Publications

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 ...	2003	12615320
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 ...	2003	12615323
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, ...	2003	12615331
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 ...	2003	12620083
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 ...	2003	12573290
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 ...	2003	12574396
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 ...	2003	12570376
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 ...	2003	12570385
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 ...	2003	12407102
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 ...	2003	12499055
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 ...	2003	12456678
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 ...	2003	12543147
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). ...	2003	12559806
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 ...	2003	12560237
8-quinolinamines and their pro prodrug conjugates as potent blood-schizontocidal antimalarial agents.	synthesis and antimalarial activities of n8-(4-amino-1-methylbutyl)-5-alkoxy-4-ethyl-6-methoxy-8-quinolinamines (5) and their pro prodrug analogues (6-7) prepared by covalently linking 5 to the redox-sensitive (8) and esterase-sensitive (9) linkers through the amide linkage are reported. the most effective 8-quinolinamines [5c (r=c5h11) and 5f (r=c8h17)] have exhibited in vitro and in vivo biological efficacy superior to that of the standard drug chloroquine against both drug-sensitive and drug- ...	2003	14527552
rheumatoid factor-like igm in plasmodium berghei (apicomplexa: haemosporida) infections of balb/c mice.	groups of female balb/c mice infected by intravenous injection with 50 erythrocytes containing plasmodium berghei vincke et lips, 1948 were sacrificed on days 3 through 12 after infection. rheumatoid factor-like igm (rf-igm) and parasite-specific igg levels were determined by enzyme-linked immunosorbent assay in serum specimens and in culture medium removed from spleen cell cultures established at sacrifice. all four mouse igg subisotypes were recognized by rf-igm molecules induced by plasmodium ...	2003	14535342
plasmepsin 4, the food vacuole aspartic proteinase found in all plasmodium spp. infecting man.	plasmepsins are aspartic proteinases of the malaria parasite, and seven groups of plasmepsins have been identified by comparing genomic sequence data available for the genes encoding these enzymes from plasmodium falciparum, plasmodium vivax, plasmodium knowlesi, plasmodium berghei, and plasmodium yoelii. the food vacuole plasmepsins typified by plasmepsin 4 from p. falciparum (pfpm4) constitute one of these groups. genes encoding the ortholog of pfpm4 have been cloned from plasmodium ovale, pla ...	2003	14550891
heterologous promoter activity in stable and transient plasmodium knowlesi transgenes.		2003	14550898
[genetic analysis of host resistance to rodent malaria in mice].		2003	14562624
inhibition of platelet adherence to brain microvasculature protects against severe plasmodium berghei malaria.	some patients with plasmodium falciparum infections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis. plasmodium berghei-infected mice are a well-recognized model of severe malaria (experimental severe malaria [esm]), and infected mice exhibit a systemic inflammatory response. because platelets are proposed to ...	2003	14573677
baculovirus virions displaying plasmodium berghei circumsporozoite protein protect mice against malaria sporozoite infection.	the display of foreign proteins on the surface of baculovirus virions has provided a tool for the analysis of protein-protein interactions and for cell-specific targeting in gene transfer applications. to evaluate the baculovirus display system as a vaccine vehicle, we have generated a recombinant baculovirus (acnpv-cspsurf) that displays rodent malaria plasmodium berghei circumsporozoite protein (pbcsp) on the virion surface as a fusion protein with the major baculovirus envelope glycoprotein g ...	2003	14599800
combination effects of chloroquine with the febrifugine and isofebrifugine mixture against a blood-induced infection with chloroquine-resistant plasmodium berghei nk65 in icr mice.	the combination effects of chloroquine with a mixture of febrifugine and isofebrifugine were evaluated against a blood-induced infection with chloroquine-resistant p. berghei nk65 in icr mice. mice in the untreated control showed a progressively increasing parasitemia leading to mouse death. a two-day dosage of 20 mg base/kg of chloroquine alone showed little effect against p. berghei nk65 infection, and all mice died from day 13 to 14 with an increasing parasitemia. a four-day dosage of 1 mg/kg ...	2003	14669265
activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule.	much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are part of the immune response that kills the parasite. the antiinflammatory cytokine transforming growth factor (tgf)-beta plays a crucial role in preventing the severe pathology of malaria in mice and tgf-beta production is associated with reduced risk of clinical malaria in humans. here we show that serum-free preparations of plasmodium fal ...	2003	14676296
isolation of plasmodium berghei ookinetes in culture using nycodenz density gradient columns and magnetic isolation.	background: large scale in vitro production of the mosquito stages of malaria parasites remains elusive, with only limited success for complete sporogonic development and only one report of development through to infective sporozoites. the initial step in this process is the production, in vitro, of ookinetes from gametocytaemic blood. methods for isolation of these ookinetes from blood cells have been described; however, in addition to yield often being low, processing time and potential for co ...	2003	14613512
