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induction of hepatic inflammatory response by plasmodium berghei sporozoites protects balb/c mice against challenge with plasmodium yoelii sporozoites.balb/c mice are about 2,000 times less susceptible to sporozoites of plasmodium berghei than to plasmodium yoelii. associated with this is the innate cellular response mounted after injection with p. berghei. host inflammatory cells do not normally attack p. yoelii during their development as exoerythrocytic forms (eefs) in the liver. we used p. berghei sporozoites to induce host inflammation that might act against developing p. yoelii eefs. mice injected with p. berghei sporozoites followed 1 h ...19938410550
tumour necrosis factor-alpha and macrophages in plasmodium berghei-induced cerebral malaria.the effect of tumour necrosis factor-alpha on malaria-infected mice was studied. c57bl/6j mice infected with plasmodium berghei k173 exhibited an increased sensitivity to exogenous tnf. injection of 15 micrograms tnf was lethal to some of the animals when given 5-7 days after infection, while when given later on in the infection (i.e. days 8-10) amounts as low as 2.5 micrograms tnf appeared to be lethal in all mice. the pathology in infected mice treated with tnf resembled that found in the brai ...19938414666
presence of an endogenous superoxide dismutase activity in three rodent malaria species.superoxide dismutase (sod) was investigated in three species of rodent malaria (plasmodium berghei, p. yoelii and p. vinckei). the isoelectric points (pi) of isozymes found in purified parasites were identical. sod activities detected by isoelectrofocusing at pl 5.0, 5.6, and 6.4 were cyanide-sensitive and could be considered as having been adopted by the parasites from the host red blood cell. the three rodent malaria parasites also contained a cyanide-resistant, hydrogen peroxide-sensitive sod ...19938415538
experimental transmission of murine malaria by the oral route.a total of 116 young male cd1 mice were orally inoculated with mouse blood; half of the animals received 0.2 ml of uninfected blood and the others were given 0.2 ml of plasmodium berghei yoelii-infected blood in six experiments performed at different times. almost 30% of the experimental mice acquired malaria as demonstrated by the observation of parasites in their blood. in no case were parasites found in the blood of control mice. rodent malaria parasites may be transmitted to cd1 mice by the ...19938415572
transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria.the polymorphic frequency of the gene for beta s-globin involved in the generation of sickle trait and sickle cell anemia in the human population is caused by the enhanced resistance of sickle trait individuals to plasmodium falciparum malaria, as supported by epidemiologic and in vitro studies. however, the mechanism for the protective effect of sickle hemoglobin in vivo has not been fully defined. the generation of transgenic mice expressing high levels of human beta s- and alpha-chains has al ...19938417791
transgenic mice expressing c-reactive protein are susceptible to infection with plasmodium yoelii sporozoites.human and rat c-reactive proteins, major acute-phase reactants, bind to sporozoites and inhibit their in vitro development in hepatocytes (a. nussler, s. pied, m. pontet, f. miltgen, l. renia, m. gentilini, and d. mazier, exp. parasitol. 72:1-7, 1991, and s. pied, a. nussler, m. pontet, f. miltgen, h. matile, p.-h. lambert, and d. mazier, infect. immun. 57:278-282, 1989). we show here that rabbit c-reactive protein has identical properties. nevertheless, infection by plasmodium yoelii sporozoite ...19938418060
binding of alanine-substituted peptides to the mhc class i protein, kd.peptides eluted from the native mhc class i molecule, kd, are generally nonamers that display a strong preference for tyr in position 2. we investigated the molecular basis for this 'consensus motif' by synthesizing a virally derived peptide, np 147-155, that is known to be presented by kd on living cells, and peptide variants of np 147-155 in which the amino acids in the different positions were sequentially replaced by ala. all of the peptides bound to purified kd molecules in vitro with high ...19938428632
selective damage of hippocampal neurons in murine cerebral malaria prevented by pentoxifylline.the effect of pentoxifylline, a phosphodiesterase inhibitor, was investigated on the development of cerebral malaria in plasmodium berghei k 173 infected c57/b16 mice. no significant differences occurred in the course of parasitemia and survival time after infection between control mice and pentoxifylline treated mice. moreover, no differences were observed between the groups with respect to the occurrence of cerebral malaria. the only striking difference was that pentoxifylline treatment select ...19938433093
magnesium deficiency affects malaria susceptibility in mice.one hundred twenty mice were fed control and magnesium-(mg) deficient diets containing 960 and 50 mg mg/kg, respectively. after 12 days, mice were inoculated with several strains of plasmodium (p). parasitemias and survivals were monitored for 20 days after infection. the mg-deficient diet protected mice against the nonlethal parasite p. chabaudi as shown by decreased parasitemia. all control mice infected with p. vinckei died from the infection. mg-deficient mice had a much lower parasitemia an ...19938440813
effects of interleukin-8 on nonspecific resistance to infection in neutropenic and normal mice.the effect of treatment with interleukin-8 (il-8), a neutrophil-activating cytokine, was investigated in normal and neutropenic mice infected with a lethal dose of pseudomonas aeruginosa, klebsiella pneumoniae, or plasmodium berghei. intraperitoneal (i.p.) il-8 treatment was associated with accelerated death when il-8 was administered shortly before i.p. infection with p. aeruginosa or shortly after i.p. infection with p. aeruginosa and k. pneumoniae. histopathological analyses demonstrated a te ...19938452358
immunological detection of cytoskeletal proteins in the exoerythrocytic stages of malaria by fluorescence and confocal laser scanning microscopy.using monospecific antibodies, the presence and distribution of tubulin, actin, myosin, intermediate filaments, and lamins were examined in the exoerythrocytic liver schizont of plasmodium berghei by conventional indirect fluorescent antibody methods and confocal laser scanning microscopy. the binding reactivity of the antibodies to parasite proteins was determined by western blot analysis. the localisation of all antibodies in control host hepatocytes followed expected distributions in both uni ...19938457799
effect of malaria infection and endotoxin-induced fever on phenacetin o-deethylation by rat liver microsomes.we have investigated the effect of malaria infection with the rodent parasite plasmodium berghei and fever induced by escherichia coli endotoxin on the metabolism of phenacetin to paracetamol by rat liver microsomes from young (4 weeks old) male wistar rats (n = 5 in control and fever groups; n = 10 in malaria-infected group). following determination of % parasitaemia, the malaria-infected group was divided into a low parasitaemia subgroup (n = 5; mean % parasitaemia = 9.87 +/- 2.6) and a high p ...19938466544
