Publications

liposomes and nanoparticles as vehicles for antibiotics.	colloidal drug carriers such as liposomes and nanoparticles are easily taken up by phagocytic cells and accumulate in the organs of the reticuloendothelial system. therefore, they hold promise as carriers for the treatment of intracellular infections with antibiotics that would normally not find easy access to intracellular sites. consequently, in in vitro and in vivo experiments the therapeutic efficacy of substances such as amphotericin b, dihydrostreptomycin, amikacin, ampicillin, stiboglucon ...	1991	1879957
immunoblot analysis of the humoral immune response to leishmania donovani infantum polypeptides in human visceral leishmaniasis.	using the immunoblot technique, we have compared the reactions of leishmania donovani infantum polypeptides with the immunoglobulin g of human sera from patients with parasitologically proven l. d. infantum infection, with suspected visceral leishmaniasis, and with other leishmaniases, protozoiases, helminthiases, and fungal or bacterial diseases. a 94-kda component reacted with all l. d. infantum-infected sera and with 75% of sera from patients with clinical and serological but no parasitologic ...	1991	1885738
isoenzyme characterization of leishmania from man, dog and sandflies in the maltese islands.	as a part of a general survey on leishmaniases and sandflies of the maltese islands, 22 leishmania stocks were isolated from human visceral (1) and cutaneous (1) cases, dogs (16) and sandflies (4). they were characterized by the analysis of 15 enzymes. the commonest mediterranean l. infantum zymodeme, mon 1, was found to cause human and canine visceral leishmaniasis; l. infantum mon 78, which has so far been isolated only in malta, was the agent of human cutaneous leishmaniasis. both zymodemes w ...	1991	1887474
direct enzyme-linked immunosorbent assay: a simple immunoassay using leishmania donovani promastigote for diagnosis of kala-azar.	for immunodiagnosis of kala-azar enzyme-linked immunosorbent assay (elisa) and immunofluorescence testing (ifat) are commonly used. in ifat, whole parasite antigen and in elisa the soluble antigen have been used. preparation of elisa antigen has certain inherent difficulties. we have developed a simple, specific, and quantitative immunoassay, "direct elisa" for diagnosis of kala-azar. intact formalinized promastigote suspension has been used to combine with the antibodies of the patient sera. th ...	1991	1890544
synthesis and biological activity of sinefungin analogues.	a series of nucleosides (2-4) that derive from adenosine by chain extension at the 5'-end have been synthesized starting from the known phosphonate 7. the latter was first combined with 4-pentenal to give 8, which underwent chemical manipulations to provide triacetate 11, which was found suitable for the adenylation step. further transformations, among them the hofmann degradation of the amide group of compound 13, and final deprotection gave nucleosides 2-4. they were considered as analogues of ...	1991	1895298
saponins of the ivy plant, hedera helix, and their leishmanicidic activity.	antileishmanial activity is reported for the first time for saponins of ivy, hedera helix l., in vitro on promastigote and amastigote forms of leishmania infantum and leishmania tropica. the compounds tested were an extract containing 60% of saponic complex (cs 60), the bidesmosides hederasaponin b, c, and d (saponin k10), their corresponding monodesmosides alpha-, beta-, and delta-hederin, and hederagenin. cs 60 and bidesmosides have shown no effect. monodesmosides were found to be as effective ...	1991	1896525
response to chemotherapy in experimental visceral leishmaniasis: t cell-dependent but interferon-gamma- and interleukin-2-independent.	the capacity of leishmania donovani-infected balb/c mice to respond to conventional chemotherapy with pentavalent antimony (sb) is t cell dependent and, in nude mice, can be restored in part by treatment with the t cell lymphokines, interferon-gamma (ifn-gamma) or interleukin-2 (il-2). to document the presumed role of endogenous ifn-gamma and il-2 in responsiveness to antileishmanial chemotherapy in the t cell-intact host, l. donovani-infected euthymic balb/c mice were treated with anti-ifn-gamm ...	1991	1899875
differential production of th1- and th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis.	recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of cd4+ t cell subsets in determining the outcome of infectious disease. in leishmania major infections, cure vs progressive disease correlates with the expansion of th1-like or th2-like cd4+ populations, respectively. we have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by l. donovani. splenic lymphocy ...	1991	1901883
cell-free biosynthesis of lipophosphoglycan from leishmania donovani. characterization of microsomal galactosyltransferase and mannosyltransferase activities.	incubation of microsomal preparations from leishmania donovani parasites with udp-[3h]galactose or gdp-[14c]mannose resulted in incorporation of radiolabel into an endogenous product that exhibited the chemical and chromatographic characteristics of the parasite's major surface glycoconjugate, lipophosphoglycan. the [3h]galactose- or [14c]mannose-labeled product was (i) cleaved by phosphatidylinositol-specific phospholipase c; (ii) deaminated by nitrous acid; and (iii) degraded into radioactive, ...	1991	1904057
role of ca2+ ion on leishmania-macrophage attachment.	leishmania donovani, the etiological agent for the disease visceral leishmaniasis, attach themselves to the macrophages for initiation of the disease. the attachment process has been found to be regulated by ca2+ ions. verapamil, a ca(2+)-channel blocker inhibits leishmania-macrophage attachment. the inhibitory effect is increased with time. nifedipine, another ca(2+)-channel blocker exhibits the same effect. the attachment process is stimulated by ca(2+)-ionophore alone. the inhibitory effects ...	1991	1904982