in-vivo antimalarial activity of some oxygenated xanthones.	a series of oxygenated xanthones was prepared so that the antimalarial activity of each compound could be evaluated in vivo, using 4-day suppressive assays against plasmodium berghei anka in balb/c mice. when given in a dose of 20 mg/kg.day for 4 days, most of the compounds produced significant chemosuppression of parasitaemia. the most active compound was 1,3,6,8-tetrahydroxyxanthone, which reduced the percentage of erythrocytes infected by 70.5%, followed by norlichexanthone (44.3%) and its is ...	2003	14613627
the role of reactive oxygen species on plasmodium melanotic encapsulation in anopheles gambiae.	malaria transmission depends on the competence of some anopheles mosquitoes to sustain plasmodium development (susceptibility). a genetically selected refractory strain of anopheles gambiae blocks plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. morphological and microarray mrna expression analysis suggest that the refractory and susceptible strains have broad physiological difference ...	2003	14623973
glutathione is involved in the antimalarial action of chloroquine and its modulation affects drug sensitivity of human and murine species of plasmodium.	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 chloroquine (cq) and amodiaquine (aq). undegraded fp accumulates in the membrane fraction and inhibits enzymes of infected cells in parallel with parasite killing. fp is demonstrably degraded by reduced glutathione (gsh) in a radical-mediated mechanism. this degradation ...	2003	14962364
double-drug development against antioxidant enzymes from plasmodium falciparum.	new drugs against malaria are urgently and continuously needed. plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems. a most important antioxidative system consists of (di)thiols which are recycled by disulfide reductases (dr), namely both glutathione reductases (gr) of the malarial parasite plasmodium falciparum and man, and the thioredoxin reductase (trxr) of p. falciparum. the aim of our interdisciplinary re ...	2003	14962365
why is the plasmodium falciparum hexose transporter a promising new drug target?	chemotherapy of malaria parasites is limited by established drug resistance and lack of novel treatment options. intraerythrocytic stages of plasmodium falciparum, the causative agent of severe malaria, are wholly dependent upon host glucose for energy. a facilitative hexose transporter (pfht), encoded by a single-copy gene, mediates glucose uptake and is therefore an attractive potential target. the authors first established heterologous expression in xenopus laevis to allow functional characte ...	2003	14498822
erythrocyte g protein-coupled receptor signaling in malarial infection.	erythrocytic mechanisms involved in malarial infection are poorly understood. we have found that signaling via the erythrocyte beta2-adrenergic receptor and heterotrimeric guanine nucleotide-binding protein (galphas) regulated the entry of the human malaria parasite plasmodium falciparum. agonists that stimulate cyclic adenosine 3',5'-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. moreover, peptides designed to inhibit ga ...	2003	14500986
quinine distribution in mice with plasmodium berghei malaria.	the disposition of a single 80 mg/kg injection of quinine base was compared in control and plasmodium berghei-infected mice. pharmacokinetic parameters were determined on repeated whole blood samples from caudal vein (experiment 1) and quinine distribution was evaluated in tissues and blood fractions from mice sacrificed two hours post dosing (experiment 2). quinine concentrations were assessed by high performance liquid chromatography with fluorometric detection. whole blood concentrations and ...	2003	14503660
metabolites of febrifugine and its synthetic analogue by mouse liver s9 and their antimalarial activity against plasmodium malaria parasite.	quinazolinone type alkaloids, febrifugine (1) and isofebrifugine (2), isolated from dichroa febrifuga roots, show powerful antimalarial activity against plasmodium falciparum. unfortunately, their emetic effect and other undesirable side effects have precluded their clinical use for malaria. because of their antimalarial potency, analogues were searched for, with the goal of preserving the strong antimalarial activity, while dramatically reducing side effects. we expected that compounds useful i ...	2003	13678413
the age-related resistance of rats to plasmodium berghei infection is associated with differential cellular and humoral immune responses.	in this study, we investigated how the age of rats would affect the course of infection of and the immune response to plasmodium berghei. both young (4-week-old) and adult rats (8-week-old) can be infected with p. berghei anka strain, with significantly higher levels of infected red blood cells in young rats. while 100% of young rats succumbed to infection, adult rats were able to clear blood parasites and no mortality was observed. analysis of cellular distribution and circulating cytokines dem ...	2003	13129529
artemisinin derivatives bearing mannich base group: synthesis and antimalarial activity.	novel artemisinin derivatives bearing mannich base group were prepared and tested for their antimalarial activity. these water-soluble artemisinin derivatives were more stable than sodium artesunate and few compounds were found to be more active against plasmodium berghei in mice than artesunic acid by oral administration. two most potent derivatives 17b and 17d were examined for their antimalarial activity against plasmodium knowlesi in rhesus monkeys.	2003	13129573
malaria parasites lacking eef1a have a normal s/m phase yet grow more slowly due to a longer g1 phase.	eukaryotic elongation factor 1a (eef1a) plays a central role in protein synthesis, cell growth and morphology. malaria parasites possess two identical genes encoding eef1a (eef1aa and eef1ab). using pbeef1a-plasmodium berghei mutants that lack an eef1a gene, we demonstrate that the level of eef1a production affects the proliferation of blood stages and parasite fitness. pbeef1a- parasites can complete the vertebrate and mosquito phases of the life cycle, but the growth phase of the asexual blood ...	2003	14651637