effect of malaria infection and endotoxin-induced fever on the metabolism of antipyrine and metronidazole in the rat.antipyrine and metronidazole were administered as a cocktail to young (4 weeks old) male wistar rats (n = 12 for each treatment) to investigate the effect of malaria infection due to the rodent parasite plasmodium berghei and escherichia coli endotoxin-induced fever on the metabolism of the two compounds in vivo. control rats received normal saline. antipyrine and metronidazole clearances were estimated from a single saliva sample while the formation clearances of their metabolites (in malaria-i ...19938466545
a new method for isolation of the intraerythrocytic stages of plasmodium and babesia from their host cells.a new method for the isolation of intraerythrocytic stages of plasmodium berghei and babesia divergens from red blood cells is described. the technique is based on hydrodynamic forces occurring in a flow channel containing a turbulent liquid current, which are capable of rupturing infected erythrocytes and removing their plasma membrane from the parasites' surface. the temperature and the concentration of cells were revealed as factors influencing the hydrodynamic forces. about 90% of the intact ...19938469669
comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.the antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive plasmodium falciparum parasites, in mice infected with p. berghei, and in aotus monkeys infected with chloroquine-resistant p. falciparum. in vitro, the mean 50% inhibitory concentration (ic50) for beta-artemether was 1.74 nm (range 1.34-1.81 nm), and this value for beta-arteether was 1.61 nm (range 1.57-1.92 nm). they were approxima ...19938470775
differentiation of toxoplasma gondii from closely related coccidia by riboprint analysis and a surface antigen gene polymerase chain reaction.the tachyzoite of the human pathogen toxoplasma gondii is morphologically indistinguishable from the proliferative stages of some other zoonotic coccidia, including sarcocystis. to determine the identity of such coccidia obtained from human tissues and other sources, we compared riboprints (through restriction enzyme analysis of the polymerase chain reaction [pcr]-amplified small subunit rrna gene) of the following protozoa: the rh and ts-4 strains of t. gondii, lines oh3 and s11, which are two ...19938470780
malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria.the in vitro production of reactive nitrogen intermediates (rni) by murine macrophages was evaluated in response to heat-stable malaria antigen and cytokines. malaria antigen, interferon-gamma (ifn-gamma) and tumour necrosis factor (tnf) induced rni production in macrophages in a dose-dependent way. rni production steadily increased over a 2-day period and was enhanced when the malaria antigen was co-incubated with ifn-gamma and/or tnf. rni production induced by either ifn-gamma or malaria antig ...19938473017
photoaffinity labeling of the t cell receptor on living cytotoxic t lymphocytes.using a direct binding assay based on photoaffinity labeling, we have studied the interaction of an antigenic peptide with mhc class i molecules and the tcr on living cells. two photoreactive derivatives of the h-2kd (kd) restricted plasmodium berghei circumsporozoite (pbcs) peptide 253-260 (yipsaeki) were used. the first derivative contained an n-terminal photoreactive iodo, 4-azido salicyloyl (iasa) group and biotin on the tcr contact residue lys259 [iasa-yipsaek(biotin)i]. as previously descr ...19938473735
expression of members of the heat-shock protein 70 family in the exoerythrocytic stages of plasmodium berghei and plasmodium falciparum.exoerythrocytic stages of plasmodium berghei cultured in hepg2-a16 hepatoma cells and those of p. falciparum in human hepatocytes transplanted under the kidney capsule of cb-17/icr scid/scid mice were used to evaluate expression of heat-shock-related stress proteins. although undetectable in the sporozoites, the expression of proteins similar in sequence of a heat-shock protein of 70 kda and a glucose-regulated protein of 78 kda was markedly induced in the hepatic stages of malaria parasites. ex ...19938475027
interleukin-1 as a possible agent for treatment of infection.treatment of experimental animals with bacterial products, such as cell wall components of gram-negative bacteria, leads to enhanced resistance to a variety of microorganisms. since interleukin-1 and other pro-inflammatory cytokines are induced by such bacterial products, it has been investigated whether these cytokines are also capable of enforcing host resistance. it has been possible to demonstrate that a low dose of interleukin-1 protects mice against death from either gram-negative or gram- ...19938477769
real-time measurement of antigenic peptide binding to empty and preloaded single-chain major histocompatibility complex class i molecules.cytotoxic t lymphocytes (ctl) recognize peptides in association with major histocompatibility complex (mhc) class i proteins, but how peptides bind to class i is not well understood. we used a fluorescence technique to measure antigenic peptide binding to a soluble, single-chain kd (sc-kd) molecule in which the kd heavy chain was connected by a 15-residue link to beta 2-microglobulin. peptides were covalently labeled at their n terminus with dansyl, and binding of dansylated kd-restricted peptid ...19938477806
differential t cell receptor photoaffinity labeling among h-2kd restricted cytotoxic t lymphocyte clones specific for a photoreactive peptide derivative. labeling of the alpha-chain correlates with j alpha segment usage.using a direct binding assay based on photoaffinity labeling, we studied the interaction of t cell receptor (tcr) with a kd-bound photoreactive peptide derivative on living cells. the kd-restricted plasmodium berghei circumsporozoite (pbcs) peptide 253-260 (yipsaeki) was reacted nh2-terminally with biotin and at the tcr contact residue lys259 with photoreactive iodo, 4-azido salicylic acid (iasa) to make biotin-yipsaek(iasa)i. cytotoxic t lymphocyte (ctl) clones derived from mice immunized with ...19938478607
the novel hydroxynaphthoquinone 566c80 inhibits the development of liver stages of plasmodium berghei cultured in vitro.the causal prophylactic activity of the novel hydroxynaphthoquinone, 566c80, was assessed against the exo-erythrocytic (ee) stages of plasmodium berghei cultured in the human hepatoma cell line, hepg2. 566c80 was found to be highly active as an inhibitor of ee development and was more active than the established causal prophylactic pyrimethamine. a 566c80 concentration of 1.85 x 10(-9) m, added 3 h after sporozoite invasion, reduced the numbers of ee forms visible at 48 h by 50 degrees o, while ...19938479795
hemoglobin catabolism and host-parasite heme balance in chloroquine-sensitive and chloroquine-resistant plasmodium berghei infections.catabolism of host hemoglobin by the malaria parasite liberates required amino acid precursors, but is also releases large amounts of potentially toxic heme that accumulates in parasite food vacuoles during intra-erythrocytic development. the schizonticidal drug chloroquine binds to free heme with high affinity and is concentrated in parasite food vacuoles. to better understand the disposition of heme within the host-parasite complex, we studied the balance of hemoglobin and heme in plasmodium b ...19938480854
