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cell contact-mediated macrophage activation for antileishmanial defense. i. lymphocyte effector mechanism that is contact dependent and noncytotoxic.leishmania are obligate intracellular protozoa in mammalian hosts. they infect and replicate within macrophages. antileishmanial host defense is largely cell mediated. we conducted studies in vitro to investigate the ability of lymphocytes to activate macrophages for antileishmanial effects. draining lymph node lymphocytes from c57bl/6 mice with cutaneous leishmania tropica major infection were co-cultured in suspension with syngeneic, starch-elicited peritoneal macrophages infected in vitro wit ...19846208278
a case of mucocutaneous leishmaniasis in saudi arabia caused by leishmania major and its response to treatment. 19836303652
frozen stored leishmania tropica vaccine: the effects of dose, route of administration and storage on the evolution of the clinical lesion. two field trials in the israel defense forces.the first field trial of frozen vaccine against cutaneous leishmaniasis yielded a 100% take rate and a high ulceration rate at a dose of four million units. two further trials were designed to investigate differences in response rates on the basis of duration of storage, sex of vaccinee, vaccination dose and method of administration. 257 soliders (151 males and 106 females) were inoculated in 1978 with an isolate of leishmania tropica major that had been stored at the temperature of liquid nitro ...19836346588
the cellular and humoral immune response in subjects vaccinated against cutaneous leishmaniasis using leishmania tropica major promastigotes.in vitro lymphocyte transformation was studied in 24 subjects 12 months after vaccination with live leishmania tropica major vaccine, in 10 normal control subjects and in three controls residing in an endemic area. the vaccines had lesions in various stages of clinical development. lymphocytes from all the subjects were studied for their response to stimulation with l. tropical major promastigotes. lymphocytes of vaccinated subjects responded to low concentrations of antigen whereas the lymphocy ...19836353318
radioiodination and identification of externally disposed membrane components of leishmania tropica.two methods, one involving a lactoperoxidase-glucose oxidase coupled reaction and the other employing the insoluble catalyst 1,3,4,6-tetrachloro-3 alpha, 6-alpha-diphenyl-glycoluril (iodo-gen), were used to label the surface membrane of promastigotes of leishmania tropica major. both methods labelled approximately 20 proteins or glycoproteins (apparent size range 10 to 110 kda) in a qualitatively similar manner, however the lactoperoxidase method labelled one additional constituent (260 kda). by ...19836355841
isolation of leishmania major yakimoff & schokhor, 1914 from psammomys obesus gretzschmar, 1828 (rodentia: gerbillidae) in algeria. 19836364474
application of the indirect fluorescent antibody test in serodiagnosis of cutaneous leishmaniasis in experimentally infected mice and naturally infected rhombomys opimus.the indirect fluorescent antibody test (ifat) was used to detect leishmanial antibodies in experimentally inoculated mice with promastigote forms of leishmania major, l. tropica and l. donovani infantum and in naturally infected rhombomys opimus captured from the area endemic for cutaneous leishmaniasis in esfahan, iran. in the mice inoculated with l. major, the leishmanial lesion appeared at the site of inoculation and the leishmanial antibody level was much higher than in mice inoculated with ...19846369653
leishmaniasis in israel: reservoir hosts, sandfly vectors and leishmanial strains in the negev, central arava and along the dead sea.the reservoir animals, sandfly vectors and strains of leishmania from foci in the southern region of israel were studied. the rodent host species are: psammomys obesus, meriones crassus and probably nesokia indica. the vector species are phlebotomus papatasi, which were caught at all collecting sites and ph. sergenti, which were collected in the area of the dead sea and in the central arava. strains of leishmania major isolated from rodents, vectors and man were serologically and enzymologically ...19846385358
monoclonal antibodies for serotyping leishmania strains.mouse monoclonal antibodies raised against leishmania tropica major were found to precipitate with the excreted factor produced by this and other leishmanial species. we suggest that a classification system for leishmania, based on selective precipitation reactions between monoclonal antibodies and the excreted factor, would remove many ambiguities that currently exist.19836411764
[study of virulence of the leishmania tropica major strains isolated from gerbils (rhombomys opimus licht.) under different landscape condition in turkmenistan]. 19806446666
[leishmania tropica major cultures isolated from the red-tailed libyan jird (meriones libycus lichtenstein, 1823) in the turkmen ssr]. 19806451790
[incidence of infestation of great gerbils (rhombanys opimus, licht.) by leishmania major during years of their population depression]. 19816453276
the isolation of leishmania major from rodents in baringo district, kenya. 19846464123
vaccination against cutaneous leishmaniasis in mice using nonpathogenic cloned promastigotes of leishmania major and importance of route of injection.in vaccination studies, mice have been injected by different routes with living promastigotes of nonpathogenic leishmania followed by cutaneous challenge with pathogenic promastigotes. parasites used for vaccination have been promastigotes of the cloned parasite lines a12 and a52 derived from leishmania major isolate l137, or long-term cultured promastigotes of the leishmaniasis recidiva isolate, l32 (l.t.tropica). none of these protozoa causes lesions after cutaneous injection to mice. disease ...19846466205
an amphipathic sulphated glycoconjugate of leishmania: characterization with monoclonal antibodies.a major glycoconjugate of leishmania tropica major identified by two monoclonal antibodies was shown to be an externally oriented, amphipathic membrane antigen shed into the culture medium in which the parasites grow. this molecule could be labelled metabolically with [3h]glucose, [3h]galactose, [32p]phosphate and [35s]sulphate. it migrated as a polydisperse band upon electrophoresis in sds-polyacrylamide gels, spanning the region of the gel corresponding to an apparent mol. wt. of 20 000-67 000 ...19846499830
