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plasmodium berghei: in vivo efficacy of albendazole in different rodent models. 19989538870
antimalarial activity of radicicol, heptelidic acid and other fungal metabolites.in the course of our screening program for artemisinin-like antimalarial compounds from microorganisms, seven fungal metabolites such as radicicol and heptelidic acid were identified as active compounds. some of them exhibited antimalarial activity in vitro against the human malaria parasite plasmodium falciparum to the extent of approximately 1/10 as potent as artemisinin. radicicol was moderately active in vivo against plasmodium berghei in mice.19989544936
enhanced immunogenicity for cd8+ t cell induction and complete protective efficacy of malaria dna vaccination by boosting with modified vaccinia virus ankara.immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. a particular sequence of subunit immunization with pre-erythrocytic antigens of plasmodium berghei, consisting of single dose priming with plasmid dna followed by a single boost with a recombinant modified vaccinia virus ankara (mva) expressing the same antigen, induced unprecedented complete protection against p. berghei sporozoite chal ...19989546783
immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from plasmodium berghei malaria parasites.the circumsporozoite protein (csp) is a target for effector ab and cell mediated immunity against malaria parasites; dna vaccination can induce both types of effector response. the immunogenicity and efficacy of two dna plasmids expressing different amounts of plasmodium berghei csp were evaluated by immunizing balb/c mice i.m. or epidermally and by varying the number of immunizations (one to three doses) and the interval between immunizations. expanding the interval gave the strongest effect, i ...19979550412
dysregulation of cytokine expression in tubulointerstitial nephritis associated with murine malaria.we examined the circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (tnf-alpha), interleukin (il)-1 alpha, il-6, granulocyte macrophage-colony stimulating factor (gm-csf), and the anti-inflammatory cytokine il-10, and their expression in kidneys acutely infected with murine malaria parasite p. berghei anka in c57bl/6j mice. groups of six mice sacrificed on days 5, 10, 15, and 20, and normal controls were used for cytokine analysis. high concentrations of tnf-alpha and ...19989551390
reduced t helper 1 responses in il-12 p40 transgenic mice.to investigate the antagonistic effect of il-12 p40 on il-12 activity in vivo, we generated transgenic (tg) mice in which p40 gene was regulated by a liver-specific promoter. three tg mouse lines were generated, and they expressed the p40 transgene predominantly in liver. serum p40 level was extremely high, and it consisted of mainly monomer and homodimer and also of higher m.w. complexes. these tg mice did not show any apparent phenotypic difference from control littermates in lymphoid cells. e ...19989551892
rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (dhfr-ts). resistance in the most important human parasite, plasmodium falciparum, initially results from an s108n mutation in the dhfr domain, with additional mutation (most commonly c59r or n51i or both) imparting much greater resistance. from a homology model of the 3-d structure of dhfr-ts, rational drug design techniques have been used to design and subsequently synthesize inhibitors able to o ...19989554869
the mosquito anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide.we have discovered that the mosquito anopheles stephensi, a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (no). elevated expression of a. stephensi no synthase (nos), which is highly homologous to characterized nos genes, was detected in the midgut and carcass soon after invasion of the midgut by plasmodium. early induction is likely primed by bacterial growth in the blood meal. later increases in a. stephensi nos expression and enzyme acti ...19989576947
glutathione peroxidase (ec 1.11.1.9) and superoxide dismutase (ec 1.15.1.1) activities in riboflavin-deficient rats infected with plasmodium berghei malaria.riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. the objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (ec 1.11.1.9; gpx) and superoxide dismutase (ec 1.15.1.1; sod) in rats infected with plasmodium berghei malaria. riboflavin in its co-enzyme form, fad, is required by glutathione reductase (ec 1.6.4.1) to regenerate gsh and gsh is an important ...19989577309
isolation and analysis of nephritic-producing immune complexes in plasmodium berghei-infected mice.a nephritic condition was developed by infecting swiss webster albino mice with the malarial parasite plasmodium berghei nk 65. these animals were tested for urinary protein and the presence of circulating immune complexes using reagent strips and a polyethylene glycol (peg) precipitation assay. the circulating immune complexes were isolated from the sera using both affinity chromatography and peg precipitation and from the kidney by acid elution. the isolated complexes were dissociated into the ...19959583966
antimalarial and cytotoxic potential of four quassinoids from hannoa chlorantha and hannoa klaineana, and their structure-activity relationships.hannoa chlorantha and hannoa klaineana (simaroubaceae) are used in traditional medicine of central african countries against fevers and malaria. four stem bark extracts from h. klaineana and four quassinoids from h. chlorantha were examined in vitro against plasmodium falciparum nf 54. the extracts displayed good activities, while the quassinoids were highly active, with ic50 values well below 1 microgram ml-1, those of chaparrinone and 15-desacetylundulatone being much lower than 0.1 microgram ...19989602388
high-level chloroquine resistance of plasmodium berghei is associated with multiple drug resistance and loss of reversal by calcium antagonists.the chloroquine resistance of plasmodium falciparum is reversed in vitro by numerous compounds, including calcium antagonists, which could enhance the accumulation of the drug in the parasite food vacuole. however, this mechanism of resistance could be insufficient when the resistance level increases. using in vitro drug trials on strains of plasmodium berghei displaying various chloroquine-resistance levels, we confirmed previous results obtained in vivo in the chloroquine-resistant strains of ...19989602389
a pathogenic role of il-12 in blood-stage murine malaria lethal strain plasmodium berghei nk65 infection.we studied whether the infection with a blood-stage murine malaria lethal plasmodium berghei nk65 induces il-12 production, and if so, how the il-12 production is involved in the protection or pathogenesis. the infection of c57bl/6 mice enhanced mrna expression of il-12 p40 and also ifn-gamma, il-4, and il-10 in both spleen and liver during the early course of the infection. it also enhanced the mrna expression of tnf-alpha, fas ligand, and cytokine-inducible nitric oxide synthase. increased il- ...19989605153