stable dna transfection of a wide range of trypanosomatids.	we have shown that the leishmania major transfection vector pr-neo (or derivatives thereof) can be introduced and stably maintained in four species complexes of pathogenic leishmania (l. tropica, l. mexicana, l. donovani, l. braziliensis), and the genera endotrypanum and crithidia; transfection of trypanosoma cruzi or trypanosoma brucei was not successful. quantitative plating assays showed that the transfection efficiencies were high in l. major and leishmania amazonensis (5x10(-5)/cell) and ab ...	1991	1906580
human recombinant migration inhibitory factor activates human macrophages to kill leishmania donovani.	a recombinant form of the first lymphokine to be discovered, migration inhibitory factor (rmif) was obtained from cos-1 cells transfected with a cdna library from a human t cell hybridoma (6). rmif has an amino acid sequence unrelated to that of any known protein. to learn more about the biology of mif, we tested its ability to effect the survival of leishmania donovani in macrophages. we found that rmif activates blood monocyte-derived macrophages in vitro to suppress the growth of and kill the ...	1991	1909737
leishmania donovani: long-term culture of axenic amastigotes at 37 degrees c.	l. donovani promastigotes were subjected to heat treatment yielding an axenic amastigote stage which was long-term cultured at 37 degrees c. no differences were observed between the growth rates of axenic amastigotes and promastigotes. flow cytometry-derived dna histograms of axenic amastigotes and promastigotes were typical of exponentially growing cell populations. moreover, axenic amastigotes were metabolically active as evidenced by the release of an immunoprecipitable extracellular acid pho ...	1991	1915747
leishmania donovani: characteristics of adenosine and inosine transporters in promastigotes of two different strains.	the nucleoside transport characteristics of two strains of leishmania donovani promastigotes were studied. strain s1, growing in fully defined medium, and strain s2 (mhom/et/67/ha3) both transported adenosine and inosine, but only strain s1 transported uridine and thymidine. competition studies in the presence of 100 microm of unlabeled adenosine, inosine, guanosine, 2'-deoxyadenosine, tubercidin, formycin b, 3'-deoxyinosine as well as uridine, thymidine and cytidine, with either 1 microm [3h]ad ...	1991	1915751
leishmania donovani: use of two different, commercially available, chemically defined media for the continuous in vitro cultivation of promastigotes.		1991	1915754
a seroepidemiological survey on leishmania infantum infection.	findings from a seroepidemiological survey of leishmania infantum (li) infection are presented. among residents in the province of rome, 2.7% (4.4% in the city of rome and 1% in the suburbs) of 374 adults were positive for specific li antibodies in indirect haemoagglutination studies. among 217 adult residents of caltanissetta province (sicily), 4.1% were positive for li antibodies (4.2% in caltanissetta city and 4% in the suburbs). serological tests for li antibodies were also carried out on st ...	1991	1915791
gastric localization of systemic leishmaniasis in a patient with aids.		1991	1916693
immunotherapy of murine visceral leishmaniasis with murine recombinant interferon-gamma and mtp-pe encapsulated in liposomes.	the efficiency of immunotherapy with murine recombinant interferon-gamma (rifn-gamma) in mouse visceral leishmaniasis caused by leishmania donovani was examined. to avoid the side effects encountered after the in vivo administration of high dosages of free ifn-gamma, this lymphokine and muramyltripeptide (mtp-pe) were encapsulated into multilamellar liposomes. we established that a combination of 5 x 10(3) u of ifn-gamma and 6 micrograms of mtp-pe, encapsulated in liposomes and given i.v. in c56 ...	1991	1919076
[autoantibodies and leishmania infection].		1991	1921552
long-range restriction maps of size-variable homologous chromosomes in leishmania infantum.	in order to clarify the interpretation of molecular karyotype polymorphisms in leishmania, the three smallest chromosomes from five cloned strains of leishmania infantum were identified by chromosome-specific anonymous dna probes. the presence in the same clone of homologous chromosomes of a different size was demonstrated. the chromosome size polymorphism appeared even more dramatic, with size variations affecting up to 20% of the chromosome, and the two smallest bands in one strain being equiv ...	1991	1922200
secreted acid phosphatase of leishmania mexicana: a filamentous phosphoglycoprotein polymer.	in the promastigote, or insect stage, most species of the parasitic protozoan leishmania secrete an acid phosphatase. the enzyme purified from the culture medium of leishmania mexicana is shown to be a complex [13.3% (wt/wt) protein, 74.4% (wt/wt) carbohydrate, and 12.3% (wt/wt) phosphate] composed of a predominant phosphorylated glycoprotein with a relative molecular mass of 100 kda and noncovalently associated high molecular mass (proteo)phosphoglycans. electron microscopy discloses long filam ...	1991	1924338
concurrent infection with leishmania donovani and leishmania major in a kenyan patient: clinical description and parasite characterization.	leishmania isolates aspirated a few months apart from the spleen of an indigenous adult male kala-azar patient from baringo district, kenya, were biochemically characterized and compared. the patient lived within a dual focus of l. donovani kalazar and l. major cutaneous leishmaniasis. a primary leishmania isolate from splenic aspirates was cryopreserved (nlb-294). the patient was treated with sodium stibogluconate for kala-azar and discharged. three months later, he had clinical relapse and ret ...	1991	1928563
suppression of leishmania donovani by oral administration of a bis(benzyl)polyamine analog.	we reported previously that intraperitoneal administration of a bis(benzyl)polyamine analog, mdl 27,695, suppressed both pentavalent antimony (sbv)-susceptible and -resistant leishmania donovani in vivo. the present studies were performed to optimize parasite suppression by parenteral administration and to evaluate the efficacy of oral treatment with mdl 27,695. l. donovani infections in balb/c mice were suppressed greater than 99% after intraperitoneal dosing for 20 days with a total dose of 15 ...	1991	1929300
