Publications

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characterization of the exometabolite of leishmania donovani as a novel glycopeptidophosphosphingolipid. 19817332589
proliferative glomerulonephritis in experimental leishmania donovani infection of the golden hamster. 19817333089
[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
leishmania donovani and leishmania braziliensis: hexokinase, glucose 6-phosphate dehydrogenase, and pentose phosphate shunt activity. 19807349998
effect of cortisone and cyclophosphamide on the immunological role of bcg in balb/c mice challenged with leishmania donovani. 19807352623
purine phosphoribosyltransferases from leishmania donovani. 19807356667
leishmaniasis: in search of new chemotherapeutic agents.members of a class of compounds designated lepidines (8-amino-6-methoxy-4-methylquinoline derivatives) were tested in a hamster-leishmania donovani model and found to have activity many-fold that of a reference drug meglumine antimoniate. one of them, 8-(7-isopropylaminoheptylamino)-6-methoxy-4-methylquinoline, was found to be 138 times as effective as the standard antimonial drug used.19807369615
inhibition of leishmania donovani amastigote-to-promastigote transformation by infected hamster spleen lymphocyte lysates.leishmania donovani amastigote-to-promastigote transformation is inhibited by homogenates of infected hamster liver and spleen. this inhibitory activity is localized in the 100,000 g pellet fraction. tests with lysates of adherent (macrophages) and nonadherent (lymphocytes) spleen cells indicated that the inhibitory activity resided in the lymphocytes, specifically in the 100,000 g pellet fraction.19807373572
incorporation of [1-14c]octadecanol into the lipids of leishmania donovani.after incubation of stationary phase leishmania donovani with [1-14c]octadecanol, about 70% of the precursor was taken up within 3 hr. wax esters and acyl moieties of glycerolipids contained most of the 14c-activity from 3 to 6 hr, because octadecanol was partly oxidized to stearate. ether moieties were only weakly labeled. after 40 hr, 1-0-alkyl and 1-0-alk-1'-enyl diacylglycerols as well as 1-0-alkyl and 1-0-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamines contained nearly all of the radio ...19807374369
a study of three isolates of leishmania donovani from patients with kala-azar in iraq. 19807377871
cultivation of leishmania donovani in vitro in a high yielding liquid culture medium. 19807380493
leishmania spp. in iraq. electrophoretic isoenzyme patterns. i. visceral leishmaniasis.leishmania donovani organisms isolated from 10 children coming from different districts in iraq, were compared between themselves, with leishmania donovani isolated in iran and the sudan, and with a leishmania sp. isolated from the viscera of a rat caught in baghdad. the comparison was 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; phosphoglucomutas ...19807385296
a comparison of skin-test responses using antigen from leishmania donovani and a lizard trypanosome.261 individuals were skin tested with leishmanin from leishmania donovani and with an antigen from a lizard trypanosome isolated in an area endemic for kala-azar in ethiopia. 83 of the 261 responded positively, with indurations of 5 mm or greater, to one antigen but negatively to the other, and 42 reacted positively to both. among the afar people of the awash valley in north-eastern ethiopia and the nyangatom people of south-western ethiopia, positive response to both antigens was high, though m ...19807385300
in vivo assay of viability of amastigotes of leishmania donovani.following intravenous (i.v.) injection of formalin-killed or ultraviolet-killed or ultraviolet-irradiated amastigotes of leishmania donovani, the parasites could be identified in mouse liver at 5 min, but most amastigotes were digested by 3 hr or between 24 and 72 hr, respectively. an in vivo assay of viability, based on these observations, suggests differences in the viability of hamster amastigote populations. the identification of dead and/or dying amastigotes in the liver 24 hr after i.v. in ...19807391863
[frequency and significance of parasitic infections in refugees from vietnam (author's transl)].in the course of the medical care which is provided for the refugees from southeast asia 100 persons were tested for intestinal parasites (helminths and protozoa). in addition serum samples were obtained from 72 of these and tested in several tests (cft, fat, iha and sft) using antigens of entamoeba histolytica, leishmania donovani, toxoplasma gondii, schistosoma spp., fasciola hepatica, echinococcus spp., trichinella spiralis and litomosoides carinii. in 49 persons infections with one, two or ...19807395245
cytophilic and opsonic antibodies in visceral leishmaniasis in mice.although acquired immunity to leishmaniasis is generally considered to be cell mediated, humoral factors may be partially responsible. the present study showed that antisera from c57bl/6j mice superinfected with leishmania donovani contained cytophilic antibody and opsonins for both the amastigote and promastigote stages of the parasite. macrophages treated with mouse hyperimmune serum in an in vitro macrophage culture system bound statistically significantly more parasites at 4 degrees c (and s ...19807399677
