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rk39: a cloned antigen of leishmania chagasi that predicts active visceral leishmaniasis.the diagnosis of visceral leishmaniasis (vl), a serious and often fatal parasitic disease caused by members of the leishmania donovani complex, remains problematic. current methods rely on clinical criteria, parasite identification in aspirate material, and serology. the latter methods use crude antigen preparations lacking in specificity. a previously described cloned antigen, rk39, of leishmania specific for all members of the l. donovani complex (l. chagasi, l. donovani, l. infantum) was very ...19968627048
leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice.leishmania major promastigotes were found to avoid activation of mouse bone marrow-derived macrophages (bmm0) in vitro for production of cytokines that are typically induced during infection with other intracellular pathogens. coexposure of bmm0 to the parasite and other microbial stimuli resulted in complete inhibition of interleukin (il) 12 (p40) mrna induction and il-12 release. in contrast, mrna and protein levels for il-1(alpha), il-1(beta), tumor necrosis factor (tnf) alpha, and inducible ...19968627163
il-2-stimulated splenocytes reduce infections by leishmania donovani in vivo.the traditional treatment of infections produced by the obligate intramacrophage protozoan leishmania donovani involves the use of antimonial drugs. because these drugs may have toxic side effects (and are sometimes ineffective), the potential efficacy of alternative therapy with lymphokine-stimulated leucocytes was assessed. macrophage-depleted c57bl/6 splenocytes from mice inoculated 2 wk earlier with l. donovani were stimulated in vitro with the interleukin-2-containing supernatant of mla 144 ...19968627506
dna polymerases from a parasitic protozoa leishmania donovani ur6: evidence of presence of a novel kind of dna polymerase.dna polymerases of leishmania donovani have been isolated and purified. the cell extract has been chromatographed on a phosphocellulose column that separated into three peaks. the activity peak 1 was further purified to homogeneity. the dna polymerase is a 64 kda polypeptide, resistant to n-ethylmaleimide and aphidicolin. it requires mncl2 and a high concentration of kcl (0.5 m) for maximal activity. it has both 3' to 5' and 5' to 3' exonuclease activities that reside in the same polypeptide.19968630018
structural organization, sequence, and expression of the chicken nramp1 gene encoding the natural resistance-associated macrophage protein 1.one of the most common causes of food poisoning in humans is salmonellosis, which is frequently caused by ingestion with salmonella-contaminated poultry products. several lines of evidence suggest that genetic factors control resistance and susceptibility of chickens to infection with salmonellae. in the mouse, innate resistance to infection with intracellular pathogens such as salmonella typhimurium, several species of mycobacteria, and leishmania donovani is controlled by the mouse chromosome ...19968634139
reactivity of various leishmanial antigens in a direct agglutination test and their value in differentiating post-kala azar dermal leishmaniasis from leprosy and other skin conditions.a direct agglutination test (dat) for the detection of post-kala azar dermal leishmaniasis (pkdl) was evaluated in conditions that simulate the disease clinically or immunologically. a reference strain of leishmania donovani (lem 1399), and antigen preparations from leishmania isolates from bangladeshi patients with post-kala azar dermal leishmaniasis or visceral leishmaniasis were used. a titre of at least 51,200 was obtained in tests of patients with pkdl with all three antigens, whereas a max ...19968642576
c-reactive protein binds to a novel ligand on leishmania donovani and increases uptake into human macrophages.c-reactive protein (crp) is a major acute phase protein of man, with serum concentrations increasing dramatically following stimulation of hepatocytes by inflammatory cytokines. however, the role of crp in inflammation and resistance to infection is still poorly understood. here, the specificity of crp binding to the surface of leishmania donovani, an obligate intracellular parasite of mononuclear phagocytes, is described. crp is shown to bind to promastigotes at the infectious metacyclic stage ...19968648114
