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[congenital malaria--a rare neonatal infection].tropical diseases are rare in childhood in european countries, but tourism and an increasing number of immigrants from countries with endemic malaria may lead to a higher incidence. our report is about a 24 year old german pregnant who was infected with malaria tropica in togo during the last trimester of pregnancy. twenty days after delivery by caesarean section one of the geminies showed symptoms of florid infection: irritability, fever, haemolytic anaemia, hepato-splenomegaly, and thrombocyto ...19902355929
suppression of both antimony-susceptible and antimony-resistant leishmania donovani by a bis(benzyl)polyamine analog.it was recently demonstrated that a bis(benzyl)polyamine analog (mdl 27695; n,n'-bis(3-[(phenylmethyl)amino]propyl)-1,7-diaminoheptane) possessed potent antimalarial activity in vitro and in vivo (a. j. bitonti, j. a. dumont, t. l. bush, m. l. edwards, d. m. stemerick, p. p. mccann, and a. sjoerdsma, proc. natl. acad. sci. usa 86:651-655, 1989). we now report that mdl 27695 also has potent antileishmanial activity, eliminating 77 to 100% of leishmania donovani amastigotes from mouse peritoneal m ...19902360812
immune response in patients with amoebiasis: evaluation of igg-subclasses.in order to evaluate the immune response with respect to igg-subclasses (igg1-igg4) in patients with extraintestinal amoebiasis, an elisa technique was established. it was the aim of this pilot study to quantify the igg subclass response and to compare the resulting pattern with other systemic protozoal infections. our results give evidence that igg4 contributes to more than one third of the total immune response, followed by igg2, igg3 and igg1. regarding the igg4 response in patients with plas ...19902360971
[strategies for prevention of human malaria. some proposals for central africa].the occurrence and the extension of chemoresistance of plasmodium falciparum to antimalaria drugs in central africa set to think about new strategies of prevention. beside chemoprophylaxis limited to certain groups at particular risks, the authors suggest to rehabilitate vector control and particularly to promote the systematized use of bed-nets impregnated with residual insecticides. prevention of lethality has to continue to use, in first instance, quinine and amino-4-quinoleins, under conditi ...19902366647
malaria exoantigens induce t-independent antibody that blocks their ability to induce tnf.much of the pathology of malaria may be due to the interactions of cytokines, especially tumour necrosis factor (tnf), with various cell types, including endothelial cells, with consequent widespread systemic effects. it has been shown previously that heat-stable exoantigens in the supernatants of blood-stage parasite cultures induced the release of tnf in vitro from activated macrophages and behaved like toxins in vivo, that mice immunized with the antigens are protected from the toxic effect a ...19902379940
antimalarial activity of a combination of 5-fluoroorotate and uridine in mice.malarial parasites, in contrast to mammalian cells, utilize orotic acid more efficiently than uracil or uridine. recently, chloroquine-susceptible and chloroquine-resistant clones of plasmodium falciparum were shown to be inhibited by 5-fluoroorotate, with a 50% inhibitory concentration of 6 nm in vitro. mammalian cells were far less sensitive to 5-fluoroorotate, particularly in the presence of uridine. in this report, the antimalarial activity of 5-fluoroorotate was tested in vivo. initially, l ...19902386369
characterization of malaria transmission by anopheles (diptera: culicidae) in western kenya in preparation for malaria vaccine trials.malaria transmission was studied for 33 mo in the villages of kisian and saradidi in western kenya in preparation for field trials of malaria vaccines. abundance estimates of anopheles gambiae giles sensu lato and anopheles funestus giles, which constituted over 99% of 26,645 anophelines collected, were compared for all-night biting collections inside houses, outdoors, and in tents. the overall numbers of anopheles per man-night were 2.3 times greater in kisian than in saradidi. for the three ty ...19902388233
cloning and analysis of beta-tubulin gene from a protoctist.we have isolated and characterized by restriction endonuclease mapping, transcription pattern, and dna sequencing a beta-tubulin gene from the coenocytic freshwater protoctist, achlya klebsiana. the gene is intronless and has a single open reading frame that encodes a 444-amino acid residue polypeptide of mr 49,856. the protein shows a high degree of homology to other beta-tubulins, 85% identity to human beta-tubulin and 89% identity to beta-tubulin of the sporozoan (also a protoctist) plasmodiu ...19902394720
inhibition of intraerythrocytic development of plasmodium falciparum by proteinase inhibitors.a group of inactivators of cysteinyl proteinases which function by covalent bond formation have been examined for their ability to inhibit the development of plasmodium falciparum within red blood cells. the most effective of these caused inactivation of the parasite near 10(-8) m concentration. the range of inhibitory action varied with peptide structure in a manner characteristic of affinity labels for proteinases suggesting that the target of inhibition was an unidentified proteinase, probabl ...19902403526
