Publications

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[plasmodium berghei (vincke & lips) infection]. 195213028089
[therapy of plasmodium berghei infection in the rat]. 195113028080
the effect of x irradiation on infections with plasmodium berghei in the white mouse. 195313022997
[relations between blood reticulocytosis and the infection of a white rat with plasmodium berghei]. 195213020258
[serological study of experimental plasmodium berghei infection in white rat; sandor's reticuloendothelial record and euglobuline i1]. 195213020090
[massive injection of plasmodium berghei into rat, for determination of effectiveness of an antimalarial; nivaquine]. 195213020089
[effect of adrenalectomy on experimental plasmodium berghei malaria in white rat]. 195213020088
[the thorn test in experimental plasmodium berghei malaria in white rat]. 195213020087
[value of the blood reticulocyte level in experimental malaria in white rats caused by plasmodium berghei]. 195213009915
the course of the blood-induced plasmodium berghei infection in the meadow mouse microtus pennsylvanicus and certain other small rodents. 195313007920
blood sugar studies on the white rat infected with plasmodium berghei. 195212996742
the effect of antibiotics on experimental malaria (plasmodium cathemerium and plasmodium berghei). 195212996741
[study in the white rat of the relations between vitamin a deficiency and experimental malaria with plasmodium berghei]. 195212988449
[results of the intracardiac or intraperitoneal injection in white mouse of large quantities of erythrocytes parasited with plasmodium berghei]. 195212988448
[demonstration and analysis of crossed immunity between two strains of plasmodium berghei]. 195212988447
[experimental plasmodium berghei malaria in the white rat]. 195212988010
[resistance of plasmodium berghei at low temperatures]. 195212987999
the absorption of inoculated blood containing plasmodium berghei from the peritoneal cavity of the mouse. 195212986700
a microchemical study of plasmodium berghei by microincineration, with a note on the microscopical demonstration of calcium. 195212986696
[plasmodium berghei vincke]. 195212982288
[plasmodium berghei vincke and lips 1948; experimental study of malaria in rodents]. 195212981439
[quantitative and qualitative study of the blood parasites during an experimental infection of white rats with plasmodium berghei]. 195212976787
crystal structure of plasmodium berghei lactate dehydrogenase indicates the unique structural differences of these enzymes are shared across the plasmodium genus.as plasmodium rely extensively on homolactic fermentation for energy production, plasmodium falciparum lactate dehydrogenase (pfldh)--the key enzyme in this process--has previously been suggested as a novel target for antimalarials. this enzyme has distinctive kinetic and structural properties that distinguish it from its human homologues. in this study, we now describe the expression, kinetic characterisation and crystal structure determination of the ldh from plasmodium berghei. this enzyme is ...200312967707
a new rodent model to assess blood stage immunity to the plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies.antibodies capable of inhibiting the invasion of plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. those targeting the 19-kd cooh-terminal domain of the major merozoite surface protein (msp)-119 are a major component of this inhibitory activity. however, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. here we use an allelic replacement approach to generate a rodent malaria para ...200312963693
studies on the use of cassia singueana in malaria ethnopharmacy.cassia singueana (family: fabaceae) is used in northern nigeria for the treatment of acute malaria attack. we investigated the activities of the methanol extract of the root bark of this plant against rodent plasmodia infection, nociception, pyrexia and inflammation in mice and rats. the studies were carried out using acetic acid-induced writhing, hot plate algesia, rodent plasmodia (plasmodium berghei) in mice; formalin test, yeast-induced pyrexia and egg-albumin-induced inflammation in rats. t ...200312963153
in vivo gene silencing in plasmodium berghei--a mouse malaria model.rna interference (rnai) has emerged as a specific and efficient tool to silence gene expression in a variety of organisms and cell lines. an important prospect for rnai technology is its possible application in the treatment of diseases using short interfering rnas (sirnas). however, the effect of sirnas in adult animals and their potential to treat or prevent diseases are yet to be fully investigated. the main goal of the present study is to find out whether it was possible to carry out rnai on ...200312963018
new methods and software tools for high throughput cdr3 spectratyping. application to t lymphocyte repertoire modifications during experimental malaria.immune repertoires of t or b cells are very often studied by complementary determining region 3 (cdr3) spectratyping. however, data obtained with this method is usually subject to a biased eye analysis. we developed recently the iseapeaks software package to retrieve and handle peak data from automated sequencers, from which cdr3 spectratype data is obtained. we describe a general strategy for cdr3 spectratype analysis based on two new specific modules and multivariate statistics. the first modu ...200312957400
