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pyronaridine: an effective antimalarial against multidrug-resistant malaria.pyronaridine, administered intramuscularly (im) to swiss mice infected with the lethal multidrug-resistant plasmodium yoelii nigeriensis, was found to exert high blood schizontocidal activity. the efficacy of doses of pyronaridine ranging from 0.625 to 30 mg (base/kg) was evaluated using a 4 day treatment schedule (drug was administered at 0, 24, 48 and 72 hrs). it was found that doses of 2.5mg/ kg and higher protected animals completely from the lethal effects of the parasite. the same degree o ...200010968405
modulation of halofantrine resistance after coadministration of halofantrine with diverse pharmacological agents in a rodent malaria model.the declining efficacy of antimalarial drugs against plasmodium falciparum strains has been reported from several endemic regions of the world. strategic evaluation of several pharmacological agents in combination with chloroquine to enhance the sensitivity of the latter against resistant parasites has been documented in several studies. however no attempts have been directed to monitor the efficacy of such biological response modifiers for reversing the resistance to halofantrine. in the presen ...200010972203
[study on recombinant bcg to prevent infections of intracellular pathogens].studies on recombinant bcg (rbcg) which my group carried out so far were reviewed. recombinant bcg which secreted alpha antigen-fused foreign antigen was constructed and tested for its ability to induce protective immunity. thus, rbcg secreting merozoite surface protein 1 (msp1) of plasmodium yoelii efficiently protected the infection more than recombinant msp 1 mixed with artificial adjuvant ras or ifa did. rbcg which secreted excess amounts of antigen 85 complex a inhibited the multiplication ...200010979272
an unusual tryptophan-rich domain characterizes two secreted antigens of plasmodium yoelii-infected erythrocytes.previously, we reported the characterization of pypag-1, a novel protective membrane protein of plasmodium yoelii-infected erythrocytes. immunization studies indicated that pypag-1 contained at least two protective epitopes. one of these determinants was associated with the n-terminal portion of pypag-1, that also included a 220 amino acid domain unusually rich in tryptophan residues. using sera from mice immunized against p. yoelii, we have identified a second related antigen, pypag-3. the pypa ...200010989141
structure of the e8 gene encoding a high molecular mass rhoptry protein of plasmodium yoelii. 200010989154
immunization with recombinant plasmodium yoelii merozoite surface protein 4/5 protects mice against lethal challenge.plasmodium yoelii merozoite surface protein 4/5 (pymsp4/5), expressed as a recombinant protein, was highly effective at protecting mice against lethal challenge with p. yoelii. there was a significant correlation between prechallenge antibody levels and peak parasitemia, suggesting that the homologues of pymsp4/5 in plasmodium falciparum are promising components of a subunit vaccine against malaria.200010992516
[study on recombinant bcg].the progress of study on recombinant bcg was stated briefly. and then our studies on recombinant bcg were mentioned. recombinant bcg secreting alpha antigen-fused merozoite surface protein 1 (msp 1) was prepared and tested for its ability to control infections of plasmodium yoelii. result turned out it controlled the infection better than recombinant msp 1 mixed with freund incomplete adjuvant did. recombinant bcg secreting excess amounts of antigen 85 complex a controlled infection of mycobacte ...200011004802
early nonspecific immune responses and immunity to blood-stage nonlethal plasmodium yoelii malaria.the early role of natural killer cells and gamma delta t cells in the development of protective immunity to the blood stage of nonlethal plasmodium yoelii infection was studied. splenic cytokine levels were measured 24 h after infection of natural killer cell-depleted immunodeficient and littermate mice or transiently t-cell-depleted normal mice. splenic gamma interferon levels were significantly increased above background in immunodeficient and littermate mice 24 h after infection. depletion of ...200011035715
a protective glycosylphosphatidylinositol-anchored membrane protein of plasmodium yoelii trophozoites and merozoites contains two epidermal growth factor-like domains.using sera from mice immunized and protected against plasmodium yoelii malaria, we identified a novel blood-stage antigen gene, pypag-2. the 2.1-kb pypag-2 cdna contains a single open reading frame that encodes a 409-amino-acid protein with a predicted molecular mass of 46.8 kda. unlike many characterized plasmodial antigens, blocks of tandemly repeated amino acids are lacking in the pypag-2 protein sequence. recombinant pypag-2, comprising the full-length protein minus the predicted n-terminal ...200011035724
effect of tumor necrosis factor on hepatic oxidative stress and antioxidant defense indices in normal and plasmodium yeolii nigeriensis infected mice.plasmodium yoelii nigeriensis (p. y. nigeriensis) produces lethal malaria infection in swiss albino mice. reactive oxygen species (ros) such as superoxide anion, hydrogen peroxide along with endogenously produced tumor necrosis factor (tnf) have been implicated in the pathogenesis of malaria.200011071400
interaction between chloroquine and diverse pharmacological agents in chloroquine resistant plasmodium yoelii nigeriensis.the effect of a number of pharmacological agents on the enhancement of antimalarial activity of chloroquine was evaluated against chloroquine resistant line of plasmodium yoelii nigeriensis (n-67). the response after combination therapy was monitored on the basis of alteration in the course of parasitaemia, the extension of mean survival time and the percent cure rate in different groups. the study was designed to compare the in vivo efficacy of a number of resistance modulating agents found eff ...200011080509
toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is involved in invasion of host cells.proteins with constitutive or transient localization on the surface of apicomplexa parasites are of particular interest for their potential role in the invasion of host cells. we describe the identification and characterization of tgama1, the toxoplasma gondii homolog of the plasmodium apical membrane antigen 1 (ama1), which has been shown to elicit a protective immune response against merozoites dependent on the correct pairing of its numerous disulfide bonds. tgama1 shows between 19% (plasmodi ...200011083833
anopheles gambiae salivary gland proteins as putative targets for blocking transmission of malaria parasites.anopheles gambiae is the primary vector of human malaria in sub-saharan africa. invasion of anopheles salivary glands by plasmodium sporozoites is a necessary step in the transmission of malaria and is likely to be mediated by specific receptor-ligand interactions. we are interested in identifying putative an a. gambiae salivary gland receptor or receptors for sporozoite invasion as a possible target for blocking malaria transmission. by using monoclonal antibodies against female-specific a. gam ...200011087838