interleukin-12-dependent mechanisms in the clearance of blood-stage murine malaria parasite plasmodium berghei xat, an attenuated variant of p. berghei nk65.the mechanism of development of host resistance to blood-stage malarial infection was studied by use of an irradiation-induced attenuated variant, plasmodium berghei xat, obtained from a lethal strain, p. berghei nk65. the infection enhanced mrna expression of interleukin (il)-12 p40 and also of interferon (ifn)-gamma, il-4, il-10, and cytokine-inducible nitric oxide synthase (inos) in spleen. treatment of these mice with anti-il-12 or anti-ifn-gamma led to the progression of parasitemia and fat ...19989607848
[ca++ ion transport blockers as reversants of the drug resistance of malarial parasites. 2. the effect of praziquantel on the resistance to chloroquine and compound r-70-zh of plasmodium berghei].the reversing action of anthelminthic praziquantel (p) on the effect of chloroquine (c) and compound r-70-zh (styrylquinazoline) was revealed on a plasmodium berghei model (white inbred mice), using a lnk65 isolate with naturally reduced sensitivity to chloroquine and its polyresistant line lnk65chlfr with acquired resistance to chloroquine/fansidar (selected in our laboratory). p (125 mg/kg) in combination with c showed a potentiating effect not only on the lnk65 isolate, but also on the lnk65c ...19989608206
precise timing of expression of a plasmodium falciparum-derived transgene in plasmodium berghei is a critical determinant of subsequent subcellular localization.the development of transfection technology for malaria parasites holds significant promise for a more detailed characterization of molecules targeted by vaccines or drugs. one asexual blood stage vaccine candidate, apical membrane antigen-1 (ama-1) of merozoite rhoptries has been shown to be the target of inhibitory, protective antibodies in both in vitro and in vivo studies. we have investigated heterologous (trans-species) expression of the human malaria plasmodium falciparum ama-1 (pf83/ama-1 ...19989614123
mortality and platelet depletion occur independently of fibrinogen consumption in murine models of tumour necrosis factor-mediated systemic inflammatory responses.tumour necrosis factor (tnf) is known to have procoagulant activity, and platelet depletion is a feature of tnf-mediated systemic inflammatory responses. the aim of this study was to investigate the role of fibrinogen consumption in the development of tnf-mediated systemic inflammatory responses and in the associated depletion of platelets. three murine models of tnf-mediated systemic inflammatory responses were examined: the systemic toxicity reactions (str) induced by tnf or lipopolysaccharide ...19989619377
transgenic mice with elevated level of cuznsod are highly susceptible to malaria infection.copper/zinc superoxide dismutase (cuznsod) catalyses the conversion of o2.- into h2o2. constitutive overexpression of cuznsod in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. in this study, we used transgenic cuznsod (tg-cuznsod) mice with elevated levels of cuznsod to determine whether overexpression of cuznsod affected the susceptibility of these mice to plasmodium infection. acute malaria is associated with oxidative stress, mediated by redox ...19989641269
novel aryl-bis-quinolines with antimalarial activity in-vivo.three rationally designed isomeric aryl-bridged bis-quinolines, n1,nx-bis(7-chloroquinolin-4-yl)phenylene-1,x-diamines, where x=2, 3 or 4, i.e. o-, m- and p-substituted analogues respectively, were synthesized and evaluated against plasmodium berghei in-vivo. the compound with x=2 had an id50 of 30 mg kg(-1), whereas the p-substituted analogue (x=4) was not statistically schizonticidal at either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg kg(-1), id50=60 mg kg(-1) ...19989643441
novel quinone methides from salacia kraussii with in vitro antimalarial activity.three novel quinone methides, i.e., 28-nor-isoiguesterin-17-carbaldehyde (1), 17-(methoxycarbonyl)-28-nor-isoiguesterin (2), and 28-hydroxyisoiguesterin (3), together with the known celastrol (5), pristimerin (6), and isoiguesterol (7), were isolated from the roots of salacia kraussii (celastraceae) by bioassay-guided fractionation. the structures of the compounds were determined by dept and 2d nmr techniques. the isolates showed antimalarial activity 30-50-fold greater than their cytotoxicity ( ...19989644053
liver ultrastructural pathology in mice infected with plasmodium berghei.as liver can be an important target organ in malaria, we performed an ultrastructural study of hepatic alterations in the final stage of plasmodium berghei infection in mice. significant hepatocyte abnormalities were found. an elevated number of cells showed mitochondria with a high electron-dense matrix and multiple changes in shape and size, alterations in the structure of golgi complex, swelling and disorganisation of both rough and smooth-surfaced endoplasmic reticulum, differently shaped pe ...19989648294
transforming growth factor beta production is inversely correlated with severity of murine malaria infection.we have examined the role of the immunomodulatory cytokine transforming growth factor (tgf)-beta in the resolution and pathology of malaria in balb/c mice. circulating levels of tgf-beta, and production of bioactive tgf-beta by splenocytes, were found to be low in lethal infections with plasmodium berghei. in contrast, resolving infections with p. chabaudi chabaudi or p. yoelii were accompanied by significant tgf-beta production. a causal association between the failure to produce tgf-beta and t ...19989653082
granulocyte-macrophage colony-stimulating factor production by t lymphocytes in plasmodium berghei-infected mice.the production of granulocyte-macrophage colony-stimulating factor (gm-csf) by lymphocytes was examined in murine malaria. when spleen cells or lymph node cells from p. berghei-infected mice were cultured in vitro with malaria antigen, the gm-csf production correlated with the incubation time up to 72 hours. when lymphocytes obtained at various days after infection were cultured with the antigen, gm-csf became detectable as early as 2 days after infection, reached a peak at day 9 and then rapidl ...19979656399
the complete sequence of plasmodium berghei merozoite surface protein-1 and its inter- and intra-species variability.the complete gene for merozoite surface protein-1 (msp-1) from plasmodium berghei has been cloned and sequenced. comparison of the p. berghei msp-1 sequence with msp-1 from other rodent parasites reveals five conserved domains interrupted by four variable blocks. these variable blocks exhibit no sequence homology but do have similar amino acid compositions. primary proteolytic processing sites are located near the boundaries between the conserved domains and the variable blocks. sequencing of th ...19989662027
characterization of a subpopulation of mouse red blood cells as preferential target for malarial invasion.cell electrophoresis was used to study a distinct subpopulation of murine red blood cells (rbc). these rbc are normally found in the spleen and bone marrow. they appear in the peripheral blood when mice are mildly bled or sucked by mosquitos. these cells have been characterized as having larger size, light density, lower electrophoretic mobility, and being more resistant to lysis with unsaturated fatty acids and in glycerol-containing medium than mature erythrocytes. all their features suggest t ...19989662186
