Publications

expression of 65- and 67-kilodalton heat-regulated proteins and a 70-kilodalton heat shock cognate protein of leishmania donovani in macrophages.	heat shock protein (hsp) expression was examined in murine bone marrow-derived macrophages infected with stationary-phase promastigotes of leishmania donovani. immunoblotting performed with a rabbit polyclonal antiserum raised against hsp60 from heliothis virescens (moth) revealed the de novo appearance of 65- and 67-kda proteins in leishmania-infected macrophages. a third protein of 60 kda, which represented murine hsp60, was also detected, and its expression did not change in response to infec ...	1993	8335360
role and effect of il-2 in experimental visceral leishmaniasis.	in experimental visceral leishmaniasis, acquired resistance is t cell-dependent, involves ifn-gamma-activated macrophages, and is expressed in the tissues by granuloma formation. resistance also correlates with ag-stimulated il-2 secretion; therefore, leishmania donovani-infected balb/c mice were treated with anti-il-2 mab or ril-2 to determine the host defense effect of il-2. in control mice, intracellular hepatic infection peaked at 2 wk and then declined coincident with granuloma development. ...	1993	8335921
[the current aspects of seroepidemiological research in combined foci of leishmaniasis].	the authors analyze the results of c-elisa, used in screening of the population in combined foci of zoonotic cutaneous leishmaniasis and visceral leishmaniasis in two types of landscapes in turkmenistan. in the deltas, on the plains [correction of planes] and oases, where the incidence of zoonotic cutaneous leishmaniasis is very high, 1.6% of the examinees were found to have antibody to l. major. the antibodies in this condition are detectable only during the acute stage of the disease and persi ...	1993	8336651
a new focus of kala-azar due to leishmania donovani sensu lato in kenya.	three masai children from kekonyokie south location, kajiado district were diagnosed with visceral leishmaniasis (kala-azar). leishmanial isolates from the patients were characterized as leishmania donovani sensu lato, by cellulose acetate electrophoresis. case histories indicated that the disease was acquired locally. a survey of 409 children at 7 local primary schools and one nursery school revealed no additional case. sandfly surveys using light traps and sticky paper traps recovered 10 speci ...	1993	8337711
leishmania tropica and leishmania infantum responsible for cutaneous leishmaniasis in greece: sixteen autochthonous cases.		1993	8337723
antileishmanial activity of the ether phospholipid ilmofosine.	the ether phospholipid ilmofosine (bm 41.440) was active in vitro against amastigotes of leishmania donovani and an antimony-resistant line of l. infantum in mouse peritoneal macrophages with ed50 values of 3.7 microm and 3.5 microm respectively. ilmofosine was also active against l. donovani in balb/c mice following oral and subcutaneous dosing, with an ed50 value of 10.5 mg/kg x 5 by the oral route.	1993	8337733
cytochrome p450 in trypanosomatids.	post-mitochondrial supernatant extracts prepared from bloodstream forms of trypanosoma brucei brucei, t. cruzi epimastigotes, leishmania donovani promastigotes and crithidia fasciculata have been found to catalyse cytochrome p450-dependent reactions. appreciable ethoxycoumarin deethylase and ethoxyresorufin deethylase activities were found in all of the above trypanosomatids, with t. cruzi epimastigotes having the highest activity (57.1 and 10.7 pmol/min/mg protein, respectively). in all four sp ...	1993	8347125
[cutaneous parasitism by leishmania (leishmania) chagasi during south american visceral leishmaniasis].	eighteen patients from the northeastern brazilian state of ceara with proven kala-azar were studied for evidence of skin parasitism: two had ulcerative or papular skin lesions and 16 had clinically normal skin. punch biopsies (3 mm) of intact paraspinal subscapular skin were performed on all patients; in those with papular or ulcerative lesions biopsies also were taken from an active site. one of each of the subscapsular biopsies and half of each biopsy from an active lesion were studied; the ot ...	1993	8353466
rectal biopsy as a diagnostic procedure of chronic visceral leishmaniasis.		1993	8354491
the structure of leishmania major amastigote lipophosphoglycan.	intracellular amastigotes of leishmania major produce 6 x 10(4) copies/cell of a lipophosphoglycan (lpg) that is structurally distinct from the lpg produced by the extracellular promastigote form of l. major, leishmania donovani, and leishmania mexicana (reviewed by mcconville, m. j. (1991) cell biol. int. rep. 15, 779-798). l. major amastigote lpg is composed of a lysoalkyl phosphatidylinositol lipid anchor that links via a diphosphorylated hexasaccharide core to a phosphoglycan (6-100 kda). th ...	1993	8360147
intraparotid leishmania donovani lymphadenitis: diagnosis by fine needle aspiration.		1993	8362595
treatment of experimental visceral leishmaniasis in a t-cell-deficient host: response to amphotericin b and pentamidine.	in experimental visceral leishmaniasis, euthymic but not athymic (nude) balb/c mice respond to conventional treatment with pentavalent antimony, indicating that the in vivo efficacy of antimony is t cell dependent. this finding correlates with frequent antimony treatment failures for t-cell-deficient patients with visceral leishmaniasis. to determine whether the in vivo efficacies of alternative antileishmanial agents also require t cells, leishmania donovani-infected euthymic and nude balb/c mi ...	1993	8363382
leishmania donovani infections in phlebotomine sandflies from the kala-azar focus at aba roba in ethiopia: dna probe compared with conventional detection methods.		1993	8369567
survivability and infectivity of viscerotropic leishmania tropica from operation desert storm participants in human blood products maintained under blood bank conditions.	to assess the potential for leishmaniasis being transmitted through blood transfusion, we studied the survival of leishmania in blood products under blood bank storage conditions. we report that l. tropica- or l. donovani-contaminated transfusable blood products are a risk to the blood supply for at least 25 days postdonation under blood bank general conditions. the blood components that have been implicated are whole blood, packed red blood cells, platelet concentrate, and frozen-deglycerolized ...	1993	8372954
