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disseminated candidiasis and hepatic malarial infection in mannose-binding-lectin-a-deficient mice.to examine the physiological functions of mannose-binding lectin a (mbl-a), we generated mice that were deficient in mbl-a and examined their susceptibilities to the microbial pathogens candida albicans and plasmodium yoelii, an accepted experimental malaria model in mouse. we found no differences in the survival rates and fungal burdens of wild-type and mbl-a(-/-) mice with disseminated c. albicans infection. the two mouse strains were also similar in their abilities to resist hepatic accumulat ...200212417723
immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with plasmodium yoelii.it is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. we set out to test this proposition in the plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. we therefore examined a defined protein mixture made of the ...200212438332
isolation and antimalarial activity of peroxydisulfate oxidation products of primaquine.five compounds formed by peroxydisulfate oxidation of primaquine were isolated using chromatographic methods and evaluated for antimalarial activity in vitro. one compound 6-methoxy-5,8 bis(4'-amino-1'-methylbutylamino)quinoline [p(1)] was found to have good gametocytocidal activity against plasmodium yoelli infected mice at 10mg kg(-1) dose in vivo.200212443782
parasite-specific immunoglobulin isotypes during lethal and non-lethal murine malaria infections.production of parasite-specific antibodies is an important component of immunity to blood stage malaria infection, as shown by several previous studies in rodent models. however, no study has addressed the induction of humoral immunity by different parasites in a genetically homogeneous host population. here, levels of parasite-specific immunoglobulin isotypes were measured during primary infections of plasmodium chabaudi and of plasmodium yoelii in inbred nih mice inoculated with cloned lines o ...200312474040
a multigene family that interacts with the amino terminus of plasmodium msp-1 identified using the yeast two-hybrid system.merozoite surface protein 1 (msp-1) is a high-molecular-weight protein expressed on the surface of the malaria merozoite in a noncovalent complex with other protein molecules. msp-1 undergoes a series of proteolytic processing events, but no precise biological role for the various proteolytic fragments of msp-1 or for the additional proteins present in the complex is known. through the use of the yeast two-hybrid system, we have isolated genes encoding proteins that interact with a region of the ...200212477792
hepatocyte cd81 is required for plasmodium falciparum and plasmodium yoelii sporozoite infectivity.plasmodium sporozoites are transmitted through the bite of infected mosquitoes and first invade the liver of the mammalian host, as an obligatory step of the life cycle of the malaria parasite. within hepatocytes, plasmodium sporozoites reside in a membrane-bound vacuole, where they differentiate into exoerythrocytic forms and merozoites that subsequently infect erythrocytes and cause the malaria disease. plasmodium sporozoite targeting to the liver is mediated by the specific binding of major s ...200312483205
[effect of nitroquine on the membrane phospholipid of intraerythrocytic plasmodium yoelii in vitro].to study the mechanism of antimalarial action of nitroquine.199912563858
[relationship between hemolymph phenol oxidase and melanization of oocysts of plasmodium yoelii in anopheles stephensi].to explore the relationship between the hemolymph phenol oxidase and melanization of oocysts.200012567462
[effect of anti-mosquito-midgut antibodies on the development of oocysts of plasmodium yoelii in anopheles stephensi].to study the effect of anti-mosquito-midgut antibodies on the development of p. yoelii in a. stephensi.200012567656
[partial sequence of sporogony stage-specific 18s ribosomal dna of plasmodium yoelii and its application for detection of parasites].to determine sequence of sporogony stage-specific (s type) 18s ribosomal rna gene of plasmodium yoelii (p. y) by265 strain, and by using it to detect the malaria parasites within vector mosquito.200112571939
[enrichment and screening of up-regulated genes of the mosquito anopheles stephensi in response to malaria parasite].to isolate and identify genes related to malaria parasite infection in vector mosquito, and to explore the mechanisms.200112572060
production and characterization of monoclonal antibodies against asexual stages of plasmodium yoelii nigeriensis.swiss mice vaccinated with plasmodium yoelii nigeriensis-soluble antigen and saponin, following a homologous 100% lethal challenge, showed 60% protection (6 out of 10 mice survived). monoclonal antibodies (mabs), generated by hybridizing the sp2/0 myeloma cells with the splenocytes of each of these ten mice, separately, were screened using enzyme-linked immunosorbent assay (elisa), and were characterized by using merozoite (mz) invasion inhibition assay in vitro, immunofluorescence assay (ifa), ...200212573112
the purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria.although there is good evidence that immunity to the blood stages of malaria parasites can be mediated by different effector components of the adaptive immune system, target antigens for a principal component, effector cd4(+) t cells, have never been defined. we generated cd4(+) t cell lines to fractions of native antigens from the blood stages of the rodent parasite, plasmodium yoelii, and identified fraction-specific t cells that had a th1 phenotype (producing il-2, ifn-gamma, and tumor necros ...200312594331
a unique insertion in plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: evolutionary and functional studies.plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (g6pd-6pgl) is a bifunctional enzyme with significant sequence similarity in both the 6pgl and g6pd domains to the plasmodium falciparum enzyme. a recombinant form of the p. berghei enzyme was found to have both g6pd and 6pgl activities, and therefore catalyses the first two steps in the pentose phosphate pathway. genes encoding very similar proteins are also found in three other malarial parasites, plasmodium yoelii, ...200312615331