effect of chloroquine on hepatic heme-oxygenase during plasmodium berghei infection in mice.hepatic heme-oxygenase and heme levels were monitored during plasmodium berghei infection and chloroquine treatment in swiss albino mice. a progressive increase in heme-oxygenase and heme levels was noticed with the rise in parasitemia. further, chloroquine treatment did not result in any change towards normal heme-oxygenase and heme content, when they were assayed a week after cessation of drug treatment. chloroquine treatment of non-parasitized and parasitized mice resulted in significant loss ...19938496005
a 54-kda protein overexpressed by chloroquine-resistant plasmodium berghei anka strain.using an insoluble chloroquine-adsorbent, a 54-kda protein (with a range of 50-60 kda) was extracted from serum of mice infected with chloroquine-resistant (cr) plasmodium berghei anka strain. immunoblotting assay with antiserum against the 54-kda protein showed that the content of the protein was higher in serum of mice infected with the cr parasites than that of mice infected with chloroquine-sensitive (cs) p berghei anka strain, and that instead of the 54-kda protein, a set of 15-, 16-, and 2 ...19938503289
reversal of chloroquine resistance in murine malaria parasites by prostaglandin derivatives.an oligomeric ester of prostaglandin b2 (oc-5186) was found to reverse chloroquine resistance in the murine malarial parasite plasmodium berghei. when mice were infected with either chloroquine-sensitive or -resistant p. berghei on day 0 (by intraperitoneal injection of 1 x 10(6) parasitized erythrocytes), they died before day 23. when treated with 15 mg/kg/day of chloroquine for the first four days of infection, all mice infected with the sensitive-strain survived, while all those infected with ...19938517483
proteolysis of a 34 kda phosphoprotein coincident with a decrease in protein kinase activity during the erythrocytic schizont stage of the malaria parasite.protein phosphorylation events may play important roles in the replication and differentiation of the malarial parasite. investigations into the lability of a plasmodium protein kinase revealed that a 34 kda parasite phosphoprotein is rapidly converted into a 19 kda fragment. coincident with this conversion is a nearly total loss of a protein kinase activity, as determined from the phosphorylation of endogenous protein substrates. both the conversion of the 34 kda protein to the 19 kda protein a ...19958520577
evaluation of resistant-reversal, cdri compound 87/209 and its possible mode of action in rodent experimental malaria.the resurgence of malaria in form of resistance against chloroquine (cq) has decreased the importance of the drug as a chemotherapeutic agent. if an agent in combination with cq can make cq resistant plasmodia susceptible to cq, the problem of drug resistance may then be solved. use of conventional drugs like verapamil, desipramine along with cq suggested the feasibility of this approach. this report is concerned with a new class of compound, cdri compound 87/209 (15 mg/kg b. wt.) which is given ...19958525290
antimalarial activity of oxidized starch and cellulose imine derivatives.with the purpose of screening potential antimalarial agents, oxidized starch imine derivatives of sulfonamides or pyrimidine - derivatives of sulfisoxazole (ml8), sulfameter (ml11) and trimethoprim (ml13) - and oxidized cellulose imine derivatives of dapsone (ml14), sulfadiazine (ml17), sulfamethoxazole (ml18), sulfisoxazole (ml19), sulfamethoxypyridazine (ml20) and sulfameter (ml22) were submitted to in vivo biological assays with mice infected with plasmodium berghei. only ml11 was 100% curati ...19958527105
effect of fatty acid treatment in cerebral malaria-susceptible and nonsusceptible strains of mice.cerebral malaria-susceptible (c57bl/6) mice infected with plasmodium berghei anka (pba) developed low parasitemia and died from typical neurological symptoms between 8 to 10 days after infection. in contrast, nonsusceptible (balb/c) mice developed high peripheral blood parasitemia and died 22-24 days later without neurological implications. daily injections of fatty acids (fa) during the first 3 days after infection protected c57bl/6 mice from cerebral symptoms but had no effect on balb/c mice. ...19958544078
syntheses and antimalarial activities of n-substituted 11-azaartemisinins.a two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with amberlyst 15 yielded 11-azaartemisinin in 65% yield. substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields n-substituted 11-azaartemisinins in similar or greater yield. when amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% ...19958544181
susceptibility to plasmodium berghei infection in rats is modulated by the acute phase response.brown norway (bn) and sprague dawley (sd) rats are known to differ in their susceptibility to infection with sporozoites of plasmodium berghei, as measured by the density of liver schizonts. because of the known inhibitory effect of non-specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. lps induced il-6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. sd rats, which a ...19958552412
the chemotherapy of rodent malaria. l. the activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. part 3: observations on 'fenozan-50f', a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane.a novel difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane ('fenozan-50f') is a potent blood schizontocide against drug-sensitive and drug-resistant rodent malaria parasites. it also exerts some action against pre-erythrocytic schizogony, is a potent gametocytocide, and exerts a direct sporontocidal effect in infected mosquitoes. in the '4-day test' the ed90s are 6.8 and 6.0 mg/kg/day for four consecutive days by the subcutaneous and oral routes respectively against drug-sensitive plasmodium be ...19938561518
expression of a plasmodium gene introduced into subtelomeric regions of plasmodium berghei chromosomes.targeted integration of exogenous dna into the genome of malaria parasites will allow their phenotype to be modulated by means of gene disruption or the stable expression of foreign and mutated genes. described here is the site-specific integration through reciprocal exchange, and subsequent expression, of a selectable marker gene into the genome of the pathogenic, bloodstage forms of the rodent malaria parasite plasmodium berghei. stable integration of a single copy of the marker gene (retained ...19968571132
plasmodium berghei: sensitivity of chloroquine-resistant and chloroquine-sensitive strains to irradiation and the effect of irradiated malaria parasites on cytochrome p450-dependent monooxygenases.differences in sensitivities of chloroquine-sensitive and chloroquine-resistant strains of plasmodium berghei were observed following irradiation of the parasites. a dose of 15 kilorads from a cobalt-60 source killed the erythrocytic stages of the chloroquine-sensitive strain and no parasitemias were observed when mice were injected with these irradiated parasites. in contrast, when the chloroquine-resistant strain was irradiated with the same dose of cobalt-60 and injected into mice, an infecti ...19958581351