antimalarial effect of agmatine on plasmodium berghei k173 strain.to study the antimalarial effect of agmatine (agm) on chloroquine-susceptible plasmodium berghei k173 strain (s strain) and the p berghei k173 resistant strain (r strain).200312956942
shared, unique and redundant functions of three members of the class i myosins (myoa, myob and myof) in motility and chemotaxis in dictyostelium.most cell types express two distinct forms of myosin i, amoeboid and short, distinguished by differences in their tail domains. both types of myosin i have been implicated in the regulation of pseudopod formation in dictyostelium discoideum. we examined three members of the myosin i family, one amoeboid, myob, and two short, myoa and myob, for shared, unique and redundant functions in motility and chemotaxis. we used computer-assisted methods for reconstructing and motion analyzing cells, and ex ...200312953059
potentiation of the antimalarial action of chloroquine in rodent malaria by drugs known to reduce cellular glutathione levels.ferriprotoporphyrin ix (fp) is released inside the food vacuole of the malaria parasite during the digestion of host cell hemoglobin. fp is detoxified by its biomineralization to hemozoin. this process is effectively inhibited by 4-aminoquinolines. as a result fp accumulates in the membrane fraction and associates with enzymes of infected cells in parallel with parasite killing. free fp is degraded by reduced glutathione (gsh). this degradation is inhibited by chloroquine (cq) and amodiaquine (a ...200312948862
cd1d-restricted nkt cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses.cd1d-restricted nkt cells are a novel t cell lineage with unusual features. they co-express some nk cell receptors and recognize glycolipid antigens through an invariant t cell receptor (tcr) in the context of cd1d molecules. upon activation through the tcr, nkt cells produce large amounts of ifn-gamma and il-4. it has been proposed that rapid cytokine output by activated nkt cells may induce bystander activation of other lymphoid lineages. the impact of cd1d-restricted nkt cell activation in th ...200312938235
age-related susceptibility and resistance to plasmodium berghei in mice and rats. 200312932766
pharmacological assessment of the role of nitric oxide in mice infected with lethal and nonlethal species of malaria.this pharmacological investigation sought to determine whether nitric oxide (no) had an antiparasitic effect and/or mediated pathology in mice infected with nonlethal p. chabaudi or lethal p. berghei. nitric oxide synthase (nos) inhibitors were evaluated for their ability to inhibit the rise in reactive nitrogen intermediates (rni) induced by bacterial lipopolysaccharide (lps) in mice. the more effective compound, aminoguanidine (ag) inhibited the rise in rni induced by p. chabaudi and increased ...200312911523
the lack of suppressor of cytokine signalling-1 (socs1) protects mice from the development of cerebral malaria caused by plasmodium berghei anka.cerebral malaria is a severe complication of infection with plasmodium berghei anka involving the th1 cytokines tnf-alpha and ifn-gamma. suppressor of cytokine signalling-1 (socs1) is an important component in the regulatory cascade controlling inflammatory responses and signalling through ifn-gamma. contrary to the expectation that socs1-deficient mice, in which ifn-gamma responses are uncontrolled and which are more sensitive to ifn-gamma, may show heightened susceptibility, mice lacking socs1 ...200312911518
the dynamics of interactions between plasmodium and the mosquito: a study of the infectivity of plasmodium berghei and plasmodium gallinaceum, and their transmission by anopheles stephensi, anopheles gambiae and aedes aegypti.knowledge of parasite-mosquito interactions is essential to develop strategies that will reduce malaria transmission through the mosquito vector. in this study we investigated the development of two model malaria parasites, plasmodium berghei and plasmodium gallinaceum, in three mosquito species anopheles stephensi, anopheles gambiae and aedes aegypti. new methods to study gamete production in vivo in combination with gfp-expressing ookinetes were employed to measure the large losses incurred by ...200312906877
protracted protection to plasmodium berghei malaria is linked to functionally and phenotypically heterogeneous liver memory cd8+ t cells.we previously demonstrated that protection induced by radiation-attenuated (gamma) plasmodium berghei sporozoites is linked to mhc class i-restricted cd8(+) t cells specific for exoerythrocytic-stage ags, and that activated intrahepatic memory cd8(+) t cells are associated with protracted protection. in this study, we further investigated intrahepatic memory cd8(+) t cells to elucidate mechanisms required for their maintenance. using phenotypic markers indicative of activation (cd44, cd45rb), mi ...200312902507
in vivo antimalarial activities of mono- and bis quaternary ammonium salts interfering with plasmodium phospholipid metabolism.we previously showed that quaternary ammonium salts have potent antimalarial activities against the blood stage of drug-resistant plasmodium falciparum. in the present study, 13 compounds of this series were comparatively assessed in murine in vivo malarial models. mice infected with plasmodium berghei were successfully treated with 11 quaternary ammonium salts in a 4-day suppressive test with a once-daily intraperitoneal administration. the dose required to decrease parasitemia by 50% (ed(50)) ...200312878525