a study of selected plasmodium yoelii messenger rnas during hepatocyte infection.we investigated the expression of several mrnas in exoerythrocytic and erythrocytic stages of plasmodium yoelii in infected mice, focusing our attention on genes thought to be involved in signal transduction (like pypka and pymap-1, encoding homologues of camp-dependent and mitogen-activated protein kinases, respectively) and cell cycle progression (those encoding the cdc2-related kinases pycrk-1, pycrk-3 and pymrk). messengers coding for enzymes involved in general processes such as dna replica ...200011087914
retrieving parasite specific liver stage gene products in plasmodium yoelii infected livers using differential display.differential display (dd) has been routinely used to identify genes whose expression pattern is altered by changes in the cellular environment and/or at different stages of development. most reports utilizing dd contain conventional dd primers that have high guanine and cytosine content and would not be expected to be optimal for plasmodium which has approximately 30-40% g+c. in an attempt to accommodate the high adenine and thymidine rich genome of plasmodium yoelii, we utilized pcr primers con ...200011087924
mercury exposure and murine response to plasmodium yoelii infection and immunization.malaria has re-emerged in amazonia over the past two decades. many factors have been proposed for this, among them changes in population distribution, failures of vector control and pharmacologic management, and local as well as global environmental changes. among the latter factors, we have studied the potential role of increasing exposures to the immunotoxic metal mercury, which is widely used in amazonia for artisanal extraction of alluvial gold deposits. we report here that hg impairs host r ...200011105781
mycobacterium bovis bacillus calmette-guérin induces protective immunity against infection by plasmodium yoelii at blood-stage depending on shifting immunity toward th1 type and inducing protective igg2a after the parasite infection.bacillus calmette-guérin (bcg)-vaccination raised dramatically the survival rates of a/j mice from infection by plasmodium yoelii 17xl at blood-stage. the analysis of the immune response of spleen cells indicated that bcg vaccination biased the immune response toward th1 type. neutralization of ifn-gamma and nitric oxide abrogated the protection. the kinetics of ab production in the course of p. yoelii 17xl infection was monitored. surprisingly, larger amounts of parasite-specific abs were produ ...200011115699
cerebral malaria in mice: interleukin-2 treatment induces accumulation of gammadelta t cells in the brain and alters resistant mice to susceptible-like phenotype.in this study, we report that infection with plasmodium yoelii 17xl, a lethal strain of rodent malaria, does not result in death in the dba/2 strain of mice. in contrast to balb/c mice, dba/2 mice developed significantly less parasitemia and never manifested symptoms of cerebral malaria (cm) on infection with this parasite. moreover, the histological changes evident in the brain of susceptible balb/c were absent in dba/2 mice. interestingly, the resistant dba/2 mice when treated with recombinant ...200111141489
dna immunization by plasmodium falciparum liver-stage antigen 3 induces protection against plasmodium yoelii sporozoite challenge.dna-based immunization of mice by plasmodium falciparum liver-stage antigen 3 (pflsa3), a novel highly conserved p. falciparum preerythrocytic antigen, was evaluated. animals developed a dominant th1 immune response (high gamma interferon t-cell responses and predominance of immunoglobulin g2a) to each of three recombinant proteins spanning the molecule. we have exploited the immunological cross-reactivity of pflsa3 with its putative homologue on sporozoites of the rodent parasite plasmodium yoe ...200111160023
host responses to plasmodium yoelii hepatic stages: a paradigm in host-parasite interaction.the liver stage of malaria, caused by the genus plasmodium, is clinically silent, but immunologically significant. ample evidence exists for an effective cd8(+) t cell response to this stage as well as the involvement of gammadeltat cells and nk1.1(int) cells in immunized animal models. in contrast, there is little information concerning responses in a naive host. here we report that several host gene expressions in the liver, spleen, and kidney of balb/c mice are altered during the liver stage ...200111160243
plasmodium yoelii: efficient in vitro invasion and complete development of sporozoites in mouse hepatic cell lines. 200011162379
polar plasmodium falciparum lipids induce lipogenesis in rat adipocytes in vitro.previous studies have shown that 'toxic malarial antigens' released by plasmodium yoelii can induce hypoglycaemia in mice and act synergistically with insulin in stimulating lipogenesis in rat adipocytes in vitro. in this study, it was shown that similar bioactivity could be detected in plasmodium falciparum culture supernatant, and the molecular basis of this activity was further investigated. boiled spent culture medium from p. falciparum cultures ('bs-pf') (exclusively released into the cultu ...200011165922
interleukin-12- and gamma interferon-dependent protection against malaria conferred by cpg oligodeoxynucleotide in mice.unmethylated cpg dinucleotides in bacterial dna or synthetic oligodeoxynucleotides (odns) cause b-cell proliferation and immunoglobulin secretion, monocyte cytokine secretion, and activation of natural killer (nk) cell lytic activity and gamma interferon (ifn-gamma) secretion in vivo and in vitro. the potent th1-like immune activation by cpg odns suggests a possible utility for enhancing innate immunity against infectious pathogens. we therefore investigated whether the innate immune response co ...200111179339
susceptibility of species a, b, and c of anopheles culicifacies complex to plasmodium yoelii yoelii and plasmodium vinckei petteri infections.the comparative susceptibilities of colonized species a, b, and c of anopheles culicifacies complex and anopheles stephensi were determined for 2 rodent malaria parasites plasmodium vinckei petteri and plasmodium yoelii yoelii. all the 3 members of the complex were found to support complete sporogony with varying success. controls, a. stephensi, become readily infected, with >70% developing oocysts. of the test groups, species a had the highest percentage of mosquitoes with oocysts (>25%) and sp ...200011191914
glucose transport in cerebral microvessels during plasmodium yoelii nigeriensis infection in mice.plasmodium yoelii infected cerebral micro vessels of mice registered a significant increase in d-[u-14c] glucose transport as compared to normal microvessels which was found to be time, temperature and concentration dependent. metabolic inhibitors galactose, manose, 2-deoxy glucose and d-glucose showed noticeable inhibition of the same.200011198395
sequence diversity and antigenic polymorphism in the plasmodium yoelii p235 high molecular mass rhoptry proteins and their genes.a gene family in plasmodium yoelii ym encodes p235, a group of high molecular mass erythrocyte-binding rhoptry proteins. sequence analysis of 6 cdna clones from the 3' end of expressed p235 genes divided them into two groups corresponding to genes on chromosomes 1, and 5 and 6, respectively. twelve partial p235 protein sequences, derived from cdna sequences from the region with greatest protein sequence similarity to plasmodium vivax rbp2, fell into three groups, together with one chimeric seque ...200111223126