interferon-gamma and the induction of protective igg2a antibodies in non-lethal plasmodium berghei infections of mice.mice treated with anti-ifn-gamma monoclonal antibodies were unable to recover from infection with an attenuated variant of p. berghei (pb xat) which causes non-lethal malaria in normal mice. on the other hand, treatment with anti-il-4 monoclonal antibodies had no effect on the course of infection. ifn-gamma was produced by spleen cells in vitro during the early phase of the infection. treatment with anti-ifn-gamma suppressed development of an anti-plasmodial igg2a immunoglobulin isotype in the s ...19958587787
sulfated polyanions inhibit invasion of erythrocytes by plasmodial merozoites and cytoadherence of endothelial cells to parasitized erythrocytes.sulfated proteoglycans have been shown to be involved in the binding of sporozoites of malaria parasites to hepatocytes. in this study, we have evaluated the effect of sulfated glycosaminoglycans on the invasion of erythrocytes by plasmodium falciparum merozoites and cytoadherence of parasitized erythrocytes (prbc) to endothelial cells. invasion of erythrocytes by hb3ec-6 (an hb3 line selected for high binding to endothelial cells) was inhibited by dextran sulfate 500k, dextran sulfate 5k, sulfa ...19968606103
attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria.nyvac-based vaccinia virus recombinants expressing the circumsporozoite protein (csp) were evaluated in the plasmodium berghei rodent malaria model system. immunization of mice with a nyvac-based csp recombinant elicited a high level of protection (60 to 100%). protection did not correlate with cs repeat-specific antibody responses and was abrogated by in vivo cd8+ t-cell depletion. protection was not enhanced by modification of the subcellular localization of csp. these results suggest the pote ...19968613376
mhc class i-dependent presentation of exoerythrocytic antigens to cd8+ t lymphocytes is required for protective immunity against plasmodium berghei.t lymphocytes are believed to play a major role in protection against malaria. previous experiments using in vivo depletion of cd8+ t cells, reconstitution with cd8+ t splenic cells, and adoptive transfer of cd8+ ctl clones demonstrated that protection against the exoerythrocytic stage of the murine strain, plasmodium berghei malaria, was cd8+ t cell-dependent. despite evidence for the critical role of cd8+ ctl, neither the cellular nor the molecular requirements for cd8+ t cell induction or for ...19968617963
dietary iron supplementation does not aggravate experimental malaria in young rats.the hypotheses that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection have been supported by some clinical and experimental evidence. in the present study, the course of plasmodium berghei infection was monitored in an experimental model of dietary iron deficiency and iron supplementation. weanling wistar rats were fed purified diets with different iron concentrations: 20 mg/kg (group d, n = 24), 50 mg/kg (group n, n = 24) and 100 mg/k ...19968632220
trafficking of plasmodium chabaudi adami-infected erythrocytes within the mouse spleen.plasmodium chabaudi adami causes a nonlethal infection in mice. we found that crisis, the time of rapidly dropping parasitemia, was abrogated by splenectomy, indicating the role of spleen in parasite killing. the factors that mediate spleen-dependent immunity are not known. an earlier study in plasmodium berghei-infected rats showed an association between increased clearance of heat-treated erythrocytes and the onset of crisis [wyler, d. j., quinn, t. c. & chen, l.-t. (1982) j. clin. invest. 67, ...19968643449
efficient binding to the mhc class i k(d) molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif.peptides eluted from the mhc class i k(d) molecule are generally nonamers that display a strong preference for tyr in position 2 and ile or leu in position 9. we investigated the binding ability of several synthetic peptides which did not fit this consensus motif. in our peptides, tyr(2) was substituted by other amino acids, i.e. leu, ile or met. these peptides were variants of the 252-260 k(d)-restricted peptide syipsaeki derived from the plasmodium berghei circumsporozoite protein. they bound ...19968654564
plasmodium berghei mouse model: antimalarial activity of new alkaloid salts and of thiosemicarbazone and acridine derivatives.sixteen compounds were synthesized and evaluated on plasmodium berghei in cd1 mouse. the nature of the salt associated to the active principle can give some advantages in the field of activity, bioavailability and toxicity. beta-resorcylic acid was chosen in this study because of its previously described antimalarial activity and its expected enhancement of quinine antimalarial activity. while treatment with subcutaneous quinine sulphate at 1 mmol/kg cured 6/10 mice, quinine beta-resorcylate cur ...19968673843
toward a novel metal-based chemotherapy against tropical diseases. 2. synthesis and antimalarial activity in vitro and in vivo of new ruthenium- and rhodium-chloroquine complexes.chloroquine free base (cq) reacts with [rh(cod)cl]2 (cod = 1,5-cyclooctadiene) and rucl3.-3h2o/zn to yield rh(cod)(cq)cl (1) and [rucl2(cq)]2 (2), respectively. the two novel metal- cq complexes, which were characterized mainly by 1d and 2d nmr spectroscopy, were tested against plasmodium berghei. the in vitro activity of 1 was comparable to that of chloroquine diphosphate (cqdp), whereas 2 was about 5 times more active. in in vivo tests at equivalent concentrations of free cq, cqdp reduced the ...19968676344
wistar rat-plasmodium berghei model does not approximate human congenital malaria.until recently, congenital malaria was thought to be rare. now, several reports suggest that more than 10% of newborns in some settings are parasitemic. the pathophysiology of transplacental transmission of plasmodium is not well understood, and no animal model of congenital malaria exists. a rodent model of malaria in pregnant females, however, has been developed. in an effort to test the usefulness of this model in the study of congenital malaria, wistar rats were injected intraperitoneally wi ...19968691374
[ca++ ion transport blockers as reversants of the drug resistance of malarial parasites. 1. the effect of verapamil on the resistance to chloroquine in vivo of plasmodium berghei and in vitro of plasmodium falciparum].the reversing action of verapamil on the effect of chloroquine was found in in vivo experiments by using a model p. berghei resistant to chloroquine, an lnk65 isolate having a naturally lower resistance to the agent, and its polyresistant strain with the acquired resistance to chloroquine and fansidar, as well as by employing the chlorine-resistant p. falciparum isolates from the south of the socialist republic of vietnam. the magnitude of this effect was related to the dose of verapamil, the fr ...19968700004
effects of artesunate on immune function in mice.to study the effects of artesunate (dihydroartemisinine-12-alpha-succinate, art) on immune function in mice.19958701764
the within-host cellular dynamics of bloodstage malaria: theoretical and experimental studies.the properties of a mathematical model of bloodstage infection with a single strain of malaria were investigated. analysing the cell population dynamics in the absence of a host immune response we demonstrate a relationship between host and parasite parameters that defines a criterion for the successful invasion and persistence of the parasite. important parameters are the rates of merozoite production and death and those of erythrocyte production, death and invasion. we present data from experi ...19968710412