isolation and partial characterization of surface membranes from leishmania donovani promastigotes.cell surface pellicular membranes (pm) were isolated from promastigote forms of leishmania donovani by differential and discontinuous sucrose gradient centrifugation procedures. the pm had a density equivalent of approximately 1.19 g/cm3. as ascertained by electron microscopy, longitudinal parallel arrays of subpellicular microtubules (mt) remained attached to the isolated pm inner lamina, and this feature was used to assess membrane fraction purity. gradient fractions having greater than or equ ...19807400994
analogues of 8-[[6-(diethylamino) hexyl]amino]-6-methoxy-4-methylquinoline as candidate antileishmanial agents.8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquinoline (i) has been shown to be highly effective against leishmania donovani in hamsters, being approximately 475 times as active as the standard meglumine antimoniate. several nuclear and side-chain analogues of i have been prepared in an attempt to further enhance the antileishmanial activity of this class of compounds. the compounds were tested against l. donovani in the golden hamster. although several analogues had meglumine antimoniate ...19807411553
leishmania donovani in the oppossum (didelphis marsupialis). 19807420255
antileishmanial effect of allopurinol and allopurinol ribonucleoside on intracellular forms of leishmania donovani. 19807426045
mechanism of lethal effect of human serum upon leishmania donovani.in order to gain greater understanding of potential host defense mechanisms against leishmania donovani, we examined the effect of nonimmune, human serum upon promastigotes and amastigotes. fresh sera were found to be lethal for promastigotes, but had no detectable effect on amastigotes. serum exposed promastigotes became immotile, did not take up neutral red dye, appeared to be disrupted, and failed to recover after further incubation in fresh media. heat labile components were required for pro ...19807430624
alkaline phosphatase levels in the serum of b10. lp-1 mice infected with leishmania donovani. 19807436608
synthesis of phospholipids in leishmania donovani. 19807450683
the micro-elisa sandwich technique for the quantitation of leishmania donovani soluble antigen. 19807458463
morphology of leishmania donovani colonies grown on blood agar plates. 19807463257
cyclic amp mediates change in superoxide dismutase activity to monitor host-parasite interaction in leishmania donovani.the present study is designed to understand the role of cyclic amp (camp) in host-parasite interaction involving leishmania donovani, the causative agent for kala-azar. when leishmania promastigotes or macrophages were pretreated with dibutyryl camp or theophylline and epinephrine, which are well defined initiators for camp release, a key enzyme of the oxygen defense system, superoxide dismutase (sod), was inhibited. at the same time, parasite interaction was considerably reduced to the level of ...19957472855
activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite leishmania donovani.in this study, we demonstrated that the protozoan parasite leishmania donovani and one of its major surface molecules, the lipophosphoglycan (lpg), can induce human immunodeficiency virus type 1 (hiv-1) expression in u1 and om-10.1, two cell lines of monocytoid origin latently infected with hiv-1. treatment of u1 cells with various concentrations of lpg (1, 5, and 10 microm) resulted in a dose-dependent secretion of tumor necrosis factor alpha (tnf-alpha). suppression of lpg-induced hiv-1 expres ...19957474154
a new breakthrough in treatment of visceral leishmaniasis in children.fifty cases of visceral leishmaniasis were admitted in children's hospital, islamabad. common clinical features were fever (100%), splenomegaly (100%), hepatomegaly (100%), anaemia (96%), abdominal distension (40%), bronchopneumonia (26%) and bleeding diathesis (22%). hb was below 7.0 g/dl in 80%, white cell count below 4 x 10(9)/cmm in 88% and platelet count below 100 x 10(9)/c4mm in 86%. all the patients showed leishmania donovani bodies in the marrow smears. fourteen patients were treated wit ...19957474290
kinetics and molecular characteristics of arginine transport by leishmania donovani promastigotes.characteristics of transport of l-arginine were studied in leishmania donovani promastigotes grown in vitro in a defined medium. the promastigotes exhibited a time-dependent, temperature-sensitive, ph-dependent and saturable uptake of arginine. metabolic inhibitors caused 81-92% inhibition, indicating that arginine influx in promastigotes is an energy requiring process. the presence of na+ ions was necessary for full activity. considerable inhibition was also noticed with valinomycin, gramicidin ...19957477101
the expression of biologically active human p53 in leishmania cells: a novel eukaryotic system to produce recombinant proteins.we have investigated the use of leishmania cells as a novel eukaryotic expression system for the production of recombinant protein. these cells are easy to maintain, requiring no co2 incubator or shaker, and can be grown in standard tissue culture media. leishmania cells can be readily transfected with plasmid dna by electroporation and transformants selected with antibiotic resistance. recent studies have shown that it is possible to express foreign genes in leishmania for the purpose of unders ...19957479067
3'-deoxy-3'-fluoroinosine as a potent antileishmanial agent. the metabolism and selective cytotoxic effect of 3'-deoxy-3'-fluoroinosine against leishmania tropica and l. donovani in vitro and in vivo.we studied the antileishmanial activity of 3'-deoxy-3'-fluoroinosine (3'-fi) against leishmania tropica and l. donovani. in in vitro cultivation, the ec50 values (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for 3'-fi against the promastigotes of l. tropica and l. donovani were 2.3 x 10(-7) and 1.0 x 10(-6) m, respectively. it was less toxic toward mouse mammary-tumor fm3a cells, a model host; the ec50 value was 1.9 x 10(-4) m. lei ...19957479655