isolation and characterization of a repetitive dna sequence from leishmania infantum: development of a visceral leishmaniasis polymerase chain reaction.	to construct a dna probe specific for protozoa that cause visceral leishmaniasis, we cloned pst i fragments of leishmania infantum genomic dna into a bluescript ii sk vector. a clone of 4.3 kb that contained a highly repetitive sequence was isolated and cut with three restriction enzymes: hae iii, rsa i, and sau 3a. after a new molecular cloning step, we isolated and sequenced a 140-basepair (bp) fragment. two oligonucleotides were synthesized to be used as primers for a polymerase chain reactio ...	1993	8372958
effects of sinefungin on growth and sterol composition of leishmania promastigotes.	the s-adenosylmethionine analogue sinefungin was tested in vitro against promastigotes of various strains of leishmania. the ic50 values for the leishmania mexicana, leishmania major, and leishmania donovani strains used were of the order of 10 ng/ml but the leishmania amazonensis strain tested was more resistant to the drug, the ic50 value being 6 micrograms/ml. sterol profiles, in which 24-alkyl (c28) sterols predominated, were relatively unaffected by sinefungin. incorporation of label derive ...	1993	8375483
mononuclear cell subpopulations and cytokine levels in human visceral leishmaniasis before and after chemotherapy.	serum cytokine levels and mononuclear cell subpopulations in the spleen and peripheral blood of patients with visceral leishmaniasis before and after antimony therapy were analyzed. the percentages of activated monocytes/macrophages, t cells, and possibly b cells; of gamma/delta t cell receptor (tcr)-bearing t cells; of cd4- cd8- alpha/beta tcr-bearing t cells; and serum levels of tumor necrosis factor-alpha (tnf alpha), interferon-gamma (ifn-gamma), and interleukin-6 (il-6) were high in patient ...	1993	8376845
macrophage-directed delivery of doxorubicin conjugated to neoglycoprotein using leishmaniasis as the model disease.	the antileishmanial potency of doxorubicin conjugated to mannose-human serum albumin (man-hsa) was tested in experimental visceral leishmaniasis. conjugation of doxorubicin did not decrease the affinity of the neoglycoprotein for the macrophage mannose receptor. conjugated doxorubicin eliminated intracellular amastigotes of leishmania donovani in peritoneal macrophages almost 12.5 times more efficiently than did the free drug and greatly reduced and possibly eliminated splenic intracellular para ...	1993	8376846
isolation of virulence genes directing surface glycosyl-phosphatidylinositol synthesis by functional complementation of leishmania.	trypanosomatid parasites of the genus leishmania cause a spectrum of widespread tropical diseases. in the vertebrate host they reside within the macrophage phagolysosome; however, the mechanisms employed in this remarkable survival strategy are not well understood. recent advances in the molecular genetics of these parasites prompted us to develop methods of functional genetic complementation in leishmania and apply them to the isolation of genes involved in the biosynthesis of the virulence det ...	1993	8378337
molecular characterization of phosphoribosylpyrophosphate synthetase from leishmania donovani.	the phosphoribosylpyrophosphate synthetase (prs) enzyme from parasitic protozoa plays a critical role in the acquisition of exogenous purine bases by providing the phosphoribosylpyrophosphate substrate for phosphoribosylation. to characterize a prs enzyme from parasitic protozoa, the prs gene was isolated from a genomic library of leishmania donovani dna. a 1936-bp sali fragment was sequenced that encompassed an open reading frame of 1113 nucleotides encoding a polypeptide of 371 amino acids and ...	1993	8390611
immunochemotherapy for visceral leishmaniasis: a controlled pilot trial of antimony versus antimony plus interferon-gamma.	twenty-four kenyan patients with visceral leishmaniasis were treated for 30 days with either conventional therapy (daily pentavalent antimony, n = 14) or experimental immunochemotherapy (daily antimony plus interferon-gamma [ifn-gamma] every other day, n = 10). all 24 patients responded clinically to treatment, and microscopic splenic aspirate scores rapidly decreased in both groups. as judged by splenic aspirate culture results, ifn-gamma-treated patients responded more quickly (50% versus 22% ...	1993	8390795
distribution of macromolecular methylations in promastigotes of leishmania donovani and impact of sinefungin.	sinefungin, an antifungal and antiparasitic nucleoside antibiotic, is a very potent antileishmanial agent both in vitro and in vivo. this molecule, structurally related to s-adenosylmethionine, is a good competitive inhibitor of methyltransferases in vitro. the aim of this report is to analyze the impact of sinefungin on methylation pattern and the subcellular localisation of methyl groups and various methylases in promastigotes of leishmania donovani. we have shown the presence of various methy ...	1993	8401471
correlates of leishmania-specific immunity in the clinical spectrum of infection with leishmania chagasi.	patients from across the spectrum of clinical manifestations of leishmania chagasi infection were evaluated for in vitro correlates of immunity. peripheral blood mononuclear cells were assayed for parasite-specific lymphoproliferation, cytokine generation, and the capacity to activate autologous macrophages to kill intracellular amastigotes. patients with acute kala-azar were generally unreactive in each of these assays. children with subclinical infection demonstrated relatively low levels of p ...	1993	8421174
molecular characterization of a kinesin-related antigen of leishmania chagasi that detects specific antibody in african and american visceral leishmaniasis.	we report the cloning of a leishmania chagasi antigen gene and an evaluation of leishmaniasis patient antibody responses to the recombinant protein, rk39. rk39 contains a 39-amino acid repeat that is part of a 230-kda protein predominant in l. chagasi tissue amastigotes. sequence analyses showed this protein, lckin, to be related to the kinesin superfamily of motor proteins. southern blot analyses demonstrated lckin-related sequences in seven species of leishmania, with conservation of the repea ...	1993	8421715
identification of two distinct cysteine proteinase genes of leishmania pifanoi axenic amastigotes using the polymerase chain reaction.	a developmentally regulated cysteine proteinase associated with an unique lysosomal organelle, the megasome, has been described for the intracellular amastigotes of the leishmania mexicana complex; this proteinase appears to be important in the survival of the parasite. degenerate primers encoding the active sites residues have been used to amplify cysteine proteinase cdna sequences from axenically cultured amastigotes of leishmania pifanoi, a member of the l. mexicana complex. based on sequence ...	1993	8426606
