Publications

efficacy of rifampicin and isoniazid in cutaneous leishmaniasis.	thirty-nine patients with cutaneous leishmaniasis caused by leishmania major were treated with rifampicin alone or in combination with isoniazid. no significant difference was found between these two therapeutic regimens, and about half of the patients were cured 2 months from the beginning of treatment. a review of rifampicin in cutaneous leishmaniasis is attached.	1987	3557792
the correlation between delayed hypersensitivity, lymphocyte activation and protective immunity in experimental murine leishmaniasis.	the growth of leishmania major and leishmania mexicana lesions and the concomitant development of delayed-type hypersensitivity (dth) to homologous or heterologous soluble antigen was studied in balb/c and cba/ca mice. although cba/ca mice are highly susceptible to l. mexicana, developing non-healing lesions, they are resistant to l. major; while balb/c mice develop non-healing lesions when infected with either species. the development of resistance was associated with the acquisition of dth whi ...	1987	3562057
variants with reduced virulence derived from leishmania major after mutagen treatment.	after several in vitro treatments of a virulent population of leishmania major with the mutagen, n-methyl-n'-nitro-n-nitrosoguanidine (mnng), five clones (vir-) were obtained that did not produce cutaneous lesions after subcutaneous injection of 10(6) promastigotes. all the control clones (vir+) obtained from the non-mutagenized parasite population produced progressive cutaneous lesions with as few as 10(3) parasites. late lesions were observed occasionally after injection of 10(7) vir- parasite ...	1987	3562060
natural focality of zoonotic cutaneous leishmaniasis in the mongolian people's republic; results and objectives of integrated research.	in the summer 1976, natural foci of zoonotic cutaneous leishmaniasis were discovered by the authors on the territory of the mongolian people's republic. in 1976-1983 the integrated research of these foci was conducted and maps of a structure of the geographical range of the pathogen were compiled taking into account the peculiarities of distribution of its carriers and vectors. great gerbils are the only identified vertebrate hosts of leishmania and their infection rate comes up to 100% in singl ...	1987	3583127
effect of glucan on leishmania major infection in balb/c mice.	the effect of glucan on leishmania major infection was studied in balb/c mice, which are highly susceptible to leishmania infection. glucan (0.45 mg), or isovolumetric dextrose, was administered intraperitoneally 7, 5, 3 and 1 day before infection with l. major promastigotes. at 3, 5, 6, 8 and 10 weeks after infection, animals were killed; the liver and spleen of each animal were weighed and the parasite burden was calculated. a significant (p less than 0.01) reduction in amastigote proliferatio ...	1987	3585970
a stable binary complex between leishmania major thymidylate synthase and the substrate deoxyuridylate. a slow-binding interaction.	the thymidylate synthase (ts) activity in leishmania major resides on the bifunctional protein thymidylate synthase-dihydrofolate reductase (ts-dhfr). we have isolated, either by sephadex g-25 chromatography or by nitrocellulose filter binding, a binary complex between the substrate deoxyuridylate (dump) and ts from l. major. the kinetics of binding support a "slow binding" mechanism in which dump initially binds to ts in a rapid, reversible pre-equilibrium step (kd approximately 1 microm), foll ...	1987	3597407
clinical diagnosis of cutaneous leishmaniasis (oriental sore).	cutaneous leishmaniasis (oriental sore) is characterized by slowly evolving inflammatory lesion(s) that are nodular, noduloulcerative, or ulcerative and that heal spontaneously with scar(s) in 3 to 12 months. in the course of a comprehensive study of cutaneous leishmaniasis due to leishmania major in an endemic focus in saudi arabia, seven clinical features of diagnostic value were identified and their approximate frequency in a selected group of 475 patients was determined. these features were: ...	1987	3597860
quantitative structure-activity relationship of triazine-antifolate inhibition of leishmania dihydrofolate reductase and cell growth.	quantitative structure-activity relationships have been formulated for the inhibition of leishmania major dihydrofolate reductase (dhfr) and for inhibition of promastigote cell growth by a series of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-substituted-phenyl)-s-triazine s. the inhibition of dhfr is best correlated by a modified variable for hydrophobicity of the 3-x substituent (pi'3), an alkoxy group indicator variable (ior), a disposable parameter (beta) obtained by iteration, and a variable ...	1987	3599028
natural infections of leishmania major in domestic dogs from alexandria, egypt.	two leishmanial isolates from dogs from alexandria, egypt, were typed serologically and biochemically as leishmania major. this is the second time that l. major has been shown to occur in dogs. the significance of these findings as a misleading phenomenon in relation to the relatively recent outbreak of infantile kala-azar in the area of alexandria is discussed.	1987	3605504
dissemination in cutaneous leishmaniasis. i. subcutaneous nodules.	in a study of cutaneous leishmaniasis (cl) caused by leishmania major in saudi arabia, 10% of the patients were found to have subcutaneous nodules (scn). the scns were usually inconspicuous, painless, and proximal to the primary skin lesions; when multiple, they showed a "sporotrichoid" configuration or appeared as "beaded cords." their number ranged from 1-16 (average 3 25 +/- 2.50; mean +/- 1 sd). in some patients, the scns seemed to be triggered by antileishmanial treatment. the clinical pict ...	1987	3610435
genomic organization, chromosomal location and transcription of dispersed and repeated tubulin genes in leishmania major.	the alpha and beta tubulin genes of leishmania major were cloned and used to study the genomic organization, chromosomal location and transcription of tubulin genes in l. major. the number of beta tubulin isogenes was determined by hybridization of probes representing the 5' and 3' ends of the cloned beta tubulin cdna sequence to genomic southern blots which showed that four complete isogenes exist on ava1 fragments of size 4.4, 3.9, 1.85 and 1.7 kilobase pairs (kb). these genes are present at a ...	1987	3614270
folylpolyglutamates in leishmania major.	the intracellular folates of the protozoan parasite leishmania major have been examined. about 95% of the exogenous [3h]folate accumulated by the protozoan is metabolized to polyglutamate conjugates within 65 hr, and the intracellular folates are about forty-fold concentrated over the folate in the medium. the predominant metabolite of folic acid is the pentaglutamate conjugate (85%), with lessor amounts of the tetraglutamate (approximately 9%) and hexaglutamate (approximately 3%), and trace (le ...	1987	3619916
