| synthesis and antimalarial evaluation of a series of piperazinyl flavones. | a series of 27 flavonoid derivatives containing a piperazinyl chain have been synthesized and tested for their antiplasmodial activity. diverse substitution patterns on piperazinyl and flavone moieties were examined and found to affect the activity differently. the most active compounds, which have a 2,3,4-trimethoxybenzylpiperazinyl chain attached to the flavone at the 7-phenol group, showed in vitro activity against chloroquine-sensitive (thai) and -resistant (fcb1,k1) plasmodium falciparum st ... | 2007 | 17166718 |
| mutating the anchor residues associated with mhc binding inhibits and deviates cd8+ t cell mediated protective immunity against malaria. | we investigated whether immune responses induced by immunization with plasmid dna are restricted predominantly to immunodominant cd8+ t cell epitopes, or are raised against a breadth of epitopes including subdominant cd8+ and cd4+ t cell epitopes. site-directed mutagenesis was used to change one or more primary anchor residues of the immunodominant cd8+ t cell epitope on the plasmodium yoelii circumsporozoite protein, and in vivo protective efficacy and immune responses against defined pycsp cd8 ... | 2007 | 17169429 |
| immunomodulatory role of chloroquine and pyrimethamine in plasmodium yoelii 17xl infected mice. | chloroquine (clq) and pyrimethamine (pyr) are used for the treatment of malaria and some autoimmune diseases; although their mechanism of action is only partially understood, their therapeutic effectiveness in the second case has been attributed to their ability to increase apoptosis of t lymphocytes. in view of the potential for immunomodulation during malaria chemotherapy, we investigated the effects of clq and pyr treatment on lymphocyte apoptosis and cytokine expression during infection with ... | 2007 | 17212767 |
| prophylactic potential of liposomized integral membrane protein of plasmodium yoelii nigeriensis against blood stage infection in balb/c mice. | triton x-114 phase separated integral membrane proteins (imps) of a multidrug resistant strain of plasmodium yoelii nigeriensis (p. yoelii) were screened for their potential to impart protection against malaria infection in balb/c mice. as revealed by immunoblotting, antibodies present in parasite specific sera from convalescent (protected) as well as immunized (partially protected) animals recognized different membrane proteins. a thorough investigation reveals that p. yoelii specific convalesc ... | 2007 | 17241709 |
| falcipain-1, a plasmodium falciparum cysteine protease with vaccine potential. | cysteine proteases (falcipains) of plasmodium falciparum are potential targets for antimalarial chemotherapy, since they have been shown to be involved in important cellular functions such as hemoglobin degradation and invasion/rupture of red blood cells during parasite life cycle. the role of falcipain-1 at the asexual blood stages of the parasite still remains uncertain. this is mainly due to a lack of methods to prepare this protein in an active form. in order to obtain biologically active fa ... | 2007 | 17242063 |
| new adamantane-based spiro 1,2,4-trioxanes orally effective against rodent and simian malaria. | new 6-arylvinyl- and 6-adamantylvinyl-substituted 1,2,4-trioxanes (13a-g and 14a,b) have been prepared and evaluated for antimalarial activity against multidrug resistant plasmodium yoelii nigeriensis in mice by both oral and intramuscular routes. while all the 6-arylvinyl-substituted trioxanes, 13a-f, showed promising activity, none of the 6-adamantylvinyl-substituted trioxanes, 13g and 14a,b, exhibited significant activity. trioxane, 13f, the most active compound of the series, provided 100% a ... | 2007 | 17266204 |
| identification of minimal cd8+ and cd4+ t cell epitopes in the plasmodium yoelii hepatocyte erythrocyte protein 17kda. | immunization of mice with subunit vaccines based on the plasmodium yoelii 17kda hepatocyte erythrocyte protein (pyhep17), orthologue of plasmodium falciparum exported protein 1 (pfexp1), induces antigen-specific immune responses and protects against sporozoite challenge. to aid in the characterization of candidate subunit vaccines based on this antigen, we have mapped the immunodominant and subdominant cd8+ and cd4+ t cell epitopes on pyhep17. using a panel of 29 15-mer synthetic peptides repres ... | 2007 | 17303242 |
| primary infection of c57bl/6 mice with plasmodium yoelii induces a heterogeneous response of nkt cells. | nkt cells are a population of innate-like lymphocytes that display effector functions and immunoregulatory properties. we characterized the nkt cell response induced in c57bl/6 mice during a primary infection with plasmodium yoelii sporozoites. we observed a heterogeneous nkt cell response that differed between liver and spleen. hepatic nkt cells found in infected livers consisted mainly of cd1d-dependent cd4+ and double-negative (dn) nkt cells, whereas cd1d-independent nkt cells exhibiting a tc ... | 2007 | 17307938 |
| long-lasting protective immune response to the 19-kilodalton carboxy-terminal fragment of plasmodium yoelii merozoite surface protein 1 in mice. | merozoite surface protein 1 (msp1) is the major protein on the surface of the plasmodial merozoite, and its carboxy terminus, the 19-kda fragment (msp1(19)), is highly conserved and effective in induction of a protective immune response against malaria parasite infection in mice and monkeys. however, the duration of the immune response has not been elucidated. as such, we immunized balb/c mice with a standard four-dose injection of recombinant plasmodium yoelii msp1(19) formulated with montanide ... | 2007 | 17314232 |
| malaria parasite induces tryptophan-related immune suppression in mice. | plasmodium spp. cause the worst parasitic diseases in humans and evade host immunity in complicated ways. activated catabolism of tryptophan in dendritic cells is thought to suppress immunity, which is mediated by an inducible rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3 dioxygenase (ido), via both tryptophan depletion and production of toxic metabolites. in various infections, including malaria, ido is known to be activated but its biological significance is unclear; therefore ... | 2007 | 17316473 |
| antimalarial properties of goniothalamin in combination with chloroquine against plasmodium yoelii and plasmodium berghei growth in mice. | malaria is a disease which is still endemic and has become a disastrous scourge because of the emergence of antimalarial drug resistant plasmodium falciparum. a new approach in addressing this is in developing a combination drug. this study is to show the enhancement of antimalarial properties, when single compound, goniothalamin combine with standard drug, chloroquine. based on 4 day test, percentage of parasite growth on treated infected mice were determined. oral treatment with 1 mg/kg bw of ... | 2006 | 17322815 |
| plasmodium yoelii: experimental evidences for the conserved epitopes between mouse and human malaria parasite, plasmodium falciparum. | bioinformatic analyses of gene homologues have revealed functionally conserved epitopes between human and rodent malaria parasites. here, we present experimental evidence for the presence of functionally and antigenically conserved domains between plasmodium falciparum and plasmodium yoelii asexual blood-stages. merozoite released soluble proteins (mrsps) from both p. falciparum and p. yoelii bound to heterologous mouse or human red blood cells, respectively. the presence of conserved antigenic ... | 2007 | 17336297 |
