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antimalarial activity of floxacrine (hoe 991) ii: studies on causal prophylactic and blood schizontocidal action of floxacrine and related dihydroacridinediones against plasmodium yoelii and p. berghei. 19826760821
susceptibility of anopheles gambiae to plasmodium yoelii nigeriensis and plasmodium falciparum. 19826763502
[new data on the circadian cycle of plasmodium. preliminary note].a frozen strain of plasmodium yoelii nigeriensis is inoculated at 4 pm, midnight and 9 am onto inbred mice. in all instances young gametocytes (type 0) appear in the blood only between 10 am and 6 pm. although the erythrocytic schizogony occurs regularly during the whole circadian period, the latency increases progressively when the infective subinoculations are made at midnight, 4 pm and 9 am. possibly, the infective merozoite can only enter the red blood cell around midnight.19806784953
[development of schizonts in cultured hepatocytes of adult rats after in vitro infection with plasmodium yoelii sporoazoites].salivary glands of a. stephensi, containing p. yoelii' sporozoites, were disrupted and added to hepatocyte cultures originated from the liver of an adult rat perfused with a collagenase solution. 47 h after this in vitro inoculation, numerous well-developed and normal-looking schizonts were found in the hepatocyte monolayer.19816797693
absence of effects of insecticides on susceptibility of anophelines to plasmodium yoelii nigeriensis. 19826810475
[in vitro infestation of adult thamnomys hepatocytes with plasmodium yoelii sporozoites; schizogony and release of infecting merozoites].hepatocytes isolated from an african rodent, thamnomys gazellae, by perfusing the liver with a solution of collagenase were cultured in modified mem medium, and infected in vitro by sporozoites of the 17 x strain of p. y. yoelii. 48 hrs. later, schizonts measuring 30 to 40 microns on average were observed in all cultures. injection of culture supernatant, harvested on day 3, into mice, was followed by a parasitaemia demonstrating that viable merozoites had been released by the schizonts.19826814716
killing of blood-stage murine malaria parasites by hydrogen peroxide.both nonlethal plasmodium yoelii and lethal plasmodium berghei were killed in vitro by hydrogen peroxide at concentrations as low as 10(-5) m. higher concentrations were required in the presence of added normal erythrocytes. injection of hydrogen peroxide in vivo significantly reduced p. yoelii parasitemia but had less effect on p. berghei.19836822428
observations on the morphology and electrophoretic variation of enzymes of the rodent malaria parasites of cameroon, plasmodium yoelii, p. chabaudi and p. vinckei.six samples of rodent blood infected with malaria parasites were isolated from cameroon. of these, 2 contained mixed infections of plasmodium vinckei and p. yoelii, 3 contained p. vinckei alone and 1 p. chabaudi alone. each isolate was cloned and the resulting lines examined for morphology of blood and mosquito forms, and for electrophoretic variation in enzymes. the p. chabaudi and p. yoelii lines were morphologically and enzymically identical to isolates of the central african republic. simila ...19836856331
specific lysis of plasmodium yoelii infected mouse erythrocytes with antibody and complement.an assay for complement-dependent antibody-mediated cytolysis of plasmodium yoelii infected mouse erythrocytes was designed. by means of a rat hyperimmune serum to p. yoelii the presence of parasite associated antigens was demonstrated on erythrocytes from p. yoelii infected mice. tests with such erythrocytes fractionated on percoll gradients showed that the target antigens for the cytotoxic antibodies were confined to the surface of only infected erythrocytes containing late stages of the paras ...19836861370
plasmodium yoelii: the thymus-dependent lymphocyte in mice immunodepressed by malaria. 19806967825
immunity to plasmodium chabaudi adami in the b-cell-deficient mouse.immunity to malaria has a multicomponent basis which requires the participation of both t- and b-lymphocyte systems. previous studies have suggested that the t-lymphocyte system has an essential role in 're-infection immunity' to malaria, but that b cells and/or their products are necessary for the host to survive acute infection and to clear the blood of parasites during chronic malaria. thus, b-cell-deficient mice and chickens died of fulminant malaria when infected with plasmodium yoelii and ...19816970898
the rodent malaria parasite plasmodium yoelii lacks both types 1 and 2 t-independent antigens. 19826977572
t cell-mediated immunity in malaria. i. the ly phenotype of t cells mediating resistance to plasmodium yoelii.cba mice that recover from plasmodium yoelii 17x infection are resistant to reinfection. t cells from these mice transfer immunity to nonimmune recipients. to analyze the nature and mode of action of these t cells, we transferred selected subsets into t cell-deprived recipients. treatment of the t cells with anti-ly-1 but not anti-ly-2 serum and c abrogated their ability to transfer immunity. a mixture of anti-ly-1 and anti-ly-2 serum-treated cells (i.e., a population devoid of ly-123 cells) tra ...19826979570
host defenses in murine malaria: immunological characteristics of a protracted state of immunity to plasmodium yoelii.random-bred icr mice recovered from infection with avirulent plasmodium yoelii were challenged at various later times with virulent p. yoelii or with another species of plasmodium, p. berghei, to characterize the immunological nature of the long-term state of immunity generated in response to the avirulent infection. it was found that recovered mice resisted lethal challenge with virulent p. yoelii through at least 416 days after primary infection. however, the quality of this immunity changed a ...19806987179
the chemotherapy of rodent malaria, xxxii. the influence of p-aminobenzoic acid on the transmission of plasmodium yoelii and p. berghei by anopheles stephensi.more oocysts of plasmodium yoelii developed in anopheles stephensi if the mosquitoes received a supplement of p-aminobenzoic acid (paba) in their diet prior to their taking an infective blood meal, than in unsupplemented control insects. the optimum concentration was 0.05% paba in 10% sucrose. this effect was not observed if the blood meal was taken prior to feeding with paba. similarly, paba administered to gametocyte-carrying mice increased the numbers of oocysts developing in mosquitoes fed o ...19806994664