leishmania tropica: protective response in c3h mice vaccinated with excreted factor crosslinked with the synthetic adjuvant, muramyl dipeptide.excreted factor, an immunosuppressive, acidic polysaccharide released by promastigotes of leishmania tropica major in culture, was chemically crosslinked to the synthetic adjuvant muramyl dipeptide via the bifunctional imidoester dimethyladipimidate and poly-l-lysine. this conjugate, an uncrosslinked mixture of the components, or each of the components alone were injected one to three times into different groups of 8- to 12-week-old c3h mice. the mice were challenged 2 weeks after the last injec ...19846499996
antidepressants cause lethal disruption of membrane function in the human protozoan parasite leishmania.the antidepressant compounds clomipramine and nitroimipramine were cidal to extracellular promastigotes of both human protozoan parasites leishmania donovani and leishmania major. clomipramine also killed amastigotes of both species within murine macrophages with no apparent toxicity to the host cells. further, amastigotes were more sensitive than promastigotes to clomipramine. clomipramine (100 micromoles per liter or 0.2 nanomole per 1 x 10(6) cells) inhibited l-proline transport in promastigo ...19846505677
development of topical treatment for cutaneous leishmaniasis caused by leishmania major in experimental animals.topical treatment, with drug-containing ointments, of cutaneous leishmaniasis caused by leishmania major in balb/c mice was studied. twenty chemotherapeutic agents having potential or established antileishmanial activity were formulated in different ointment and cream bases. only 15% paromomycin sulfate with 12% methylbenzethonium chloride, 12% benzethonium chloride, 12% cetalkonium chloride, or 12% dimethyl sulfoxide, all incorporated in white soft paraffin (united kingdom patent application no ...19846517557
cutaneous leishmaniasis in kenya: transmission of leishmania major to man by the bite of a naturally infected phlebotomus duboscqi.one leishmanial stock was isolated from a phlebotomus duboscqi female captured in baringo district, kenya, and others from papular lesions that developed at sites where this sandfly had fed on a man. when characterized by cellulose acetate electrophoresis (eight enzymes examined), these isolates proved to be identical to known leishmania major strains from man and a rodent (arvicanthis sp.) and different from l. donovani and l. adleri, which also occur in baringo. this is the first case of human ...19846533846
comparison of the effect of various stimuli on the leishmaniacidal capacity of human monocytes in vitro.leishmania organisms are obligate intracellular parasites of mammalian mononuclear phagocytes in vivo. in order to study the interactions of these parasites and mononuclear phagocytes, we have used a model of infection of leishmania major in human monocytes in vitro. the presence of intracellular parasites did not alter the normal secretion of lysozyme or result in increased secretion of prostaglandin e2 (pge2) or superoxide anion by the monocytes. addition of concanavalin a (con a), which binds ...19846589101
specific suppression of responses to leishmania tropica by a cloned t-cell line.most clinical cases of cutaneous leishmaniasis caused by leishmania tropica major consist of self-healing lesions that are associated with the development of strong specific cell-mediated immunity (cmi) detected by delayed-type hypersensitivity (dth). at the other extreme are susceptible individuals who develop persistent or diffuse forms of the disease. this spectrum of cutaneous leishmaniasis can be reproduced in in-bred mouse strains according to their genetic constitution. balb/c mice are ex ...19836604879
murine cutaneous leishmaniasis: resistance in reconstituted nude mice and several f1 hybrids infected with leishmania tropica major.after cutaneous injection of promastigotes of an isolate of the intramacrophage protozoan parasite, leishmania tropica major, mouse strains develop chronic cutaneous lesions or show a resolving pattern of disease. on this basis, they can be classified as resistant (e.g. cba/h and c57bl/6) or susceptible (e.g. balb/c, balb/c.h-2b and balb/c.h-2k). hypothymic nude (nu/nu) mice of either balb/c, cba/h or c57bl/6 genotype are susceptible to chronic disease. however, nude mice of these genotypes, inc ...19836606002
induction by specific t lymphocytes of intracellular destruction of leishmania major in infected murine macrophages.the following cell populations derived from lymph nodes of mice primed in vivo with living leishmania major promastigotes were tested for their capacity to induce parasiticidal activity in l. major-infected macrophages: a l. major-primed lymph node cells, draining lymph node cells from mice primed by a subcutaneous injection of living l. major in freund's complete adjuvant; b l. major-specific t blasts, i.e. blast t cells resulting from in vitro challenge of primed lymph node cells with l. major ...19846609335
[leishmania major (yakimoff et shokkor 1914), the agent of gafsa boil]. 19836673648
an apparent association of enzymic variants of leishmania major with specific geographical areas in israel.isolates of leishmania major from man, psammomys obesus, meriones crassus and phlebotomus papatasi from three separate areas of israel were characterised using isoenzyme electrophoresis. three enzymic variants of phosphogluconate dehydrogenase (6pgd) were seen, the distribution of which is correlated with the different geographical areas.19836673846
quantitation of leishmania tropica major by its ability to form distinct colonies on agar-based media.the growth of the pathogen leishmania tropica major on agar-based media was studied to further develop techniques that can be used to quantitate the number of viable organisms in infected tissues. individual, intact amastigotes formed distinct, countable colonies on four different agar-based media. however, the largest colonies (0.35 mm) and highest plating efficiency (greater than 90%) were found on media formulated with a heart-infusion agar base. use of this media in the quantitation of the o ...19836674456
leishmania major: culture media, mouse strains, and promastigote virulence and infectivity.promastigotes of leishmania major were isolated from an infected mouse in two media, blood agar and schneider's medium + 30% fetal calf serum, and maintained continuously for over 1 year. infectivity studies in two strains of mice, outbred cd1 strain and inbred balb/c strain, showed that promastigotes grown in schneider's medium maintained infectivity to balb/c mice throughout the period of cultivation. infectivity to cd1 strain mice was progressively lost. promastigotes grown in blood agar medi ...19846723897