generation of cytokines in human visceral leishmaniasis: dissociation of endogenous tnf-alpha and il-1 beta production.	the role of tnf-alpha in visceral leishmaniasis is ambivalent, the eventual outcome of this infection, cure or generalization, being determined by the relative amounts of cytokines produced in vivo. since release, by monocytes/macrophages, of tnf-alpha and interleukins 1 beta (il-1 beta) and il-6 is important in both the induction and effector phases of the immune responses, these mediators were determined in sera and cell culture supernatants of seventeen l. donovani infected patients in brazil ...	1991	1937561
development of leishmania donovani in phlebotomus argentipes & ph. papatasi fed on kala-azar patients in bihar.	a total of 258 laboratory bred ph. argentipes was fed on untreated parasitologically confirmed kala-azar patients. successful development of parasites was noted in 0.54 per cent ph. argentipes fed during the day and 5.33 per cent fed during the night. however, none of the 245 laboratory bred ph. papatasi fed on the same patients, was found positive for successful development of l. donovani in the foregut.	1991	1937591
epidemiology of kala-azar in rural bihar (india) using village as a component unit of study.	it is assumed that some features like intra-macrophage habitat of the leishmania parasites, rare availability of infected macrophages in peripheral blood for vector sandflies to suck in, short flight range of sandflies, non-availability of an animal reservoir encountered in visceral leishmaniasis indicate slow and limited transmission potential and even so epidemics occur every 15 to 20 yr. to verify if these assumptions are true, the natural history of kala-azar was studied, using an endemic vi ...	1991	1937592
role of inorganic nitrogen oxides and tumor necrosis factor alpha in killing leishmania donovani amastigotes in gamma interferon-lipopolysaccharide-activated macrophages from lshs and lshr congenic mouse strains.	the capacity of mature bone-marrow-derived macrophages and resident peritoneal macrophages from lshr versus lshs congenic mice to kill intracellular leishmania donovani amastigotes when activated by recombinant gamma interferon-lipopolysaccharide (rifn-gamma-lps) was examined. ifn-gamma alone in doses up to 100 u/ml was unable to activate macrophages to kill l. donovani amastigotes in vitro; lps was a necessary secondary stimulus. similarly, lps alone in doses up to 100 ng/ml produced no leishma ...	1991	1937752
gamma interferon-activated human macrophages and toxoplasma gondii, chlamydia psittaci, and leishmania donovani: antimicrobial role of limiting intracellular iron.	iron-saturated transferrin did not reverse the intracellular killing or inhibition of toxoplasma gondii, chlamydia psittaci, or leishmania donovani by gamma interferon-activated human macrophages. deferoxamine, an iron chelator, also did not impair replication within unstimulated macrophages. limiting the availability of intracellular iron is an unlikely mechanism in human macrophage activity against these three diverse pathogens.	1991	1937829
serodiagnosis of indian kala-azar: evaluation of ifa, elisa and ciep tests.	the sensitivity and specificity of three serological tests viz. indirect immunofluorescent antibody test (ifat), enzyme linked immunosorbent assay (elisa) and counterimmunoelectrophoresis (ciep) for the diagnosis of indian kala-azar were evaluated. of the 209 patients in whom leishmania donovani parasite could be demonstrated in bone marrow, 207 (99.04 per cent) could be diagnosed with ifat, 203 (96.6 per cent) with ciep and 208 (99.5 per cent) with elisa. none of these serological tests was pos ...	1991	1940218
leishmanin skin test in clinical and subclinical kala-azar cases.	leishmanin skin test was done on 25 active kala-azar (ka) patients, 41 healthy persons residing with ka patients and 14 treated cases of ka. all active cases of ka were leishmanin test negative. nine out of 41 (21.9 per cent) healthy household members gave positive reaction to leishmanin antigen. these persons were previously exposed to leishmania donovani infection which was overcome by developing cell mediated immunity. the infection in these persons remained subclinical or asymptomatic. this ...	1991	1940219
the leishmania donovani lipophosphoglycan t lymphocyte-reactive component is a tightly associated protein complex.	lymphocytes from mice immunized with leishmania donovani (lpg) were specifically stimulated to proliferate in vitro by purified lpg or its delipidated congener, phosphoglycan. the response was dose dependent and required prior immunization with either lpg or phosphoglycan. proliferation was eliminated by specific depletion of thy-1+ cells with antisera and c and the proliferating t cell subset was shown to be cd4+cd8-. tests of various lpg fragments indicated that the t cell stimulation was asso ...	1991	1940354
gelatinous transformation of the bone marrow and leishmania donovani infection.	to the best of our knowledge, gelatinous transformation of the marrow has not been described in association with leishmania donovani infection. here we report one such case.	1991	1942208
nucleotide sequence of the leishmania donovani medrna gene.		1991	1945857
a leishmania infantum enzymatic variant, causative agent of cutaneous leishmaniasis in north tunisia.		1991	1949140
evidence of subjects sensitized to leishmania infantum on the french mediterranean coast: differences in gamma interferon production between this population and visceral leishmaniasis patients.	the marseilles region is an endemic area for visceral mediterranean leishmaniasis, but although the number of dog cases, the parasite's main host, is very high, only a few people develop the disease. we looked for sensitized healthy subjects among 25 healthy individuals living in this area by studying their in vitro lymphoproliferative response to leishmania infantum antigens and gamma interferon synthesis. we found that 65% of tested subjects were sensitized against l. infantum. we compared the ...	1991	1956699