characterisation of the rhoph2 gene of plasmodium falciparum and plasmodium yoelii.the high molecular mass protein complex (rhoph) in the rhoptries of the malaria parasite consists of three distinct polypeptides with estimated sizes in plasmodium falciparum of 155kda (pfrhoph1), 140kda (pfrhoph2) and 110kda (pfrhoph3). using a number of reagents, including a new mab 4e10 that is specific for the pfrhoph complex, it was shown that the rhoph complex is synthesised during schizogony and transferred intact to the ring stage in newly invaded erythrocytes. the genes encoding rhoph1 ...200312615335
gene gun-based co-immunization of merozoite surface protein-1 cdna with il-12 expression plasmid confers protection against lethal plasmodium yoelii in a/j mice.the carboxyl-terminal region of the merozoite surface protein-1 (msp1) is a leading candidate for a vaccine against malaria in the erythrocytic stage. in this study, we investigated the utility of interleukin-12 (il-12) cdna as an adjuvant for malaria dna vaccine in a mouse challenge model. we found that co-immunization of expression plasmids encoding a c-terminal 15-kda fragment of msp1 (msp1-15) with the il-12 gene using a gene gun significantly increased the protective immunity against malari ...200312615440
ovary specific immune response during plasmodium yoelii yoelii infection in malaria vector anopheles stephensi (diptera:insecta).innate immune related polypeptides expression during three gonotrophic cycles in the ovaries of major disease vector mosquito a. stephensi has been analyzed following infection by malaria parasite, p. yoelii yoelii. seventeen polypeptides were induced in the ovaries of various stages due to parasitic infection. most of proteins were induced systemically during early stages of infection suggesting the possibility of immune related signalling process. the reduction in the quantity of protein conte ...200212622212
the dendritic cell-specific chemokine, dendritic cell-derived cc chemokine 1, enhances protective cell-mediated immunity to murine malaria.cell-mediated immunity plays a crucial role in the control of many infectious diseases, necessitating the need for adjuvants that can augment cellular immune responses elicited by vaccines. it is well established that protection against one such disease, malaria, requires strong cd8(+) t cell responses targeted against the liver stages of the causative agent, plasmodium spp. in this report we show that the dendritic cell-specific chemokine, dendritic cell-derived cc chemokine 1 (dc-ck1), which i ...200312626578
prophylactic effect of multi-herbal extract 'agbo-iba' on malaria induced in mice.to determine the efficacy of a multi-herbal preparation extract of 'agbo-iba' on rodent malaria induced in mice.200212638827
identification and characterization of a conserved, stage-specific gene product of plasmodium falciparum recognized by parasite growth inhibitory antibodies.we have identified a novel conserved protein of plasmodium falciparum, designated d13, that is stage-specifically expressed in asexual blood stages of the parasite. the predicted open reading frame (orf) d13 contains 863 amino acids with a calculated molecular mass of 99.7 kda and displays a repeat region composed of pentapeptide motives. northern blot analysis with lysates of synchronized blood stage parasites showed that d13 is highly expressed at the mrna level during schizogony. the first n' ...200312654839
a plasmodium yoelii yoelii erythrocyte binding protein that uses duffy binding-like domain for invasion: a rodent model for studying erythrocyte invasion. 200312706804
the histone h4 gene of plasmodium falciparum is developmentally transcribed in asexual parasites.histones are abundant nuclear core proteins that are present in all eukararyotes and are responsible for linking chromosomes and packaging them into tight chromatin aggregates. the histone h2a, h2b, and h3 genes and a partial sequence of the histone h4 gene from plasmodium falciparum have been previously identified and share a high level of nucleotide sequence identity. in this study, we compare the histone h4 sequence of the human malaria p. falciparum with the sequences of two mouse malarias, ...200312739134
trypsin and aminopeptidase activities in blood-fed females anopheles dirus (diptera: culicidae) of differing susceptibility to plasmodium yoelii nigeriensis.midgut proteolytic enzymes contribute to the success or failure of plasmodium infection of the mosquito. the present study investigated trypsin and aminopeptidase activities in the midgut of two strains of anopheles dirus selected for susceptibility and refractoriness to plasmodium yoelii nigeriensis. at intervals of 6 hours following a bloodmeal, the midguts of fully engorged female mosquitos were dissected, homogenized, and assayed for enzyme activity. no differences trypsin activity (nmole/mi ...200212757211
plasmodium yoelii: semiquantitative analyses of circumsporozoite protein gene expression during the sporogonic development of p. y. yoelii and p. y. nigeriensis in the mosquito vector anopheles stephensi.malaria infection in the mosquito vector can be modulated by the vertebrate host, mosquito factors, and interactions between different parasite populations. modulation of parasite development can be assessed through the study of gene expression. the present report describes a specific, sensitive, and nonradioactive method that permits assessment of parasite load and quantification of circumsporozoite protein gene expression during the sporogonic stages of plasmodium yoelii yoelii and p. y. niger ...200312760638
glycosylphosphatidyl-inositols in murine malaria: plasmodium yoelii yoelii.glycosylphosphatidyl-inositols (gpis) are vital major glycoconjugates in intraerythrocytic stages of plasmodium. here, we report on the biosynthesis and the characterization of gpis synthesized by the murine malarial parasite p. yoelii yoelii ym. parasitized erythrocytes were labeled in vivo and in vitro with either radioactive nucleotide sugar precursors, ethanolamine or glucosamine. the pathway leading to the formation of gpi precursors was found to resemble that described for p. falciparum; h ...200312770786
a short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic beta-sulfonyl-endoperoxides.the syntheses and in vitro antimalarial screening of 50 bridged, bicyclic endoperoxides of types 9-13 are reported. in contrast to antimalarial trioxanes of the artemisinin family, but like yingzhaosu a and arteflene, the peroxide function of compounds 9-13 is contained in a 2,3-dioxabicyclo[3.3.1]nonane system 6. peroxides 9 and 10 (r(1) = oh) are readily available through a multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a toco reaction). beta-sul ...200312773055