[an entomological survey in the focus of zoonotic cutaneous leishmaniasis (leishmania major) of sidi bouzid (tunisia) in 1985].	an entomological survey carried out in 1985 in the zoonotic cutaneous leishmaniasis foci of the center of tunisia (sidi bouzid governorate), showed the presence of 7 phlebotomine species. phlebotomus (p) papatasi, the most abundant species (84.6%), was essentially trapped in rodent burrows. its anthropophily was demonstrated by man-baiting catch. the highest population density was observed during july and august, for p. papatasi. its role in the transmission of z. c. l. in tunisia is discussed. ...	1987	3621397
development of sandfly forms of leishmania major in sucrose solutions.	stages of leishmania developing in the vector include different morphs that are exposed first to ingested blood and then to sugar meals. this study sought to determine whether stages occurring in the latter medium could be induced by culturing in sugar-based media. in sucrose solutions, l. major continued to divide and multiplied by 38-46%. paramastigotes and aflagellates are forms present in late stages of leishmania infection in phlebotomus papatasi. they constituted 79% of the forms in sucros ...	1987	3625431
laboratory investigations on the survival and fecundity of phlebotomus duboscqi (diptera, psychodidae), a vector of leishmania major in kenya.	the gonotrophic cycle, survival and reproductive potential of adult female phlebotomus duboscqi, a vector of leishmania major in baringo district, kenya was investigated in the laboratory. the sandflies were fed on hamster and apples as a sugar source and were placed in vials for oviposition. the feeding and care for oviposition was repeated for as long as the flies lived. the longest period p. duboscqi survived after taking the first blood meal was 45 days. the flies completed up to eight gonot ...	1987	3629141
a macrophage immunosuppression induced by leishmania major in balb/c mice.	the purpose of the present study is to investigate the status of the reticuloendothelial system (res) phagocytic function in relation to leishmania major infection in highly susceptible balb/c mice. the res phagocytosis was monitored by: intravascular clearance of carbon colloid; tissue distribution 99mtechnetium labelled sulphur colloid in res organs; and serum lysozyme enzyme level. the kinetics of res phagocytosis during l. major infection was also studied at 0, 3, 5, 7 and 8 weeks post-infec ...	1987	3629142
experimental cutaneous leishmaniasis. ii. a possible role for prostaglandins in exacerbation of disease in leishmania major-infected balb/c mice.	leishmania major infection in genetically susceptible balb/c mice is associated with the development of chronic primary lesions as well as multiple metastatic lesions. spleen cells from these mice were shown to have depressed in vitro responses to concanavalin a (con a) that coincided with the development of indomethacin-sensitive suppressor cells. depressed responses to con a were noted as early as 1 wk after parasite inoculation and correlated with the increased production of prostaglandin e2 ...	1987	3100619
macrophage activation for antileishmanial defense by an apparently novel mechanism.	activation of macrophages by lymphokines (including interferon-gamma; ifn-gamma) is presently considered to be a major host defense mechanism against a number of intracellular microorganisms. in a series of earlier studies that made use of mice undergoing spontaneous resolution of footpad infections with leishmania major, we obtained evidence suggesting that a subpopulation of leishmania-sensitized lymph node t lymphocytes could activate antimicrobial effects in leishmania-infected macrophages b ...	1987	3100630
cellular and humoral immunity to leishmania major in genetically susceptible mice after in vivo depletion of l3t4+ t cells.	depletion of critical t cell subsets in vivo by treatment with anti-l3t4 antibody (mab gk1.5) enables balb/c mice to heal subsequent leishmania major infection. to investigate the mechanisms by which healing is established, anti-leishmania cellular and humoral responses in anti-l3t4-treated balb/c mice were compared to those in control balb/c and genetically resistant c57bl/6 mice. lymph node and spleen cells were harvested from l. major-infected animals at 1, 2, 3, 4, and 8 wk post-infection an ...	1987	3112230
involvement of specific lyt-2+ t cells in the immunological control of experimentally induced murine cutaneous leishmaniasis.	the involvement of lyt-2+ t cells in the immunological control of cutaneous leishmaniasis was assessed by studying the course of the disease in mice in which the number of these cells was reduced by treatment with anti-lyt-2 monoclonal antibody (mab). administration of anti-lyt-2 mab exacerbated leishmania major-induced cutaneous lesions in both genetically resistant and susceptible mice. this effect correlated with a drastic reduction in the number of specific lyt-2+ t cells generated during in ...	1987	3119350
antigen-stimulated lymphokines from patients with cutaneous leishmaniasis induce monocyte killing of leishmania major intracellular amastigotes.	the specific immune response of patients with cutaneous leishmaniasis including the ability of their lymphokines to enhance the monocytes' leishmaniacidal activity was studied. in 16 patients with cutaneous leishmaniasis, their concanavalin a-induced lymphocyte proliferative responses, interferon-gamma and interleukin 2 activities and the ability of their concanavalin a-induced lymphokines to kill monocyte intracellular amastigotes were not different from normal controls. antigen-stimulated lymp ...	1987	3121732
in vitro activity of sulfonamides and sulfones against leishmania major promastigotes.	we examined the susceptibility of promastigotes of leishmania major to sulfonamides and sulfones in vitro. in a completely defined medium only sulfamoxole, sulfaquinoxaline, and dapsone were inhibitory; the concentrations required for 50% inhibition of the rate of growth were 150, 600, and 600 microm, respectively. eleven other sulfa drugs were ineffective at concentrations up to 2 mm. the growth inhibition was similar to that observed in procaryotes: the cells continued logarithmic growth for s ...	1987	3435106
heterologous protection in murine cutaneous leishmaniasis.	mice immunized with a glycolipid antigen (gl) of leishmania major plus adjuvant are relatively resistant to subsequent infection with this protozoan parasite. the gl is affinity purified on the monoclonal antibody wic-79.3 which is l. major-specific and does not react with l. donovani. when another monoclonal, wic-108.3, which cross-reacts with several leishmania species, is used to affinity purify gl from l. donovani, the eluted material can partially protect genetically resistant mice against ...	1987	3436638
isolation of leishmania major from a naturally infected vervet monkey (cercopithecus aethiops) caught in kiambu district, kenya.		1987	3437365