| plasmodium yoelii: influence of antimalarial treatment on acquisition of immunity in balb/c and dba/2 mice. | the effect of antimalarial drugs on immune responses to the malaria infection is evaluated in vivo using two experimental self-cured rodent models. balb/c and dba/2 mice were infected by plasmodium yoelii 17xnl and 17xl strains, respectively, and then treated with different doses of antimalarial drugs: chloroquine (228mg/kg or 114mg/kg of the body weight) or artesunate (78mg/kg or 39mg/kg). the effect of antimalarial drugs on host immune responses was evaluated by parasitemia, splenocyte ifn-gam ... | 2007 | 17336298 |
| antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo. | the in vitro and in vivo efficacy and drug-drug interactions of the novel semi-synthetic endoperoxide artemisone with standard antimalarials were investigated in order to provide the basis for the selection of the best partner drug. | 2007 | 17337512 |
| uninfected mosquito bites confer protection against infection with malaria parasites. | despite decades of research and multiple initiatives, malaria continues to be one of the world's most debilitating infectious diseases. new insights for malaria control and vaccine development will be essential to thwart the staggering worldwide impact of this disease (a. bjorkman and a. bhattarai, acta trop. 94:163-169, 2005); ultimately successful vaccine strategies will undoubtedly be multifactorial, incorporating multiple antigens and targeting diverse aspects of the malaria parasites' biolo ... | 2007 | 17339356 |
| effect of plasmodium yoelii nigeriensis infection on hepatic and splenic glutathione-s-transferase(s) in swiss albino and db/+ mice: efficacy of mefloquine and menadione in antimalarial chemotherapy. | the present report deals with the status of hepatic and splenic glutathione-s-transferase (gst) activities in mice during experimental infection with plasmodium yoelii nigeriensis and subsequent treatment of infected mice with mefloquine (mf) and menadione (md). the infection caused significant decline in the hepatic and splenic glutathione-s-transferase (gst) activities of albino and db/+ mice. the decline was observed in the levels of both cytosolic and microsomal gst(s) of liver and spleen in ... | 2007 | 17352848 |
| [effect of anti-midgut-protein-ingredient antibodies of anopheles stephensi on the oocysts of plasmodium yoelii]. | to observe the inhibitory effect of the antibodies against midgut-protein-ingredient of anopheles stephensi on the oocysts of plasmodium yoelii. | 2006 | 17366975 |
| plasmodium yoelii: combinatorial expression of variants of the 235 kda rhoptry antigen during infection. | the 235 kda rhoptry protein py235 of plasmodium yoelii, has been implicated in erythrocyte invasion by the merozoite forms of the parasite. py235 is encoded by a large, highly polymorphic gene family, members of which appear to be differentially transcribed. however, it is not clear how many variants are expressed at the protein level during an infection cycle and whether or not these variants are expressed selectively or combinatorially. certain monoclonal antibodies to py235 have been shown to ... | 2007 | 17368448 |
| ctla-4 blockade differentially influences the outcome of non-lethal and lethal plasmodium yoelii infections. | an immune response against malaria has to be tightly controlled. the production of pro-inflammatory cytokines is required to control parasites but the same cytokines are also involved in severe malaria. we have shown that ctla-4 expression during plasmodium berghei malaria dampens the immune response. this strain provokes a pro-inflammatory immune response that is associated with the pathology of cerebral malaria. accordingly a blockade of ctla-4 during the blood-stage of p. berghei malaria lead ... | 2007 | 17398134 |
| plasmodium yoelii: contribution of oocysts melanization to natural refractoriness in anopheles dirus. | it is well known that anopheles dirus is naturally refractory to rodent malaria parasite, plasmodium yoelii, but the mechanism is still largely unknown. here, we found that some p. yoelii taken into an. dirus could develop into oocysts, but oocysts were partially melanized at 7 days and completely melanized at 15 days post-infectious blood meal. transmission electronic microscopy could find the melanized p. yoelii oocysts in an. dirus as early as 5 days post-infection, with a few haemocytes atta ... | 2007 | 17416360 |
| re-evaluating acridine orange for rapid flow cytometric enumeration of parasitemia in malaria-infected rodents. | methods facilitating research in malaria are of pivotal relevance. flow cytometry offers the possibility of rapid enumeration of parasitemia. it relies on staining the parasite dna to distinguish between infected and non-infected red blood cell (rbc) populations. unfortunately, in rodents abundant reticulocyte rna interferes with the application of the method. this results in time-consuming sample preparation protocols that offer no clear advantage over microscopic counting. we re-evaluated the ... | 2007 | 17421026 |
| sub-cellular localization and post-translational modifications of the plasmodium yoelii enolase suggest moonlighting functions. | enolase (2-phospho-d-glycerate hydrolase; ec 4.2.1.11) is one of the glycolytic enzymes, whose levels are highly elevated in malaria parasite infected red blood cells. in several organisms, enolases have been shown to have diverse non glycolytic (moonlighting) biological functions. as functional diversity of a protein would require diverse sub-cellular localization, the possibility of involvement of plasmodium enolase in moonlighting functions was examined by investigating its sub-cellular distr ... | 2007 | 17437631 |
| role of tgf-beta and pge2 in t cell responses during plasmodium yoelii infection. | during an acute blood-stage malaria infection, t cell responses to malaria and other bystander antigens are inhibited. plasmodium infection induces strong cytokine responses that facilitate parasite clearance but may interfere with t cell functions, as some of the soluble immune mediators induced are also general inhibitors of t cell responses. using a malaria mouse model, we have analyzed the cytokines produced by dendritic cells in response to p. yoelii infection that have potential t cell inh ... | 2007 | 17474154 |
| malaria vaccines. | more than 120 years after alphonse laveran's discovery of the blood-stage malaria parasite, there is no licensed malaria vaccine and malaria remains the world's most serious parasitic disease. efforts to develop a vaccine have been thwarted by the complexity of the parasite's life cycle and the ability of the parasite to suppress and evade the immune response. currently, there are several candidate vaccines in clinical trials and many more candidate vaccines that have shown efficacy in animal mo ... | 2007 | 17485348 |
| identifying and characterising the plasmodium falciparum rhoph3 plasmodium vivax homologue. | four plasmodium species cause malaria in humans, plasmodium falciparum being the most widely studied to date. all plasmodium species have paired club-shaped organelles towards their apical extreme named rhoptries that contain many lipids and proteins which are released during target cell invasion. p. falciparum rhoph3 is a rhoptry protein triggering important immune responses in patients from endemic regions. it has also been shown that anti-rhoph3 antibodies inhibit in vitro invasion of erythro ... | 2007 | 17511961 |