cpg oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kda carboxyl-terminal fragment of plasmodium yoelii merozoite surface protein-1 (msp1(19)) formulated in oil-based montanides.the 19kda carboxyl-terminal fragment of plasmodium yoelii merozoite surface protein-1 (msp1(19)), an analog of the leading falciparum malaria vaccine candidate, induces protective immunity to challenge infection when formulated with complete/incomplete freund's adjuvant (cfa/ifa), an adjuvant unsuitable for use in humans. in this study, we investigate montanide isa51 and montanide isa720 as well as cpg oligodeoxynucleotide (odn) as adjuvants for induction of immunity to msp1(19). mice immunized ...200312798636
anopheles gambiae collagen iv genes: cloning, phylogeny and midgut expression associated with blood feeding and plasmodium infection.a prerequisite for understanding the role that mosquito midgut extracellular matrix molecules play in malaria parasite development is proper isolation and characterisation of the genes coding for components of the basal lamina. here we have identified genes coding for alpha1 and alpha2 chains of collagen iv from the major malaria vector, anopheles gambiae. conserved sequences in the terminal nc1 domain were used to obtain partial gene sequences of this functional region, and full sequence was is ...200312814648
comparison of antimalarial activity of the alkaloidal fraction of hydrangea macrophylla var. otaksa leaves with the hot-water extract in icr mice infected with plasmodium yoelii 17 xl.the antimalarial activity of the fractions isolated from the leaves of hydrangea macrophylla seringe var. otaksa makino was evaluated against plasmodium yoelii 17 xl in mice. four different fractions were prepared in the usual manner to obtain an alkaloid fraction. all mice treated with the fraction containing febrifugine and isofebrifugine mixture at 1 mg/kg twice a day for 5 consecutive days survived during the experiment, and the change of mean parasitemia level showed almost the same pattern ...200312820231
different responses of three rodent plasmodia species, plasmodium yoelii 17xl, p. berghei nk65 and p. chabaudi as on treatment with febrifugine and isofebrifugine mixture from hydrangea macrophylla var. otaksa leaf in icr mice.the antimalarial activity of hydrangea macrophylla var. otaksa alkaloids was evaluated against plasmodium yoelii 17xl, p. berghei nk65 and p. chabaudi as in icr mice. for trials in p. yoelii 17xl or p. chabaudi as infections, mice were infected intraperitoneally with 10(5), 10(6) and 10(7) parasitized erythrocytes, respectively, and in p. berghei nk65 infections, mice were infected intraperitoneally with 10(3), 10(4) and 10(5) parasitized erythrocytes, respectively. three days after injection, m ...200312820234
utility of the dried blood on filter paper as a source of cytokine mrna for the analysis of immunoreactions in plasmodium yoelii infection.we examined the utility of dried blood on filter paper for the source of cytokine messenger rna (mrna). total rna was isolated from the dried blood of mice infected with plasmodium yoelii, and cdna was amplified by reverse transcription-polymerase chain reaction (rt-pcr). as a reference, we extracted total rna from peripheral blood collected at the same time as the preparation for dried blood. there was no difference in cytokine mrna expression between the two sources; the dried blood on filter ...200312826305
early self-regulatory mechanisms control the magnitude of cd8+ t cell responses against liver stages of murine malaria.following immunization with plasmodium yoelii sporozoites, the cd8(+) t cell population specific for the syvpsaeqi epitope expressed in sporozoite and liver stages of this malaria parasite revealed the existence of a short term ag presentation process that translated into a single clonal burst. further expansion of this cd8(+) t cell population in conditions of sustained ag exposure and additional supply of naive cells was inhibited by regulatory mechanisms that were developed as early as 24-48 ...200312847268
novel antimalarial antibodies highlight the importance of the antibody fc region in mediating protection.parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. the success of passive immunization suggests that immunoglobulin (ig)-based therapies are effective. to further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric igg1 and iga1 and a single-chain diabody specific for the c-terminal 19-kda region of plasmodium yoelii merozoite surface protein 1 (msp119), ...200312855589
in vitro activities of 25 quinolones and fluoroquinolones against liver and blood stage plasmodium spp.the in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of plasmodium falciparum and against liver stages of plasmodium yoelii yoelii and p. falciparum were studied. all compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant p. falciparum grown in red blood cells. this inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. grepafloxacin, trovafloxacin, and ciprofloxacin were the most ...200312878530
the infectivity of plasmodium yoelii in different strains of mice.we evaluated the effect of using medium 199 alone and medium 199 supplemented with 5% normal mouse serum, 5% fetal calf serum, 5% bovine serum albumin or 5% albumax on plasmodium yoelii sporozoite yield from infected mosquitoes and infectivity in balb/c mice. the sporozoites yield, as well as their infectivity, was statistically lower (p = 0.0031) when unsupplemented medium 199 was used to separate sporozoites from infected mosquitoes. although medium 199 supplemented with albumax led to lower s ...200312880263
[study on the relationship between intracellular free calcium and melanization in oocysts of plasmodium yoelii].to study the change of intracellular free ca2+ in the oocyst when it melanized and to find out the relationship between the melanized oocyst and its intracellular level of free ca2+ in a plasmodium-refractory strain of anopheles dirus.200312884616