two distinct types of non-specific immunosuppression in murine malaria.a comparative study of non-specific immunosuppression by malaria has been carried out in five situations: in both unvaccinated and vaccinated mice infected with the lethal plasmodium yoelii or the lethal plasmodium berghei, and in the unvaccinated non-lethal p. yoelii infection. spleen cells showed a suppressive effect on the normal blastogenic response to mitogens. this suppression was strongest in the mice vaccinated before infection with the lethal p. yoelii and in those infected with non-let ...19807011609
host defenses in murine malaria: analysis of plasmodial infection-caused defects in macrophage microbicidal capacities.macrophage-dependent killing of facultative intracellular bacteria was markedly impaired by overt erythrocytic plasmodium yoelii or plasmodium berghei infection of mice. p. yoelii infection was capable of ablating not only the macrophage microbicidal capacity of "normal" animals but also the bactericidal capacities of "activated" macrophages. the uptake by spleen and liver of an intravenous challenge of listeria monocytogenes was not altered by plasmodial infection, but within hours of injection ...19817012000
endotoxin-induced serum factor kills malarial parasites in vitro.we investigated the possibility that malarial parasites may be killed by nonspecific soluble mediators, such as those in tumor necrosis serum, that are obtained from mice given macrophage-activating agents like corynebacterium parvum or mycobacterium bovis bcg, followed by endotoxin. such sera killed parasites in vitro after overnight incubation; killing was measured directly by using an in vivo infectivity assay. parasite infectivity was not decreased by incubation in sera from mice given c. pa ...19817021427
vaccination to prevent transmission of plasmodium yoelii malaria.it was possible to block the transmission of infection of the rodent malaria parasite plasmodium yoelii nigeriensis to anopheles stephensi mosquitoes by immunizing mice with a vaccine containing formalin-fixed gametes. both intramuscular and intravenous routes were effective, immunity was achieved with a single dose and the immunity persisted for 6 months at least. transmission-blocking immunity was found to reside in a serum factor, probably antibody, and to be directed against extracellular ga ...19827070834
killing of the malarial parasite plasmodium yoelii in vitro by cells of myeloid origin.cytotoxic effects of mouse cells on plasmodium yoelii were sought directly by incubating parasitized red cells with cells of various kinds for 16 h and then determining the percentage parasite survival in vivo, in terms of infectivity for the mouse. cell populations rich in lymphocytes, e.g. lymph node and spleen, were less active than peritoneal cells and blood. parasite killing by peritoneal cells was associated with macrophages: treatment with anti-macrophage serum (ams) or depletion by adher ...19827070836
studies on the role of host serum in the retention of malarial sporozoites by isolated perfused rat liver.the binding of host serum components to malarial sporozoites has been proposed as a mechanism for the specific phagocytic uptake of these parasites, and hence the specificity of host infection (schulman et al., 1981). we therefore observed the kinetics of uptake of sporozoites of plasmodium yoelii nigeriensis and p. gallinaceum by isolated perfused rat livers in the presence of homologous or heterologous sera. in the homologous system (p. y. nigeriensis sporozoites in rat serum) sporozoite uptak ...19827080155
[retarded schizogony of plasmodium yoelii yoelii in rodents treated with ethionine or subjected to a methionine deficiency: histological and ultrastructural studies].histological and ultrastructural aspects of acute and chronic pre-erythrocytic schizonts of p. yoelii yoelii were studied with: a) acute schizonts in normal rodents; b) chronic schizonts induced in rodents receiving ethionine injections or on a low methionine diet; experimentally induced chronic schizonts frequently have the same histological aspect as those observed in wild thamnomys from africa. the ultrastructural evolution of the vacuole system described by seureau et al. in acute schizonts ...19827081885
[in vitro infection of adult thamnomys hepatocytes by sporozoites of plasmodium yoelii: development of schizonts and release of infective merozoites]. 19827081893
a cage replacement experiment involving introduction of genes for refractoriness to plasmodium yoelii nigeriensis into a population of anopheles gambiae (diptera: culicidae). 19827086849
survival of mice injected with plasmodium vinckei or plasmodium yoelii xl by the footpad route.nih-white mice were injected with varying doses of plasmodium vinckei or plasmodium yoelii lethal via the hind footpad (fp), intraperitoneal (ip), subcutaneous (sc) routes. survival was dependent on the dose of the inoculum and route of injection. injection via the ip and sc routes led to higher mortality than the fp route. the results showed that at a dose of 10 4 parasitized erythrocytes injected ip led to 100% mortality, whereas the same dose injected via the fp route gave protection.19827125059
elevated levels of phospholipase b in mice infected and challenged with plasmodium yoelii.marked increases in phospholipase b activity were measured in spleen homogenates and sera of cd-1 mice given a primary infection of plasmodium yoelii. the rise in enzyme activity paralleled parasitemia and splenomegaly, all reaching maximum values 14 days after infection. maximum enzyme activity and splenomegaly were noted 5 days after challenge in mice given a secondary infection indicating an anamnesticlike response following a subsequent contact with the infecting parasite. these observations ...19827131182
murine malaria: blood clearance and organ sequestration of plasmodium yoelii-infected erythrocytes.this study examined the mechanisms of clearance of plasmodium yoelii-infected erythrocytes (rbc) from the peripheral circulation of mice. parasitized rbc labeled with 51cr were cleared from the blood of normal c57bl/6 mice at a much more rapid rate than were nonparasitized rbc, and preincubation of parasitized rbc in antiplasmodial antibody failed to significantly enhance clearance. this apparent antibody-independent clearance mechanism was markedly abrogated by splenectomy, indicating a major r ...19827141688
a comparison of saponin with other adjuvants for the potentiation of protective immunity by a killed plasmodium yoelii vaccine in the mouse.the protective immunity conferred by subcutaneous injection of outbred cd-1 mice with a killed plasmodium yoelii (ym strain) vaccine was strongly potentiated by saponin. by adjusting the dose of antigen, the number of immunizations and the number of living parasites in the challenge infection, conditions were defined where antigen alone was non-protective but 100% protection was obtained by the addition of saponin. inbred balb/c, cba/ca and c57 b1 mice were much less responsive than the cd-1 mic ...19827145465