immunobiological studies on experimental visceral leishmaniasis. iv. kinetics of evolution of disease-promoting versus host-protective cells of monocyte-macrophage lineage and their characterization.the evolution of cells of the monocyte-macrophage lineage (mml cells) in the spleen of leishmania donovani (ld) infected balb/c mice was studied. spleen cells were fractionated on a discontinuous percoll gradient and adherent cells (ac) were purified from fractionated spleen cells by adherence steps that appeared at the interfaces of 25-35%, 35-40%, 40-45% and 45-50% percoll gradients. the ac were characterized as mml cells on the basis of positive staining for non-specific esterase. adherent ce ...19957481559
splenomegaly in baringo district, kenya, an area endemic for visceral leishmaniasis and malaria.the relationship between splenomegaly and visceral leishmaniasis (vl) was investigated during a cross-sectional study in 2,941 individuals in baringo district, kenya, where both malaria and vl are endemic. spleen size was correlated with presence of malaria parasites in thick blood films and with evidence of present or past leishmania donovani infection as determined by serology and history. marked splenomegaly (hackett grade 3 or greater) significantly correlated with present or previous leishm ...19957483000
identification of differentially expressed leishmania donovani genes using arbitrarily primed polymerase chain reactions.arbitrarily primed polymerase chain reactions (ap-pcr) were used to amplify polymorphic dna fragments from the genomes of a variety of geographic isolates of leishmania donovani (ld). from the latter, five polymorphic dna fragments were cloned and sequence analysis identified 15 unique clones. northern blot analysis showed that 13 of the 15 clones hybridized to transcribed rnas isolated from ld. eight of these 13 ap-pcr clones specifically hybridized to ld rnas that were differentially expressed ...19957489912
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
the nadp-linked aldehyde reductase of leishmania donovani.an enzyme that oxidizes ethanol to acetaldehyde in the presence of nadp (but not nad) and reduces acetaldehyde to ethanol in the presence of nadph (but not nadh) is present in leishmania donovani promastigotes. the activity is present only in the supernatant fraction obtained from sonication of the cells and high speed centrifugation. the km and vm values were evaluated for propanol and propionaldehyde as well as for ethanol and acetaldehyde in cells obtained from late log and 3-day stationary p ...19957496384
the chemical synthesis of leishmania donovani phosphoglycan via polycondensation of a glycobiosyl hydrogenphosphonate monomer.a polycondensation of 2,3,6-tri-o-benzoyl-4-o-(2,3,4-tri-o-benzoyl-beta-d-galactopyranosyl)-al pha-d-mannopyranosyl hydrogenphosphonate in the presence of trimethylacetyl chloride has been used to synthesize a linear poly[beta-d-galactopyranosyl-(1-->4)-alpha-d-mannopyranosyl phosphate] representing the phosphoglycan part of the lipophosphoglycan from leishmania donovani.19957497476
problems in the treatment of kala-azar: case report.frequent relapses after treatment for visceral leishmaniasis and apparent parasitological cure is not commonly reported. seven year old boy who relapsed four times with clinical and parasitological evidence of the disease at each two months follow-up period is presented. he had leishimania donovani kenya strain. after treatment, review would be after two months, six months and twelve months periods. splenic aspirates were routinely done weekly and on the last day of each treatment. the drugs adm ...19957498017
cutaneous lesions in hamsters caused by leishmania donovani promastigotes derived from axenic amastigotes. 19957498035
temperature-induced rapid increase in cytoplasmic free ca2+ in pathogenic leishmania donovani promastigotes.we demonstrate that the cytoplasmic free ca2+ concentration in three virulent leishmania donovani promastigote strains is maintained at 20-30 nm level whereas the avirulent promastigotes maintain [ca2+]i at 80-100 nm. rapid exposure of virulent promastigotes to higher physiological temperature increases [ca2+]i many-fold. use of cacl2, egta and mn2+ confirmed that both release of ca2+ from internal pool(s) and influx from outside milieu are responsible for this increase in [ca2+]i. application o ...19957498487
post-kala-azar dermal leishmaniasis mimicking leprosy: experience with 4 patients, with some unusual features in 1.we report on 4 cases of post-kala-azar dermal leishmaniasis (pkdl). history of kala-azar was available in all 4 patients. slit-skin smears (sss) for leishmania donovani (ld) bodies were negative in all 4. in 3 patients hypopigmented lesions were present over the face. papules and nodules over his lips, tongue, scrotum and dactylitis were some unusual features observed in 1 patient. histopathological examination showed ld bodies in 2 patients; histopathology was nonspecific in the other 2. all th ...19957500822
ribosomes of leishmania are a target for the aminoglycosides.ribosomes of leishmania, a parasitic protozoan (member of the order of kinetoplastidae), were purified on a sucrose density gradient. two different types of ribosomes were isolated from the promastigotes: cytoplasmic (88s and 91s from l. tropica and l. donovani, respectively) and mitochondrial (75s in both species). both types of ribosome dissociated into their subunits at low mg2+ concentration (1-2 mm) as follows: 67s and 49s for the 91s cytoplasmic ribosomes of l. donovani and 61s and 43s for ...19957501642