leishmaniasis in aids patients: results of leukocytoconcentration, a fast biological method of diagnosis.leukocytoconcentration is an easy, fast and inexpensive technique for the diagnosis of leishmaniasis from peripheral blood. the technique involves concentration of blood parasites on a small surface of a microscope slide while the red blood cells are removed by lysis. the results, compared with those of other methods (examination of cultures of blood samples and bone marrow smears), were very good and accurate. all but one of our cases of leishmaniasis were patients with hiv co-infection. leukoc ...19968653821
a simple method for maintaining, detecting and recovering virulent leishmania donovani in hamsters.the ability of hamsters (mesocricetus auratus) to retain amastigotes of leishmania donovani at cutaneous sites was examined. following intradermal inoculation of l. donovani stationary phase culture promastigotes in fore and hind footpads, nasal area and belly skin, cultures of aspirates taken fortnightly from these sites showed that amastigotes can survive in the skin for up to 10 months without visceralizing. hairless cutaneous sites were better at retaining l. donovani amastigotes than the ha ...19968659325
kinetics and stoichiometry of a proton/myo-inositol cotransporter.voltage clamp recording was used to measure steady-state and presteady-state currents mediated by a myo-inositol transporter cloned from leishmania donovani and expressed in xenopus oocytes. application of myo-inositol resulted in inward currents, which did not require external sodium and which were increased by increasing the extracellular proton concentration and by membrane hyperpolarization. alkalinization of the extracellular space occurred concomitantly with myo-inositol influx. correlatio ...19968663013
the developmental expression of leishmania donovani a2 amastigote-specific genes is post-transcriptionally mediated and involves elements located in the 3'-untranslated region.leishmania donovani is a protozoan parasite that exists as a free-living promastigote in the sandfly insect vector and as an amastigote inside the mammalian host macrophage phagolysosome compartment. the l. donovani a2 genes have been described previously as developmentally expressed in amastigotes but can be induced experimentally in promastigotes by a combination of ph and temperature shifts, conditions that mimic the phagolysosomal compartment of the macrophage cell. considering the importanc ...19968663340
(s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(s)-hpmpa]: a purine analogue with trypanocidal activity in vitro and in vivo.the unique features of purine salvage systems of pathogenic haemoflagellates render them selectively susceptible to the cytotoxic effects of purine analogues. a series of acyclic nucleoside phosphonates were evaluated for activity against pathogenic haemoflagellates in vitro. one of the phosphonylmethoxyalkylpurines, namely (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(s)-hpmpa], was active in vitro against bloodstream forms of trypanosoma brucei rhodesiense, t. b. gambiense, multidrug-re ...19968665394
visceral leishmaniasis and renal tuberculosis in a patient on maintenance haemodialysis. 19968671866
disposition of antimony after the administration of n-methylglucamine antimoniate to dogs.a study was carried out in dogs to define the pharmacokinetic profile of antimony and to define a better therapeutic protocol for the treatment of canine leishmaniasis. six healthy beagle dogs received 100 mg/kg of n-methylglucamine antimoniate containing 27.2 per cent of antimony intravenously, intramuscularly and subcutaneously. after intravenous administration the plasma concentration of antimony decreased rapidly and after 240 minutes it was lower than the ed50 values suggested for leishmani ...19968677619
comparative study of infectivity caused by promastigotes of leishmania infantum mon-1, l. infantum mon-24 and l. donovani mon-18.the mechanisms which permit leishmania to survive inside macrophages are not totally understood although it is known that prolonged culture in vitro results in loss of virulence. one of the cell surface molecules often implicated in virulence mechanisms is the glycoprotein of 63 kda (gp63). in this work we studied changes in infectivity of l. infantum promastigotes maintained in vitro by subcultures, correlated with the proteolytic activity of gp63. it was observed that l. infantum mon-1 promast ...19968682411
protozoan infections in the male genital tract.we reviewed the literature on protozoan infections in the male genital tract, with special reference to histopathological findings and their repercussions on different andrological functions.19968683676