malaria circumsporozoite protein inhibits protein synthesis in mammalian cells.native plasmodium circumsporozoite (cs) protein, translocated by sporozoites into the cytosol of host cells, as well as recombinant cs constructs introduced into the cytoplasm by liposome fusion or transient transfection, all lead to inhibition of protein synthesis in mammalian cells. the following findings suggest that this inhibition of translation is caused by a binding of the cs protein to ribosomes. (i) the distribution of native cs protein translocated by sporozoites into the cytoplasm as ...19989669999
the efficiency of antigen recognition by cd8+ ctl clones is determined by the frequency of serial tcr engagement.using h-2kd-restricted ctl clones, which are specific for a photoreactive derivative of the plasmodium berghei circumsporozoite peptide pbcs(252-260) (syipsaeki) and permit assessment of tcr-ligand interactions by tcr photoaffinity labeling, we have previously identified several peptide derivative variants for which tcr-ligand binding and the efficiency of ag recognition deviated by fivefold or more. here we report that the functional ctl response (cytotoxicity and ifn-gamma production) correlat ...19989670927
transgenic expression of a mosquito-stage malarial protein, pbs21, in blood stages of transformed plasmodium berghei and induction of an immune response upon infection.pbs21 is a surface protein of the ookinete of plasmodium berghei, which can induce a potent transmission-blocking immune response. pbs21 is normally expressed only by parasite stages in the mosquito, i.e., female gametes/zygotes, ookinetes, and oocysts. however, the pbs21 gene is transcribed in female gametocytes which circulate in the bloodstream of the host, where translation of the resulting mrna is totally repressed. episomal transfection has been used to investigate whether expression of pb ...19989673276
isolation of merozoite rhoptries, identification of novel rhoptry-associated proteins from plasmodium yoelii, p. chabaudi, p. berghei, and conserved interspecies reactivity of organelles and proteins with p. falciparum rhoptry-specific antibodies.rhoptries were isolated from merozoites of p. yoelii (17 xl), p. chabaudi adami and p. berghei (k-173), using sucrose gradient density centrifugation. mouse antisera was prepared against the organelles and characterized. antibodies specific for a known p. yoelii rhoptry protein were used to identify gradient fractions containing rhoptries and electron microscopy was used to confirm rhoptry enrichment and organelle morphology. western blotting analysis of the gradients with organelle-specific ant ...19989676705
rodent malaria in rats exacerbated by milk protein, attenuated by low-protein vegetable diet.young male wistar rats were fed a purified, vegetable, low-protein diet containing 6% protein from maize gluten and 2% from soy protein isolate, or comparable diets in which maize gluten was replaced partly or completely by the equivalent amount of a milk protein concentrate. diets with adequate protein level (16% or 22%) served as a control. at 21 or 31 days of age, the rats were infected with 3000 or 100000 erythrocytes parasitized with plasmodium berghei. results reported include body weight, ...19989705196
an in vivo model to study the anti-malaric capacity of plant extracts.an in vivo model to study the antimalaric effect of plant extracts is described. white mice (25-30 g body weight) are treated subcutaneously with 0.6 ml of the diluted extract starting seven days before p. berghei infection; treatment continues until death or for 30 days. simultaneously 0.2 ml of the extract are applied per os starting three days before infection. in a test of the model, treated and non-treated animals differed in body weight, survival time, haematocrite, parasitemia development ...19989711350
cloned lines of plasmodium berghei anka differ in their abilities to induce experimental cerebral malaria.infection with plasmodium berghei anka is usually lethal. the parasite causes in some mouse strains a neurovascular syndrome, experimental cerebral malaria (ecm), involving immunopathological reactions. the effects on the development of ecm of the mouse genetic background have been clearly demonstrated, but nothing is known about the effects of the clonal diversity of the parasite. we showed that various cloned lines derived from a polyclonal line of p. berghei anka caused ecm but that the exten ...19989712753
upregulation of major histocompatibility complex (mhc) antigen in nephritis associated with murine malaria infection.the importance of immune complexes in the pathogenesis of malarial nephritis is well established. the expression was studied of major histocompatibility complex (mhc) class i and class ii antigens and the infiltration of inflammatory cells, with their possible roles in cellular immune reactions in the pathogenesis of nephritis in a murine malaria model. thirty-six kidney sections obtained on days 5, 8-10, 15, and 20 from c57bl/6j mice acutely infected with plasmodium berghei and uninfected contr ...19989713350
in situ analysis of adhesion molecule expression in kidneys infected with murine malaria.the expression of intercellular adhesion molecule-1 (icam-1), the ligand leucocyte function antigen-1 (lfa-1, cd11a), and complement receptor type 3 (cr3, or mac-1, cd11b) has been studied in murine kidneys acutely infected with the fatal malaria parasite plasmodium berghei anka. thirty-six kidney sections from five groups of c57bl/6j mice on day 5, 10, 15, and 20 post-infection, and normal controls, were stained with monoclonal antibodies against icam-1, lfa-1, and mac-1. there was markedly enh ...19989713351
picroliv prevents oxidation in serum lipoprotein lipids of mastomys coucha infected with plasmodium berghei.picroliv, an iridoid glycoside mixture from the root and rhizome of picrorhiza kurrooa, at the dose of 6 mg/kg p.o. for two weeks provided significant protection against the generation of lipid peroxidation products in serum beta-lipoproteins of p. berghei infected m. coucha. incubation of normal rat hepatocytes with very low density lipoprotein or low density lipoprotein isolated from infected animals caused significant generation of lipid peroxides followed by a decrease in the viability of th ...19989717447
malaria parasites contain two identical copies of an elongation factor 1 alpha gene.elongation factor 1alpha (ef-1alpha) is an abundant protein in eukaryotic cells, involved chiefly in translation of mrna on the ribosomes, and is frequently encoded by more than one gene. here we show the presence of two identical copies of the ef-1alpha gene in the genome of three malaria parasites, plasmodium knowlesi, p. berghei and p. falciparum. they are organized in a head-to-head orientation and both genes are expressed in a stage specific manner at a high level, indicating that the small ...19989719506