the plasmodium falciparum knob-associated pfemp3 antigen is also expressed at pre-erythrocytic stages and induces antibodies which inhibit sporozoite invasion.the expression of the pfemp3 gene and the corresponding pfemp3 knob-associated protein in the pre-erythrocytic stages of plasmodium falciparum was demonstrated by rt-pcr, western blots, ifat and iem. the antigen was found on the surface of the sporozoite and in the cytoplasm of mature hepatic stage parasites. immunological cross-reactivity was observed with sporozoites from the rodent malaria parasites plasmodium yoelii yoelii and plasmodium berghei and was exploited to assess a potential role o ...200111223132
conserved regions of the plasmodium yoelii rhoptry protein rhoph3 revealed by comparison with the p. falciparum homologue. 200111223137
detection of plasmodium yoelii stage mrna in balb/c mice.relatively little information is available concerning the expression of parasite genes during the liver stage of plasmodium infection, mostly because of low-level infection of host hepatocytes and the lack of purification techniques for the liver stage parasites. we have determined the optimal dosage of plasmodium yoelii sporozoite inoculum and routes of inoculation, which are intravenous tail vein and the intrahepatic portal circulation. to determine which route was optimal, balb/c mice were in ...200111227890
a potent antimalarial activity of hydrangea macrophylla var. otaksa leaf extract against plasmodium yoelii 17xl in mice.the antimalarial activity of the hot-water extract of hydrangea macrophylla var. otaksa leaves was evaluated against plasmodium yoelii 17xl in mice. non-treated control mice died from 6 to 7 days after infection, but mice treated with the leaf extract survived during the experiment. mice given the extract orally showed low parasitemia levels during administration. following a transient recrudescence of malaria parasites in the bloodstream of treated mice, no parasites could be detected by a micr ...200111267930
effect of poly iclc treatment on hepatic oxidative stress and antioxidant defense indices in plasmodium yoelii nigeriensis infected mice.plasmodium yoelii nigeriensis (p. y. nigeriensis) produces lethal malaria infection in swiss albino mice. reactive oxygen species (ros) are important mediators of tissue injury during malaria infection.200111286134
gene targeting in the rodent malaria parasite plasmodium yoelii.it is anticipated that the sequencing of plasmodium falciparum genome will soon be completed. rodent models of malaria infection and stable transformation systems provide powerful means of using this information to study gene function in vivo. to date, gene targeting has only been developed for one rodent malaria species, plasmodium berghei. another rodent species, plasmodium yoelii, however, is favored to study the mechanisms of protective immunity to the pre-erythrocytic stages of infection an ...200111295181
plasmodium falciparum homologue of the genes for plasmodium vivax and plasmodium yoelii adhesive proteins, which is transcribed but not translated.the 235-kda family of rhoptry proteins in plasmodium yoelii and the two reticulocyte binding proteins of p. vivax comprise a family of proteins involved in host cell selection and erythrocyte invasion. here we described a member of the gene family found in p. falciparum (pfrh3) that is transcribed in its entirety, under stage-specific control, with correct splicing of the intron, but appears not to be translated, probably due to two reading frameshifts at the 5' end of the gene.200111349024
human antibodies against plasmodium falciparum liver-stage antigen 3 cross-react with plasmodium yoelii preerythrocytic-stage epitopes and inhibit sporozoite invasion in vitro and in vivo.the plasmodium falciparum liver-stage antigen 3 (lsa3), a recently identified preerythrocytic antigen, induces protection against malaria in chimpanzees. using antibodies from individuals with hyperimmunity to malaria affinity purified on recombinant or synthetic polypeptides of lsa3, we identified four non-cross-reactive b-cell epitopes in plasmodium yoelii preerythrocytic stages. on sporozoites the p. yoelii protein detected has a molecular mass similar to that of lsa3. t-cell epitopes cross-r ...200111349050
immunogenicity and protective efficacy of a plasmodium yoelii hsp60 dna vaccine in balb/c mice.the gene encoding the 60-kda heat shock protein of plasmodium yoelii (pyhsp60) was cloned into the vr1012 and vr1020 mammalian expression vectors. groups of 10 balb/c mice were immunized intramuscularly at 0, 3, and 9 weeks with 100 microg of pyhsp60 dna vaccine alone or in combination with 30 microg of pmurgmcsf. sera from immunized mice but not from vector control groups recognized p. yoelii sporozoites, liver stages, and infected erythrocytes in an indirect fluorescent antibody test. two week ...200111349057
effect of beta-arteether treatment on erythrocytic methemoglobin reductase system in plasmodium yoelii nigeriensis infected mice.the methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin (hb) and methemoglobin (methb) in blood. exposure of red blood cells to an oxidative stress (pathological/physiological) may cause impairment in this equilibrium.200111360434
antibodies specific for heat shock proteins in human and murine malaria.heat shock proteins (hsps) are immunodominant antigens recognized by the host immune system in various infectious diseases. we analyzed hsp-specific antibodies, including immunoglobulin g (igg), igm and iga, in sera from malaria patients in thailand by using an enzyme-linked immunosorbent assay. all of the antibodies to hsp90 were remarkably increased in the patients compared with those in controls, while only igm to hsp70 or iga to hsp65 was significantly elevated. further experiments showed th ...200111369272
distribution and characterisation of the 235 kda rhoptry multigene family within the genomes of virulent and avirulent lines of plasmodium yoelii.in the rodent malaria species, plasmodium yoelii, a multi-gene family (py235) encodes a 235 kda rhoptry protein. this protein is believed to be involved in merozoite attachment and invasion of red blood cells. only two members of py235 have been sequenced so far. using genomic dna from the virulent p. yoelii ym line we have pcr amplified additional members of this gene family. these >8 kb full length clones have been cloned and sequenced. based on differences within the tri-amino acid repeat str ...200111378199
inhibition of plasmodium yoelii blood-stage malaria by interferon alpha through the inhibition of the production of its target cell, the reticulocyte.the effect of a recombinant hybrid human interferon alpha (ifn-alpha) (which cross-reacts with murine cells) on c57bl/6 mice infected with plasmodium yoelii sporozoites or parasitized erythrocytes was determined. ifn-alpha did not inhibit the development of the parasite in the liver, but it did reduce the blood parasite load and the hepatosplenomegaly induced by the infection in mice injected with blood-stage parasites. the extent of anemia in ifn-alpha-treated and control mice was similar, desp ...200111389041