mechanical transmission of leishmania major by glossina morsitans morsitans (diptera: glossinidae). 19846726762
[comparative electron microscopy study of leishmania major and l. tropica in experimental infestation of the sandfly phlebotomus papatasi].for the first time comparative study was conducted of the ultrastructure of promastigotes of leishmania major and l. tropica in the organism of phlebotomus papatasi which for the first species of leishmania is and for the second species is not a natural invertebrate host. during the bloodsucking on mesocricetus auratus experimentally infected with leishmania sandflies perceive amastigotes of both l. major and l. tropica. in the midgut of the sandfly both species of leishmania pass into the stage ...19846728513
[interepidemic surveillance of a cutaneous leishmaniasis focus in senegal].the cutaneous leishmaniasis is rampant in an endemo -epidemic way in the region of thiès, senegal. at the occasion of an epidemic observed between 1975 and 1978, the ecological study of the focus of keur moussa , led by dedet and al., permitted to discover, for the first time in west africa, the structure of a cutaneous leishmaniasis focus. the most important part of the present laboratory work consists in the observation of that wild anthropozoonosis due to leishmania tropica major, having as v ...19846738336
leishmania major: identification of stage-specific antigens and antigens shared by promastigotes and amastigotes.a battery of antisera to leishmania major was used to identify stage-specific antigens, or antigens expressed predominantly in amastigotes or promastigotes. at least 30 protein antigens common to amastigotes and promastigotes could be detected in 35s-methionine labelled preparations. they ranged in molecular weight from 25 000 to 165 000. two amastigote specific antigens and five antigens expressed predominantly in the amastigote were detected in biosynthetically-labelled preparations. five prom ...19846739119
immunogenic proteins of leishmania major during mouse infection.mice of different strains (c3h/he, a/jax, dba/2, balb/c and cba/ca) were infected intracutaneously with leishmania major. antibody production was analysed on the antigens of the promastigote form of the parasite which had previously been separated by sds-polyacrylamide gel electrophoresis and transferred to nitrocellulose sheets. the kinetics of igg antibody production were determined and the major immunogenic proteins of the parasite were identified for each strain of mouse. it was found that: ...19846739122
the activity against trypanosoma cruzi and cutaneous leishmaniasis, and toxicity, of moxipraquine (349c59).a novel 8-aminoquinolone compound, 8(6-4' 3-hydroxybutyl)piperazin-1'-ylhexylamino)-6-methoxyquinoline di(hydrogen maleate), moxipraquine, 349c59, was shown to be active against experimental infections with trypanosoma cruzi. it was effective in suppressing parasitaemia but did not eradicate the infection from mice or guinea-pigs. other clinically tested drugs, including nifurtimox, were likewise incapable of eradicating the parasite from infected mice. moxipraquine was less potent against mouse ...19806776663
[leishmania infantum nicolle, 1908, the agent of the autochthonous oriental sore. apropos of the biochemical identification of 2 strains isolated in the eastern pyrenees].two strains of parasites isolated from cases of oriental sore in the pyrénées-orientales were identified by electrophoretic analysis of eight isoenzymes (pgm, pgi, g-6-pdh, 6-pgdh, idh, mdh, me and got). both strains were identical with leishmania infantum nicolle, 1908, which normally causes visceral leishmaniasis. it is probable that, in the mediterranean region, some cutaneous lesions observed within the area of visceral leishmaniasis are caused by this species rather than by leishmania tropi ...19806780226
[meriones shawi (duvernoy, 1842) [rodentia, gerbillidae] a reservoir of leishmania major, yakimoff and schokhor, 1914 [kinetoplastida, trypanosomatidae] in south morocco (author's transl)].for the first time a report is made of meriones shawi (duvernoy, 1842) infected by leishmania major yakimoff and shokhor, 1914. the parasite was observed in two of 28 meriones captured in the immediate vicinity of the tata administrative center (south morocco). m. shawi, because it is sub-commercial with man and abundant, is very likely one of the reservoirs of human cutaneous leishmaniasis in this area.19826807510
therapeutic effect of rifampicin and isoniazid against leishmania tropica major. 19836832881
leishmania tropica major: effect of paromomycin and pentamidine on polyamine levels in the skin of normal and infected mice.the polyamine content of the skin of balb/c and c3h mice was determined at intervals, after injecting leishmania tropica major. in balb/c mice, putrescine and spermidine levels increased three- to seven-fold; in c3h mice, spontaneous recovery occurred after 3 weeks, accompanied by a reduction in putrescine and spermidine levels. ornithine decarboxylase activity was negligible in normal, uninfected skin of both balb/c and c3h mice, but increased steadily during infection. treatment with drugs tha ...19836852166
chemotherapeutic activity of rifampicin on leishmanial amastigotes and promastigotes in vitro.rifampicin reduced the in vitro growth of leishmania tropica major promastigotes and amastigotes: 100 micrograms/ml reducing the growth of amastigotes on day 2 and 250 to 500 micrograms/ml reducing the growth of promastigotes on day 1. a distinct effect of solvents was noted. methanol, dimethylsulfoxide and tween 80 appeared to increase drug effectiveness. pretreatment of l. tropica major promastigotes with 200 micrograms/ml rifampicin for 3 days had no effect on either macrophage engulfment of ...19836853121
action of leishmanial excreted factor (ef) on human lymphocyte blast transformation.the effect of leishmania tropica major excreted factor (ef) on human immune and normal mononuclear peripheral blood cells has been studied. the response of lymphocytes to stimulation either specifically with leishmanial antigens or non-specifically with phytohemagglutinin (pha) in the presence of ef was tested by the uptake of 3 [h]thymidine. the results showed that ef inhibits the response of cells from immune donors to leishmanial antigens and from normal donors to pha or ppd. adherent and non ...19836866562
