	1992	1636090
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 ...	1992	1636887
[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.	1992	1642393
phosphorylation of proteins in virulent promastigotes from leishmania major.	protein kinases are present in the plasma membrane of the human parasite leishmania. a marked increase in enzyme activity has been detected as cultures entered into the stationary phase of growth. since avirulent parasites can be separated from virulent forms by the peanut agglutinin (pna), we have examined the change in the protein kinase activity of l. major during growth in vitro and the difference in phosphorylation with virulent promastigotes (pna-) of l. major. marked similarities were fou ...	1993	7670538
mapping human t cell epitopes in leishmania gp63. identification of cross-reactive and species-specific epitopes.	both a conserved surface metalloprotease of leishmania, gp63 as well as certain gp63-derived peptides, have been shown to have immunoprophylactic potential in mouse models of leishmaniasis. in addition, pbmc from individuals with cutaneous, mucosal, or cured visceral leishmaniasis respond in vitro to both native and rgp63. in this report, we mapped human t cell epitopes within gp63. t cells from leishmaniasis patients responded in vitro to certain peptides of gp63 by proliferation and ifn-gamma ...	1993	7678627
repeated induction of nitric oxide synthase and leishmanicidal activity in murine macrophages.	murine macrophages express high levels of nitric oxide (no) synthase and produce large amounts of no when stimulated with interferon-gamma plus lipopolysaccharide in vitro. the expression of no synthase peaks at 12 h after stimulation and declines rapidly to the background level by 72 h. these macrophages can be repeatedly reactivated to express similar levels of no synthase. the reactivation is not due to newly divided cells since peritoneal macrophages which do not divide in vitro and j774 cel ...	1993	7684689
leishmania major-specific, cd4+, major histocompatibility complex class ii-restricted t cells derived in vitro from lymphoid tissues of naive mice.	several studies indicate that the outcome of experimental murine cutaneous leishmaniasis caused by leishmania major (lm) is determined by immunological events occurring shortly after infection. these events lead to outgrowth of either protective cd4+ t cells in the c57bl/6 mouse, which cures, or exacerbative cells in the balb/c mouse, which succumbs to disease. potential factors influencing the outgrowth of protective or exacerbative t cells include antigen-presenting cells (apc), cytokines, and ...	1993	7686209
pre-exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activity.	murine macrophages produce nitric oxide (no) from l-arginine on stimulation with lipopolysaccharide (lps), alone or with interferon-gamma (ifn-gamma). the effect of incubation of macrophages with low concentrations of lps on no synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, j774, and peritoneal macrophages from cba mice. cells which had been incubated with lps produced significantly lower amounts of no, and expressed lower levels of no synthase activit ...	1993	7686861
phagocytosis and induction of nitric oxide synthase in murine macrophages.	the murine macrophage cell line, j774, produced little or no detectable levels of nitric oxide (no) when stimulated with interferon-gamma (ifn-gamma) alone in vitro. however, they expressed high levels of no synthase and produced large amounts of no when cultured with ifn-gamma in the presence of lipopolysaccharide (lps). the synergistic action of lps can be replaced by ingestion by the macrophages of zymosan, staphylococcus aureus or leishmania major in a dose-dependent manner. in contrast, the ...	1993	7691724
monoclonal antibodies directed against leishmania secreted acid phosphatase and lipophosphoglycan. partial characterization of private and public epitopes.	leishmania promastigotes, the stage of the parasite characteristic for the sandfly vector, express an abundant glycoconjugate, called lipophosphoglycan, at their surface. lipophosphoglycan consists of lysoalkyl-sn-glycerophosphoinositol linked to a phosphosaccharide core conserved in all species, which is connected to po4-6gal beta 1,4man alpha 1 repeats with species-specific substitutions at the gal residue; the repeats are capped by conserved and species-specific oligosaccharides. most leishma ...	1993	7693464