two conformationally vicinal thiols at the active site of leishmania donovani adenosine kinase.inactivation of adenosine kinase (adk) from leishmania donovani correlates with the modification of two conformationally vicinal cysteine residues. in contrast, adk from hamster liver, despite being sensitive to monothiol-blocking reagents, was insensitive to dithiol modifiers. inactivation kinetics and substrate-protection studies along with double-modification experiments successively with n-ethylmaleimide in the presence of ado and sodium m-arsenite-2,3-dimercaptopropanol or diazenedicarboxyl ...19968687385
a 7-month-old girl with fever and bleeding. 19968602061
models of relapse of experimental visceral leishmaniasis.to establish models for studying recurrence of visceral leishmaniasis, a growing problem in t cell-deficient patients, two approaches were investigated: treatment of euthymic balb/c mice with quiescent leishmania donovani infection with t cell-depleting or anti-cytokine antibodies and serial observation of acutely infected nude balb/c mice after an initial antileishmanial response induced by amphotericin b treatment. in chronically infected euthymic mice, maintenance of acquired immunity and pre ...19968603949
microbicidal mechanisms of liver macrophages in experimental visceral leishmaniasis.to study the differential microbicidal potentials of liver macrophages, the oxygen-dependent and oxygen-independent pathways in kupffer cells and immigrant macrophages of leishmania donovani-infected balb/c mice were investigated. hydrogen peroxide assay was performed using horse radish peroxidase-dependent oxidation of phenol red to quantitate the reactive oxygen species produced. to examine the oxygen-independent pathway, the enzymes n-acetyl-beta-glucosaminidase (nag) and beta-glucuronidase ( ...19968611190
pentamidine uptake in leishmania donovani and leishmania amazonensis promastigotes and axenic amastigotes.a transport system for pentamidine in leishmania donovani and leishmania amazonensis promastigotes and axenic amastigotes has been identified and characterized. pentamidine is not metabolized by these parasites. its uptake process is saturable, carrier-mediated and energy-dependent. this drug does not inhibit purine or pyrimidine uptake, whereas it inhibits uptake of several amino acids non-competitively and that of putrescine and spermidine competitively. the results suggest that pentamidine sh ...19968615840
the genomic organization of the hsp83 gene locus is conserved in three leishmania species. 19968617351
serological diagnosis of visceral leishmaniasis by a dot-enzyme immunoassay for the detection of a leishmania donovani-related circulating antigen.field medicine in tropical areas needs laboratory assays which are inexpensive and easy to perform. to meet this need a semi-quantitative dot-enzyme immunoassay (eia) was developed for the detection of an l. donovani-related circulating antigen and tested for clinical relevance in the diagnosis of visceral leishmaniasis (vl). the dot-eia probes serum spotted on nitrocellulose for the presence of the antigen using a monoclonal antibody raised against l. donovani promastigotes, a peroxidase-conjug ...19968690934
kinetics of entry of virulent and avirulent strains of leishmania donovani into macrophages: a possible role of virulence molecules (gp63 and lpg).specific receptors may be involved in the process of attachment of leishmania donovani promastigotes to macrophage surfaces and their subsequent internalization. two virulent strains of indian l. donovani (ag83 and ge-i) were found to enter into macrophages much faster than the avirulent ones (ur6). these virulent promastigotes express surface glycoprotein (gp63) and lipophosphoglycan (lpg) to a greater extent than avirulent strains. we examined their interaction with macrophages as a function o ...19968691373
biosynthesis of lipophosphoglycan from leishmania major: solubilization and characterization of a (beta 1-3)-galactosyltransferase.lipophosphoglycan (lpg), is the major cell surface molecule of promastigotes of all leishmania species. it is comprised of three domains: a conserved glycosylphosphatidylinositol anchor linked to a repeating phosphorylated disaccharide (p2; po4-6gal beta 1-4man alpha 1-) backbone and capped with a neutral oligosaccharide. in leishmania major the backbone is substituted at the c(o)3 of the galp residue with side chains containing galp, glcp and arap residues whereas in leishmania donovani the bac ...19968694771