[immediate inhibition of the infectivity of gametocytes of plasmodium yoelii nigeriensis by serum from rodents infected for 5 days]. 19827181381
plasmodium yoelii: antibody and the maintenance of immunity in balb/c mice. 19817238723
[studies on antimalarial drug. ii. the causal prophylactic activity of antimalarial in animal model. part i. plasmodium yoelii-anopheles stephensi system (author's transl)]. 19817257809
immunization to produce a transmission-blocking immunity in plasmodium yoelii malaria infections. 19817268856
plasmodium yoelii: genetic analysis of crosses between two rodent malaria subspecies. 19817274370
hypergammaglobulinemia and erythrocyte autoantibody complicate enzyme immunoassay of antimalarial antibody.enzyme immunoassay of specific antimalarial antibody in sera from plasmodium yoelii-infected mice was complicated by hypergammaglobulinemia and erythrocyte (rbc) autoantibody. malarious serum had higher immunoglobulin levels which resulted in a substantial nonspecific adsorption of antibody to antigen uncoated microliter wells even in the presence of a surfactant. since it was possible that some of the antibody binding to solid phase-bound malarial antigen was also due to nonspecific adsorption, ...19817334130
protective monoclonal antibodies recognising stage-specific merozoite antigens of a rodent malaria parasite.immunity to malaria is mediated, at least in part, by antibody. resistance to infection has been passively transferred with immune serum or its immunoglobulin fraction in human, simian and rodent malaria. however, because of the structural and antigenic complexity of the malaria parasites, it has proved difficult to identify and characterise those parasite antigens against which protective antibody is directed. we have produced several hybrid cell lines secreting monoclonal antibodies against th ...19807360274
[experimental production of variants with lowered preference for polychromatophilic erythrocytes in plasmodium yoelii (author's transl)].after 25 massive passages of a plasmodium yoelii-population (strain 17x) in the phase of high parasitization of mature erythrocytes, parasites with markedly lowered preference for immature erythrocytes could be isolated. of 3 isolates in 3 independent experiments, one showed a distinctly lower preference than the other two. with very high infecting doses, the isolates caused in most mice high parasitization of mature erythrocytes and death. the original strain had been kept in mice by passage of ...19807414678
variable expression of virulence in the rodent malaria parasite plasmodium yoelii yoelii.the expression of the virulence character in the virulent line (ym) of plasmodium yoelii yoelii was investigated. the level of virulence was measured by counting the parasitaemia of the mature red blood cells. several sub-clones were isolated from the virulent line ym and each was tested for its level of virulence. out of 10 sub-clones 1 showed a marked decrease in virulence. however, transmission of this sub-clone through mosquitoes fully restored its virulence. a clone isolated from the progen ...19807422362
radioimmunoassay for detecting antibodies against murine malarial parasite antigens: monoclonal antibodies recognizing plasmodium yoelii antigens.a solid-phase radioimmunoassay (spria) in microtiter wells was established for detecting antibodies against plasmodium yoelii ag. the spria was found 1) to require as little as 5 micrograms of crude parasite ag per well, 2) to be able to detect 0.5 ng of monoclonal ab, and 3) to be 10(4) times more sensitive than the indirect fluorescent ab staining technique. in a modification of the above assay using intact rbc as an ag, hyperimmune serum showed significant binding to the surface of erythrocyt ...19807430638
the role of the liver in immunity to blood-stage murine malaria.mice vaccinated with fixed parasitized red blood cells and bordetella pertussis can clear an otherwise lethal plasmodium yoelii infection in 7 days; this protection is abolished by splenectomy before vaccination. most mice splenectomized following vaccination were able to clear their infections, although their recovery was delayed. when labelled parasitized red cells were injected into mice during an infection, splenic uptake fell from day 3 onwards while uptake by the liver increased. lymphocyt ...19807439934
characterization of surface proteins and glycoproteins on red blood cells from mice infected with haemosporidia: plasmodium yoelii infections of balb/c mice.lactoperoxidase-catalysed radio-iodination was used to compare the surface proteins on red cells from plasmodium yoelii-infected with normal balb/c mice. the profile of radio-iodinated proteins separated by sds-polyacrylamide gel electrophoresis was different for infected blood of similar parasitaemia from mice inoculated with different doses of the parasite. inoculation with different doses of the parasite. inoculation with the lower dose resulted in the appearance of a major radio-iodinated pr ...19807443294
malaria in asplenic mice: effects of splenectomy, congenital asplenia, and splenic reconstitution on the course of infection.in investigations on the role of the spleen in host defense against malaria, we studied the course of murine malaria in three groups of mice with altered splenic function: congenitally asplenic mice, adult-splenectomized mice, and adult-splenectomized mice which were reconstituted with spleen-cell suspensions. intact mice infected with either plasmodium yoelii or p. chabaudi adami experienced infections which resolved spontaneously, with low mortality. congenitally asplenic and splenectomized-re ...19807446805
immune phagocytosis of plasmodium yoelii-infected erythrocytes by macrophages and eosinophils.unstimulated peritoneal cells from c57bl mice were allowed to phagocytose in vitro different mixtures of percoll-separated parasitized and non-parasitized erythrocytes (pe and npe) from the blood of mice infected with plasmodium yoelii in the presence of immune and normal serum. immune serum caused a significant enhancement of phagocytosis, and both the number of pe adhering to and/or ingested by 100 macrophages and the number of the latter cells engaged in phagocytosis was increased. the effect ...19807460387
the chemotherapy of rodent malaria. lii. response of plasmodium yoelii ssp. ns to mefloquine and its enantiomers.a comparison was made between the blood schizontocidal action in mice of racemic mefloquine hydrochloride and the free bases of its (+)- and (-)-enantiomers (ro 13-7224 and ro 13-7225) against chloroquine-resistant plasmodium yoelii ssp. ns. the racemic hydrochloride was two to three times as active against this parasite in mice as either of the enantiomer free bases, which were of similar activity to each other. under drug selection pressure, the parasites acquired resistance in approximately t ...19957495359
