Publications

synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin.	fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction of fluoroalkyl alcohols with dihydroartemisinin by different methods (bf3,et2o or tmscl catalysis or mitsunobu reaction). ethers 4a-d derived from primary fluoroalkyl alcohols were obtained in moderate to good yields by these methods. ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols and phenol using the mitsunobu reaction. although in vitro antimalarial activities of ethers toward plasm ...	1998	9767645
bisquinolines. 2. antimalarial n,n-bis(7-chloroquinolin-4-yl)heteroalkanediamines.	n,n-bis(7-chloroquinolin-4-yl)heteroalkanediamines 1-11 were synthesized and screened against plasmodium falciparum in vitro and plasmodium berghei in vivo. these bisquinolines had ic50 values from 1 to 100 nm against p. falciparum in vitro. six of the 11 bisquinolines were significantly more potent against the chloroquine-resistant w2 clone compared to the chloroquine-sensitive d6 clone. for bisquinolines 1-11 there was no relationship between the length of the bisquinoline heteroalkane bridge ...	1998	9784111
from noxiustoxin to shiva-3, a peptide toxic to the sporogonic development of plasmodium berghei.	this communication reviews shortly the main structural and functional characteristics of noxiustoxin, a 39 amino acid residue peptide, maintained closely packed by three-disulfide bridges and its effects on excitable membranes. shiva-3, a cecropin like-peptide composed of 38 amino acid residues is also briefly reviewed. its design and synthesis was made possible by the expertise gained through the work previously performed with noxiustoxin. one of the most prominent functional characteristics of ...	1998	9792185
structural information on a cecropin-like synthetic peptide, shiva-3 toxic to the sporogonic development of plasmodium berghei.	this study is a contribution towards the understanding of the mode of action of shiva-3 and more generally that of cecropin-like peptides. structural information on shiva-3 (a cecropin-like synthetic peptide) in water and in a membrane-mimicking environment (trifluoroethanol alcohol, sds) were obtained using analytical centrifugation, cd and nmr spectroscopies. a total of 20 converged structures were retained on the basis of 197 non-redundant experimental constraints, including 166 distance cons ...	1998	9799128
malaria infection of the mosquito anopheles gambiae activates immune-responsive genes during critical transition stages of the parasite life cycle.	six gene markers have been used to map the progress of the innate immune response of the mosquito vector, anopheles gambiae, upon infection by the malaria parasite, plasmodium berghei. in addition to four previously reported genes, the set of markers included nos (a nitric oxide synthase gene fragment) and ichit (a gene encoding two putative chitin-binding domains separated by a polythreonine-rich mucin region). in the midgut, a robust response occurs at 24 h post-infection, at a time when malar ...	1998	9799221
characterisation of the cdc2-related kinase 2 gene from plasmodium knowlesi and p. berghei.	the complete sequence of the cdc2-related kinase 2 (crk2) gene from plasmodium knowlesi and from p. berghei was determined. in both species, the crk2 gene is closely linked to an elongation factor 1 alpha gene. the two crk2 proteins are highly homologous to the p. falciparum pfpk5 protein. the crk2 gene of both species is expressed at a low level during the asexual cell-cycle within the host erythrocytes. the p. berghei crk2 mrna is also present in gametocytes and in stages during development in ...	1998	9803415
convulsions due to increased permeability of the blood-brain barrier in experimental cerebral malaria can be prevented by splenectomy or anti-t cell treatment.	experimental cerebral malaria (ecm) can be induced in c57b1 mice by infection with plasmodium berghei k173 parasites. behavioral changes shortly before they die of ecm may reflect disturbance of the integrity of the blood-brain barrier (bbb). folic acid elicits strong convulsive activity if the permeability of the bbb is increased. administration of folic acid to mice during development of ecm induced convulsions. interventions known to prevent fatal outcome from ecm, such as splenectomy or trea ...	1998	9806067
plasmodium yoelii: identification of rhoptry proteins using monoclonal antibodies.	thirteen monoclonal antibodies, obtained after immunization of mice with plasmodium yoelii schizonts, were selected using immunofluorescence assay: they all presented typical fluorescence patterns of rhoptries. this antigen localization was confirmed by immunoelectron microscopy. the molecular weights of the recognized antigens are 68, 80, 105, 130 and 140 kda as determined by immunoprecipitation and immunoblot under reducing and nonreducing conditions. these values are very similar to these of ...	1998	9806867
evidence for multiple pathologic and protective mechanisms of murine cerebral malaria.	murine cerebral malaria (cm) induced by plasmodium berghei anka kills susceptible mice within 24 to 48 h of onset of symptoms and is characterized by the production of inflammatory cytokines in the brain. c57bl/6j mice are sensitive to lethal cm, while a/j mice are resistant. these strains of mice were immunized with an adjuvant vaccine of killed whole-blood-stage parasites. the immunization protected c57bl/6 mice from lethal cm following virulent challenge. the same immunization increased the i ...	1998	9826380
a novel antiprotozoal aminosteroid from saracha punctata.	a new aminosteroid, 3beta-amino-22,26-epiminocholest-5-ene named sarachine (1), and two known flavonoids, eriodictyol (2) and 7-o-beta-d-glucopyranosyl-eriodictyol (3), were isolated from the leaves of saracha punctata. the alkaloid was found to inhibit the growth of leishmania braziliensis promastigotes (100% at 25 microm) and of trypanosoma cruzi epimastigotes in culture (50% at 25 microm) and showed a strong in vitro antiplasmodial activity with an ic50 of 25 nm.	1998	9834160
blocked hepatic-stage parasites and decreased susceptibility to plasmodium berghei infections in balb/c mice.	the balb/c strain of mice is comparatively more resistant to sporozoite infections of plasmodium berghei than the c57bl6 strain. infection with live sporozoites results in the formation of small hepatic forms in the balb/c liver that persist for as long as 6 days. upon infection with small numbers of sporozoites, some of the parasites are destroyed in the liver whereas the rest persist as blocked forms. when larger numbers of sporozoites are injected the same process occurs but, in addition, a f ...	1998	9836306