protective role of platelets in chronic (balb/c) and acute (cba/j) plasmodium berghei murine malaria.the role of blood platelets in the pathogenesis of malaria remains unclear. in this study we investigated the role of experimentally caused thrombocytopaenia in chronic (balb/c) and acute (cba/j) plasmodium-berghei-induced murine malaria. a group of 30 balb/c mice were rendered thrombocytopaenic by injection of anti-mouse platelet serum given every 2 days from day 2 to day 8 after malaria infection. compared with the control group, thrombocytopaenic mice showed a greater mortality. the kaplan-me ...19979731108
proteasome inhibitors block development of plasmodium spp.proteasomes degrade most of the proteins inside eukaryotic cells, including transcription factors and regulators of cell cycle progression. here we show that nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the 20s proteasome, inhibit development of the exoerythrocytic and erythrocytic stages of the malaria parasite. although lactacystin-treated plasmodium berghei sporozoites are still invasive, their development into exoerythrocytic forms (eef) is inhibited in vitro ...19989756786
synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin.fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction of fluoroalkyl alcohols with dihydroartemisinin by different methods (bf3,et2o or tmscl catalysis or mitsunobu reaction). ethers 4a-d derived from primary fluoroalkyl alcohols were obtained in moderate to good yields by these methods. ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols and phenol using the mitsunobu reaction. although in vitro antimalarial activities of ethers toward plasm ...19989767645
bisquinolines. 2. antimalarial n,n-bis(7-chloroquinolin-4-yl)heteroalkanediamines.n,n-bis(7-chloroquinolin-4-yl)heteroalkanediamines 1-11 were synthesized and screened against plasmodium falciparum in vitro and plasmodium berghei in vivo. these bisquinolines had ic50 values from 1 to 100 nm against p. falciparum in vitro. six of the 11 bisquinolines were significantly more potent against the chloroquine-resistant w2 clone compared to the chloroquine-sensitive d6 clone. for bisquinolines 1-11 there was no relationship between the length of the bisquinoline heteroalkane bridge ...19989784111
from noxiustoxin to shiva-3, a peptide toxic to the sporogonic development of plasmodium berghei.this communication reviews shortly the main structural and functional characteristics of noxiustoxin, a 39 amino acid residue peptide, maintained closely packed by three-disulfide bridges and its effects on excitable membranes. shiva-3, a cecropin like-peptide composed of 38 amino acid residues is also briefly reviewed. its design and synthesis was made possible by the expertise gained through the work previously performed with noxiustoxin. one of the most prominent functional characteristics of ...19989792185
structural information on a cecropin-like synthetic peptide, shiva-3 toxic to the sporogonic development of plasmodium berghei.this study is a contribution towards the understanding of the mode of action of shiva-3 and more generally that of cecropin-like peptides. structural information on shiva-3 (a cecropin-like synthetic peptide) in water and in a membrane-mimicking environment (trifluoroethanol alcohol, sds) were obtained using analytical centrifugation, cd and nmr spectroscopies. a total of 20 converged structures were retained on the basis of 197 non-redundant experimental constraints, including 166 distance cons ...19989799128
malaria infection of the mosquito anopheles gambiae activates immune-responsive genes during critical transition stages of the parasite life cycle.six gene markers have been used to map the progress of the innate immune response of the mosquito vector, anopheles gambiae, upon infection by the malaria parasite, plasmodium berghei. in addition to four previously reported genes, the set of markers included nos (a nitric oxide synthase gene fragment) and ichit (a gene encoding two putative chitin-binding domains separated by a polythreonine-rich mucin region). in the midgut, a robust response occurs at 24 h post-infection, at a time when malar ...19989799221
characterisation of the cdc2-related kinase 2 gene from plasmodium knowlesi and p. berghei.the complete sequence of the cdc2-related kinase 2 (crk2) gene from plasmodium knowlesi and from p. berghei was determined. in both species, the crk2 gene is closely linked to an elongation factor 1 alpha gene. the two crk2 proteins are highly homologous to the p. falciparum pfpk5 protein. the crk2 gene of both species is expressed at a low level during the asexual cell-cycle within the host erythrocytes. the p. berghei crk2 mrna is also present in gametocytes and in stages during development in ...19989803415
convulsions due to increased permeability of the blood-brain barrier in experimental cerebral malaria can be prevented by splenectomy or anti-t cell treatment.experimental cerebral malaria (ecm) can be induced in c57b1 mice by infection with plasmodium berghei k173 parasites. behavioral changes shortly before they die of ecm may reflect disturbance of the integrity of the blood-brain barrier (bbb). folic acid elicits strong convulsive activity if the permeability of the bbb is increased. administration of folic acid to mice during development of ecm induced convulsions. interventions known to prevent fatal outcome from ecm, such as splenectomy or trea ...19989806067
plasmodium yoelii: identification of rhoptry proteins using monoclonal antibodies.thirteen monoclonal antibodies, obtained after immunization of mice with plasmodium yoelii schizonts, were selected using immunofluorescence assay: they all presented typical fluorescence patterns of rhoptries. this antigen localization was confirmed by immunoelectron microscopy. the molecular weights of the recognized antigens are 68, 80, 105, 130 and 140 kda as determined by immunoprecipitation and immunoblot under reducing and nonreducing conditions. these values are very similar to these of ...19989806867
evidence for multiple pathologic and protective mechanisms of murine cerebral malaria.murine cerebral malaria (cm) induced by plasmodium berghei anka kills susceptible mice within 24 to 48 h of onset of symptoms and is characterized by the production of inflammatory cytokines in the brain. c57bl/6j mice are sensitive to lethal cm, while a/j mice are resistant. these strains of mice were immunized with an adjuvant vaccine of killed whole-blood-stage parasites. the immunization protected c57bl/6 mice from lethal cm following virulent challenge. the same immunization increased the i ...19989826380
a novel antiprotozoal aminosteroid from saracha punctata.a new aminosteroid, 3beta-amino-22,26-epiminocholest-5-ene named sarachine (1), and two known flavonoids, eriodictyol (2) and 7-o-beta-d-glucopyranosyl-eriodictyol (3), were isolated from the leaves of saracha punctata. the alkaloid was found to inhibit the growth of leishmania braziliensis promastigotes (100% at 25 microm) and of trypanosoma cruzi epimastigotes in culture (50% at 25 microm) and showed a strong in vitro antiplasmodial activity with an ic50 of 25 nm.19989834160