[molecular cloning of plasmodium yoelii dynamin-like protein (pydyn) gene and the immunological character of its domains].to identify and clone a new full orf gene of pydyn (plasmodium yoelii dynamin-like protein), and examine the protection of their expression products.200312905715
pilot survey of expressed sequence tags (ests) from the asexual blood stages of plasmodium vivax in human patients.plasmodium vivax is the most widely distributed human malaria, responsible for 70-80 million clinical cases each year and large socio-economical burdens for countries such as brazil where it is the most prevalent species. unfortunately, due to the impossibility of growing this parasite in continuous in vitro culture, research on p. vivax remains largely neglected.200312914668
evaluation of the antimalarial properties and standardization of tablets of azadirachta indica (meliaceae) in mice.the antimalarial activities of the tablet suspension of the bark and leaf of azadirachta indica were evaluated on plasmodium yoelli nigeriensis infected mice. the tablet suspensions exhibited high prophylactic, mode-rate suppressive and a very minimal curative schizonticidal effect. no animal was cured of the infection in the curative test and there was not much increase in the survival time of the animals compared with the control. the tablet suspensions from the leaf and bark at a concentratio ...200312916083
mining microorganism est databases in the quest for new proteins.microorganisms with large genomes are commonly the subjects of single-round partial sequencing of cdna, generating expressed sequence tags (ests). usually there is a great distance between gene discovery by est projects and submission of amino acid sequences to public databases. we analyzed the relationship between available ests and protein sequences and used the sequences available in the secondary database, clusters of orthologous groups (cog), to investigate ests from eight microorganisms of ...200312917813
immunization of retrovirus-transfected dendritic cells induces specific cytotoxic t lymphocytes for two distinct malarial peptides presented by kd molecule.plasmodium yoelli sporozoite surface protein 2 (pyssp2) is considered as an important antigen for protection studies in malaria vaccine development. for the liver stage protection, anti-pyssp2 cytotoxic t lymphocyte (ctl) activity in balb/c mice was investigated by immunization of genetically engineered bone marrow-derived dendritic cells (dcs) expressing pyssp2 peptides. retrovirus-transfected bone marrow cells cultured with gmcsf and il-4 for 7 days demonstrated 70-80% of dcs with high cd11c, ...200312946436
successful induction of cd8 t cell-dependent protection against malaria by sequential immunization with dna and recombinant poxvirus of neonatal mice born to immune mothers.in some parts of africa, 50% of deaths attributed to malaria occur in infants less than 8 mo. thus, immunization against malaria may have to begin in the neonatal period, when neonates have maternally acquired abs against malaria parasite proteins. many malaria vaccines in development rely upon cd8 cells as immune effectors. some studies indicate that neonates do not mount optimal cd8 cell responses. we report that balb/c mice first immunized as neonates (7 days) with a plasmodium yoelii circums ...200312960342
identification of a ubiquitin family protein as a novel neutrophil chemotactic factor.neutrophil chemotaxis is a process that is essential for the recruitment of neutrophils to an inflamed site. in the present study, we found a remarkable increase in neutrophil chemotactic activity in the lysate of red blood cells (rbc) of mice infected with murine malaria, plasmodium yoelii. a neutrophil chemotactic factor with an apparent molecular weight of 17 kda (ip17) was isolated from rbc by a combination of anion-exchange chromatography on de52 and cation-exchange chromatography on mono s ...200312963022
abc transporters and drug resistance in parasitic protozoa.parasitic protozoa are responsible for a wide spectrum of diseases in humans and domestic animals. the main line of defence available against these organisms is chemotherapy. however, the application of chemotherapeutic drugs has resulted in the development of resistance mechanisms, which limit the number of antiprotozoal drugs that are effective in the treatment and control of parasitic diseases. knowledge about the resistance mechanisms involved may allow the development of new drugs that mini ...200313678838
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 ...200314498822
analysis of immunological nonresponsiveness to the 19-kilodalton fragment of merozoite surface protein 1 of plasmodium yoelii: rescue by chemical conjugation to diphtheria toxoid (dt) and enhancement of immunogenicity by prior dt vaccination.the plasmodium merozoite surface protein 1 (msp1) is a leading vaccine candidate for protecting against the blood stage of malaria. previous studies have shown that the 19-kda carboxyl terminus of this protein is able to induce protective immunity in some monkey and mouse strains. we show that immunization with the recombinant plasmodium yoelii 19-kda fragment of msp1 (msp1(19)) expressed in saccharomyces cerevisiae (ymsp1(19)) can induce protective antibodies in several inbred mouse strains and ...200314500491
geraniol-derived 1,2,4-trioxanes with potent in-vivo antimalarial activity.geraniol, an abundantly available naturally occurring allylic alcohol, has been used as a starting material to prepare a series of 6-[alpha-(3'-aryl-3'-hydroxypropyl)vinyl]-1,2,4-trioxanes. some of these novel trioxanes have shown very promising antimalarial activity against multi-drug resistant plasmodium yoelii in mice by both intramuscular (im) and oral routes.200314505646
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 ...200314550891
gene structure and ookinete expression of the chitinase genes of plasmodium vivax and plasmodium yoelii. 200314550896
immunity to blood-stage murine malarial parasites is mhc class ii dependent.to determine whether mhc class ii antigen presentation is essential for the induction of protective immunity against blood-stage malarial parasites, we used gene-targeted knockout (ko) mice to follow the time-course of nonlethal plasmodium yoelii and plasmodium chabaudi infections in two models of mhc class ii deficiency. infection of mhc class ii ko (a(-/-)) mice with either parasite species resulted in an unremitting hyperparasitemia, whereas mhc-intact control mice resolved their parasitemia. ...200314556985