studies on the control of visceral leishmaniasis: validation of the falcon assay screening test--enzyme-linked immunosorbent assay (fast-elisa) for field diagnosis of canine visceral leishmaniasis.	the falcon assay screening test-enzyme-linked immunosorbent assay (fast-elisa), the latest version of the enzyme-linked immunosorbent assay, uses antigen-coated beads. a 96-well plate can be run in 20 min without electricity or expensive equipment. we compared the fast-elisa, a standard elisa, and an indirect immunofluorescent assay (ifa) for evaluation of canine leishmaniasis under field conditions using samples from 161 dogs from our longitudinal study in the endemic area of jacobina, bahia, b ...	1993	8427377
leishmania donovani-reactive th1- and th2-like t-cell clones from individuals who have recovered from visceral leishmaniasis.	infections in humans by leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (vl), or in a self-limiting asymptomatic infection. in murine models of the infection employing leishmania major, the course of the disease can be directed into a vl-like syndrome by interleukin-4 (il-4)-producing th2 cells, or cure may result by th1 cells secreting gamma interferon (ifn-gamma). the present study examined the potential of human t cells to generate th1 or th2 responses to l ...	1993	8432588
immunobiological studies on experimental visceral leishmaniasis. iii. cytokine-mediated regulation of parasite replication.	the role of t-cell-derived cytokines in the regulation of leishmania donovani replication was studied in a murine model. it was observed that in h-2d mice at the early and later stages of the disease ifn-gamma-secreting t cells predominate, whereas in between the above stages il-4-secreting t cells predominate. possibly, il-4 abrogates the protective ability of ifn-gamma and thereby exponential parasite growth is ensured at the active stage of the disease. by contrast, h-2b mice were possibly in ...	1993	8434228
fine needle aspiration cytology of the spleen in visceral leishmaniasis.	we describe the fine needle aspiration cytologic study of 210 splenic aspirates from patients clinically diagnosed as having visceral leishmaniasis. of these, 147 aspirates were found to be positive for leishmania donovani bodies. we highlighted the cytomorphology of these positive smears. a majority of the cases showed an increase in the number and size of reticuloendothelial cells, with altered shapes, variations in the cytoplasm and decreased white pulp elements. in some of these cases (10%), ...	1993	8434499
pure protein from leishmania donovani protects mice against both cutaneous and visceral leishmaniasis.	a protein purified from leishmania donovani promastigotes, dp72, was shown to partially protect balb/c mice against a challenge by this parasite. immunized mice infected i.v. with 10(7) l. donovani promastigotes showed a 0, 60, and 78% reduction in liver parasite burden compared with the control mice at each time point examined after challenge, 1, 20, and 108 days, respectively. western blotting demonstrated that the sera from the immune mice, which reacted specifically with dp72 in lysates of l ...	1993	8450215
[prevalence of anti-leishmania antibodies in parenteral drug addicts. yield value of 2 study techniques].	the prevalence of antibodies anti-leishmania in intravenous drug addict (ivda) patients suspect of visceral leishmaniasis (vl) and the diagnostic profitability of two tests for detecting anti-leishmania antibodies were studied.	1993	8450694
effector role of blood monocytes in experimental visceral leishmaniasis.	in balb/c mice, liver granulomas provoked by visceral infection with intracellular leishmania donovani are rapidly populated by influxing blood monocytes. to determine the host defense effector role of these mononuclear phagocytes, we treated three populations of infected animals with 5c6, an anti-type 3 complement receptor monoclonal antibody (mab), which inhibits monocyte recruitment into inflamed tissues. in naive balb/c mice, injections of 5c6 impaired the initial acquisition of antileishman ...	1993	8454335
endemic visceral leishmaniasis in a dog from texas.	visceral leishmaniasis was diagnosed by cytology and positive indirect immunofluorescent antibody titers to leishmania donovani in a 7-month-old female basenji dog from texas. clinical and laboratory findings included weight loss, hematochezia, hyperglobulinemia, hypoalbuminemia, anemia, and neutrophilic leukocytosis. evidence of response to treatment with diminazene aceturate and ketoconazole included improvement in the abnormal clinical, hematologic, and biochemical findings, decreased serum g ...	1993	8455178
comparative susceptibility of african green monkeys (cercopithecus aethiops) to experimental infection with leishmania leishmania donovani and leishmania leishmania infantum.	the leishmaniases are global health problems that affect both humans and animals. the availability of nonhuman primate models is desirable for such important areas as testing candidate vaccines and newly developed chemo- and immunotherapeutic agents. visceral leishmaniasis was experimentally induced in african green monkeys (cercopithecus aethiops) by intravenously inoculating 10(7) amastigotes/kg of body weight of either leishmania leishmania donovani of human origin (group 1) or l. l. infantum ...	1993	8459677
expression of lipophosphoglycan, high-molecular weight phosphoglycan and glycoprotein 63 in promastigotes and amastigotes of leishmania mexicana.	the abundant surface glycoconjugate of leishmania promastigotes, lipophosphoglycan (lpg), forms a blue-colored complex (lambda max = 649 nm) with the cationic dye stains-all, which can be quantitated densitometrically on polyacrylamide gels of cell lysates. promastigotes of leishmania mexicana, leishmania major and leishmania donovani yield values of 1-3 x 10(6) lpg molecules cell-1. in amastigotes the lpg content is down-regulated below the detection limit (< 10(3) molecules cell-1) in l. mexic ...	1993	8459823
diagnosis of visceral leishmaniasis in hiv-infected individuals using peripheral blood smears.	to compare the clinical and laboratory features of visceral leishmaniasis (kala-azar) in hiv-infected and non-infected subjects, and to determine the presence of leishmania amastigotes in circulating leukocytes using peripheral blood smears.	1993	8466685
cyclophosphamide blocks both antigen-specific and polyclonal immunoglobulin responses in experimental visceral leishmaniasis.	cyclophosphamide (cy) has been shown to modulate antibody responses in a wide range of diseases both in humans and experimental animals. our results in syrian hamsters infected with leishmania donovani have shown that cy blocks specific and polyclonal antibody production both in vivo and in vitro. this effect was achieved by weekly 100 mg/kg doses and also by a 300 mg/kg single dose. although cy provokes a significant decrease in b-cell numbers in infected animals, this cannot explain the suppre ...	1993	8468122