leishmania major: a very sensitive dot-blot elisa for detection of parasites in cutaneous lesions.	there is a need for accurate, rapid and early diagnosis of leishmaniasis, which would distinguish between the benign and severe forms of the disease. we have used a monoclonal antibody directed to a polymorphic, species-specific antigen in diagnostic assays for leishmaniasis. the dot-blot enzyme-linked immunosorbent assay described here can detect as few as 300 culture promastigotes and 20,000 amastigotes of leishmania major with no cross-reaction with other species and no background from skin m ...	1987	3437821
cutaneous leishmaniasis caused by leishmania major in baringo district, kenya.	leishmania major was isolated from lesions of a patient suffering from cutaneous leishmaniasis in baringo district of kenya. isoenzyme mobilities of this strain were compared with those of l. major, l. donovani, l. aethiopica and l. tropica reference strains and also l. major from a sand fly, phlebotomus duboscqi, and a rodent, arvicanthis niloticus, trapped in the same region. the patient's isolate had similar banding patterns to the l. major reference strain and also the rodent and the sand fl ...	1987	3445343
immunological parameters of visceral leishmaniasis of leishmania major-infected golden hamsters.	we can consider the leishmania major-infected hamster as an interesting model of visceral leishmaniasis. every hamster infected with l. major strain 70 by peritoneal route developed visceral dissemination of the parasite. when immunological parameters were considered, we saw data quite similar to those presented by visceral leishmaniasis patients: negative leishmanin skin test and presence of anti-leishmania antibody. histopathological analysis showed dissemination of the parasite mainly to live ...	1987	3445875
topical treatment of new and old world cutaneous leishmaniasis in experimental animals.	the effect of topical treatment with 15% paromomycin sulphate and 12% methylbenzethonium chloride in white soft paraffin on cutaneous leishmaniasis in balb/c mice was studied. the saudi arabian strain of leishmania major, although being the most virulent to the mice, showed the highest susceptibility to this treatment. after 10 days treatment, parasites were totally eliminated from the treated lesion and healing was complete. 3 american strains were also tested: l. mexicana amazonensis; l. brazi ...	1987	3449988
isolation of leishmania major from phlebotomus papatasi in tunisia.		1987	3449994
vaccination against cutaneous leishmaniasis in a murine model. i. induction of protective immunity with a soluble extract of promastigotes.	balb/c mice can be protected against a fatal leishmania major infection by immunization with whole radio-attenuated promastigotes; however, neither the antigens responsible for protection nor the protective immunologic mechanisms have been defined. in this study, the ability of promastigote fractions to elicit similar immunity to that obtained with whole organisms, and the immune responses associated with such protection were analyzed. intraperitoneal immunization with a soluble, membrane-free p ...	1987	3495599
kinetics of cell-mediated immunity developing during the course of leishmania major infection in 'healer' and 'non-healer' mice: progressive impairment of response to and generation of interleukin-2.	leishmania major (l. major)-infected mice of 'non-healer' (balb/c) and 'healer' (c57bl/6) mouse-strain origin were studied with regard to the kinetics of cell-mediated immunity developing during the course of the disease. cells obtained from lymph nodes draining l. major-infected footpads were comparatively analysed for their representation in the respective l3t4+, lyt-2+ and sig+ lymphocyte subsets; they were studied for their capacity to release interleukin-2 and to proliferate in response to ...	1987	3499384
vaccination against cutaneous leishmaniasis in a murine model. ii. immunologic properties of protective and nonprotective subfractions of soluble promastigote extract.	we have previously demonstrated that balb/c mice can be protected against a fatal infection with leishmania major by i.p. immunization with a soluble leishmanial antigen (sla) preparation in conjunction with the adjuvant, corynebacterium parvum (cp). in this study, sla was separated into nine distinct fractions by anion exchange liquid chromatography, and the fractions were analyzed for their ability to stimulate t cells obtained from immunized mice, to be recognized by vaccine-induced antibodie ...	1987	3499465
identification of t-cell-reactive antigens that protect balb/c mice against leishmania major.		1987	3501959
identification of leishmania genes encoding proteins containing tandemly repeating peptides.	a genomic leishmania major dna expression library was screened using antibodies raised against l. major membranes. two different clones were identified that encoded proteins containing regions of tandemly repeated peptides. clone 20 encodes a repetitive peptide of 14 amino acids, while clone 39 encodes a repetitive peptide of 10 amino acids. dna from clone 20 hybridized with two rna species of 9,500 and 5,200 nucleotides in length, while dna from clone 39 hybridized to a single rna species of 7, ...	1987	3502718
gerbillus pyramidum is a host of leishmania major in the sinai peninsula.		1987	3503651
hybrid formation within the genus leishmania?	leishmanial organisms isolated from a desert rodent (psammomys obesus) and a feral dog (canis familiaris) in the eastern province of saudi arabia were isoenzymically distinct from leishmania major and l. arabica, organisms usually associated with human and wild animal cutaneous leishmaniasis in this area. further examination of isoenzyme banding patterns of cloned populations of these organisms, together with karyotyping using orthogonal field alternation gel electrophoresis and the use of highl ...	1987	3508260
murine cutaneous leishmaniasis: susceptibility correlates with differential expansion of helper t-cell subsets.	balb/c mice develop fatal illness following infection with leishmania major despite expansion of helper l3t4+ t cells in the draining lymph nodes and spleen. healer mice, either genetically resistant c57bl/6 or balb/c that have been pretreated with monoclonal antibody gk 1.5, also develop expanded numbers of l3t4+ t cells at the time of healing. lymph node cells from healer mice produce gamma-interferon in vitro and message for gamma-interferon can be recovered from the lymph nodes during healin ...	1987	2964247
modulation of the pattern of development of experimental disseminated leishmaniasis by corynebacterium parvum.	balb/c mice are extremely susceptible to leishmania major. in this mouse strain, the parasite multiplies progressively and rapidly disseminates to distant visceral and cutaneous sites. the present studies show, however, that if balb/c mice are infected with the l major as an admixture with formalin-killed corynebacterium parvum, they rapidly acquire the capacity to restrain the multiplication of the parasite at the site of inoculation, and prevent its dissemination to distant visceral sites. mor ...	1987	3468194