involvement of macrophage scavenger receptors in protection against murine malaria.	macrophage scavenger receptor a (msr-a) deficient mice msr-a(-/-) were infected by the intraperitoneal injection of the plasmodium berghei nk65 strain in the erythrocytic stage. the msr-a(-/-) mice died significantly earlier than the control mice (p=0.060). in the surviving mice, two peaks of parasitemia were observed: the first 5-7 days and the second at 2-3 weeks after infection. death of all msr-a(-/-) mice occurred at either peak of parasitemia, suggesting that msr-a protects mice from sever ...	1998	9840609
[utility of gamma rays in prophylaxis of transmissible malaria by blood transfusion].	this study was carried out to evaluate the fortuitons advantage of using gamma irradiation in the prophylaxis of transmissible malaria by blood transfusion, with mice as the experimental model. in the first step, when the infected blood with plasmodium berghei was submitted to 2,500 rad and 5,000 rad, with or without metronidazol, there was no success, because the animals presented parasitaemia and died after inoculation of irradiated blood. however, there was partial success in the second step, ...	1998	9859699
differential reactivity of brain microvascular endothelial cells to tnf reflects the genetic susceptibility to cerebral malaria.	upon infection with plasmodium berghei anka (pba), various inbred strains of mice exhibit different susceptibility to the development of cerebral malaria (cm). tumor necrosis factor-alpha (tnf) and interferon-gamma (ifn-gamma) have been shown to be crucial mediators in the pathogenesis of this neurovascular complication. brain microvascular endothelial cells (mvec) represent an important target of both cytokines. in the present study, we show that brain mvec purified from cm-susceptible (cm-s) c ...	1998	9862335
protection from plasmodium berghei infection by priming and boosting t cells to a single class i-restricted epitope with recombinant carriers suitable for human use.	the desirability of inducing cytotoxic t cell responses to defined epitopes in humans has led to the development of a variety of recombinant delivery systems. recombinant protein particles derived from a yeast retrotransposon (ty) and the modified ankara vaccinia (mva) virus can deliver large epitope strings or even whole proteins. both have previously been administered safely in humans. immunization with recombinant ty and mva containing a single plasmodium berghei class i-binding epitope provi ...	1998	9862371
peptide modification or blocking of cd8, resulting in weak tcr signaling, can activate ctl for fas- but not perforin-dependent cytotoxicity or cytokine production.	this study describes a form of partial agonism for a cd8+ ctl clone, s15, in which perforin-dependent killing and ifn-gamma production were lost but fas (apo1 or cd95)-dependent cytotoxicity preserved. cloned s15 ctl are h-2kd restricted and specific for a photoreactive derivative of the plasmodium berghei circumsporozoite peptide pbcs 252-260 (syipsaeki). the presence of a photoactivatable group in the epitope permitted assessment of tcr-ligand binding by tcr photoaffinity labeling. selective a ...	1998	9862728
plasmodium berghei anka: purification of large numbers of infectious gametocytes.		1998	9501851
the differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector.	using serum or infected blood from danish volunteers and plasmodium falciparum-infected mozambican patients, respectively, the impact of curative doses of chloroquine and pyrimethamine/sulfadoxine upon infectivity of p. falciparum to anopheles arabiensis and an. gambiae or of p. berghei to an. stephensi was studied. both treatments cleared circulating p. falciparum gametocytes within 28 days. before this clearance, chloroquine enhanced infectivity to an. arabiensis, whereas pyrimethamine/sulfado ...	1998	9502601
malaria transmission. has the ignition key been found?		1998	9521315
identification of xanthurenic acid as the putative inducer of malaria development in the mosquito.	malaria is transmitted from vertebrate host to mosquito vector by mature sexual blood-living stages called gametocytes. within seconds of ingestion into the mosquito bloodmeal, gametocytes undergo gametogenesis. induction requires the simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal temperature to 5 degrees c below that of the vertebrate host, and a rise in ph from 7.4 to 8.0-8.2. in vivo the mosquito bloodmeal has a ph of between 7.5 and 7.6. it is thought that in viv ...	1998	9521324
orally active antimalarial 3-substituted trioxanes: new synthetic methodology and biological evaluation.	on the basis of a mechanistic understanding of the mode of action of artemisinin-like antimalarials, a series of structurally simple 3-aryl-1,2,4-trioxanes 5 was designed and was prepared in three to five operations from commercial reactants. the 3-aryl group was attached in each case as a nucleophile. in an electronically complementary fashion, 3-(fluoroalkyl)-trioxanes 6 were prepared via attachment of electrophilic fluoroalkyl esters. both in vitro and in vivo antimalarial evaluations of thes ...	1998	9526568
plasmodium berghei: in vivo efficacy of albendazole in different rodent models.		1998	9538870
antimalarial activity of radicicol, heptelidic acid and other fungal metabolites.	in the course of our screening program for artemisinin-like antimalarial compounds from microorganisms, seven fungal metabolites such as radicicol and heptelidic acid were identified as active compounds. some of them exhibited antimalarial activity in vitro against the human malaria parasite plasmodium falciparum to the extent of approximately 1/10 as potent as artemisinin. radicicol was moderately active in vivo against plasmodium berghei in mice.	1998	9544936
enhanced immunogenicity for cd8+ t cell induction and complete protective efficacy of malaria dna vaccination by boosting with modified vaccinia virus ankara.	immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. a particular sequence of subunit immunization with pre-erythrocytic antigens of plasmodium berghei, consisting of single dose priming with plasmid dna followed by a single boost with a recombinant modified vaccinia virus ankara (mva) expressing the same antigen, induced unprecedented complete protection against p. berghei sporozoite chal ...	1998	9546783
dysregulation of cytokine expression in tubulointerstitial nephritis associated with murine malaria.	we examined the circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (tnf-alpha), interleukin (il)-1 alpha, il-6, granulocyte macrophage-colony stimulating factor (gm-csf), and the anti-inflammatory cytokine il-10, and their expression in kidneys acutely infected with murine malaria parasite p. berghei anka in c57bl/6j mice. groups of six mice sacrificed on days 5, 10, 15, and 20, and normal controls were used for cytokine analysis. high concentrations of tnf-alpha and ...	1998	9551390
