Publications

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
reduced numbers of cd4+ suppressor cells with subsequent expansion of cd8+ protective t cells as an explanation for the paradoxical state of enhanced resistance to leishmania in t-cell deficient balb/c mice.	compared to their normal, t-cell competent counterparts, balb/c mice that have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells (txb) were found to be resistant to leishmania major. even though txb mice possess less than 30% of the normal number of t cells in their lymphoid organs, they generated a protective immune response that prevented the progressive multiplication of the parasite in the primary cutaneous lesion and its dissemination to distant visceral site ...	1991	1826673
monoclonal antibodies that react with leishmania (viannia) naiffi.	monoclonal antibodies were raised against leishmania (viannia) naiffi, which recently has been characterized as a new species. balb/c mice were immunized with membrane-enriched fractions of a mixture of l. (v.) naiffi isolates. subsequent fusion of immunized splenocytes with ns-1 myeloma cells resulted in the production of 5 mabs (n1-n5). screening by elisa and indirect immunofluorescence against an extensive cross-panel of leishmania strains revealed that n3 was species-specific and could thus ...	1991	1919913
effect of hyper-osmotic stress on alanine content of leishmania major promastigotes.	earlier studies showed that leishmania major promastigotes are sensitive to osmotic conditions. a reduction in osmolality caused the cells to shorten and to rapidly release most of their large internal pool of alanine. in this study some effects of hyper-osmotic stress were examined. an increase in osmolality of the culture medium from 308 to 625 mosm/kg caused only a small decrease in growth rate. when cells grown in the usual culture medium (308 mosm/kg) were washed, resuspended in iso-osmotic ...	1991	1997677
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 ...	1991	1762629
transmission and scanning em-immunogold labeling of leishmania major lipophosphoglycan in the sandfly phlebotomus papatasi.	previous studies using immunostaining and light microscopy demonstrated expression of leishmania major lipophosphoglycan (lpg) on parasites developing in the sandfly gut from 2 days post infection. by days 4 to 7 post infection, there appeared to be large amounts of parasite-free lpg deposited on/in the microvilli and epithelial cells lining the thoracic midgut, while forward migration of parasites and the morphological changes which accompany metacyclogenesis were associated with developmental ...	1991	1935998
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
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
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
expression of t-cell-associated serine proteinase 1 during murine leishmania major infection correlates with susceptibility to disease.	the expression of t-cell-associated serine proteinase 1 (mtsp-1) in vivo during leishmania major infection was analyzed in genetically resistant c57bl/6 mice and in genetically susceptible balb/c mice. using a monoclonal antibody as well as an rna probe specific for mtsp-1 to stain tissue sections, we found t cells expressing mtsp-1 in skin lesions and spleens of mice of both strains. in skin lesions, mtsp-1-positive t cells could be detected as early as 3 days after infection. most importantly, ...	1991	1937831
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
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
characterization of effector functions of v-raf/mil- and v-myc-transformed murine splenic macrophage cell lines.	we have characterized several of the cytocidal effector functions of a series of cell lines derived by recombinant retroviral transformation of individual clones of c3h/hej mouse splenic macrophages. the three cell lines described in this report (4.01, 4.07, 4.14) all expressed equivalent tumoricidal activity against p815 tumor target cells. however they differed in their high avidity binding of tumor cells (4.01 = 4.14 greater than 4.07), as well as in the killing of leishmania major (4.01 = 4. ...	1991	1873823
identification and characterization of host-protective t-cell epitopes of a major surface glycoprotein (gp63) from leishmania major.	by using a series of overlapping synthetic peptides that cover more than 75% of the amino acid sequence of the major surface glycoprotein (gp63) from leishmania major, 11 t-cell epitopes in cba and balb/c mice have been identified. six of the peptides were recognized by t cells of cba mice recovered from l. major infection, while one was recognized by the t cells from balb/c mice recovered from the infection following sublethal doses of gamma-irradiation. lymph node cells from mice immunized wit ...	1991	1997399
a test for genetic exchange in mixed infections of leishmania major in the sand fly phlebotomus papatasi.	we tested if genetic exchange was observable between two strains of leishmania major (trypanosomatidae) during mixed infection of the sand fly phlebotomus papatasi. previous studies suggested that genetic exchange may occur in natural populations of leishmania at a low frequency, but experimental crosses examining small numbers of progeny (less than 60) did not reveal hybrid parasites. accordingly, a strategy was devised to increase the number of progeny that could be screened by 100-fold. clona ...	1991	1880760