blocked hepatic-stage parasites and decreased susceptibility to plasmodium berghei infections in balb/c mice.the balb/c strain of mice is comparatively more resistant to sporozoite infections of plasmodium berghei than the c57bl6 strain. infection with live sporozoites results in the formation of small hepatic forms in the balb/c liver that persist for as long as 6 days. upon infection with small numbers of sporozoites, some of the parasites are destroyed in the liver whereas the rest persist as blocked forms. when larger numbers of sporozoites are injected the same process occurs but, in addition, a f ...19989836306
involvement of macrophage scavenger receptors in protection against murine malaria.macrophage scavenger receptor a (msr-a) deficient mice msr-a(-/-) were infected by the intraperitoneal injection of the plasmodium berghei nk65 strain in the erythrocytic stage. the msr-a(-/-) mice died significantly earlier than the control mice (p=0.060). in the surviving mice, two peaks of parasitemia were observed: the first 5-7 days and the second at 2-3 weeks after infection. death of all msr-a(-/-) mice occurred at either peak of parasitemia, suggesting that msr-a protects mice from sever ...19989840609
are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?to investigate the involvement of oxidative tissue damage in the pathogenesis of murine cerebral malaria (cm), brain levels of protein carbonyls, 3,4-dihydroxyphenylalanine (dopa), o-tyrosine, and dityrosine were measured during plasmodium berghei anka (pba) and p. berghei k173 (pbk) infections. during pba infection in a cm model, brain levels of the substances were similar to those in uninfected mice. the role of phagocyte-derived reactive oxygen species in the pathogenesis of cm was examined i ...19999841842
[utility of gamma rays in prophylaxis of transmissible malaria by blood transfusion].this study was carried out to evaluate the fortuitons advantage of using gamma irradiation in the prophylaxis of transmissible malaria by blood transfusion, with mice as the experimental model. in the first step, when the infected blood with plasmodium berghei was submitted to 2,500 rad and 5,000 rad, with or without metronidazol, there was no success, because the animals presented parasitaemia and died after inoculation of irradiated blood. however, there was partial success in the second step, ...19989859699
differential reactivity of brain microvascular endothelial cells to tnf reflects the genetic susceptibility to cerebral malaria.upon infection with plasmodium berghei anka (pba), various inbred strains of mice exhibit different susceptibility to the development of cerebral malaria (cm). tumor necrosis factor-alpha (tnf) and interferon-gamma (ifn-gamma) have been shown to be crucial mediators in the pathogenesis of this neurovascular complication. brain microvascular endothelial cells (mvec) represent an important target of both cytokines. in the present study, we show that brain mvec purified from cm-susceptible (cm-s) c ...19989862335
protection from plasmodium berghei infection by priming and boosting t cells to a single class i-restricted epitope with recombinant carriers suitable for human use.the desirability of inducing cytotoxic t cell responses to defined epitopes in humans has led to the development of a variety of recombinant delivery systems. recombinant protein particles derived from a yeast retrotransposon (ty) and the modified ankara vaccinia (mva) virus can deliver large epitope strings or even whole proteins. both have previously been administered safely in humans. immunization with recombinant ty and mva containing a single plasmodium berghei class i-binding epitope provi ...19989862371
peptide modification or blocking of cd8, resulting in weak tcr signaling, can activate ctl for fas- but not perforin-dependent cytotoxicity or cytokine production.this study describes a form of partial agonism for a cd8+ ctl clone, s15, in which perforin-dependent killing and ifn-gamma production were lost but fas (apo1 or cd95)-dependent cytotoxicity preserved. cloned s15 ctl are h-2kd restricted and specific for a photoreactive derivative of the plasmodium berghei circumsporozoite peptide pbcs 252-260 (syipsaeki). the presence of a photoactivatable group in the epitope permitted assessment of tcr-ligand binding by tcr photoaffinity labeling. selective a ...19989862728
treatment with liposome-bound recombinant human tumor necrosis factor-alpha suppresses parasitemia and protects against plasmodium berghei k173-induced experimental cerebral malaria in mice.our study describes liposomes (conventional or sterically stabilized) as carrier systems for recombinant human tumor necrosis factor-alpha (rhtnf-alpha) to increase its protective efficacy against plasmodium berghei-induced experimental cerebral malaria (ecm) in mice. rhtnf-alpha was either covalently coupled to the outer surface of preformed liposomes or encapsulated into the liposomes. for coupling to the liposomes, reactive thiol groups were introduced in rhtnf-alpha by reaction with n-succin ...19999862761
[study in the combining quantity of con a-binding sites on membrane surface of artesunate-resistance strain of plasmodium berghei].to study the production mechanism of plasmodium berghei (pb) in resisting artesunate.19979863083
synthesis and antiprotozoal activities of some new triazine derivatives including a new antitrypanosomal agent: sipi-1029.two series of compounds, 1,2-dihydro-2,2-dimethyl-4, 6-diamino-1-(omega-haloalkyloxy)-s-triazines and o, o'-bis (4, 6-diamino-1, 2-dihydro-2, 2-disubstituted-s-triazin-l-yl) alkanediols were synthesized and tested against plasmodium berghei and trypanosoma evansi in mice. most title compounds showed good antimalarial activity and compounds iic-e showed good antitrypanosomal effect. after further studies on pharmacology, toxicology, pharmacokinetics and efficacy on infected cattles compound iie ( ...19969863252
gamma delta t-cell function in pathogenesis of cerebral malaria in mice infected with plasmodium berghei anka.mice depleted of gammadelta t cells by monoclonal antibody treatment and infected with plasmodium berghei anka did not develop cerebral malaria (cm). in striking contrast, delta0/0 mice infected with p. berghei developed cm despite their gammadelta t-cell deficiency. gammadelta t cells appear to be essential for the pathogenesis of cm in mice having experienced normal ontogeny but not in mice genetically deprived of gammadelta t cells from the beginning of life.19999864254
developmental regulation of a plasmodium gene involves the generation of stage-specific 5' untranslated sequences.the b7 gene of plasmodium berghei, highly conserved within the genus plasmodium, encodes a nuclear protein most likely involved in chromatin assembly. in this study we describe the transcription pattern of b7 during asexual multiplication and sexual differentiation of the parasites in the blood of the vertebrate host. two alternative transcripts have been identified: one, 1.4 kb in length is specific for asexual blood stages; the other, 1.8 kb in length is specific for sexually differentiated ce ...19989879886
stable expression of green fluorescent protein in blood and mosquito stages of plasmodium berghei. 19989879905