reduced t helper 1 responses in il-12 p40 transgenic mice.	to investigate the antagonistic effect of il-12 p40 on il-12 activity in vivo, we generated transgenic (tg) mice in which p40 gene was regulated by a liver-specific promoter. three tg mouse lines were generated, and they expressed the p40 transgene predominantly in liver. serum p40 level was extremely high, and it consisted of mainly monomer and homodimer and also of higher m.w. complexes. these tg mice did not show any apparent phenotypic difference from control littermates in lymphoid cells. e ...	1998	9551892
rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.	pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (dhfr-ts). resistance in the most important human parasite, plasmodium falciparum, initially results from an s108n mutation in the dhfr domain, with additional mutation (most commonly c59r or n51i or both) imparting much greater resistance. from a homology model of the 3-d structure of dhfr-ts, rational drug design techniques have been used to design and subsequently synthesize inhibitors able to o ...	1998	9554869
the mosquito anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide.	we have discovered that the mosquito anopheles stephensi, a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (no). elevated expression of a. stephensi no synthase (nos), which is highly homologous to characterized nos genes, was detected in the midgut and carcass soon after invasion of the midgut by plasmodium. early induction is likely primed by bacterial growth in the blood meal. later increases in a. stephensi nos expression and enzyme acti ...	1998	9576947
glutathione peroxidase (ec 1.11.1.9) and superoxide dismutase (ec 1.15.1.1) activities in riboflavin-deficient rats infected with plasmodium berghei malaria.	riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. the objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (ec 1.11.1.9; gpx) and superoxide dismutase (ec 1.15.1.1; sod) in rats infected with plasmodium berghei malaria. riboflavin in its co-enzyme form, fad, is required by glutathione reductase (ec 1.6.4.1) to regenerate gsh and gsh is an important ...	1998	9577309
deletion of plasmodium berghei-specific cd4+ t cells adoptively transferred into recipient mice after challenge with homologous parasite.	the immune response to malaria parasites includes t cell responses that reduce parasites by effector t cell responses and by providing help for antibody responses. some parasites are more sensitive to antibody and others are more sensitive to cell-mediated immunity. we demonstrate that cultured cd4(+) t cells that produce interferon gamma and interleukin 2, but not interleukin 4, in response to stimulation with the rodent parasite plasmodium berghei can reduce but not eliminate parasites in vivo ...	1998	9465082
dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria.	the pathogenesis of human cerebral malaria (cm) remains unresolved. in the most widely used murine model of cm, the presence of t lymphocytes and/or interferon (ifn)-gamma is a prerequisite. ifn-gamma is the key inducer of indoleamine 2,3-dioxygenase (ido), which is the catalyst of the first, and rate-limiting, step in the metabolism of tryptophan (trp) along the kynurenine (kyn) pathway. quinolinic acid (qa), a product of this pathway, is a neuro-excitotoxin, like glutamic acid (glu) and aspart ...	1998	9466588
a family of chimeric erythrocyte binding proteins of malaria parasites.	proteins sequestered within organelles of the apical complex of malaria merozoites are involved in erythrocyte invasion, but few of these proteins and their interaction with the host erythrocyte have been characterized. in this report we describe maebl, a family of erythrocyte binding proteins identified in the rodent malaria parasites plasmodium yoelii yoelii and plasmodium berghei. maebl has a chimeric character, uniting domains from two distinct apical organelle protein families within one pr ...	1998	9448314
treatment with liposome-bound recombinant human tumor necrosis factor-alpha suppresses parasitemia and protects against plasmodium berghei k173-induced experimental cerebral malaria in mice.	our study describes liposomes (conventional or sterically stabilized) as carrier systems for recombinant human tumor necrosis factor-alpha (rhtnf-alpha) to increase its protective efficacy against plasmodium berghei-induced experimental cerebral malaria (ecm) in mice. rhtnf-alpha was either covalently coupled to the outer surface of preformed liposomes or encapsulated into the liposomes. for coupling to the liposomes, reactive thiol groups were introduced in rhtnf-alpha by reaction with n-succin ...	1999	9862761
gamma delta t-cell function in pathogenesis of cerebral malaria in mice infected with plasmodium berghei anka.	mice depleted of gammadelta t cells by monoclonal antibody treatment and infected with plasmodium berghei anka did not develop cerebral malaria (cm). in striking contrast, delta0/0 mice infected with p. berghei developed cm despite their gammadelta t-cell deficiency. gammadelta t cells appear to be essential for the pathogenesis of cm in mice having experienced normal ontogeny but not in mice genetically deprived of gammadelta t cells from the beginning of life.	1999	9864254
are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?	to investigate the involvement of oxidative tissue damage in the pathogenesis of murine cerebral malaria (cm), brain levels of protein carbonyls, 3,4-dihydroxyphenylalanine (dopa), o-tyrosine, and dityrosine were measured during plasmodium berghei anka (pba) and p. berghei k173 (pbk) infections. during pba infection in a cm model, brain levels of the substances were similar to those in uninfected mice. the role of phagocyte-derived reactive oxygen species in the pathogenesis of cm was examined i ...	1999	9841842
red cell selectivity in malaria: a study of multiple-infected erythrocytes.	to characterize red cell susceptibility to invasion in malaria, a selectivity index (si) was calculated as the ratio of observed number of multiple-infected red cells to that expected from a random process (poisson distribution). in patients with falciparum malaria (n = 100) si decreased with increasing parasitaemia (p < 0.001), and correlated inversely with plasma lactate concentrations, chosen prospectively as a measure of disease severity (r = -0.36, p < 0.001). for parasitaemias < 5%, the si ...	1999	10450440
