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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
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
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
plasmodium berghei and plasmodium yoelii: molecular karyotypes of drug-resistant lines. 19999920047
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: 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
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
stable expression of green fluorescent protein in blood and mosquito stages of plasmodium berghei. 19989879905
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
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
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
[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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
plasmodium berghei: in vivo efficacy of albendazole in different rodent models. 19989538870
orally active antimalarial 3-substituted trioxanes: new synthetic methodology and biological evaluation.on the basis of a mechanistic understanding of the mode of action of artemisinin-like antimalarials, a series of structurally simple 3-aryl-1,2,4-trioxanes 5 was designed and was prepared in three to five operations from commercial reactants. the 3-aryl group was attached in each case as a nucleophile. in an electronically complementary fashion, 3-(fluoroalkyl)-trioxanes 6 were prepared via attachment of electrophilic fluoroalkyl esters. both in vitro and in vivo antimalarial evaluations of thes ...19989526568
identification of xanthurenic acid as the putative inducer of malaria development in the mosquito.malaria is transmitted from vertebrate host to mosquito vector by mature sexual blood-living stages called gametocytes. within seconds of ingestion into the mosquito bloodmeal, gametocytes undergo gametogenesis. induction requires the simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal temperature to 5 degrees c below that of the vertebrate host, and a rise in ph from 7.4 to 8.0-8.2. in vivo the mosquito bloodmeal has a ph of between 7.5 and 7.6. it is thought that in viv ...19989521324
malaria transmission. has the ignition key been found? 19989521315
the differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector.using serum or infected blood from danish volunteers and plasmodium falciparum-infected mozambican patients, respectively, the impact of curative doses of chloroquine and pyrimethamine/sulfadoxine upon infectivity of p. falciparum to anopheles arabiensis and an. gambiae or of p. berghei to an. stephensi was studied. both treatments cleared circulating p. falciparum gametocytes within 28 days. before this clearance, chloroquine enhanced infectivity to an. arabiensis, whereas pyrimethamine/sulfado ...19989502601
plasmodium berghei anka: purification of large numbers of infectious gametocytes. 19989501851
role of macrophages in experimental malaria: iv--bioassay of silica in immunity against plasmodium berghei infection.silica treated mice when challenged with plasmodium berghei showed increase in duration of prepatent(pp) and survival period (sp) and median survival day(msd) as compared with controls. daily parasite density curve during the course of infection was similar to control. response to the parasite challenge, however, was dependent on the dose of silica. no increase in sp at 0.7 mg and in pp at 35 mg (cumulative doses) dose was observed. a dose upto 5 mg per mouse before challenge resulted in protect ...19979475062
babesia bovis: genome size, number of chromosomes and telomeric probe hybridisation.pulsed field gel electrophoresis of intact chromosomes of babesia bovis revealed four chromosomes in the haploid genome. a telomere probe, derived from plasmodium berghei, hybridised to eight sfii restriction fragments of genomic b. bovis dna digests indicating the presence of four chromosomes. a small subunit (18s) ribosomal rna gene probe hybridised to the third chromosome only. the genome size of b. bovis is estimated to be 9.4 million base pairs. the sizes of chromosomes 1, 2, 3 and 4 are es ...19979467743
dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria.the pathogenesis of human cerebral malaria (cm) remains unresolved. in the most widely used murine model of cm, the presence of t lymphocytes and/or interferon (ifn)-gamma is a prerequisite. ifn-gamma is the key inducer of indoleamine 2,3-dioxygenase (ido), which is the catalyst of the first, and rate-limiting, step in the metabolism of tryptophan (trp) along the kynurenine (kyn) pathway. quinolinic acid (qa), a product of this pathway, is a neuro-excitotoxin, like glutamic acid (glu) and aspart ...19989466588