| plasmodium yoelii sporozoites with simultaneous deletion of p52 and p36 are completely attenuated and confer sterile immunity against infection. | malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. the formation of a parasitophorous vacuole (pv) establishes their intracellular niche. recently, two members of the 6-cys domain protein family, p52 and p36, were each shown to play an important albeit nonessential role in plasmodium berghei sporozoite infectivity for the rodent host. here, we generated p52/p36-d ... | 2007 | 17517871 |
| delineation of epitopes on the py235 rhoptry antigen of plasmodium yoelii ym. | the 235-kda antigenic rhoptry protein py235 of plasmodium yoelii is encoded by a large, highly polymorphic gene family. monoclonal antibodies to some of these antigens have been shown to attenuate the virulence of the lethal ym strain of the parasite, converting a potentially fatal ym infection to a fulminating one typical of the nonlethal 17x strain, by inducing a switch in target cell preference from mature red blood cells to reticulocytes. the reason for this is not known but would suggest th ... | 2007 | 17537175 |
| orally active antimalarials: synthesis and bioevaluation of a new series of steroid-based 1,2,4-trioxanes against multi-drug resistant malaria in mice. | a new series of steroid-based 1,2,4-trioxanes 7a-f, 8a-f and 9b-e have been synthesized and evaluated for their antimalarial activity against multi-drug resistant plasmodium yoelii in swiss mice by oral route. the biological activity shows a strong dependence on the size and the nature of the steroidal side chain. pregnane-based trioxanes 8a-f show better activity profile than trioxanes 7a-f and 9b-e, derived from cholesterol and tigogenine, respectively. | 2007 | 17548195 |
| enhanced malaria parasite transmission from helminth co-infected mice. | helminth infections are prevalent in malaria-endemic areas, yet the potential for helminths to alter malaria transmission has not been closely examined. we used the echinostoma caproni-plasmodium yoelii murine model of co-infection to assess the impact of helminth co-infection on malaria transmission. in four replicate experiments, anopheles stephensi mosquitoes exposed to co-infected mice five days post-malaria infection had a higher rate of infectivity (80.1%, n = 241) than those exposed to ma ... | 2007 | 17556610 |
| chronic steroid administration does not suppress plasmodium development and maturation. | the objective of this study was to investigate the influence of constant steroid uptake on the plasmodium yoelii infection rate and parasite maturation. on the animal model, we examined the effect(s) of dexamethasone (dx), the general drug used for self-treatment by thai villagers. ten female icr mice were subjected to oral administration of 0.5 mg/kg dx for 40 days, whereas other ten were given drinking water only before p. yoelii 17x (lethal) strain inoculation. parasite-infected erythrocytes ... | 2007 | 17557154 |
| eurycoma longifolia extract-artemisinin combination: parasitemia suppression of plasmodium yoelii-infected mice. | eurycoma longifolia, locally known as 'tongkat ali' is a popular local medicinal plant that possess a lot of medicinal properties as claimed traditionally, especially in the treatment of malaria. the claims have been proven scientifically on isolated compounds from the plant. the present study is to investigate the anti malaria properties of eurycoma longifolia standardized extract (root) (ta164) alone and in combination with artemisinin in vivo. combination treatment of the standardized extract ... | 2007 | 17568384 |
| variable expression of the 235 kda rhoptry protein of plasmodium yoelii mediate host cell adaptation and immune evasion. | the severity of infections caused by the malaria parasite plasmodium is in part due to the rapid multiplication cycles in the blood of an infected individual. a fundamental step in this phenomenon is the invasion of selected erythrocytes of the host by the parasite. the py235 rhoptry protein multigene family of the rodent malaria parasite plasmodium yoelii has been implicated in mediating host cell selection during erythrocyte invasion and virulence. here we show using quantitative real-time pol ... | 2007 | 17590237 |
| genetically attenuated p36p-deficient plasmodium berghei sporozoites confer long-lasting and partial cross-species protection. | immunisation with live, radiation-attenuated sporozoites (ras) or genetically attenuated sporozoites (gas) of rodent plasmodial parasites protects against subsequent challenge infections. we recently showed that immunisation with plasmodium berghei gas that lack the microneme protein p36p protects mice for a period of up to 4 months. here, we show that the period of full protection induced by p36p(-)-sporozoites lasts 12 and 18 months in c57bl6 and balb/c mice, respectively. full protection is a ... | 2007 | 17604034 |
| targeting antigen to mhc class i and class ii antigen presentation pathways for malaria dna vaccines. | an effective malaria vaccine which protects against all stages of plasmodium infection may need to elicit robust cd8(+) and cd4(+) t cell and antibody responses. to achieve this, we have investigated strategies designed to improve the immunogenicity of dna vaccines encoding the plasmodium yoelii pre-erythrocytic stage antigens pycsp and pyhep17, by targeting the encoded proteins to the mhc classes i and ii processing and presentation pathways. for enhancement of cd8(+) t cell responses, we targe ... | 2007 | 17604849 |
| effect of chloroquine on gene expression of plasmodium yoelii nigeriensis during its sporogonic development in the mosquito vector. | the anti-malarial chloroquine can modulate the outcome of infection during the plasmodium sporogonic development, interfering with plasmodium gene expression and subsequently, with transmission. the present study sets to identify plasmodium genes that might be regulated by chloroquine in the mosquito vector. | 2007 | 17605769 |
| plasmodium strain determines dendritic cell function essential for survival from malaria. | the severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. however, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. since immunity is initiated by dendritic cells (dcs), we compared their phenotype and function following infection with either a nonlethal or lethal s ... | 2007 | 17616976 |
| protracted sterile protection with plasmodium yoelii pre-erythrocytic genetically attenuated parasite malaria vaccines is independent of significant liver-stage persistence and is mediated by cd8+ t cells. | irradiation-attenuated sporozoite vaccinations confer sterile protection against malaria infection in animal models and humans. persistent, nonreplicating parasite forms in the liver are presumably necessary for the maintenance of sterile immunity. a novel vaccine approach uses genetically attenuated parasites (gaps) that undergo arrested development during liver infection. the fate of gaps after immunization, their persistence in vaccinated animals, and the immune mechanisms that mediate protec ... | 2007 | 17624848 |
| comparative kinomics of plasmodium organisms: unity in diversity. | phosphorylation by protein kinases is a very common and crucial process in many signal transduction pathways in eukaryotes. this review describes comparative protein kinase analysis of two apicomplexa plasmodium falciparum (3d7 strain) and plasmodium yoelii yoelii (17xnl strain) which are causative agents of malaria in human and african rat respectively. sensitive bioinformatics techniques enable identification of 82 and 60 putative protein kinases in p. falciparum and p. yoelii yoelii respectiv ... | 2007 | 17627589 |