the influence of host haematocrit on the blood feeding success of anopheles stephensi: implications for enhanced malaria transmission.two studies were carried out to determine the effect of the rodent malaria plasmodium yoelii nigeriensis on the blood feeding success of anopheles stephensi. initially, pairs of mice with similar packed cell volume (pcv) (measured by haematocrit) were selected. following infection of one of the pair its pcv gradually fell. at various times post-infection, a comparison was made of the bloodmeal size (haemoglobin content) of mosquitoes feeding on these mice. the bloodmeal sizes increased with para ...200111393821
changes in rodent-erythrocyte methemoglobin reductase system produced by two malaria parasites, viz. plasmodium yoelii nigeriensis and plasmodium berghei.the methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin and methemoglobin in blood. exposure of red blood cells to oxidative stress (pathological/physiological) may cause impairment to this equilibrium. we studied the status of erythrocytic methemoglobin and the related reductase system during plasmodium yoelii nigeriensis infection in mice and p. berghei infection in mastomys. malaria infection was induced by intraperitoneal inoculation with 10(6) ...200111435127
dendritic cells can initiate protective immune responses against malaria.an understanding of the antigen presentation mechanisms that mediate induction of protective immune responses against malaria is essential for the development of successful immunization approaches. here we show that dendritic cells presenting plasmodium yoelii sporozoite antigens are able to activate specific cd4(+) and cd8(+) t cells and initiate protective immune responses against malaria in mice.200111447201
recombinant proteins produced by vaccinia virus vectors can be incorporated within the virion (imv form) into different compartments.vaccinia virus (vv) is one of the largest and most complex of animal viruses, with a virion that contains about 100 different polypeptides. assembly of the viral proteins occurs in discrete cytoplasmic sites leading to formation of two infectious forms, an abundant (>90%) intracellular mature virus (imv) with an envelope, and a minor extracellular enveloped virus (eev) with an extra membrane acquired from the trans-golgi network. it has been shown that while eev contains in the outer membrane ce ...200111448027
swift development of protective effector functions in naive cd8(+) t cells against malaria liver stages.we generated t cell receptor transgenic mice specific for the liver stages of the rodent malaria parasite plasmodium yoelii and studied the early events in the development of in vivo effector functions in antigen-specific cd8(+) t cells. differently to activated/memory cells, naive cd8(+) t cells are not capable of exerting antiparasitic activity unless previously primed by parasite immunization. while naive cells need to differentiate before achieving effector status, the time required for this ...200111457892
reversal of type 2 diabetes in mice by products of malaria parasites. ii. role of inositol phosphoglycans (ipgs).we have previously shown that infection with plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. inositol phosphoglycans (ipgs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (gpis), and act as second messengers mediating insulin action. the c57bl/ks-db/db and c57bl/6j-ob/ob mice offer good models fo ...200111461192
midgut specific immune response of vector mosquito anopheles stephensi to malaria parasite plasmodium.innate immune-related polypeptides expression in midgut in the ageing vector mosquito a. stephensi following infection by malaria parasite, plasmodium yoelii yoelii has been studied. twenty polypeptides were induced by an infected blood meal during various stages of adult life. a 24 kda polypeptide was induced generally in most of the stages. maximum parasite induced polypeptides i.e. 22, 33, 111, 122, 127, 140, 143 and 146 kda were found in 5 days of post blood feeding (pbf) which coincides wit ...200111495292
in vitro antibody response to the tetrapeptide repeats of plasmodium falciparum circumsporozoite protein by splenocytes from mice infected with p. yoelii yoelii.the antibody response to the recombinant protein, r32tet32, which contained the repetitive sequence (nanp)n of plasmodium falciparum csp was determined in c57bl/6 mice during the course of nonlethal infection with plasmodium yoelii 17x. marked suppression of the igg antibody response to r32tet32 occurred when mice were immunized at peak parasitemia (on day 16). in vitro antibody responses of spleen cells from acutely infected mice to r32tet32 were similarly suppressed. stimulation of normal sple ...200111503901
effects of malaria infection on vitellogenesis in anopheles gambiae during two gonotrophic cycles.we report changes in the abundance of vitellogenin (vg) mrna, and concentration of haemolymph vg and ovarian vitellin (vn) in anopheles gambiae following infection with plasmodium yoelii nigeriensis. a parasite-induced reduction in vg mrna abundance was first detected 24 h after feeding on an infective blood meal, when ookinetes were invading the midgut. during a second gonotrophic cycle post-infection, developing oocysts reduced vg mrna abundance by up to 33% and the effect was detected from 2 ...200111520358
comparison of the protective efficacy of yeast-derived and escherichia coli-derived recombinant merozoite surface protein 4/5 against lethal challenge by plasmodium yoelii.the gene encoding the plasmodium yoelii homologue of p. falciparum merozoite surface proteins 4 (msp4) and 5 (msp5) has been expressed in escherichia coli and saccharomyces cerevisiae. the protein contains a single epidermal growth factor (egf)-like domain and is expressed in a form lacking the predicted n-terminal signal and glycosyl phosphatidylinositol (gpi) attachment sequences. the recombinant protein derived from e. coli (ecmsp4/5) was highly effective at protecting mice against lethal cha ...200111535314
the 235 kda rhoptry protein of plasmodium (yoelii) yoelii: function at the junction.all malaria parasites are obligate intracellular organisms that must clearly recognise and discriminate between different cells during their life cycle. invasion into a cell is a multi-step event that is marked by initial attachment proceeding to irreversible junction formation and penetration. a 235 kda rhoptry protein (py235) in the rodent malaria, plasmodium yoelii yoelii has been shown to be involved in red blood cell (rbc) binding and is involved in a new mechanism of clonal phenotypic vari ...200111551627
interaction between two domains of the p. yoelii msp-1 protein detected using the yeast two-hybrid system.several model systems of plasmodia have demonstrated the potential of the merozoite surface protein, msp-1, to induce protective immunity. however, little is known about the function of this protein or its interaction with other surface molecules that may also serve as immunological targets. to identify potentially significant inter- and intra-molecular interactions involving msp-1, we have utilized the yeast two-hybrid system. a cdna activation domain library was constructed from the erythrocyt ...200111551629