an experimental model for canine visceral leishmaniasis.	seven mixed-breed dogs were challenged with either promastigotes or amastigotes of leishmania donovani infantum strains recently isolated from naturally infected dogs. different routes and numbers of parasites were utilized and each dog was monitored for at least 1 year post-infection. anti-parasite specific antibody levels were measured by enzyme-linked immunosorbence, immunofluorescence, crossed-immune electrophoresis and western blotting on crude antigen. western blotting on two pure parasite ...	1991	1956700
a simple method for cryopreservation of leishmania donovani promastigotes.	cryopreservation of promastigotes of l. donovani in nnn and tobie's media was attempted. the media containing the promastigotes were kept directly at -80 degrees c. the cryopreserved media were examined for living promastigotes after 9, 12, 15, 20, 23, 26, 29, 32, 42, 56, 65 and 126 days after the culture tubes were brought directly from -80 degrees c to room temperature and examined after 30 min. all tubes showed living promastigotes which were used for further growth with no apparent morpholog ...	1991	1959955
inhibition of human seminal fluid and leishmania donovani phosphatases by molybdate heteropolyanions.	inhibition of a tartrate-resistant acid phosphatase (acp) from leishmania donovani and the tartrate-sensitive acp from human seminal fluid (prostatic acp) was examined using a series of 13 molybdate-containing heteropolyanions. the heteropolyanions were divided into four groups based on the number of molybdenum atoms they contain: group i, mo4; group ii, mo6-8; group iii, mo12; group iv, mo18. two of the four groups, those consisting of compounds that contain either an mo4 unit or an mo18 unit w ...	1991	1995614
the purine-2-deoxyribonucleosidase from crithidia luciliae. purification and trans-n-deoxyribosylase activity.	crude extracts of crithidia luciliae catalysed a deoxyribosyl transfer from purine deoxynucleosides to free purine bases. fractionation of a 0-80% (nh4)2so4 fraction from c. luciliae on deae-cellulose resulted in the separation of three nucleosidase activities. two of these were ribonucleosidases, one specific for inosine, uridine and xanthosine and the other for inosine and guanosine, whereas the third activity was specific for purine deoxyribonucleosides. this pattern is similar to that found ...	1991	2026165
leishmania donovani: characterization of a 38-kda membrane protein that cross-reacts with the mammalian g-protein transducin.	we investigated the presence in leishmania donovani promastigotes of proteins with homology to the g-proteins known to mediate signal transduction in other organisms. [alpha 32p]gtp binding experiments revealed the presence in the promastigote membrane of gtp-binding sites with high affinity and specificity. experiments with antisera directed against mammalian g-proteins showed that the promastigotes possess a 38-kda protein (p38) which strongly reacts with an antiserum directed against a decape ...	1991	2026215
a rapid and simple diagnostic test for active visceral leishmaniasis.	we have developed an immunodot assay for the serodiagnosis of active visceral leishmaniasis (avl) which utilizes protein a colloidal gold as the visualizing agent. the test is simple, requires few reagents, and can be completed in two hours. it is sensitive and specific for active visceral leishmaniasis, and generally correlates with the elisa. either whole blood or sera in minute quantities may be used as test antibody. in addition, the use of the protein a gold immunodot is shown to detect ant ...	1991	2035748
antigenic specificity of the 72-kilodalton major surface glycoprotein of leishmania braziliensis braziliensis.	we examined the expression and the antigenicity of the major surface polypeptides of leishmania braziliensis braziliensis and leishmania donovani chagasi, parasites which commonly coexist in the same endemic areas of bolivia. sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles from surface-iodinated promastigotes showed the presence of a unique iodinatable polypeptide of 72 kda on the l. b. braziliensis surface and of two major components of 65 and 50 kda exposed at the su ...	1991	2037677
metacyclogenesis of leishmania spp: species-specific in vitro transformation, complement resistance, and cell surface carbohydrate and protein profiles.	metacyclic (stationary) and logarithmic (log) forms of promastigotes of leishmania donovani and leishmania major were characterized in several ways. the highly active metacyclic forms were larger with more protein and less carbohydrate. the flagellum increased in length 2.4 times in l. major as compared to 1.8 times in l. donovani. resistance to complement-mediated lysis by normal human serum of in vitro grown leishmania promastigotes was related to the species, the growth phase in culture, and ...	1991	2040953
hydrolysis of carcinogen--dna adducts by three classes of deoxyribonucleosidase to their corresponding bases.	we have investigated three different enzymes, each of which splits the glycosidic bonds of normal deoxyribonucleosides, for their ability to cleave acid-sensitive carcinogen-dna adducts: leishmania donovani purine deoxyribonucleosidase; lactobacillus helveticus trans-n-deoxyribosylase; and purine nucleoside phosphorylase. twenty-eight substrates were assayed using one or more of the enzymes, monitoring free base formation by reverse-phase hplc and a diode array detector. products were characteri ...	1991	2044194
leishmania donovani in hamsters: stimulation of non-specific resistance by some novel glycopeptides and impact on therapeutic efficacy.	several glycopeptides structurally related to muramyl dipeptide (mdp) have been synthesized and evaluated for their ability to stimulate the non-specific resistance of hamsters against l. donovani infection. these compounds have been named cdri compounds. the synthetic procedure used for compounds 86/448 and 84/212 is described. mdp and its synthetic congeners were administered as immunostimulants at a prophylactic dose of 3 mg/kg at two weeks interval. the challenge infection (1 x 10(7) amastig ...	1991	2044704
renal involvement in canine leishmaniasis. a light-microscopic, immunohistochemical and electron-microscopic study.	in a prospective survey in the isle of elba, 413 dogs affected by naturally acquired leishmania infantum infection were identified out of a controlled population of 1,500 resident mongrel dogs. in all the 34 randomly selected dogs of different breed, age, and duration of disease, the presence of glomerular lesions which defined mainly two categories of glomerulonephritis (gn) was observed. the first group was characterized by mesangial-cell proliferation either with focal features (11 dogs), or ...	1991	2046828