lipophosphoglycan of leishmania major that vaccinates against cutaneous leishmaniasis contains an alkylglycerophosphoinositol lipid anchor.	the major cell surface glycoconjugate of leishmania major, a putative parasite receptor for macrophages, is a lipophosphoglycan containing 81.6% (wt/wt) carbohydrate, 17.0% (wt/wt) phosphate, and 1.4% (wt/wt) lipid. it has been purified to homogeneity by hydrophobic chromatography and consists of a polydisperse family of molecules with mr 5000-40,000. it contains galactose, mannose, glucose, arabinose, glucosamine, and inositol in the molar ratio of 51:21:5:6:1:1. the lipophosphoglycan has a com ...	1987	3480520
reductions in methotrexate and folate influx in methotrexate-resistant lines of leishmania major are independent of r or h region amplification.	the methotrexate (mtx) and folate transport properties of five mtx-resistant lines of leishmania major have been examined. these resistant lines all show a decreased vmax for mtx influx, with no change in apparent affinity (kt). the vmax of folate influx is also proportionately decreased without alteration in kt, supporting our proposal that there is a single carrier mediating influx of both ligands. amplifications of two regions of dna, the r region (encoding dihydrofolate reductase-thymidylate ...	1987	3654626
metacyclogenesis is a major determinant of leishmania promastigote virulence and attenuation.	the in vivo virulence patterns of promastigote populations defined on the basis of agglutination by the lectin peanut agglutinin (pna) were studied for various cloned lines of leishmania major. promastigotes derived from logarithmic-phase cultures, which were routinely 100% agglutinated at 100 micrograms of pna per ml, were relatively avirulent for balb/c mice. the relative virulence of stationary-phase promastigotes appeared to be attributable to the proportion of nonagglutinable (pna-) promast ...	1987	3666964
leishmania major: the suitability of east african nonhuman primates as animal models for cutaneous leishmaniasis.	the susceptibility of four species of east african nonhuman primates to experimental infection with leishmania major was investigated. four syke's monkeys (cercopithecus mitis), two vervet monkeys (cercopithecus aethiops), two baboons (papio cynocephalus), and two brown bushbabies (galago garnettii) were each inoculated intradermally on the left eyelid, left ear, and nose with 0.1 ml of medium containing 1 x 10(7) promastigotes of a characterized l. major strain. all the nonhuman primates except ...	1987	3678449
dna synthesis in promastigotes of leishmania major and l. donovani.	the requirement of protozoan parasites for pre-formed purines affords the opportunity for quantitation of nucleic acid synthesis from incorporation of radioactively labeled purines into dna and rna. we have developed rapid and simple assays to quantitate dna and rna synthesis in promastigotes of leishmania major and l. donovani from the incorporation of [3h]hypoxanthine. dna but not rna synthesis in l. major or l. donovani promastigotes was inhibited by aphidicolin (50% inhibition by 0.2-0.3 mic ...	1987	2437451
studies on intracellular killing of leishmania major and lysis of host macrophages by immune lymphoid cells in vitro.	exposure of leishmania major-infected cba/t6 mouse macrophages to lymph node cells (lnc) from infected animals led to antigen-specific killing of the micro-organisms. the effect depended on the number of added lnc, the duration of incubation with macrophages, and the presence of lps in the incubation fluids. incubation with immune lnc also resulted in lysis of part of the infected cells, however without release of live amastigotes, as parasites were destroyed intracellularly before macrophages w ...	1987	2448731
electron microscopy of amplified dna forms in antifolate-resistant leishmania.	three independently derived antifolate-resistant leishmania major cell lines overproduce the bifunctional protein thymidylate synthase-dihydrofolate reductase (ts-dhfr) by amplification of a region of dna (r-region dna) that contains the gene for ts-dhfr. on orthogonal-field-alteration gel electrophoresis (ofage), the extrachromosomal r-region dnas are circular molecules, and different forms of r-region dna within these cell lines are resolved. the r-region dnas migrate aberrantly on ofage with ...	1987	2822697
peripheral nerve involvement in cutaneous leishmaniasis (old world).	a review of 288 skin biopsy specimens from cutaneous leishmaniasis lesions caused by leishmania major showed assorted nerve changes in 14 biopsy specimens (5%). ten patients had perineural inflammatory cell infiltrate consisting of either lymphocytes or a mixture of lymphocytes, plasma cells, and macrophages. four patients had inflammatory cell invasion of the nerves (neuritis), and in one of them the inflammation was granulomatous and associated with nerve destruction. amastigotes were seen ins ...	1987	2824388
biochemistry and regulation of folate and methotrexate transport in leishmania major.	promastigotes of the protozoan parasite leishmania major exhibit high affinity uptake of folate (kt = 0.7 microm) and methotrexate (mtx) (kt = 1.8 microm) which is saturable and sensitive to metabolic poisons. influx of folate and mtx is competitively inhibited by 5-formyltetrahydrofolate and p-aminobenzoic acid-glutamate, but not by 4-deoxy-4-amino-10-methylpteroate, biopterin, or pteroate. a single carrier is inferred for both folate and mtx transport, as the ki of each inhibitor for both fola ...	1987	2886498
trypsin and chymotrypsin-like enzymes of the sandfly phlebotomus papatasi infected with leishmania and their possible role in vector competence.	phlebotomus papatasi (scopoli) is susceptible to infection with leishmania major yakimov & schokov and resistant to l. donovani laveran & mesnil. the possibility that susceptibility depends on midgut levels of trypsin and chymotrypsin-like (esterolytic) enzymes was investigated. infection with l. major reduced the trypsin-like activity to 93.5% and 86% of the control value at 20 and 30 h post feeding and increased it to 106% at 52 h. infection with l. donovani reduced trypsin-like activity to 64 ...	1987	2979536
leishmania promastigotes are recognized by the macrophage receptor for advanced glycosylation endproducts.	in this paper we demonstrate the involvement of the macrophage receptor for advanced glycosylation endproducts (age) in the phagocytosis of leishmania major promastigotes. blocking of this receptor with the ligand, age-bsa, leads to a 50% decrease in phagocytosis relative to controls, and a comparable decrease in the respiratory burst. the inhibition of phagocytosis by age-bsa was specific to leishmania. the binding of zymosan or c3bi-rbc and the phagocytosis of igg-rbc or latex beads was not af ...	1987	3025330