transfected plasmodium knowlesi produces bioactive host gamma interferon: a new perspective for modulating immune responses to malaria parasites.transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (ifn-gamma) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. using the primate malaria parasite plasmodium knowlesi, we explored the conditions for expressing host cytokines ...200312874315
in vivo antimalarial activity of vernonia amygdalina.extracts from the leaves and root bark of vernonia amygdalina are assessed for antimalarial activity against drug-sensitive plasmodium berghei in mice. a standard inoculum of 1 x 10(7) infected erythrocytes is used, and leaf and root-bark extracts of 500 mg/kg, 250 mg/kg or 125 mg/kg are used in a four-day suppression test and a rane test of established infection. leaf extract produced 67% suppression of parasitaemia in the four-day test, while root-bark extract produced 53.5% suppression. these ...200312866916
antimalarial activity of cinchona-like plants used to treat fever and malaria in brazil.for centuries, malaria was treated with the bark of cinchona calisaya and cinchona succirubra plants named "quinas" in brazil, from which the quinine molecule was isolated. other plant species known also as "quinas" are used to treat fever and malaria, like deianira erubescens (roots and leaves), strychnos pseudoquina (bark), and remijia ferruginea (bark). based on this popular knowledge, we evaluated the in vivo antimalarial activity of the ethanol crude extracts of these plant species in mice ...200312860318
soap, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development.an essential, but poorly understood part of malaria transmission by mosquitoes is the development of the ookinetes into the sporozoite-producing oocysts on the mosquito midgut wall. for successful oocyst formation newly formed ookinetes in the midgut lumen must enter, traverse, and exit the midgut epithelium to reach the midgut basal lamina, processes collectively known as midgut invasion. after invasion ookinete-to-oocyst transition must occur, a process believed to require ookinete interaction ...200312828632
different responses of three rodent plasmodia species, plasmodium yoelii 17xl, p. berghei nk65 and p. chabaudi as on treatment with febrifugine and isofebrifugine mixture from hydrangea macrophylla var. otaksa leaf in icr mice.the antimalarial activity of hydrangea macrophylla var. otaksa alkaloids was evaluated against plasmodium yoelii 17xl, p. berghei nk65 and p. chabaudi as in icr mice. for trials in p. yoelii 17xl or p. chabaudi as infections, mice were infected intraperitoneally with 10(5), 10(6) and 10(7) parasitized erythrocytes, respectively, and in p. berghei nk65 infections, mice were infected intraperitoneally with 10(3), 10(4) and 10(5) parasitized erythrocytes, respectively. three days after injection, m ...200312820234
plasmodium falciparum: new vector with bi-directional promoter activity to stably express transgenes. 200312810052
the chemotherapy of rodent malaria. lxi. drug combinations to impede the selection of drug resistance, part 4: the potential role of 8-aminoquinolines.the influence of combinations containing the blood schizontocides chloroquine (cq) or mefloquine (mef), together with the 8-aminoquinolines (8aq) primaquine (pq) or the new, long-acting compound, tafenoquine (taf), on the rate of selection of resistance to the individual compounds was examined using the asexual, intra-erythrocytic stages in rodent malaria models. the two main procedures used were a 'serial technique' (st) and the '2%- relapse technique' (2%rt). the st provided evidence for the c ...200312803854
validation of the hexose transporter of plasmodium falciparum as a novel drug target.chemotherapy of malaria parasites is limited by established drug resistance and lack of novel targets. intraerythrocytic stages of plasmodium falciparum are wholly dependent on host glucose for energy. glucose uptake is mediated by a parasite-encoded facilitative hexose transporter (pfht). we report that o-3 hexose derivatives inhibit uptake of glucose and fructose by pfht when expressed in xenopus oocytes. selectivity of these derivatives for pfht is confirmed by lack of inhibition of hexose tr ...200312792024
a short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic beta-sulfonyl-endoperoxides.the syntheses and in vitro antimalarial screening of 50 bridged, bicyclic endoperoxides of types 9-13 are reported. in contrast to antimalarial trioxanes of the artemisinin family, but like yingzhaosu a and arteflene, the peroxide function of compounds 9-13 is contained in a 2,3-dioxabicyclo[3.3.1]nonane system 6. peroxides 9 and 10 (r(1) = oh) are readily available through a multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a toco reaction). beta-sul ...200312773055
intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain.plasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ecm), exhibit a systemic inflammatory response. most investigators hypothesize that leukocytes bind to endothelial cells via intercellular adhesion molecule 1 (icam-1), which causes endothelial damage, increased microvascular permeability, and, ultimately, death. icam-1-deficient mice on an ecm-susceptible c57bl/6 background were significantly (p = .04) protected from p. berghei mortality compared with ic ...200312769195
chemokine receptor ccr2 is not essential for the development of experimental cerebral malaria.infection with plasmodium berghei anka induces cerebral malaria in susceptible mice. brain-sequestered cd8(+) t cells are responsible for this pathology. we have evaluated the role of ccr2, a chemokine receptor expressed on cd8(+) t cells. infected ccr2-deficient mice were as susceptible to cerebral malaria as wild-type mice were, and cd8(+) t-cell migration to the brain was not abolished.200312761155
om-174, a new adjuvant with a potential for human use, induces a protective response when administered with the synthetic c-terminal fragment 242-310 from the circumsporozoite protein of plasmodium berghei.the goal of this project was the evaluation of a novel immunomodulatory adjuvant for human use, om-174, which is a soluble adjuvant derived from escherichia coli lipid a. for this study, we used a synthetic peptide, known for its safety and reproducibility and the murine model of balb/c mice. the long peptide (pbcs 242-310) used corresponds to the c-terminal region of the circumsporozoite protein (csp) that is the major protein on the surface of plasmodium sporozoites. subcutaneous injections of ...200312744882
efficacy comparison of intravenous artelinate and artesunate in plasmodium berghei-infected sprague-dawley rats.this paper reports the comparative antimalarial efficacy of intravenous artelinate and artesunate in rats. prior to efficacy experiments, a plasmodium berghei-sprague-dawley rat model of malaria was developed, in which the clearance effects of intravenous drugs could be readily compared. in efficacy experiments, groups of p. berghei-infected rats were given 3 daily intravenous treatments of artelinate or artesunate at molar equivalent dose rates (total of 0-191.2 micromoles/kg). artelinate was s ...200312741507
the histone h4 gene of plasmodium falciparum is developmentally transcribed in asexual parasites.histones are abundant nuclear core proteins that are present in all eukararyotes and are responsible for linking chromosomes and packaging them into tight chromatin aggregates. the histone h2a, h2b, and h3 genes and a partial sequence of the histone h4 gene from plasmodium falciparum have been previously identified and share a high level of nucleotide sequence identity. in this study, we compare the histone h4 sequence of the human malaria p. falciparum with the sequences of two mouse malarias, ...200312739134
predominant cell-mediated immunity in the oral mucosa: gene gun-based vaccination against infectious diseases.direct immunization via epithelial surfaces has been considered for many vaccine approaches, including dna vaccines. it remains to be determined, however, which body site is suitable for genetic vaccination.200312727024
[long circulating nanocapsules: interest in the treatment of severe malaria with halofantrine].the aim of the work was to develop a new submicronic delivery system that can be used with poorly water soluble drugs for which sustained circulating concentrations are necessary. this system consists of oily core surrounded by a shell made of a copolymer of poly (d,l-lactid) and poly (ethylene glycol). covalent coupling between the hydrophylic poly (ethylene glycol) and poly (d,l lactid) and high molecular weight of the poly (ethylene glycol) chains yield long circulating particles after intra- ...200312714932
transformation of sporozoites into early exoerythrocytic malaria parasites does not require host cells.malaria parasite species that infect mammals, including humans, must first take up residence in hepatic host cells as exoerythrocytic forms (eef) before initiating infection of red blood cells that leads to malaria disease. despite the importance of hepatic stages for immunity against malaria, little is known about their biology and antigenic composition. here, we show that sporozoites, the parasites' transmission stage that resides in the mosquito vector salivary glands, can transform into earl ...200312707302
chloroquine-induced masking of a lipid that promotes ferriprotoporphyrin ix dimerization in malaria.mice infected with the nyu-2 strain of plasmodium berghei were used to study the effect of chloroquine on masking of a lipid that promotes ferriprotoporphyrin ix dimerization. more than 40% of this lipid was masked and unable to promote dimerization in membrane ghosts from erythrocytes of untreated, infected mice. thus, preparations of membrane ghosts dimerized 57 +/- 6 nmol of ferriprotoporphyrin ix during a 2-h incubation, whereas the lipids extracted from these preparations dimerized 101 +/- ...200312697766
cytokine and chemokine responses in a cerebral malaria-susceptible or -resistant strain of mice to plasmodium berghei anka infection: early chemokine expression in the brain.a comparative study was carried out on cytokine and chemokine responses in a cerebral malaria (cm)-susceptible or -resistant strain of mice (c57bl/6 or balb/c respectively) in plasmodium berghei anka infection. c57bl/6 mice died by 10 days after infection when parasitemia was approximately 15-20% with cerebral symptoms, while balb/c mice survived until week 3 after infection. although both strains showed t(h)1-skewed responses on day 4 after infection, significantly higher levels of ifn-gamma, t ...200312697663