[malaria parasite dna and rna changes connected with acquired resistance to chloroquine]. 19968714121
antimalarial properties of soy-bean fat emulsions.intralipid and ivelip are commercial preparations of soy-bean lipid extracts used for intravenous supplementation of lipids in various clinical conditions. they were found to inhibit the growth of plasmodium falciparum in culture with an ic50 of 8.07 +/- 2.13 and 13.32 +/- 2.05 mg.ml-1, respectively. intralipid rapidly and efficiently inhibited nucleic acid synthesis in cultured p. falciparum, exhibiting full inhibitory activity in less than 2 h. ivelip injected intraperitoneally, was found by t ...19958719958
the course of plasmodium berghei, p. chabaudi and p. yoelii infections in beta-thalassaemic mice.in order to study the effects of acclimatization of plasmodium in beta-thalassaemic mice, we used a mouse model of beta-thalassaemia (dba/2j/beta-thal/beta-thal), similar to that observed in humans. we acclimatized 3 rodent malarias (p. berghei, p. chabaudi and p. yoelii) in dba/2j and dba/2j/beta-thal mice lines, by 4 intraperitoneal serial transfers. all 3 rodent malarias developed in red blood cells of beta-thalassaemic mice without losing their virulence. there was no delay in infection and ...19968728990
patterns of haemozoin accumulation in tissue.a sensitive fluorometric method for assaying malarial pigment, haemozoin, has been developed and used to determine the haemozoin content of blood and tissue samples. plasmodium falciparum rings and trophozoites were found to contain 23 and 339 ng haemozoin/10(6) parasitized red blood cells (prbcs), respectively. unsynchronized plasmodium berghei nk65 or anka parasites from infected mice contained 27 and 61 ng haemozoin/10(6) prbcs, respectively. an exponential accumulation of haemozoin within 18 ...19968728992
[erythrocyte immunity and regulating factors in mice infected with plasmodium berghei anka strain].after seventy-two icr mice were inoculated with plasmodium berghei anka strain, parasitaemia was revealed in all animals inoculated in two to seven days. during the course the number of malaria parasites increased rapidly from 2.3 +/- 1.3 x 10(3) on d2 to 93.7 +/- 1.8 x 10(3) on d7, the number of erythrocytes increased from 8.2 +/- 0.9 x 10(12)/l on d0 to 11.1 +/- 1.0 x 10(12)/l on d2 and then decreased gradually, reaching 1.9 +/- 0.4 x 10(12)/l on d7, and the number of white blood cells appeare ...19958732077
comparison of adjuvant formulations for cytotoxic t cell induction using synthetic peptides.we have investigated the capacity of synthetic peptides delivered in different adjuvant formulations to induce cytotoxic t lymphocyte (ctl) responses to a class i h-2kd-restricted plasmodium berghei circumsporozoite epitope, cs 252-260. using three immunogen formulations: soybean emulsion; montanide isa720; and lipopeptide (p3-cs), we first evaluated the effects of immunization routes on ctl induction. no ctl response was induced in mice immunized s.c. or i.p. with cs peptide formulated in soybe ...19968735553
pyrrolo[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines as conformationally restricted analogues of the antibacterial agent trimethoprim.conformationally restricted analogues of the antibacterial agent trimethoprim (tmp) were designed to mimic the conformation of drug observed in its complex with bacterial dihydrofolate reductase (dhfr). this conformation of tmp was achieved by linking the 4-amino function to the methylene group by one- and two-carbon bridges. a pyrrolo[2,3-d]pyrimidine, a dihydro analogue, and a tetrahydropyrido[2,3-d]pyrimidine were synthesized and tested as inhibitors of dhfr. one analogue showed activity equi ...19968735847
immunity to plasmodium berghei exoerythrocytic forms derived from irradiated sporozoites.the nature of immunity generated by plasmodium berghei exoerythrocytic (ee) stages developing from irradiated sporozoites was studied using in vivo parameters of host protection on immunization with irradiated sporozoites and in vitro parameters of inhibition of sporozoite invasion and ee form development by serum antibodies from immunized mice. on in vivo challenge of immunized mice by sporozoites, protection was observed in an irradiation-dose-dependent manner. this finding stresses that prote ...19968740544
participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria.we determined the requirement for selected lymphocyte subsets and cytokines in the pathogenesis of experimental murine cerebral malaria (cm) by using gene-targeted knockout and mab-suppressed mice. plasmodium berghei anka infection induced cm in a 0/0 mice, which lack expression of surface mhc class ii glycoproteins and consequently express a severe and chronic reduction in numbers of cd4+ t cells. however, when a 0/0 mice, which are on a c57bl/6 x 129 genetic background, or immune-intact c57bl/ ...19968759747
naphthylisoquinoline alkaloids exhibit strong growth-inhibiting activities against plasmodium falciparum and p. berghei in vitro--structure-activity relationships of dioncophylline c.the growth-inhibiting activities of naturally occurring naphthylisoquinoline alkaloids against asexual blood stages of plasmodium falciparum (nf 54, clone a1a9) and p. berghei (anka) were studied in vitro. three of the alkaloids [7-epi-dioncophylline a (8b), dioncolactone a (4), and 5'-o-demethyl-8-o-methyl-7-epidioncophylline a (11)] displayed good activities against both parasites, with median inhibitory concentrations (ic50) of 1-5 micrograms/ml. dioncophylline c (2), however, was even better ...19968762401
comparison of numerous delivery systems for the induction of cytotoxic t lymphocytes by immunization.a variety of vaccine delivery systems including peptides with various adjuvants, recombinant particles, live recombinant viruses and bacteria and plasmid dna were tested for their ability to induce cd8+ cytotoxic t lymphocytes (ctl) against a well-defined epitope (amino acids 252-260) from the circumsporozoite (cs) protein of plasmodium berghei. we compared routes of immunization that would be applicable for the administration of a malaria vaccine in humans. the majority of these vaccines did no ...19968765044
antimalarial activity of novel arylene bis(methylketone) compounds.because of the spread of drug-resistant plasmodium species, there is an urgent need for novel effective antimalarial agents. a series of arylene bis(methylketone) compounds were screened in vitro against a number of plasmodium falciparum clones and in vivo against plasmodium berghei. 2-amino-4-(3,5-diacetylphenyl)amino-1,6-dimethylpyrimidinium chloride (cytokine network inc. [cni]-h0294) was the most effective of the compounds in vitro, with an ic50 of 1.5-4.0 microm against parasite clones with ...19968769633
the large difference in infectivity for mice of plasmodium berghei and plasmodium yoelii sporozoites cannot be correlated with their ability to enter into hepatocytes.sporozoites of p. yoelii nigeriensis are 50-100-times more infective to mice than the strain nk65 of p. berghei. to study the mechanisms involved in this striking difference in the infectivity of these closely related species of malaria parasites, we have developed a quantitative pcr targeted to parasite-specific ribosomal rna. using this method, we detect rna from a single sporozoite, and exo-erythorcytic forms of rna in the livers of mice injected with 200 sporozoites. we find that 20 h after ...19968784767