deletion of plasmodium berghei-specific cd4+ t cells adoptively transferred into recipient mice after challenge with homologous parasite.the immune response to malaria parasites includes t cell responses that reduce parasites by effector t cell responses and by providing help for antibody responses. some parasites are more sensitive to antibody and others are more sensitive to cell-mediated immunity. we demonstrate that cultured cd4(+) t cells that produce interferon gamma and interleukin 2, but not interleukin 4, in response to stimulation with the rodent parasite plasmodium berghei can reduce but not eliminate parasites in vivo ...19989465082
circulating tumour necrosis factor alpha is not involved in the development of cerebral malaria in plasmodium berghei-infected c57bl mice.administration of neutralizing anti-tnf alpha antibodies did not prevent plasmodium berghei induced cerebral malaria (cm) in c57bl/6 mice, when given at different dosages and time intervals. elevated concentrations of immunoreactive tnf alpha were found in the circulation but no bioactive tnf alpha could be detected in mice developing cm. furthermore, elevated tnf alpha receptor concentrations were measured in the plasma of mice developing cm. plasma of these mice neutralized bioactive recombina ...19979458469
a family of chimeric erythrocyte binding proteins of malaria parasites.proteins sequestered within organelles of the apical complex of malaria merozoites are involved in erythrocyte invasion, but few of these proteins and their interaction with the host erythrocyte have been characterized. in this report we describe maebl, a family of erythrocyte binding proteins identified in the rodent malaria parasites plasmodium yoelii yoelii and plasmodium berghei. maebl has a chimeric character, uniting domains from two distinct apical organelle protein families within one pr ...19989448314
antiplasmodial triterpene from vernonia brasiliana.the hexane extract from leaves of vernonia brasiliana (l.) druce (compositae) was active in vitro against plasmodium falciparum and in vivo in mice infected with plasmodium berghei. this extract was subjected to a bioassay-guided fractionation protocol based on the in vitro model. lupeol was identified as a compound responsible for the activity, inhibiting the p.falciparum growth by 45% when tested at 25 micrograms/ml. however, this triterpene was inactive in vivo when 15 mg/kg were administered ...19979434611
n-acetyl penicillamine a protector of plasmodium berghei induced stress organ injury in mice.n-acetyl penicillamine (nap), a derivative of penicillamine and copper chelator has been employed as a potential protector of host stress organ injury during plasmodium berghei infection in mice. intramuscular injection of nap (60 mg kg-1 body wt for 10 days) to p. berghei mice was able to restrict the hepato- and splenomegaly. the mortality rate of infected mice was decreased by 50% by nap. the decreased protein and lipid peroxidation and increased copper contents during p. berghei were almost ...19979425620
polyamine metabolism in various tissues during pathogenesis of chloroquine-susceptible and resistant malaria.the pathophysiological impact of infections with chloroquine-susceptible (cqs) and chloroquine-resistant (cqr) strains of plasmodium berghei in mastomys natalensis was studied with respect to changes in polyamine profiles in various tissues. both cqs and cqr infections produced similar changes in polyamine profiles of various tissues. maximum increase was recorded in spleen followed by liver and lungs. renal, cardiac and cerebral tissues did not register significant changes. an increase in sperm ...19979415968
gene targeting in malaria parasites.gene targeting, which permits alteration of a chosen gene in a predetermined way by homologous recombination, is an emerging technology in malaria research. soon after the development of techniques for stable transformation of red blood cell stages of plasmodium falciparum and plasmodium berghei, genes of interest were disrupted in the two species. the main limitations of gene targeting in malaria parasites result from the intracellular growth and slow replication of these parasites. on the othe ...19979405198
transfection of malaria parasites.the stable genetic transformation of three phylogenetically diverse species of plasmodium, the parasitic etiological agent of malaria, is now possible. the parasite is haploid throughout the vast majority of its life cycle. therefore with the single selectable marker activity and protocols currently available, it is possible not only to express introduced transgenes but also to study the effects of site-specific homologous recombination such as gene knockout. transgene expression will allow the ...19979405197