t cell response in malaria pathogenesis: selective increase in t cells carrying the tcr v(beta)8 during experimental cerebral malaria.	to characterize the t cells involved in the pathogenesis of cerebral malaria (cm) induced by infection with plasmodium berghei anka clone 1.49l (pba 1.49l), the occurrence of the disease was assessed in mice lacking t cells of either the alphabeta or gammadelta lineage (tcralphabeta(-/-) or tcrgammadelta(-/-)). tcrgammadelta(-/-) mice were susceptible to cm, whereas all tcralphabeta(-/-) mice were resistant, suggesting that t cells of the alphabeta lineage are important in the genesis of cm. the ...	1999	10464176
up-regulation of cytokines in glomerulonephritis associated with murine malaria infection.	malaria infections often cause glomerulonephritis (gn), and multiple factors have been implicated in the pathogenesis of glomerular injury. the role of cytokines in malaria associated glomerulonephritis has not been clearly defined. to study the importance of cytokines in malarial nephritis, we investigated the expression of tumour necrosis factor-alpha (tnf-alpha), interleukin-1alpha (il-1alpha), il-6, il-10 and granulocyte macrophage-colony stimulating factor (gm-csf) in kidneys acutely infect ...	1999	10469263
metal chelators/antioxidants: approaches to protect erythrocytic oxidative stress injury during plasmodium berghei infection in mastomys coucha.	desferal, n-acetyl penicillamine (metal chelators) and propylgallate, catechin, and reduced glutathione (antioxidants) suppressed the erythrocytic oxidative damage generated during plasmodium berghei infection in mastomys coucha. superoxide anion and lipid peroxide levels were increased and on the contrary, superoxide dismutase activity was noticeably decreased in the infected erythrocytes. metal chelators/antioxidant treatment to infected animals resulted in restoration of o(2)(-), lpo and sod ...	1999	10479467
comparative evaluation of methods of malaria parasite density determination in blood samples from patients & experimental animals.	three methods for the quantitation of parasitaemia in malaria were compared with the standard method for ascertaining the accuracy in patients, plasmodium berghei infected mice and p. knowlesi infected rhesus monkeys. technique i, where parasitaemia was calculated from the number of prbcs in 10,000 rbcs in thin blood film and the total rbc count of the host, was used as the standard. technique ii, where parasitaemia was calculated based on the number of prbcs per wbc and average total wbc count ...	1999	10489738
plasmodium berghei: a new rat model for assessment of blood schizonticidal activity.		1999	10502471
plasmodium berghei: induction of aminopeptidase in malaria-resistant strain of anopheles gambiae.		1999	10502473
the a-domain and the thrombospondin-related motif of plasmodium falciparum trap are implicated in the invasion process of mosquito salivary glands.	sporozoites from all plasmodium species analysed so far express the thrombospondin-related adhesive protein (trap), which contains two distinct adhesive domains. these domains share sequence and structural homology with von willebrand factor type a-domain and the type i repeat of human thrombospondin (tsp). increasing experimental evidence indicates that the adhesive domains bind to vertebrate host ligands and that trap is involved, through an as yet unknown mechanism, in the process of sporozoi ...	1999	10508153
effects of plasmodium berghei infection on cytochromes p-450 2e1 and 3a2.	metabolism and disposition of most drugs used to treat malaria are substantially altered in malaria infection. few data are available that specify effects of malaria infection on drug metabolism pathways in humans or animal model systems. in this report, studies were undertaken to determine the effect of plasmodium berghei infection on cytochrome p-450 (cyp450) 2e1 and 3a2-mediated metabolism and enzyme expression in rat liver microsomes. malaria infection (mal) resulted in significant decreases ...	1999	10510746
iron acquisition by plasmodium spp.		1999	10511692
potentiation by febrifugine of host defense in mice against plasmodium berghei nk65.	the effect of febrifugine, the main alkaloidal constituent of an antimalarial crude drug, dichroa febrifuga lour., on protective immunity in mice infected with erythrocytic stage plasmodium berghei nk65 was investigated. febrifugine was administered orally, at a dose of 1 mg/kg/day, to mice before and/or after they were infected intraperitoneally with 2 x 10(6) parasitized red blood cells. then, mortality and the levels of parasitemia and plasma no3- [a degradation product of nitric oxide (no)] ...	1999	10535750
gene gun intradermal dna immunization followed by boosting with modified vaccinia virus ankara: enhanced cd8+ t cell immunogenicity and protective efficacy in the influenza and malaria models.	in influenza and malaria, cd8+ t cells play an important role in protective immunity in mice. an immunization strategy consisting of dna priming followed by boosting with recombinant modified vaccinia virus ankara (mva) induces complete protection, associated with high levels of cd8+ t cells, against plasmodium berghei sporozoite challenge in mice. intradermal delivery of dna with a gene gun requires smaller amounts of dna than intramuscular injection, in order to induce similar levels of immune ...	1999	10547421
ctrp is essential for mosquito infection by malaria ookinetes.	the malaria parasite suffers severe population losses as it passes through its mosquito vector. contributing factors are the essential but highly constrained developmental transitions that the parasite undergoes in the mosquito midgut, combined with the invasion of the midgut epithelium by the malaria ookinete (recently described as a principal elicitor of the innate immune response in the plasmodium-infected insect). little is known about the molecular organization of these midgut-stage parasit ...	1999	10562534
conservation of a gliding motility and cell invasion machinery in apicomplexan parasites.	most apicomplexan parasites, including the human pathogens plasmodium, toxoplasma, and cryptosporidium, actively invade host cells and display gliding motility, both actions powered by parasite microfilaments. in plasmodium sporozoites, thrombospondin-related anonymous protein (trap), a member of a group of apicomplexan transmembrane proteins that have common adhesion domains, is necessary for gliding motility and infection of the vertebrate host. here, we provide genetic evidence that trap is d ...	1999	10579715
targeted disruption of the plasmodium berghei ctrp gene reveals its essential role in malaria infection of the vector mosquito.	ctrp (circumsporozoite protein and thrombospondin-related adhesive protein [trap]-related protein) of the rodent malaria parasite plasmodium berghei (pbctrp) makes up a protein family together with other apicomplexan proteins that are specifically expressed in the host-invasive stage 1. pbctrp is produced in the mosquito-invasive, or ookinete, stage and is a protein candidate for a role in ookinete adhesion and invasion of the mosquito midgut epithelium. to demonstrate involvement of pbctrp in t ...	1999	10587361