deficiency in beta1,3-galactosyltransferase of a leishmania major lipophosphoglycan mutant adversely influences the leishmania-sand fly interaction.to study the function of side chain oligosaccharides of the cell-surface lipophosphoglycan (lpg), mutagenized leishmania major defective in side chain biosynthesis were negatively selected by agglutination with the monoclonal antibody wic79.3, which recognizes the galactose-containing side chains of l. major lpg. one such mutant, called spock, lacked the ability to bind significantly to midguts of the natural l. major vector, phlebotomus papatasi, and to maintain infection in the sand fly after ...19968702802
visceral leishmaniasis emerging as an important opportunistic infection in hiv-infected persons living in areas nonendemic for leishmania donovani.visceral leishmaniasis is an important infection in patients infected with human immunodeficiency virus and living in areas endemic for leishmania sp. leishmaniasis, however, is rarely suspected in patients residing in nonendemic countries.19968712898
the fml (fucose mannose ligand) of leishmania donovani. a new tool in diagnosis, prognosis, transfusional control and vaccination against human kala-azar.the fucose-mannose ligand (fml) of leishmania donovani is a complex glycoproteic fraction. its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from natal, rio grande do norte, brazil. the fml-elisa test, showed 100% sensitivity and 96% specificity, identifying patients with overt kala-azar (p < 0.001, when compared to normal sera), and subjects with subclinical infection. more than 20% apparently healthy subjects with positive reaction to fml deve ...19968713607
oxygen-dependent leishmanicidal activity of stimulated macrophages.peritoneal macrophages pretreated with different stimulants were analysed and compared with their respective controls for their ability to kill intracellular pathogenic l. donovani, (mhom/in/1983/ag83) an isolate from indian subcontinent. stimulation of macrophages by zymosan showed a higher microbicidal activity as compared to that by pma. a correlation between microbicidal activity of the macrophages and the parameters related to respiratory burst activity such as liberation of o2-, production ...19968717413
killing of leishmania donovani amastigotes by poly iclc in hamsters.in vitro as well as in vivo studies suggest that cytokine-induced synthesis of nitric oxide (no) from l-arginine is a major effector mechanism against intracellular pathogens. in this study, we demonstrate that golden hamsters infected with leishmania donovani amastigotes upon treatment with polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly iclc), a potent interferon inducer and immune enhancer, in combination with l-arginine, develop the capacity to eli ...19969162526
modulation of host cell intracellular ca2+.during the course of evolution, protozoan parasites have developed strategies to subvert the immune response of their host in order to multiply, reproduce and survive. one of these inherited strategies is their capacity to modulate the host cell transductional mechanisms in their favor. alteration of host cells ca(2-) homeostasis following interaction and/or invasion by protozoan parasites such as leishmania donovani, trypanosoma cruzi, plasmodium falciparum or entamoeba histolytica has been rep ...199615275223
the role of ca2+ in the process of cell invasion by intracellular parasites.in order to replicate, many parasites must invade host cells. changes in the intracellular ca(2+) concentration ([ca(2+)](i)) of different parasites and tissue culture cells during their interaction have been studied. an increase in cytosolic ca(2+) in trypanosoma cruzi trypomastigotes occurs after association of the parasites with host cells. ca(2+) mobilization in the host cells also takes place upon contact with t. cruzi trypomastigotes, leishmania donovani amastigotes or plasmodium falciparu ...199615275256
[validation of therapeutic test in the diagnosis and treatment of kala-azar in children].the author studied the value of therapeutic test for the diagnosis and treatment of kala-azar in children by comparing two groups of patients. the identification of leishmania donovani in smears of bone marrow confirmed the diagnosis in all fifty seven patients of the control group. in another group with sixteen children, the diagnosis was based on the successful response to the treatment with meglumine antimonate. in none of the patients of the second group the protozoa was identified and the d ...199514688993