erythrocyte-binding activity of plasmodium yoelii apical membrane antigen-1 expressed on the surface of transfected cos-7 cells.malaria merozoite surface and apical organellar molecules facilitate invasion into the host erythrocyte. the underlying molecular mechanisms of invasion are poorly understood, and there are few data to delineate roles for individual merozoite proteins. apical membrane antigen-1 (ama-1) is a conserved apicomplexan protein present in the apical organelle complex and at times on the surface of plasmodium and toxoplasma zoites. ama-1 domains 1/2 are conserved between plasmodium and toxoplasma and ha ...200111551631
the 22 kda component of the protein complex on the surface of plasmodium falciparum merozoites is derived from a larger precursor, merozoite surface protein 7.the gene coding for merozoite surface protein 7 has been identified and sequenced in three lines of plasmodium falciparum. the gene encodes a 351 amino acid polypeptide that is the precursor of a 22-kda protein (msp7(22)) on the merozoite surface and non-covalently associated with merozoite surface protein 1 (msp1) complex shed from the surface at erythrocyte invasion. a second 19-kda component of the complex (msp7(19)) was shown to be derived from msp7(22) and the complete primary structure of ...200111551634
complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen.we report that complete protection against malaria and total inhibition of liver stage development and parasitemia was obtained in 100% of balb/c mice primed with a replication-defective recombinant adenovirus expressing the circumsporozoite (cs) protein of plasmodium yoelii (adpycs), followed by a booster with an attenuated recombinant vaccinia virus, expressing the same malaria antigen, vacpycs. we found increased levels of activated cs-specific cd8(+) and cd4(+) t cells, higher anti-sporozoit ...200111553779
possibility of false-positive detection for sporozoites in mosquitos (diptera: culicidae) by nested polymerase chain reaction using plasmodium yoelii genomic dna.anopheles stephensi liston and an. saperoi bohart and ingram infected with the rodent malaria parasite plasmodium yoelii nigeriense. they were examined 12 and 19 days after blood feeding for sporozoites in head with anterior thorax (ht) and oocysts in abdomen with posterior thorax (ab) by light microscopy and by the nested polymerase chain reaction (nested pcr-based on the amplification of the sequences of the small subunit ribosomal rna gene). the detection rate of parasite dna by nested pcr in ...200111556576
apoptotic deletion of th cells specific for the 19-kda carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection.immunity induced by the 19-kda fragment of merozoite surface protein 1 is dependent on cd4+ th cells. however, we found that adoptively transferred cfse-labeled th cells specific for an epitope on plasmodium yoelii 19-kda fragment of merozoite surface protein 1 (peptide (p)24), but not ova-specific t cells, were deleted as a result of p. yoelii infection. as a result of infection, spleen cells recovered from infected p24-specific t cell-transfused mice demonstrated reduced response to specific a ...200111564808
generation of cytotoxic t lymphocytes by mhc class i ligands fused to heat shock cognate protein 70.immunization with gp96 and heat shock cognate protein 70 (hsc70) purified with in vivo bound naturally occurring peptides or bound to synthetic peptides by in vitro reconstitution has been shown to induce peptide-specific cytotoxic t lymphocytes (ctl). in addition, mycobacterial heat shock protein 70 covalently fused to ovalbumin (ova)-derived fragments has been shown to generate mhc class i-restricted ctl responses. here, we genetically fused five different ctl epitopes, including peptides deri ...200111581168
resistance to malarial infection is achieved by the cooperation of nk1.1(+) and nk1.1(-) subsets of intermediate tcr cells which are constituents of innate immunity.we previously reported that the major expanding lymphocytes were intermediate tcr (tcr(int)) cells (mainly nk1.1(-)) during malarial infection in mice. cell transfer experiments of tcr(int) cells indicated that these t cells mediated resistance to malaria. however, tcr(int) cells always contain nk1.1(+)tcr(int) cells (i.e., nkt cells) and controversial results (nkt cells were effective or not for resistance to malaria) have been reported by different investigators. in this study, we used cd1d((- ...200111591113
cd4+ t cells are required for hsp65 expression in host macrophages and for protection of mice infected with plasmodium yoelii.we have reported that macrophages expressing heat-shock protein 65 play an essential role in protection of mice infected with plasmodium yoelii. in this study, we investigated the function and expression mechanism of hsp65 in macrophages of mice infected with p. yoelii. c57bl/6 (b6) mice are susceptible to infection with the lethal (l) strain but resistant to infection with the non-lethal (nl) strain of p. yoelii. the percentage of apoptotic macrophages in mice infected with the l strain was hig ...200111595577
malaria-induced apoptosis in mosquito ovaries: a mechanism to control vector egg production.many insects are able to adjust their egg production according to physiological conditions such as nutrient supply and mating success. one way in which this is achieved is by resorption of some, or all, of the ovarian follicles at some stage during oogenesis. we have shown that the mosquito anopheles stephensi responds in this manner when ookinetes of the malaria parasite plasmodium yoelii nigeriensis first begin to invade the midgut. little is known about the initiation and regulation of follic ...200111683433
synthesis of new arylaminoquinoxalines and their antimalarial activity in mice.2-arylaminoquinoxalines were prepared by the condensation of 2-chloroquinoxaline with the appropriate mannich bases in the presence of hcl. to synthesize the mannich bases, 4-acetamidophenol was reacted with formaldehyde and dialkylamine to yield 3-[(dialkylamino) methyl]-4-hydroxyacetanilide, followed by hydrolysis. antimalarial activities of the new arylaminoquinoxalines were evaluated against the rodent malaria parasite plasmodium yoelii at a dose of 75 mg kg(-1). three compounds synthesized ...200111697550
characterization of the ornithine aminotransferase from plasmodium falciparum.the ornithine aminotransferase from plasmodium falciparum 3d7 was cloned, functionally expressed, and characterized. the gene exists as a single copy in the malarial genome and is located on chromosomes 6/7/8. the deduced amino acid sequence was found to be 85% identical to a similar sequence discovered in plasmodium yoelii, 82% identical to a partial sequence from plasmodium vivax, and 42-53% identical to ornithine aminotransferases from other eukaryotes. the enzyme had a very narrow substrate ...200111704268
properties of the plasmodium falciparum homologue of a protective vaccine candidate of plasmodium yoelii.we describe an unusual tryptophan-rich protein of plasmodium falciparum that contains threonine-rich repeats. the protein is encoded by a 2.5 kb gene with a two-exon structure including a short at-rich intron that is spliced out of the mature message. the 5' end of the gene encodes a hydrophobic region, which is assumed to be a signal peptide. the peptide sequence is characterised by a tryptophan-rich region and a block of degenerate threonine repeats. the protein is synthesised throughout the a ...200111704272