promastigote infectivity in leishmania infantum.	different clones and subpopulations of clones of leishmania infantum were analyzed for their infective potential in vitro. infectivity for macrophage-like cells (p388d1) and the response to a challenge with normal human serum enabled a clear differentiation between infective and non/low-infective populations. the results were confirmed by determination of parasite burdens in the spleens of infected golden hamsters. long-term cultivation assays in vitro were used to test the influence of differen ...	1991	2047365
involvement of membrane-associated tnf in the killing of leishmania donovani parasites by macrophages.	a killing process is described where macrophages destroy 3h thymidine prelabeled leishmania parasites during the process of phagocytosis. this phagocytosis associated killing may represent a first line of defense and reduces drastically the amount of parasites homing in the macrophages. treatment of the macrophages with anti-tnf antibody inhibited the phagocytosis associated killing. soluble tnf had no effect on leishmania parasites. macrophages performed the killing process in the complete abse ...	1991	2049029
antigen processing and presentation: modelling with leishmania.	most foreign antigens are "processed" by apc into a form in which they can bind mhc molecules and be recognised by the tcr. functional and immuno-gold labelling studies have been used to determine the putative sites of mhc-ag interaction following uptake of leishmania donovani into a phagolysosome. during infection with this parasite in vivo, upregulation of class ii occurs. based on studies using scid mice, nk cells appear to contribute little to this process. during chronic infection, however, ...	1991	2049030
chemostat cultures of leishmania donovani promastigotes and trypanosoma brucei procyclic trypomastigotes.		1991	2052036
synthesis and antileishmanial activity of some 1- or 2-(dihydroxyalkyl) and 3-(dihydroxyalkoxy)pyrazolo [3,4-d] pyrimidines.	several new derivatives of 4-amino-, 4,6-diamino- and 4-hydrazino-[3,4-d]pyrimidine dihydroxyalkyl substituted in the 1 or 2 positions, or dihydroxyalkoxy substituted in the 3 position have been synthesized. some of these compounds were evaluated for their activity against leishmania infantum in mice. the highest degree of antileishmanial activity was displayed by the 4-amino-1-(dihydroxyalkyl) derivatives which yielded parasite inhibition values nearly comparable with that of glucantime in a st ...	1991	2054043
use of in vitro method to assess different brands of anti-leishmanial drugs.	reports in the literature indicate the use of animal models for testing newer anti-leishmanial drugs in vivo. however, in certain established cell lines and macrophages in vitro models have the advantage over the in vivo system of simplicity and speed with which the results can be obtained. a simple in vitro system using peritoneal exudate macrophages of balb/c mice infected with leishmania donovani promastigotes has been tested for its use in determining the efficacy of several new drugs. two w ...	1991	2056963
[application of monoclonal antibodies against leishmania donovani, ii. detection of circulating antigen in sera of visceral leishmaniasis before and after treatment].	monoclonal antibodies l12f7 against the target antigen of l. donovani promastigotes were used for the detection of circulating antigen (cag) from sera of visceral leishmaniasis patients. the results showed that of 118 serum samples from visceral leishmaniasis tested, 105 were positive (88.9%). 55 normal serum samples were negative. no cross reaction with sera from patients with vivax malaria, schistosomiasis, leprosy and brucellosis, was found. the authors suggested that this assay may be used a ...	1991	2065447
visceral leishmaniasis in southern sudan.	reports made by médecins sans frontières in khartoum on an outbreak of visceral leishmaniasis among displaced people from the western upper nile prompted an investigation at ler hospital, the second largest in the region. in a 10 d period during april 1989, 100 persons with visceral leishmaniasis were identified. of these, 82% were men; 67% were aged 20 to 39 years. except for the absence of ulcerated skin lesions, the clinical features corresponded to those traditionally described in the sudan. ...	1991	2068759
lipophosphoglycan masks recognition of the leishmania donovani promastigote surface by human kala-azar serum.	markedly elevated titers of anti-leishmanial antibodies are a hallmark of kala-azar. we investigated the role played by the lipophosphoglycan (lpg) in determining the reactivity of kala-azar serum with the surface of leishmania donovani promastigotes. in assays performed with liver parasites there was negligible agglutination or fluorescent staining of lpg-bearing promastigotes by kala-azar serum, but strong reactivity in both assays with the use of an l. donovani mutant strain (r2d2) that lacks ...	1991	2071901
leishmania donovani lipophosphoglycan selectively inhibits signal transduction in macrophages.	the effect of purified lipophosphoglycan (lpg) of leishmania donovani on signal transduction and gene expression in murine bone marrow-derived macrophages was investigated. lpg stimulated the rapid expression of both c-fos and tnf genes within 30 min after exposure, suggesting that the interaction of lpg with its receptor stimulated a specific signal transduction pathway. macrophages pretreated with lpg for 3 h became unresponsive to subsequent stimulation with lps and the activators of protein ...	1991	1707920
plasma membrane of leishmania donovani.	plasma membrane of leishmania donovani promastigotes was isolated by disrupting the cells in dounce homogenizer and found to be having two fractions m1 and m2. chemical analysis of the two membrane fractions revealed that m1 had less rna content and high sterol-phospholipid molar ratio than m2. m1 was also rich in membrane marker enzymes, e.g., 5' nucleotidase and acid phosphatase. glucose-6-phosphatase, the marker enzyme of endoplasmic reticulum was higher in m2 fraction. the electron micrograp ...	1991	1717541