partial purification and characterization of a murine malaria parasite, plasmodium berghei specific aldolase.cell-free p. berghei contains 26.1 times more aldolase activity as compared to normal mouse erythrocytes. subcellular fractionation of cell-free parasite showed maximum enzyme activity in the soluble fraction. the parasite enzyme was active in a narrow ph range of 7.8-8.0. of the enzyme activity 90% was lost within 2 weeks at 4 degrees c. slight inhibition was observed with specific inhibitors atp, pyrophosphate (ppi) and pep. the f1, 6dp km was 0.025 mm.19979394614
effects of plasmodium berghei infection on arteether metabolism and disposition.arteether (ae) is primarily deethylated to dihydroqinghaosu (dqhs) in rats and humans. conversion of ae to dqhs was impaired in microsomes from rats infected with plasmodium berghei. the km for ae was 175.1 +/- 49.1 and 124.4 +/- 115.1 mumol/l, and vmax was 2.24 +/- 0.45 and 1.22 +/- 0.67 nmol ae formed/mg protein/min in control and infected microsomes (p < 0.05), respectively. calculated intrinsic clearance (clint = initial vmax/km) for ae was only 4% lower in infected microsomes. apparent phar ...19979380774
interleukin-10 modulates susceptibility in experimental cerebral malaria.in this study, we examined the effects of interleukin-10 (il-10) on the outcome of experimental cerebral malaria (cm), a lethal neurological syndrome that occurs in susceptible strains of mice after infection with plasmodium berghei anka (pba). constitutive il-10 mrna levels were significantly higher in the spleen and brain of resistant animals. in vivo neutralization of endogenous il-10 in cm-resistant mice induced the neurological syndrome in 35.7% of these mice, as opposed to 7.7% in controls ...19979378491
partial nucleotide sequence and organisation of extrachromosomal plastid-like dna in plasmodium berghei.the murine malaria parasite plasmodium berghei contains a plastid-like extrachromosomal genome. this genome is 30.7 kb in size and is transcriptionally active as shown by rt-pcr. dna sequence analysis of the genome reveals 69.9-95.5% homology to sequences of the 35-kb extrachromosomal circle found in the human malaria species plasmodium falciparum. homologous sequences include regions of genes for the ssu-rrna, lsu-rrna, rpo b and clusters of t-rnas. sequence variation between the two plasmodium ...19979373142
naphthylisoquinoline alkaloids against malaria: evaluation of the curative potentials of dioncophylline c and dioncopeltine a against plasmodium berghei in vivo.naphthylisoquinoline alkaloid-containing extracts from species of the families dioncophyllaceae and ancistrocladaceae and purified alkaloids derived therefrom were shown to exhibit antiparasitic activity in plasmodium berghei-infected mice. several extracts and alkaloids, especially dioncophylline c and dioncopeltine a, isolated from triphyophyllum peltatum (dioncophyllaceae), displayed high levels of activity. dioncopeltine a was able to suppress parasitemia almost totally, while dioncophylline ...19979371362
regulation of heme polymerizing activity and the antimalarial action of chloroquine.mice infected with plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin ix (fp) polymerization. six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase i (hpa i). for chloroquine-susceptible (cs) p. berghei, the rate of fp polymerization decreased from 541 +/- 42 (mean +/- standard deviation; n = 12) to 51 +/- 19 (n = 8) nmol of fp polymeri ...19979371350
synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue.the antimalarial activities of ferrocenic compounds mimicking chloroquine and active upon chloroquine-resistant strains of plasmodium falciparum were evaluated. four 7-chloro-4-[[[2-[(n,n-substituted amino)methyl]ferrocenyl]methyl]amino]quinoline derivatives have been synthesized; one of them, 1a, showed high potent antimalarial activity in vivo on mice infected with plasmodium berghei n. and plasmodium yoelii ns. and was 22 times more potent against schizontocides than chloroquine in vitro agai ...19979371235
expression of major histocompatibility complex antigens on mouse brain microvascular endothelial cells in relation to susceptibility to cerebral malaria.the physiopathology of experimental cerebral malaria (cm), an acute neurological complication of plasmodium berghei anka (pba) infection, involves interferon-gamma (ifn-gamma) and tumour necrosis factor-alpha (tnf-alpha), two cytokines that are known to modulate major histocompatibility complex (mhc) molecule expression. the aim of this study was to evaluate whether the genetic susceptibility to cm is related to the constitutive or ifn-gamma-induced expression of mhc molecules on brain microvess ...19979370924