induction of protective immunity against malaria by priming-boosting immunization with recombinant cold-adapted influenza and modified vaccinia ankara viruses expressing a cd8+-t-cell epitope derived from the circumsporozoite protein of plasmodium yoelii.we immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus ankara), both expressing a cd8(+)-t-cell epitope derived from malaria sporozoites. this vaccination regimen elicited high levels of protection against malaria. this is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated.200314557672
oxidative phosphorylation and rotenone-insensitive malate- and nadh-quinone oxidoreductases in plasmodium yoelii yoelii mitochondria in situ.respiration, membrane potential, and oxidative phosphorylation of mitochondria of plasmodium yoelii yoelii trophozoites were assayed in situ after permeabilization with digitonin. adp induced an oligomycin-sensitive transition from resting to phosphorylating respiration in the presence of oxidizable substrates. a functional respiratory chain was demonstrated. in addition, the ability of the parasite to oxidize exogenous nadh, as well as the insensitivity of respiration to rotenone and its sensit ...200414561763
identification and expression analysis of abc genes in plasmodium yoelii and p. berghei.the atp-binding cassette (abc) proteins are one of the largest evolutionarily conserved families. they are characterized by the presence of highly conserved nucleotide-binding sites (nbs). in the present study, we identified abc genes in rodent plasmodia. we queried the plasmodium yoelii genome with the abc signature motif and retrieved 15 contigs. sequences were classified into seven abc families by blast comparison. conservation of the five signature abc motifs in the p. yoelii contigs was exa ...200414564508
expression profiles of peroxiredoxin proteins of the rodent malaria parasite plasmodium yoelii.patterns of expression of the 2-cys and 1-cys peroxiredoxin (prx) proteins of the rodent malaria parasite plasmodium yoelii during its life cycle were observed by immunofluorescent antibody staining and confocal laser scanning microscopy. 2-cys prx was expressed in the parasite cytoplasm throughout the life cycle, and the thioredoxin (trx)-peroxidase activity of 2-cys prx revealed with the recombinant protein suggested that the prx is constitutively expressed and, thus, likely plays a housekeepi ...200314572508
differential induction of tgf-beta regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal plasmodium yoelii infections.transforming growth factor-beta is an essential moderator of malaria-induced inflammation in mice. in this study, we show that the virulence of malaria infections is dependent upon the cellular source of tgf-beta and the timing of its production. c57bl/6 mice infected with a nonlethal (py17x) strain of plasmodium yoelii produce tgf-beta from 5 days postinfection; this correlates with resolution of parasitemia, down-regulation of tnf-alpha, and full recovery. in contrast, infection with the letha ...200314607947
the role of the 19-kda region of merozoite surface protein 1 and whole-parasite-specific maternal antibodies in directing neonatal pups' responses to rodent malaria infection.maternal abs generated as a result of prior exposure to infectious agents such as the malaria parasite are transferred from the mother through the placenta to the fetus. numerous studies have attributed the resistance to malaria infection observed in neonates and infants up to 6 mo of age to the presence of maternally derived abs. however, recent studies have produced conflicting results suggesting that alternative protective mechanisms may be responsible. although the presence of maternally der ...200314607952
aspartic proteases from plasmodium chabaudi: a rodent model for human malaria.intraerythrocytic malaria parasites degrade haemoglobin to provide nutrients for their own growth and maturation. plasmodium aspartic proteases known as plasmepsins play an important role on haemoglobin degradation and are being studied as drug targets for chemotherapy of malaria. the rodent model for human malaria, plasmodium chabaudi, is an experimentally good model for therapy drug design. the gene encoding an aspartic protease precursor (proplasmepsin) from the rodent malaria parasite p. cha ...200314636976
monoclonal antibody mg96 completely blocks plasmodium yoelii development in anopheles stephensi.in spite of research efforts to develop vaccines against the causative agent of human malaria, plasmodium falciparum, effective control remains elusive. the predominant vaccine strategy focuses on targeting parasite blood stages in the vertebrate host. an alternative approach has been the development of transmission-blocking vaccines (tbvs). tbvs target antigens on parasite sexual stages that persist within the insect vector, anopheline mosquitoes, or target mosquito midgut proteins that are pre ...200314638789
effect of dietary p-aminobenzoic acid on murine plasmodium yoelii infection.plasmodia species, unlike humans, can utilize p-aminobenzoic acid (paba) for the de novo generation of folate. plasmodial enzymes for the synthesis of paba via the shikimate pathway are being investigated as novel targets for malaria chemotherapy. we show that, despite the presence of biosynthetic machinery to synthesize paba, plasmodium yoelii, a rodent malaria species, requires exogenous dietary paba for survival. mice fed low-paba diets do not die from lethal doses of p. yoelii. the initiatio ...200314639551
onset of hepatic erythropoiesis after malarial infection in mice.plasmodium yoelii-infected erythrocytes were injected into mice with or without 6.5 gy irradiation. this irradiation suppressed erythropoiesis and induced severe immunosuppression. however, these mice showed a rather delayed infection, suggesting that fresh erythrocytes may become malarial targets. in other words, malarial infection did not persist without newly generated erythrocytes in mice. we then examined erythropoiesis in the liver and bone marrow of mice with malaria. surprisingly, erythr ...200314665382