glycoinositol phospholipids from american leishmania and trypanosoma spp: partial characterization of the glycan cores and the human humoral immune response to them.	the glycoinositol phospholipid (gipl) profiles of american leishmania spp. (l. mexicana and l. braziliensis), leishmania donovani, and american trypanosoma spp. (t. cruzi and t. rangeli) were compared. the major gipls in these parasites include tetraglycosyl-, pentaglycosyl-, and hexaglycosylphosphatidylinositol. these were partially identified by their comigration by high-performance thin-layer chromatography with purified l. major gipls, gas-liquid chromatography of the monosaccharides release ...	1991	1719024
patients infected with leishmania donovani chagasi can have antibodies that recognize heat shock and acidic ribosomal proteins of trypanosoma cruzi.		1991	1723150
fluorescent antibody titres after recovery from visceral leishmaniasis.		1991	1723840
antileishmanial activity of hamycin: a polyene antibiotic.	hamycin, a polyene antibiotic, now in extensive use in the treatment of candidiasis and otomycosis, is found to be remarkably effective in killing leishmania donovani promastigotes in a liquid medium at a concentration of 0.2 microgram/ml. the glucose stimulated respiration and the uptake of 2-deoxy-d[u-14c]-glucose was inhibited in cells treated with the drug at a growth inhibitory concentration. an immediate release of isotopic glucose from preloaded cells could be demonstrated after exposure ...	1992	1731803
solution structure of the lipophosphoglycan of leishmania donovani.	the three-dimensional solution structure of the repeating -po4-6gal beta 1-4man alpha 1- disaccharide fragment of the lipophosphoglycan (lpg) derived from leishmania donovani has been determined by use of a combination of homo- and heteronuclear nmr spin coupling constant measurements together with restrained molecular mechanical minimization and molecular dynamics simulations. the fragment exists with limited mobility in solution about the gal beta 1-4man linkages, whereas in contrast a variety ...	1992	1731920
total synthesis of uracil analogues of sinefungin.	analogues of sinefungin derivatives 18a and 18b have been prepared from uridine and l-aspartic acid. the key step in the synthesis was the coupling of the radical derived from 14 with the unsaturated amide 13. the latter was produced from the known n-hydroxy-2-thiopyridone ester of l-aspartic acid 12 with the olefin 11. thus, the essential carbon skeleton was constructed by way of two radical coupling reactions. these analogues as well as 1a and 1b synthesized previously were tested for their an ...	1992	1732534
stimulus-response coupling in monocytes infected with leishmania. attenuation of calcium transients is related to defective agonist-induced accumulation of inositol phosphates.	mononuclear phagocytes infected with leishmania have been shown to have defective responses to extracellular stimuli. to investigate the potential relationship of these findings to alterations in calcium-dependent signaling pathways, the regulation of [ca2+]i concentrations was examined in human peripheral blood monocytes infected with amastigotes of leishmania donovani. measurements of [ca2+]i in fura-2-loaded monocytes were made at the single cell level by microfluorimetry. in normal monocytes ...	1992	1737935
leishmania donovani: antagonistic effect of s-adenosyl methionine on ultrastructural changes and growth inhibition induced by sinefungin.	sinefungin, an antifungal and antiparasitic nucleoside antibiotic, is a very potent antileishmanial agent in vitro and in vivo (bachrach et al. 1980, febs letters 121, 287-291; neal et al. 1985, transactions of the royal society of tropical medicine and hygiene 79, 85-122). it was previously shown that this molecule is a competitive inhibitor of adomet for transmethylases (paolantonacci et al. 1986, molecular and biochemical parasitology 21, 47-54; avila et al. 1987, molecular and biochemical pa ...	1992	1740179
effects of hypoxia and acute osmotic stress on intermediary metabolism in leishmania promastigotes.	this study further explores the effects of hypoxia and acute osmotic stress on intermediary metabolism of leishmania major and leishmania donovani. late log phase promastigotes were washed and incubated with glucose as the sole exogenous carbon source, and rates of glucose consumption and product formation were measured as a function of osmotic strength (610, 305, and 167 mosm kg-1) and po2 (95, 10, and 0% o2) in the presence of 5% co2. very mild hypoxia dramatically altered flux through the pat ...	1992	1741010
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
an indirect fluorescent antibody (ifa) test for the serodiagnosis of kala-azar.	the ifa test developed using leishmania donovani promastigote and amastigote antigens showed very high antibody titre in clinically and parasitologically established cases (30) of kala-azar, the geometrical mean reciprocal titre (gmrt) being 870 +/- 5.4 and 5370 +/- 1.80 respectively with the two antigens. in contrast, the gmrt of normal subjects of endemic area was only 12.44 +/- 6.19 and 80.35 +/- 1.66 respectively with these antigens. none of the subjects from non-endemic area suffering with ...	1992	1296950
indirect fluorescent antibody test in the serodiagnosis of visceral leishmaniasis in bangladesh.	indirect fluorescent antibody test (ifat) was found to be 100% sensitive and 100% specific when tested with sera from 125 parasitologically proven kala-azar patients, 100 healthy controls and 50 sick control cases. promastigotes of both l. enriettii and l. donovani as well as amastigotes of l. enriettii were found equally satisfactory as antigen for ifat. from the results of the present study, it is concluded that ifat is a highly sensitive as well as specific serological test for the diagnosis ...	1992	1303085