molecular characterization of the cell cycle-regulated thymidylate synthase gene of saccharomyces cerevisiae.	the complete nucleotide sequence of a 1.8-kilobase dna fragment containing the cell cycle-regulated thymidylate synthase gene (tmp 1) of the yeast saccharomyces cerevisiae is presented. this analysis has revealed a 912-base pair open reading frame which encodes a 304-amino acid residue protein with a calculated mr of 35,007. the tmp1-6 and cdc21-1 mutant alleles of this gene also have been sequenced, and both show single base pair changes which would result in different amino acid substitutions. ...	1987	3031048
loss of granule myeloperoxidase during in vitro culture of human monocytes correlates with decay in antiprotozoa activity.	human monocytes maintained in culture lose microbicidal activity against intracellular protozoa which has been correlated with attenuation of the respiratory burst. the granule enzyme myeloperoxidase, which can markedly amplify hydrogen peroxide-dependent antimicrobial activity, is also lost in vitro. adherent monocytes were examined immediately, 3 and 10-14 days following explantation, for the magnitude of the stimulated respiratory burst and for cellular myeloperoxidase. fresh cells generated ...	1987	3034086
the third component of complement (c3) is responsible for the intracellular survival of leishmania major.	leishmania are obligate intracellular parasites of mononuclear phagocytes. we and others have shown that the promastigote form of all species of leishmania activates complement from non-immune serum and that this activation can result in parasite lysis. this work, as well as earlier in vivo studies, suggested that complement is an important component of host defence against leishmaniasis. we now present evidence that parasite complement fixation, in addition to increasing parasite phagocytosis, ...	1987	3035377
distinctive cellular immunity in genetically susceptible balb/c mice recovered from leishmania major infection or after subcutaneous immunization with killed parasites.	genetically susceptible balb/c mice are refractory to further infection after recovery from leishmania major infection after a sublethal dose of gamma-irradiation. in contrast, mice immunized with killed promastigotes s.c. develop exacerbated lesions after infection. both groups of mice produce only a low level of specific antibody and no detectable cytotoxic t cells, but do have a strong antigen-specific dth, which is adoptively transferable with lyt-1+2-, l3t4+ t cells. kinetic and histologica ...	1987	3295049
mycobacterium bovis bcg-induced protection against cutaneous and systemic leishmania major infections of mice.	we examined the protective effects of mycobacterium bovis bacillus calmette-guérin (bcg) administration on leishmania major infections of balb/c and p/j mice. there were two treatment protocols. in the first, the footpads of naive animals were inoculated with mixtures of l. major and bcg (viable or heat killed) or the soluble mycobacterial antigen, purified protein derivative. viable bcg, but not heat-killed bcg or purified protein derivative, inoculated with l. major amastigotes into the footpa ...	1987	3298065
cytoplasmic polyhedrosis viruses in phlebotomus papatasi inhibit development of leishmania major.	cytoplasmic polyhedrosis viruses (cpv's) were observed in wild-caught and laboratory-reared phlebotomus papatasi. chronic cpv pathology of the midgut, characterized by structural aberrations in the epithelium and the peritrophic membrane, interfered with blood digestion and rendered the sand flies refractory to leishmania major infections. rates of natural and artificial l. major infections were inversely correlated to the incidence of cpv infections. the interaction between viruses and protozoa ...	1987	3298600
leishmania infecting man and wild animals in saudi arabia. 3. leishmaniasis in psammomys obesus cretzschmar in al-ahsa oasis.	zoonotic cutaneous leishmaniasis (zcl) is hyperenzootic in psammomys obesus in al-ahsa oasis in saudi arabia: 93% of 202 specimens of this rodent examined had signs of the infection. leishmania major and l. arabica were isolated from both normal ear skin as well as from ears with slight to severe lesions. l. major was the predominant species and gave rise to characteristic lesions that consisted of swelling, rounding of the edges, hyperpigmentation, ulceration, necrosis and, in advanced cases, s ...	1987	3306886
the generation of infective stage leishmania major promastigotes is associated with the cell-surface expression and release of a developmentally regulated glycolipid.	a monoclonal antibody, 3f12, was generated which reacted specifically against infective or metacyclic stage leishmania major promastigotes, but not with noninfective promastigotes obtained from log phase cultures. the antibody recognized a cell surface and released molecule that could be metabolically labeled with [14c]glucose, [3h]mannose, [3h]galactose, and [3h]palmitic acid, but not with [35s]methionine or [3h]leucine. the molecule was the major species surface-labeled by [3h]sodium borohydri ...	1987	3312412
prophylactic immunization against experimental leishmaniasis. vi. comparison of protective and disease-promoting t cells.	in previous studies, we reported that mice immunized i.v. with lethally irradiated leishmania major promastigotes developed substantial resistance to a subsequent l. major infection. however, such protection could be totally suppressed by prior s.c. injection with the same antigens. both the protective immunity and the inhibition of its induction could be adoptively transferred with specific lyt-2- t cells. here, we present evidence showing that protection and disease promotion resulting from i. ...	1987	3312413
resistance and susceptibility of mice to leishmania major: a view from melbourne.		1987	3326623
anti-infectious responses in leishmania major-infected balb/c mice injected with recombinant granulocyte-macrophage colony-stimulating factor.		1987	3326625
the histopathology of naturally-occurring cutaneous leishmaniasis in the reservoir host, psammomys obesus.	ears from infected psammomys obesus, the gerbil reservoir host of leishmania major, were histopathologically studied. the histopathology was a chronic localized infection consisting of an epithelioid granuloma with greatly increased populations of mast cells, melanocytes and melanophores; ulceration was present and parasites were always very few and inside parasitophorus vacuoles.	1987	3326687
cell-mediated responses and protection elicited by a carbohydrate-lipid-containing fraction extracted from leishmania major promastigotes.	carbohydrate-lipid-containing fractions (clf) extracted from leishmania major promastigotes and recognized by sera from immune but not from normal human donors were evaluated for their capacity to elicit cell-mediated responses. it was found that one of these fractions, clf-1, stimulated the in vitro response of lymphocytes from immune but not from normal human donors. a similarly extracted fraction from l. donovani parasites also elicited an in vitro response by cells from donors immune to l. m ...	1988	3338094