the combined epidermal growth factor-like modules of plasmodium yoelii merozoite surface protein-1 are required for a protective immune response to the parasite.we have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (egf)-like modules of plasmodium yoelii merozoite surface protein-1 (msp-1) protected mice against challenge with this malaria parasite. bacterial plasmids containing sequences coding for the individual modules fused to glutathione s-transferase (gst) have now been made. the fusion protein containing the combined egf-like modules was recognized by anti-parasite antibodies ...19957501423
induction of murine cytotoxic t lymphocytes against plasmodium falciparum sporozoite surface protein 2.sporozoite surface protein 2 has been identified as a target of malaria vaccines designed to produce protective cd8+ cytotoxic t lymphocytes (ctl) because mice immunized with mastocytoma cells expressing a fragment of plasmodium yoelii sporozoite surface protein 2 (pyssp2) are protected against malaria by an immune response that requires cd8+ ctl. to define ctl epitopes in the plasmodium falciparum sporozoite surface protein 2 (pfssp2), spleen cells (sc) from mice immunized with irradiated sporo ...19947517870
influenza and vaccinia viruses expressing malaria cd8+ t and b cell epitopes. comparison of their immunogenicity and capacity to induce protective immunity.we compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. the cd8+ t cell epitope of the circumsporozoite (cs) protein of plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. these recombinant viruses were found to be equally efficient at inducing cs-specific cd8+ t cells in mice. a third recombinant virus, which expresses a b cell epit ...19947525709
plasmodium yoelii yoelii 17xl msp-1: fine-specificity mapping of a discontinuous, disulfide-dependent epitope recognized by a protective monoclonal antibody using expression pcr (e-pcr). 19957534725
identification of a nonameric h-2kk-restricted cd8+ cytotoxic t lymphocyte epitope on the plasmodium falciparum circumsporozoite protein.class i-restricted cd8+ cytotoxic t lymphocytes (ctl) against the circumsporozoite protein (csp) protect mice against the rodent malaria parasite, plasmodium yoelii, and vaccines designed to produce protective ctl against the p. falciparum csp (pfcsp) are under development. humans and b10.br (h-2k) mice have been shown to have cd8+ ctl activity against a 23-amino-acid region of the pfcsp (residues 368 to 390 from the pfcsp 7g8 sequence) that is too long to bind directly to class i major histocom ...19957537251
development of antimalaria immunity in mice lacking ifn-gamma receptor.ifn-gamma receptor deficient (ifn-gamma r-/-) mice, immunized with different developmental stages of malaria parasites, were used to define the mechanisms of protection against the various stages of this infection. ifn-gamma r-/- mice failed to develop protective immunity against plasmodium yoelii sporozoites or liver stages, upon immunization with a single dose of irradiated sporozoites, whereas in immunized wild-type mice, parasite development was strongly inhibited. immunized wild-type mice e ...19957537305
hla-a2-restricted cytotoxic t lymphocyte responses to multiple plasmodium falciparum sporozoite surface protein 2 epitopes in sporozoite-immunized volunteers.cd8+ ctl specific for the plasmodium yoelii sporozoite surface protein 2 (pyssp2) protect mice against malaria. for this reason, vaccines designed to induce ctl against p. falciparum ssp2 (pfssp2) are under development. optimal development of pfssp2 as a component of human malaria vaccines requires characterization of hla class i-restricted ctl against this ag. for this purpose, pbmc from four hla-a2+ human volunteers immunized with p. falciparum irradiated sporozoites were stimulated with a rec ...19957541824
[a preliminary study on the inhibitory action of target-primaqine on the exoerythrocytic forms of plasmodium yoelii yoelii].target-primaquine (tpq)--the primaquine entrapped by galactosylneoglycoalbumin (g-nga), was given intravenously (iv) to wistar rats 2 h after sporozoite inoculation. the sporozoite viability (spv) of tpq 20 mg/kg group was revealed to be 1.2% 42 h after inoculation, which showed a decline of about 6% as compared to the control; besides, degeneration or retardation of development was present in 90% of eef. in tpq 10 mg/kg and pq 20 mg/kg groups, the spv were 2.8% and 5.0%, respectively, showing d ...19957554159
attempted isolation of the gene encoding the 21 kd plasmodium berghei ookinete transmission blocking antigen from plasmodium yoelli and plasmodium vivax.the 21kd ookinete antigen of plasmodium berghei (pbs 21) has been shown to elicit an effective and long lasting transmission blocking immune response in mice. having cloned and sequenced this antigen (paton et al. 1993) the sequence was compared to the genes of the same family previously identified in p. falciparum, p. gallinaceum (kaslow et al. 1989) and p. reichenowi (lal et al. 1990). four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. ...19947565129
cloning and structural analysis of the gene for camp-dependent protein kinase catalytic subunit from plasmodium yoelii.we isolated the gene encoding the camp-dependent protein kinase catalytic subunit (capk[c]) from plasmodium yoelii by screening a genomic library for the dna fragment as produced by the polymerase chain reaction. the deduced protein of 341 amino acids conserves residues that are important for the function of serine/threonine protein kinases and shows the highest homology to capk[c]s of other organisms. however, p. yoelii capk[c] has 8 residues, which are perfectly conserved in capk[c]s of other ...19957578264
humoral response to a carboxyl-terminal region of the merozoite surface protein-1 plays a predominant role in controlling blood-stage infection in rodent malaria.the developmental stages of malaria parasites that infect e are responsible for the morbidity and mortality associated with this disease. one of the leading candidates for a blood-stage vaccine against malaria is a surface protein of merozoites, the infectious stages for e, designated merozoite surface protein-1 (msp-1). the rodent malarial parasite plasmodium yoelii yoelii (py) has provided a model system for the study of this ag, and previous studies from our laboratory had demonstrated that t ...19957602100