leishmania tropica major in mice: vaccination against cutaneous leishmaniasis in mice of high genetic susceptibility.balb/c and balb/c.h-2b mice are genetically susceptible to development of persistent and severe disease following cutaneous injection of promastigotes of the protozoan parasite, leishmania tropica major, whereas c57bl/6 are relatively resistant. resistance in c57bl/6 can be further increased by intraperitoneal injection of living, but not killed, promastigotes prior to cutaneous challenge. severely diseased balb/c mice can show resistance to development of a second cutaneous lesion but apparentl ...19836870673
the effect of diaminoalkyl-anthraquinone derivatives on the growth of the promastigotes of leishmania tropica minor, l. t. major, l. donovani and l. aethiopica.by combining knowledge of polyamine biosynthesis and its inhibition by various analogues with that on the activity of synthetic anthraquinones, a series of six anthraquinone derivatives were synthesized. their ability to inhibit the growth of leishmanial promastigotes in vitro was used as a preliminary screen to check their potential as new antileishmanial chemotherapeutics. they were tested against four strains, representing four different species; leishmania tropica major, l. tropica minor, l. ...19836870913
leishmania mexicana and leishmania tropica major: adoptive transfer of immunity in mice. 19806965278
[ecology of a reservoir of cutaneous leishmaniasis in the region of thiès (senegal, west africa). 6. characterization and types of isolated leishmania strains].the authors studied the characterisation and typing of leishmania strains isolated in the keur-moussa focus from human lesions (4 strains), from the digestive tract of phlebotomus duboscqi (i strain) and from the rodents mastomys erythroleucus (2 strains) and tatera gambiana (2 strains). they used the following criteria: amastigote measurements, kinetoplast ultrastructure, pathogenicity in mice and hamsters, isoenzymes, kinetoplast and nuclear dna buoyant densities and the adler test. the result ...19827105287
short communications. a case of cutaneous leishmaniasis with the isolation of the parasite.cutaneous leishmaniasis of the zoonotic, rural type caused by leishmania major was dignosed in a czechoslovak citizen returning from iraq. a leishmania strain was isolated for the first time in czechoslovakia from the skin lesion on the right forearm of the patient. no treatment was necessary because spontaneous healing of the lesion was well under way.19827106657
[ecology of a focus of cutaneous leishmaniasis in the thiès region (senegal, west africa). 4. spontaneous infestation and biology of phlebotomus duboscqi neveu-lemaire 1906].following their epidemiological investigation on the cutaneous leishmaniasis focus of keur moussa, the authors study the sandfly fauna. the species phlebotomus duboscqi is abundant (1,532 samples out of 8,411 sandflies collected between december 1976 and june 1979) and located inside the rodent burrows which have been found to be their larval breeding sites. five p. duboscqi females out of 356 dissected were infected by leishmania major promastigotes.19827168882
[ecology of a focus of cutaneous leishmaniasis in the thiès region (senegal, west africa). 6. characterization and typing of the strains of leishmania isolated].the authors studied the characterisation and typing of leishmania strains isolated in the keur-moussa focus from human lesions (4 strains), from the digestive tract of phlebotomus duboscqi (i strain) and from the rodents mastomys erythroleucus (2 strains) and tatera gambiana (2 strains). they used the following criteria: amastigote measurements, kinetoplast ultrastructure, pathogenicity in mice and hamsters, isoenzymes, kinetoplast and nuclear dna buoyant densities and the adler test. the result ...19827168884
a radioattenuated leishmania major vaccine markedly increases the resistance of cba mice to subsequent infection with leishmania mexicana mexicana.vaccinating cba mice with radioattenuated leishmania major amastigotes but not with radioattenuated l. mexicana mexicana amastigotes rendered them highly resistant to subsequent infection with l. m. mexicana. unvaccinated cba mice were highly susceptible to infection with l. m. mexicana producing rapidly growing non-ulcerating cutaneous lesions. two manifestations of resistance were induced in vaccinated animals depending on the timing of the challenge infection: no lesions appeared at the site ...19827179418
[interrelationship characteristics of leishmania major with various mammalian species]. 19807207384
[ecology of a focus of cutaneous leishmaniasis in the area of thies, senegal, west africa. 4. spontaneous infestation and biology of phlebotomus duboscqi neveu-lemaire 1906].following their epidemiological investigation on the cutaneous leishmaniasis focus of keur moussa, the authors study the sandfly fauna. the species phlebotomus duboscqi is abundant (1532 samples out of 8411 sandflies collected between december 1976 and june 1979) and located inside the rodent burrows which have been found to be their larval breeding sites. five p. duboscqi females out of 356 dissected were infected by leishmania major promastigotes.19807226361
[experimental proof of the heterogeneous composition of natural leishmania major populations for the virulence trait]. 19817322024
systemic infection of leishmania tropica (major) in various strains of mice.the spleen cells of different strains of mice were cultured and examined for the presence of viable promastigotes one to three months following a cutaneous inoculation of 1 to 2 x 10(6) promastigotes of leishmania tropica (major). the spleen cultures of all five strains tested (balb/c, dba/3, c3h, cba and c57b1/6) contained organisms. viable parasites were present in the spleen of resistant strains (c3h, cba, c57b1/6) even after recovery from their cutaneous lesion. the possible implication of t ...19817330948
[the application of a numerical method to the taxonomy of the genus leishmania ross, 1903,--the recognition of 146 original lines in the old world. use of allozymic characters. epidemiological and phyletic significance (author's transl)].using enzyme characters determined by starch gel electrophoresis, the authors have applied the method of numerical taxonomy to the genus leishmania ross, 1903. eight isoenzymes (pgi, me, pgm, got, g-6-pdh, 6-pgdh, mdh and idh) of 146 old world strains are examined. 35 electromorphs, corresponding to equivalent number of isoenzymes, are identified by this method, and then grouped into 14 zymodemes. these zymodemes were used as operational taxonomy units (otu) and pairs were compared, using jaccar ...19817337375