ity influences the production of ifn-gamma by murine splenocytes stimulated in vitro with salmonella typhimurium.	the ity-lsh-bcg genetic locus in the mouse has been documented to confer innate resistance to at least three intracellular pathogens: salmonella typhimurium, leishmania donovani, and mycobacterium. expression of the resistance gene(s) results in a slower net growth of these pathogens in the reticuloendothelial system early postinfection. although it is clear that the resident macrophages in resistant mice are functionally superior with regard to antimicrobial activity, the exact mechanism(s) und ...	1993	8473743
amphotericin b in resistant kala-azar in bihar.	during the recent epidemic of kala-azar in bihar, we identified a group of patients who were unresponsive to the two commonly used drugs--sodium stibogluconate and pentamidine. we evaluated the use of amphotericin b in these patients because it has been shown to be active in experimental animals against amastigotes and promastigotes, it has been found to be useful in south american patients and is now recommended by the world health organization as a second line drug.	1993	8477209
cloning and characterization of differentially expressed genes from in vitro-grown 'amastigotes' of leishmania donovani.	leishmanial parasites routinely undergo cyclic differentiation from promastigotes to amastigotes during their life cycle. this process involves both morphological and macromolecular changes. to study such changes, we used a axenic culture system which permits the continuous generation and cycling of leishmania donovani from promastigotes to 'amastigotes' in vitro. cdna libraries were constructed from poly(a)+ rna isolated from both the pro- and amastigote forms. using differential cdna hybridiza ...	1993	8479459
leishmania donovani parasites in the nasal secretions, tonsillopharyngeal mucosa, and urine centrifugates of visceral leishmaniasis patients in kenya.	in the early 1930s, investigators of visceral leishmaniasis stated that leishman-donovan bodies are found in body fluids of kala-azar patients, for example, in urine, feces, semen, and nasal and pharyngeal secretions. based on this finding, we investigated the diagnostic potential of nasal secretions, tonsillopharyngeal mucosal swabs, and urine centrifugates inoculated into schneider's drosophila medium (containing antibiotics and antifungal agents) as well as with giemsa-stained smears. consequ ...	1993	8480861
alteration of leishmania donovani infection levels by selective impairment of macrophage signal transduction.	leishmania donovani is an obligate intracellular protozoan which residues and multiples in macrophages. the molecular basis for this host-parasite interaction is poorly understood. targeting a signal transduction pathway in the macrophage would allow this parasite to manipulate cellular gene expression, and this may aid in ensuring its survival. we demonstrate that in macrophages infected with l. donovani for 18 h, c-fos gene expression mediated through protein kinase a was unaffected under cond ...	1993	8482844
effect of new diamidines against leishmania donovani infection.	the impact of interamidine distance on antileishmanial activity of new aryldiamidines have been evaluated against amastigotes of l. donovani in hamster. of the 20 compounds tested, only four (2,8-diamidino-9,10-dihydrodibenzoxepin; 2,7-diamidinoxanthone; 2,7-diamidinothioxanthone and 2,7-diamidinoxanthene) showed significant inhibition (more than 80%) of multiplication of amastigotes in spleen. the interamidine distance in the structure appears to have bearing on antileishmanial activity. the ob ...	1993	8500833
lipophosphoglycan antigen shedding by leishmania donovani.	the biochemical characterizations of lipophosphoglycans from various leishmania species reported by other workers may or may not contain several types of lipophosphoglycan molecules. this is the first report in which a specific lipophosphoglycan has been defined by both its antigenic and electrophoretic properties. furthermore, a purification procedure for this specific lipophosphoglycan is described and some biochemical characterizations are presented. phospholipase c and the so-called phosphat ...	1993	8508171
herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans.	leishmaniasis is a major tropical disease for which current chemotherapies, pentavalent antimonials, are inadequate and cause severe side effects. it has been reported that trifluralin, a microtubule-disrupting herbicide, is inhibitory to leishmania amazonensis. in this study, the in vitro effect of trifluralin on different species of trypanosomatid protozoans was determined. in addition to l. amazonensis, trifluralin is effective against leishmania major and leishmania tropica, which cause cuta ...	1993	8516314
serological diagnosis of leishmaniasis: on detecting infection as well as disease.	serological tests are very frequently used in epidemiological surveys of leishmaniasis and other parasitoses. their sensitivity and specificity are generally defined with respect to parasitism and disease, rather than infection. the reason is that known positives are those individuals most likely to yield parasites, or who have distinctive clinical signs, and concomitantly high antibody titres. this paper investigates the performance of one serological method, the indirect fluorescent antibody t ...	1993	8519330
characterization of a filtrable 3'-nucleotidase of leishmania donovani.	a plasma membrane 3'-nucleotidase (3'-ribonucleotide phosphohydrolase, ec 3.1.3.6) having a apparent subunit molecular mass of 38 kda but filtrable through a centriprep-10 microconcentrator (amicon) membrane was purified from leishmania donovani promastigotes. the enzyme activity has an optimum at ph around 7.5. edta strongly inhibited the enzyme activity which was fully restored only by co2+, from various metal ions added. citrate ions, zn2+ or dithiothreitol were also strongly inhibitory. the ...	1993	8218386
leishmania donovani: in vitro evidence of hepatocyte damage by kupffer cells and immigrant macrophages in a murine model.	infection with leishmania donovani leads to activation of liver macrophages. the role of different macrophage populations of liver in this infection is not clearly defined. thus, the mechanism involved in hepatocyte damage was studied by coculturing hepatocytes with two populations of liver macrophages, the kupffer cells and immigrant macrophages. the results indicated maximum tissue damage at peak infection in both the macrophage populations cocultured with hepatocytes (p < 0.001). kupffer cell ...	1993	8224088