antimalarial effects of c18 fatty acids on plasmodium falciparum in culture and on plasmodium vinckei petteri and plasmodium yoelii nigeriensis in vivo.following the demonstration of the antimalarial effect of the long chain saturated alcohol n-hentriacontanol ((ch2)29ch2oh), isolated from the bolivian endemic solanaceous plant cuatresia sp., we have tested the effect of the c18 fatty acids oleic, elaidic, linoleic, and linoleic on malaria parasites. these fatty acids inhibited the parasitemic development in mice infected with plasmodium vinckei petteri or with plasmodium yoelii nigeriensis in a 4-day suppressive test. to gain a deeper discernm ...19957628573
induction of protective polyclonal antibodies by immunization with plasmodium yoelii circumsporozoite protein multiple antigen peptide vaccine. 19957636221
complexity of the cytokine and antibody response elicited by immunizing mice with plasmodium yoelii circumsporozoite protein plasmid dna.the number, type, and location of cytokine- and ab-secreting cells activated in mice immunized and boosted with plasmid dna encoding the circumsporozoite protein of the malarial parasite plasmodium yoelii (pycsp) were monitored. the initial humoral response was localized to the draining lymph nodes and was characterized by production of igg1 anti-pycsp abs and the th2 cytokine il-4. in contrast, the secondary response was dominated by ifn-gamma production (a th1 cytokine) and the secretion of ig ...19957636255
dietary fish oils and long-term malaria protection in mice.previous studies indicate a suppressive influence of fish oils on rodent malaria. the present work was carried out to study (i) the dose-effect relation between dietary fish oils and lethality of primary malaria infection in mice; (ii) the modifying influence of vitamin e; and (iii) the effect of previous fish oil feeding on parasitemia and lethality of a rechallenge infection. for two or four weeks, groups of weanling male mice were fed a standard laboratory diet or one of eight purified diets ...19957637564
multiple genes code for high-molecular-mass rhoptry proteins of plasmodium yoelii.we have examined the number of genes coding for a group of high-molecular-mass rhoptry protein(s) in the malaria parasite plasmodium yoelii, and studied variation in the gene family within the parasite's genome. a region of the genes was amplified using oligonucleotides based on conserved dna sequences and the products cloned. the sequences could be divided into 7 groups by restriction-fragment-length polymorphism. further variation was detected by sequence analysis; 11 different sequences were ...19957637695
estimation of the time required by the malaria parasites to cross the digestive tract to reach blood in mice inoculated by the oral route.in a previous report we described the transmission of the malaria parasites by the oral route in a murine model. later, we performed some experiments to demonstrate the transmission of malaria infection by cannibalism. now we commence to look for the site, mechanism and stages of the parasite involved in crossing the alimentary canal to reach blood and start the infection. to know the invasive stage of the parasite and the way it penetrates, we wanted first to find the level of the digestive tra ...19947637998
murine complement reduces infectivity of plasmodium yoelii to mosquitoes.the alternative pathway of complement in the mouse serum significantly reduced, but did not eliminate, the infectivity of plasmodium yoelii to anopheles stephensi. the reduction of the infectivity is mainly due to the inability of the zygote to transform into the ookinete in the mosquito midgut.19957642309
effector functions of circumsporozoite peptide-primed cd4+ t cell clones against plasmodium yoelii liver stages.previously, cd4+ t cell lines and clones were isolated after immunization of balb/c and c57bl/6 mice with the py1 peptide, a 21-mer synthetic peptide corresponding to a n-terminal segment of the circumsporozoite protein of plasmodium yoelii. the clones were separated into the th1 and th2 subsets on the basis of lymphokine production. it was observed that immunization with the py1 peptide induced preferentially th1 cells in balb/c and th2 cells in c57bl/6 mice. these clones were then tested for t ...19937679428
synthetic peptides based on conserved plasmodium falciparum antigens are immunogenic and protective against plasmodium yoelii malaria.two synthetic polypeptides containing multiple b- and t-cell epitopes derived from the conserved regions of two vaccine candidate antigens namely msa-1 and resa of human malarial parasite p. falciparum were studied for immunogenicity and protectivity. both constructs elicited strong antibody and lymphocyte proliferation responses in balb/c mice immunized with the carrier-free peptides. in an elisa, these peptides also bound antibodies present in the sera from the p. vivax infected humans as well ...19937685076
priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces cd8+ t-cell-mediated protective immunity against malaria.live vectors expressing foreign antigens have been used to induce immunity against several pathogens. however, for the virulent rodent malaria parasite plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. we generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of p. yoelii known to be recognized by cd8+ t cells and demonstrated ...19937685119
immunization with the malaria heat shock like protein hsp70-1 enhances transmission to the mosquito.mosquitoes fed on mice infected with plasmodium yoelii after an immunization with the i72 recombinant form of the heat shock protein hsp70-1 developed significantly more oocysts than mosquitoes fed on controls. this effect was due to a marked increase in the relative numbers of gametocytes during the early stages of infection. a comparison of blood-induced and sporozoite-initiated infection showed that these gametocytes were derived from merozoites released from the liver. the stimulus for incre ...19957718511
plasmodium yoelii: 17-kda hepatic and erythrocytic stage protein is the target of an inhibitory monoclonal antibody.infected hepatocytes are important targets for malaria vaccines. to identify plasmodium yoelii proteins expressed in infected hepatocytes, we immunized balb/c byj mice with p. yoelii liver stage schizonts and produced a panel of monoclonal antibodies (mabs). an igg1 mab, navy yoelii liver stage 3 (nyls3), had the strongest reactivity against liver stage parasites and was selected for further characterization. the mab does not recognize p. yoelii sporozoites, but recognizes liver stage parasites ...19957729477