[studies on the antigens of invasive stages of plasmodium yoelii and plasmodium berghei].	to detect the rhoptry and surface proteins of invasive stages of plasmodium yoelii and p. berghei with monoclonal antibodies.	2003	15108514
neuropeptide-containing cells in the cortex and striatum of mice with cerebral malaria.	central nervous system tissue of mice infected with plasmodium berghei anka (pba) exhibits similar histopathological features to those in post-mortem human cerebral malaria (cm) tissue. in this study, the neurochemical characteristics of pba-infected and control mice were compared. substance p-containing neurones were almost completely lost from the cortex and striatum of pba-infected mice seven days after inoculation, whereas the intensity of calbindin immunolabelling was increased compared wit ...	2003	15206748
recent developments in marine indole alkaloid synthesis.	the manzamine alkaloids such as manzamine a, b, and c belongs to a unique family of cyctotoxic beta-carbline linked azacycles, which have been isolated from several marine sponges. manzamine a has recently been shown to exhibit in vivo antimalarial activity against parasite plasmodium berghei. further progress was added recently by the isolation of the new and closely related members such as nakadomarin a, as well as an ingenious proposal for their biosynthetic pathway. martefragin a, isolated f ...	2003	15206780
molecular biology and biochemistry of malarial parasite pyrimidine biosynthetic pathway.	metabolic pathways in the malarial parasite are markedly different from the host, eg, hemoglobin, fatty acids, folate and nucleic acids. understanding of metabolic function will illuminate new chemotherapeutic targets for drug development, including the identification of target(s) for drugs in current use. the parasite-contained pyrimidine biosynthetic pathway is essential for growth and development in the human host. plasmodium falciparum carbonic anhydrase, producing hco3- as a pyrimidine prec ...	2003	19230569
the role of nitric oxide and its up/downstream molecules in malaria: cytotoxic or preventive?	the current study investigated the involvement of nitric oxide (no) and related molecules in malaria target organs of outbred mf1 mice during lethal plasmodium berghei and non-lethal p. c. chabaudi infections, in order to evaluate whether changes in no production are beneficial or detrimental to the host. a number of methods have been applied to test this hypothesis, including griess microassay, electrochemical assay, rt-pcr and western blot. the results show that reactive nitrogen intermediate ...	2003	19230570
short report: lethal malaria in cytosolic phospholipase a2- and phospholipase a2iia-deficient mice.	lipid mediators play important roles in the pathogenesis of malaria. phospholipase a2s are enzymes involved in the production of these mediators, and they function in inflammation. among them, cytosolic phospholipase a2 (cpla2) is a key enzyme in the metabolism of arachidonic acid, the first intermediate in the production of lipid mediators. plasmodium berghei anka causes cerebral malaria in cl57b/6 mice, and we recently produced cpla2-deficient mice with this background. with the expectation of ...	2004	15211007
a small peptide (cel-1000) derived from the beta-chain of the human major histocompatibility complex class ii molecule induces complete protection against malaria in an antigen-independent manner.	cel-1000 (dgqeekagvvstgliggg) is a novel potential preventative and therapeutic agent. we report that cel-1000 confers a high degree of protection against plasmodium sporozoite challenge in a murine model of malaria, as shown by the total absence of blood stage infection following challenge with 100 sporozoites (100% protection) and by a substantial reduction (400-fold) of liver stage parasite rna following challenge with 50,000 sporozoites. cel-1000 protection was demonstrated in a/j (h-2(a)) a ...	2004	15215094
the mb2 gene family of plasmodium species has a unique combination of s1 and gtp-binding domains.	identification and characterization of novel plasmodium gene families is necessary for developing new anti-malarial therapeutics. the products of the plasmodium falciparum gene, mb2, were shown previously to have a stage-specific pattern of subcellular localization and proteolytic processing.	2004	15222903
progress in dna-based heterologous prime-boost immunization strategies for malaria.	an effective vaccine against malaria is urgently required to relieve the immense human suffering and mortality caused by this parasite. a successful subunit vaccine against the liver stage of malaria will require the induction of high levels of protective t cells. despite success in small animal models, dna vaccines fail to induce strong cellular immune responses in humans. however, dna vaccines can induce a t-cell response that can be strongly boosted by recombinant viral vectors. we have evalu ...	2004	15233731
increased parasitaemia and delayed parasite clearance in schistosoma mansoni and plasmodium berghei co-infected mice.	identifying factors that contribute to malaria susceptibility, severity and treatment failure remains one of the major research areas in malaria control strategies. in the present study, we superinfected schistosoma mansoni infected mice with a lethal strain plasmodium berghei anka to assess whether or not infection with s. mansoni affects parasite development, parasitaemia and parasite reduction or clearance following antimalarial treatment. mice infected with p. berghei alone were used as cont ...	2004	15234665