cytokine interactions in experimental cutaneous leishmaniasis. interleukin 4 synergizes with interferon-gamma to activate murine macrophages for killing of leishmania major amastigotes.	we investigated the effect of recombinant murine interleukin 4 (il 4) in the absence or presence of recombinant murine interferon-gamma (ifn-gamma) on adherent bone-marrow macrophages (m phi), peritoneal exudate and resident peritoneal m phi from susceptible balb/c m phi, which were pulse-infected with leishmania major amastigotes (am), il 4 (5-100 u/ml) failed to activate any of these m phi populations for killing of intracellular am. however, in the presence of low concentrations of ifn-gamma ...	1991	1900240
simultaneous transient expression assays of the trypanosomatid parasite leishmania using beta-galactosidase and beta-glucuronidase as reporter enzymes.	we describe a transient transfection protocol for cultured leishmania major promastigotes, utilizing escherichia coli genes encoding beta-galactosidase and beta-glucuronidase inserted into an expression vector derived from the dihydrofolate reductase-thymidylate synthase locus. less than 0.1 pg of either reporter enzyme can be detected with a simple fluorimetric assay, and transfection of 10 micrograms of either reporter construct yields activities at least 100-fold over background. simultaneous ...	1991	1908808
differential production of th1- and th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis.	recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of cd4+ t cell subsets in determining the outcome of infectious disease. in leishmania major infections, cure vs progressive disease correlates with the expansion of th1-like or th2-like cd4+ populations, respectively. we have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by l. donovani. splenic lymphocy ...	1991	1901883
activation of human t lymphocytes by leishmania lipophosphoglycan.	this study describes leishmania antigen-induced activation of lymphocytes isolated from kenyan donors, previously treated for visceral leishmaniasis, and from danish and kenyan controls. peripheral blood mononuclear cells (pbmc) from cured kala-azar patients proliferated and produced interferon-gamma in vitro in response to lipophosphoglycan (lpg) isolated from leishmania major. the proliferative response was mainly due to activation of cd2-positive t cells. pbmc from controls did not respond to ...	1991	1902000
establishment of resistance to leishmania major infection in susceptible balb/c mice requires parasite-specific cd8+ t cells.	although cd4+ t cells are generally accepted to be responsible for the determination of resistance to infection in experimental murine cutaneous leishmaniasis, a contribution of cd8+ lymphocytes to immunity can be demonstrated under certain well-defined conditions. normally highly susceptible balb/c mice can be rendered resistant to infection with leishmania major promastigotes by a single injection of monoclonal anti-cd4 antibodies at the beginning of infection. mice treated in such a way can h ...	1991	1909563
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. ...	1991	1746981
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 ...	1991	1761547
enhanced antiparasitic activity of lipophilic tetracyclines: role of uptake.	it 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 ...	1991	1803991
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 ...	1991	1809242
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 ...	1991	1820201
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
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
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
role of t cells in immunity to the intracellular pathogen, leishmania major.		1992	1485362
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
leishmaniasis and the arabian gulf.		1992	1285153
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
[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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
[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
leishmanin skin test survey in a focus of high endemicity of leishmania major in jordan.		1993	8103629
cloning and characterization of a golgi-associated gtp-binding protein homologue from leishmania major.	this paper describes the cloning of a golgi-associated gtp-binding protein homologue from leishmania major. the gene was isolated using degenerate oligonucleotides to conserved sequences amongst the small gtp-binding proteins in a polymerase chain reaction on genomic dna of the l. major cloned line v121. the reading frame of one clone showed high similarity to the rab/ypt subfamily of small gtp-binding proteins. a full length copy of the gene was isolated from a lambda gt10 v121 genomic library ...	1993	8114828
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
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
mutational analysis of a signal sequence required for protein secretion in leishmania major.	in eukaryotes, amino-terminal extensions, signal sequences, mediate the translocation of lysosomal, membrane and secreted proteins into the lumen of the endoplasmic reticulum (er). structure/function studies indicate that eukaryotic signal sequences are composed of 3 distinct domains, a positively charged amino-terminal domain, a central hydrophobic domain, and a polar carboxy-terminal domain. in an attempt to better understand protein trafficking in leishmania we have constructed strains of lei ...	1993	8139617
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