expression of a channel-like pathway for adenosine transport in leishmania donovani promastigotes.l. donovani promastigotes (mhom/et/67/ha3) transport adenosine by a route that is sensitive to inhibition by a nonspecific channel blocker, propranolol. at the logarithmic and stationary phases of growth, the transport of 1 microm-3h-adenosine was significantly inhibited (40-50%) by 100 microm-propranolol. in contrast, a strain of leishmania donovani promastigotes clonally selected to grow in defined medium was only slightly (approximately 10%) inhibited at the logarithmic but not at the station ...19937507902
a peg-elisa for the detection of leishmania donovani antigen in circulating immune complexes.leishmanial antigen in circulating immune complexes (cic) from sera of cotton-rats experimentally infected with leishmania donovani and visceral leishmaniasis patients (vlp) was detected using a polyethylene glycol (peg) enzyme-linked immunosorbent assay (peg-elisa). the immune complexes were precipitated in the cold with 12% peg (average m(r) 6000) and then dissociated with glycine-hcl buffer. the dissociated antigen bound to the plate was then detected by peroxidase-labelled rabbit antibody ra ...19947512290
leishmania donovani flagellum-specific epitopes mediating host-parasite interactions.monoclonal antibodies were developed against flagellar components of promastigotes of leishmania donovani. the monoclonal antibody produced by clone a11 (mab a11) recognised epitopes in the polypeptides with molecular weights of 86, 66 and weakly 53 kda. these epitopes were found to be distributed along the flagellum and at the anterior end of promastigotes. the mab a11 of igg1 isotype strongly agglutinated the promastigotes of l. donovani. the prior treatment of promastigotes of l. donovani wit ...19947516230
deficient expression of co-stimulatory molecules on leishmania-infected macrophages.co-stimulatory signals are necessary for the full activation of t cells for growth and effector function. as co-stimulatory molecules are normally regulated in their expression, it has been suggested that microorganisms enhance their expression on host antigen-presenting cells (apc), thus allowing efficient generation of anti-microbial immunity. we here describe experiments which demonstrate that infection of macrophages, both in vitro and in vivo, by the protozoan parasite leishmania donovani f ...19947525308
distribution of lipophosphoglycan-associated epitopes in different leishmania species and in african trypanosomes.monoclonal antibody (mab) ca7ae binds specifically to the phosphorylated gal-beta 1,4-man disaccharide repeat epitope of leishmania donovani lipophosphoglycan (lpg). this mab detected the repeat epitope in most but not all of a wide variety of leishmania species and strains examined. mab ca7ae also bound to both glycoprotein and carbohydrate antigens in medium from l. donovani promastigote cultures. specifically, mab ca7ae bound the delipidated form of lpg, the phosphoglycan, and a glycoprotein ...19947528916
developmental gene expression in leishmania donovani: differential cloning and analysis of an amastigote-stage-specific gene.leishmania protozoans are the causative agents of leishmaniasis, a major parasitic disease in humans. during their life cycle, leishmania protozoans exist as flagellated promastigotes in the sand fly vector and as nonmotile amastigotes in the mammalian hosts. the promastigote-to-amastigote transformation occurs in the phagolysosomal compartment of the macrophage cell and is a critical step for the establishment of the infection. to study this cytodifferentiation process, we differentially screen ...19947545921
costimulation and the regulation of antimicrobial immunity.the regulated expression of costimulatory molecules is a major factor limiting t-cell responses to self-antigens. however, the development of effective antimicrobial immunity requires that these molecules be induced on a variety of tissues, but most notably on macrophages. here, paul kaye discusses the regulation of costimulatory molecules on macrophages and suggests that microbial interference in this process has important implications for immune regulation.19957546205
functional expression and subcellular localization of a high-km hexose transporter from leishmania donovani.we have used expression in xenopus oocytes to characterize a new hexose transporter from the parasitic protozoan leishmania donovani. this transporter utilizes the hexoses glucose, fructose, and mannose as substrates. a substrate saturation curve for 2-deoxy-d-glucose reveals a very high km, estimated to be approximately 150 mm. immunolocalization of the protein with an antibody directed against the cooh terminus indicates that the transporter is present primarily in the parasite plasma membrane ...19957547915
[effects of cytokine-activated macrophages on intracellular leishmania].the effects of activated macrophages on leishmania donovani amastigotes and nitrite (no2-) release were determined by in vitro inducement of macrophage activation with recombinant ifn-r, tnf-alpha, and ril-3. the results indicated that rifn-r or rtnf-alpha at 40,000u/l was able to induce a significant but modest level of macrophage activity, and synergistic effect of rifn-r and rtnf-alpha was apparent in the induction of macrophage activation. 48 hours after macrophages were induced with both ri ...19957553143