partial protection against malaria by immunization with leishmania enriettii expressing the plasmodium yoelii circumsporozoite protein.since infection with leishmania species induces cd4+ and cd8+ anti-leishmania t cells, we assessed protection against malaria by immunization with leishmania enriettii transfected with the gene encoding the plasmodium yoelii circumsporozoite protein (pycsp). the recombinant plasmid appeared to be a circular episome in the host cells. reverse transcription pcr showed that the pycsp was trans-spliced by the addition of the 39-bp spliced leader of l. enriettii at its 5' end. the transfectant expres ...19957770079
malaria-induced reduction of fecundity during the first gonotrophic cycle of anopheles stephensi mosquitoes.anopheles stephensi mosquitoes which had fed upon mice infected with plasmodium yoelii nigeriensis malaria parasites produced significantly fewer eggs than mosquitoes fed on an uninfected mouse. fecundity reduction was more pronounced when the bloodmeal contained malaria gametocytes and the mosquitoes developed oocysts. egg production and haematin excretion were correlated for uninfected bloodfed mosquitoes; the presence of p.y.nigeriensis in the blood affected this relationship. reduced fecundi ...19957787226
sequence of the gene encoding the n-terminal portion of the plasmodium yoelii yoelii 17xl merozoite surface protein-1 (msp-1).the nucleotide (nt) sequence of the 5' portion of the gene encoding the plasmodium yoelii yoelii (pyy) 17xl merozite surface protein-1 (msp-1) was determined by direct sequencing of both strands of the polymerase chain reaction (pcr) product. this report completes the entire coding region of the pyy 17xl msp-1 gene which we have found to be identical to the nt sequence of the pyy ym msp-1 [lewis, mol. biochem. parasitol. 36 (1989) 271-282], despite independent selection of parasite clones, passa ...19947828902
characterization of liver lymphomyeloid cells in mice infected with plasmodium yoelii sporozoites.we have isolated, characterized and quantified the immunocompetent cells present in the extravascular hepatic compartment at various stages after plasmodium yoelii malaria infection with sporozoites. cytological analyses revealed a predominantly lymphoid population. in mice with a primary infection, the predominant cells were cd4+, cd8+ and b lymphocytes. in fully protected mice, cd3+ cd4- cd8- and polymorphonuclear cells, particularly eosinophils, were most common. the significance of changes i ...19947835930
induction of long-lasting immunity to plasmodium yoelii malaria with whole blood-stage antigens and copolymer adjuvants.we previously reported that protection of mice from nonlethal plasmodium yoelii malaria by immunization with whole killed blood-stage parasites was dependent on the adjuvant and that adjuvants influenced both the specificity and isotype of ab. additional studies with the most effective formulations were undertaken to better define the protective responses and 100% protection from lethal p. yoelii malaria was produced by three immunizations with ag in copolymer p1004 and detoxified ralps as adjuv ...19957836760
plasmodium yoelii in mice: differential induction of cytokine gene expression during hyporesponsiveness induction and restimulation.acute plasmodium yoelii murine malaria is associated with a marked depression of splenic t cell responses. the present study was undertaken to address the question if a defect in t cell proliferation results from a relative increase of a non-t cell population in the spleen or real biological changes occurring in t cells of the spleen after infection. when animals were acutely infected, the splenic cells responded poorly to cross-linked anti-cd3 mab, con a, and pwm stimulation. at this stage, a v ...19957842488
induction of protective polyclonal antibodies by immunization with a plasmodium yoelii circumsporozoite protein multiple antigen peptide vaccine.monoclonal abs against the repeat region of the circumsporozoite protein (csp) completely protect mice against plasmodium yoelii (py), but synthetic peptide and recombinant protein vaccines designed to produce only abs to the pycsp repeat region have never been reported to consistently provide protection. this lack of protection in the rodent model system has predicted the poor protection achieved in humans after immunization with synthetic peptide and recombinant protein p. falciparum csp vacci ...19957876549
protection against malaria by immunization with a plasmodium yoelii circumsporozoite protein nucleic acid vaccine.nucleic acid vaccines provide an exciting new alternative approach to developing the multiantigen vaccines designed to induce protective antibody and t-cell responses against plasmodium proteins that many experts believe will be required for effective protection against malaria. as a first step in this process, we produced a plasmid dna vaccine that includes the gene encoding the p. yoelii circumsporozoite protein (pycsp). this vaccine induced higher levels of antibodies and cytotoxic t lymphocy ...19947879419
blood-stage malaria infection in diabetic mice.infection of mice with blood-stage plasmodium yoelii and p. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (stz). injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in stz-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of stz) remained hyperglycaemic with no ...19957882567
the relative contribution of antibodies, cd4+ and cd8+ t cells to sporozoite-induced protection against malaria.protective immunity against plasmodium yoelii, induced by sporozoite immunization, was investigated using a quantitative method based on the measurement of plasmodial ribosomal rna in the liver of sporozoite-challenged mice. the relative importance of the different immune mechanisms induced by sporozoite immunization was determined by evaluating quantitatively the anti-parasite activity of antibodies, cd4+ and cd8+ t cells. the role of antibodies was determined by passive transfer of immune sera ...19937902331
immunity to erythrocytic stages of malarial parasites.in those individuals who live in endemic areas, immunity to malaria is slow to develop and stage-specific. the nature and antigenic specificity of this response, which may involve components of both cell-mediated and humoral immunity, is not well understood. rodent models provide useful systems to explore the spectrum of host responses that may contribute to resolution of erythrocytic-stage infection or possibly to pathogenesis. moreover, these models allow identification of plasmodial molecules ...19947909653