| typing plasmodium yoelii microsatellites using a simple and affordable fluorescent labeling method. | the rodent malaria parasite plasmodium yoelii has been an important animal model for studying malaria pathology and host-parasite interactions. compared with other rodent malaria parasites such as plasmodium chabaudi, however, genetic mapping studies on p. yoelii have been limited, partly due to the absence of genetic markers and the lack of well characterized phenotypes. taking advantage of the available genome sequence, we initiated a project to develop a high-resolution microsatellite (ms) ma ... | 2007 | 17658627 |
| enhancement of antibody and cellular immune responses to malaria dna vaccines by in vivo electroporation. | we evaluated the effectiveness of in vivo electroporation (ep) for the enhancement of immune responses induced by dna plasmids encoding the pre-erythrocytic plasmodium yoelii antigens pycsp and pyhep17 administered intramuscularly and intradermally to mice. ep resulted in a 16- and 2-fold enhancement of antibody responses to pycsp and pyhep17, respectively. immunization with 5 microg of dna via ep was equivalent to 50 microg of dna via conventional needle, thus reducing by 10-fold the required d ... | 2007 | 17669562 |
| synthesis and biological evaluation of potential modulators of malarial glutathione-s-transferase(s). | glutathione-s-transferase(s) (e.c.2.5.1.18, gsts) have been investigated in parasitic protozoans with respect to their biochemistry and they have been identified as potential vaccine candidates in protozoan parasites and as a target in the synthesis of new antiparasitic agents. in a search towards the identification of novel biochemical targets for antimalarial drug design, the area of plasmodium glutathione metabolism provides a number of promising chemotherapeutic targets. gst activity was det ... | 2007 | 17674815 |
| immunogenicity of plasmodium yoelii merozoite surface protein 4/5 produced in transgenic plants. | malaria is a major global health problem for which effective control measures are urgently needed. considerable effort has been focused on the development of effective vaccines against the causative parasite and protective vaccine trials are now being reported. due to the relative poverty and lack of infrastructure in malaria-endemic areas, a successful immunisation strategy will depend critically on cheap and scaleable methods of vaccine production, distribution and delivery. one promising tech ... | 2008 | 17681344 |
| cd8+ t lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. | the success of immunization with irradiated sporozoites is unparalleled among the current vaccination approaches against malaria, but its mechanistic underpinnings have yet to be fully elucidated. using a model mimicking natural infection by plasmodium yoelii, we delineated early events governing the development of protective cd8(+) t-cell responses to the circumsporozoite protein. we demonstrate that dendritic cells in cutaneous lymph nodes prime the first cohort of cd8(+) t cells after an infe ... | 2007 | 17704784 |
| exposure of plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity. | malaria sporozoites migrate through several cells prior to a productive invasion that involves the formation of a parasitophorous vacuole (pv) where sporozoites undergo transformation into exo-erythorcytic forms (eefs). the precise mechanism leading to sporozoite activation for invasion is unknown, but prior traversal of host cells is required. during cell migration sporozoites are exposed to large shifts in k(+) concentration. we report here that incubation of sporozoites to the intracellular k ... | 2007 | 17714805 |
| protective properties and surface localization of plasmodium falciparum enolase. | the enolase protein of the human malarial parasite plasmodium falciparum has recently been characterized. apart from its glycolytic function, enolase has also been shown to possess antigenic properties and to be present on the cell wall of certain invasive organisms, such as candida albicans. in order to assess whether enolase of p. falciparum is also antigenic, sera from residents of a region of eastern india where malaria is endemic were tested against the recombinant p. falciparum enolase (r- ... | 2007 | 17785475 |
| extended immunization intervals enhance the immunogenicity and protective efficacy of plasmid dna vaccines. | effective vaccines against infectious diseases and biological warfare agents remain an urgent public health priority. studies have characterized the differentiation of effector and memory t cells and identified a subset of t cells capable of conferring enhanced protective immunity against pathogen challenge. we hypothesized that the kinetics of t cell differentiation influences the immunogenicity and protective efficacy of plasmid dna vaccines, and tested this hypothesis in the plasmodium yoelii ... | 2007 | 17913540 |
| malaria protection in beta 2-microglobulin-deficient mice lacking major histocompatibility complex class i antigens: essential role of innate immunity, including gammadelta t cells. | it is still controversial whether malaria protection is mediated by conventional immunity associated with t and b cells or by innate immunity associated with extrathymic t cells and autoantibody-producing b cells. given this situation, it is important to examine the mechanism of malaria protection in beta(2)-microglobulin-deficient (beta(2)m(-/-)) mice. these mice lack major histocompatibility complex class i and cd1d antigens, which results in the absence of cd8(+) t cells and natural killer t ... | 2007 | 17916163 |
| macrophage-mediated but gamma interferon-independent innate immune responses control the primary wave of plasmodium yoelii parasitemia. | in most models of blood-stage malaria infection, proinflammatory immune responses are required for control of infection and elimination of parasites. we hypothesized therefore that the fulminant infections caused in mice by the lethal strain of plasmodium yoelii (17xl) might be due to failure to activate a sufficient inflammatory response. here we have compared the adaptive cd4+ t-cell and innate immune response to p. yoelii 17xl with that induced by the self-resolving, nonlethal strain of p. yo ... | 2007 | 17923512 |
| expression and biochemical characterization of the plasmodium falciparum dna repair enzyme, flap endonuclease-1 (pffen-1). | flap endonuclease-1 (fen-1) is a structure-specific endonuclease that is critical for the resolution of single-stranded dna flap intermediates that form during long patch dna base excision repair (ber). this investigation reports that plasmodium species encode fen-1 homologs. protein sequence analysis revealed the n and i domains of plasmodium falciparum (pffen-1) and plasmodium yoelii (pyfen-1) to be homologous to fen-1 from other species. however, each possessed an extended c domain which had ... | 2008 | 17928073 |