tumor necrosis factor production by human macrophages stimulated in vitro by plasmodium falciparum.production of tumor necrosis factor by human macrophages may be induced in vitro by cytoadherent and noncytoadherent strains of plasmodium falciparum, with an optimal ratio of one to three parasitized erythrocytes per macrophage. centrifuged and heated crude culture supernatants have the same effect, thus showing the existence of a thermostable soluble factor able to induce this expression. in vitro kinetic experiments have shown that the secretion of tumor necrosis factor appears early, with a ...19902403531
public-health epidemiology in vanuatu.vanuatu, which formerly was known as the new hebrides, is an archipelago in the southwest pacific ocean with a tropical humid climate. the national health system and the state of health of the population generally are satisfactory. the main diseases of public-health importance are malaria and tuberculosis. their epidemiology and control are discussed. an epidemic of plasmodium falciparum malaria, which commenced in 1980, is described; this possibly can be explained by an increase in chloroquine- ...19902403624
treatment of severe malaria by exchange transfusion. 19902403649
plasmodium falciparum: studies on mature exoerythrocytic forms in the liver of the chimpanzee, pan troglodytes.mature exoerythrocytic forms (eef) of plasmodium falciparum from the chimpanzee were examined by light- and transmission electron microscopy from a liver biopsy taken on day 6 after sporozoite inoculation. infectivity of the sporozoites obtained from whole mosquitoes which were membrane fed on cultured gametocytes was about 4-6%. in comparison, salivary gland sporozoites added to human hepatocytes in vitro had only a developmental percentage of 0.02 to 0.05% at day 5. the eef found in the liver ...19902403931
flavin analogs with antimalarial activity as glutathione reductase inhibitors.10-(4'-chlorophenyl)-3-methylflavin has antimalarial activity in vitro and in vivo (cowden et al., j med chem 31: 799, 1988). this flavin analog and two of its derivatives were found to inhibit the antioxidant flavoenzyme glutathione reductase from human erythrocytes in its isolated form as well as in hemolysates. the mixed-type inhibition was completely reversible, the ki-values being of the order of 1 microm. surprisingly, the drugs were not competitive with fad, but with gssg, one of the enzy ...19902404494
plasmodium falciparum: two antigens of similar size are located in different compartments of the rhoptry.two previously described antigens, ama-1 and qf3, which are located in the rhoptries of plasmodium falciparum merozoites have polypeptides of similar relative molecular masses. on immunoblots, antibodies to both antigens recognized polypeptides of relative molecular mass 80,000 and 62,000 in all isolates tested. two-dimensional electrophoresis showed that the isoelectric points of the two antigens were different. qf3 being more basic than ama-1. ama-1 was soluble in triton x-114 whereas qf3 part ...19902404781
chemical crosslinking of plasmodium falciparum glycoprotein, pf200 (190-205 kda), to the s-antigen at the merozoite surface.merozoites were isolated from plasmodium falciparum cultures labeled with [3h]mannose and [35s]methionine and treated with a cleavable homobifunctional crosslinker, dithiobis(succinimidyl) propionate. the crosslinked complexes were immunoprecipitated with mab.5b1 directed against the major merozoite surface glycoprotein. pf200 (mw 190-205), and reduced with dithiothreitol. crosslinked immunocomplexes did not contain the second major merozoite surface glycoprotein, pf50 (mw 45-55 kda), or other m ...19902404782
mefloquine for malaria. 19902405246
quantitation of antisporozoite immunoglobulins in the hemolymph of anopheles stephensi after bloodfeeding.passage of rat antibodies induced by plasmodium falciparum circumsporozoite protein (anti-cs igg) from the bloodmeal into the hemocoel of uninfected anopheles stephensi mosquitoes was quantified using enzyme-linked immunosorbent assay (elisa) techniques. anti-cs igg were present in hemolymph immediately upon cessation of mosquito feeding. titers peaked at 3 hr post-ingestion then declined steadily, becoming negligible at 18 hr. substantial titers were present in the bloodmeal at 24 hr post-inges ...19902405724
an abc-elisa for malaria serology in the field.an avidin biotin peroxidase complex enzyme-linked immunosorbent assay (abc-elisa) was examined for the diagnosis of malaria in a controlled area in sudan gezira. the titers of the abc-elisa coincided with those of the ifat. the method was more sensitive than the ordinary elisa as the final enzyme reaction was amplified through the use of the abc system. this allowed the resulting color spots on the dried plate wells to be read clearly with the naked eye. this test can be carried out without usin ...19902405725
effect of malaria chemoprophylaxis on the development of antibodies to plasmodium falciparum in expatriates living in west africa.we studied the relationship between exposure to malaria, the use of long-term chemoprophylaxis with chloroquine, and the prevalence of sporozoite antibodies in 446 expatriates who had lived in 7 west african countries for 6 months-41 years. filter paper blood samples from 12% of the subjects had antibodies to the repeat region of the plasmodium falciparum circumsporozoite protein, with a positive correlation between enzyme-linked immunosorbent assay (elisa) absorbance and years of exposure (r = ...19902405726