p-selectin contributes to severe experimental malaria but is not required for leukocyte adhesion to brain microvasculature.plasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ecm), exhibit many of the hallmarks of a systemic inflammatory response, with organ damage in brain, lung, and kidneys. identification of the molecules mediating pathogenesis of the inflammatory response, such as leukocyte adhesion, may lead to new therapies. indeed, mice lacking the cell adhesion molecule p-selectin were significantly (p = 0.005) protected from death due to p. berghei malaria compared wi ...200312654808
expression of inducible nitric oxide synthase (inos) mrna in target organs of lethal and non-lethal strains of murine malaria.nitric oxide (no) is a putative mediator of the immunological and/or pathological responses to malaria, consequently it is a potential target for novel drug therapy. numerous cell types increase expression of inducible nitric oxide synthase (inos) under inflammatory conditions, the most relevant stimuli being cytokines and endotoxins. in this study the expression of inos mrna in several target organs (brain, liver, spleen) of malaria have been investigated in mf1 mice during lethal plasmodium (p ...200212654089
regulation of murine cerebral malaria pathogenesis by cd1d-restricted nkt cells and the natural killer complex.nkt cells are specialized cells coexpressing nk and t cell receptors. upon activation they rapidly produce high levels of interferon-gamma (ifn-gamma) and interleukin-4 (il-4) and are therefore postulated to influence t(h)1/t(h)2 immune responses. the precise role of the cd1/nkt cell pathway in immune response to infection remains unclear. we show here that cd1d-restricted nkt cells from distinct genetic backgrounds differentially influence t(h)1/t(h)2 polarization, proinflammatory cytokine leve ...200312648456
leptin and leptin receptors during malaria infection in mice.leptin, which is involved in a range of physiological processes, could be an important factor in the pathogenesis of malaria. we found that levels of leptin in serum and urine in plasmodium berghei-infected mice increased progressively after infection, reaching a maximum value on day 6 post-infection. serum values were approximately five-fold higher in infected mice than in non-infected controls. a similar relation was found for values of leptin in urine. soluble leptin receptor levels also incr ...200212641196
influence of cd4+cd25+ t cells on plasmodium berghei nk65 infection in balb/c mice.cd4(+) t cells co-expressing cd25 (cd4(+)cd25(+) t cells) have been identified as immunoregulatory suppressors modulating autoimmune response. beside that, autoimmune response was supposed to be associated with malaria infection. based on these data, we hypothesised that cd4(+)cd25(+) t cells may influence protective immunity to malaria parasites, while suppressing autoimmune response arising throughout the course of malarial infection. to test this possibility, we evaluated the kinetics of cd4( ...200312633655
the effect of 10 alpha-trifluoromethylhydroartemisinin on plasmodium berghei infection and its toxicity in experimental animals.the antimalarial activity of 10 alpha-trifluoromethylhydroartemisinin (tfmha) was compared to that of dihydroartemisinin (dha) in the plamodium berghei mouse model. treatment with tfmha in mice infected with a p. berghei chloroquine-sensitive strain at 25 mg/kg for 3, 5, and 7 d, or dha at the same dose for 7 d showed the parasite was eliminated from the host within 2.6 d. the radical cure and survival rates of these mice up to 60 d after infection were 90-100%. in mice infected with the p. berg ...200212625149
orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy.in only two steps and in 70% overall yield, naturally occurring trioxane artemisinin (1) was converted on a gram scale into c-10-carba trioxane dimer 3. this new, very stable dimer was then transformed easily in one additional step into four different dimers 4-7. alcohol and diol dimers 4 and 5 and ketone dimer 7 are 10 times more antimalarially potent in vitro than artemisinin (1), and alcohol and diol dimers 4 and 5 are strongly growth inhibitory but not cytotoxic toward several human cancer c ...200312620083
a unique insertion in plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: evolutionary and functional studies.plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (g6pd-6pgl) is a bifunctional enzyme with significant sequence similarity in both the 6pgl and g6pd domains to the plasmodium falciparum enzyme. a recombinant form of the p. berghei enzyme was found to have both g6pd and 6pgl activities, and therefore catalyses the first two steps in the pentose phosphate pathway. genes encoding very similar proteins are also found in three other malarial parasites, plasmodium yoelii, ...200312615331