mutations in the cytochrome b gene of plasmodium berghei conferring resistance to atovaquone.	the molecular lesions which underlie the resistance of the malaria parasites to atovaquone, a coenzyme q analogue, were investigated. resistant clones of plasmodium berghei anka strain were isolated following prolonged propagation in mice in the presence of increasing doses of the drug, and their cytochrome b gene sequenced. three mutations were detected, t-c substitution at nt 431, g-a at nt 399 and g-t at nt 850, resulting in amino acid changes in the putative cytochrome b product at residues ...	1999	10593174
a single-chain antibody fragment specific for the plasmodium berghei ookinete protein pbs21 confers transmission blockade in the mosquito midgut.	mouse monoclonal antibody 13.1 (mab 13.1) directed against pbs21, a 21-kda sexual-stage surface protein of plasmodium berghei, is known to inhibit oocyst development from gametocytes and ookinetes in the mosquito midgut. to examine the properties and potential uses of a single-chain antibody fragment (scfv) for blocking transmission of malaria parasites to mosquitoes, we have cloned and sequenced the genes encoding variable regions of the immunoglobulin heavy and light chains (v(h) and v(l)) of ...	1999	10593175
the aspartic proteinase from the rodent parasite plasmodium berghei as a potential model for plasmepsins from the human malaria parasite, plasmodium falciparum.	the gene encoding an aspartic proteinase precursor (proplasmepsin) from the rodent malaria parasite plasmodium berghei has been cloned. recombinant p. berghei plasmepsin hydrolysed a synthetic peptide substrate and this cleavage was prevented by the general aspartic proteinase inhibitor, isovaleryl pepstatin and by ro40-4388, a lead compound for the inhibition of plasmepsins from the human malaria parasite plasmodium falciparum. southern blotting detected only one proplasmepsin gene in p. berghe ...	1999	10601635
memory phenotype cd8(+) t cells persist in livers of mice protected against malaria by immunization with attenuated plasmodium berghei sporozoites.	natural exposure to plasmodium parasites induces short-lived protective immunity. in contrast, exposure to radiation-attenuated sporozoites (gamma spz) promotes long-lasting protection that is in part mediated by cd8(+) t cells that target exoerythrocytic stage antigens. the mechanisms underlying the maintenance of long-lasting protection are currently unclear. the liver is a repository of plasmodium antigens and may support the development and / or homing of memory t cells. while activated cd8( ...	1999	10602007
in vitro and in vivo evaluation of betulinic acid as an antimalarial.	the lupane-type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the tanzanian tree uapaca nitida müll-arg. (euphorbiaceae). the in vitro antiplasmodial ic50 values of betulinic acid against chloroquine resistant (k1) and sensitive (t9-96) plasmodium falciparum were found to be 19.6 micrograms/ml and 25.9 micrograms/ml, respectively. the in vitro activities of several related triterpenes were also evaluated. betulin was found to be inactive at 500 micrograms/ml ...	1999	10190183
antimalarial activity of 3-hydroxyalkyl-2-methylene-propionic acid derivatives.	several baylis-hillman adducts and their derivatives were synthesized and evaluated as targeted potential anti-malarials. the compounds 4, 7 and 9 were found to have highest potency against p. falciparum in vitro. the in vivo test result of compound 4 and 9 against p. berghei demonstrated activity at 80 mg/kg dose level.	1999	10201838
irradiated sporozoites prime mice to produce high antibody titres upon viable plasmodium berghei sporozoite challenge, which act upon liver-stage development.	c57bl6 mice were protected against plasmodium berghei sporozoite challenge by immunization with live 12 krad dose-irradiated sporozoites, but not by 20 krad dose-irradiated sporozoites. immunization with 12 krad irradiated sporozoites generated low levels of antibody reactive to liver-stage parasites (titres of 1/100). inoculation of as few as 100 live p. berghei sporozoites induced complete host protection accompanied by a very quick and high boost of antibody titres up to 1/4000. this sporozoi ...	1999	10205797
synthesis and antimalarial activity of 11 dispiro-1,2,4,5-tetraoxane analogues of wr 148999. 7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecanes substituted at the 1 and 10 positions with unsaturated and polar functional groups.	eleven novel dispiro-1,2,4,5-tetraoxanes 3 bearing unsaturated and polar functional groups were designed to enhance the oral antimalarial activity of the prototype tetraoxane 2 (wr 148999). with the exception of 3g and 3h, tetraoxanes 3 were available via the peroxidation of corresponding cyclohexanone derivatives in h2so4/ch3cn. tetraoxanes 3g and 3h were prepared by hydrolysis of ester tetraoxanes 3e and 3i, respectively. five of the 11 tetraoxanes were inactive, but six tetraoxanes had ic50 v ...	1999	10212135
the putative gene for the first enzyme of glutathione biosynthesis in plasmodium berghei and plasmodium falciparum.	the putative gene for gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione biosynthesis, has been characterized both in plasmodium berghei and plasmodium falciparum. protein sequence comparison between these two species reveals large conserved regions sharing more than 80% similarity, separated by less conserved portions. when the comparison is extended to known gamma-glutamylcysteine synthetases from other eukaryotes, a number of high similarity blocks are observed which m ...	1999	10215022
ty virus-like particles, dna vaccines and modified vaccinia virus ankara; comparisons and combinations.	three types of vaccine, all expressing the same antigen from plasmodium berghei, or a cd8+ t cell epitope from that antigen, were compared for their ability to induce cd8+ t cell responses in mice. higher levels of lysis and numbers of ifn-gamma secreting t cells were primed with ty virus-like particles and modified vaccinia virus ankara (mva) than with dna vaccines, but none of the vaccines were able to protect immunised mice from infectious challenge even after repeated doses. however, when th ...	1999	10223332
thiolated recombinant human tumor necrosis factor-alpha protects against plasmodium berghei k173-induced experimental cerebral malaria in mice.	the introduction of reactive thiol groups in recombinant human tumor necrosis factor (tnf) alpha (rhtnf-alpha) by the reagent succinimidyl-s-acetylthioacetate resulted in the formation of a chemically stabilized rhtnf-alpha trimer (rhtnfalpha-at; as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis). rhtnfalpha-at showed a substantially enhanced protective efficacy against the development of experimental murine cerebral malaria (ecm) after intravenous injection com ...	1999	10223910