malaria toxins: effects on murine spleen and bone marrow cell proliferation and cytokine production in vitro.the ability of deproteinated malaria exoantigens from plasmodium falciparum (pf-mt) and p. berghei anka (pba-mt) to activate murine haematopoietic cells was analysed in vitro. malaria toxins (mt) of both plasmodium species induced cell proliferation and the production of ifn-gamma in overnight and long-term (5 days) spleen and bone marrow cultures and a reduction of the number of tnf-alpha spot forming cells (sfc). when added to cells of malaria-experienced animals, mt decreased the number of il ...19979368898
malaria toxins from p. chabaudi chabaudi as and p. berghei anka cause dyserythropoiesis in c57bl/6 mice.the lack of correlation between parasitaemia and anaemia in severe malaria indicates that factors in addition to schizont rupture or erythrophagocytosis contribute to anaemia. we asked whether malaria toxin (mt) from plasmodium berghei or p. chabaudi might impair erythropoiesis. daily intraperitoneal injection of mt into c57bl/6 mice induced a transient reduction of rbc values by 25-30% after about 2 weeks, followed by increased haematopoiesis in the spleen as compared to mice receiving uninfect ...19979368897
ctl induction using synthetic peptides delivered in emulsions--critical role of the formulation procedure.emulsions have been used with variable degrees of success to deliver antigen to stimulate immune responses. we have investigated three different ways of incorporating peptide antigen into soybean emulsions to induce ctl responses in mice. two of these emulsions (oil-in-water, o/w, and water-in-oil-in-water, w/o/w) had peptide incorporated at the formulation stage, while the third had peptide added to a pre-formed o/w emulsion. high levels of ctl activity were induced when peptide was dispersed i ...19979364682
the novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite plasmodium falciparum in vitro and rodent parasites plasmodium berghei and plasmodium yoelii in vivo.previous studies have shown that licochalcone a, an oxygenated chalcone, exhibits antileishmanial and antimalarial activities. the present study was designed to examine the antimalarial activity of an analog of licochalcone a, 2,4-dimethoxy-4'-butoxychalcone (2,4mbc). 2,4mbc inhibited the in vitro growth of both a chloroquine-susceptible (3d7) and a chloroquine-resistant (dd2) strain of plasmodium falciparum in a [3h]hypoxanthine uptake assay. the in vivo activity of 2,4mbc was tested in mice in ...19979359735
a protein particle vaccine containing multiple malaria epitopes.ty virus-like particles consist of a single protein species that can be produced in yeast. recombinant ty-vlps carrying a string of up to 15 defined cytotoxic t lymphocyte (ctl) epitopes from plasmodium species prime protective ctl responses in mice following a single administration without adjuvant. effective processing of epitopes from the string was demonstrated in vitro and in vivo and was not affected by flanking sequences.19979359112
cytokine profile suggesting that murine cerebral malaria is an encephalitis.cerebral malaria (cm) remains a poorly understood and life-threatening complication of malaria caused by the parasite plasmodium falciparum. the discovery that murine cm caused by plasmodium berghei anka and human cm are both characterized by production of inflammatory cytokines, especially tumor necrosis factor alpha (tnf-alpha), led to a revival of the suggestion that p. berghei cm may have value as a model of the human disease. in this study, quantitative reverse transcription-pcr was used to ...19979353082
recognition of the parasite infected cell surface determinants by homologous antiserum raised against infected cell membranes.identification of neo-antigenic determinant(s) on parasite infected cell surface is important to control intracellular infections. such determinant(s) on the surface of intact plasmodium berghei infected erythrocytes have not been conclusively demonstrated. to generate polyclonal antiserum selectively recognizing the parasite infected cell surface determinant(s), in natural state, we have examined the efficacy of the homologous immunizations, in balb/c mice, with the membrane rich preparation of ...19979342738
molecular immune responses of the mosquito anopheles gambiae to bacteria and malaria parasites.immune responses of the malaria vector mosquito anopheles gambiae were monitored systematically by the induced expression of five rna markers after infection challenge. one newly isolated marker encodes a homologue of the moth gram-negative bacteria-binding protein (gnbp), and another corresponds to a serine protease-like molecule. additional previously described markers that respond to immune challenge encode the antimicrobial peptide defensin, a putative galactose lectin, and a putative serine ...19979326640
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