studies on visceral leishmania tropica infection in balb/c mice. i. clinical features and cellular changes.the visceral and lethal infection produced in balb/c mice by leishmania tropica (major) is accompanied by splenomegaly, anaemia and reversal of albumin-to-globulin ratio. the percentages of both b and t cells are decreased in the spleen. the spleen and lymph nodes become populated with large ig-, thy 1.2- 'null' cells. the similarity of some of these parameters with those produced in human kala-azar is discussed.19817337976
polyamines and the growth of leishmanial parasites.the relation between the grown of leishmanial parasites and polyamine biosynthesis was studied. polyamines, mainly putrescine and spermidine, accumulated in macrophages infected with leishmania tropica major promastigotes grown in vitro. similar results were obtained, when tissues of balb/c mice infected with l. tropica major were examined. a consistent increase in cellular putrescine and spermidine levels was observed in infected skin and spleen. with the accumulation of putrescine, a concomita ...19817339304
[serological study of leishmania clones from experimentally and naturally infected sandflies].a serological study of leishmania clones from experimentally and naturally infected sand flies was undertaken. the cloning was done by means of fonbrun's micromanipulator. serological studies were conducted according to adler's method in safjanova's modification. among the clones of phlebotomus papatasi experimentally infected with leishmania tropica major and l. gymnodactyli four were found to be serologically identical with l. tropica major, and two had close antigene relationships with both i ...19807383698
leishmania spp. in iraq. electrophoretic isoenzyme patterns. ii. cutaneous leishmaniasis.leishmania organisms isolated from the sores of patients in iraq suffering from cutaneous leishmaniasis were compared between themselves and with leishmania major, l. tropica and l. donovani, all of which had been identified on clinical and geographical grounds. the comparisons were made by examination of the electrophoretic mobilities of seven soluble enzymes: malic enzyme e.c.1.1.1.40; glucose phosphate isomerase e.c.5.3.1.9; glucose-6-phosphate dehydrogenase e.c.1.1.1.49; phosphoglucomutase e ...19807385297
[characteristics of the relationship between gerbils and leishmania major]. 19807393132
the experimental chemotherapy of leishmaniasis, vi. the development of rodent models for cutaneous infection with l. major and l. mexicana amazonensis.two models have been established of leishmanial infections in random-bred tfw albino mice, one with leishmania major lv39 and the other with l. mexicana amazonensis lv38. these parasites produce consistent lesions when injected subcutaneously a short distance anterior to the base of the tail. consistent infections could not be produced in the mice with other lines of the l. mexicana group of skin-dwelling protozoa, nor with a line of l. braziliensis guyanensis (lv475). the development of procedu ...19807396564
location in the source chromosome of the 180-kb minichromosome of leishmania major and characterization of the novel junction.the 180-kb ld1 minichromosome of leishmania major (m180) is a large inverted duplication which arises spontaneously from a megabasic chromosome. in this work this locus has been located in the source chromosome at a telomeric position. both the novel junction created in the middle of the minichromosome, as well as its counterpart region in the source chromosome were cloned and sequenced. two inverted repeats, which could give rise to two imperfect stem-loops, and an a + t-rich dna sequence were ...19957477097
cloning and characterization of the ribosomal l11 gene from leishmania spp. 19957477109
development of a safe live leishmania vaccine line by gene replacement.vaccination with live leishmania major has been shown to yield effective immunization in humans; however, this has been discontinued because of problems associated with virulence of the available vaccine lines. to circumvent this, we tested the ability of a dhfr-ts- null mutant of l. major, obtained by gene targeting, to infect and then to vaccinate mice against challenge with virulent l. major. survival and replication of dhfr-ts- in macrophages in vitro were dependent upon thymidine, with para ...19957479765
efficacy of the herbicide trifluralin against four p-glycoprotein-expressing strains of leishmania.drug resistance has emerged as a major obstacle to chemotherapy for many infectious diseases. trifluralin, an antimicrotubule herbicide, is a new experimental drug for treatment of leishmaniasis. here, we found that it was effective against two strains of leishmania that express the multidrug-resistant genes ldmdr1 and lmpgpa and two strains that express proteins that are immunologically cross-reactive with mammalian p glycoproteins. these results suggest that trifluralin is not subject to count ...19957492115
evidence from genotypic and phenotypic markers that an attenuated line outgrows a virulent one in a mixed population of leishmania major promastigotes cultured in vitro.two cloned lines of leishmania major promastigotes, one attenuated (co1h) and one virulent (co1r), differing in molecular karyotype and expression of the major surface glycoprotein (gp63), were mixed to produce two heterogeneous populations: mp-1 (100 co1r promastigotes/co1h promastigote); and mp-2 (10,000 co1r promastigotes/co1h promastigote). the mixed populations were cultured for 1 month in vitro in ho-mem medium and sub-samples taken on days 4 and 30 were subjected to electrophoresis so tha ...19957495361
protective effect of leflunomide on the natural course of leishmania major-induced disease in genetically susceptible balb/c mice.leflunomide has been reported as an immunomodulating agent which acts on a variety of cells including t- and b-lymphocytes. cd4+ t-lymphocytes are essential for the type of disease that develops after infection with the protozoan parasite leishmania major. a variety of immunological interventions has been shown to modulate disease development. therefore, the effect of leflunomide on the development of parasite-induced lesions and the ensuing immune response was investigated in genetically suscep ...19957499024
leishmania major parasites share an epitope with the murine cd3-t cell receptor complex.after immunization of balb/c mice with a low molecular mass fraction (frd; < or = 31 kda) isolated from a soluble extract of leishmania major promastigotes, a panel of monoclonal antibodies (mab) was obtained. one of these antibodies (mab 9c) recognized a cytosol-associated antigen from l. major of approximately 21 kda as shown by western blot and immunoprecipitation. in addition, mab 9c reacted with surface structures of murine splenic t cells and t cell clones. reactivity was confined to murin ...19947510231