can malaria dna vaccines on their own be as immunogenic and protective as prime-boost approaches to immunization?to develop a multi-stage, multi-antigen, multi-immune response-inducing vaccine against malaria we have focused on dna vaccines because of their simplicity of construction and modification, ease of mixing, and effectiveness in inducing cd8+ t cell responses. dna malaria vaccines induce cd8+ t cell dependent protection in mice and cd8+ ctl in rhesus monkeys and humans after intramuscular needle administration. clinical trials in normal, healthy humans are in progress or planned, assessing alterna ...200011713810
in vitro beta-hematin formation assays with plasma of mice infected with plasmodium yoelii and other parasite preparations: comparative inhibition with quinoline and endoperoxide antimalarials.formation of beta-hematin in vitro could be catalyzed in the presence of various preparations related to the malaria parasite viz., the cell free homogenate of plasmodium yoelii, lipid extract of the parasite homogenate, purified malarial hemozoin and synthetic beta-hematin. plasma from mice infected with p. yoelii also catalyzed in vitro beta-hematin formation with highly significant efficiency. the plasma based beta-hematin formation assay was highly sensitive, as the background absorbance was ...200111720077
tacrk3 encodes a novel theileria annulata protein kinase with motifs characteristic of the family of eukaryotic cyclin dependent kinases: a comparative analysis of its expression with tacrk2 during the parasite life cycle.the tacrk3 gene from the bovine apicomplexan parasite theileria annulata, encodes a 46 kda polypeptide with strong homology to the eukaryotic family of cyclin-dependent kinases. tacrk3 does not show significant alignment with any particular cdk group, other than the pfmrk kinases from the related apicomplexans plasmodium falciparum and plasmodium yoelii. it has a putative bipartite nuclear localization signal and is located to parasite nuclei by ifat. protein levels are constitutive throughout d ...200111733137
the high molecular mass rhoptry protein, rhoph1, is encoded by members of the clag multigene family in plasmodium falciparum and plasmodium yoelii.malarial merozoite rhoptries contain a high molecular mass protein complex called rhoph. rhoph is composed of three polypeptides, rhoph1, rhoph2, and rhoph3, encoded by distinct genes. using monoclonal antibody-purified protein complex from both plasmodium falciparum and plasmodium yoelii, peptides were obtained by digestion of rhoph1 and their sequence determined either by mass spectrometry or edman degradation. in both species the genes encoding rhoph1 were identified as members of the cytoadh ...200111738712
determining liver stage parasite burden by real time quantitative pcr as a method for evaluating pre-erythrocytic malaria vaccine efficacy.the detection and quantitation of blood stage parasitaemia is typically used as a surrogate endpoint for estimating the efficacy of vaccines targeted against the hepatic stage, as well as the erythrocytic stage, of the parasite. however, this does not provide an adequate means of evaluating the efficacy of vaccines, which may be only partially effective at the liver-stage. this is a particular concern for effective evaluation of immune enhancement strategies for candidate pre-erythrocytic stage ...200111738713
a physiochemical mechanism of hemozoin (beta-hematin) synthesis by malaria parasite.malaria parasite homogenate, the lipid extracts, and an unsaturated fatty acid, linoleic acid, which have been shown to promote beta-hematin formation in vitro, were used to investigate the mechanism of hemozoin biosynthesis, a distinct metabolic function of the malaria parasite. in vitro beta-hematin formation promoted by plasmodium yoelii homogenate, the lipid extracts, and linoleic acid were blocked by ascorbic acid, reduced glutathione, sodium dithionite, beta-mercaptoethanol, dithiothreitol ...200211779214
stage-specific transcription of distinct repertoires of a multigene family during plasmodium life cycle.members of a multigene family in the rodent malaria parasite plasmodium yoelii yoelii code for 235-kilodalton proteins (py235) that are located in the merozoite apical complex, are implicated in virulence, and may determine red blood cell specificity. we show that distinct subsets of py235 genes are expressed in sporozoites and hepatic and erythrocytic stages. antibodies to py235 inhibited sporozoite invasion of hepatocytes. the switch in expression profile occurred immediately after transition ...200211786645
improved immunogenicity and efficacy of the recombinant 19-kilodalton merozoite surface protein 1 by the addition of oligodeoxynucleotide and aluminum hydroxide gel in a murine malaria vaccine model.vaccination of mice with yeast-secreted plasmodium yoelii-derived 19-kilodalton merozoite surface protein 1 (ymsp1(19)) has been shown to afford protection from challenge with a lethal strain of p. yoelii. sterile immunity can be achieved when msp1(19) is emulsified in freund adjuvant but not when it is adsorbed to aluminum hydroxide gel (alum). because complete freund adjuvant is not an acceptable adjuvant for use in humans, alternative adjuvants must be identified for formulating msp1(19) as a ...200211796601
protective immune responses to the 42-kilodalton (kda) region of plasmodium yoelii merozoite surface protein 1 are induced by the c-terminal 19-kda region but not by the adjacent 33-kda region.vaccination of mice with the 42-kda region of plasmodium yoelii merozoite surface protein 1 (msp1(42)) or its 19-kda c-terminal processing product (msp1(19)) can elicit protective antibody responses in mice. to investigate if the 33-kda n-terminal fragment (msp1(33)) of msp1(42) also induces protection, the gene segment encoding msp1(33) was expressed as a glutathione s-transferase (gst) fusion protein. c57bl/6 and balb/c mice were immunized with gst-msp1(33) and subsequently challenged with the ...200211796616
laser capture microdissection and molecular analysis of plasmodium yoelii liver-stage parasites. 200211814581
chromosomal mapping of the host resistance locus to rodent malaria (plasmodium yoelii) infection in mice.the disease outcome in malaria caused by the protozoan parasite plasmodium is influenced by host genetic factors. to identify host genes conferring resistance to infection with the malaria parasite, we undertook chromosomal mapping using a whole-genome scanning approach in cross-bred mice. nc/jic mice all died with high parasitemia within 8 days of infection with 1 x 10(5) parasitized erythrocytes. in contrast, 129/svj mice all completely excluded malaria parasites from the circulation and remai ...200111862405