a member of a conserved plasmodium protein family with membrane-attack complex/perforin (macpf)-like domains localizes to the micronemes of sporozoites.pore-forming proteins are employed by many pathogens to achieve successful host colonization. intracellular pathogens use pore-forming proteins to invade host cells, survive within and productively interact with host cells, and finally egress from host cells to infect new ones. the malaria-causing parasites of the genus plasmodium evolved a number of life cycle stages that enter and replicate in distinct cell types within the mosquito vector and vertebrate host. despite the fact that interaction ...200414668008
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 ...200314676296
gene targeting demonstrates that the plasmodium berghei subtilisin pbsub2 is essential for red cell invasion and reveals spontaneous genetic recombination events.the plasmodium merozoite proteases involved in the crucial process of erythrocyte invasion are promising targets for novel malaria control strategies. we report here the characterization of the subtilisin-like protease sub2 from the rodent parasites plasmodium berghei and plasmodium yoelii, leading the way to in vivo functional studies of this enzyme. the kinetics of expression and subcellular localization imply a central role for sub2 in erythrocyte invasion. through the use of gene targeting s ...200414678331
full-malaria 2004: an enlarged database for comparative studies of full-length cdnas of malaria parasites, plasmodium species.full-malaria (http://fullmal.ims.u-tokyo.ac.jp), a database for full-length cdnas from the human malaria parasite, plasmodium falciparum has been updated in at least three points. (i) we added 8934 sequences generated from the addition of new libraries, so that our collection of 11,424 full-length cdnas covers 1375 (25%) of the estimated number of the entire 5409 parasite genes. (ii) all of our full-length cdnas and genbank est sequences were mapped to genomic sequences together with publicly av ...200414681428
8-quinolinamines conjugated with amino acids are exhibiting potent blood-schizontocidal antimalarial activities.alanine, lysine, ornithine and valine conjugated to primaquine and other 8-quinolinamine antimalarials were prepared for blood-schizontocidal antimalarial activity evaluation. the analogues were examined in vivo against plasmodium berghei (drug-sensitive strain) and plasmodium yoelii nigeriensis (highly virulent multi-drug-resistant strain) infected mice models. n(1)-[4-(5-butoxy-4-ethyl-6-methoxy-8-quinolylamino)pentyl]-(2s)-2,6-diaminohexanamide (20) which showed curative activity at 5mg/kg in ...200414697789
orally active amino functionalized antimalarial 1,2,4-trioxanes.using readily available trioxanes 6a-b, a new series of amino functionalized 1,2,4-trioxanes 8a-e and 9a-e have been prepared and evaluated for antimalarial activity against multi-drug resistant plasmodium yoelii in swiss mice model. several of these novel trioxanes are orally more active than the parent trioxanes 6a-b. antimalarial activity of amino functionalized trioxane 9a, the most potent compound in the series, is very close to that of beta-arteether.200414698181
escape of malaria parasites from host immunity requires cd4+ cd25+ regulatory t cells.infection with malaria parasites frequently induces total immune suppression, which makes it difficult for the host to maintain long-lasting immunity. here we show that depletion of cd4(+)cd25(+) regulatory t cells (t(reg)) protects mice from death when infected with a lethal strain of plasmodium yoelii, and that this protection is associated with an increased t-cell responsiveness against parasite-derived antigens. these results suggest that activation of t(reg) cells contributes to immune supp ...200414702631
cpg oligodeoxynucleotide and montanide isa 51 adjuvant combination enhanced the protective efficacy of a subunit malaria vaccine.unmethylated cpg dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (odns) serve as strong immunostimulatory agents in mice, monkeys and humans. we determined the adjuvant effect of murine cpg odn 1826 on the immunogenicity and protective efficacy of the saccharomyces cerevisiae-expressed 19-kda c-terminal region of merozoite surface protein 1 (ymsp1(19)) of the murine malaria parasite plasmodium yoelii. we found that in c57bl/6 mice, following sporozoite challen ...200414742540
members of the merozoite surface protein 7 family with similar expression patterns differ in ability to protect against plasmodium yoelii malaria.previously, we described the isolation of the plasmodium yoelii sequence-related molecules p. yoelii msp-7 (merozoite surface protein 7) and p. yoelii msrp-2 (msp-7-related protein 2) by their ability to interact with the amino-terminal end of p. yoelii msp-1 in a yeast two-hybrid system. one of these molecules was the homologue of plasmodium falciparum msp-7, which was biochemically isolated as part of the shed msp-1 complex. in the present study, with antibodies directed against recombinant pr ...200414742548
a new modular protein of cryptosporidium parvum, with ricin b and lccl domains, expressed in the sporozoite invasive stage.the recombinant sa35 peptide has been described as an antigenic portion of a larger cryptosporidium parvum protein. we identified and characterized the encoding cpa135 gene and the entire protein, cpa135. the cpa135 gene was found to consist of a single exon of 4671 bp, and the mrna transcribed in the sporozoites was identified. the predicted 1556 amino-acid protein showed the presence of domains which are widely conserved also in other unrelated phylogenetic groups (i.e. a ricin b and a lccl mo ...200414747151
protective t cell immunity against malaria liver stage after vaccination with live sporozoites under chloroquine treatment.in this study we present the first systematic analysis of the immunity induced by normal plasmodium yoelii sporozoites in mice. immunization with sporozoites, which was conducted under chloroquine treatment to minimize the influence of blood stage parasites, induced a strong protection against a subsequent sporozoite and, to a lesser extent, against infected rbc challenges. the protection induced by this immunization protocol proved to be very effective. induction of this protective immunity dep ...200414764721