leishmania major: glycolipid antigens recognized by immune human sera.	extraction of whole promastigotes with a mixture of hexane-isopropanol yielded two carbohydrate-lipid fractions immunologically active against immune sera from patients with cutaneous leishmaniasis (cl): clf-1 and clf-2. thin layer chromatography (tlc) separated both fractions into eight bands labeled a-h. four of these bands, rf 0.19, 0.25, 0.39 and 0.48 (a, b, c and e, respectively) were recognized by antibody from patients with cl in a solid phase radioimmunoassay. antigens were also detected ...	1988	3344001
purification and characterization of a metabolite-regulated pyruvate kinase from leishmania major promastigotes.	the pyruvate kinase (atp:pyruvate 2-o-phosphotransferase, ec 2.7.1.40) of leishmania major promastigotes is a multimer of 59 kda subunits having an mr 181000. it is activated by its substrate phosphoenolpyruvate (pep) in a positively cooperative manner, and heterotropically by fructose 1,6-bisphosphate (fbp). kinetics with regard to the phosphate acceptor adenosine 5'-diphosphate (adp), mgcl2, and kcl are hyperbolic and unaffected by fbp. the enzyme is strongly inhibited by the reaction product ...	1988	3344004
characterization of the 'unusual' mobility of large circular dnas in pulsed field-gradient electrophoresis.	large circular amplified dnas (30 and 85 kb) present in methotrexate-resistant leishmania major appear to migrate anomalously in pulsed field-gradient electrophoresis (pfge), exhibiting pulse time-dependent mobility and migrating along a different apparent path relative to the large linear chromosomal dnas. quantitative studies indicate that the relative pulse-time dependence is actually conferred by the mobility properties of the large linear dnas. one contributing factor to the difference in m ...	1988	3344223
salivary gland lysates from the sand fly lutzomyia longipalpis enhance leishmania infectivity.	leishmaniasis is a parasitic disease transmitted by phlebotomine sand flies. the role of sand fly saliva in transmission of the disease was investigated by injecting mice with leishmania major parasites in the presence of homogenized salivary glands from lutzomyia longipalpis. this procedure resulted in cutaneous lesions of leishmania major that were routinely five to ten times as large and contained as much as 5000 times as many parasites as controls. with inocula consisting of low numbers of l ...	1988	3344436
molecular cloning of the major surface antigen of leishmania.	the gene encoding gp63, the major surface glycoprotein of leishmania promastigotes, was isolated from leishmania major using a synthetic oligonucleotide probe based on the nh2-terminal protein sequence of purified gp63. dna sequence analysis and the translated amino acid sequence indicate that gp63 is synthesized as precursor molecule having both an nh2-terminal preregion (signal peptide) and an adjacent proregion. this structure is consistent with the protease activity of gp63 since many other ...	1988	3346625
differences in lsh gene control over systemic leishmania major and leishmania donovani or leishmania mexicana mexicana infections are caused by differential targeting to infiltrating and resident liver macrophage populations.	earlier studies had shown that the viscerotropic nih 173 strain of cutaneous leishmania major fails to come under lsh gene control. visceral leishmania donovani lv9 and another viscerotropic cutaneous strain, leishmania mexicana mexicana lv4, are controlled by lsh. the results of double-infection experiments presented here show that expression of lsh resistance against l. mexicana mexicana was enhanced in the presence of l. donovani, whereas l. major still failed to come under lsh gene control, ...	1988	3356462
invasion of murine dendritic cells by leishmania major and l. mexicana mexicana.		1988	3357100
immunochemical characterization of a glyco-inositol-phospholipid membrane antigen of leishmania major.	a low m.w. polymorphic glyco-inositol-phospholipid (gipl) of leishmania major was studied by using three different mab. this molecule is shown to be distinct from the previously described lipophosphoglycan of l. major in its m.w., antigenic properties, expression during parasite growth, and kinetics of synthesis and catabolism. gipl is shown to be released from the parasite surface in a water-soluble form, probably by an endogenous phospholipase. gipl is also detectable on the surface of infecte ...	1988	3397542
inoculation of balb/c mice against leishmania major infection with leishmania-derived antigens isolated by gel filtration.	gel filtration can be used as a substitute for preparative polyacrylamide gel electrophoresis in the preparation of an immunogenic, partly purified, fraction isolated from lysates of leishmania promastigotes. this fraction, the molecular weight of which ranged from 70,000 to 53,000, when administered to balb/c mice in associated with muramyl dipeptide induced resistance against cutaneous leishmaniasis.	1988	3403672
a simplified microtechnique for measuring human lymphocyte proliferation after stimulation with mitogen and specific antigen.	cutaneous leishmaniasis is a parasitic disease characterized by a marked cell-mediated response. in vitro measurements of this response in humans have so far been used to a limited extent probably because of the relatively large amounts of blood demanded for conventional cell proliferation studies. the microtechnique here described enables lymphocyte proliferation to be performed with small amounts of blood (100 microliter) which can be obtained by finger prick, and do not require ficoll separat ...	1988	3418126
histopathological studies of leishmania major infection in mice.		1988	3418139
development of leishmania major in the phlebotomine sandflies, phlebotomus papatasi (scopoli) and phlebotomus langeroni (nitzulescu).	laboratory bred phlebolomus papatasi and p. langeroni were examined for their susceptibility to develop leishmania major promastigotes under laboratory conditions. promastigotes were demonstrated in the gut of both species when they were given sugar 24 hr before or after an infective blood meal and in flies offered only an infective blood. the overall infection rate was slightly higher in p. langeroni than p. papatasi. head promastigotes were detected in p. papatasi provided with sugar 24 hr bef ...	1988	3421642
a molecular shape analysis and quantitative structure-activity relationship investigation of some triazine-antifolate inhibitors of leishmania dihydrofolate reductase.	molecular shape analysis (msa) is used to develop quantitative structure-activity relationships (qsars) for a set of 45 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-substituted-phenyl)-s-triazine inhibitors of leishmania major dihydrofolate reductase (dhfr). the msa-qsars are equally significant to a qsar developed by r. g. booth et al. [1987) j. med. chem. 30, 1218) using linear free energy descriptors. however, the msa-qsars have the same general form as all other qsars developed for dhfr inhibit ...	1988	3178219