altered immune response of interferon regulatory factor 1-deficient mice against plasmodium berghei blood-stage malaria infection.	nitric oxide (no) is a short-lived biological mediator which can be induced in various cell types and is able to cause many metabolic changes in target cells. inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of no production by transcriptional upregulation of inducible nitric oxide synthase. in the present study, we used mice devoid of functional interferon regulatory factor 1 by targeted gene disruption (irf-1(-/-)) to investigate the role of no ...	1999	10225884
gamma interferon production is critical for protective immunity to infection with blood-stage plasmodium berghei xat but neither no production nor nk cell activation is critical.	we have examined the roles of gamma interferon (ifn-gamma), nitric oxide (no), and natural killer (nk) cells in the host resistance to infection with the blood-stage malarial parasite plasmodium berghei xat, an irradiation-induced attenuated variant of the lethal strain p. berghei nk65. although the infection with p. berghei xat enhanced nk cell lytic activity of splenocytes, depletion of nk1.1(+) cells caused by the treatment of mice with anti-nk1.1 antibody affected neither parasitemia nor ifn ...	1999	10225894
green fluorescent protein as a marker in plasmodium berghei transformation.	we present a new marker that confers both resistance to pyrimethamine and green fluorescent protein-based fluorescence on the malarial parasite plasmodium berghei. a single copy of the cassette integrated into the genome is sufficient to direct fluorescence in parasites throughout the life cycle, in both its mosquito and vertebrate hosts. erythrocyte stages of the parasite that express the marker can be sorted from control parasites by flow cytometry. pyrimethamine pressure is not necessary for ...	1999	10225926
glutathione-s-transferase activity in malarial parasites.	glutathione-s-transferase (gst) activity has been detected in rodent (plasmodium berghei, p. yoelii), simian (p. knowlesi) and human (p. falciparum) malarial parasites, and in different intraerythrocytic stages of p. knowlesi (schizont > ring > trophozoite). in chloroquine-resistant strains of rodent and human malarial parasites gst activity significantly increases compared to sensitive strains. further, the increase in enzyme activity is directly related to drug pressure of resistant p. berghei ...	1999	10320651
plasmodium berghei development in irradiated sporozoite-immunized c57bl6 mice.	the c57bl6 strain of mice is highly susceptible to plasmodium berghei sporozoite infections and consequently requires repeated immunizations with irradiated sporozoites to obtain protective immunity. after a live sporozoite challenge in the immunized hosts, hepatic-stage parasites found in the liver after 48 h are of different sizes--small schizonts corresponding to blocked forms (derived from irradiated sporozoites), and schizonts of intermediate size (derived from live sporozoites). large schi ...	1999	10340322
identification of the transcription initiation site of the asexually expressed rrna genes of the malaria parasite plasmodium berghei.	the start site of the a-type ribosomal rna transcription units of the rodent malaria parasite, plasmodium berghei, has been identified. the two a-type units cannot be distinguished within the transcription unit, yet exist as single copies on different chromosomes. gene transcription initiates 820 bp upstream of the a-type small subunit (ssu) ribosomal gene and two major processing sites were mapped 610 and 611 nucleotides upstream of the ssu in the external transcribed spacer region. surprisingl ...	1999	10340484
role of eicosanoids in the pathogenesis of murine cerebral malaria.	because microvascular damage is a common feature of cerebral malaria, we have examined the role eicosanoid metabolites (prostaglandins and leukotrienes) in experimental cerebral malaria. eighty icr mice were infected with plasmodium berghei anka, with 40 uninfected mice as controls. half of the infected mice were treated on days 4 and 5 with aspirin, a prostaglandin synthesis inhibitor. infected mice started to die of cerebral malaria on day 6, and by day 17, all infected mice died. in contrast, ...	1999	10348246
malaria parasite-specific th1-like t cells simultaneously reduce parasitemia and promote disease.	cd4+ t cells have been implicated in immunity to the blood stages of malaria and cytokines associated with both monocyte and t cell activation have been implicated in disease. to determine whether specific t cells capable of inhibiting parasite growth can also mediate pathology we have transfused populations of plasmodium berghei-specific t cells into normal and immunodeficient naive mice. we observed that they could inhibit parasite growth but were unable to save the animals which exhibited sig ...	1999	10354354
involvement of lipids in ferriprotoporphyrin ix polymerization in malaria.	approximately 70% of the initial ferriprotoporphyrin ix polymerizing activity in cell-free preparations of erythrocytes infected with plasmodium berghei was recovered in a chloroform extract. no polymerizing activity remained in the residue. in studies to identify substances that promote fp polymerization, arachidonic, linoleic, oleic, and palmitoleic acids, 1-mono- and di-oleoylglycerol, and the detergents, sds, tween 80, and n-octyl-glucopyranoside, were active. tri-oleoylglycerol, cholesterol ...	1999	10354512
antimalarial activity of extracts of malaysian medicinal plants.	in vitro and in vivo studies revealed that malaysian medicinal plants, piper sarmentosum, andrographis paniculata and tinospora crispa produced considerable antimalarial effects. chloroform extract in vitro did show better effect than the methanol extract. the chloroform extract showed complete parasite growth inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period (andrographis paniculata) as compared to methanol extract of drug dose of 2.5 mg/ml but under incubation time of 48 ...	1999	10363840
analysis of stage specificity of promoters in plasmodium berghei using luciferase as a reporter.		1999	10377003
structure and expression of an adhesive protein-like molecule of mosquito invasive-stage malarial parasite.	invasion of the malarial parasite into a vector mosquito begins when the motile ookinete transverses the gut epithelium. adhesive proteins that may mediate this invasive process have not been identified to date. we found that a molecule with an adhesive protein-like structure was expressed in the ookinete of plasmodium berghei. this protein is structurally homologous to circumsporozoite protein and thrombospondin-related adhesive protein (trap)-related protein, ctrp, of plasmodium falciparum. we ...	1999	10377190