antibodies to leishmania (l) glycolipids and gangliosides in sera of patients with visceral or with zoonotic l. major leishmaniasis.		1993	7802494
the squash blot technique and the detection of leishmania major in phlebotomus papatasi in tunisia.	this study describes the preliminary applications of the squash blot technique in tunisia, to detect leishmania major in naturally infected phlebotomus papatasi. 309 p. papatasi among 364 female sandflies squashed on to nylon gene screen dna transfer membranes, were identified using the 3.2 kb ribosomal p. papatasi specific dna probe described by ready et al. a second hybridization using the taq1 dna probe described by smith et al. (1989) allowed the detection and identification of the parasite ...	1993	7802506
in vitro secretion of cytokines by human mononuclear cells of individuals during and after cutaneous leishmaniasis infection.	human peripheral blood mononuclear cells were incubated in the presence of leishmania major promastigotes. the culture supernatants were collected after 24 and 72 h and the cytokine content was measured. it was found that mononuclear cells from cured individuals, in the presence of l. major promastigotes, had increased leishmanicidal activity and secreted increased levels of interferon gamma (ifn gamma), interleukin-2 (il-2) and tumour necrosis factor alpha (tnf). the levels of il-6, on the othe ...	1993	7877848
course of leishmania infection in beta 2-microglobulin-deficient mice.	mice homozygous for a beta 2-microglobulin (beta 2-m) gene disruption lack the beta 2-m protein and are deficient in functional major histocompatibility complex class i (mhc i) molecules. the mutant mice have normal numbers of cd4+8- t helper cells but lack mhc i-directed cd4-8+ alpha/beta t cells. the beta 2-m mutant and wild-type mice were infected with leishmania major or l. mexicana, which cause cutaneous leishmaniasis in the old and new world, respectively. in both mutant and wild-type mice ...	1993	7901152
an avirulent lipophosphoglycan-deficient leishmania major clone induces cd4+ t cells which protect susceptible balb/c mice against infection with virulent l. major.	an avirulent clone of leishmania major was used to immunize susceptible balb/c mice against challenge with virulent l. major. by using the immunized animals as a source of cells, cd4+ parasite-specific t-cell lines could be generated in vitro which, when adoptively transferred to naive balb/c recipients, conferred marked protection against challenge with virulent l. major. compared with cd4+ parasite-specific t-cell lines generated from nonimmunized balb/c mice infected with l. major, the protec ...	1993	7901166
cytokines in the differentiation of th1/th2 cd4+ subsets in leishmaniasis.	leishmania major infect only macrophages in the host, where they reside in endolysosomal compartments into which mhc class ii molecules co-localize. experimental infection in mice has provided a useful model for the differentiation of th1 cd4+ effector lymphocytes that are required for the generation of ifn-gamma that activates the macrophage to a microbicidal state. genetically susceptible balb/c mice aberrantly activate th2 cd4+ effector cells that are ineffective in arresting infection. incre ...	1993	7905485
[importance of the different t lymphocytes subsets in immunity of mice against an intracellular protozoan parasite: leishmania major].	the resolution of lesions in mice experimentally infected with l. major requires the expansion of cd4+ t cells specific for parasite antigens which release or express on their membranes lymphokines typical of those secreted by cd4+ th1 cells. these lymphokines activate macrophages containing l. major to a parasiticidal state through the production of molecules toxic for the parasite. the anti-leishmania effector function of parasite-specific cd4+ th1 cells was found dependent upon their fine spe ...	1993	7906028
leishmania major: characterisation and expression of a cytoplasmic stress-related protein.	the dna sequence of a single-copy gene from leishmania major has been determined and shown to share sequence identity with eukaryotic heat shock protein-70-related genes. conserved features of the deduced open reading frame include amino acids implicated in atp binding and a putative calmodulin-binding domain. antibodies generated to the recombinant fusion protein recognise a 70-kda molecule of pi 6.0. this molecule is constitutively expressed and localises to the cytoplasm in all stages of the ...	1993	7916697