antimalarial activities of tithonia diversifolia (asteraceae) and crossopteryx febrifuga (rubiaceae) on mice in vivo.	ethanolic extracts of the aerial part of tithonia diversifolia and the stem bark of crossopteryx febrifuga were investigated against early, residual (repository) and established malaria infections in vivo using swiss albino mice at a dose range of 50-400 mg/kg per day. chloroquine at 5 mg/kg per day was used as the positive control for the early and established infections while pyrimethamine at 1.2 3/kg per day was used as the positive control for the residual infection test. dose dependent chem ...	2004	15234749
mosquito--malaria interactions: a reappraisal of the concepts of susceptibility and refractoriness.	this paper considers the available literature on the transmission of malaria by insects and concludes that, in contrast to the commonly held view (that implies mosquitoes are naturally vectors of malaria), it is more useful to consider that mosquitoes, like plants, normally express a variety of gene products, which together render the host resistant to infection. the consequences of this hypothesis upon current research are that when studying the passage of the malarial parasite through a compet ...	2004	15242703
plasmodium induces swelling-activated clc-2 anion channels in the host erythrocyte.	intraerythrocytic growth of the human malaria parasite plasmodium falciparum depends on delivery of nutrients. moreover, infection challenges cell volume constancy of the host erythrocyte requiring enhanced activity of cell volume regulatory mechanisms. patch clamp recording demonstrated inwardly and outwardly rectifying anion channels in infected but not in control erythrocytes. the molecular identity of those channels remained elusive. we show here for one channel type that voltage dependence, ...	2004	15272009
fluoroartemisinin: trifluoromethyl analogues of artemether and artesunate.	the synthesis of a series of c-10 trifluoromethyl ethers of artemisinin has been achieved from key bromide 8, itself carried out in two steps from artemisinin. the substitution of 8 with methanol, ethanol, or succinic acid allowed the access of c-10 cf(3) analogues of beta-artemether, beta-arteether, or artesunate, respectively, in good yields (up to 89%). the presence of the cf(3) group at c-10 of artemisinin clearly increased the chemical stability under simulated stomach acid conditions. for ...	2004	15115411
identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity.	plasmodium falciparum, the causative agent of malaria, relies extensively on glycolysis coupled with homolactic fermentation during its blood-borne stages for energy production. selective inhibitors of the parasite lactate dehydrogenase (ldh), central to nad(+) regeneration, therefore potentially provide a route to new antimalarial drugs directed against a novel molecular target. a series of heterocyclic, azole-based compounds are described that preferentially inhibit p. falciparum ldh at sub-mi ...	2004	15117937
calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite.	transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (xa). using a plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that xa triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their ...	2004	15137943
orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase exist as multienzyme complex in human malaria parasite plasmodium falciparum.	plasmodium falciparum, the causative agent of the most lethal form of human malaria, totally depends on de novo pyrimidine biosynthetic pathway. orotate phosphoribosyltransferase (oprt) and orotidine 5'-monophosphate decarboxylase (ompdc), the fifth and sixth enzymes in the pathway catalyzing formation of uridine 5'-monophosphate (ump), remain largely uncharacterized in the protozoan parasite. in this study, we achieved purification of oprt and ompdc to near homogeneity from p. falciparum cultiv ...	2004	15147974
malaria: the calcium connection.		2004	15152234
bioimmunotherapy of rodent malaria: co-treatment with recombinant mouse granulocyte-macrophage colony-stimulating factor and an enkephalin fragment peptide tyr-gly-gly.	we have earlier shown that recombinant mouse granulocyte-macrophage colony-stimulating factor (rmgm-csf) and methionine-enkephalin co-treatment can protect mice from malaria. we now report the bioimmunotherapeutic effect of rmgm-csf and a synthetic enkephalin fragment peptide tyr-gly-gly (tgg) co-treatment on blood-induced plasmodium berghei infection in swiss mice. mice were completely aparasitimic following co-treatment with rmgm-csf (10.0 microg/kg) and tgg (2.0 mg/kg x 3 per day, intraperito ...	2004	15158686
t cell receptor-ligand interactions: a conformational preequilibrium or an induced fit.	kinetic parameters of t cell receptor (tcr) interactions with its ligand have been proposed to control t cell activation. analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. as a model system, association and dissociation of a soluble tcr (st1) and its specific ligand, an azidobenzoic acid derivative of the peptide syipsaek-(aba)i (residues 252-260 from plasmodium berghei circumsporozoite protein), bound to class i mhc h-2k( ...	2004	15178754
new evidences of antimalarial activity of bidens pilosa roots extract correlated with polyacetylene and flavonoids.	bidens pilosa is among the several plants used in brazil to treat malaria. it was demonstrated that crude extracts from roots prepared with 80% ethanol by percolation are active in vitro against plasmodium falciparum and the activity is correlated with the presence of polyacetylene and flavonoids. this extract was submitted to column chromatography with ether and ether methanol (1:1) and two fractions, enriched in polyacetylene and flavonoids, respectively, were obtained. the extract and the fra ...	2004	15182902