engima of therapeutic failure in visceral leishmaniasis.		1993	8226600
defective galactofuranose addition in lipophosphoglycan biosynthesis in a mutant of leishmania donovani.	a mutant cell line of leishmania donovani (r2d2), previously selected for resistance to the cytotoxic lectin ricin agglutinin, was found to be totally deficient in the synthesis and expression of lipophosphoglycan, a dominant surface virulence factor. the metabolic defect in r2d2 parasites responsible for its lipophosphoglycan (lpg-) phenotype was investigated in this study. following metabolic labeling of r2d2 parasites with either [3h]galactose or [3h]mannose, the main glycosylphosphatidylinos ...	1993	8226951
post-kala-azar dermal leishmaniasis: a light and electron microscopic study of 18 cases.	post-kala-azar dermal leishmaniasis (pkdl) is caused by the protozoan parasite, leishmania donovani, and is seen in patients with history of having been treated earlier for the visceral disease form, kala-azar, caused by the same organism. the findings from 18 patients with pkdl are described in this study. the skin manifestations ranged from hypopigmented macules to infiltrated plaques and nodules. histopathologic examination revealed a cellular infiltrate of lymphocytes, plasma cells, and macr ...	1993	8227608
studies on mitochondrial atpase of leishmania donovani using digitonin-permeabilized promastigotes.	mitochondrial atpase of leishmania donovani was characterized using digitonin-permeabilized promastigotes and the results were compared with those from isolated mitochondria. maximum mitochondrial atpase activity was obtained in promastigotes permeabilized with digitonin at a final concentration of 20 microm and the specific activity of the enzyme was 46% and 57% higher than that of homogenized and sonicated promastigotes, respectively. at concentrations above 20 microm digitonin inhibited atpas ...	1993	8232420
uptake and turnover of glucose in leishmania donovani.	glucose uptake and metabolism by leishmania donovani promastigotes was studied using d-[14c]glucose in combination with the silicone oil centrifugation technique on organisms preadapted to different growth rates and glucose availability in the chemostat. the uptake step was differentiated from the subsequent metabolism by separation in time rather than by using non-metabolisable analogues. the uptake of glucose was measured as a function of time and/or the external glucose concentration on cells ...	1993	8232421
evaluation of the direct agglutination test as an immunodiagnostic tool for kala-azar in india.	the direct agglutination test (dat) has been assessed as a diagnostic procedure for visceral leishmaniasis. fifty-six of 58 sera (96.5%) from confirmed cases of visceral leishmaniasis, whose bone marrow aspirates contained leishmania donovani amastigotes, had agglutinating antibodies above the cut-off titre of 1:800. none of the sera from healthy control subjects from non-endemic or endemic areas had anti-leishmanial antibodies. similarly, none of the sera obtained from cases of malaria or tuber ...	1993	8236390
the treatment of kala-azar in the sudan with sodium stibogluconate: a randomized trial of three dosage regimens.	in a randomized study in the sudan, 3 different regimens of sodium stibogluconate were compared in patients with parasitologically confirmed kala-azar (visceral leishmaniasis): 10 mg/kg for 30 d (38 patients), 20 mg/kg for 30 d (29 patients), and 20 mg/kg for 15 d (37 patients). treatment failures were defined as death, partial response, relapse, or the development of post-kala-azar dermal leishmaniasis. the hazard ratio for failure of 20 mg/kg for 30 d vs. 10 mg/kg for 30 d 2.1 (95% confidence ...	1993	8236402
post-kala-azar dermal leishmaniasis.		1993	8240186
in vitro action of new organometallic compounds against trypanosomatidae protozoa.	the effects of 10 newly synthesized organometallic rhodium complexes (5 of rh(i), 4 of rh(iii) and one of rh(iv) complex salt) and 2 antimony (iii) complexes against epimastigote forms of trypanosoma cruzi and promastigote forms of leishmania donovani have been studied in vitro. of the 10 rhodium complexes tested three proved 100% efficient in inhibiting the growth of the epimastigote forms of t. cruzi while only one worked against the promastigote forms of l. donovani. the two antimony complexe ...	1993	8240449
phenotype of recombinant leishmania donovani and trypanosoma cruzi which over-express trypanothione reductase. sensitivity towards agents that are thought to induce oxidative stress.	trypanothione reductase is thought to be important in maintaining an intracellular reducing environment in trypanosomatids. to investigate the role of trypanothione reductase we transfected leishmania donovani and trypanosoma cruzi with an expression vector containing the l. donovani trypanothione reductase gene and achieved over-expression of enzyme activity (10-14-fold) in transformed cells. following treatment of l. donovani cells with the thiol-oxidizing agent diamide, the ability to regener ...	1993	8243474
physical delineation of the minimal chromosomal segment encompassing the murine host resistance locus bcg.	the host resistance locus bcg determines resistance of mice to infection with intracellular pathogens such as certain species of mycobacteria, salmonella typhimurium, and leishmania donovani. bcg maps on the proximal portion of mouse chromosome 1, very tightly linked to villin (vil), with the gene order and intergene distances tp-1-(1 cm)-d1mcg105-(0.1 cm)-lambda mm1c165/vil/bcg-(0.2 cm)-lambda mm1c136-(0.3 cm)-des-(0.1 cm)-inha. in an effort to clone genomic sequences overlapping bcg, we have u ...	1993	8244383
[serologic diagnosis of canine leishmaniasis: the dot-elisa as a simple alternative to conventional elisa].	serology is an important tool for the diagnosis of canine leishmaniasis, since the direct detection of the parasite remains negative in many cases. a dot-elisa was developed, which can be read without using a photometer. for this purpose assay strips were prepared, which were divided into a control field (staining indicates normal function of reagents) and four reaction fields. the reaction fields were coated with four different concentrations of leishmania antigen and allowed semiquantitative r ...	1993	8248908
phlebotomus (larroussius) perfiliewi naturally infected with dermotropic leishmania infantum at tenes, algeria.		1993	8249062
field application of an elisa using redefined leishmania antigens for the detection of visceral leishmaniasis.	two soluble antigens from leishmania donovani of 116 kda and 70 kda molecular mass, and a soluble mixture of crude antigens, were used in an enzyme-linked immunosorbent assay (elisa) for the detection of visceral leishmaniasis (vl) in the field, and compared with the direct agglutination test (dat). the tests were carried out on 8 vl patients, 34 normal individuals from an area endemic for the disease, and 68 former visceral leishmaniasis patients 1-5 years after treatment. the 70 kda elisa and ...	1993	8249071