hormonal modulation of sex differences in resistance to leishmania major systemic infections.	differences in susceptibility to intravenously inoculated leishmania major were observed in male and female mice of the balb/canpt, dba/2n, and dba/2j strains and (balb/canpt x dba/2n)f1 hybrids. in all cases, males had significantly higher liver parasite burdens than females. orchidectomy of balb/c males resulted in a 20% decrease in the number of parasites in the liver compared with either normal or sham-gonadectomized controls. additionally, testosterone treatment of female balb/c mice result ...	1988	3182082
selective inhibition of leishmania dihydrofolate reductase and leishmania growth by 5-benzyl-2,4-diaminopyrimidines.	the classical anti-microbial antifolates trimethoprim, pyrimethamine, and cycloguanil are poor inhibitors of purified dihydrofolate reductase (dhfr) from leishmania major. they show no selectivity for leishmania dhfr relative to the human enzyme, and it is not surprising that they are ineffectual as anti-leishmanial agents. several 5-(substituted-benzyl)-2,4-diaminopyrimidines have been screened as inhibitors for purified l. major and human dhfrs. these compounds inhibit leishmania dhfr with i50 ...	1988	3185614
structure and expression of the hsp 70 gene family of leishmania major.	the parasitic protozoan leishmania major differentiates in vitro, from the insect-adapted promastigote to the mammalian infective amastigote, in response to a temperature shift from 25 degrees c to 37 degrees c. we studied the genes encoding 70 kilodalton heat shock proteins (hsp 70 genes) in leishmania substocks, which vary in their capability to differentiate. in total, four hsp 70 genes are arranged in tandem with intergenic regions of about 380 bp. these hsp 70 genes are 89% conserved at the ...	1988	3186441
the ultrastructure of leishmania major in the foregut and proboscis of phlebotomus papatasi.		1988	3194371
lymphokine-induced macrophage resistance to infection with leishmania major.	resistance to infection is an effector activity of macrophages that is induced by the cooperation of several molecularly distinct factors in lk: ifn and another nonifn macrophage activation factor. unlike many other effector activities of activated macrophages, signal sequence is not critical for induction of resistance to infection. nor is the activation of macrophages for resistance to infection dependent upon the presence of t lymphocytes in the culture vessel: t cell-depleted peritoneal cell ...	1988	3202039
peanut lectin agglutination and isolation of infective forms of leishmania major.		1988	3232177
the isolation of leishmania major zymodeme lon1 from man in niger.		1988	3232179
[clinico-epidemiologic forms of cutaneous leishmaniasis in tunisia].	from an analysis of 1,546 cases of cutaneous leishmaniasis collected throughout tunisia three clinico-epidemiological forms could be determined. these forms are due to three different species of leishmania and are observed in different geographical areas. sporadic cutaneous leishmaniasis (scl), 63 cases. this form is found in northern tunisia, in known foci of kala-azar. 96% of the patients have a single, small, ulcerated and crusty lesion on the face surrounded by an important zone of infiltrat ...	1988	3242407
amplified dnas in laboratory stocks of leishmania tarentolae: extrachromosomal circles structurally and functionally similar to the inverted-h-region amplification of methotrexate-resistant leishmania major.	we describe the structure of amplified dna that was discovered in two laboratory stocks of the protozoan parasite leishmania tarentolae. restriction mapping and molecular cloning revealed that a region of 42 kilobases was amplified 8- to 30-fold in these lines. southern blot analyses of digested dnas or chromosomes separated by pulsed-field electrophoresis showed that the amplified dna corresponded to the h region, a locus defined originally by its amplification in methotrexate-resistant leishma ...	1988	3244352
the discovery and preliminary characterization of a novel trypanosomatid parasite from rattus norvegicus and stray dogs from alexandria, egypt.	a survey of rodents and dogs was carried out in alexandria and its environs to see if an animal reservoir was associated with an outbreak of infantile kala-azar in this area. three rodent species, rattus rattus, rattus norvegicus and mus musculus, were commonly trapped and examined. a flagellate parasite was isolated from the spleens of two r. norvegicus. it was typed serologically by excreted factor serotyping and enzymologically by thick starch electrophoresis of four of its enzymes: gpi, g6pd ...	1988	3257073
susceptibility to murine cutaneous leishmaniasis correlates with the capacity to generate interleukin 3 in response to leishmania antigen in vitro.	spleen cells from genetically susceptible balb/c mice infected with leishmania major produced higher levels of il-3 in response to leishmania antigens or concanavalin-a in vitro compared to that of genetically resistant cba mice throughout the course of infection. the capacity to generate il-3 in balb/c mice increased with disease progression. the correlation between susceptibility to l. major infection and the capacity of spleen cells to produce il-3 also extends to other mouse strains. thus ge ...	1988	3257416
lysis of murine macrophages infected with intracellular pathogens by interleukin 2-activated killer (lak) cells in vitro.	to determine if murine lymphocytes activated by interleukin 2 (il-2) were cytotoxic against syngeneic elicited peritoneal macrophages (m phi) infected with intracellular pathogens, splenocytes that had been cultured with il-2 for 5 or 10 days were studied in vitro. these cells, [lymphokine-activated killer (lak) cells] showed significantly greater cytotoxicity against m phi infected with leishmania major or legionella pneumophila than against uninfected m phi. preferential cytotoxicity against i ...	1988	3259166
resistance to cutaneous leishmaniasis in nude mice injected with l3t4+ t cells but not with ly-2+ t cells.	the importance of t cells in resistance to infection with the intracellular protozoan parasite leishmania major is substantiated by the susceptibility to infection of athymic nude mice of both resistant and susceptible strains. however, the relative roles of different t cell subpopulations remain controversial. in order to address this issue, selected l3t4+ ly-2- or l3t4- ly-2+ t cell subpopulations from normal mice were adoptively transferred into athymic nude recipients of the same strain, and ...	1988	3259538
polyclonal b-cell stimulation by l3t4+ t cells in experimental leishmaniasis.	the well-established polyclonal b-cell stimulation in the lymphoid organs in mice infected with leishmania major is thought to be dependent on t cells. here we present clear experimental evidence that this is indeed the case by showing that balb/c-derived, l3t4-positive l. major-specific t cells induce syngeneic b cells to polyclonal proliferation and immunoglobulin production.	1988	3260894