decreased sensitivity to meglumine antimoniate (glucantime) of leishmania infantum isolated from dogs after several courses of drug treatment.	although unresponsiveness to antimonial drugs in human leishmaniasis appears to be increasing, resistance to antimony in leishmania is not well documented. treatment of leishmaniasis in dogs, the domestic reservoir of l. infantum, with meglumine antimoniate (glucantime) is a common practice in many mediterranean countries. the dogs, however, remain highly infective to the phlebotomine vectors, even after several courses of treatment. a study was therefore carried out to test the comparative susc ...	1992	1304703
partial characterization of leishmania chagasi promastigote peptidases.		1992	1308575
interactions between immunity and chemotherapy in the treatment of the trypanosomiases and leishmaniases.	the immune status of a host infected with trypanosoma spp. or leishmania spp. can play an important role in successful chemotherapy. in animal models, treatment of african trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. an intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. similarly, an efficient cell-mediated immune responses is r ...	1992	1308932
anemia in experimental visceral leishmaniasis in hamsters.	experimental infection of hamsters with leishmania donovani caused visceral leishmaniasis in which hematological changes occurred. the infected hamsters were anemic and reticulocyte counts were high. no significant change in the serum erythropoietin level was noted. red cell membrane na(+)-k(+)-atpase and acetylcholinesterase activities increased. osmotic fragility of the erythrocytes from infected animals increased. the level of 2,3-diphosphoglycerate of the red cells increased with the degree ...	1992	1310731
multiple forms of chromosome i, ii and v in a restricted population of leishmania infantum contrasting with monomorphism in individual strains suggest haploidy or automixy.	we have resolved the molecular karyotypes of 22 leishmania infantum strains isolated between 1980 and 1988 in a restricted geographic area and belonging to zymodemes mon-11, -29 and -33. three strains were isolated from sandflies and all the others from human cutaneous lesions. a high degree of karyotypic homology is observed among these strains, contrasting with the highly polymorphic mon-1 strains isolated in the same area. we have analysed the time-dependent evolution of size variants of chro ...	1992	1311052
effect of bioamines on uptake of promastigotes of leishmania donovani by hamster peritoneal macrophages.	epinephrine and norepinephrine inhibit attachment of leishmania donovani promastigotes to cultured hamster peritoneal macrophages. the inhibition was significant at catecholamine concentrations of 10(-4) and 10(-5) m and occurred when they were added to the cell mixtures, or after pre-treatment of either macrophages or parasites. inhibition of attachment after pre-treatment was less marked than when the catecholamines were added to parasite-cell mixtures. similar results were obtained with dibut ...	1992	1313882
inhibition of expression of major histocompatibility complex class ii molecules in macrophages infected with leishmania donovani occurs at the level of gene transcription via a cyclic amp-independent mechanism.	among the important pleiotropic responses to gamma interferon (ifn-gamma) during the activation of macrophages (m phi) is the increased expression of major histocompatibility complex class ii genes. in the present study, infection with leishmania donovani was shown to inhibit in parallel the induction by ifn-gamma of h-2 a beta gene transcription, class ii mrna accumulation, and h-2 ad protein expression in cells of the murine macrophage cell line p388d1. treatment of p388d1 cells with either th ...	1992	1314226
the indian langur: preliminary report of a new nonhuman primate host for visceral leishmaniasis.	described are the susceptibility of the indian langur (presbytis entellus) to leishmania donovani and the consequent haematological and serum biochemical changes. the host response to antileishmanial chemotherapy and the immunological profile were also examined. each langur was inoculated intravenously with 1 x 10(8) amastigotes; a spleen biopsy carried out on day 35 post-infection (p.i.) revealed 10-13 l. donovani bodies per 500 cell nuclei, which reached a maximum of 130-195 at death (day 105- ...	1992	1314709
visceral leishmaniasis in the balb/c mouse: antimony tissue disposition and parasite suppression after the administration of free stibogluconate.	balb/c mice with an acute or chronic leishmania donovani infection were treated with intravenous sodium stibogluconate solution and the parasite suppressions determined in the spleen, liver and femur bone marrow. antimony concentrations in these and other tissues were determined by hydride generation-atomic absorption spectrophotometry. there was little correlation between tissue antimony levels one hour after treatment and drug efficacy. it would appear that the peak tissue antimony concentrati ...	1992	1319700
purification and properties of 3'-nucleotidase of leishmania donovani.	a surface membrane 3'-nucleotidase from leishmania donovani promastigotes has been purified to sds/page homogeneity. the enzyme has apparent subunit molecular mass of 38 kda, pi 5.8 and a broad ph optimum, 5.5-7.5. edta partially inhibited the enzyme activity, which was fully restored by co2+; mg2+, ca2+ or mn2+ had no effect on the activity. zncl2 or dithiothreitol at 1 mm was inhibitory at ph 7.5, but was without effect at ph 5.5, whereas at both ph values 5 mm of either compound inhibited the ...	1992	1322126
effect of sodium stibogluconate and pentamidine on in vitro multiplication of leishmania donovani in peritoneal macrophages from infected and drug-treated balb/c mice.	the in vitro antileishmanial activity of sodium stibogluconate (ssg) and pentamidine in peritoneal macrophages from three different groups of animals (i.e. normal, leishmania donovani-infected and drug-treated balb/c mice) is reported. peritoneal macrophages were extracted from all these animals and infected in vitro with l. donovani promastigotes. after 24 h, the infected macrophages (with amastigotes) were exposed to various concentrations of ssg (10-90 micrograms/ml) and pentamidine (0.1-5.0 ...	1992	1322361