leishmanin and tuberculin sensitivity in leishmaniasis in the sudan, with special reference to kala-azar.	the application of leishmanin and tuberculin skin tests was studied in patients with leishmaniasis in the sudan. 35 cases of active kala-azar and 3 relapse cases were leishmanin negative. 81% of patients treated for kala-azar showed a positive reaction after 6 months. 17 of 29 patients with post kala-azar dermal leishmaniasis (pkdl) were leishmanin positive. 2 of 16 patients with kala-azar tested with tuberculin were positive; one was diagnosed as tuberculosis. in 7 initially tuberculin negative ...	1993	8249072
sequence and genomic organization of the hsp70 genes of leishmania amazonensis.	the sequence and genomic organization of hsp70 genes in leishmania amazonensis were examined. maps of overlapping cosmid clones revealed that seven l. amazonensis hsp70 genes are organized into a 24-kb locus containing 3.5-kb tandem repeats. cosmids covering a different chromosomal region indicated that an eighth hsp70 sequence is located at a distant site. southern blot data suggested the existence of additional hsp70 genes or pseudogenes. one complete 3.5-kb genomic repeat unit, including codi ...	1993	8139614
proton nmr lipid profile of leishmania donovani promastigotes.	the proton nuclear magnetic resonance (nmr) lipid profile of leishmania donovani was obtained in the one-dimensional and two-dimensional modes. partial assignments of lipid classes and individual lipids were obtained purely from the proton nmr spectrum of the mixture. a more complete assignment and quantitative analysis was achieved by prior separation of the lipids by high pressure liquid chromatography (hplc) followed by proton nmr analysis of the fractions. this work showed that proton nmr sp ...	1993	8139618
effect of a bis(benzyl)polyamine analogue, and dl-alpha-difluoromethylornithine on parasite suppression and cellular polyamine levels in golden hamster during leishmania donovani infection.	we examined the antileishmanial activity of dl-alpha-difluoromethylornithine (dfmo) and a bis(benzyl)polyamine analogue (mdl 27695; n,n'-bis (3-[(phenyl-methyl)amino] propyl) 1,7-diaminoheptane) in l. donovani infected golden hamsters. dfmo, an enzyme activated irreversible inhibitor of ornithine decarboxylase, the rate limiting enzyme in polyamine biosynthesis, has potent antileishmanial activity. when given as a 2% solution in drinking water 2 days after infection and continued for 4 days, it ...	1993	8140036
[visceral leishmaniasis and hiv infection: the diagnostic and therapeutic problems].	we present the case of an hiv-seropositive drug addict patient whose seropositivity was unknown until admission to hospital, where he presented with a clinical picture of fever splenomegaly and weight loss. a diagnosis of visceral leishmaniasis was established. we stress the diagnostic difficulties well expressed in the need to repeat the bone marrow aspirate to detect the presence of leishmanias. the lack of response to conventional antimonial therapy is discussed as well as the role of pentami ...	1993	8140923
[cellular immunity and vaccination against cutaneous leishmaniasis. recent progress and prospects].	review of leishmaniasis immunopathogenesis, the models in the laboratory animals, and the last advances in the experimental vaccine administration. in recent years, there have been important progresses that have contributed substantially to classify the role of the interleukins and other chemical mediators in the immunologic response. all these advances open the door to the production of better and more immunogenic vaccines, that in a near future will be employed advantageous in the human beings ...	1993	8143026
a type 1 dna topoisomerase from the kinetoplast hemoflagellate leishmania donovani.	a type 1 dna topoisomerase has been purified from the nuclei of the kinetoplast hemoflagellate leishmania donovani using polyethylene glycol fractionation and chromatography on hydroxylapatite, phosphocellulose and phenylsepharose column. the relaxation activity is atp independent. mg2+ is an essential cofactor for the reaction with an optimum at 10 mm. mg2+ can be substituted by mn2+ at 5 mm concentration. the relaxation reaction exhibits a salt optimum at 100 mm kcl. the enzyme can not remove ...	1993	8144168
lipid peroxidation in hepatic microsomal membranes isolated from mice in health and in experimental leishmaniasis.	normal hepatic microsomal membranes when exposed in vitro to different free radicals, cause membrane damage by lipid peroxidation which could be monitored by the analysis of malonaldehyde formation and measurement of membrane microviscosity. lipid peroxidation in vivo, when examined in hepatic microsomal membranes in experimental leishmaniasis, reveals a direct relationship between membrane microviscosity and the extent of lipid peroxidation. scavengers of free radicals and peroxides such as sup ...	1993	8144171
the in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis.	the in-vitro activity of a group of antifungal compounds known to inhibit ergosterol synthesis was investigated against leishmania donovani grown as intracellular amastigotes in the human leukaemia monocyte cell line, thp-1. toxicity on the host cells was assessed using the colorimetric mtt assay. compounds inhibiting 2,3 oxidosqualene lanosterol cyclase; ro 43-3815, ro 43-5955, ro 43-8208, ro 42-6589 and ro 43-0688 displayed high activity with a median effective dose (ed50) of 0.6, 0.9, 3.5, 2. ...	1993	8144423
importance of bone marrow culture for diagnosis of kala azar.	kala azar was diagnosed in 45 clinically suspected cases following bone marrow smear examination and in vitro culture of the aspirate. bone marrow aspiration smear examination revealed amastigotes in 27 cases (60%). in vitro culture of the aspirate demonstrated leishmania parasites in 44 cases (97.8%). a total of 18 cases (40%) were negative for amastigotes in smear examinations but parasites could be demonstrated by culturing the same aspirates. the in vitro culture of bone marrow is necessary ...	1993	8052823
[leishmaniasis in peninsular spain. a historical-bibliographic review (1912-1985)].	a bibliographic-historical review of leishmaniasis in spain during the period 1912-1985 is carried out. the bibliographical prospecting has allowed to collect a total of 402 works; out of them only 79 are included in this review. from reading them, it can be deduced that, starting from its discovery in the coast of levante in 1912, leishmaniasis has been a very well known disease in spain, during the first third of our century, period in which a remarkable prevalence took place, as it follows fr ...	1993	7732292