leishmania major-specific cd8+ t cells are inducers and targets of nitric oxide produced by parasitized macrophages.lines of leishmania major-specific cd8+ t cells were derived from the lymph nodes and spleens of cba mice, immune following resolution of a primary infection, 7 days after secondary challenge with viable l. major. specific stimulation of these cd8+ t cells by bone marrow-derived macrophages infected with l. major led to the release of interferon-gamma by cd8+ t cells and nitric oxide by macrophages. interestingly, the nitric oxide released by bone marrow-derived macrophages down-regulated the pr ...19947510243
cell-mediated responses of immunized vervet monkeys to defined leishmania t-cell epitopes.a population of vervet monkeys was immunized with killed parasites and infected with leishmania major promastigotes either by needle or by infected-fly bite. the responses of recovered monkeys to mitogens, killed parasites, and molecularly defined t-cell epitopes were then compared with those of control animals. peripheral blood mononuclear cells (pbmc) from both naive and recovered animals proliferated strongly in response to both b- and t-cell mitogens, although the responses of the recovered ...19947513306
tissue expression of inducible nitric oxide synthase is closely associated with resistance to leishmania major.previous studies with inhibitors of inducible nitric oxide synthase (inos) suggested that high-output production of nitric oxide (no) is an important antimicrobial effector pathway in vitro and in vivo. here, we investigated the tissue expression of inos in mice after infection with leishmania major. immunohistochemical staining with an inos-specific antiserum revealed that in the cutaneous lesion and draining lymph nodes (ln) of clinically resistant mice (c57bl/6), inos protein is found earlier ...19947520472
vaccination of the leishmania major susceptible balb/c mouse. i. the precise selection of peptide determinant influences cd4+ t cell subset expression.balb/c mice are susceptible to cutaneous leishmaniasis upon infection with leishmania major while c57bl/6 are not. there is a major promastigote surface protease (psp or gp63) which is available in both native and recombinant forms, and for which the primary amino acid sequence is known. immunization with psp has been shown to offer some protection against challenge with the live organism. therefore, we attempted to develop a peptide vaccine with psp peptides. in the first experiments, recall pr ...19947521670
differential effects of blockade of cd28-b7 on the development of th1 or th2 effector cells in experimental leishmaniasis.infection of inbred strains of mice with leishmania major is a well-characterized model for analysis of the development of effector cd4+ subsets of the th1 and th2 types in vivo. we co-administered a fusion protein, ctla4ig, that blocks the cd28-b7 costimulatory pathway important for optimal t cell activation, to assess the relative role for this pathway during maturation of th1 and th2 cells in vivo. surprisingly, ctla4ig administered within the first week of infection completely abrogated prog ...19947523517
nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens.to discover how nitric oxide (no) synthesis is controlled in different tissues as cells within these tissues combat intracellular pathogens, we examined three distinctively different experimental murine models designed for studying parasite-host interactions: macrophage killing of leishmania major; nonspecific protection against tularemia (francisella tularensis) by mycobacterium bovis (bcg); and specific vaccine-induced protection against hepatic malaria with plasmodium berghei. each model para ...19947537721
expression of murine vcam-1 in vitro and in different models of inflammation in vivo: correlation with immigration of monocytes.vcam-1 (vascular cell adhesion molecule-1) is a cytokine-inducible adhesion molecule which is known to mediate adhesion of mononuclear cells to endothelial cells in vitro via binding to the integrin vla-4 (very late antigen-4). to further elucidate the role and regulation of vcam-1 in vivo, we compared in vitro and in vivo expression of vcam-1 in response to cytokines and investigated immunohistochemically the expression of vcam-1 in three murine models of experimental inflammation. these models ...19947538407
altered immune responses in mice lacking inducible nitric oxide synthase.nitric oxide (no) is important in many biological functions. it is generated from l-arginine by the enzyme no synthase (nos). the cytokine-inducible nos (inos) is activated by several immunological stimuli, leading to the production of large quantities of no which can be cytotoxic. to define the biological role of inos further, we generated inos mutant mice. these are viable, fertile and without evident histopathological abnormalities. however, in contrast to wild-type and heterozygous mice, whi ...19957539113
[the possible use of gramicidin for the treatment of zoonotic cutaneous leishmaniasis]. 19957539520
effect of pge2 and of agents that raise camp levels on macrophage activation induced by ifn-gamma and tnf-alpha.the effect of prostaglandin (pg) e2 on macrophage activation by interferon-gamma (ifn-gamma) and tumor necrosis factor-alpha (tnf-alpha) was evaluated. murine macrophages infected with leishmania enriettii or leishmania major were activated by exposure to ifn-gamma (10-50 u/ml) and tnf-alpha (30-3000 u/ml), leading to intracellular parasite destruction within 24-48 h. leishmanicidal activity was markedly increased when activation was performed in the presence of pge2 (10(-9)-10(-7) m) or arachid ...19957543922
the killing of leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the fc epsilon rii/cd23 surface antigen.serum ige concentrations and the expression of the low-affinity receptor for ige (fc epsilon rii/cd23) are increased in cutaneous leishmaniasis or after immune challenge with leishmania antigens. in vitro, the ligation of cd23 by ige-anti-ige immune complexes (ige-ic) or by anti-cd23 monoclonal antibody (mab) induces nitric oxide (no) synthase and the generation of various cytokines by human monocytes/macrophages. the present study shows that ige-ic, via cd23 binding, induce intracellular killin ...19957544003