mosquito-plasmodium interactions in response to immune activation of the vector.during the development of plasmodium sp. within the mosquito midgut, the parasite undergoes a series of developmental changes. the elongated ookinete migrates through the layers of the midgut where it forms the oocyst under the basal lamina. we demonstrate here that if aedes aegypti or anopheles gambiae, normally susceptible to plasmodium gallinaceum and p. berghei, respectively, are immune activated by the injection of bacteria into the hemocoel, and subsequently are fed on an infectious bloodm ...19999920043
plasmodium: immunization with carboxyl-terminal regions of msp-1 protects against homologous but not heterologous blood-stage parasite challenge.a leading candidate for a vaccine targeted at the erythrocytic stages of plasmodial parasite development is the merozoite surface protein-1 (msp-1). we have previously shown that the carboxyl-terminal region of msp-1 derived from plasmodium yoelii yoelii 17xl, expressed as a fusion protein with glutathione s-transferase (gst-pyc2), can immunize mice against an otherwise lethal homologous challenge infection. this protection has been shown to be predominantly mediated by antibodies. we report her ...19999920045
plasmodium berghei: identification of an mdr-like gene associated with drug resistance.amplification, mutations, or overexpression of the pfmdr1 gene have been associated with multiple drug resistance in some strains of plasmodium falciparum. in order to better understand this potential mechanism of drug resistance, we are currently investigating putative mdr homologues in vivo in the rodent malaria plasmodium berghei. we have identified and partially sequenced a gene that is amplified in a mfq-resistant (mfqr) line. using degenerate primers, a 579-bp fragment was amplified by pcr ...19999920046
plasmodium berghei and plasmodium yoelii: molecular karyotypes of drug-resistant lines. 19999920047
t cell recognition of hapten. anatomy of t cell receptor binding of a h-2kd-associated photoreactive peptide derivative.to elucidate the structural basis of t cell recognition of hapten-modified antigenic peptides, we studied the interaction of the t1 t cell antigen receptor (tcr) with its ligand, the h-2kd-bound plasmodium berghei circumsporozoite peptide 252-260 (syipsaeki) containing photoreactive 4-azidobenzoic acid (aba) on p. berghei circumsporozoite lys259. the photoaffinity-labeled tcr residue(s) were mapped as tyr48 and/or tyr50 of complementary determining region 2beta (cdr2beta). other tcr-ligand conta ...19999920911
heterogeneous ribosome populations are present in plasmodium berghei during development in its vector.the genome of the rodent malaria parasite, plasmodium berghei, contains two sets of variant ribosomal rna (rrna) genes, termed the a and s types, that are expressed predominantly during the vertebrate and mosquito stages of the parasite's development respectively. using in situ hybridization, we have examined the transcriptional activity of the a- and s-type rrna genes, and the switch in expression of the ribosome populations that occurs after parasite transmission to the mosquito. by detection ...19999987126
the development of murine cerebral malaria does not require nitric oxide production.nitric oxide (no) production has been suggested to be required for the development of cerebral malaria. however, the importance of this molecule for the appearance of this pathology is debated. to assess whether murine cerebral malaria is no dependent, we investigated the course of blood-stage plasmodium berghei anka (pba) infections in inducible nitric oxide synthase (inos)-deficient mice. parasitaemia, haematological alterations, survival and development of cerebral malaria were not affected b ...199910028526
treatment with recombinant human tumour necrosis factor-alpha reduces parasitaemia and prevents plasmodium berghei k173-induced experimental cerebral malaria in mice.the present study shows that treatment with recombinant human tumour necrosis factor-alpha (rhtnf-alpha) can suppress parasitaemia and prevents development of experimental cerebral malaria (ecm) in plasmodium berghei k173-infected mice. mice received rhtnf-alpha treatment either by subcutaneous injection of free or liposome-encapsulated rhtnf-alpha or sustained intraperitoneal administration of rhtnf-alpha given via mini-osmotic pumps. low-dose treatment with a subcutaneous bolus injection of rh ...199910070656
the biosynthesis and post-translational modification of pbs21 an ookinete-surface protein of plasmodium berghei.radiolabelled methionine incorporation into synchronised plasmodium berghei gametocytes or ookinete cultures, showed that pbs21 is not synthesised in bloodstage parasites; synthesis was detected within three hours of induction of gametogenesis; synthesis was triggered at gametogenesis, not by fertilisation. we show native pbs21 to be a hydrophobic membrane protein that was insensitive to cleavage by phosphatidylinositol phospholipase c (pi-plc), but sensitive to alkaline hydroxylamine, and parti ...199910080386
role of glutathione in the detoxification of ferriprotoporphyrin ix in chloroquine resistant plasmodium berghei.the reduction in hemozoin content is a well known feature of chloroquine-resistant plasmodium berghei. using nk65-derived lines displaying increasing resistance levels, we observed an inverse relationship between the hemozoin content, and the glutathione (gsh) and glutathione s-transferase (gst) levels. treatment of highly chloroquine-resistant-infected mice with buthionine sulfoximine (bso), which has previously been shown to partially reverse this chloroquine resistance, led to a significant i ...199910080390
subtle mutagenesis by ends-in recombination in malaria parasites.the recent advent of gene-targeting techniques in malaria (plasmodium) parasites provides the means for introducing subtle mutations into their genome. here, we used the trap gene of plasmodium berghei as a target to test whether an ends-in strategy, i.e., targeting plasmids of the insertion type, may be suitable for subtle mutagenesis. we analyzed the recombinant loci generated by insertion of linear plasmids containing either base-pair substitutions, insertions, or deletions in their targeting ...199910082556
role of macrophages in experimental malaria: v--effect of ethyl palmitate on macrophages in plasmodium berghei infected mice.ethyl palmitate (ep) was used as a macrophage cytotoxin. the response of p. berghei after exposing the macrophage to ep was opposite to what was seen with other agents like silica, antimacrophage serum and freund's complete adjuvant. ep at dose of 5 mg and above decreased the survival period (sp), median survival day (msd) and parasite density 24 hrs. before death (k values). prepatent period (pp) was lower at doses 10 mg and 20 mg per day for 5 days before challenge compared to their correspond ...199710085642
in vitro and in vivo evaluation of betulinic acid as an antimalarial.the lupane-type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the tanzanian tree uapaca nitida müll-arg. (euphorbiaceae). the in vitro antiplasmodial ic50 values of betulinic acid against chloroquine resistant (k1) and sensitive (t9-96) plasmodium falciparum were found to be 19.6 micrograms/ml and 25.9 micrograms/ml, respectively. the in vitro activities of several related triterpenes were also evaluated. betulin was found to be inactive at 500 micrograms/ml ...199910190183