applicability of direct agglutination test (dat) at a rural health setting in bangladesh and feasibility of local antigen production.	as part of a large-scale sero-epidemiological survey on visceral leishmaniasis (vl) carried out in mymensingh district of bangladesh, applicability of dat was assessed at the level of a rural health setting in trishal (upazila) subdistrict. despite the relatively less optimal conditions encountered, 5854 inhabitants from 7 villages appendant to trishal were assessed for vl. the demographic distribution for sero-positivity obtained at the rural setting was comparable to that found by dat as execu ...	1993	7802488
visceral leishmaniasis in teresina, n. e. brazil: towards a dna probe kit and its adaptation to processing blood-contaminated samples.	the lmet2 chemiluminescent dna probe is a valuable tool for identifying parasites of the leishmania donovani -complex in sand flies, dogs and human samples. recent blood meals in sand flies or blood contamination of tissue samples inhibited probe sensitivity, whether radiolabelled or chemiluminescent detection systems were used. treatment of membranes with protease before hybridisation restored positive signal. alternatively samples could be lysed with protease and applied to membranes with a va ...	1993	7802496
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 ...	1993	7678428
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 ...	1993	7691945
monoclonal antibodies directed against leishmania secreted acid phosphatase and lipophosphoglycan. partial characterization of private and public epitopes.	leishmania promastigotes, the stage of the parasite characteristic for the sandfly vector, express an abundant glycoconjugate, called lipophosphoglycan, at their surface. lipophosphoglycan consists of lysoalkyl-sn-glycerophosphoinositol linked to a phosphosaccharide core conserved in all species, which is connected to po4-6gal beta 1,4man alpha 1 repeats with species-specific substitutions at the gal residue; the repeats are capped by conserved and species-specific oligosaccharides. most leishma ...	1993	7693464
human serum resistant promastigotes of leishmania infantum in the midgut of phlebotomus perniciosus.	promastigotes of leishmania infantum develop from early-stage normal human serum (nhs) sensitive forms to a partially nhs resistant stage in the midgut of phlebotomus perniciosus. this development begins about day 7 after the sandfly has taken its initial infective bloodmeal. the onset of partial nhs-resistance occurs when mass proliferation of midgut promastigotes is already completed and the parasites have begun to differentiate into small, highly motile cells. in this parasite/vector interrel ...	1993	8094588
dynamic interaction between leishmania infection in mice and th1-type cd4+ t-cells: complexity in outcome without a requirement for th2-type responses.	the interaction between leishmania parasites and th1 cells is investigated using a simple mathematical model of immunological responses and parasite population growth within the host. the model generates patterns of resistance and susceptibility to infection that mirror observed trends in experimental infections of mice and of humans exposed to infection in areas of endemic transmission. the heterogeneity in outcome predicted by the model can arise either through differences in the values of the ...	1993	8095327
leishmania donovani surface glycoconjugate gp36 is the major immunogen component of the fucose-mannose ligand (fml).	leishmania donovani promastigote glycoconjugate ligands, studied in our laboratory, that interact with the internalization receptors on balb/c macrophages: the 'fucose mannose ligand' (fml), the 'phosphate mannogalactan ligand' (pmgl), and the 'lipopeptidephosphoglycan' (lppd), interfered also with interaction between amastigotes and host cells in vitro. among the three compounds studied, the fml was shown to be the most potent inhibitor of both promastigote and amastigote internalization, and t ...	1993	8096110
synthesis and antiparasitic activity of new 1-nitro, 1-amino and 1-acetamido 9-acridinones.	the synthesis of 1-amino-10-alkyl-9-acridinones 4 and 5 and of homologous 9-thio-acridinones 7 and 8 are described. similarly, the synthesis of 1-nitro-4-(2'-aminoethylamino)-9-acridinones 13 and 15, is described. compound 4 was used as starting material for the preparation of 10-alkyl-9-acridinone dimers 6, bridged with an alpha,omega-diamido chain. compound 15 was selected for biological investigations on pathogenic parasite strains, and a promising antiamoebic activity could be shown.	1993	8098606
high-resolution linkage map in the vicinity of the host resistance locus bcg.	the mouse chromosome 1 locus bcg determines natural resistance/susceptibility of inbred mouse strains to infection with antigenically unrelated intracellular parasites, including several mycobacterium species, salmonella typhimurium, and leishmania donovani. in our effort to clone bcg, we have constructed a high-resolution genetic linkage map in the vicinity of the gene. we have developed eight new highly polymorphic markers (simple sequence repeats) corresponding to cloned genes (vil, inha, des ...	1993	8100801
molecular characterization of the ldmdr1 multidrug resistance gene from leishmania donovani.	the ldmdr1 gene that confers resistance to multiple structurally dissimilar hydrophobic drugs in leishmania donovani has been isolated within a 5.4-kb xmai fragment from a genomic library of l. donovani dna and its protein coding region sequenced. the longest open reading frame within ldmdr1 encodes a 146.5-kda protein of 1341 amino acids, designated ldmdr1. the primary structure and predicted membrane topology of ldmdr1 indicates that it is a member of the p-glycoprotein superfamily with the gr ...	1993	8103567
measurement of serum antibodies against native leishmania gp63 distinguishes between ongoing and previous l. donovani infection.	an enzyme-linked immunosorbent assay (elisa) using native gp63 for detection of serum antibodies to leishmania was evaluated. the test identified antibodies in sera from 16 of 16 visceral leishmaniasis (vl) patients and 9 of 12 sera from patients with trypanosoma brucei infection. in comparison, sera from 80 danish controls and 40 control donors from a malaria endemic area of ghana without known exposure to leishmania were negative, as were sera from 12 kenyan malaria patients and 9 schistosomia ...	1993	8105816