defective stimulus-response coupling in human monocytes infected with leishmania donovani is associated with altered activation and translocation of protein kinase c.	stimulus-response coupling through protein kinase c (pkc) was shown to be defective in mononuclear phagocytes (m phi) infected with leishmania donovani. phorbol 12-myristate 13-acetate (pma)-induced oxidative burst activity and protein phosphorylation were markedly attenuated in infected m phi. these results were not explained either by quantitative alterations in amounts of pkc or by altered phorbol ester binding but were related to defects in kinase activation. analysis in vitro of the kinetic ...	1992	1323839
a shuttle vector which facilitates the expression of transfected genes in trypanosoma cruzi and leishmania.	a trypanosoma cruzi expression vector has been constructed using sequences derived from the flanking regions of the glyceraldehyde 3-phosphate dehydrogenase (ggapdh) genes. the neomycin phosphotransferase (neor) gene was incorporated as a selectable marker. using electroporation we have introduced this vector into both t. cruzi and leishmania cells and conferred g418 resistance. transformation is mediated by large extrachromosomal circular elements composed of head-to-tail tandem repeats of the ...	1992	1324472
an alignment of 17 deduced protein sequences from plant, fungi, and ciliate h(+)-atpase genes.	seventeen protein sequences of h(+)-atpases from plants (arabidopsis thaliana, nicotiana plumbaginifolia, lycopersicum esculentum), fungi (saccharomyces cerevisiae, schizosaccharomyces pombe, zygosaccharomyces rouxii, neuropora crassa, candida albicans), and a parasitic ciliate (leishmania donovani) have been aligned. twenty sequence fragments were identified which were conserved in h(+)-, na+/k(+)-, and ca++ plasma membrane-atpases. in addition, a total of 118 residues not located in these frag ...	1992	1328178
hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice.	hexadecylphosphocholine (he-pc), a novel phospholipid derivative, was tested against leishmania donovani and leishmania infantum, the causative agents of visceral leishmaniasis. in vitro, promastigotes were highly susceptible to he-pc; the 50% inhibitory concentrations were between 0.89 and 2.25 micrograms/ml for the different leishmanial strains. in vivo, a marked antileishmanial activity in infected balb/c mice could be demonstrated after oral administration of he-pc. whereas parasite suppress ...	1992	1329624
a kinetoplast dna probe diagnostic for leishmania infantum.	a 196 bp fragment of cloned kinetoplast (k) dna of leishmania infantum has been sequenced and shown to be diagnostic for this species. the dna from 10(4)-10(5) promastigotes was routinely and specifically detected in crude dot blots of whole cells lysed in situ, and there was no cross-hybridization with 10(6) cells of l. major, l. tropica, l. killicki, l. aethiopica, l. braziliensis and l. mexicana. a low degree of hybridization was found with l. donovani and l. chagasi. this probe will be of pa ...	1992	1331940
case for the panel. visceral leishmaniasis: i. unusual interrelationships between immature erythrocytes and both parasites and mature erythrocytes.		1992	1332239
antileishmanial drug targeting through glycosylated polymers specifically internalized by macrophage membrane lectins.	antileishmanial chemotherapy is hampered by the location of the parasite within the phagolysosome of the macrophage, which restricts the bioavailability of many potentially useful antileishmanial drugs. in this study, the possibility of using antileishmanial drugs targeted to the infected macrophages by means of a chemical linkage to a neutral mannose-substituted poly-l-lysine carrier molecule was explored. the study was performed in an in vitro model with leishmania donovani-infected murine mac ...	1992	1332591
rapid and sensitive detection of leishmania kinetoplast dna from spleen and blood samples of kala-azar patients.	following sequence analysis of a leishmania donovani kinetoplast dna (kdna) minicircle, we have developed synthetic oligonucleotides for use in the polymerase chain reaction (pcr). with these primers, we have amplified l. donovani kdna from splenic aspirates and blood samples taken from kala-azar patients. treatment of the samples for pcr requires only limited dna purification by lysis in sds, digestion with proteinase k, phenol extraction and ethanol precipitation of the resulting nucleic acid. ...	1992	1333582
kala azar--diagnostic dilemma.		1992	1334051
detection of circulating antigen by mcab-ast for evaluating the efficacy of anti-leishmania chemotherapy.	we have adapted the simple and sensitive mcab-antigen spot test (ast) for evaluating the efficacy of anti-leishmania chemotherapy. serum samples from 37 kala-azar patients were tested by mcab-ast, and all showed definite positive reactions before treatment. after a course of antimony treatment, 20 turned negative, coupled with the disappearance of clinical symptoms; another 12 cases responded with weak positivity accompanied by an improvement of clinical manifestations; and the remaining 5 antim ...	1992	1337480
[kala-azar acquired in croatia].	six weeks after his return from a two-week vacation in croatia a 52 year-old janitor from graz complained of loss of appetite, fever, headache, and a 9-kg weight loss. the spleen was enlarged to 16cm as measured by sonography. laboratory tests revealed pancytopenia, a prolonged prothrombin time and elevation of serum ldh concentration. while repeated bone marrow biopsy showed no signs of leishmaniasis, high antibody titers against leishmania antigen led to the diagnosis of kala-azar. the indirec ...	1992	1337639
amplification and molecular cloning of the ornithine decarboxylase gene of leishmania donovani.	a strain of leishmania donovani has been described that is resistant to dl-alpha-difluoromethylornithine (dfmo), an inhibitor of ornithine decarboxylase (od-case) activity, and contains 15-fold greater amounts of odcase activity and protein than the wild type strain from which it was derived (coons, t., hanson, s., bitonti, a.j., mccann, p.p., and ullman, b. (1990) mol. biochem. pharmacol. 39, 77-90). from this mutant strain, another odcase overproducing l. donovani strain, dfmo16, was generated ...	1992	1339439
lymphatic leishmaniasis.		1992	1341896