outbreak of kala-azar in bombay.a chance diagnosis of kala-azar in a patient referred from acworth leprosy home in bombay was followed up, resulting in an investigation of a total of 25 patients (inpatients and residents) for the presence of the disease. 30.3% of the patients investigated were found to be suffering from the disease. this confirms the earlier suspicion that bombay and especially the acworth leprosy home is an endemic area for kala-azar.199510740690
cross-reactive studies in visceral leishmaniasis: comparison of antigens of some leishmania species in kenya.little is known about the common antigens of the various strains of leishmania in kenya, and their possible role in immunity to disease. kenyan isolates of leishmania donovani, l. major and l. tropica were cultured, crude antigens prepared and electrophoresced in sodium dodecyl sulphate-polyacrylamide gel electrophoresis (sds-page). immunoblots by pooled sera from cutaneous and visceral leishmaniasis patients revealed common antigens within the 110-116kd, 70kd and the 63kd ranges. only the 112-1 ...199512160441
screening of metal ion chelators against leishmania donovani-infected syrian hamsters.leishmania donovani-infected syrian hamsters were treated intraperitoneally with 0.23 mmoles/kg/day of edta, egta, heedta and 100 mg/kg/day of pentostam r. the control group received 0.1 ml of phosphate buffered saline. after 30 days of treatment, the animals were sacrificed. of the pentostam-treated animals, 5 out 6 had negative spleen cultures, while all the chelator and pbs-treated ones yielded parasites. while all the pentostam-treated animals had negative bone marrow cultures, only 1 out of ...199512160448
comparison of giemsa and acridine orange stains for the diagnosis of leishmania donovani in biopsies of infected hamsters.identical impression smears of spleen, liver and bone marrow biopsy materials from leishmania donovani-infected hamsters were stained using either acridine orange or giemsa. spleen parasite-loads calculated from the two stains for identical biopsy material were significantly different from each other. however, liver and bone marrow parasite- loads calculated from either giemsa-stained or acridine orange-stained biopsies were not significantly different from each other. this study has shown that ...199512160449
determination of the optimal edta and pentostam concentration in the treatment of leishmania donovani-infected laboratory animal rodent models. 199512160454
screening of metal ion chelators against leishmania donovani-infected balb/c mice. 199512160455
inhibition of mononuclear cell procoagulant activity by lipophosphoglycan of leishmania donovani.background: since fibrin formation is an expression of the response of the host to parasite spread, the lipophosphoglycan (lpg) of leishmania donovani and its carbohydrate fragment (pg) were examined for their capacity to inhibit procoagulant activity (pca) production by human mononuclear cells stimulated with escherichia coli endotoxin in vitro. methods: the putative inhibitory effect of lpg and its pg fragment was evaluated on the basis of their in vitro capacity to prolong significantly the t ...199511866718
cloning and expression of the adenine phosphoribosyltransferase gene from leishmania donovani. 19958719249
characterization of the respiratory chain of leishmania donovani promastigotes.inhibition analysis of respiration of leishmania donovani promastigotes in resting, starved and permeabilized cells in the presence of classical electron transfer complex inhibitors such as rotenone, thenoyltrifluoroacetone and antimycin demonstrated the absence of complex i component of the respiratory chain in this organism. cyanide failed to completely block the oxygen uptake (residual 25-30%) even at high concentrations. the alternative oxidase inhibitor for trypanosoma brucei, salicylhydrox ...19958720174
evaluation of antibody responses in indian kala-azar by immunoblot.when infected with leishmania species, patients develop specific antibodies that constitute the basis of serodiagnosis. using western blot analysis we studied the specificity of anti-leishmania donovani antibodies in patients with visceral leishmaniasis, healthy subjects living in an endemic and non-endemic areas, and patients of other infectious diseases like malaria, leprosy, tuberculosis and tropical splenomegaly. sera from patients with kala-azar recognised numerous antigens that had a molec ...19958624503
standardization of leishmania dovovani parasite inoculum dose and route of challenge for use in infectivity studies: is it necessary? 19958689982