| plasmodium yoelii: correlation of up-regulated prophenoloxidase and phenoloxidases with melanization induced by the antimalarial, nitroquine. | although knowledge of the mosquito immune response has recently improved, less is known about the impact of antimalarial drugs on mosquito immunity. in the present study, we found that nitroquine, an effective antimalaria drug, could also induce melanotic encapsulation of plasmodium by anopheles stephensi. the melanization rate of the nitroquine treated group was 60.8%. to explore the effect of nitroquine on mosquito immunity, we determined the increase in activity of phenoloxidases (po) enzyme, ... | 2008 | 17936755 |
| il-12p40-independent induction of protective immunity upon multiple plasmodium berghei irradiated sporozoite immunizations. | both ifn-gamma and il-12 play critical roles in defence against malaria. in a previous study, using plasmodium yoelii model, c57bl/6 ifn-gamma receptor deficient mice (ifn-gammar-/-) failed to develop protective immunity after a single immunization with irradiated sporozoites, but were protected after multiple immunizations. in contrast, in another study, balb/c ifn-gamma gene knockout mice (ifn-gamma-/-) and balb/c il-12-deficient mice (il-12p40-/- and il-12p35-/-) were unable to mount protecti ... | 2007 | 17944743 |
| malaria causal prophylactic activity of imidazolidinedione derivatives. | a series of acid-stable carboxamide derivatives of 2-guanidinoimidazolidinedione (5a-c and 6a-c) were prepared as potential malaria prophylactic and radical cure agents. the new compounds showed moderate to good causal prophylactic activity in mice infected with plasmodium yoelii sporozoites. three compounds were further tested for causal prophylactic activity in rhesus monkeys infected with plasmodium cynomolgi sporozoites, and all showed a delay in patency from 13 to 40 days at 30 mg/kg/day x ... | 2007 | 17967003 |
| release of hepatic plasmodium yoelii merozoites into the pulmonary microvasculature. | plasmodium undergoes one round of multiplication in the liver prior to invading erythrocytes and initiating the symptomatic blood phase of the malaria infection. productive hepatocyte infection by sporozoites leads to the generation of thousands of merozoites capable of erythrocyte invasion. merozoites are released from infected hepatocytes as merosomes, packets of hundreds of parasites surrounded by host cell membrane. intravital microscopy of green fluorescent protein-expressing p. yoelii para ... | 2007 | 17997605 |
| [in vitro observation on effect of nitric oxide on exflagellation of plasmodium yoelii]. | to observe the effect of nitric oxide (no) on exflagellation of malaria parasite. | 2007 | 18038779 |
| orally active 1,2,4-trioxepanes: synthesis and antimalarial activity of a series of 7-arylvinyl-1,2,4-trioxepanes against multidrug-resistant plasmodium yoelii in swiss mice. | 7-arylvinyl-1,2,4-trioxepanes 7a-d, 8a-d, 9a-d, 10a-d, 11a-c, and 12a-c, prepared by photooxygenation of homoallylic alcohols 5a-d, were evaluated against multi-drug resistant plasmodium yoelii nigeriensis in swiss mice by oral and intramuscular routes. trioxepane 11c, the most active compound of the series, showed more than 98% suppression of parsitaemia at 96 mg/kg by both oral and intramuscular routes. this is the first report on in vivo active 1,2,4-trioxepanes. | 2008 | 18054238 |
| congenicity and genetic polymorphism in cloned lines derived from a single isolate of a rodent malaria parasite. | many of the most commonly studied lines of the rodent malaria parasite plasmodium yoelii yoelii originated from a single parasite isolate designated 17x. amongst these lines, however, are parasites that exhibit variation in genotype and phenotype (e.g. growth rate). we describe here the results of a comparative genetic analysis between cloned lines of 17x that differ in growth rate, using nucleotide sequences of specific genes and patterns of genome-wide amplified fragment length polymorphism (a ... | 2008 | 18068827 |
| suppression of lethal plasmodium yoelii malaria following protective immunization requires antibody-, il-4-, and ifn-gamma-dependent responses induced by vaccination and/or challenge infection. | immunization with plasmodium yoelii merozoite surface protein (pymsp)-8 protects mice from lethal malaria but does not prevent infection. using this merozoite surface protein-based vaccine model, we investigated vaccine- and infection-induced immune responses that contribute to protection. analysis of prechallenge sera from rpymsp-8-immunized c57bl/6 and balb/c mice revealed high and comparable levels of ag-specific igg, but differences in isotype profile and specificity for conformational epito ... | 2008 | 18097046 |
| class ii-restricted protective immunity induced by malaria sporozoites. | the irradiated-sporozoite vaccine elicits sterile immunity against plasmodium parasites in experimental rodent hosts and human volunteers. based on rodent malaria models, it has been proposed that cd8+ t cells are the key protective effector mechanism required in sporozoite-induced immunity. to investigate the role of class ii-restricted immunity in protective immunity, we immunized beta2-microglobulin knockout (beta2m-/-) mice with irradiated plasmodium yoelii or p. berghei sporozoites. sterile ... | 2008 | 18160479 |
| ruthenium(ii) polypyridyl complexes: potential precursors, metalloligands, and topo ii inhibitors. | neutral and cationic mononuclear complexes containing both group 15 and polypyridyl ligands [ru(kappa3-tptz)(pph3)cl2] [1; tptz=2,4,6-tris(2-pyridyl)-1,3,5-triazine], [ru(kappa3-tptz)(kappa2-dppm)cl]bf4 [2; dppm=bis(diphenylphosphino)methane], [ru(kappa3-tptz)(pph3)(pa)]cl (3; pa=phenylalanine), [ru(kappa3-tptz)(pph3)(dtc)]cl (4; dtc=diethyldithiocarbamate), [ru(kappa3-tptz)(pph3)(scn)2] (5) and [ru(kappa3-tptz)(pph3)(n3)2] (6) have been synthesized. complex 1 has been used as a metalloligand in ... | 2008 | 18171055 |
| a combined transcriptome and proteome survey of malaria parasite liver stages. | for 50 years since their discovery, the malaria parasite liver stages (ls) have been difficult to analyze, impeding their utilization as a critical target for antiinfection vaccines and drugs. we have undertaken a comprehensive transcriptome analysis in combination with a proteomic survey of ls. green fluorescent protein-tagged plasmodium yoelii (pygfp) was used to efficiently isolate ls-infected hepatocytes from the rodent host. genome-wide ls gene expression was profiled and compared with othe ... | 2008 | 18172196 |
| plasmodium infection and endotoxic shock induce the expansion of regulatory dendritic cells. | during an acute plasmodium infection, uncontrolled proinflammatory responses can cause morbidity and mortality. regulation of this response is required to prevent immunopathology. we therefore decided to investigate a recently characterized subset of regulatory dendritic cells (dcs) that expresses low levels of cd11c and high levels of cd45rb. during a plasmodium yoelii infection, these regulatory cd11clowcd45rbhigh dcs become the prevalent cd11c-expressing cells in the spleen, overtaking the co ... | 2008 | 18178809 |
| inhibition of glutathione-s-transferase from plasmodium yoelii by protoporphyrin ix, cibacron blue and menadione: implications and therapeutic benefits. | the rapidly developing resistance to drugs used for prophylaxis and treatment of malaria makes the identification of novel drug targets necessary. glutathione-s-transferase (gst, e.c. 2.5.1.18), an important enzyme of the glutathione (gsh) cycle, is considered to be an essential detoxification enzyme in malarial parasites. selective inhibition of this enzyme from malarial parasites by various classes of inhibitors may be viewed as a potential chemotherapeutic strategy to combat malaria. purified ... | 2008 | 18180958 |