ectopic expression of a cecropin transgene in the human malaria vector mosquito anopheles gambiae (diptera: culicidae): effects on susceptibility to plasmodium.	genetically altering the disease vector status of insects using recombinant dna technologies is being considered as an alternative to eradication efforts. manipulating the endogenous immune response of mosquitoes such as the temporal and special expression of antimicrobial peptides like cecropin may result in a refractory phenotype. using transgenic technology a unique pattern of expression of cecropin a (ceca) in anopheles gambiae was created such that ceca was expressed beginning 24 h after a ...	2004	15185949
real-time, in vivo analysis of malaria ookinete locomotion and mosquito midgut invasion.	invasion of the anopheles mosquito midgut by the plasmodium ookinete is a critical step in the malaria transmission cycle. we have generated a fluorescent p. berghei transgenic line that expresses gfp in the ookinete and oocyst stages, and used it to perform the first real-time analysis of midgut invasion in the living mosquito as well as in explanted intact midguts whose basolateral plasma membranes were vitally stained. these studies permitted detailed analysis of parasite motile behaviour in ...	2004	15186403
imaging movement of malaria parasites during transmission by anopheles mosquitoes.	malaria is contracted when plasmodium sporozoites are inoculated into the vertebrate host during the blood meal of a mosquito. in infected mosquitoes, sporozoites are present in large numbers in the secretory cavities of the salivary glands at the most distal site of the salivary system. however, how sporozoites move through the salivary system of the mosquito, both in resting and feeding mosquitoes, is unknown. here, we observed fluorescent plasmodium berghei sporozoites within live anopheles s ...	2004	15186404
comparative and functional genomics of the innate immune system in the malaria vector anopheles gambiae.	in much of africa, the mosquito anopheles gambiae is the major vector of human malaria, a devastating infectious disease caused by plasmodium parasites. vector and parasite interact at multiple stages and locations, and the nature and effectiveness of this reciprocal interaction determines the success of transmission. many of the interactions engage the mosquito's innate immunity, a primitive but very effective defense system. in some cases, the mosquito kills the parasite, thus blocking the tra ...	2004	15199960
duffy antigen is important for the lethal effect of the lethal strain of plasmodium yoelii 17xl.	we studied the potential role of the duffy antigen and glycophorin a as receptors for rodent malaria parasite invasion of erythrocytes. parasitemia increased exponentially after infection with plasmodium berghei nk65, p. chabaudi, and p. vinckei in duffy antigen knockout, glycophorin a knockout, and wild-type mice, indicating that the duffy antigen and glycophorin a are not essential for these malaria parasites. however, parasitemia of the duffy antigen knockout mice infected with p. yoelii 17xl ...	2004	15278442
a plasmodium berghei reference line that constitutively expresses gfp at a high level throughout the complete life cycle.	green fluorescent protein (gfp) is a well-established reporter protein for the examination of biological processes. this report describes a recombinant plasmodium berghei, pbgfpcon, that constitutively expresses gfp in a growth responsive manner in its cytoplasm from a transgene that is integrated into the genome and controlled by the strong promoter from a p. berghei elongation factor-1alpha gene. all life cycle forms of pbgfpcon except for male gametes can be easily visualized by fluorescent m ...	2004	15279948
mulinane-type diterpenoids from azorella compacta display antiplasmodial activity.	two mulinane-type diterpenoids were isolated from azorella compacta; namely 20-hydroxymulin-11,13-dienyl acetate and 13,14-dihydroxymulin-11-en-20-oic acid. the structures were elucidated by analysis of their spectroscopic data. these compounds, as well as three previously isolated diterpenes, were evaluated as potential in vivo growth inhibitors of plasmodium berghei nk 65 on infected mice at an intraperitoneal dose of 10 mg/kg/day. sixty percent and forty-two percent growth inhibition were obt ...	2004	15280000
[preparation and identification of monoclonal antibodies against the region ii+ motif in circumsporozoite protein of plasmodium falciparum].	to develop and identify the monoclonal antibodies (mcabs) against region ii+ motif in circumsporozoite protein of plasmodium falciparum.	2004	15281447
intravital microscopy demonstrating antibody-mediated immobilisation of plasmodium berghei sporozoites injected into skin by mosquitoes.	previous studies have shown that mosquitoes inject plasmodium sporozoites into avascular portions of the skin of their rodent host rather than directly into the blood circulation. then, over time, these sporozoites move into the circulation, from where they reach the liver to initiate a malaria infection. by use of intravital microscopy of the skin, we present direct morphological evidence of mosquito probing that introduces sporozoites into avascular tissue, of the migration of these sporozoite ...	2004	15313126
identification of an antimalarial synthetic trioxolane drug development candidate.	the discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. this irreversible redox reaction produces carbo ...	2004	15318224
quantitative plasmodium sporozoite neutralization assay (tsna).	the circumsporozoite (cs) protein is the major surface protein of plasmodium sporozoites. antibodies to the immunodominant repeat domain of cs immobilize sporozoites and prevent infection of hepatocytes. plasmodium falciparum vaccines containing cs repeats are undergoing human trials in endemic areas, and proof of efficacy has been obtained. the correlates of protection are under investigation. levels of anti-repeat antibodies in the serum of the human volunteers have been measured mostly by enz ...	2004	15350520