visceral leishmaniasis: use of the polymerase chain reaction in an epidemiological study in baringo district, kenya.the polymerase chain reaction was applied to capillary blood spots dried on filter paper from 20 parasitologically proved cases of visceral leishmaniasis (vl), 21 subclinical cases, and 11 healthy controls in a longitudinal study of anthroponotic vl in baringo district, kenya. leishmania deoxyribonucleic acid (dna) was detected 10.5 months before diagnosis and up to 3 years after diagnosis and apparently successful treatment. subclinical cases can have detectable circulating parasite dna in thei ...19958560520
l-alanine: 4,5-dioxovalerate transaminase in leishmania donovani that differs from mammalian enzyme.leishmania protozoans are the causative agents of leishmaniasis, a major parasitic disease in humans. the parasites manifest a nutritional requirement for heme compounds since they are deficient in heme biosynthesis. in this study we have demonstrated for the first time the presence of the enzyme l-alanine: 4,5-dioxovalerate transaminase in leishmania donovani. this enzyme catalyzes the synthesis of 5-aminolevulinic acid (ala), the first committed step in heme synthesis. thus the defect in heme ...19958564368
[imported visceral leishmaniasis (kala azar) in a german infant].we here report the case of a 1 4/12 year old girl with visceral leishmaniasis. returning from a trip to mallorca she presented with pancytopenia, splenomegaly and fever and was admitted to hospital with suspected malignancy. diagnosis was established microscopically from bone marrow smear and confirmed by pcr-assisted amplification of leishmania-specific dna from peripheral blood. treatment was conducted with stibogluconate for 25 days. defervescence and improvement of clinical symptoms was seen ...19958569138
cloning and expression of the hypoxanthine-guanine phosphoribosyltransferase from leishmania donovani.the gene encoding the hypoxanthine-guanine phosphoribosyltransferase (hgprt) enzyme from leishmania donovani has been cloned and sequenced. the hgprt open reading frame encoded a polypeptide of 211 amino acids that exhibited 3 regions of significant homology with other eukaryotic hgprts and a c-terminal tripeptide compatible with a glycosomal targeting signal. northern blot analysis of l. donovani rna revealed two hgprt transcripts, a 1.9-kb mrna and a 1.7-kb transcript. the expression of the 1. ...19958577321
in vivo and in vitro cytokine profiles and mononuclear cell subsets in sicilian patients with active visceral leishmaniasis.sera from sicilian patients with confirmed visceral leishmaniasis (leishmania donovani infantum) were analysed at the moment of the diagnosis, during the course of the disease and after clinical recovery, for the concentration of il-10, ifn-gamma, il-4 and il-2. the results show high concentrations of il-10 and ifn-gamma in the sera at the beginning of infection that return to the normal range following successful chemotherapy. by contrast, pbmc stimulated in vitro with ag and mitogen produced l ...19958580385
visceral and cutaneous leishmaniasis comparative ultrastructure of host-parasite interactions.the comparative ultrastructure of host-parasite interactions is described for the first time in patients with visceral (vl) and cutaneous (cl) leishmaniasis. in patients with vl, the parasite invades the bone marrow (bm) macrophages (mcs) and neutrophils, while in patients with cl, the parasite invades the dermal fibroblasts in addition to mcs. the skin mcs seem to have more lethal effects on the parasite than the bm mcs; this is possibly due to the presence of numerous melanosomes with acid pho ...19958586879
visceral leishmaniasis in somalia. circulating antibodies as measured by dat, immunofluorescence and elisa.sera from patients with visceral leishmaniasis (vl) (n = 26), healthy residents of mogadishu (n = 157), inhabitants of a village in an endemic area (n = 276) and healthy swedes (n = 60) were examined using the direct agglutination test (dat), immunofluorescence (if) and elisa for antibodies against leishmania donovani. the study was carried out in order to provide baseline data for antibody responses in visceral leishmaniasis as existing in somalia and to explore which one of these methods would ...19958592766