specificity and inhibitory activity of antibodies to plasmodium falciparum aldolase.the multiplication of plasmodium falciparum within rbc is energy-dependent and the glucose consumption of infected rbc is increased more than 50 times over the consumption of normal rbc. high levels of glycolytic enzymes such as fructose-1,6-diphosphate aldolase (p41) have been detected in infected rbc. expression of the cloned aldolase gene of p. falciparum in escherichia coli resulted in an enzymatically active polypeptide with a high sp. act. and the recombinant p41 aldolase was used for enzy ...19902406342
plasmodium falciparum: increased and multiple invasion during short periods of time.we describe how to obtain an increased merozoite invasion of plasmodium falciparum into human erythrocytes during short periods of time. using this procedure, infected erythrocytes show multiple invasions (2-4 merozoites per erythrocyte), amplifying, several times, the effects of parasite entry into host cells. the procedure yields synchronous cultures (2-h age range) with parasitemia as high as 15%. it is possible to reach parasitemia of 50% or higher allowing for a 6-h invasion period.19902406430
antimalarial properties of imipramine and amitriptyline.dietary riboflavin deficiency is known to diminish malarial parasitemia. in this study, we determined whether imipramine and amitriptyline, drugs which inhibit riboflavin metabolism, have antimalarial efficacy. in addition, we evaluated whether these drugs, like other antimalarial agents, increase the hemolytic response to ferriprotoporphyrin ix (fp). the growth of plasmodium falciparum (fcr3) in the absence and presence of these drugs (10 to 75 microm) was measured by determining (3h)hypoxanthi ...19902406432
s-antigen localization in the erythrocytic stages of plasmodium falciparum.localization of the s-antigen of plasmodium falciparum isolate fcq27/png, from papua new guinea, was studied by post-embedding immunoelectron microscopy using affinity-purified rabbit antibodies raised against the repeat region of the antigen. labelling was found in the parasitophorous vacuole (pv) space of early to late schizonts and in pv-related vesicles within the erythrocyte cytoplasm of schizont-infected cells. other subcellular structures within the erythrocyte cytoplasm were not labelled ...19902406433
dihydrofolate reductase mutations and chromosomal changes associated with pyrimethamine resistance of plasmodium falciparum.the nucleotide sequence of the dihydrofolate reductase-thymidylate synthase (dhfr-ts) gene in pyrimethamine-resistant (pyrr) mutants of plasmodium falciparum selected in vitro was examined to determine if specific mutations in dhfr were associated with drug resistance. we analysed the sequence of genomic dna from strain fcr3, from eight previously isolated pyrr parasites derived from fcr3, and from strain honduras-1. we found that: (1) five pyrr fcr3 mutants, fcr3-d4-d8, had an identical nucleot ...19902406591
binding of plasmodium falciparum rhoptry proteins to mouse erythrocytes and their possible role in invasion.rhoptry proteins of plasmodium falciparum merozoites, of 140, 130, and 110 kda, identified by co-precipitation with mab.1b9, bind selectively to mouse erythrocytes and reticulocytes. the properties of binding are shown to correlate with invasion of p. falciparum into mouse erythrocytes. invasion of two strains of p. falciparum 7g8 and fcr-3, into mouse erythrocytes was examined, and was found to differ significantly. the 7g8 strain invades mouse erythrocytes at a rate of 40-60% compared to invas ...19902406596
quinine-induced hearing loss.sensorineural hearing loss due to quinine therapy for malaria has frequently been mentioned in the literature but has not been a subject of research during the last decades. the global spreading of chloroquine-resistant falciparum malaria brings about an increasing use of quinine. the ototoxicity of quinine can accurately be studied with ultrahigh frequency audiometry (up to 20 khz). the case of a 29-year-old man suffering from falciparum malaria disease who got a reversible hearing loss from qu ...19902406680
t-cell antigens and epitopes in malaria vaccine design. 19902407434
tumor necrosis factor enhances neutrophil-mediated killing of plasmodium falciparum.we developed a radiometric assay by which the antiplasmodial effects of phagocytic cells can be quantitated. this assay was used to examine the effects of recombinant human tumor necrosis factor alpha (tnf-alpha) on the killing of plasmodium falciparum by human neutrophils. data presented demonstrated that neutrophils engulf and destroy p. falciparum, but substantial killing of parasites required the presence of either heat-labile or heat-stable opsonins. while recombinant tnf-alpha at concentra ...19902407658
malaria: triple whammy for a traveler. 19902407874
[rapid staining methods for the detection of malaria parasites]. 19852408783
characterisation of p. falciparum antigenic determinants isolated from a genomic expression library by differential antibody screening.a genomic expression library of p.falciparum has been differentially screened with a number of immune sera. the response of 9 clones to the various sera is presented, together with the dna sequence encoding the epitopes. all but one clone are extremely a+t rich and unlike the other p.falciparum epitopes described, are not composed of amino acid repeats. one clone, which responds specifically with a protective serum, has been analysed in detail. the epitope is carried on a 160kd antigen which is ...19852409532