novel antigen identification method for discovery of protective malaria antigens by rapid testing of dna vaccines encoding exons from the parasite genome.we describe a novel approach for identifying target antigens for preerythrocytic malaria vaccines. our strategy is to rapidly test hundreds of dna vaccines encoding exons from the plasmodium yoelii yoelii genomic sequence. in this antigen identification method, we measure reduction in parasite burden in the liver after sporozoite challenge in mice. orthologs of protective p. y. yoelii genes can then be identified in the genomic databases of plasmodium falciparum and plasmodium vivax and investig ...200414977966
synthesis and antimalarial activity of a new series of trioxaquines.trioxanes 8a-b, easily accessible in two steps from allylic alcohol 6a-b, on reductive amination with 4-aminoquinolines 4a-c furnish a new series of trioxaquines 9a-b, 10a-b, 11a-b in 32-77% yields. dicitrate salts of these trioxaquines have been evaluated for antimalarial activity against multidrug resistant plasmodium yoelii in mice model.200414980628
differential transcriptome profiling identifies plasmodium genes encoding pre-erythrocytic stage-specific proteins.invasive sporozoite and merozoite stages of malaria parasites that infect mammals enter and subsequently reside in hepatocytes and red blood cells respectively. each invasive stage may exhibit unique adaptations that allow it to interact with and survive in its distinct host cell environment, and these adaptations are likely to be controlled by differential gene expression. we used suppression subtractive hybridization (ssh) of plasmodium yoelii salivary gland sporozoites versus merozoites to id ...200414982620
nitric oxide protects against chloroquine resistant plasmodium yoelii nigeriensis parasites in vitro.malaria is a life-threatening disease of global concern. the role of nitric oxide in the clearance of malarial parasites is still under debate. several reports suggest a possible role for nitric oxide in the protection during initial stages of malarial infection. in the present study, we demonstrate that the nitric oxide in combination with low concentrations of chloroquine controls the parasitaemia in vitro. activated peritoneal macrophages co-cultured with lipopolysaccharide+interferon-gamma o ...200314990311
short report: modulation of mycobacterium tuberculosis infection by plasmodium in the murine model.a large proportion of people with latent tuberculosis live in malaria-endemic areas, so co-infection with these two organisms is likely to be common. to determine whether there might be a biologic interaction between these two pathogens in vivo, we infected mice with mycobacterium tuberculosis and then with a non-lethal strain of plasmodium yoelii eight weeks later. mice chronically infected with m. tuberculosis simulate the equilibrium between pathogen and host thought to exist in human latent ...200414993625
plasmodium yoelii: identification and partial characterization of an mdr1 gene in an artemisinin-resistant line.the molecular mechanisms by which the malarial parasite has managed to develop resistance to many antimalarial drugs remain to be completely elucidated. mutations in the pfmdr1 gene of plasmodium falciparum, as well as an increase in pfmdr1 copy number, have been associated with resistance to the quinoline-containing antimalarial drugs. we investigated the mechanisms of drug resistance in plasmodium using a collection of p. yoelii lines with different drug resistance profiles. the mdr1 gene of p ...200415040683
[protective immune mechanisms induced by cellular vaccine made of the erythrocytic plasmodium yoelii].to explore the characteristics of protective immunity against plasmodium yoelii (p.y.) infection by asexual blood-stages cellular vaccine.200415052774
inhibition of 19-kda c-terminal region of merozoite surface protein-1-specific antibody responses in neonatal pups by maternally derived 19-kda c-terminal region of merozoite surface protein-1-specific antibodies but not whole parasite-specific antibodies.immunizing pregnant women with a malaria vaccine is one approach to protecting the mother and her offspring from malaria infection. however, specific maternal abs generated in response to vaccination and transferred to the fetus may interfere with the infant's ability to respond to the same vaccine. using a murine model of malaria, we examined the effect of maternal 19-kda c-terminal region of merozoite surface protein-1 (msp1(19)) and plasmodium yoelii abs on the pups' ability to respond to imm ...200415100300
[the internal control role of ribosomal protein s7 in the defense of anopheles dirus against plasmodium infection].to investigate the role of ribosomal protein s7 (rps7) in the defense of anopheles dirus against infection.200315108511
[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.200315108514
[assay of haemolymph protein concentration in anopheles stephensi].to ascertain the changes of haemolymph protein concentration in adult anopheles stephensi mosquitoes under different feeding conditions.200315108524
a plasmodium gene family encoding maurer's cleft membrane proteins: structural properties and expression profiling.upon invasion of the erythrocyte cell, the malaria parasite remodels its environment; in particular, it establishes a complex membrane network, which connects the parasitophorous vacuole to the host plasma membrane and is involved in protein transport and trafficking. we have identified a novel subtelomeric gene family in plasmodium falciparum that encodes 11 transmembrane proteins localized to the maurer's clefts. using coimmunoprecipitation and shotgun proteomics, we were able to enrich specif ...200415140830
b6 mice and plasmodium yoelii. 200415238680
[morphological characteristics of plasmodium yoelii schizonts in ghost erythrocytes].to observe the morphological characteristics of plasmodium yoelii schizogony in their ghost erythrocytes.200415266827
effects of autacoid inhibitors and of an antagonist on malaria infection in mice.the effects of p-chlorophenylalanine, an inhibitor of serotonin synthesis, indomethacin, an inhibitor of prostaglandin synthesis, cyproheptadine, a serotonin, bradykinin and histamine antagonist, were assessed separately and in combination with chloroquine (cq) in vom strains of swiss albino mice (18-22 g) of either sex infected intraperitoneally with 1 x 10(7) plasmodium yoelii nigeriensis-induced malaria. as prophylactic, these agents reduced from 31.9 +/- 4.5 to 16.1 +/- 8.1% the level of par ...200415273821