characterization of a unique aspartate-rich protein of the set/taf-family in the human malaria parasite, plasmodium falciparum, which inhibits protein phosphatase 2a.a search for physiological inhibitors of protein phosphatases led to the identification of a plasmodium falciparum (pf) cdna that had the potential to code for an aspartate-rich protein and hence named arp. the pfarp was virtually identical to its plasmodium berghei counterpart in gene structure and protein sequence. the pfarp coding sequence contained two introns, and the predicted protein contained 269 amino acid residues. its primary structure showed significant similarity to eukaryotic prote ...200312615323
a gene-family encoding small exported proteins is conserved across plasmodium genus.a gene-family, named sep, encoding small exported proteins conserved across plasmodium species has been identified. sep proteins (13-16 kda) contain a predicted signal peptide at the nh(2)-terminus, an internal hydrophobic region and a polymorphic, low-complexity region at the carboxy-terminus. one member of the plasmodium berghei family, pbsep1, encodes an integral membrane protein expressed along the entire erythrocytic cycle. immunolocalisation results indicated that pbsep1 is targeted to the ...200312615320
plasmodium berghei: analysis of the gamma-glutamylcysteine synthetase gene in drug-resistant lines.the rapid emergence of multidrug-resistant plasmodium falciparum is a worldwide concern. despite the magnitude of the problem, the mechanisms involved in this phenomenon are not well understood. one current proposal suggests that toxic heme molecules are degraded by glutathione (gsh), and that anti-malarial drugs, such as chloroquine (cq), inhibit this degradation, thus implicating gsh in drug resistance. furthermore, in some strains of plasmodium berghei and p. falciparum, chloroquine resistanc ...200212594957
perforin-dependent brain-infiltrating cytotoxic cd8+ t lymphocytes mediate experimental cerebral malaria pathogenesis.experimental cerebral malaria (ecm) resulting from plasmodium berghei anka infection involves t lymphocytes. however, the mechanisms of t cell-mediated pathogenesis remain unknown. we found that, in contrast to ecm-susceptible c57bl6 mice, perforin-deficient (pfp-ko) mice were resistant to ecm in the absence of brain lesions, whereas cytoadherence of parasitized erythrocytes and massive accumulation of activated/effector cd8 lymphocytes were observed in both groups of mice. ecm is induced in pfp ...200312574396
relationship of chloroquine-induced redistribution of a neutral aminopeptidase to hemoglobin accumulation in malaria parasites.to study the relationship between neutral aminopeptidase activity and hemoglobin accumulation in malaria parasites, we treated mice infected with plasmodium berghei nyu-2 with chloroquine intraperitoneally in doses ranging from 0.3 to 3 micromol per 25 g mouse. preparations of infected erythrocytes (normalized to represent 1000 parasites per 1000 erythrocytes) hydrolyzed 1200 nmol of leucine-p-nitroanilide per minute per milliliter of packed erythrocytes, which was 10x more than that of uninfect ...200312573290
[effect of daphnetin on the exo-erythrocytic stage of rodent malaria].to investigate the activity of daphnetin(dpnt) against the exo-erythrocytic stage of rodent malaria.200112572020
[the antimalarial mechanism of artemisinin and its derivatives]. 200112571953
[analysis on karyotypes of anka strain of plasmodium berghei].to analyze the molecular karyotypes of anka strain of plasmodium berghei and demonstrate the size and number of chromosomes.200112571949
[partial sequence of sporogony stage-specific 18s ribosomal dna of plasmodium yoelii and its application for detection of parasites].to determine sequence of sporogony stage-specific (s type) 18s ribosomal rna gene of plasmodium yoelii (p. y) by265 strain, and by using it to detect the malaria parasites within vector mosquito.200112571939
new semisynthetic quassinoids with in vivo antimalarial activity.on the basis of a comparative analysis for stability in mouse serum between 15-o-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-o-accetyl ...200312570385
synthesis and in vitro and in vivo antimalarial activity of n1-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine derivatives.three series of monoquinolines consisting of a 1,4-bis(3-aminopropyl)piperazine linker and a large variety of terminal groups were synthesized. our aim was to prove that in related bisquinoline, it is the second quinoline moiety that is responsible for cytotoxicity and that it is not an absolute requirement for overcoming resistance to chloroquine (cq). eleven compounds displayed a higher selectivity index (ratio cc50/ic50 activity) than cq, and one of them cured mice infected by plasmodium berg ...200312570376
[the synergistic action of guanghuoxiang volatile oil and sodium artesunate against plasmodium berghei and reversal of sa-resistant plasmodium berghei].to study the synergistic action of a combination of guanghuoxiang volatile oil (b) and sodium artesunate (sa) against plasmodium berghei (p. b) and the resistance-reversal activity against sa-resistant p. b (p. b sa-r).200012567719
[role of tnf-alpha and icam-1 in pathogenesis of cerebral malaria].to investigate the role of tnf-alpha and icam-1 in the pathogenesis of cerebral malaria.200012567686
the schizontocidal activity of daphnetin against malaria parasites in vitro and in vivo.to investigate the in vitro and in vivo schizontocidal activity of daphnetin.200012567659