rationale for development of a synthetic vaccine against plasmodium falciparum malaria.protective immunity against malaria can be obtained by vaccination with irradiated sporozoites. the protective antigens known as circumsporozoite (cs) proteins, are polypeptides that cover the surface membrane of the parasite. the cs proteins contain species-specific immunodominant epitopes formed by tandem repeated sequences of amino acids. here it is shown that the dominant epitope of plasmodium falciparum is contained in the synthetic dodecapeptide asn-ala-asn-pro-asn-ala-asn-pro-asn-ala-pro ...19852409595
routine procedures for examination of stool and blood for parasites.the diagnosis of a parasitic infection depends upon demonstration of the organism in stool, blood, or tissue specimens, and a variety of relatively simple procedures is available for this purpose. in this article, the author describes those procedures that are most frequently used on a routine basis.19852410850
a blood stage antigen of plasmodium falciparum shares determinants with the sporozoite coat protein.a cdna clone expressing a plasmodium falciparum blood-stage antigen in escherichia coli was identified by colony immunoassay using immune human sera. antibodies affinity-purified on extracts of this clone reacted with both asexual blood stages and sporozoites of p. falciparum, recognizing a mr23,000 protein in the blood stages. the nucleotide sequence of the cdna revealed a signal peptide and an internal hydrophobic sequence typical of transmembrane anchor sequences. located 3' to the putative a ...19852410913
[recent findings on the molecular biology of plasmodium antigens].the cloning of several genes coding for plasmodium antigens has allowed to determine the nucleotide sequence of these genes and to deduce the amino acid sequence of the antigens. in this review we summarize the first results concerning the csp of p. knowlesi and p. falciparum as well as several antigens from the asexual erythrocytic stages. these antigens show the unique feature to contain one or several antigenic determinants composed of repetitive units.19852411439
ubiquity of the repetitive epitope of the cs protein in different isolates of human malaria parasites.sporozoites of the human malaria plasmodium falciparum and plasmodium vivax obtained from a large number of endemic areas were screened with species-specific monoclonal antibodies that recognize the repeated epitopes of the respective circumsporozoite (cs) proteins. by using a two-site immunoradiometric assay, it was determined that all the parasite isolates of a given species react with a single monoclonal antibody, indicating the presence of a common repeated epitope. polyacrylamide gel electr ...19852411813
the malaria sporozoite vaccine: parasitology's brave new world. 19852411830
[antigenic specificity of antiplasmodium antibodies in an endemic area: an attempt at correlation with the induction of protective immunity].asexual blood-stage antigens from plasmodium falciparum related to the development of protective immunity in an endemic area were identified by statistical comparison of antigens recognized by adult immune sera with those recognized by non-immune subjects (children). after metabolic labelling of parasites in culture and immunoprecipitation, target antigens of seric antibodies were separated by polyacrylamide gel electrophoresis/sds and detected by fluorography. two groups of antigens were thus i ...19852412483
two apparently nonrepeated epitopes on gametes of plasmodium falciparum are targets of transmission-blocking antibodies.one-site and two-site immunoradiometric assays have been developed against an antigen on gametocytes of plasmodium falciparum, using monoclonal antibodies (mabs) which block transmission of the parasites to mosquitoes. three such mabs have been studied, each of which immunoprecipitates a complex of three gamete surface proteins of apparent mr 260,000, 59,000, and 53,000 from triton x-100 extracts of the parasites. the assays showed that the mabs recognized one or the other of two distinct, nonre ...19852412959
two plasmodium falciparum merozoite surface polypeptides share epitopes with a single mr 185 000 parasite glycoprotein.the malarial parasite plasmodium falciparum synthesizes a major glycoprotein (gp) of mr 185 000 during its asexual blood cycle. immunoprecipitation of [35s]methionine- or [3h]glucosamine-labeled schizont antigens indicated that two groups of polypeptides were distinguished with anti-gp 185 mouse monoclonal antibodies: group a was composed of glycosylated molecules of mr 185 000, 120 000, 90 000, 88 000, 46 000, and 40 000 while group b contained, in addition to gp 185, polypeptides of mr 152 000 ...19852414658
thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence.plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. knobs appear on infected erythrocytes and are the points of attachment to endothelium. sequestration may protect the parasite from splenic destruction and may play a role in the pathogenesis of cerebral malaria. correlates of sequestration have been developed in vitro using cultured human endothelium and a ...19852414670