studies on heme and heme oxygenase during plasmodium berghei infection in golden hamsters.heme and heme degrading enzymes namely heme-oxygenase (ho) and biliverdin reductase (br) were monitored in liver and spleen during plasmodium berghei infection in golden hamsters. there was a sequential rise in the levels of heme and ho with the rise in parasitaemia. br was also significantly increased in these organs following infection.19958786168
the malaria sporozoite's journey into the liver.perhaps the most challenging event of the malaria parasite's lifecycle is the sporozoite's journey to the hepatocyte. because few parasites are injected by the mosquito, they must be efficiently and rapidly targeted to hepatocytes, where they will invade and develop into merozoites, the form of the parasite infective for red blood cells. little is known about how sporozoites make their way to the liver and subsequently invade hepatocytes. some evidence suggests that they are initially trapped by ...19968805080
antimalarial and toxic effects of the acyclic nucleoside phosphonate (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine in plasmodium berghei-infected mice.plasmodium berghei-infected mice died with low levels of parasitemia after repeated intraperitoneal administration (five times at 15 mg kg of body weight-1 every other day) of the in vitro active antimalarial acyclic nucleoside phosphonate (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(s)-hpmpa]. toxicological studies showed that the main cause of death resulted from (s)-hpmpa-induced nephrotoxicity. although concomitant intraperitoneal administration of the tubular epithelium transport bl ...19968807044
malaria, blood glucose, and the role of tumour necrosis factor (tnf) in mice.hypoglycaemia in falciparum malaria is associated with a poor prognosis and is correlated with mortality. high levels of serum tnf are also correlated with disease severity and mortality, and it has been suggested that tnf may cause the hypoglycaemia. however hypoglycaemia in mice infected with plasmodium chabaudi or the lethal strain of p. yoelii ym is related to hyperinsulinaemia. its development was not prevented by treatments which diminished tnf activity or production without affecting leve ...19968809132
a method for the quantitative assessment of malaria parasite development in organs of the mammalian host.a non-radioactive pcr method was developed to quantify the development of malaria parasites in the infected host. this was achieved by using plasmodium genus-specific primers corresponding to the parasite's small subunit ribosomal rna genes. the quantification of the pcr product was performed by high performance liquid chromatography, and calibration curves were obtained by amplification from defined quantities of purified plasmodium genomic dna. using this method, it was possible to quantify de ...19968813659
sequence analysis of the apical membrane antigen-1 genes (ama-1) of plasmodium yoelii yoelii and plasmodium berghei. 19968813699
re-investigation of the circumsporozoite protein-based induction of sterile immunity against plasmodium berghei infection.although the circumsporozoite protein (csp) of the malaria parasite is the most immunologically characterized protein, the goal of using this protein in an effective vaccine has not yet been realized. monoclonal antibody against the repetitive immunodominant b-epitope of the csp can protect mice from malaria, but vaccines that induce antibody against this epitope do not consistently induce protection. toward developing a rationale for a csp-based effective vaccine, we have re-investigated the ab ...19968817831
identification of a plasmodium berghei antigen sharing common features with p. falciparum and p. chabaudi parasitophorous-vacuole membrane antigens.on the basis of immunological cross-reactivity, we identified a 43-kda plasmodium berghei antigen with homology to the exp-1 antigen from p. falciparium. the p. berghei antigen was recognized by an antibody directed against an epitope on the c-terminus of the p. falciparum exp-1 protein. this antigen is localized on the surface of the parasite and shares peptide sequence homology with the p. chabudi antigen ag3008. to investigate further the role of the p. berghei antigen, we designed antisense ...19968825207
the erythrocytic schizogony of two synchronized strains of plasmodium berghei, nk65 and anka, in normocytes and reticulocytes.by a modified percoll-glucose centrifugation technique the rings and young trophozoites of two strains of plasmodium berghei, nk65 and anka, were separated from the other erythrocytic stages and inoculated into mice. the subsequent infection was followed for anka in normal mice and for nk65 in normal mice and in mice with high-grade reticulocytosis induced by injections of phenylhydrazine. the duration of the erythrocytic schizogony of the nk65 strain was shown to be independent of the age of th ...19968825215
4-aminoquinoline analogs of chloroquine with shortened side chains retain activity against chloroquine-resistant plasmodium falciparum.we have synthesized several 4-aminoquinolines with shortened side chains that retain activity against chloroquine-resistant isolates of plasmodium falciparum malaria (w. hofheinz, c. jaquet, and s. jolidon, european patent 94116281.0, june 1995). we report here an assessment of the activities of four selected compounds containing ethyl, propyl, and isopropyl side chains. reasonable in vitro activity (50% inhibitory concentration, < 100 nm) against chloroquine-resistant p. falciparum strains was ...19968843292
heme oxygenase and related indices in chloroquine-resistant and -sensitive strains of plasmodium berghei.chloroquine-resistant (cqr) and -sensitive (cqs) plasmodium berghei k173 strains possessed significant activities of heme oxygenase, biliverdin reductase and heme polymerase. heme oxygenase and biliverdin reducatase activities of cqr were significantly higher (7-10 fold) as compared to that of cqs p. berghei, whereas heme polymerase showed a reverse trend (two-fold decrease). however, a 10-fold increase in heme, three-fold increase in ferriprotoporphyrin ix and a two-fold increase in hemozoin le ...19958847167
induction of anti-malarial transmission blocking immunity with a recombinant ookinete surface antigen of plasmodium berghei produced in silkworm larvae using the baculovirus expression vector system.we have studied pbs21, a major ookinete surface protein of plasmodium berghei, for the development of a model transmission blocking immunogen. in the mouse, recombinant pbs21 expressed in the escherichia coli expression system (ecrpbs21) is not as effective in inducing transmission blocking antibodies as native pbs21 (npbs21), possibly because of differences in post-translational processing between ecrpbs21 and npbs21. in an attempt to improve the efficacy of the recombinant molecule, we describ ...19968852407