analysis of variables associated with promotion of resistance and its abrogation in t cell-reconstituted nude mice infected with leishmania major.	upon intradermal challenge with the protozoan parasite leishmania major, some mouse strains develop chronic cutaneous lesions, whereas other mouse strains show a resolving pattern of disease. the importance of t cell-dependent immunity in resistance to cutaneous leishmaniasis is substantiated by the susceptibility to infection of athymic nude mice of both resistant and susceptible strains. small numbers of t lymphocytes from uninfected euthymic mice promote resistance in nude mice but t cells fr ...	1988	3264023
induction of activated macrophages in c3h/hej mice by avirulent salmonella.	a single injection of viable salmonella typhimurium sl3235, an avirulent organism blocked in the aromatic pathway, induced the generation of activated peritoneal macrophages in three different c3h mouse strains, including macrophage-defective c3h/hej mice. macrophages obtained from immunized mice were cytotoxic for b16 melanoma cells, p815 mastocytoma cells, and tu-5 fibrosarcoma cells and microbicidal in vitro for the obligate, intracellular, protozoan parasite leishmania major. the capacity of ...	1988	3279120
complement binding by two developmental stages of leishmania major promastigotes varying in expression of a surface lipophosphoglycan.	the binding of complement by two developmentally distinct stages of leishmania major has been studied. noninfective log phase growth (log) promastigotes (serum sensitive) activate complement with deposition of covalently bound c3b onto the surface of the parasite. infective, peanut agglutinin (pna-) metacyclic stage promastigotes (serum resistant) also bear mainly c3b after incubation in serum, but a major portion of deposited c3 is present as a 110 x 10(3) mol wt c3 fragment. whereas deposition ...	1988	3280727
cutaneous leishmaniasis in jordan: biochemical identification of human and psammomys obesus isolates as leishmania major.	as part of a series of epidemiological and ecological studies of leishmaniasis in jordan, we have made functional studies of four isolates from human lesions and from ear lesions of three field-collected psammomys obesus. primary isolates were subcultured, frozen stabilates prepared and balb/c mouse infectivity experiments initiated. each mouse was inoculated with 4-8 x 10(4) promastigotes into a hind footpad. quantitative evaluation of the footpads showed enlargement three to four weeks postino ...	1988	3041929
gm-csf produced by recombinant vaccinia virus or in gm-csf transgenic mice has no effect in vivo on murine cutaneous leishmaniasis.	the hemopoietic growth and differentiation regulators, granulocyte-macrophage colony-stimulating factor (gm-csf) and the multipotential stimulating factor (multi-csf) have been shown to have major effects on the effector function of mature macrophages. in this study we have examined the effect of recombinant gm-csf and multi-csf expressed transiently from recombinant vaccinia virus, or constitutively in gm-csf transgenic mice on the development of cutaneous leishmaniasis, caused by leishmania ma ...	1988	3047351
macrophage activation in vitro by lymphocytes from leishmania major infected healer and non-healer mice.	peritoneal macrophages from cba/t6 (healer) and balb/c (non-healer) mice were infected with leishmania major (lv39) in vitro. the microorganism replicated at the same rate in macrophages from either strain. exposure of infected cells to lymph node cells (lnc) from infected syngeneic animals led to intracellular killing of the parasite by macrophages from both strains, provided lps was present in the incubation medium. in vitro-propagated l.major-specific t-cell blasts activated macrophages from ...	1988	3050799
secondary structure of the promastigote surface protease of leishmania.	by raman spectroscopic analysis we have determined the secondary structure of the promastigote surface protease, named psp or gp63, of leishmania major. it consist of nearly 50% antiparallel beta-strand, and less than 20% alpha-helix. these results are contrasted with the predominantly alpha-helical vsgs of the african trypanosomes and the alpha-helical metalloprotease thermolysin. the psp of leishmania thus represents a novel kind of membrane-anchored protease.	1988	3058516
dissemination in cutaneous leishmaniasis. ii. satellite papules and subcutaneous induration.	in a field study of cutaneous leishmaniasis (cl) due to leishmania major, zymodeme lon-4, in an endemic focus in saudi arabia, 80 patients in a group of 643 patients (12.44%) were found to have multiple, inflammatory, satellite papules (sp) around one or more cl lesions. the sp often appeared to erupt after commencement of antileishmanial treatment. they showed a range of morphology and pathology, and comparisons with corresponding cl lesions showed important differences. amastigotes were seen i ...	1988	3069759
immunoregulation of cutaneous leishmaniasis. t cell lines that transfer protective immunity or exacerbation belong to different t helper subsets and respond to distinct parasite antigens.	balb/c mice can be protected against a normally fatal leishmania major infection by immunization with a partially purified, soluble subfraction of the parasite (fraction 9). in this study, we demonstrate that a t cell line established against fraction 9, designated line 9, transfers protection equivalent to that obtained by active immunization. in contrast, t cell lines (lines 1 and 9.2) responsive to a nonprotective soluble fraction (fraction 1) not only failed to protect balb/c mice against l. ...	1988	2903212
cutaneous host defense in leishmaniasis: interaction of isolated dermal macrophages and epidermal langerhans cells with the insect-stage promastigote.	leishmania species are obligate intracellular pathogens of mononuclear phagocytes. successful infection depends on sequestration of the promastigote (insect form) within host cells, allowing transformation into the relatively hardy amastigote stage. promastigotes are killed readily by circulating phagocytes and nonimmune serum, suggesting that cutaneous infection is initiated within a permissive cell in the epidermis or dermis. from large sections of primate skin dermal macrophages and epidermal ...	1988	2828237
an experimental model system for leishmaniasis. an ultrastructural study on cultured macrophages exposed to leishmania parasites and sodium stibogluconate.	to facilitate studies on the effect of chemotherapeutic agents on the host-parasite interaction in leishmaniasis, we have developed an experimental model for infecting mouse peritoneal macrophages in culture with recently-isolated leishmania donovani promastigotes. as the drug action is often dependent on concentration, the distribution of sodium stibogluconate, which is the commonly used drug for treatment of leishmaniasis, was studied in various parts of the macrophages by energy dispersive x- ...	1988	2841954