[effect of nippostrongylus brasiliensis induced alterations in t helper cell subsets on plasmodium berghei infection in mice].to observe the anti-p. berghei ability of c57bl/6 mice after infected with nippostrongylus brasiliensis alterations in t helper cell subsets in the course of plasmodium infection, and the effect of the alteration on host's prognoses.200012567637
[studies on pharmacokinetics of chloroquine in mice infected with chloroquine-resistant strain of plasmodium berghei].to compare the pharmacokinetic differences of chloroquine in normal mice and the mice infected with the n and the rc strains of plasmodium berghei.200012567636
[study on inducing an artemisinin-resistant line of plasmodium berghei].to induce a line of plasmodium berghei with resistance to artemisinin.200212567543
[distribution of chloroquine in mitochondria, microsome and acid-precipitated protein from plasmodium berghei]. 199912563846
[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.199912563809
[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.199912563771
ccr5 deficiency decreases susceptibility to experimental cerebral malaria.infection of susceptible mouse strains with plasmodium berghei anka (pba) is a valuable experimental model of cerebral malaria (cm). two major pathologic features of cm are the intravascular sequestration of infected erythrocytes and leukocytes inside brain microvessels. we have recently shown that only the cd8+ t-cell subset of these brain-sequestered leukocytes is critical for progression to cm. chemokine receptor-5 (ccr5) is an important regulator of leukocyte trafficking in the brain in resp ...200312560237
encapsulation of peptides in biodegradable microspheres prolongs their mhc class-i presentation by dendritic cells and macrophages in vitro.biodegradable microspheres (ms) consisting of poly(d,l-lactide-co-glycolide) (plga) represent a promising alternative to conventional adjuvants. the adjustable pulsatile release of encapsulated material from such ms offers the potential to mimic the priming and boosting injections of conventional immunization regimens. in this paper, we demonstrate that ms can serve as antigen reservoirs in antigen presenting cells (apc), so that antigen is presented for extended periods of time (up to 9 days). ...200312559806
oral artesunate prevents plasmodium berghei anka infection in mice.artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial artemisinin was compared with chloroquine in c57bl/6 mice infected with plasmodium berghei anka (pba). a 7-day oral administration of artesunate prevented parasitaemia at 10 mg/kg/day. however, recrudescence of parasitaemia and cerebral malaria occurred upon cessation of treatment followed by death within 28 days. however, a 14-day course of artesunate (100 mg/kg/day) prevented completely the development of parasitaem ...200312543147
heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non-mutagenic in vitro.heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated from a marine tunicate collected in zamboanga, philippines, as part of a program to screen natural products for antiparasitic activity. an in vitro antimalarial activity similar to that of quinine was found against the chloroquine-sensitive strain plasmodium falciparum 3d7. the in vitro antimalarial activity was about 20 times the in vitro cytotoxic activity against l5178y mouse lymphocytes. a single subcutaneous adm ...200212503881
azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of plasmodium berghei.transmission of malaria parasites from vertebrate blood to the mosquito vector depends critically on the differentiation of the gametocytes into gametes. this occurs in response to environmental stimuli encountered by the parasite in the mosquito bloodmeal. male gametogenesis involves three rounds of dna replication and endomitosis, and the assembly de novo of 8 motile axonemes. azadirachtin, a plant limnoid and insecticide with an unkown mode of action, specifically inhibits the release of moti ...200212503686
cam kinase ii-alpha activity, levels and ca/calmodulin dependent phosphorylation of substrate proteins in mice brain during fatal murine cerebral malaria.the activity and levels of cam kinase ii-alpha was investigated in the cytosolic and membrane fraction of mice cerebral cortex and cerebellum using an experimental model of fatal murine cerebral malaria (fmcm). in parallel, ca(2+)/calmodulin dependent phosphorylation of target substrate proteins was studied using syntide-2 as substrate. pathology of fmcm resulted in decreased cam kinase-ii activity in both cortex and cerebellum though western analysis revealed no appreciable changes in the level ...200312499055
immune response of anopheles gambiae to the early sporogonic stages of the human malaria parasite plasmodium falciparum.deciphering molecular interactions between the malaria parasite and its mosquito vector is an emerging area of research that will be greatly facilitated by the recent sequencing of the genomes of anopheles gambiae mosquito and of various plasmodium species. so far, most such studies have focused on plasmodium berghei, a parasite species that infects rodents and is more amenable to studies. here, we analysed the expression pattern of nine an.gambiae genes involved in immune surveillance during de ...200212485988
regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria.plasmodium falciparum malaria in humans and animal models of this disease have revealed changes in the infected host that are consistent with a systemic inflammatory response. although it has been proposed that endothelial cell adhesion molecules (cam) contribute to the adhesive interactions of plasmodium-infected erythrocytes and immune cells with vascular endothelial cells, ecam expression has not been systematically studied in plasmodium-infected animals.200212483543
cutting edge: a new tool to evaluate human pre-erythrocytic malaria vaccines: rodent parasites bearing a hybrid plasmodium falciparum circumsporozoite protein.malaria vaccines containing the plasmodium falciparum circumsporozoite protein repeat domain are undergoing human trials. there is no simple method to evaluate the effect of vaccine-induced responses on p. falciparum sporozoite infectivity. unlike the rodent malaria plasmodium berghei, p. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. we generated a recombinant p. berghei parasite bearing p. falciparum circumsporozoite prote ...200212471098
cloning and characterization of four anopheles gambiae serpin isoforms, differentially induced in the midgut by plasmodium berghei invasion.the genomic locus srpn10 of the malaria vector anopheles gambiae codes for four alternatively spliced serine protease inhibitors of the serpin superfamily. the four 40- to 42-kda isoforms differ only at their c terminus, which bears the reactive site loop, and exhibit protein sequence similarity with other insect serpins and mammalian serpins of the ovalbumin family. inhibition experiments with recombinant purified srpn10 serpins reveal distinct and specific inhibitory activity of three isoforms ...200312456678
on the pathogenic role of brain-sequestered alphabeta cd8+ t cells in experimental cerebral malaria.cerebral malaria (cm) develops in a small proportion of persons infected with plasmodium falciparum and accounts for a substantial proportion of the mortality due to this parasite. the actual pathogenic mechanisms are still poorly understood, and in humans investigations of experimental cm are unethical. using an established plasmodium berghei-mouse cm model, we have investigated the role of host immune cells at the pathological site, the brain. we report in this study the detailed quantificatio ...200212444144
soluble major histocompatibility complex-peptide octamers with impaired cd8 binding selectively induce fas-dependent apoptosis.fluorescence-labeled soluble major histocompatibility complex class i-peptide "tetramers" constitute a powerful tool to detect and isolate antigen-specific cd8(+) t cells by flow cytometry. conventional "tetramers" are prepared by refolding of heavy and light chains with a specific peptide, enzymatic biotinylation at an added c-terminal biotinylation sequence, and "tetramerization" by reaction with phycoerythrin- or allophycocyanin-labeled avidin derivatives. we show here that such preparations ...200312407102
chromosome number, genome size and polymorphism of european and south african isolates of large babesia parasites that infect dogs.pulsed-field gel electrophoresis of intact chromosomes from 2 isolates of each of the 2 most pathogenic species of large babesia parasites that infect dogs, i.e. babesia canis (european species) and b. rossi (south african species), revealed 5 chromosomes in their haploid genome. the size of chromosomes 1-5 was found to be different in the 2 species, ranging from 0.8 to 6.0 mbp. the genome size was estimated to be approximately 14.5 mbp for b. canis and 16 mbp for b. rossi, respectively. within ...200212403319
the chemotherapy of rodent malaria. lx. the importance of formulation in evaluating the blood schizontocidal activity of some endoperoxide antimalarials.the activities of artemisinin (qhs) and a number of its semi-synthetic analogues, as well as fenozan b07 (b07), a synthetic 1,2,4-trioxane, and arteflene (atf), a synthetic surrogate of yingzhaosu, were compared in mice infected with drug-sensitive plasmodium berghei or chloroquine-resistant p. yoelii ssp. ns. the studies were stimulated by the observation that b07, in certain aqueous preparations, appears to be equipotent by the subcutaneous (sc) or oral (po) routes in the rodent model but not ...200212396319
antimalarial activity of yingzhaosu a analogues.iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu a analogues 2. in some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting materials. some of the cyclic peroxides 2 showed significant antimalarial activities in vitro and in vivo.200212361400
a malaria scavenger receptor-like protein essential for parasite development.malaria parasites suffer severe losses in the mosquito as they cross the midgut, haemolymph and salivary gland tissues, in part caused by immune responses of the insect. the parasite compensates for these losses by multiplying during the oocyst stage to form the infectious sporozoites. upon human infection, malaria parasites are again attenuated by sustained immune attack. here, we report a single copy gene that is highly conserved amongst plasmodium species that encodes a secreted protein named ...200212354219
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