the efficacy of inhibitors involved in spermidine metabolism in plasmodium falciparum, anopheles stephensi and trypanosoma evansi.in the present study, we have tested the effect of different polyamine inhibitors of the spermidine metabolizing enzymes deoxyhypusine synthase and homospermidine synthase in different chloroquine resistant plasmodium falciparum strains, in the mosquito anopheles stephensi (diptera: culicidae) and in a trypanosoma evansi clone i from strain stib 806 k china. recent experiments have shown that agmatine is a growth inhibitor of the malaria parasite p. falciparum (kaiser et al. 2001) in vitro. a co ...200415278440
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 ...200415278442
transcriptome of axenic liver stages of plasmodium yoelii.plasmodium liver stages or early exo-eythrocytic forms (eefs) contain antigens that are essential for achieving sterile, protective immunity against malaria. yet, attempts at identifying these antigens have been hampered by the challenge of obtaining large numbers of purified eefs, uncontaminated with hepatocyte material. using a recently described system for producing axenically cultured eefs from plasmodium yoelii, we have constructed a cdna library and generated 1453 expressed sequence tags ( ...200415279962
improvement of glucose homeostasis in obese diabetic db/db mice given plasmodium yoelii glycosylphosphatidylinositols.we have previously reported that infection with plasmodium yoelii, plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (stz)-diabetic mice. p yoelii glycosylphosphatidylinositols (gpis) were extracted in chloroform:methanol:water (cmw) (10:10:3), purified by high-performance thin layer chromatography (hptlc) and tested for their insulin-mimetic activities. the effects of p yo ...200415281017
dendritic cells induce immunity and long-lasting protection against blood-stage malaria despite an in vitro parasite-induced maturation defect.dendritic cells (dc) suffer a maturation defect following interaction with erythrocytes infected with malaria parasites and become unable to induce protective malaria liver-stage immunity. here we show that, by contrast, maturation-arrested dc in vitro are capable of the successful induction of antigen-specific gamma interferon (ifn-gamma) and interleukin 4 (il-4) t-cell responses, antibody responses, and potent protection against lethal blood-stage malaria challenge in vivo. similar results wer ...200415322030
cytokine and antibody production during the course of resolution in plasmodium yoelii 17xl-infected balb/c mice treated with febrifugine and isofebrifugine mixture from leaves of hydrangea macrophylla var. otaksa.cytokine and antibody production was investigated during the course of resolution of primary infection in plasmodium yoelii 17xl-infected balb/c mice treated with a mixture of febrifugine and isofebrifugine. the infected mice in an untreated control group showed a progressively increasing parasitemia, leading to mouse death. in contrast, infected mice given the mixture orally showed low parasitemia levels during administration. following a transient increase in parasitemia in the bloodstream of ...200415338283
disruption of plasmodium berghei merozoite surface protein 7 gene modulates parasite growth in vivo.merozoite invasion of red blood cells is crucial to the development of the parasite that causes malaria. merozoite surface proteins (msps) mediate the first interaction between parasite and erythrocyte. in plasmodium falciparum, they include a complex of products from at least 3 genes (msp1, msp6, and msp7), one of which, msp7, is part of a gene family containing 3 and 6 adjacent members in plasmodium yoelii and plasmodium falciparum, respectively. we have identified and disrupted msp7 in the pl ...200515339842
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 ...200415361248
resistance reversal action of ketoconazole against mefloquine resistance of plasmodium yoelii nigeriensis.ketoconazole at 200 mg/kg dose has been found to exert marginal antimalarial action against multidrug resistant (mdr) plasmodium yoelii nigeriensis (p. yoelii nigeriensis) in swiss mice with 25% protection (2/8 mice) while at lower ketoconazole dose i.e., 75-100 mg/kg, 14.28% mice were protected. mefloquine (mfq) (at 8 and 16 mg/kg) exerted suppressive action against mdr p. yoelii nigeriensis resulting in 25 and 14.28% protection of mice respectively. combined treatment with ketoconazole and mef ...200415363936
plasmodium yoelii: activity of azithromycin in combination with pyrimethamine or sulfadoxine against blood and sporozoite induced infections in swiss mice.the efficacy of pyrimethamine or sulfadoxine administered in combination with azithromycin was examined in a rodent malaria model. outbred swiss mice infected with blood stage parasites were treated from day 0 to day 3 and efficacy of different regimens was monitored in terms of the curative response and the delay time to reach 2% parasitaemia (2% dt). administration of azithromycin alone at 60 mg/kg/day produced curative response while lower doses showed marginally delayed 2% dt. a marked poten ...200415363937
the py235 proteins: glimpses into the versatility of a malaria multigene family.py235 rhoptry proteins, encoded by a multigene family of the rodent malaria parasite plasmodium yoelii, combine a functional role in invasion with one of immune evasion, and have homologues in malaria parasites of humans. investigations of py235 are summarised and the perspectives for dissecting the molecular and biological mechanisms underlying these crucial phenomena are discussed.200415374009
[immunity of peritoneal monocytes against plasmodium yoelii infected erythrocytes].to test the immunity of peritoneal monocytes against plasmodium yoelii infected red blood cells (target cells).200415379267
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 ...200415385485
oral immunization with a combination of plasmodium yoelii merozoite surface proteins 1 and 4/5 enhances protection against lethal malaria challenge.oral immunization of mice with escherichia coli-expressed plasmodium yoelii merozoite surface protein 4/5 or the c-terminal 19-kda fragment of merozoite surface protein 1 induced systemic antibody responses and protected mice against lethal malaria infection. a combination of these two proteins administered orally conferred improved protection compared to that conferred by either protein administered alone.200415385527
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