plasmodium yoelii uses the murine duffy antigen receptor for chemokines as a receptor for normocyte invasion and an alternative receptor for reticulocyte invasion.erythrocyte invasion by malaria parasites is a complex multistep process involving parasite and erythrocyte receptors. it is a critical stage in the parasite life cycle and, therefore, a logical step in which to intervene to prevent or ameliorate disease. rodent models of malaria, commonly plasmodium yoelii, are frequently used for studies of malaria pathogenesis. little is known, however, about the invasion machinery of rodent malaria parasites. we have found previously that mice congenic for a ...200211929753
susceptibility of the mosquitoes anopheles minimus, an. sinensis, and an. saperoi (diptera: culicidae) from the ryukyu archipelago, japan, to the rodent malaria plasmodium yoelii nigeriense.the susceptibility of three anopheline mosquitoes, anopheles minimus theobald, an. sinensis wiedemann, and an. saperoi bohart & ingram, from the ryukyu archipelago to the rodent malaria, plasmodium yoelii nigeriense was examined to find new vectors other than an. stephensi liston for rodent malaria studies in the laboratory. the survival rate of the mosquitoes after feeding on mice infected with p. y. nigeriense was also examined. the beech strain of an. stephensi from india was compared with an ...200211931249
[synthesis of primaquine analogues and their antimalarial activity in mice].ten 4-methyl-5-substituted-phenoxy-6-methoxy-8-[(1-ethyl-4-amino) butylamino] quinolines (10a-j) have been synthesized and evaluated preliminarily for both suppressive and causal prophylactic antimalarial activities. the results of preliminary screening test showed that three of these compounds exhibited significant activity against plasmodium yoelii in mice, among which 10c was 4-8 times as effective as primaquine. moreover, 10c was superior to primaquine in suppressive test against plasmodium ...199811938965
the role of il-18 in blood-stage immunity against murine malaria plasmodium yoelii 265 and plasmodium berghei anka.a possible protective role of il-18 in host defense against blood-stage murine malarial infection was studied in balb/c mice using a nonlethal strain, plasmodium yoelii 265, and a lethal strain, plasmodium berghei anka. infection induced an increase in mrna expression of il-18, il-12p40, ifn-gamma, and tnf-alpha in the case of p. yoelii 265 and an increase of il-18, il-12p40, and ifn-gamma in the case of p. berghei anka. the timing of mrna expression of il-18 in both cases was consistent with a ...200211971017
plasmodium yoelii sporozoites infect cd36-deficient mice. 200211971649
antagonist effect of chloroquine and tumor necrosis factor on hepatic oxidative stress and antioxidant defense in normal and plasmodium yoelii nigeriensis-infected mice.plasmodium yoelii nigeriensis (p. y. nigeriensis) produces lethal malaria infection in swiss albino mice. tumor necrosis factor (tnf) has been implicated in the pathogenesis of malaria by production of reactive oxygen species. chloroquine is a traditionally used antimalarial and has been postulated to inhibit tnf secretion during malaria infection.200211980364
antigen-presenting cell function during plasmodium yoelii infection.antigen-presenting cells (apc) play a key role in orchestrating immune responses. t-cell proliferative responses are inhibited during the erythrocyte stages of malaria infection, and a number of studies have suggested that apc are responsible for this phenomenon. in the present studies we examine individual components of the t-cell-activating function of apc: expression of costimulatory and major histocompatibility complex (mhc) class ii proteins, the ability to process and present antigen to t ...200212010983
single-chain antibodies produced by phage display against the c-terminal 19 kda region of merozoite surface protein-1 of plasmodium yoelii reduce parasite growth following challenge.antibodies have the potential to be therapeutic reagents for malaria. here we describe the production of a novel phage antibody display library against the c-terminal 19kda region of the plasmodium yoelii ym merozoite surface protein-1 (msp1(19)). in vivo studies against homologous lethal malaria challenge show an anti-parasite effect in a dose dependent manner, and analysis by plasmon resonance indicates binding to the antigen is comparable to the binding of a protective monoclonal antibody. th ...200212034110
expression of recombinant plasmodium falciparum subtilisin-like protease-1 in insect cells. characterization, comparison with the parasite protease, and homology modeling.serine proteases play crucial roles in erythrocyte invasion by merozoites of the malaria parasite. plasmodium falciparum subtilisin-like protease-1 (pfsub-1) is synthesized during maturation of the intraerythrocytic parasite and accumulates in a set of merozoite secretory organelles, suggesting that it may play a role in host cell invasion or post-invasion events. we describe the production, purification, and characterization of recombinant pfsub-1 and comparison with the authentic protease dete ...200212052828
polyspecific malaria antibodies present at the time of infection inhibit the development of immunity to malaria but antibodies specific for the malaria merozoite surface protein, msp1, facilitate immunity.serum taken from mice immune to malaria as a result of infection and drug cure, or from mice immunized with a recombinant form of the merozoite surface protein, msp1, can provide passive protection of recipient mice against the lethal parasite, plasmodium yoelii ym. however, recipients of msp1-immune serum go on to develop long-term immunity, whereas recipients of serum from mice naturally immune to malaria rapidly lose their resistance to infection. we demonstrate that 'infection/cure' serum su ...200212060317
persistence of protective immunity to malaria induced by dna priming and poxvirus boosting: characterization of effector and memory cd8(+)-t-cell populations.the persistence of immunity to malaria induced in mice by a heterologous dna priming and poxvirus boosting regimen was characterized. mice were immunized by priming with dna vaccine plasmids encoding the plasmodium yoelii circumsporozoite protein (pycsp) and murine granulocyte-macrophage colony-stimulating factor and boosting with recombinant vaccinia encoding pycsp. balb/c mice immunized with either high-dose (100 microg of p pycsp plus 30 microg of pgm-csf) or low-dose (1 microg of p pycsp plu ...200212065488
[effect of dihydroquinghaosu on the development of plasmodium yoelii yoelii in anopheles stephensi].to observe the effect of dihydro qinghaosu (dqhs) on the development of plasmodium yoelii yoelii in anopheles stephensi and to explore the possibility of whether dqhs has preventive effect against malaria.199812078286
identification of t cell epitopes on the 33-kda fragment of plasmodium yoelii merozoite surface protein 1 and their antibody-independent protective role in immunity to blood stage malaria.merozoite surface protein 1 (msp1) of malaria parasites undergoes proteolytic processing at least twice before invasion into a new rbc. the 42-kda fragment, a product of primary processing, is cleaved by proteolytic enzymes giving rise to msp1(33), which is shed from the merozoite surface, and msp1(19), which is the only fragment carried into a new rbc. in this study, we have identified t cell epitopes on msp1(33) of plasmodium yoelii and have examined their function in immunity to blood stage m ...200212097400