circumsporozoite protein of plasmodium vivax: gene cloning and characterization of the immunodominant epitope.the gene encoding the circumsporozoite (cs) protein of the human malaria parasite plasmodium vivax has been cloned. the deduced sequence of the protein consists of 373 amino acids with a central region of 19 tandem repeats of the nonapeptide asp-arg-ala-asp/ala-gly-gln-pro-ala-gly. a synthetic 18-amino acid peptide containing two tandem repeats binds to a monoclonal antibody directed to the cs protein of plasmodium vivax and inhibits the interaction of this antibody with the native protein in sp ...19852414847
reactivity of a monoclonal antibody produced to the histidine-rich protein of plasmodium lophurae with plasmodium falciparum.monoclonal antibodies were produced against the histidine-rich protein of plasmodium lophurae and tested for reactivity with plasmodium falciparum antigens. one anti-histidine-rich protein monoclonal antibody showed immunological cross-reactivity with polypeptides of p. falciparum synthesized in vivo and in vitro.19852415817
sequence of a cdna encoding a small polymorphic histidine- and alanine-rich protein from plasmodium falciparum.we describe the expression in escherichia coli, isolation by immunological screening and complete nucleotide sequence of a cdna clone from the malaria parasite plasmodium falciparum. the deduced amino acid sequence contains separate blocks of repetitive hexapeptide and pentapeptide sequences and we have confirmed that these represent epitopes by reaction of the corresponding synthetic peptides with human antibodies. as the predicted size is mr 21,000 and the overall composition is 30% his and 29 ...19852415925
human-human hybridomas secreting monoclonal antibodies to the mr 195,000 plasmodium falciparum blood stage antigen.using the human lymphoblastoid cell line, gm 4672, and pbl of gambian adults immune to plasmodium falciparum (pf) malaria, we have produced human-human hybridomas and selected those that produce mab against pf antigens. the fusion frequency, using pwm-stimulated donor lymphocytes was between 6.8 x 10(-5) and 1.5 x 10(-6). using immune fluorescence, immune precipitation, and pf in vitro growth inhibition, we cloned four hybridomas that reacted with the pf mr 195,000 schizont/merozoite protein. th ...19862416867
antigens induced on erythrocytes by p. falciparum: expression of diverse and conserved determinants.red blood cells that are infected with the malaria parasite plasmodium falciparum express new antigens on their surface. in a study of these antigens in the erythrocytes of naturally infected children in the gambia, an antibody-mediated agglutination assay revealed an extreme degree of antigenic diversity. serum samples from each of ten children in the convalescent stage of malaria infection reacted with infected cells from the same child but generally not with infected cells from the other chil ...19862417315
a specific s-antigen of plasmodium falciparum is expressed in a proportion of primary isolates in brazil, thailand and papua new guinea.the expression by plasmodium falciparum of a specific s-antigen has been examined in primary isolates in different regions of the world using a monoclonal antibody that recognizes an epitope within a known repeated amino acid sequence. the epitope was expressed by a small proportion of primary isolates in each of brazil, thailand and papua new guinea, demonstrating that this s-antigen gene is widespread. the data are consistent with the possibility that the occurrence of p. falciparum strains ex ...19852417391
human lymphocyte responses to plasmodium falciparum merozoite antigens. a functional assay of protective immunity?merozoites obtained from cutaneous cultures of plasmodium falciparum were used as antigen for an in vitro lymphocyte assay. antigen specific proliferative responses were observed with lymphocytes from individuals with long-standing immunity to p. falciparum. donors whose last p. falciparum challenge occurred within the year preceding the assay exhibited lymphocyte responses significantly higher than those from donors whose infection was more remote. this suggests that a lymphocyte dependent assa ...19852417392
laboratory diagnosis of malaria. 19852417946
use of low molecular weight dextrans in cerebral malaria. 19852417947
analysis of plasmodium falciparum growth in culture using acridine orange and flow cytometry.the growth of plasmodium falciparum in cultures of human red blood cells was studied using acridine orange to stain rna and dna, followed by flow cytometric analysis. the cycle of the parasite is characterized by a period of growth, prior to initiation of dna synthesis, in which a significant increase in red fluorescence is observed, with only a small change in green fluorescence. following this phase, which is formally similar to the g1 period in mammalian cells, initiation of dna synthesis is ...19862418101
invasion of erythrocytes in vitro by plasmodium falciparum can be inhibited by monoclonal antibody directed against an s antigen.a monoclonal antibody has been produced which binds to the heat stable s antigen present in the fcq-27/png isolate of plasmodium falciparum. this monoclonal antibody also inhibits the invasion in vitro of erythrocytes by malarial merozoites thus demonstrating that the s antigens of plasmodium falciparum may be a target of protective immune responses.19852419821