plasmodium berghei ookinetes induce nitric oxide production in anopheles pseudopunctipennis midguts cultured in vitro.	the anopheles pseudopunctipennis nitric oxide synthase gene (apnos) was identified and its partial sequence showed high homology with nos from a. stephensi, a. gambiae (putative sequence), and drosophila melanogaster. apnos was mainly expressed in male and female adult mosquitoes and was induced by a blood meal. nitric oxide (no) was produced by in vitro-cultured mosquito midguts inoculated by enema with plasmodium berghei ookinetes, saccharomyces cerevisiae, gram-positive bacteria (micrococcus ...	2004	15350609
effector and memory cd8+ t cells as seen in immunity to malaria.	transgenic (tg) mice carrying a t-cell receptor (tcr) specific for a cd8(+) t-cell epitope expressed in pre-erythrocytic stages of plasmodium yoelii has proven to be a valuable tool to advance our understanding of this anti-parasite t-cell response, as it occurs in vivo. the visualization of cd8(+) t cells in vivo and ex vivo greatly facilitated research aimed at characterizing basic features of this t-cell response such as the kinetics of differentiation and proliferation and the in vivo antige ...	2004	15361248
a profound alteration of blood tcrb repertoire allows prediction of cerebral malaria.	cerebral malaria (cm) is one of the severe complications of plasmodium infection. in murine models of cm, talphabeta cells have been implicated in the neuropathogenesis. to obtain insights into the tcrb repertoire during cm, we used high throughput cdr3 spectratyping and set up new methods and software tools to analyze data. we compared pbl and spleen repertoires of mice infected with plasmodium berghei anka that developed cm (cm(+)) or not (cm(-)) to evidence modifications of the tcrb repertoir ...	2004	15383590
merozoite surface protein 4/5 provides protection against lethal challenge with a heterologous malaria parasite strain.	immunization with merozoite surface protein 4/5 (msp4/5), the murine malaria homologue of plasmodium falciparum msp4 and msp5, has been shown to protect mice against challenge by parasites expressing the homologous form of the protein. the gene encoding msp4/5 was sequenced from a number of plasmodium yoelii isolates in order to assess the level of polymorphism in the protein. the gene was found to be highly conserved among the 13 p. yoelii isolates sequenced, even though many of the same isolat ...	2004	15385485
inducible peroxidases mediate nitration of anopheles midgut cells undergoing apoptosis in response to plasmodium invasion.	plasmodium berghei invasion of anopheles stephensi midgut cells causes severe damage, induces expression of nitric-oxide synthase, and leads to apoptosis. the present study indicates that invasion results in tyrosine nitration, catalyzed as a two-step reaction in which nitric-oxide synthase induction is followed by increased peroxidase activity. ookinete invasion induced localized expression of peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of nitrite and h(2)o(2) ...	2004	15456781
conditional mutagenesis using site-specific recombination in plasmodium berghei.	reverse genetics in plasmodium, the genus of parasites that cause malaria, still faces major limitations. only red blood cell stages of this haploid parasite can be transfected. consequently, the function of many essential genes in these and subsequent stages, including those encoding vaccine candidates, cannot be addressed genetically. here, we establish conditional mutagenesis in plasmodium by using site-specific recombination and the flp/frt system of yeast. site-specific recombination is ind ...	2004	15465918
proteome analysis of rhoptry-enriched fractions isolated from plasmodium merozoites.	the rhoptries of plasmodium species participate in merozoite invasion and modification of the host erythrocyte. however, only a few rhoptry proteins have been identified using conventional gene identification protocols. to investigate the protein organization of this organelle and to identify new rhoptry proteins, merozoite rhoptries from three different plasmodium rodent species were enriched by sucrose density gradient fractionation, and subjected to proteome analysis using multidimensional pr ...	2004	15473688
antimalarial activity of bidens pilosa l. (asteraceae) ethanol extracts from wild plants collected in various localities or plants cultivated in humus soil.	bidens pilosa (asteraceae), a medicinal plant used worldwide, has antimalarial activity as shown in previous work. this study tested ethanol extracts from wild plants collected in three different regions of brazil and from plants cultivated in various soil conditions. the extracts were active in mice infected with p. berghei: doses of < or =500 mg/kg administered by oral route reduced malaria parasitaemia and mouse mortality; higher doses were found to be less effective. tested in vitro against ...	2004	15476304
plasmodium berghei: dehydroepiandrosterone sulfate reverses chloroquino-resistance in experimental malaria infection; correlation with glucose 6-phosphate dehydrogenase and glutathione synthesis pathway.	in plasmodium falciparum-infected cells or in p. berghei infected mice, increase of reduced glutathione (gsh) levels confers resistance to chloroquine (cq). gsh is synthesized within the cells through a complex biochemical pathway composed of several well known enzymes, in which glucose-6-phosphate dehydrogenase (g6pd) plays an important role. the physiological hormone dehydroepiandrosterone sulfate (dheas) is a potent inhibitor of g6pd activity, and g6pd deficiency is known to exert antimalaria ...	2004	15476661
in vitro and in vivo antimalarial studies of striga hermonthica and tapinanthus sessilifolius extracts.	the antimalarial activities of the methanol extracts of striga hermonthica (whole plant) and tapinanthus sessilifolius (leaves), commonly used in northern nigeria for the treatment of malaria, were evaluated. in the in vitro antiplasmodial analysis, the extracts of t. sessilifolius and s. hermonthica utilized in the study, displayed mild to weak activities with ic50 values of 200.5 and 274.8 microg/ml respectively. this was investigated, using the multidrug resistant plasmodium falciparum, k1 st ...	2004	15490799