immunogold labeling and cerium cytochemistry of the enzyme ecto-5'-nucleotidase in promastigote forms of leishmania species.	we have applied both enzyme cytochemistry and immunological labeling techniques to characterize the enzyme 5'-nucleotidase (5'-nase), at the ultrastructural level, in promastigote forms of four leishmania species: leishmania amazonensis, leishmania mexicana, leishmania donovani and leishmania chagasi. the cerium phosphate staining was localized at the surface of the cell body, the flagellum and the flagellar pocket membranes of all the parasites studied. the immunogold labelling technique confir ...	1993	8107602
calcium dependent thiol protease caldonopain and its specific endogenous inhibitor in leishmania donovani.	a calcium dependent proteolytic enzyme was detected in the lysed promastigotes of leishmania donovani, the causative agent of kala-azar. the protease was able to hydrolyse an added substrate, azocasein and showed high affinity for calcium. rate of azocasein digestion was primarily slow but boosted up after eight hours. it was not inactivated when heated at 55 degrees c for 15 min at ph 7.4. sulfhydryl reagents significantly reduced the enzymic activity but trypsin-like protease inhibitors hardly ...	1993	8107694
licochalcone a, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of leishmania.	licochalcone a, an oxygenated chalcone isolated from the roots of chinese licorice plant, inhibited the growth of both leishmania major and leishmania donovani promastigotes and amastigotes. the structure of the licochalcone a was established by mass and nuclear magnetic resonance spectroscopies and by synthesis, and its purity was verified by high-pressure liquid chromatography. the 50% inhibition of growth of logarithmic- and stationary-phase promastigotes of l. major, as measured by [3h]thymi ...	1993	8109916
antileishmanial activities of mycotoxin mt 81 and its derivatives.		1993	8112762
protein tyrosine phosphatase activity in leishmania donovani.	l. donovani promastigotes were grown to late-log and 3-day stationary phase to determine the level of protein tyrosine phosphatase activity in crude extracts and in fractions following gel filtration column chromatography. over 90% of the activity was soluble in a low salt extraction buffer in both phases of growth. several peaks of activity were resolved following gel filtration of the crude extracts indicating that multiple tyrosine phosphatases are present in these cells. tyrosine phosphatase ...	1993	7935346
immunostimulant activity of a novel lipopeptide and its protective action against leishmania donovani.	novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (dth) response to ovalbumin in guinea pigs. lipopeptide 86/450 also stimulated antibody and dth responses in albino mice and enhanced nonspecifically macrophage migration index (mmi), phagocytic activity and incorporation of [14c] glucosamine in peritoneal macrophages of the treated animals. proliferative response of splenocytes from lipopeptide 86/450 treated animals was sig ...	1993	8301018
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 ...	1993	7507902
leishmania donovani: isolation of a concanavalin-a specific antigen and its evaluation for serodiagnosis of visceral leishmaniasis.	a glycoconjugate antigen of 27-39 kda was isolated from a cell-free extract of leishmania donovani by affinity chromatography using a concanavalin-a sepharose-4b column and eluted with 0.5 m alpha-methylmannoside. the antigen was recognized specifically by sera from kala-azar (visceral leishmaniasis) patients and did not react with sera from tuberculosis, leprosy or malaria patients. the antigen may therefore be useful in developing a serodiagnostic assay for visceral leishmaniasis.	1992	1281399
western blot analysis of antibodies to leishmania infantum antigens: potential of the 14-kd and 16-kd antigens for diagnosis and epidemiologic purposes.	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-l. infantum antibodies in patients with visceral leishmaniasis (including patients with acquired immunodeficiency syndrome [aids]) and in healthy subjects living in an endemic area. sera from patients with visceral leishmaniasis recognized numerous antigens that had a molecular mass range of 12-120 kd. the 14-, 16- ...	1992	1281966
the isolation and cultivation of leishmania infantum from apparently normal skin of visceral leishmaniasis patients in northern pakistan.		1992	1287916
incrimination of phlebotomus (larroussius) orientalis as a vector of visceral leishmaniasis in western upper nile province, southern sudan.		1992	1287918
axenic cultivation of amastigotes of leishmania donovani and leishmania major and their infectivity.	two clones of promastigotes, one of leishmania donovani and one of l. major, and an uncloned stock of l. major were axenically transformed to heat-shock amastigotes, at 35 and 37 degrees c, respectively. of the four different culture media tested, a relatively cheap, liquid medium, rblm, was found to be the best, both for the transformation of the promastigotes and the serial, axenic cultivation of the amastigotes. in an experiment of 30 days duration, serial cultivation, in an atmosphere with 5 ...	1992	1288430
metabolic n-hydroxylation of diminazene in vitro.	the two n-hydroxylated derivatives (amide oximes) and the corresponding amides of the trypanocidal diamidine diminazene (berenil, cas 536-71-0) have been synthesized. these reference compounds made it possible to investigate the in vitro metabolism of the amidine functionalities of diminazene. diminazene metabolites were detected for the first time, in the form of the corresponding mono- and di(amide oxime), after incubation with 12000 g supernatants from rabbit liver homogenates and careful wor ...	1992	1288516
the activity of hydroxynaphthoquinones against leishmania donovani.	the hydroxynaphthoquinones, buparvaquone, 250c80 and 56w82, showed high activity in vitro against leishmania donovani amastigotes in mouse peritoneal macrophages, with ed50 values of 0.05, 2.95 and 13.82 microm, respectively. fourteen other hydroxynaphthoquinones were tested, of which only 566c80 and 608c86 showed significant activity against amastigotes. buparvaquone, 250c80 and 56w82 were also highly-active against cultured promastigotes. in a balb/c mouse model, treatment with 100 mg/kg/day f ...	1992	1289357
[phlebotomus perniciosus newstead, 1911 naturally infected by promastigotes in the region of nice (france)].	the authors report the results of investigations in nice from july, 16 to august, 3, 1991. the 2,098 phlebotomes captured represent three species: phlebotomus perniciosus, phlebotomus ariasi and sergentomyia minuta. two species: p. perniciosus and p. ariasi are infected with promastigotes. about 4% of dissected females are parasited. this is the first description in france of p. perniciosus infected.	1992	1292799