antimalarial activity of 3-hydroxyalkyl-2-methylene-propionic acid derivatives.several baylis-hillman adducts and their derivatives were synthesized and evaluated as targeted potential anti-malarials. the compounds 4, 7 and 9 were found to have highest potency against p. falciparum in vitro. the in vivo test result of compound 4 and 9 against p. berghei demonstrated activity at 80 mg/kg dose level.199910201838
irradiated sporozoites prime mice to produce high antibody titres upon viable plasmodium berghei sporozoite challenge, which act upon liver-stage development.c57bl6 mice were protected against plasmodium berghei sporozoite challenge by immunization with live 12 krad dose-irradiated sporozoites, but not by 20 krad dose-irradiated sporozoites. immunization with 12 krad irradiated sporozoites generated low levels of antibody reactive to liver-stage parasites (titres of 1/100). inoculation of as few as 100 live p. berghei sporozoites induced complete host protection accompanied by a very quick and high boost of antibody titres up to 1/4000. this sporozoi ...199910205797
synthesis and antimalarial activity of 11 dispiro-1,2,4,5-tetraoxane analogues of wr 148999. 7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecanes substituted at the 1 and 10 positions with unsaturated and polar functional groups.eleven novel dispiro-1,2,4,5-tetraoxanes 3 bearing unsaturated and polar functional groups were designed to enhance the oral antimalarial activity of the prototype tetraoxane 2 (wr 148999). with the exception of 3g and 3h, tetraoxanes 3 were available via the peroxidation of corresponding cyclohexanone derivatives in h2so4/ch3cn. tetraoxanes 3g and 3h were prepared by hydrolysis of ester tetraoxanes 3e and 3i, respectively. five of the 11 tetraoxanes were inactive, but six tetraoxanes had ic50 v ...199910212135
the putative gene for the first enzyme of glutathione biosynthesis in plasmodium berghei and plasmodium falciparum.the putative gene for gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione biosynthesis, has been characterized both in plasmodium berghei and plasmodium falciparum. protein sequence comparison between these two species reveals large conserved regions sharing more than 80% similarity, separated by less conserved portions. when the comparison is extended to known gamma-glutamylcysteine synthetases from other eukaryotes, a number of high similarity blocks are observed which m ...199910215022
ty virus-like particles, dna vaccines and modified vaccinia virus ankara; comparisons and combinations.three types of vaccine, all expressing the same antigen from plasmodium berghei, or a cd8+ t cell epitope from that antigen, were compared for their ability to induce cd8+ t cell responses in mice. higher levels of lysis and numbers of ifn-gamma secreting t cells were primed with ty virus-like particles and modified vaccinia virus ankara (mva) than with dna vaccines, but none of the vaccines were able to protect immunised mice from infectious challenge even after repeated doses. however, when th ...199910223332
thiolated recombinant human tumor necrosis factor-alpha protects against plasmodium berghei k173-induced experimental cerebral malaria in mice.the introduction of reactive thiol groups in recombinant human tumor necrosis factor (tnf) alpha (rhtnf-alpha) by the reagent succinimidyl-s-acetylthioacetate resulted in the formation of a chemically stabilized rhtnf-alpha trimer (rhtnfalpha-at; as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis). rhtnfalpha-at showed a substantially enhanced protective efficacy against the development of experimental murine cerebral malaria (ecm) after intravenous injection com ...199910223910
altered immune response of interferon regulatory factor 1-deficient mice against plasmodium berghei blood-stage malaria infection.nitric oxide (no) is a short-lived biological mediator which can be induced in various cell types and is able to cause many metabolic changes in target cells. inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of no production by transcriptional upregulation of inducible nitric oxide synthase. in the present study, we used mice devoid of functional interferon regulatory factor 1 by targeted gene disruption (irf-1(-/-)) to investigate the role of no ...199910225884
gamma interferon production is critical for protective immunity to infection with blood-stage plasmodium berghei xat but neither no production nor nk cell activation is critical.we have examined the roles of gamma interferon (ifn-gamma), nitric oxide (no), and natural killer (nk) cells in the host resistance to infection with the blood-stage malarial parasite plasmodium berghei xat, an irradiation-induced attenuated variant of the lethal strain p. berghei nk65. although the infection with p. berghei xat enhanced nk cell lytic activity of splenocytes, depletion of nk1.1(+) cells caused by the treatment of mice with anti-nk1.1 antibody affected neither parasitemia nor ifn ...199910225894
green fluorescent protein as a marker in plasmodium berghei transformation.we present a new marker that confers both resistance to pyrimethamine and green fluorescent protein-based fluorescence on the malarial parasite plasmodium berghei. a single copy of the cassette integrated into the genome is sufficient to direct fluorescence in parasites throughout the life cycle, in both its mosquito and vertebrate hosts. erythrocyte stages of the parasite that express the marker can be sorted from control parasites by flow cytometry. pyrimethamine pressure is not necessary for ...199910225926
glutathione-s-transferase activity in malarial parasites.glutathione-s-transferase (gst) activity has been detected in rodent (plasmodium berghei, p. yoelii), simian (p. knowlesi) and human (p. falciparum) malarial parasites, and in different intraerythrocytic stages of p. knowlesi (schizont > ring > trophozoite). in chloroquine-resistant strains of rodent and human malarial parasites gst activity significantly increases compared to sensitive strains. further, the increase in enzyme activity is directly related to drug pressure of resistant p. berghei ...199910320651
plasmodium berghei development in irradiated sporozoite-immunized c57bl6 mice.the c57bl6 strain of mice is highly susceptible to plasmodium berghei sporozoite infections and consequently requires repeated immunizations with irradiated sporozoites to obtain protective immunity. after a live sporozoite challenge in the immunized hosts, hepatic-stage parasites found in the liver after 48 h are of different sizes--small schizonts corresponding to blocked forms (derived from irradiated sporozoites), and schizonts of intermediate size (derived from live sporozoites). large schi ...199910340322
identification of the transcription initiation site of the asexually expressed rrna genes of the malaria parasite plasmodium berghei.the start site of the a-type ribosomal rna transcription units of the rodent malaria parasite, plasmodium berghei, has been identified. the two a-type units cannot be distinguished within the transcription unit, yet exist as single copies on different chromosomes. gene transcription initiates 820 bp upstream of the a-type small subunit (ssu) ribosomal gene and two major processing sites were mapped 610 and 611 nucleotides upstream of the ssu in the external transcribed spacer region. surprisingl ...199910340484