recombinant bcg expressing the leishmania surface antigen gp63 induces protective immunity against leishmania major infection in balb/c mice.we have cloned and expressed the gp63 gene of leishmania major in bcg to develop a recombinant vaccine against zoonotic cutaneous leishmaniasis. two different expression systems were investigated. the first system consists of pan, a mycobacterium paratuberculosis promoter, which drives expression of orf2, an open reading frame in is900. this system allows the production of heterologous polypeptides as hybrids with the orf2 gene product. the second expression system relies on the production of an ...19957551026
scid mice reconstituted with oct-2-deficient lymphocytes can cure leishmania major infection and generate normal antigen-specific t cells. 19957558177
sand fly vector saliva selectively modulates macrophage functions that inhibit killing of leishmania major and nitric oxide production.the saliva of phlebotomus papatasi, a sand fly vector for leishmania major, contains a factor that exacerbates leishmaniasis and may be required for the establishment of infection with leishmania in nature. we have examined the effect of sand fly saliva on various macrophage functions in vitro. our data demonstrate that although saliva does not alter uptake of l. major by macrophages, it inhibits the ability of ifn-gamma to activate macrophages to kill the intracellular parasite. this inhibition ...19957561045
regulation of interleukin 12 p40 expression through an nf-kappa b half-site.interleukin 12 (il-12) is an inducible cytokine composed of 35- and 40-kda subunits that is critical for promoting t helper type 1 development and cell-mediated immunity against pathogens. the 40-kda subunit, expressed by activated macrophages and b cells, is induced by several pathogens in vivo and in vitro and is augmented or inhibited by gamma interferon (ifn-gamma) or il-10, respectively. control of il-12 p40 expression is therefore important for understanding resistance and susceptibility t ...19957565674
changes in lipophosphoglycan and gene expression associated with the development of leishmania major in phlebotomus papatasi.stage-specific molecular and morphogenic markers were used to follow the kinetics of appearance, number, and position of metacyclic promastigotes developing during the course of l. major infection in a natural vector, phlebotomus papatasi. expression of surface lipophosphoglycan (lpg) on transformed promastigotes was delayed until the appearance of nectomonad forms on day 3, and continued to be abundantly expressed by all promastigotes thereafter. an epitope associate with arabinose substitution ...19957567096
diversity among leishmania isolates from the sudan: isoenzyme homogeneity of l. donovani versus heterogeneity of l. major.leishmania isolates from patients in the sudan suffering from either visceral or cutaneous leishmaniasis were characterized using a battery of 12 enzymes. aspartate aminotransferase separated the l. donovani isolates into 2 distinct zymodemes, but the overall results showed no significant geographical variation among l. donovani isolates. in contrast, the isolates of l. major were polymorphic, exhibiting differences in nucleoside hydrolase, 6-phosphogluconate dehydrogenase, superoxide dismutase, ...19957570863
structure of leishmania lipophosphoglycan: inter- and intra-specific polymorphism in old world species.the most abundant surface macromolecule on the promastigote stage of leishmanial parasites is a polymorphic lipophosphoglycan (lpg). we have elucidated the structures of two new lpgs, from leishmania tropica (lrc-l36) and l. aethiopica (lrc-l495), and investigated the nature of intra-specific polymorphism in the previously characterized lpg of l. major (lrc-l456 and -l580). these molecules contain a phosphoglycan chain, made up of repeating po4-6gal beta 1-4man units and a conserved hexaglycosyl ...19957575413
molecular comparison of the mitochondrial and cytoplasmic hsp70 of trypanosoma cruzi, trypanosoma brucei and leishmania major.we compared the expression and localization of the mitochondrial and cytoplasmic hsp70 of the protozoans trypanosoma cruzi, trypanosoma brucei and leishmania major. the mitochondrial protein is encoded by multiple mrna in all species, while the cytoplasmic protein is encoded by a single mrna. in all three species, the mitochondrial hsp70 is concentrated in the kinetoplast, a submitochondrial structure that houses the unusual dna (kdna) that characterizes this group of organisms, while the cytopl ...19957581323
[leishmaniasis: new diagnostic approaches]. 19957582649
experimental immunization against cutaneous leishmaniasis using leishmania major subcellular fractions alone or in combination with phlebotomus duboscqi gut antigens.leishmania major-derived flagella and nuclear fractions, and a combination of flagella and sand fly gut antigens were assessed for protection against l. major infection in balb/c mice. mice immunized with flagella antigen developed a severe infection while nuclear fraction-immunized animals were partially protected at the onset of infection from week 1 to 4 post challenge. a combination/cock tail of flagella and sand fly gut antigens protected animals at a later stage from week 10 to 14 post-inf ...19957588148
protective vaccination with promastigote surface antigen 2 from leishmania major is mediated by a th1 type of immune response.leishmania major promastigote surface antigen-2 complex (psa-2) comprises a family of three similar but distinct polypeptides. the three psa-2 polypeptides were purified from cultured promastigotes by a combination of detergent phase separation and monoclonal antibody affinity chromatography. intraperitoneal vaccination of c3h/he mice with psa-2 with corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent l. major. sig ...19957591056
the sensitivity of leishmania species to aminosidine.the aminoglycoside, aminosidine exhibited ed50s of between 1 and 5 microm against the amastigotes of leishmania major and leishmania tropica in mouse peritoneal macrophages whereas other strains causing new world cutaneous leishmaniasis such as leishmania braziliensis were more refractory. aminosidine was also active against all but one of the leishmania donovani strains tested and when combined with sodium stibogluconate, the drug showed marked potentiation against the amastigotes of l. donovan ...19957592170
ubiquinone biosynthesis in leishmania major promastigotes.promastigotes of leishmania major contain a ubiquinone which has a side chain made up of nine isoprene subunits (uq9). incorporation of radioactivity from [14c] acetate and [14c] mevalonate into ubiquinone as well as the identification of hydroxymethylglutaryl coenzyme a reductase (hmg coa reductase), and mevalonate kinase indicate that the isoprenoid portion of the molecule is synthesized by the acetate-mevalonate pathway as in mammalian cells. incorporation of [14c] tyrosine into ubiquinone is ...19957601585