partial purification and characterization of a soluble protein phosphatase from leishmania donovani promastigotes.a soluble protein phosphatase from the promastigote form of the parasitic protozoan leishmania donovani was partially purified using sephadex g-100, deae-cellulose and again sephadex g-100 columns. the partially purified enzyme showed a native molecular weight of about 42,000 in both sephadex g-100 and sucrose density gradient centrifugation. the sedimentation constant, stokes radius and frictional ratio were found to be 3.43s, 2.8 nm and 1.20 respectively. the enzyme preferentially utilized pho ...19958594423
detection of leishmania in the blood of early kala-azar patients with the aid of the polymerase chain reaction.samples from 39 patients with symptoms suggestive of early visceral leishmaniasis were independently assayed by microscopy of tissue smears, enzyme-linked immunosorbent assay (elisa) and polymerase chain reaction (pcr) of blood deoxyribonucleic acid. of these patients, 19 were confirmed as positive or negative by all 3 tests; 11 patients (28%) negative by smear were positive by elisa and pcr; and 7 (18%) were positive by pcr alone. these results demonstrate the high sensitivity of the non-invasi ...19958594675
sudanese mucosal leishmaniasis: epidemiology, clinical features, diagnosis, immune responses and treatment.the epidemiology, clinical features, pathology, immune responses, diagnosis and treatment of 14 patients with mucosal leishmaniasis in the sudan are described. the condition occurred mainly in adult males, particularly in certain closely related tribes from the western sudan. it affected the mucosa of the upper respiratory tract and/or the oral mucosa and sometimes followed treated kala azar. the parasites were sometimes confined to the mucosa, sometimes spread to the lymph nodes, and rarely inf ...19958594683
acute phase protein concentrations predict parasite clearance rate during therapy for visceral leishmaniasis.visceral leishmaniasis (vl) remains a major health problem in kenya and other parts of africa, central america and asia. currently, splenic aspirate smear and culture are the standard methods of monitoring therapy and relapse. acute phase reactant markers, c-reactive protein (crp), serum amyloid a protein (saa) and alpha 1-acid glycoprotein (agp) were evaluated as less invasive techniques for monitoring therapy in 59 patients with vl before, during and after therapy. crp, saa and agp were elevat ...19958594695
lack of serological specificity of recombinant heat shock protein of leishmania donovani.in order to identify a specific recombinant antigen of leishmania donovani with potential use for diagnosis, a cdna library was constructed in lambda zap ii expression vector. on screening the cdna library using pooled sera from indian patients with kala azar, 20 antibody reactive clones were identified. these were subcloned into pbluescript phagemid by an in vivo excision procedure. the molecular weights of the expressed recombinant proteins varied from 15 to 70 kda and the cdna insert sizes va ...19958595923
[parasitic diseases of the liver].the liver seems to be very attractive for many parasites which may either inhabit the organ or pass through during their normal development or may be carried to the liver leading to destruction there. malaria parasites have a short developmental stage in the hepatocytes, but they do not damage the organ. for the leishmanias (leishmania donovani complex) are the kupffer cells are the target cells causing visceral leishmaniasis or kala azar. nematodes of the ascarid group have a special affinity f ...19958600687
clinicopathological study of clinically undiagnosed cases of kala-azar with special reference to grading of parasites.clinicopathological study of 34 clinically undiagnosed cases of kala-azar has been undertaken with a view to establish the diagnosis and correlate the quantitative grading of leishmania donovani in bone marrow/splenic aspirates with clinical features and duration of disease. the ages of the patients were between 5 and 45 years. the duration of illnesses ranged from 2-24 months with 47% having 2 months' duration. splenomegaly was less than 7 cm in 70.5% cases. anaemia, leucopenia and mild thrombo ...19958522820
increased expression of ld1 genes transcribed by rna polymerase i in leishmania donovani as a result of duplication into the rrna gene locus.eukaryotic protein-coding genes are generally transcribed by rna polymerase ii (pol ii), which has a lower transcription rate than that of pol i. we report here the duplication of two ld1 genes into the rrna locus and their resultant transcription by pol i. the multigenic ld1 locus is present in a 2.2-mb chromosome in all stocks of leishmania spp. and is also present in multicopy 200- to 450-kb linear chromosomes or multicopy circular dnas in over 15% of stocks examined. genomic rearrangement in ...19958524251