intrasplenic immunization with infected hepatocytes: a mouse model for studying protective immunity against malaria pre-erythrocytic stage.malaria liver forms are the target of antibody or t-cell-mediated immune mechanisms induced by previous or subsequent developmental stages of the parasite. the potential for vaccine development of antigens expressed exclusively in the liver stages has not been fully explored partly because of the lack of an experimental animal model. here we show that protective immunity against sporozoite-induced infection with plasmodium yoelii and p. berghei can be obtained by intrasplenic injection of a smal ...19947913914
sporogonic development of plasmodium yoelii in five anopheline species.sporogonic development of plasmodium yoelii yoelii 17xnl was examined in 5 species of anopheles mosquitoes; a. albimanus, a. dirus, a. freeborni, a. gambiae, and a. stephensi. the kinetics of ookinete formation differed among species. in a. freeborni, a. gambiae, and a. stephensi, mature ookinetes formed synchronously at 8 hr, then quickly subsided. in a. albimanus and a. dirus, ookinete formation was more protracted, and ookinete densities peaked from 12 to 24 hr. losses in parasite abundance d ...19947931901
in vitro survival and retention of infectivity of plasmodium yoelii sporozoites over extended periods of time.the ability to maintain sporozoites in vitro should render the biological mechanism of sporozoite infectivity amenable to experimental analysis. with this in mind, plasmodium yoelii py17x(nl) clone 1.1 sporozoites were incubated at 4, 24, or 37 c for 0, 8, or 24 hr in tissue culture medium m199 with 5% normal mouse serum and penicillin-streptomycin. balb/c mice were challenged intravenously with 5,000 in vitro-incubated sporozoites and then evaluated daily for parasitemia beginning on day 3 post ...19947931920
a gene coding for a high-molecular mass rhoptry protein of plasmodium yoelii.we describe the deduced amino acid sequence for a gene encoding a high molecular mass rhoptry protein of plasmodium yoelii. the sequence was obtained from an ecori genomic clone that overlaps a short drai fragment isolated previously. the open reading frame consists of 2294 codons and putative hydrophobic signal and membrane anchor sequences were identified. similarity with sequence from a clone coding for part of a plasmodium vivax reticulocyte-binding protein was noted. based on the sequence a ...19947935623
protection against malaria by immunization with plasmid dna encoding circumsporozoite protein.immunization with irradiated sporozoites protects animals and humans against malaria, and the circumsporozoite protein is a target of this protective immunity. we now report that adjuvant-free intramuscular injection of mice with plasmid dna encoding the plasmodium yoelii circumsporozoite protein induced higher levels of antibodies and cytotoxic t lymphocytes against the p. yoelii circumsporozoite protein than did immunization with irradiated sporozoites. mice immunized with this vaccine had an ...19947937907
interleukin 12 induction of interferon gamma-dependent protection against malaria.intraperitoneal injection of recombinant interleukin 12 (ril-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge or administration of a single dose of 150 ng of ril-122 days before challenge protected 100% of balb/c mice against challenge with 10(2) plasmodium yoelii sporozoites. ril-12-induced protection was eliminated in all mice by administration of a monoclonal antibody against interferon gamma and in 50% of mice by administration of ng-monomethyl-l-arginine, a comp ...19947938013
plasmodium yoelii: brefeldin a-sensitive processing of proteins targeted to the rhoptries.we have shown that a family of high-molecular-mass proteins can be detected in lysates of parasitized erythrocytes using antibodies specific for a plasmodium yoelii rhoptry protein. when these polypeptides are biosynthetically labeled in the presence of brefeldin a or at 15 degrees c, their electrophoretic mobility on polyacrylamide gels is decreased. removal of the drug restores the size of the polypeptides to that in the absence of the drug. these results indicate that the proteins undergo a p ...19947957749
in vitro development of infectious liver stages of p. yoelii and p. berghei malaria in human cell lines.the preerythrocytic stages of the malaria parasite are the focus of intense efforts to identify new immunological and pharmacological methods for the control of the malaria parasite. the study of the malaria hepatic stages requires an in vitro system to facilitate the analysis of parasite/host cell interactions and the characterization of exoerythrocytic form (eef) antigens. at the present time, only the rodent malaria, plasmodium berghei, and the human malaria, plasmodium vivax, develop into ma ...19947957756
anaemia and resistance to malaria in transgenic mice expressing human tumour necrosis factor.transgenic mice carrying a modified human tumour necrosis factor (hutnf)/beta-globin gene construct linked to the t-cell-specific locus control region of the human cd2 gene express hutnf in their t cells which is released into the circulation and causes the development of a wasting syndrome. we now report that the mice develop anaemia, probably through enhanced erythrophagocytosis rather than inhibition of reticulocyte production. thus autologous erythrocytes, as well as sheep erythrocytes, were ...19947959874
efficacy of azithromycin as a causal prophylactic agent against murine malaria.the efficacy of the newly marketed azalide azithromycin was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria. drug was administered once; plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined. for parenterally administered drug, 160 mg of azithromycin or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective. o ...19947986022
immunotoxicity of mono-nitrotoluenes in female b6c3f1 mice: i. para-nitrotoluene.para-nitrotoluene (p-nitrotoluene) is used primarily as an intermediate in the production of various dyes, explosives, pharmaceuticals, and in the production of rubber and agricultural products. previous investigations indicated that p-nitrotoluene was mutagenic in the ames test and that other mono-substituted nitrotoluenes bound covalently to hepatic macromolecules. the objective of these studies was to evaluate the potential immunotoxicity of p-nitrotoluene in mice exposed by the oral route. m ...19947988386
immunotoxicity of mono-nitrotoluenes in female b6c3f1 mice: ii. meta-nitrotoluene.the nitrotoluenes are chemicals used in dyes, agricultural products, pharmaceuticals and explosives. in the present studies, the toxicology and immunotoxicity of meta-nitrotoluene (m-nitrotoluene) were evaluated. mice, exposed to m-nitrotoluene at dose levels of 200, 400 and 600 mg/kg/body weight for 2 weeks by gastric gavage, gained body weight over the treatment period to a slightly greater extent than the control groups. of the selected organs weighed, the liver and kidney of mice exposed to ...19947988387