role of eicosanoids in the pathogenesis of murine cerebral malaria.because microvascular damage is a common feature of cerebral malaria, we have examined the role eicosanoid metabolites (prostaglandins and leukotrienes) in experimental cerebral malaria. eighty icr mice were infected with plasmodium berghei anka, with 40 uninfected mice as controls. half of the infected mice were treated on days 4 and 5 with aspirin, a prostaglandin synthesis inhibitor. infected mice started to die of cerebral malaria on day 6, and by day 17, all infected mice died. in contrast, ...199910348246
malaria parasite-specific th1-like t cells simultaneously reduce parasitemia and promote disease.cd4+ t cells have been implicated in immunity to the blood stages of malaria and cytokines associated with both monocyte and t cell activation have been implicated in disease. to determine whether specific t cells capable of inhibiting parasite growth can also mediate pathology we have transfused populations of plasmodium berghei-specific t cells into normal and immunodeficient naive mice. we observed that they could inhibit parasite growth but were unable to save the animals which exhibited sig ...199910354354
involvement of lipids in ferriprotoporphyrin ix polymerization in malaria.approximately 70% of the initial ferriprotoporphyrin ix polymerizing activity in cell-free preparations of erythrocytes infected with plasmodium berghei was recovered in a chloroform extract. no polymerizing activity remained in the residue. in studies to identify substances that promote fp polymerization, arachidonic, linoleic, oleic, and palmitoleic acids, 1-mono- and di-oleoylglycerol, and the detergents, sds, tween 80, and n-octyl-glucopyranoside, were active. tri-oleoylglycerol, cholesterol ...199910354512
antimalarial activity of extracts of malaysian medicinal plants.in vitro and in vivo studies revealed that malaysian medicinal plants, piper sarmentosum, andrographis paniculata and tinospora crispa produced considerable antimalarial effects. chloroform extract in vitro did show better effect than the methanol extract. the chloroform extract showed complete parasite growth inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period (andrographis paniculata) as compared to methanol extract of drug dose of 2.5 mg/ml but under incubation time of 48 ...199910363840
analysis of stage specificity of promoters in plasmodium berghei using luciferase as a reporter. 199910377003
structure and expression of an adhesive protein-like molecule of mosquito invasive-stage malarial parasite.invasion of the malarial parasite into a vector mosquito begins when the motile ookinete transverses the gut epithelium. adhesive proteins that may mediate this invasive process have not been identified to date. we found that a molecule with an adhesive protein-like structure was expressed in the ookinete of plasmodium berghei. this protein is structurally homologous to circumsporozoite protein and thrombospondin-related adhesive protein (trap)-related protein, ctrp, of plasmodium falciparum. we ...199910377190
extracellular processing and presentation of a 69-mer synthetic polypetide to mhc class i-restricted t cells.the classical pathway for mhc class-i-restricted ag presentation processes cytosolic ag synthesized in or delivered into the cytosol for binding to mhc class i molecules in the er. alternatively, ag may be processed and bind class i molecules in endocytic compartments or at the cell surface after regurgitation of processed peptides. we show that a 69-mer synthetic polypeptide that carries the optimal 9-mer kd-restricted epitope from the plasmodium berghei circumsporozoite protein, pbcs 245-253, ...199910378682
gene organization of rab6, a marker for the novel golgi of plasmodium. 199910391383
dipeptide derivatives of primaquine as transmission-blocking antimalarials: effect of aliphatic side-chain acylation on the gametocytocidal activity and on the formation of carboxyprimaquine in rat liver homogenates.dipeptide derivatives of primaquine (pq) with reduced oxidative deamination to the inactive metabolite carboxyprimaquine were synthesized and evaluated as a novel class of transmission-blocking antimalarials. methods; antimalarial activity was studied using a model consisting of mefloquine-resistant plasmodium berghei anka 25r/10, balb c mice, and anopheles stephensi mosquitoes. metabolic studies were performed with rat liver homogenates, and the incubates were analyzed by hplc.199910397619
cloning and characterization of the merozoite surface antigen 1 gene of plasmodium berghei.merozoite surface antigen 1 (msa1) is a promising candidate for vaccine development against malaria parasites. here, we report the complete nucleotide sequence of the gene encoding the precursor to this major surface antigen of plasmodium berghei strain anka using cdna library screening and polymerase chain reaction techniques. a single open reading frame of 5,376 basepairs encoding a protein with a calculated molecular mass of 197 kd was defined. the protein contains a putative signal peptide o ...199910403333
synthesis and antimalarial activity of cyclic peroxides, 1,2,4,5, 7-pentoxocanes and 1,2,4,5-tetroxanes.a variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. in both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. for some cyclic peroxides, which were found to be highly effective in vitro, the study in vivo has been also conducted.199910411480
infectivity of plasmodium berghei sporozoites delivered by intravenous inoculation versus mosquito bite: implications for sporozoite vaccine trials.plasmodium berghei sporozoites delivered by mosquito bite were more infectious to outbred cd-1 mice than were sporozoites delivered by intravenous inoculation. the route of challenge also affected vaccine efficacy. in view of these findings and the fact that mosquito bites are the natural mode of sporozoite delivery, infectious mosquito bites should be considered the challenge protocol of choice for sporozoite vaccine efficacy trials.199910417207
antimalarial activity and cytotoxicity of (-)-roemrefidine isolated from the stem bark of sparattanthelium amazonum.(-)-roemrefidine, an aporphine alkaloid isolated from sparattanthelium amazonum martius (hernandiaceae) a vine from bolivia, has been found to be active against both resistant and sensitive strains of plasmodium falciparum in vitro and against p. berghei in mice. the compound demonstrated no cytotoxic activity against three cell lines (kb, hep-2 and hela).199910418333
an alternate pathway for type 1 t cell differentiation.ifn-regulatory factor-1 (irf-1) gene-disrupted mice are defective in il-12 and il-18 gene expression at the transcriptional and post-translational level respectively. the mutant mouse mounts a type 2 t cell response upon bacterial infection because of the impaired induction of the il-12 p40 gene and ifn-gamma-producing type 1 t cells are not induced. we showed here, however, that different pathogens activate a novel pathway for inducing ifn-gamma-producing type 1 t cells even in an irf-1-deficie ...199910421776
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