influence of the bcg locus on macrophage response to the dimorphic fungus candida albicans.the bcg/ity/lsh gene (candidate nramp) controls natural resistance to several parasites, such as mycobacterium bovis, leishmania donovani, and salmonella typhimurium. using two macrophage (m phi) cell lines (b10r and b10s) derived from mouse strains congenic at bcg, we found that m phi s from resistant mice (b10r m phi s) act more effectively against the two morphogenetic forms of the dimorphic fungus candida albicans compared with m phi s from susceptible mice (b10s m phi s). moreover, when ass ...19957558336
evaluation of cleaving agents other than trypsin in direct agglutination test for further improving diagnosis of visceral leishmaniasis.trypsin treatment of leishmania promastigote antigen has proved to be indispensible in the direct agglutination test (dat) for the diagnosis of visceral leishmaniasis (vl) and canine visceral leishmaniasis (cvl). in the present study four antigen batches were prepared with pronase (400 micrograms/ml), lipase (0.45% [wt/vol]), pancreatin (0.3% [wt/vol]), or 2-mercaptoethanol (2-me) (1.2% [vol/vol]) at a ratio of 20:1 versus promastigote packed cell volume or a density of 10(8)/ml. batches prepare ...19957559934
drug cytotoxicity assay for african trypanosomes and leishmania species.the trypanosomes and leishmania species are parasitic protozoa that afflict millions of people throughout the world. if not treated, african trypanosomiasis and visceral leishmaniasis are fatal. the available drugs are severely limited by toxicity, marginal efficacy, the requirement for parenteral administration, and spreading drug resistance. in this study, a spectrophotometric assay was developed and validated for measuring the cytotoxicity of test compounds against axenically cultured bloodst ...19957561203
lipid peroxidation of erythrocytes during anemia of the hamsters infected with leishmania donovani.visceral leishmaniasis has been found to be associated with severe anemia and premature lysis of erythrocytes. peroxidative damage of red cells has been noted in several hemolytic anemias. present study shows enhanced formation of methemoglobin in hamsters infected with leishmania donovani. increased formation of malonyldialdehyde and diene conjugate has been noted in the erythrocytes of the infected animals with the progress of anemia. results showed decreased activities of protective enzymes l ...19957565650
functional expression of a myo-inositol/h+ symporter from leishmania donovani.the vast majority of surface molecules in such kinetoplastid protozoa as members of the genus leishmania contain inositol and are either glycosyl inositol phospholipids or glycoproteins that are tethered to the external surface of the plasma membrane by glycosylphosphatidylinositol anchors. we have shown that the biosynthetic precursor for these abundant glycolipids, myo-inositol, is translocated across the parasite plasma membrane by a specific transporter that is structurally related to mammal ...19957565702
a specialized pathway affecting virulence glycoconjugates of leishmania.for virulence and transmission, the protozoan parasite leishmania must assemble a complex glycolipid on the cell surface, the lipophosphoglycan (lpg). functional complementation identified the gene lpg2, which encodes an integral golgi membrane protein implicated in intracellular compartmentalization of lpg biosynthesis. ipg2- mutants lack only characteristic disaccharide-phosphate repeats, normally present on both lpg and other surface or secreted molecules considered critical for infectivity. ...19957569927
visceral leishmaniasis in somalia: prevalence of markers of infection and disease manifestations in a village in an endemic area.prevalence and disease manifestations of visceral leishmaniasis (vl) were studied in a somali village in an area which has long been known to be endemic for vl. demographic data were collected from 102 households, comprising 438 inhabitants. clinical examination was performed of 306 individuals, 72% of the 426 eligible persons. of these, 276 (90%) agreed to give blood and 246 (80%) to be skin tested with leishmanin. leishmanin reactions were positive; in 26% anti-leishmania antibodies were detec ...19957570862
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
leishmania donovani: titration of antibodies to the fucose-mannose ligand as an aid in diagnosis and prognosis of visceral leishmaniasis.the fucose-mannose ligand (fml) is a complex glycoprotein fraction present on promastigotes and amastigotes of leishmania donovani. it participates in parasite interaction with host macrophages in a species-specific pattern. we have tested its use in immunodiagnosis of visceral leishmaniasis (vl) in a recent outbreak in rio grande do norte, north-east brazil. enzyme-linked immunosorbent assay (elisa) of low concentrations of fml in 462 sera showed 100% sensitivity and 96% specificity. the fml-el ...19957570874
human cutaneous leishmaniasis caused by leishmania donovani sensu stricto in yemen. 19957570877
liposomal amphotericin b (ambisome) in the treatment of complicated kala-azar under field conditions.an open trial of liposomal amphotericin b (ambisome [l-amb]; vestar, san dimas, ca) for treatment of complicated visceral leishmaniasis was performed in sudan. forty-nine patients were treated, and there were six deaths (12% mortality); these were not attributed to therapy. thirty-seven patients were selected for the trial because of (1) relapse after treatment with a combination of pentavalent antimony (sbv) and aminosidine, (2) incomplete parasitological response to sbv and aminosidine, or (3) ...19957578729