extracellular processing and presentation of a 69-mer synthetic polypetide to mhc class i-restricted t cells.	the classical pathway for mhc class-i-restricted ag presentation processes cytosolic ag synthesized in or delivered into the cytosol for binding to mhc class i molecules in the er. alternatively, ag may be processed and bind class i molecules in endocytic compartments or at the cell surface after regurgitation of processed peptides. we show that a 69-mer synthetic polypeptide that carries the optimal 9-mer kd-restricted epitope from the plasmodium berghei circumsporozoite protein, pbcs 245-253, ...	1999	10378682
gene organization of rab6, a marker for the novel golgi of plasmodium.		1999	10391383
dipeptide derivatives of primaquine as transmission-blocking antimalarials: effect of aliphatic side-chain acylation on the gametocytocidal activity and on the formation of carboxyprimaquine in rat liver homogenates.	dipeptide derivatives of primaquine (pq) with reduced oxidative deamination to the inactive metabolite carboxyprimaquine were synthesized and evaluated as a novel class of transmission-blocking antimalarials. methods; antimalarial activity was studied using a model consisting of mefloquine-resistant plasmodium berghei anka 25r/10, balb c mice, and anopheles stephensi mosquitoes. metabolic studies were performed with rat liver homogenates, and the incubates were analyzed by hplc.	1999	10397619
cloning and characterization of the merozoite surface antigen 1 gene of plasmodium berghei.	merozoite surface antigen 1 (msa1) is a promising candidate for vaccine development against malaria parasites. here, we report the complete nucleotide sequence of the gene encoding the precursor to this major surface antigen of plasmodium berghei strain anka using cdna library screening and polymerase chain reaction techniques. a single open reading frame of 5,376 basepairs encoding a protein with a calculated molecular mass of 197 kd was defined. the protein contains a putative signal peptide o ...	1999	10403333
synthesis and antimalarial activity of cyclic peroxides, 1,2,4,5, 7-pentoxocanes and 1,2,4,5-tetroxanes.	a variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. in both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. for some cyclic peroxides, which were found to be highly effective in vitro, the study in vivo has been also conducted.	1999	10411480
infectivity of plasmodium berghei sporozoites delivered by intravenous inoculation versus mosquito bite: implications for sporozoite vaccine trials.	plasmodium berghei sporozoites delivered by mosquito bite were more infectious to outbred cd-1 mice than were sporozoites delivered by intravenous inoculation. the route of challenge also affected vaccine efficacy. in view of these findings and the fact that mosquito bites are the natural mode of sporozoite delivery, infectious mosquito bites should be considered the challenge protocol of choice for sporozoite vaccine efficacy trials.	1999	10417207
antimalarial activity and cytotoxicity of (-)-roemrefidine isolated from the stem bark of sparattanthelium amazonum.	(-)-roemrefidine, an aporphine alkaloid isolated from sparattanthelium amazonum martius (hernandiaceae) a vine from bolivia, has been found to be active against both resistant and sensitive strains of plasmodium falciparum in vitro and against p. berghei in mice. the compound demonstrated no cytotoxic activity against three cell lines (kb, hep-2 and hela).	1999	10418333
an alternate pathway for type 1 t cell differentiation.	ifn-regulatory factor-1 (irf-1) gene-disrupted mice are defective in il-12 and il-18 gene expression at the transcriptional and post-translational level respectively. the mutant mouse mounts a type 2 t cell response upon bacterial infection because of the impaired induction of the il-12 p40 gene and ifn-gamma-producing type 1 t cells are not induced. we showed here, however, that different pathogens activate a novel pathway for inducing ifn-gamma-producing type 1 t cells even in an irf-1-deficie ...	1999	10421776
new 4-aminoquinoline mannich base antimalarials. 1. effect of an alkyl substituent in the 5'-position of the 4'-hydroxyanilino side chain.	a new series of 4-aminoquinoline mannich base derivatives have been synthesized, in which the 3'-diethylamino function of amodiaquine (aq) is replaced by a 3'-tert-butylamino group and an aliphatic hydrocarbon entity is incorporated into the 5'-position of the 4'-hydroxyanilino side chain. seven alkyl mannich base derivatives were screened and found to be active against both chloroquine-sensitive and -resistant strains of plasmodium falciparum in vitro. the propyl and isopropyl alkyl derivatives ...	1999	10425085
morphological analysis of isolated rhoptries from plasmodium yoelii, p. berghei, and p. chabaudi merozoites.		1999	10425155
new type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against plasmodium malaria parasite.	febrifugine (1) and isofebrifugine (2), isolated from the roots of dichroa febrifuga lour. (chinese name: cháng shan), are active principles against malaria. adducts of 1 and 2 with acetone, df-1 (3) and df-2 (4), respectively, were obtained using silica gel and acetone. they showed high activity against p. falciparum malaria in vitro. compound 3 was found to be equally effective against p. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. ...	1999	10447961
hepatic hematopoiesis in adult mouse during experimental rodent malaria.	during rodent malaria the development of the hematopoiesis in the liver was observed. this fact was used as a model for the study of the conditions and the features of the extramedullary hematopoietic differentiation, following the state of anaemia induced by parasitemia with plasmodium berghei. histological and ultrastructural data on the hepatic hematopoiesis are presented.	1999	11845448
[isolation and quantitation of chloroquine-binding proteins in plasmodium berghei].	to isolate and quantitate chloroquine (cq)-binding proteins in both cq-sensitive (cs) and cq-resistant (cr) plasmodium berghei.	1999	12563771
[differences in haemozoin production and pathogenicity between chloroquine-sensitive and chloroquine-resistant strains of plasmodium berghei].	to better understand the differences in haemozoin formation and pathogenicity between chloroquine-sensitive(n) and chloroquine-resistant(rc) strains of plasmodium berghei.	1999	12563809
[distribution of chloroquine in mitochondria, microsome and acid-precipitated protein from plasmodium berghei].		1999	12563846