antibody mediated strain-specific agglutination of plasmodium falciparum--parasitized erythrocytes visualized by ethidium bromide staining. 19852419822
rabbit and human antibodies to a repeated amino acid sequence of a plasmodium falciparum antigen, pf 155, react with the native protein and inhibit merozoite invasion.the plasmodium falciparum-derived antigen of mr 155,000 designated pf 155, deposited in the membrane of infected erythrocytes, contains at least two blocks of tandemly repeated amino acid sequences. the peptide glu-glu-asn-val-glu-his-asp-ala, which corresponds to a subunit of a c-terminally located repeat, was synthesized. rabbits immunized with the octapeptide conjugated with either keyhole limpet hemocyanine or tetanus toxoid formed antibodies against the octapeptide. these antibodies reacted ...19862419897
antibodies against circumsporozoite proteins of plasmodium falciparum induced by natural infection.sera from 10 individuals who lived in a malaria endemic area, 10 patients with acute uncomplicated falciparum malaria and 10 patients with cerebral malaria and hyperimmune mouse serum were tested for their reactivities against plasmodium falciparum sporozoite antigens by western blot analysis using 125i-labeled staphylococcal protein a as the detecting reagent. these sera were shown by indirect immunofluorescence and/or circumsporozoite precipitation test to have antibodies reacting against the ...19852420015
[future of vaccination: vaccines of the future]. 19852420263
ribose metabolism and nucleic acid synthesis in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes infected with plasmodium falciparum.the metabolism of pentose-phosphate was investigated in plasmodium falciparum-infected normal and glucose-6-phosphate dehydrogenase (g6pd)-deficient human red blood cells in vitro. 5'-phosphoribosyl-1-pyrophosphate (prpp) content of infected normal red blood cells was increased 50-60-fold at the parasite trophozoite growth stage over that of uninfected cells. the prpp increment in infected g6pd-deficient cells at comparable stage and parasitemia was only 40% of the value in normal infected cells ...19862420826
a rhoptry antigen of plasmodium falciparum contains conserved and variable epitopes recognized by inhibitory monoclonal antibodies.four monoclonal antibodies produced against plasmodium falciparum recognize an antigen in merozoites that is localized in rhoptries, as judged by a punctate, double dot fluorescence pattern. all four antibodies bound to the same affinity purified antigen in a two site immunoradiometric assay. immunoprecipitation of antigen by monoclonal antibody followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis yielded protein bands of 80, 66 and 42 kda. western blotting gave bands of 80 and ...19862421161
antigenic diversity and size diversity of plasmodium falciparum antigens in isolates from gambian patients. i. s-antigens.ring-stage asexual parasites of p. falciparum were collected from six gambian children and the s-antigens radiolabelled by 3h-glycine uptake during in vitro culture up to rupture of infected cells and merozoite release. ouchterlony double diffusion of boiled culture supernatants against a panel of adult gambian sera identified one s-antigen precipitin arc for five isolates and two precipitin arcs for one isolate. five of the six isolates were serologically distinct. analysis of s-antigens by com ...19862421225
antigenic diversity and size diversity of p. falciparum antigens in isolates from gambian patients. ii. the schizont surface glycoprotein of molecular weight approximately 200 000.a panel of monoclonal antibodies has been shown previously to identify both serologically diverse and serologically conserved epitopes on a major polymorphic surface protein of p. falciparum schizonts from culture-adapted isolates. the molecular nature of the antigen recognized by eight of these monoclonal antibodies was studied with three isolates analyzed directly from patients in the gambia. malarial (glyco) proteins were labelled by biosynthetic uptake of 3h-glucosamine or 3h-leucine during ...19862421226
an asparagine-rich protein from blood stages of plasmodium falciparum shares determinants with sporozoites.we describe a cdna clone derived from mrna of asexual blood-stages of the malaria parasite plasmodium falciparum. this clone, designated ag319, expresses a p.falciparum antigen fused to beta-galactosidase in escherichia coli. human antibodies from papua new guinea were affinity-purified by adsorption to extracts of ag319 immobilized on cnbr-sepharose. the antibodies reacted predominantly with p. falciparum polypeptides of mr 220,000 and 160,000, and a number of ill-defined lower molecular weight ...19862421257
temporal relationships on macromolecular synthesis during the asexual cell cycle of plasmodium falciparum.the over-all synthesis of dna, rna and protein was studied during the asexual cell cycle of plasmodium falciparum. a method for stringent synchronization of the culture was developed. rates of synthesis of the three macromolecules were determined every four hours by labelling the parasites with radioactive precursors during 30 min pulses. there was a peak of synthesis of dna at 44 hours. between 33 and 45 hours the rate of synthesis of dna was exponential. maximum rna synthesis was reached at 36 ...19852421464