molecular cloning and characterization of a leishmania donovani alpha-tubulin gene.we have isolated a cdna for an alpha-tubulin mrna from l. donovani promastigotes and determined its complete nucleotide sequence. both nucleotide and deduced amino acid sequence analysis of this cdna showed significant similarity with a previously reported, partial sequence of an l. enriettii alpha-tubulin and the complete sequence of human alpha-tubulin. further, the in vitro translated l. donovani alpha-tubulin gene product was specifically immunoprecipitated with a monoclonal antibody against ...19957581339
leishmania donovani: cellular control of ornithine decarboxylase in promastigotes.ornithine decarboxylase, a key enzyme in polyamine biosynthesis, is essential for normal cell growth and proliferation. furthermore, the inhibition of this enzyme is a potential way of controlling such growth. in order to shed light on the role of ornithine decarboxylase in regulation of leishmania growth we examined the activity of this enzyme during the life cycle of these organisms. exponentially growing leishmania promastigotes were resuspended at a density of 3 x 10(6) cells/ml. 2 x 10(7) c ...19957584631
attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with leishmania donovani: selective inhibition of signaling through janus kinases and stat1.the induction of gene transcription in response to gamma interferon is impaired in mononuclear phagocytes infected with leishmania donovani, and the mechanisms involved are not fully understood. the changes in gene expression brought about by gamma interferon are thought to involve transient increases in the activities of cellular protein tyrosine kinases, including the janus kinases jak1 and jak2, leading to tyrosine phosphorylation of the transcription factor stat1. to investigate the mechanis ...19957591091
disruption of the murine interleukin-4 gene inhibits disease progression during leishmania mexicana infection but does not increase control of leishmania donovani infection.the growths of both cutaneous leishmaniasis and visceral leishmaniasis caused by leishmania mexicana and leishmania donovani, respectively, were measured in interleukin-4 (il-4) knockout mice (il-4-/-) and compared with those of similarly infected wild-type (il-4+/+) control mice. while large, nonhealing, cutaneous lesions containing large numbers of parasites developed in il-4+/+ mice subcutaneously infected with 5 x 10(6) l. mexicana amastigotes in the shaven rump, in il-4-/- mice no lesions w ...19957591152
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
cloning and expression of a leishmania donovani gene instructed by a peptide isolated from major histocompatibility complex class ii molecules of infected macrophages.the studies reported here describe the isolation of peptides from mhc class ii molecules of murine macrophages infected with leishmania donovani, and the use of the derived peptide sequences to rescue the pathogen peptide donor protein. the isolation of the peptides was carried out by comparing the rp hplc profile of peptides extracted from infected macrophages with the peptides extracted from noninfected cells. several distinct hplc peaks unique to infected macrophages were sequenced. one of th ...19957595213
biochemical changes in heat stressed promastigotes of leishmania donovani.on exposing promastigotes of l. donovani (dd-8) to 34 degrees c for 30 hr, the flagella were shed, and size was decreased with 10% viability loss. the in vitro and in vivo infectivity of two forms was more or less similar. the 45ca2+ uptake by the transformed cells was increased as compared to normal cells. activity of 5'-nucleotidase was increased while activity of mg(2+)-atpase remained same. parasite antioxidant enzymes were also significantly altered by heat shock. there was significant incr ...19957601493
tumour necrosis factor-alpha (cachectin) in human visceral leishmaniasis.generally speaking, the cell mediated immunity plays a pivotal role in the host resistance against the protozoal parasite of the genus leishmania. the polypeptide hormone cachectin (tumour necrosis factor-alpha) which is produced mainly by macrophages, is a primary mediator in the pathogenesis of infection, injury and inflammation. depending on its concentration, duration of cell exposure and presence of other mediators in the cellular environment, the net biological effect of this peptide regul ...19957602171
migration of leishmania donovani amastigotes in cerebrospinal fluid. 19957603249
trypanothione reductase from leishmania donovani. purification, characterisation and inhibition by trivalent antimonials.trypanothione reductase was purified to homogeneity from leishmania donovani promastigotes transfected with the expression plasmid ptex-ldtr. the physical, spectral and kinetic properties were found to be similar to those obtained from other pathogenic trypanosomatids. the substrates trypanothione disulfide and nadph exhibit michaelis-menten saturation kinetics with km values of 36 microm and 9 microm, respectively, the former yielding a kcat/km of 5.0 x 10(6) m-1 s-1. like other trypanothione r ...19957607216
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
a family of putative receptor-adenylate cyclases from leishmania donovani.leishmania parasites are exposed to pronounced changes in their environment during their life cycle as they migrate from the sandfly midgut to the insect proboscis and then into the phagolysosomes of the vertebrate macrophages. the developmental transformations that produce each life cycle stage of the parasite may be signaled in part by binding of environmental ligands to receptors which mediate transduction of extracellular signals. we have identified a family of five clustered genes in leishm ...19957615561