mosquito-plasmodium interactions in response to immune activation of the vector.	during the development of plasmodium sp. within the mosquito midgut, the parasite undergoes a series of developmental changes. the elongated ookinete migrates through the layers of the midgut where it forms the oocyst under the basal lamina. we demonstrate here that if aedes aegypti or anopheles gambiae, normally susceptible to plasmodium gallinaceum and p. berghei, respectively, are immune activated by the injection of bacteria into the hemocoel, and subsequently are fed on an infectious bloodm ...	1999	9920043
plasmodium: immunization with carboxyl-terminal regions of msp-1 protects against homologous but not heterologous blood-stage parasite challenge.	a leading candidate for a vaccine targeted at the erythrocytic stages of plasmodial parasite development is the merozoite surface protein-1 (msp-1). we have previously shown that the carboxyl-terminal region of msp-1 derived from plasmodium yoelii yoelii 17xl, expressed as a fusion protein with glutathione s-transferase (gst-pyc2), can immunize mice against an otherwise lethal homologous challenge infection. this protection has been shown to be predominantly mediated by antibodies. we report her ...	1999	9920045
plasmodium berghei: identification of an mdr-like gene associated with drug resistance.	amplification, mutations, or overexpression of the pfmdr1 gene have been associated with multiple drug resistance in some strains of plasmodium falciparum. in order to better understand this potential mechanism of drug resistance, we are currently investigating putative mdr homologues in vivo in the rodent malaria plasmodium berghei. we have identified and partially sequenced a gene that is amplified in a mfq-resistant (mfqr) line. using degenerate primers, a 579-bp fragment was amplified by pcr ...	1999	9920046
plasmodium berghei and plasmodium yoelii: molecular karyotypes of drug-resistant lines.		1999	9920047
t cell recognition of hapten. anatomy of t cell receptor binding of a h-2kd-associated photoreactive peptide derivative.	to elucidate the structural basis of t cell recognition of hapten-modified antigenic peptides, we studied the interaction of the t1 t cell antigen receptor (tcr) with its ligand, the h-2kd-bound plasmodium berghei circumsporozoite peptide 252-260 (syipsaeki) containing photoreactive 4-azidobenzoic acid (aba) on p. berghei circumsporozoite lys259. the photoaffinity-labeled tcr residue(s) were mapped as tyr48 and/or tyr50 of complementary determining region 2beta (cdr2beta). other tcr-ligand conta ...	1999	9920911
heterogeneous ribosome populations are present in plasmodium berghei during development in its vector.	the genome of the rodent malaria parasite, plasmodium berghei, contains two sets of variant ribosomal rna (rrna) genes, termed the a and s types, that are expressed predominantly during the vertebrate and mosquito stages of the parasite's development respectively. using in situ hybridization, we have examined the transcriptional activity of the a- and s-type rrna genes, and the switch in expression of the ribosome populations that occurs after parasite transmission to the mosquito. by detection ...	1999	9987126
the development of murine cerebral malaria does not require nitric oxide production.	nitric oxide (no) production has been suggested to be required for the development of cerebral malaria. however, the importance of this molecule for the appearance of this pathology is debated. to assess whether murine cerebral malaria is no dependent, we investigated the course of blood-stage plasmodium berghei anka (pba) infections in inducible nitric oxide synthase (inos)-deficient mice. parasitaemia, haematological alterations, survival and development of cerebral malaria were not affected b ...	1999	10028526
treatment with recombinant human tumour necrosis factor-alpha reduces parasitaemia and prevents plasmodium berghei k173-induced experimental cerebral malaria in mice.	the present study shows that treatment with recombinant human tumour necrosis factor-alpha (rhtnf-alpha) can suppress parasitaemia and prevents development of experimental cerebral malaria (ecm) in plasmodium berghei k173-infected mice. mice received rhtnf-alpha treatment either by subcutaneous injection of free or liposome-encapsulated rhtnf-alpha or sustained intraperitoneal administration of rhtnf-alpha given via mini-osmotic pumps. low-dose treatment with a subcutaneous bolus injection of rh ...	1999	10070656
the biosynthesis and post-translational modification of pbs21 an ookinete-surface protein of plasmodium berghei.	radiolabelled methionine incorporation into synchronised plasmodium berghei gametocytes or ookinete cultures, showed that pbs21 is not synthesised in bloodstage parasites; synthesis was detected within three hours of induction of gametogenesis; synthesis was triggered at gametogenesis, not by fertilisation. we show native pbs21 to be a hydrophobic membrane protein that was insensitive to cleavage by phosphatidylinositol phospholipase c (pi-plc), but sensitive to alkaline hydroxylamine, and parti ...	1999	10080386
role of glutathione in the detoxification of ferriprotoporphyrin ix in chloroquine resistant plasmodium berghei.	the reduction in hemozoin content is a well known feature of chloroquine-resistant plasmodium berghei. using nk65-derived lines displaying increasing resistance levels, we observed an inverse relationship between the hemozoin content, and the glutathione (gsh) and glutathione s-transferase (gst) levels. treatment of highly chloroquine-resistant-infected mice with buthionine sulfoximine (bso), which has previously been shown to partially reverse this chloroquine resistance, led to a significant i ...	1999	10080390
subtle mutagenesis by ends-in recombination in malaria parasites.	the recent advent of gene-targeting techniques in malaria (plasmodium) parasites provides the means for introducing subtle mutations into their genome. here, we used the trap gene of plasmodium berghei as a target to test whether an ends-in strategy, i.e., targeting plasmids of the insertion type, may be suitable for subtle mutagenesis. we analyzed the recombinant loci generated by insertion of linear plasmids containing either base-pair substitutions, insertions, or deletions in their targeting ...	1999	10082556
the chemotherapy of rodent malaria. lvi. studies on the development of resistance to natural and synthetic endoperoxides.	chloroquine-sensitive plasmodium berghei n and chloroquine-resistant p. yoelii ssp. ns were exposed to selection pressure, in the '2% relapse technique', from artemisinin, artesunate, a bicyclic, synthetic endoperoxide ro 41-3823 (an analogue of arteflene) or fenozan b07, a synthetic 1,2,4-trioxane endoperoxide. whereas resistance against artemisinin did develop to a moderate level in both parasites, only a low level of resistance or none developed to the other compounds, and resistant parasites ...	1999	10656034