| efficient development of plasmodium liver stage-specific memory cd8+ t cells during the course of blood-stage malarial infection. | immunity to plasmodium liver stages in individuals in malaria-endemic areas is inextricably linked to concomitant blood-stage parasitemia. although plasmodium sporozoite infection induces measurable cd8+ t cell responses, the development of memory t cells during active erythrocytic infection remains uncharacterized. using transgenic t cells, we assessed antigen-specific effector cd8+ t cell responses induced by normal (norspz) and radiation-attenuated (irrspz) plasmodium yoelii sporozoites. the ... | 2007 | 18190264 |
| orally active esters of dihydroartemisinin: synthesis and antimalarial activity against multidrug-resistant plasmodium yoelii in mice. | a series of artemisinin derived esters 7a-j, incorporating pharmacologically privileged substructure, such as biphenyl, adamantane and fluorene, have been prepared and evaluated for antimalarial activity against multidrug-resistant (mdr) plasmodium yoelii nigeriensis by oral route. several of these compounds were found to be more active than the antimalarial drugs beta-arteether 4 and artesunic acid 5. ester 7i, the most active compound of the series, provided 100% and 80% protection to the infe ... | 2008 | 18206370 |
| new active drugs against liver stages of plasmodium predicted by molecular topology. | we conducted a quantitative structure-activity relationship (qsar) study based on a database of 127 compounds previously tested against the liver stage of plasmodium yoelii in order to develop a model capable of predicting the in vitro antimalarial activities of new compounds. topological indices were used as structural descriptors, and their relation to antimalarial activity was determined by using linear discriminant analysis. a topological model consisting of two discriminant functions was cr ... | 2008 | 18212104 |
| an efficient strategy for gene targeting and phenotypic assessment in the plasmodium yoelii rodent malaria model. | in this report, we describe a cloning procedure for gene replacement by double homologous recombination in plasmodium yoelii, which requires only one digestion and ligation step. this significantly shortens the time required to complete the production of the targeting vector. furthermore, for more efficient phenotypic evaluation of the gene knockout parasites, we have also introduced a fluorescent protein cassette into the targeting vector. this allows for a more rapid assessment of parasite gro ... | 2008 | 18242728 |
| malaria parasites require tlr9 signaling for immune evasion by activating regulatory t cells. | malaria is still a life-threatening infectious disease that continues to produce 2 million deaths annually. malaria parasites have acquired immune escape mechanisms and prevent the development of sterile immunity. regulatory t cells (tregs) have been reported to contribute to immune evasion during malaria in mice and humans, suggesting that activating tregs is one of the mechanisms by which malaria parasites subvert host immune systems. however, little is known about how these parasites activate ... | 2008 | 18250459 |
| immunogenicity and efficacy of a dna vaccine in aged mice. | the immunogenicity and protective efficacy of a dna vaccine encoding the circumsporozoite protein of the plasmodium yoelii malaria parasite was evaluated in young (2 months) versus aged (>26 months) balb/c mice. the primary and secondary humoral immune response of aged mice was 19- and 7-fold lower, respectively, than that of similarly treated young animals (p < .01). cytotoxic t lymphocyte activity in aged mice was also lower than in younger animals. the vaccine response of aged animals was cha ... | 1998 | 18314558 |
| truncation of plasmodium berghei merozoite surface protein 8 does not affect in vivo blood-stage development. | merozoite surface protein 8 (msp8) has shown promise as a vaccine candidate in the plasmodium yoelii rodent malaria model and has a proposed role in merozoite invasion of erythrocytes. however, the temporal expression and localisation of msp8 are unusual for a merozoite antigen. moreover, in plasmodium falciparum the msp8 gene could be disrupted with no apparent effect on invitro growth. to address the invivo function of full-length msp8, we truncated msp8 in the rodent parasite plasmodium bergh ... | 2008 | 18359107 |
| anti-protozoan activities of harungana madagascariensis stem bark extract on trichomonads and malaria. | the ethanolic stem bark extract of harungana madagascariensis (hypericaceae), (choisy) poir were evaluated for their activities on trichomonas gallinae (rivolta) stabler isolated from the pigeon (columba livia). it was also tested for their anti-malarial activity on n67 plasmodium yoelii nigeriensis (in vivo) in mice and on plasmodium falciparum isolates in vitro. | 2008 | 18372133 |
| counter-regulatory anti-parasite cytokine responses during concurrent plasmodium yoelii and intestinal helminth infections in mice. | malaria and helminth infections are two of the most prevalent parasitic diseases globally. while concomitant infection is common, mechanisms contributing to altered disease outcomes during co-infection remain poorly defined. we have previously reported exacerbation of normally non-lethal plasmodium yoelii malaria in balb/c mice chronically infected with the intestinal trematode echinostoma caproni. the goal of the present studies was to determine the effect of helminth infection on ifn-gamma and ... | 2008 | 18396282 |
| synthesis and structure-activity relationships of 4-pyridones as potential antimalarials. | a series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against plasmodium falciparum in vitro and murine plasmodium yoelii in vivo. these were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. relative to clopidol the most active compounds show >500-fold improvement in ic50 for inhibition of p. falciparum in vitro and about 100-fold imp ... | 2008 | 18396855 |
| high mobility group protein hmgb2 is a critical regulator of plasmodium oocyst development. | the sexual cycle of plasmodium is required for transmission of malaria from mosquitoes to mammals, but how parasites induce the expression of genes required for the sexual stages is not known. we disrupted the plasmodium yoelii gene encoding high mobility group nuclear factor hmgb2, which encodes a dna-binding protein potentially implicated in transcriptional regulation of malaria gene expression. we investigated its function in vivo in the vertebrate and invertebrate hosts. deltapyhmgb2 parasit ... | 2008 | 18400754 |
| il-10 from cd4cd25foxp3cd127 adaptive regulatory t cells modulates parasite clearance and pathology during malaria infection. | the outcome of malaria infection is determined, in part, by the balance of pro-inflammatory and regulatory immune responses. failure to develop an effective pro-inflammatory response can lead to unrestricted parasite replication, whilst failure to regulate this response leads to the development of severe immunopathology. il-10 and tgf-beta are known to be important components of the regulatory response, but the cellular source of these cytokines is still unknown. here we have examined the role o ... | 2008 | 18401464 |