complete protection against plasmodium yoelii by adoptive transfer of a cd8+ cytotoxic t-cell clone recognizing sporozoite surface protein 2.balb/c mice immunized with irradiated plasmodium yoelii sporozoites produce antibodies and cytotoxic t lymphocytes against the circumsporozoite protein and against a 140-kda protein, sporozoite surface protein 2 (pyssp2). approximately 50% of mice immunized with p815 cells transfected with the gene encoding pyssp2 are protected against malaria, and this protection is reversed by in vivo depletion of cd8+ t cells. to determine if cd8+ t cells against pyssp2 are adequate to protect against malaria ...19948005684
[effects of four drugs on intraerythrocytic plasmodium yoelii of early and late stages].erythrocytes of mice infected with plasmodium yoelii of early stage (esp) were separated from those infected with late stage (lsp), by a single density-gradient centrifugation in 19% diatrizoate meglumine. after centrifugation, the differential counts of esp and lsp were 84.9% and 87.4%, respectively. the stage-dependent effects of nitroquine (nq), pyrimethamine (pyr), perphenazine (per) and metronidazole (met) were studied with [3h]adenosine incorporation into esp and lsp in vitro using chloroq ...19938010072
immunization against malaria with a recombinant protein.we have expressed in bacteria the c-terminal part of plasmodium yoelii merozoite surface protein-1 (msp1) containing the two epidermal growth factor-like domains. the protein, either alone or fused to glutathione s-transferase, was highly effective as a vaccine and protected mice against challenge infection. reduction and alkylation abolished the protection obtained with the protein. this shows for the first time the absolute requirement of the disulphide-bonded conformation for immunogenicity. ...19948015856
neuropathological studies on plasmodium yoelii nigeriensis-induced malaria in mice.malaria infection in mice was produced by intraperitoneal inoculation of 10(6) erythrocytes parasitized with plasmodium yoelii nigeriensis, a virulent strain of murine malaria. about one week after infection parasitaemia ranged between 60 and 80%, and 100% mortality was observed. infected animals were killed 6 days after infection to allow the examination of brain tissue. electron microscopical observations revealed marked damage to cerebral vascular vessel walls with separation of muscular laye ...19948040397
nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin.expression of inducible nitric oxide (no) synthase has been shown to inhibit the development of several pathogens, including fungi, bacteria, parasites, and viruses. however, there is still controversy as to whether this effector mechanism can inhibit the development of human pathogens. we now report that gamma interferon (ifn-gamma) induces the elimination of plasmodium falciparum-infected primary human hepatocytes from cultures and that the antimalarial activity is dependent on no. infection w ...19948063424
plasmodium yoelii in mice: antigen reactivity of cd4- and cd8-bearing t cells.mice infected with plasmodium yoelii (265 by, a nonlethal strain) after recovering from parasitemia become resistant to reinfection. in the present study, we have attempted to define the role of t cell subsets in primary vs secondary p. yoelii infection. we have evaluated the in vivo effects of selective depletion of each subset of t cells on the course of infection and also investigated the in vitro expansion of each subset in response to homologous antigen. depletion of cd4- or cd8-bearing t c ...19938102089
the role of cd4+ t cells in immunity to malaria sporozoites.balb/c mice are strongly protected against malaria after immunization with plasmodium yoelii (py) sporozoites, and this is an important model for malaria vaccine development in humans. this paper explores the role of cd4+ cells in the induction of the antimalarial immune response. the method used has been to treat animals with anti-cd4 mab before immunization, resulting in a profound depletion of cd4+ t cells. the primary finding is that mice are not protected by sporozoite immunization after de ...19938103069
t-cell recognition of a cross-reactive antigen(s) in erythrocyte stages of plasmodium falciparum and plasmodium yoelii: inhibition of parasitemia by this antigen(s).in the current study, we investigated the presence of a cross-reactive antigen(s) in the erythrocyte stage from plasmodium yoelii (265 by strain) and plasmodium falciparum through recognition by t cells primed in vivo with antigens from each of these parasites. balb/c mice are naturally resistant to p. falciparum but are susceptible to p. yoelii infection. mice that had recovered from p. yoelii primary infection became resistant to a second infection. a higher in vitro proliferative response to ...19938104901
in vitro and in vivo chloroquine-potentiating action of strychnos myrtoides alkaloids against chloroquine-resistant strains of plasmodium malaria.crude alkaloids of strychnos myrtoides gilg & busse, empirically used as an adjuvant to chloroquine (cq) in malagasy herbal remedies, were practically devoid of intrinsic in vitro and in vivo antimalarial activity. however, when combined with cq at a dose level much lower than their ic50 value, they markedly enhanced in vitro the effectiveness of the synthetic drug against a cq-resistant strain of plasmodium falciparum. they also enhanced in vivo cq activity against a resistant strain of plasmod ...19948134408
alterations of uninfected red blood cells in malaria.red blood cell (rbc) negative charges and resistance to linoleic acid (lna)-induced lysis were studied in plasmodium yoelii-infected mice and in malaria (p. falciparum)-affected individuals. rbcs from mice infected with p. yoelii showed a progressive decrease in the net surface negative charges at 24 h after infection, reaching a minimal value on day 3, followed by a second phase that was characterised by a recovery to normal levels on day 6. resistance to linoleic acid follows similar kinetics. ...19948153129
[schizogony of plasmodium yoelii nigeriensis. role of latent merozoites].several procedures were employed to try to specify the schizogonic cycle of plasmodium yoelii nigeriensis. the percoll-glucose gradient technique for concentrating the very young stages (rings and young trophozoites), allowing a very precise follow up of the development of the parasitaemia during the first schizogonic cycles. a method for studying the prepatencies, providing an approximation of the number of merozoites inoculated. a comparison between the numbers of merozoites present in the blo ...19938154783
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