a novel dna repair enzyme containing rna recognition, g-patch and specific splicing factor 45-like motifs in the protozoan parasite toxoplasma gondii.we report the cloning and functional characterization of the full-length cdna and gene encoding a toxoplasma gondii dna repair enzyme designated tgdre. the gene is composed of three exons separated by two introns of 780 and 630 bp, and encodes a protein with a predicted molecular mass of 49.6 kda. the native tgdre protein, with a molecular mass of 60 kda, is only detected in the virulent tachyzoite stage of t. gondii. however, the transcript is present in both asexual parasite stages, virulent t ...200212135477
in vivo active antimalarial isonitriles.building on the lead from antimalarial isonitriles 1-4 of marine origin, several easily accessible synthetic isonitriles were assessed for their antimalarial activity against plasmodium falciparum (in vitro) and multidrug resistant plasmodium yoelii in swiss mice model (in vivo). isonitrile 11 has shown promising activity in both these assays.200212161115
identification, expression, and functional characterization of maebl, a sporozoite and asexual blood stage chimeric erythrocyte-binding protein of plasmodium falciparum.maebl is a chimeric erythrocyte binding protein reported in rodent malaria parasites plasmodium yoelii and plasmodium berghei, that has the gene structure similar to erythrocyte binding proteins, but n-terminal homology to subdomains i and ii of apical membrane antigen-1. we report here the sequence analysis and gene structure of the plasmodium falciparum maebl gene. we have cloned and expressed a putative red cell binding domain, m2, of this gene in escherichia coli, purified the recombinant pr ...200212165387
identification and disruption of the gene encoding the third member of the low-molecular-mass rhoptry complex in plasmodium falciparum.the low-molecular-mass rhoptry complex of plasmodium falciparum consists of three proteins, rhoptry-associated protein 1 (rap1), rap2, and rap3. the genes encoding rap1 and rap2 are known; however, the rap3 gene has not been identified. in this study we identify the rap3 gene from the p. falciparum genome database and show that this protein is part of the low-molecular-mass rhoptry complex. disruption of rap3 demonstrated that it is not essential for merozoite invasion, probably because rap2 can ...200212183575
in vivo depletion of cd11c+ dendritic cells abrogates priming of cd8+ t cells by exogenous cell-associated antigens.cytotoxic t lymphocytes (ctl) respond to antigenic peptides presented on mhc class i molecules. on most cells, these peptides are exclusively of endogenous, cytosolic origin. bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for mhc i presentation of exogenous antigens. this mechanism permits cross-presentation of pathogen-infected cells and the priming of ctl responses against intracellular microbial infections. here, we report a novel diphtheria toxin-based system ...200212196292
ntp technical report on the toxicity studies of a chemical mixture of 25 groundwater contaminants administered in drinking water to f344/n rats and b6c3f(1) mice.toxicity studies were performed with a chemically defined mixture of 25 groundwater contaminants, using dose levels considered to have environmental relevance. the mixture contained 19 organic compounds and six metals (shown below); the selection of these compounds was based primarily on the frequency of their occurrence in united states environmental protection agency surveys of groundwater contamination in the vicinity of hazardous waste disposal sites. this report focuses primarily on 26-week ...199312209189
structure-activity relationships of the antimalarial agent artemisinin. 7. direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates.on the basis of earlier reported quantitative structure-activity relationship studies, a series of 9beta-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. several of the new compounds 7 and 10-14 were synthesized employing the key synthetic intermediate 23. in a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisi ...200212213073
comparative characterization of hexose transporters of plasmodium knowlesi, plasmodium yoelii and toxoplasma gondii highlights functional differences within the apicomplexan family.chemotherapy of apicomplexan parasites is limited by emerging drug resistance or lack of novel targets. pfht1, the plasmodium falciparum hexose transporter 1, is a promising new drug target because asexual-stage malarial parasites depend wholly on glucose for energy. we have performed a comparative functional characterization of pfht1 and hexose transporters of the simian malarial parasite p. knowlesi (pkht1), the rodent parasite p. yoelii (pyht1) and the human apicomplexan parasite toxoplasma g ...200212238947
plasmodium yoelii sporozoites infect syndecan-1 deficient mice. 200212270630
genome sequence and comparative analysis of the model rodent malaria parasite plasmodium yoelii yoelii.species of malaria parasite that infect rodents have long been used as models for malaria disease research. here we report the whole-genome shotgun sequence of one species, plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite plasmodium falciparum clone 3d7. a synteny map of 2,212 p. y. yoelii contiguous dna sequences (contigs) aligned to 14 p. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. of abou ...200212368865
nature and specificity of the required protective immune response that develops postchallenge in mice vaccinated with the 19-kilodalton fragment of plasmodium yoelii merozoite surface protein 1.immunity induced by the 19-kda fragment of plasmodium yoelii merozoite surface protein 1 (msp1(19)) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. however, the specificity of the active immune response postinfection has not been defined. in particular, it is not known whether anti-msp1(19) antibodies that arise following infection alone are sufficient for protection. we developed systems to investigate wh ...200212379677
merozoite surface protein 1-specific immune response is protective against exoerythrocytic forms of plasmodium yoelii.one of the difficulties in developing an effective malaria vaccine is the antigenic change of the parasite during the life cycle. it is desirable that vaccine-induced protective immunity be effective at different stages of parasite development. merozoite surface protein 1 (msp1) is a candidate vaccine antigen against blood-stage malaria, but it is also expressed in the exoerythrocytic forms. it was not known, however, whether the anti-msp1 immune response is effective against the liver-stage mal ...200212379684
haem polymerase as a novel target of antimalarial action of cyproheptadine.an antihistaminic drug, cyproheptadine (20-25mg/kg x 4 days), showed significant schizontocidal activity in the blood against a lethal multidrug-resistant (mdr) strain of plasmodium yoelii nigeriensis (highly resistant to chloroquine, mefloquine, and quinine); the protection of mice ranged between 75 and 100%. a combination of cyproheptadine (15 mg/kg) and chloroquine improved antimalarial activity compared to treatment with either drug alone, whereas a combination of cyproheptadine with quinine ...200212392821
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