potential vaccine antigens of the asexual blood-stages of plasmodium falciparum.we have constructed a cdna clone library that contains many natural immunogens of the asexual blood-stages of plasmodium falciparum. the corresponding parasite antigens have been identified with antisera raised against the antigens expressed in escherichia coli or with monospecific human antibodies purified on adsorbents prepared from various clones. sequencing studies on the clones have revealed that many malaria antigens contain extensive sequence repeats. these repeats encode antigenic epitop ...19852422079
plasmodium falciparum transmission blocking monoclonal antibodies recognize monovalently expressed epitopes.target proteins of transmission blocking monoclonal antibodies (moabs) are present on the surface of plasmodium falciparum macrogametes with mr of 48,000 and 45,000 and on the surface of developing ookinetes with mr of 25,000. other moabs directed against the same proteins were not able to reduce the number of oocysts in mosquitoes. a combination of a blocking moab with a non-blocking one potentiated the transmission blocking effect. this implies that at least two different epitopes are present ...19852422080
epitope map and processing scheme for the 195,000-dalton surface glycoprotein of plasmodium falciparum merozoites deduced from cloned overlapping segments of the gene.dna fragments from human malaria parasites were cloned into lambda gt11 to produce a genomic dna expression library. a pool of monoclonal antibodies (mabs) recognizing three domains of the 195-kda major merozoite surface glycoprotein (gp195) reacted with seven clones expressing malaria antigens. mabs recognizing the 83-kda product of gp195 reacted with the clones, but mabs recognizing a glycosylated 45-kda and a nonglycosylated 45-kda domain did not. restriction enzyme mapping revealed that the ...19862422662
microscopic and flow cytophotometric analysis of parasitemia in cultures of plasmodium falciparum vitally stained with hoechst 33342--application to studies of antimalarial agents.conditions for rapid vital staining of plasmodium falciparum infected human erythrocytes were 1 microgram/ml of the dye hoechst 33342 for 15 min in the standard culture medium at 37 degrees c. fixed and stained cultures were analyzed by fluorescence microscopy and flow cytophotometry. the usefulness of this type of analysis for in vitro studies of antimalarial agents was demonstrated using three such agents--cyclosporin a, chloroquine, and pyrimethamine.19862422821
the circumsporozoite antigen: the gene and the antigen. 19852422999
the wellcome trust lecture. genes for antigens of plasmodium falciparum. 19862423947
antigen-specific and mhc-restricted plasmodium falciparum-induced human t lymphocyte clones.we established and analyzed human t lymphocyte clones induced by crude plasmodium falciparum antigens of schizont-enriched asexual blood stages. peripheral blood mononuclear cells (pbmc) were stimulated for 6 days with antigen, and the t cell blasts were separated and were transferred to limiting dilution cultures with antigen, irradiated pbmc, and recombinant interleukin 2. the following observations were made. malaria antigen (m.ag) induced similar proportions of t blasts in pbmc from infected ...19862424980
genetic control of the immune response in mice to a plasmodium falciparum sporozoite vaccine. widespread nonresponsiveness to single malaria t epitope in highly repetitive vaccine.different h-2 congenic strains of mice were immunized with a p. falciparum sporozoite vaccine currently being tested in humans, or with different segments of the vaccine molecule. specific igg production or lymph node cell proliferation in response to different antigens was then determined. only four of seven strains (representing three of eight possible different class ii restriction molecules) responded to the vaccine. of those restriction molecules, only one, i-ab, was associated with a respo ...19862425037
suppression of parasite-specific response in plasmodium falciparum malaria. a longitudinal study of blood mononuclear cell proliferation and subset composition.the present longitudinal study was designed to characterize immunosuppression during acute plasmodium falciparum infection, during the treatment and up to 1 month after the acute stage. the proliferative responses of blood mononuclear cells (bmnc) isolated from non-immune and semi-immune malaria patients and controls to mitogens and two plasmodium-derived stimulators (merozoites, meroz, and soluble purified antigen, spag) and non-related antigens were measured by [3h]thymidine incorporation. bmn ...19862425416
development of a sporozoite malaria vaccine. 19862425647
augmented antibody response to live attenuated measles vaccine in children with plasmodium falciparum parasitaemia.the impact of malarial infection on the humoral immunological response to measles virus antigen was studied in 184 children aged 8-19 months in guinea-bissau. pre- and post-immunization measles serology was performed using dried blood on absorbent paper and the elisa technique. blood smears obtained at the time of vaccination and 2 and 4 weeks afterwards were examined for malaria parasites. pre-vaccination antibodies to measles were found in 44 out of 184 children (24%). plasmodium falciparum wa ...19862425725