plasmodium berghei: efficacy and safety of combinations of chloroquine and promethazine in chloroquine resistant infections in gravid mice.	efficacy and safety of combinations ofchloroquine (cq) and doses of promethazine (pr) against cq resistant plasmodium berghei infections in gravid mice was evaluated. parasites were cleared faster in mice treated with cq combined with doses of pr ranging from 20mg/kg to 50mg/kg (3.4 +/- 0.5 to 2.7 +/- 0.7) compared with cq alone (4.7 +/- 0.8) (p<0.5). parturition resulting in live pups in animals treated with cq and 20mg/ kg and 30mg/kg of pr (81%) was significantly higher than in animals treate ...	2004	15490800
a protective merozoite protein of plasmodium falciparum shares an epitope with surface antigens of paramecium.	a plasmodium falciparum cdna expression clone, lambdapf9, had been identified earlier as a protective epitope, using anti-lambdapf9 antibodies and combinatorial phagotopes. a segment of the pf9 gene showed homology with paramecium immobilization surface antigens such as 51b, 51a and 156g. a synthetic pf9-peptide was designed from this region, and specific antibodies were raised. each of these anti-pf9 antibodies and combinatorial reagents, as well as anti-paramecium 51b antibodies, recognized th ...	2004	15491471
plasmodium falciparum carbonic anhydrase is a possible target for malaria chemotherapy.	plasmodiumfalciparum is responsible for the majority of life-threatening cases of human malaria. the global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. carbonic anhydrase (ca) is present at high levels in human red cells and in p. falciparum. existence of at least three isozymes of the alpha < class was demonstrated in p. falciparum and a rodent malarial parasite plasmodium berghei. the major isozyme ca1 was purified and ...	2004	15499996
anti-malarial activity of some xanthones isolated from the roots of andrographis paniculata.	four xanthones were isolated from the roots of andrographis paniculata using a combination of column and thin-layer chromatographic methods. they were characterized as (i) 1,8-di-hydroxy-3,7-dimethoxy-xanthone, (ii) 4,8-dihydroxy-2,7-dimethoxy-xanthone, (iii) 1,2-dihydroxy-6,8-dimethoxy-xanthone and (iv) 3,7,8-trimethoxy-1-hydroxy xanthone by ir, ms and nmr spectroscopic methods. in vitro study revealed that compound 1,2-dihydroxy-6,8-dimethoxy-xanthone possessed substantial anti-plasmodial acti ...	2004	15507344
rifampicin antagonizes the effect of choloroquine on chloroquine-resistant plasmodium berghei in mice.	chloroquine (cq)-resistant plasmodium falciparum appears to decrease cq accumulation in its food vacuole by enhancing its efflux via an active membrane pump, which has been reported to be a p-glycoprotein-like transporter. rifampicin (rif) is a p-glycoprotein inhibitor and also has some antimalarial activity. it is hoped that a combination of choloroquine-rifampicin (cq + rif) would be advantageous in the treatment of cq-resistant malaria. swiss albino mice were inoculated with cq-resistant p. b ...	2004	15507775
essential role of membrane-attack protein in malarial transmission to mosquito host.	after ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. these ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. here we report that a microneme protein with a membrane-attack complex and perforin (macpf)-related domain, which we name membrane-attack ookinete protein (maop), is produced in the ookinete stag ...	2004	15520375
a malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites.	membrane skeletons are structural elements that provide mechanical support to the plasma membrane and define cell shape. here, we identify and characterize a putative protein component of the membrane skeleton of the malaria parasite. the protein, named pbimc1a, is the structural orthologue of the toxoplasma gondii inner membrane complex protein 1 (tgimc1), a component of the membrane skeleton in tachyzoites. using targeted gene disruption in the rodent malaria species plasmodium berghei, we sho ...	2004	15533999
detection of a new cerebral malaria susceptibility locus, using cba mice.	human cerebral malaria (cm) during acute plasmodium falciparum infection is a serious neurological complication that leads to coma and death. p. berghei anka infection of cba mice is a useful experimental model of cm. to identify host susceptibility loci, we performed chromosomal mapping in crossbred populations of both cm-susceptible cba and cm-resistant dba/2 mice. one significant region for a cm-susceptible locus in cba mice was mapped to h2 region on chromosome 17, tentatively designated cms ...	2004	15536567
increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium.	products of the kynurenine pathway of tryptophan metabolism have been implicated in the pathogenesis of murine and human cerebral malaria. indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme in this pathway and we have developed an immunohistochemical method for its detection in tissues from normal and malaria-infected mice. mice were infected with plasmodium berghei anka, a murine model of cerebral malaria, or p. berghei k173, a non-cerebral malaria model. vascular endothelial cel ...	2004	15542091
activity of benzothiazoles and chemical derivatives on plasmodium falciparum.	malaria is a major health concern particularly in africa which has about 90% of the worldwide annual clinical cases. the increasing number of drug-resistant plasmodium falciparum justifies the search for new drugs in this field. antimalarial activity of 2-substituted 6-nitro- and 6-amino-benzothiazoles and their anthranilic acids has been tested. an in vitro study has been performed on w2 and 3d7 strains of p. falciparum and on clinical isolates from malaria-infected patients. toxicity has been ...	2004	15552398
identification and characterisation of rama homologues in rodent, simian and human malaria species.		2004	15555735
in vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability.	a series of protein farnesyltransferase inhibitor ester prodrugs of fti-2148 (17) were synthesized in order to evaluate the effects of ester structure modification on antimalarial activity and for further development of a farnesyltransferase inhibitor with in vivo activity. evaluation against p. falciparum in red blood cells showed that all the investigated esters exhibited significant antimalarial activity, with the benzyl ester 16 showing the best inhibition (ed50=150 nm). additionally, compou ...	2004	15556768
functional characterization of an lccl-lectin domain containing protein family in plasmodium berghei.	using bioinformatic, proteomic, immunofluorescence, and genetic cross methods, we have functionally characterized a family of putative parasite ligands as potential mediators of cell-cell interactions. we name these proteins the limulus clotting factor c, coch-5b2, and lgl1 (lccl)-lectin adhesive-like protein (lap) family. we demonstrate that this family is conserved amongst plasmodium spp. it possesses a unique arrangement of adhesive protein domains normally associated with extracellular prote ...	2004	15562607
genetically modified plasmodium parasites as a protective experimental malaria vaccine.	malaria is a mosquito-borne disease that is transmitted by inoculation of the plasmodium parasite sporozoite stage. sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. using expression profiling, we previously ide ...	2004	15580261
a surface phospholipase is involved in the migration of plasmodium sporozoites through cells.	plasmodium sporozoites, injected by mosquitoes into the skin of the host, traverse cells during their migration to hepatocytes where they continue their life cycle. the mechanisms used by the parasite to rupture the plasma membrane of the host cells are not known. here we report the presence of a phospholipase on the surface of plasmodium berghei sporozoites (p. berghei phospholipase; pb pl) and demonstrate that it is involved in the establishment of a malaria infection in vivo. pb pl is highly ...	2004	15590623
[construction of the subtracted cdna libraries related to artemisinin-resistance of plasmodium berghei].	to construct the subtracted cdna libraries related to artemisinin-resistance of plasmodium berghei using suppression subtractive hybridization pcr (ssh pcr).	2004	15597707
[additive therapeutic effect of a combination of artemether and daphnetin against plasmodium berghei in mice].	to investigate the therapeutic effect of a combination of artemether and daphnetin against plasmodium berghei anka strain in mice.	2004	15597713
the chemotherapy of rodent malaria. lxii. drug combinations to impede the selection of drug resistance, part 5: rates of development of resistance to some inhibitors of folate metabolism and to artesunate.	in recent years infection with chloroquine-resistant plasmodium falciparum has been combatted with two long-acting antimalarials, pyrimethamine and sulfadoxine, in the combination known as fansidar that exerts a strong, synergistic action on the asexual stages of the parasite. this second-line regimen, however, is failing increasingly because of the selection of resistant clones in endemic areas, and effective, safe, alternative drugs or drug combinations that are also affordable are urgently ne ...	2004	15667710
comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasites.	to compare the schizontocidal activity of recrystallized or crude daphnetin against malaria parasites in vivo.	2004	15745243
the plasmodium circumsporozoite protein is involved in mosquito salivary gland invasion by sporozoites.	plasmodium sporozoites develop in oocysts on the midgut wall of the mosquito and are released into the hemocoel. approximately 15-20% of oocyst sporozoites will successfully attach to and invade salivary glands, their target organ. we have previously shown that the major surface protein of sporozoites, the circumsporozoite (cs) protein, binds specifically to salivary glands and not to other mosquito organs exposed to circulating hemolymph. in addition, a peptide from the n-terminal portion of cs ...	2004	14668012
a proteomic analysis of malaria biology: integration of old literature and new technologies.	the genomic revolution has brought a new vitality into research on plasmodium, its insect and vertebrate hosts. at the cellular level nowhere is the impact greater than in the analysis of protein expression and the 'assembly' of the supramolecular machines that together comprise the functional cell. the repetitive phases of invasion and replication that typify the malaria life cycle, together with the unique phase of sexual differentiation provide a powerful platform on which to investigate the ...	2004	15582521
the role of programmed cell death in plasmodium-mosquito interactions.	many host-parasite interactions are regulated in part by the programmed cell death of host cells or the parasite. here we review evidence suggesting that programmed cell death occurs during the early stages of the development of the malaria parasite in its vector. zygotes and ookinetes of plasmodium berghei have been shown to die by programmed cell death (apoptosis) in the midgut lumen of the vector anopheles stephensi, or whilst developing in vitro. several morphological markers, indicative of ...	2004	15582523
[cerebral malaria, a key role for endothelial cells?].	five to six hundred millions of people, throughout the world, suffer from malaria and more than one million die each year as a consequence, in about 20% of the cases, of cerebral malaria, an important complication of plasmodium falciparum infection (holding & snow, 2001). despite many studies, the physiopathology of these cerebral occurrences is not understood, especially concerning the intricacy and respective roles of the various mechanisms identified: sequestration of parasitized red cells in ...	2004	15662934