visceral leishmaniasis: a rare cause of unexplained pyrexia in a renal allograft recipient. 19957617099
don't forget visceral leishmaniasis in transplant patients. 19957624007
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
diagnosis of canine visceral leishmaniasis with a dot-enzyme-linked immunosorbent assay.the maintenance and transmission of human visceral leishmaniasis in an endemic area usually requires a mammalian reservoir. though universal reservoir elimination has previously been effective in controlling this disease in countries where the primary reservoir is the dog, selective elimination would be preferable. to guide this selection process, we performed a prospective, single, blind, cohort study evaluating the dot-enzyme-linked immunosorbent assay (dot-elisa) in 130 canines from both ende ...19957625531
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
effects of bis(benzyl)polyamine analogs on leishmania donovani promastigotes.a number of bis(benzyl)polyamine analogs were found to be potent inhibitors of leishmania donovani growth in vitro (ic50 = 4.3-25 microm). structural variations appear to have important effects on the biological functions of these analogs. subinhibitory concentration of all of the analogs with the exception of mdl 27994 could rescue the cells from dl-alpha-difluoromethylornithine toxicity. the analogs inhibited macromolecular synthesis as evaluated by [3h]thymidine, [14c]uracil, and [35s]methion ...19957628565
leishmania donovani in hamsters: stimulation of non-specific resistance by novel lipopeptides and their effect in antileishmanial therapy.several novel type of lipopeptides were synthesized and evaluated for their ability to stimulate non-specific resistance against leishmania donovani infection. peritoneal macrophages isolated from young male hamsters treated with muramyl dipeptide (mdp) and various synthetic lipopeptides (6 mg/kg i.p.) 7 days earlier, were cultured in vitro and challenged 24 h later with l. donovani promastigotes. one lipopeptide, central drug research institute (cdri) compound 86/450, exhibited significantly hi ...19957628580
kinetoplastid membrane protein-11 (kmp-11) is differentially expressed during the life cycle of african trypanosomes and is found in a wide variety of kinetoplastid parasites.an abundant 11-kda membrane protein was purified from african trypanosomes by organic solvent extraction and octyl-sepharose chromatography. this protein cross-reacts with monoclonal antibodies originally generated against the lipophosphoglycan-associated protein of leishmania donovani. immunoblot analysis showed that the 11-kda molecule was present in a variety of species of kinetoplastids. it was found in several species and subspecies of african trypanosomes and was present in low amounts in ...19957630374
isolation and characterization of the gene encoding the surface membrane 3'-nucleotidase/nuclease of leishmania donovani.leishmania donovani and related trypanosomatid protozoa possess an externally oriented surface membrane enzyme capable of hydrolyzing both 3'-nucleotides and nucleic acids. by virtue of these activities, this 3'-nucleotidase/nuclease (3'-nt/nu), previously shown to be analogous to fungal and plant class-i single-strand-specific nucleases, is thought to play a critical role in the salvage of purines, essential for the survival of these organisms. the 43-kda 3'-nt/nu was purified from l. donovani ...19957630383
molecular cloning, characterization, and expression in escherichia coli of iron superoxide dismutase cdna from leishmania donovani chagasi. 19957642321
high constitutive levels of heat-shock proteins in human-pathogenic parasites of the genus leishmania.we have analysed the transcription of three heat-shock genes, hsp70, hsp83 and clpb, in the protozoan parasite leishmania. all three heat-shock genes are transcribed constitutively and not heat-inducibly. however, we find that two major heat-shock proteins, hsp70 and hsp83, are synthesized at elevated rates during heat stress. we conclude that the cellular stress response in leishmaniae is regulated exclusively on a post-transcriptional level much in contrast with all other eukaryotes examined s ...19957646449
the ity/lsh/bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the nramp1 gene.in mice, natural resistance or susceptibility to infection with intracellular parasites is determined by a locus or group of loci on chromosome 1, designated bcg, lsh, and ity, which controls early microbial replication in reticuloendothelial organs. we have identified by positional cloning a candidate gene for bcg, nramp1, which codes for a novel macrophage-specific membrane transport protein. we have created a mouse mutant bearing a null allele at nramp1, and we have analyzed the effect of suc ...19957650477
leishmanial cholecystitis and colitis in a patient with visceral leishmaniasis. 19957660434
characterization of leishmania isolated from patients with kala-azar and post kala-azar dermal leishmaniasis in bangladesh. 19957660453
characterization of 'old world' leishmania species using amplified minicircle variable regions as molecular probes. 19957660454
immunoglobulin g subclass-specific antileishmanial antibody responses in indian kala-azar and post-kala-azar dermal leishmaniasis.antileishmanial antibody responses in the sera of indian kala-azar (ka) and post-ka dermal leishmaniasis (pkadl) patients were analyzed by enzyme-linked immunosorbent assay (elisa) and immunoblot experiments using immunoglobulin g (igg) class- and subclass-specific reagents. all sera showed antileishmanial reactivities in igg elisa which followed the order igg1 > igg2 > igg3, with very little igg4. immunoblot analysis with igg class-specific reagents revealed variable patterns of reactivity by k ...19957664174