studies on zoonotic cutaneous leishmaniasis among a group of temporary workers in north sinai governorate, egypt.leishmaniasis (cutaneous, cl. and visceral, vl.) is an increasing public health problem in the mediterranean region. from a practical point of view, zcl is the most important and distributed form in egypt. consequently, it was aimed to study the status of zcl among a group of temporary workers in north sinai governorate. the results showed that (i) rodent populations are more or less common in al arish city (rattus rattus and r. norvegicus), bir lehfan (gerbillus pyramidum) and abo oegela (g. py ...19957602176
the cation-independent mannose-6-phosphate receptor binds to soluble gpi-linked proteins via mannose-6-phosphate.the cation-independent mannose-6-phosphate/insulin-like growth factor ii receptor has been observed to bind to soluble forms of glycosyl-phosphatidylinositol-linked molecules, one of mammalian origin (rat thy-1) and two of protozoan origins. of the two phosphate groups found on the soluble forms of the protozoan glycosyl-phosphatidylinositol-linked molecules: (i) the internal mannose-6-phosphate diester (which forms a part of the ethanolamine bridge) and (ii) the inositol-1,2 cyclic phosphate gr ...19957607332
endogenous il-12 is required for control of th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice.we investigated the mechanisms by which treatment with anti-il-12 ab prevents cure of infection with leishmania major in resistant c57bl/6 mice. consistent with delayed production of il-12, anti-il-12 abs could be administered as late as 2 wk after infection to exacerbate disease. starting at 2 wk of infection, the cultured lymph node cells from mice treated with either polyclonal or monoclonal anti-il-12 abs persistently generated 3- to 10-fold more il-4 and il-10 in response to l. major ag com ...19957608551
the rflp analysis of the beta-tubulin gene region in new world leishmania.we have examined the similarities and differences in the organization of tubulin genes in new world leishmania by restriction endonuclease digestion of genomic dna and southern blot analysis, using heterologous and homologous tubulin gene probes. as judged by the hybridization pattern and the restriction fragment length polymorphism (rflp), there were large differences in both the restriction and hybridization patterns of the beta-tubulin sequences between stocks of the mexicana and braziliensis ...19957609983
the regulation of immunity to leishmania major.experimental infection with the intracellular protozoan leishmania major constitutes a particularly versatile model for assessing the role of cd4+ subset development in the host response to infectious disease. the association of th1 development with control of infection, and of th2 cell development with progressive disease, has been well established. the capacity to manipulate the outcome, using distinct immunologic interventions, in both genetically resistant and susceptible mice has identified ...19957612219
comparison of new and old world leishmanins in an endemic region of brazil.the control of leishmaniasis depends on a knowledge of the magnitude of the disease and of exposure to it. delayed-type hypersensitivity testing can detect prior exposure to the parasite, but there is little agreement regarding the choice of an antigen for such testing. new and old world leishmanins were tested in a study of patients with confirmed prior cutaneous leishmaniasis (cl), patients with confirmed prior american visceral leishmaniasis (avl), and controls from areas in espírito santo, b ...19957620013
expansion of gamma delta+ t cells in balb/c mice infected with leishmania major is dependent upon th2-type cd4+ t cells.t cells belong to either the alpha beta+ or gamma delta+ lineage as defined by their antigen receptor. although both t-cell subsets have been shown to be involved in the immune response to the parasite leishmania major, very little is known about possible interactions between these two populations. in this study, using a mouse model of infection with l. major, we showed that expansion of a subset of gamma delta+ t cells in vivo is dependent upon the presence of alpha beta+ cd4+ t cells. moreover ...19957622222
identification of intra- and interspecific leishmania genetic polymorphisms by arbitrary primed polymerase chain reactions and use of polymorphic dna to identify differentially regulated genes.arbitrary primed polymerase chain reactions (ap-pcr) were used to amplify different polymorphic genomic dna fragments from various old world leishmania species. using four 10-mer ap primers, geographic isolates of l. donovani and various old world species of leishmania could be readily distinguished from one another by the pattern of amplified dna products. our studies confirmed two important characteristics of ap-pcr: its abilities to amplify a consistent pattern of dna fragments from the genom ...19957624284
in vivo evaluation of immune responses in leishmaniasis: the use of cross-species leishmanin preparations for skin testing.skin test reactivity to two commercial preparations of leishmania major leishmanin was evaluated in leishmaniasis patents from ethiopia (l. aethiopica) and nicaragua (probably l. braziliensis complex). the purpose of using different preparations of l. major was to evaluate whether l. major skin test antigens could generally be used to detect leishmaniasis due to l. aethiopica and l. braziliensis. one preparation was superior in identifying the majority (83-90%) of confirmed cases of local cutane ...19957625529
activity of pentostam (sodium stibogluconate) against cutaneous leishmaniasis in mice treated with neutralizing anti-interferon-gamma antibody.studies with leishmania donovani in the mouse have demonstrated that an intact t cell compartment is required for effective anti-leishmanial therapy using pentavalent antimony compounds such as pentostam (sodium stibogluconate), suggesting that the in vivo efficacy of drug treatment is at least partially immune-based. similarly, leishmania-infected, immunodeficient human patients including those with acquired immunodeficiency syndrome (aids) generally relapse following therapy with antimonials. ...19957625533
determinant flanking regions and the design of appropriate vaccines. 19957625680
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