concomitant natural infection with l. donovani and l. major: a case report from iraq.this is a case report of kala-azar with cutaneous leishmaniasis. upon admission, the patient had fever, hepatosplenomegaly and an ulcer on her cheek. the patient responded to pentostam. isoenzyme studies of parasite isolates from the bone marrow and from the cutaneous lesion revealed that these were l. donovani and l. major, respectively. this is the first report in iraq of a proven concomitant infection with two species of leishmania parasites.19958525713
recent kala-azar cases in india: isozyme profiles of leishmania parasites.in this study, three who recommended reference strains of leishmania donovani (dd8), l. tropica (k27) and l. major (5 askh) were compared by isozyme analysis of 9 soluble enzymes using cellulose acetate electrophoresis (cae). the isozyme profile of the three species showed distinct electrophoretic mobilities of the enzymes studied. this technique was applied to study the enzyme patterns of 8 clinical isolates of visceral leishmaniasis (vl) and two post kala-azar dermal leishmaniasis (pkdl) colle ...19958543361
diagnostic and prognostic value of k39 recombinant antigen in indian leishmaniasis.the recombinant product (rk39) of the 39 amino acid repeats encoded by a kinesin-like gene of visceral leishmania spp. was further evaluated by enzyme-linked immunosorbent assay (elisa) for its diagnostic potential in indian kala-azar (vl) and post kala-azar dermal leishmaniasis (pkdl). anti-rk39 antibodies were highly positive in 20 symptomatic cases, including 6 resistant to single or double chemotherapy, but became negligible or absent in 9 recently cured patients. endpoint titration of sampl ...19958544037
is phlebotomus (larroussius) orientalis a vector of visceral leishmaniasis in south-west ethiopia? 19958546034
inhibition of hiv-1-induced syncytia formation and infectivity by lipophosphoglycan from leishmania.in hiv-1 infection, the appearance of syncytia-inducing (si) isolates is associated with a more rapid decline of cd4+ cells and progression to aids. agents that inhibit either virus infection or syncytia formation have the potential to be therapeutically useful. lipophosphoglycan (lpg), the major glycoconjugate of leishmania, was recently shown to be a potent nonspecific inhibitor of viral membrane fusion. in this study, lpg demonstrated a dose-dependent inhibition of hiv-1-induced syncytia form ...19958548328
immunotherapy with il-2-stimulated splenocytes reduces in vitro the level of leishmania donovani infection in peritoneal macrophages.a study was done in vitro to determine if il-2-stimulated lymphocytes (lak cells) would activate infected macrophages to reduce their burden of leishmania donovani. macrophage-depleted splenocytes from normal or infected c57bl/6 (h-2b; lshs) mice, stimulated in vitro by the il-2-containing supernatant of the mla 144 cell line or by ril-2, significantly reduced the number of syngeneic resting peritoneal macrophages infected by l. donovani; lak cells from infected animals were significantly more e ...19958550297
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
interleukin-4 and interferon-gamma production by leishmania stimulated peripheral blood mononuclear cells from nonexposed individuals.interferon-gamma (ifn-gamma) and interleukin-4 (il-4) production by leishmania reactive peripheral blood mononuclear cells (pbmc) from non-exposed individuals was investigated. ifn-gamma was measured in culture supernatants after antigen stimulation. for the measurement of il-4, antigen stimulated cells were pulsed with pma and ionomycin before il-4 release was measured. l. donovani and l. major antigens induced il-4 production (105-1748 pg/ml) in 13 and seven cultures, and ifn-gamma production ...19957899822
alteration of pulmonary macrophage function by respiratory syncytial virus infection in vitro.alveolar macrophages (al) are the first line of defense against inhaled pathogens and are exposed to virus during the course of a respiratory syncytial virus (rsv) infection. interference of virus with alveolar macrophage functions may contribute to the risk of acquiring secondary bacterial infections during or after respiratory tract infections with rsv or other viral agents. we studied whether murine al get infected with rsv and whether they support viral replication in vitro. in addition, the ...19957995946
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
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