[pancytopenia and septic temperatures 1 year after mediterranean travel in a 29-year-old patient]. 19957665330
leish-kit, a stable direct agglutination test based on freeze-dried antigen for serodiagnosis of visceral leishmaniasis.in order to increase the application potential of the direct agglutination test (dat) for the detection of anti-leishmania antibodies in human serum samples, we developed an antigen based on stained and freeze-dried leishmania donovani promastigotes. we describe here the evaluation of the performance of the dat based on this freeze-dried antigen. it was shown that the freeze-dried antigen remains fully active, even after storage at 56 degrees c for 18 months. with a cutoff value of 1:1,600, the ...19957665640
antibody responses of visceral leishmaniasis patients to gp63, a major surface glycoprotein of leishmania species.a major surface glycoprotein of leishmania parasites, gp63, is highly conserved among species and is expressed in both infective and intracellular stages. although much is known about its role in entry and survival in host macrophages, patient antibody responses to this glycoprotein have not been well characterized. the prevalence of anti-gp63 antibody in sera of leishmaniasis patients was evaluated by elisa. sera from most acute visceral leishmaniasis patients (84%) from brazil and sudan had no ...19937678428
il-10 inhibits the synthesis of migration inhibitory factor and migration inhibitory factor-mediated macrophage activation.il-10, in addition to being a cytokine synthesis-inhibitory factor, is a cytokine that exerts multiple effects on various cell types. recombinant human migration inhibitory factor (mif) inhibits the migration of human monocytes as well as that of guinea pig and murine macrophages. in addition, it has recently been shown to activate human monocyte-derived macrophages to suppress the growth of and/or kill both intracellular parasites and extracellular tumor targets in vitro and to have adjuvant ac ...19937691945
monoclonal antibodies directed against leishmania secreted acid phosphatase and lipophosphoglycan. partial characterization of private and public epitopes.leishmania promastigotes, the stage of the parasite characteristic for the sandfly vector, express an abundant glycoconjugate, called lipophosphoglycan, at their surface. lipophosphoglycan consists of lysoalkyl-sn-glycerophosphoinositol linked to a phosphosaccharide core conserved in all species, which is connected to po4-6gal beta 1,4man alpha 1 repeats with species-specific substitutions at the gal residue; the repeats are capped by conserved and species-specific oligosaccharides. most leishma ...19937693464
immunochemotherapy for a systemic intracellular infection: accelerated response using interferon-gamma in visceral leishmaniasis.to determine if cytokine immunotherapy accelerates the response to conventional treatment in visceral leishmaniasis (kala-azar), previously untreated indian patients were given antimony for 30 days (n = 15) or antimony plus interferon-gamma (ifn-gamma; n = 16). after 10 days, 10 (63%) of 16 patients treated with antimony plus ifn-gamma versus 1 (7%) of 15 randomized to antimony alone were considered cured of parasites (p < .005). on day 20, 14 (93%) of 15 versus 6 (40%) of 15 patients, respectiv ...19957706829
evaluation of recombinant gp63, the major leishmania surface glycoprotein, as a diagnostic molecule for leishmaniasis in vervet monkeys. 19947709873
indian kala-azar caused by leishmania tropica.kala-azar, or visceral leishmaniasis, in india is generally assumed to be a result of infection with leishmania donovani. 15 parasite isolates collected over the past 10 years from patients with classical disease were typed by monoclonal antibodies, isoenzymes, and kdna analysis. 4 were shown to be l tropica, a species historically associated with cutaneous disease and more recently a mild "visceralising" disease from the desert storm experience. the results confirm that l tropica is a co-endemi ...19957715298
potent inhibition of viral fusion by the lipophosphoglycan of leishmania donovani.lipophosphoglycan (lpg) is an amphiphile produced by leishmania. its chemical structure consists of a hydrophilic flexible polymer of repeating po4-6gal beta 1-4man alpha 1 units (on average 16 units) linked via a hexasaccharide core to a lyso-1-o-alkyl-p1 membrane anchor. in the study of viral fusion we report in this paper, we have introduced lpg into human erythrocyte ghost (heg) membranes, with the purpose of understanding how the lpg-induced surface-structural changes may modulate the inter ...19957718571
[studies on the effect of deltamethrin bath treatment of hamsters infected with leishmania donovani for interrupting kala-azar transmission].phlebotomus chinensis were fed respectively on two groups of cricetulus barabensis infected with leishmania donovani, of which one group had received deltamethrin bath and the other was not treated with insecticide bath. the results showed that all the sandflies in the former group died within 24 hours, while those in the latter group had a high survival rate. among the 165 sandflies examined, 114 (69.1%) became infected. the promastigotes not only developed well in the midgut, but also invaded ...19947720208
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