upregulation of reactive oxygen and nitrogen intermediates in plasmodium berghei infected mice after rescue therapy with chloroquine or artemether.plasmodium berghei anka infected c57b1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. when parasitaemia reached 10%, p. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. artemether and chloroquine were highly efficient. functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen interm ...19968858461
an exploration of the structure-activity relationships of 4-aminoquinolines: novel antimalarials with activity in-vivo.the structure-activity relationships of bisquinolines, a potentially important group of novel antimalarial drugs, were studied. the high-temperature (180-250 degrees c) synthesis of 4-aminoquinolines, including bisquinolines, by nucleophilic displacement was both fast and efficient several bisquinolines including (+/-)-trans-n1,n2-bis(7-trifluoroquinolin-4-yl)cyclohexane-1, 2-diamine and 1r,2r-(-)-, 1s,2s-(+)-, (+/-)-trans- and cis-n1, n2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine exhibit ...19968887736
a chromatin-associated protein is encoded in a genomic region highly conserved in the plasmodium genus.a single copy gene, pbb7, encoding a putative 26 kda acidic protein has been isolated from plasmodium berghei and appears to be part of a genomic region well conserved within the plasmodium genus. the deduced amino acid sequence exhibits significant blocks of similarity with nucleosome assembly proteins from yeast and man. the nuclear localization of the natural protein and its close association with chromatin during the entire erythrocytic cycle of the parasite have been demonstrated using spec ...19968892296
release of malaria circumsporozoite protein into the host cell cytoplasm and interaction with ribosomes.to date, the circumsporozoite (cs) protein has been implicated in guiding malaria sporozoites to the liver [cerami et al., cell 70, 1992, 1021-1033]. here we show that shortly after invasion, p. berghei and p. yoelii sporozoites lie free in the invaded cell and release considerable amounts of cs protein into the cytoplasm. the intracytoplasmic deposition of cs protein begins during the attachment of the sporozoite to the host cell surface and reaches its peak during the first 4-6 h after invasio ...19968898331
recombinant plasmodium falciparum dihydrofolate reductase-based in vitro screen for antifolate antimalarials.we describe the system for screening the effective antifolate antimalarials that uses the recombinant plasmodium falciparum dhfr domain of the bifunctional dhfr-ts expressed in escherichia coli, and were designed with amino acid alterations found in the dhfr genes of the antifolate resistant strains. the validity of the screen was verified by the subsequent examination of several substituted pyrrolo[2,3-d]pyrimidines for their antimalarial activity. among the 120 chemical derivatives, 5 compound ...19968898337
correlation between enhanced vascular permeability, up-regulation of cellular adhesion molecules and monocyte adhesion to the endothelium in the retina during the development of fatal murine cerebral malaria.the relationships between increased vascular permeability to protein, monocyte adherence to the endothelium, and expression of the cell adhesion molecules, intercellular adhesion molecule-1 (icam-1) and vascular cell adhesion molecule-1 (vcam-1) in the central nervous system microvasculature were studied during the progression of fatal murine cerebral malaria. cba mice were inoculated with plasmodium berghei anka, and changes in the retinal microvasculature were examined on days 3, 5, and 7 post ...19968909263
facilitation of rift valley fever virus transmission by plasmodium berghei sporozoites in anopheles stephensi mosquitoes.certain mosquito species are susceptible to viral infection but cannot transmit the virus due to a salivary gland barrier. we hypothesized that such species could transmit virus if the mosquito were infected with both virus and malaria parasites. malaria sporozoites disrupt the integrity of mosquito salivary glands and, in so doing, may destroy salivary gland barriers to viral transmission. to examine this postulate, the model system of rift valley fever (rvf) virus and a rodent parasite, plasmo ...19968916797
apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase.a novel fungal metabolite, apicidin [cyclo(n-o-methyl-l-tryptophanyl-l -isoleucinyl-d-pipecolinyl-l-2-amino-8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal activity in vitro against apicomplexan parasites has been identified. it is also orally and parenterally active in vivo against plasmodium berghei malaria in mice. many apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and n ...19968917558
molecular electronic properties of a series of 4-quinolinecarbinolamines define antimalarial activity profile.a detailed computational study on a series of 4-quinolinecarbinolamine antimalarials was performed using the semiempirical austin model 1 (am1) quantum chemical method to correlate the electronic features with antimalarial activity and to illuminate more completely the fundamental molecular level forces that affect the function and utility of the compounds. ab initio (3-21g level) calculations were performed on mefloquine, the lead compound in this series, to check the reliability of the am1 met ...19968917651
experimental congenital toxocariasis: effect on foetal future immune response.congenital parasitic infections may not lead to any overt clinical effects but could modulate the foetal future immune response to the same parasite depending on whether sensitization or tolerance has occurred in utero. in this study, pregnant female mice were infected with toxocara canis eggs at different gestational age, then the offspring were next challenged with toxocara eggs 6 weeks after birth and their immune response was assessed by estimation of the eosinophilic count and serum ige con ...19968918035
cell surface glycosaminoglycans are not obligatory for plasmodium berghei sporozoite invasion in vitro.the malaria circumsporozoite (cs) protein binds to glycosaminoglycan chains from heparan sulfate proteoglycans present on the basolateral surface of hepatocytes and hepatoma cells in vitro. when injected into mice, cs protein is rapidly cleared from the blood circulation by hepatocytes. the binding region for the hspgs is the evolutionarily conserved region ii-plus of the cs protein. here we have asked whether the presence of glycosaminoglycans on the plasma membrane of target cells is required ...19968920011
dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (lrp) and heparan sulfate proteoglycans.speed and selectivity of hepatocyte invasion by malaria sporozoites have suggested a receptor-mediated mechanism and the specific interaction of the circumsporozoite (cs) protein with liver-specific heparan sulfate proteoglycans (hspgs) has been implicated in the targeting to the liver. here we show that the cs protein interacts not only with cell surface heparan sulfate, but also with the low density lipoprotein receptor-related protein (lrp). binding of 125i-cs protein to purified lrp occurs w ...19968920859
a one-step lysis procedure for 18s ribosomal rna-based diagnosis of infection by plasmodium species. 19968921197