| experimental asexual blood stage malaria immunity. | this unit describes three methods for investigating the immune response to murine malaria parasites. immunization protocols using recombinant fragments of the merozoite surface protein-1 of plasmodium yoelii, whole blood stage malaria parasites, and live infection with parasitized red blood cells from a plasmodium-infected donor are provided. methods for chemotherapeutic drug care of plasmodium-infected mice and for inducing malaria by adoptive transfer of antigen-specific t cells are included. ... | 2001 | 18432755 |
| isolation and antimalarial activity of new morphinan alkaloids on plasmodium yoelii liver stage. | decoction of strychnopsis thouarsii is used in the malagasy traditional medicine to combat malaria. we have shown that this traditional remedy prevents malaria infection by targeting plasmodium at its early liver stage. bioassay-guided fractionation of s. thouarsii stem barks extracts, using a rodent plasmodium yoelii liver stage parasites inhibition assay, led to isolate the new morphinan alkaloid tazopsine (1) together with sinococuline (2) and two other new related morphinan analogs, 10-epi-t ... | 2008 | 18456502 |
| targeted deletion of sap1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection. | malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of uis (upregulated in infectious sporozoites) genes. a number of uis gene products are essential for the establishment of the intrahepatocytic niche. however, the factors that regulate the expression of genes involved in gain of infectivity for the liver are unknown. herein, we show that a conserved plasmodium sporozoite low-complexity asparagine-rich protein, sap1 (sporozoite asparagine-rich protein 1), h ... | 2008 | 18466298 |
| active immunisation with rama does not provide protective immunity against plasmodium yoelii challenge despite its association with protective responses in endemic populations. | the rhoptry associated membrane antigen (rama) of plasmodium falciparum has been proposed as a potential candidate for inclusion in a multivalent subunit vaccine against malaria. previous studies have found that the rama gene is refractory to genetic deletion in vitro and is conserved in a range of clinical isolates. importantly, two independent studies demonstrated that antibodies against the c-terminal region of rama are associated with immunity in endemic populations of both asia and africa. ... | 2008 | 18468741 |
| heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection. | the clinically silent plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. we report here that expression of heme oxygenase-1 (ho-1, encoded by hmox1) is upregulated in the liver following infection by plasmodium berghei and plasmodium yoelii sporozoites. ho-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of ho-1, also inc ... | 2008 | 18474360 |
| the oligomerization domain of c4-binding protein (c4bp) acts as an adjuvant, and the fusion protein comprised of the 19-kilodalton merozoite surface protein 1 fused with the murine c4bp domain protects mice against malaria. | highly purified protein antigens are usually poor immunogens; in practice, adjuvants are needed to obtain satisfactory immune responses. plasmodium yoelii 19-kda merozoite surface protein 1 (msp1(19)) is a weak antigen, but mice vaccinated with this antigen in strong adjuvants can survive an otherwise lethal parasite challenge. fusion proteins comprising this antigen fused to the oligomerization domain of the murine complement inhibitor c4-binding protein (c4bp) and a series of homologues have b ... | 2008 | 18474650 |
| interactions between dendritic cells and cd4+ t cells during plasmodium infection. | during infection, dendritic cells (dcs) encounter pathogenic microorganisms that can modulate their function and shape the t cell responses generated. during the process of t cell activation, dcs establish strong, long-lasting interactions with naïve t cells. | 2008 | 18495039 |
| a structural annotation resource for the selection of putative target proteins in the malaria parasite. | protein structure plays a pivotal role in elucidating mechanisms of parasite functioning and drug resistance. moreover, protein structure aids the determination of protein function, which can together with the structure be used to identify novel drug targets in the parasite. however, various structural features in plasmodium falciparum proteins complicate the experimental determination of protein structures. limited similarity to proteins in the protein data bank and the shortage of solved prote ... | 2008 | 18500983 |
| effector cd8+ t lymphocytes against liver stages of plasmodium yoelii do not require gamma interferon for antiparasite activity. | the protective immune response against liver stages of the malaria parasite critically requires cd8(+) t cells. although the nature of the effector mechanism utilized by these cells to repress parasite development remains unclear, a critical role for gamma interferon (ifn-gamma) has been widely assumed based on circumstantial evidence. however, the requirement for cd8(+) t-cell-mediated ifn-gamma production in protective immunity to this pathogen has not been directly tested. in this report, we ... | 2008 | 18519561 |
| comparison of male reproductive success in malaria-refractory and susceptible strains of anopheles gambiae. | in female mosquitoes that transmit malaria, the benefits of being refractory to the plasmodium parasite are balanced by the immunity costs in the absence of infection. male mosquitoes, however, gain no advantage from being refractory to blood-transmitted parasites, so that any costs associated with an enhanced immune system in the males limit the evolution of female refractoriness and has practical implications for the release of transgenic males. | 2008 | 18534029 |
| immunomodulator effect of picroliv and its potential in treatment against resistant plasmodium yoelii (mdr) infection in mice. | the present study was envisaged to evaluate potential of combination therapy comprising of immunomodulator picroliv and antimalarial chloroquine against drug resistant plasmodium yoelii (p. yoelii) infection in balb/c mice. | 2008 | 18551251 |
| rodent plasmodium: population dynamics of early sporogony within anopheles stephensi mosquitoes. | early sporogony of plasmodium parasites involves 2 major developmental transitions within the insect vector, i.e., gametocyte-to-ookinete and ookinete-to-oocyst. this study compared the population dynamics of early sporogony among murine rodent plasmodium (plasmodium berghei, plasmodium chabaudi, plasmodium vinckei, and plasmodium yoelii) developing within anopheles stephensi mosquitoes. estimates of absolute densities were determined for gametocytes, ookinetes, and oocysts for 108 experimental ... | 2008 | 18576764 |
| assessment and improvement of the plasmodium yoelii yoelii genome annotation through comparative analysis. | the sequencing of the plasmodium yoelii genome, a model rodent malaria parasite, has greatly facilitated research for the development of new drug and vaccine candidates against malaria. unfortunately, only preliminary gene models were annotated on the partially sequenced genome, mostly by in silico gene prediction, and there has been no major improvement of the annotation since 2002. | 2008 | 18586738 |
| plasmodium yoelii: novel rhoptry proteins identified within the body of merozoite rhoptries in rodent plasmodium malaria. | the biogenesis, organization and function of the rhoptries are not well understood. antisera were prepared to synthetic peptides prepared as multiple antigenic peptides (maps) obtained from a plasmodium yoelii merozoite rhoptry proteome analysis. the antisera were used in immunofluorescence and immunoelectron microscopy of schizont-infected erythrocytes. twenty-seven novel rhoptry proteins representing proteases, metabolic enzymes, secreted proteins and hypothetical proteins, were identified in ... | 2008 | 18606406 |
| plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine kupffer cells. | plasmodium sporozoites traverse kupffer cells on their way into the liver. sporozoite contact does not elicit a respiratory burst in these hepatic macrophages and blocks the formation of reactive oxygen species in response to secondary stimuli via elevation of the intracellular camp concentration. here we show that increasing the camp level with dibutyryl cyclic adenosine monophosphate (db-camp) or isobutylmethylxanthine (ibmx) also modulates cytokine secretion in murine kupffer cells towards an ... | 2008 | 18656478 |
| effective induction of high-titer antibodies by viral vector vaccines. | protein-in-adjuvant vaccines have shown limited success against difficult diseases such as blood-stage malaria. here we show that a recombinant adenovirus-poxvirus prime-boost immunization regime (known to induce strong t cell immunogenicity) can also induce very strong antigen-specific antibody responses, and we identify a simple complement-based adjuvant to further enhance immunogenicity. antibodies induced against a blood-stage malaria antigen by this viral vector platform are highly effectiv ... | 2008 | 18660818 |
| myd88/il-18-dependent pathways rather than tlrs control early parasitaemia in non-lethal plasmodium yoelii infection. | plasmodium falciparum gpi contributes to malaria pathology by inducing cytokine release. it has been shown to be recognized through tlr2 and to a lesser extent tlr4 in vitro. however, previous findings on the role of tlrs in parasite clearance or pathology in vivo are conflicting. thus, we analyzed the impact of tlr-signalling on protection using the p. yoelii infection model. deficiency of single tlrs as well as triple tlr2/4/9-deficiency had no impact on parasitaemia. in contrast, mice deficie ... | 2008 | 18692153 |
| identification and characterization of the plasmodium yoelii pyp140/ron4 protein, an orthologue of toxoplasma gondii ron4, whose cysteine-rich domain does not protect against lethal parasite challenge infection. | previously, we identified a plasmodium yoelii ym 140-kda merozoite protein, designated pyp140, which formed a complex with apical membrane antigen 1 (ama1). furthermore, we produced a nonprotective monoclonal antibody (mab), 48f8, that immunoprecipitated metabolically labeled pyp140 and localized the protein to the merozoite's apical end and, less frequently, to the merozoite surface, as observed by immunofluorescence assay (ifa). here, using mab 48f8, we have identified the pyp140 gene by scree ... | 2008 | 18710865 |
| attenuated plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity. | malaria continues to devastate sub-saharan africa owing to the emergence of drug resistance to established antimalarials and to the lack of an efficacious vaccine. plasmodium species have a unique streamlined purine pathway in which the dual specificity enzyme purine nucleoside phosphorylase (pnp) functions in both purine recycling and purine salvage. to evaluate the importance of pnp in an in vivo model of malaria, we disrupted pypnp, the gene encoding pnp in the lethal plasmodium yoelii ym str ... | 2008 | 18758447 |
| protective immunity induced by daily bites from irradiated mosquitoes infected with plasmodium yoelii. | individuals in malaria endemic regions do not develop fully protective immune responses against plasmodium liver stage infections. in high transmission areas, individuals can be exposed to more than two infective mosquito bites daily. their exposure to plasmodium sporozoites, therefore, is in the form of small and frequent doses. this is very different from individuals studied in controlled immunization trials where the delivery of large numbers of radiation-attenuated sporozoites in a limited n ... | 2008 | 18761489 |
| memory cd8 t cell responses exceeding a large but definable threshold provide long-term immunity to malaria. | infection of mice with sporozoites of plasmodium berghei or plasmodium yoelii has been used extensively to evaluate liver-stage protection by candidate preerythrocytic malaria vaccines. unfortunately, repeated success of such vaccines in mice has not translated readily to effective malaria vaccines in humans. thus, mice may be used better as models to dissect basic parameters required for immunity to plasmodium-infection than as preclinical vaccine models. in turn, this basic information may aid ... | 2008 | 18780790 |
| quantitative measurement of plasmodium-infected erythrocytes in murine models of malaria by flow cytometry using bidimensional assessment of syto-16 fluorescence. | flow cytometry is a powerful tool for measuring parasitemias in murine malaria models used to test new antimalarials. measurement of the emission of the nonpermeable nucleic acid dye yoyo-1 (at 530 and 585 nm after excitation at 488 nm) allowed the unambiguous detection of low parasitemias (> or =0.01%) but required prolonged fixation and permeabilization of the sample. thus, we tested whether this issue could be overcome by use of the cell-permeant dye syto-16 with this same bidimensional metho ... | 2009 | 18785271 |
| new functionalized 1,2,4-trioxepanes: synthesis and antimalarial activity against multi-drug resistant p. yoelii in mice. | a series of new amino functionalized 1,2,4-trioxepanes 8-16 and ester functionalized 1,2,4-trioxepanes 17-19 have been synthesized and evaluated against multi-drug resistant plasmodium yoelii in swiss mice. amino functionalized trioxepanes 14, the most active compound of the series, showed 100% clearance of parasitaemia by oral route on day 4 and 75% protection to the treated mice beyond day 28. | 2008 | 18789862 |
| malvac: database of malarial vaccine candidates. | the sequencing of genomes of the plasmodium species causing malaria, offers immense opportunities to aid in the development of new therapeutics and vaccine candidates through bioinformatics tools and resources. | 2008 | 18811938 |
| dynamic balance of pstat1 and pstat3 in c57bl/6 mice infected with lethal or nonlethal plasmodium yoelii. | signal transducer and activator of transcription (stat) proteins play an important role in cytokine signaling pathways and regulation of immune responses. the balance of the phosphorylated (activated) stat1 (pstat1) and stat3 (pstat3) has been documented in cancer immunology. in this study, we investigated the dynamic balance of pstat1 and pstat3 in c57bl/6 mice infected with either a nonlethal (py17xnl) or lethal (py17xl) strain of plasmodium yoelii. both py17xnl and py17xl infections induced a ... | 2008 | 18954557 |
| atp/adp binding to a novel nucleotide binding domain of the reticulocyte-binding protein py235 of plasmodium yoelii. | the mechanism by which a malaria merozoite recognizes a suitable host cell is mediated by a cascade of receptor-ligand interactions. in addition to the availability of the appropriate receptors, intracellular atp plays an important role in determining whether erythrocytes are suitable for merozoite invasion. recent work has shown that atp secreted from erythrocytes signals a number of cellular processes. to determine whether atp signaling might be involved in merozoite invasion, we investigated ... | 2008 | 18957411 |