[the use of leukinferon in treating zoonotic cutaneous leishmaniasis. 1. research on an experimental model in mice].	leukinferon, a drug made in this country, represents a complex of cytokines of the immune response first phase with the predominating activities of interleukin-1, tumor necrosis factor, macrophage- and leukocyte-inhibiting factors and alpha-interferon; its effects on the murine immune system and on peritoneal macrophagal culture are diverse. leukinferon activates phagocytosis and killing of l. major promastigotes with peritoneal macrophages. in vivo leukinferon in combination with monomycin had ...	1993	8028564
persistence of virulent leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host.	the persistence of leishmania major parasites in mice resistant to infection was investigated by the polymerase chain reaction and in vitro culture methods. parasite-specific dna was detected in the lymph nodes, spleens, bone marrow, and livers of c57bl/6 mice 1 year after their recovery from infection. live parasites were also recovered from these tissues (except liver tissues) and were used to establish in vitro isolates. pulsed-field gel electrophoresis, southern blotting, and western blot (i ...	1993	8093358
thioxanthenes inhibit multiplication of leishmania major and its attachment to human monocytes in vitro.		1993	8096111
t cell response in murine leishmania mexicana amazonensis infection: production of interferon-gamma by cd8+ cells.	the immune response to leishmania major has been the subject of many investigations. however, leishmania includes many species with different clinical manifestations. in this report, we studied the t cell response to l. mexicana amazonensis, a new world species, in a murine model. we found that, similar to l. major, an old world species, resistant c57bl/6 mice produced a high level of ifn-gamma and a low level of il-4. conversely, susceptible balb/c mice produced a much lower level of ifn-gamma ...	1993	8097471
recombinant interleukin 12 cures mice infected with leishmania major.	resistant c57bl/6 mice infected with leishmania major are self-healing, whereas susceptible balb/c mice fail to contain cutaneous infection and subsequently undergo fatal visceral dissemination. these disparate outcomes are mediated by dissimilar expansions of t helper type 1 (th1) and th2 cd4+ t lymphocyte subsets in vivo during cure and progression of disease. because interleukin 12 (il-12) has potent t cell growth and interferon gamma (ifn-gamma) stimulatory effects, we studied its effect on ...	1993	8097524
transfected leishmania expressing biologically active ifn-gamma.	infection of susceptible balb/c mice with leishmania major leads to progressive infection with the failure to expand and activate th1 cd4+ t cells that elaborate ifn-gamma, a critically implicated cytokine for control of disease. we used the recently described capacity to express foreign genes in trypanosomatids to introduce into leishmania the murine ifn-gamma gene on a drug-selectable plasmid under the constitutive control of intergenic tubulin sequences. several clones of l. major were establ ...	1993	8098724
resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective t helper type 1 immune response.	resistance to leishmania major in mice is associated with the appearance of distinct t helper type 1 (th1) and th2 subsets. t cells from lymph nodes draining cutaneous lesions of resistant mice are primarily interferon gamma (ifn-gamma)-producing th1 cells. in contrast, t cells from susceptible mice are principally th2 cells that generate interleukin 4 (il-4). although existing evidence is supportive of a role for ifn-gamma in the generation of th1 cells, additional factors may be required for a ...	1993	8098733
natural killer cells are a source of interferon gamma that drives differentiation of cd4+ t cell subsets and induces early resistance to leishmania major in mice.	infection of mice with the protozoan leishmania major provides an excellent model to define the factors involved in t helper (th) subset development, since th1 cells confer protection in resistant strains of mice, whereas th2 cells are associated with the fatal outcome of susceptible mice. we previously found that interferon gamma (ifn-gamma) was required for th1 cell development after infection of mice with l. major. in this report, we evaluate the contribution of natural killer (nk) cells to i ...	1993	8101861