localization of ribosomal rna and pbs21-mrna in the sexual stages of plasmodium berghei using electron microscope in situ hybridization.a reproducible technique for the ultrastructural localization of rnas in malaria parasites has been developed which combines excellent structural preservation with high hybridization signals. signals obtained following in situ hybridization with an antisense rrna probe which recognizes all forms of small subunit (ssu) rrna correlate with the density of ribosomes in the parasite cytoplasm and show that a) the male gametocyte has only 12 to 25% the ribosomes found in the female cell and asexual pa ...19968929565
mitochondrial heme oxygenase of mastomys coucha.while studying the fate of heme generated during malaria infection, it was observed that mitochondrial preparations were highly enriched with heme compared to other subcellular particles. with this background, the present study aimed to determine the status of mitochondrial heme oxygenase and compare it with the microsomal enzyme. mitochondrial and microsomal preparations were obtained from liver, spleen, kidney and brain of normal, inducer (cobalt chloride and hemin)-treated and plasmodium berg ...19968930130
synthesis and immunostimulant activity of novel analogs of human casein fragment (54-59).structural analogs of the hexapeptide sequence 54-59 (a) human casein, reported to stimulate immune response, were synthesized and evaluated for immunostimulant activity. hexapeptide 91/409 (c), 90/649 (d) and 91/361 (e) stimulated higher antibody titre and delayed type of hyper-sensitivity (dth) response than the natural casein hexapeptide in balb/c mice-sheep red blood cells (srbc) and guinea pig-ovalbumin models. these peptides also induced higher stimulation of non-specific immune response a ...19968933167
molecular cloning and antigenic mapping of heat-shock protein 70 from the malaria species plasmodium berghei.we have isolated a 70-kd heat-shock protein (hsp-70) cdna from plasmodium berghei. a cdna clone encoding the p. berghei hsp-70 was isolated and sequenced, demonstrating that it is highly homologous with other plasmodium hsp-70s. one of the common features is a series of ggmp amino acid repeats at the carboxy terminus; there is also a long, at-rich 5' untranslated region, a hallmark of other malarial rnas. hydropathy and antigenicity analyses suggest the presence of two hydrophilic domains. recom ...19968940993
heat-labile and heat-stimulable heme polymerase activities in plasmodium berghei. 19968946392
plasmodium berghei: infectivity of mice to anopheles stephensi mosquitoes.the infectivity of p. berghei-infected to mice to mosquitoes declines rapidly 2 to 5 days after blood inoculation, in spite of rising numbers of gametocytes in the blood. this pattern is typical of many malaria infections and various factors, particularly specific and nonspecific immune responses, have previously been implicated in the decline. here we report that (1) simple physiological changes in the mouse blood, namely, falling ph and bicarbonate levels induced by high parasitaemias, are res ...19968948326
[effect of momordica charantia l. in mice infected with plasmodium berghei].according to the world health organization malaria is one of the major public health problems in brazil and all over developing countries, where 80% of the population use traditional medicine to solve their primary medical problems. both treatment and control of this parasitosis have become difficult, because of parasite strains that are resistant to conventional drugs, such as chloroquine. that makes the search for new antimalarial drugs not only important but urgent. we aimed therefore at eval ...19968966309
cd8 beta increases cd8 coreceptor function and participation in tcr-ligand binding.to study the role of cd8 beta in t cell function, we derived a cd8 alpha/beta-(cd8-/-) t cell hybridoma of the h-2kd-restricted n9 cytotoxic t lymphocyte clone specific for a photoreactive derivative of the plasmodium berghei circumsporozoite peptide pbcs 252-260. this hybridoma was transfected either with cd8 alpha alone or together with cd8 beta. all three hybridomas released interleukin 2 upon incubation with l cells expressing kd-peptide derivative complexes, though cd8 alpha/beta cells did ...19968976201
induction of sustained and elevated immune responses to weakly immunogenic synthetic malarial peptides by encapsulation in biodegradable polymer microspheres.biodegradable microspheres (ms) based on poly(d,l-lactide) and poly(d,l-lactide-coglycolide) have the capacity to release encapsulated antigens over defined lengths of time depending on their composition and to elicit and sustain strong and long-lasting immune responses to protein antigens. in the present study, two synthetic multiple antigenic peptides (map), p30b2 and (nanp)6p2p30, were incorporated into ms of different compositions. p30b2 and (nanp)6p2p30 are composed of one or two universal ...19968994320
15-deoxyspergualin, an immunosuppressive agent, used in organ transplantation showed suppressive effects on malarial parasites.deoxyspergualin (dsg), which was discovered to be an immunosuppressive agent, was examined for its in vivo effect on parasites of rodent malaria. although the mice that were not treated by dsg had an increased parasite percentage (% parasitemia) until they died, those that were treated with dsg had a decreased parasitemia and finally had 0% parasites. the spleens of infected mice became small by dsg treatment. parasitemia of mice increased again after dsg treatment was stopped. however, dsg was ...19978996739
circumsporozoite protein is required for development of malaria sporozoites in mosquitoes.malaria parasites undergo a sporogonic cycle in the mosquito vector. sporozoites, the form of the parasite injected into the host during a bloodmeal, develop inside oocysts in the insect midgut, then migrate to and eventually invade the salivary glands. the circumsporozoite protein (cs), one of the major proteins synthesized by salivary gland sporozoites, is a surface-associated molecule which is important in sporozoite infectivity to the host. here, by gene targeting, we created plasmodium berg ...19979002517
resistance to cerebral malaria in tumor necrosis factor-alpha/beta-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and t helper type 1 response.tumor necrosis factor (tnf) induced by plasmodium berghei anka (pba) infection was suggested to play an important role in the development of cerebral malaria (cm). we asked whether tnf-alpha/beta double-deficient mice, which have a complete disruption of the tnf-signaling pathways, are protected from cm and what might be the possible mechanisms of protection. pba infection induces fatal cm in wild-type mice, which die within 5 to 8 days with severe neurological signs. in contrast, tnf-alpha/beta ...19979006341
further characterization of a 58 kda plasmodium berghei phosphoprotein as a cochaperone.molecular chaperones are important for proper protein folding during protein biogenesis. this report describes a protein from plasmodium berghei which is 30% identical and 40% similar to a recently described mammalian cochaperone, or heat shock protein 70 interacting protein. the p. berghei cochaperone accumulates throughout the trophozoite stage and decreases during the schizont stage. the stage specific expression is consistent with its presumed role in protein folding or protein-protein inter ...19969010839
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