experimental basis for the development of a synthetic vaccine against plasmodium falciparum malaria sporozoites.malaria continues to cause extensive morbidity and mortality in man. the exact number of individuals affected is not known. estimates vary from 200 to 400 million, and more than one million die each year. protective immunity against malaria can be obtained by vaccination with irradiated sporozoites. the protective antigens are polypeptides (circumsporozoite [cs] proteins) which cover the surface membrane of the parasite. cs proteins contain species-specific immunodominant epitopes, formed by tan ...19862426050
antigenic repeat structures in proteins of plasmodium falciparum.the majority of malaria antigens that have been cloned contain short sequence repeats which encode antigenic epitopes that are naturally immunogenic. synthetic peptides have been used to show that natural antibody responses to a strain-specific plasmodium falciparum s antigen are largely directed against epitopes encoded in an 11-amino acid sequence that is repeated approximately 100 times in the molecule. a 16-amino acid peptide conjugated to bovine serum albumin induced antibodies specific for ...19862426051
predicted conformations for the immunodominant region of the circumsporozoite protein of the human malaria parasite plasmodium falciparum.the circumsporozoite protein of the human malaria parasite plasmodium falciparum contains multiple tandem repeats of the amino acid sequence asn-ala-asn-pro. the repeated sequence encompasses the immunodominant region of the protein, and antibodies raised against it are potent inhibitors of invasion and development of sporozoites in cultured hepatocytes. using a modified build-up procedure, we have explored a large number of possible helical and near-helical conformations of a terminally blocked ...19862426702
occurrence of a common epitope in circumsporozoite proteins of plasmodium falciparum isolated from different areas in thailand.fifteen isolates of p. falciparum sporozoites obtained from patients with acute falciparum malaria from various malaria endemic areas in thailand were tested for the presence of a common antigenic determinant in their cs protein molecules. sds-page and western blot analysis using mab or human serum antibodies specific to the cs proteins of the parasites revealed a common epitope shared in the cs proteins of all strains of p. falciparum tested. however, the cs proteins exhibited m.w. variation wh ...19862426796
plasmodium falciparum: rapid quantification of parasitemia in fixed malaria cultures by flow cytometry.a rapid and sensitive method is described for the determination of parasitemia in plasmodium falciparum cultures using the fluorescence activated cell sorter and dna-binding fluorochrome, 33258 hoechst. conditions were selected to permit its application to the screening of assays with numerous samples. parasites suspended in culture medium were mixed with an equal volume of aqueous fixative (10% w/v formaldehyde, 4% w/v d-glucose in tris-saline ph 7.3), stained in a 20 microm final dye concentra ...19862427357
immunogenicity of plasmodium falciparum antigenic determinants produced by escherichia coli recombinant clones.the immunogenicity of two parasite antigens produced by escherichia coli as proteins fused to beta-galactosidase was investigated in three animal species: mice, rabbits and squirrel monkeys. 2l protein carries 71 amino acids of a parasite antigen and 11.1 protein carries 23 repeats of a 9-amino-acid repetitive unit. the humoral response was studied using indirect immunofluorescence and immunoprecipitation. the results indicate that immunization of mice, rabbits and squirrel monkeys using sds-den ...19862428279
synthetic plasmodium falciparum circumsporozoite peptides elicit heterogenous l3t4+ t cell proliferative responses in h-2b mice.the ability of synthetic p. falciparum (nanp)n circumsporozoite peptides to elicit murine t cell proliferative responses was studied. when c57bl/6, c3h, and dba/2 mice were injected with (nanp)40, only c57bl/6 (h-2b)-immune lymph node cells proliferated on restimulation in vitro with the same peptide. by using anti-i-a monoclonal antibodies or spleen cells from congenic h-2b mice as a source of antigen-presenting cells, the t cell proliferative response was shown to be restricted to the i-ab reg ...19862428881
immunization of aotus monkeys with recombinant proteins of an erythrocyte surface antigen of plasmodium falciparum.recent studies have identified and characterized a ring-infected erythrocyte surface antigen (resa) of the human malaria parasite plasmodium falciparum with a relative molecular mass (mr) of approximately 155,000 (refs 1-7). resa is localized in the micronemes of merozoites and also the membrane of red cells infected with ring-stage parasites. it is thought to be released through the apical pore from the rhoptry at the time of merozoite invasion. because antibodies directed against this antigen ...19862429187
function of the blood-cerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis.we tested the hypothesis that cerebral malaria is caused by blood-brain barrier inflammation and cerebral edema. in a group of 157 thai patients with strictly defined cerebral malaria, cerebrospinal fluid (csf) opening pressures were normal in 79% and were lower in fatal cases than in survivors (means +/- 1 sd, 144 +/- 58 and 167 +/- 51 mm csf, respectively, p = 0.051). csf: serum albumin ratios (x 10(3)) in 39 of them were significantly higher than in 61 british controls (medians 8.5 and 5.5, r ...19862429567
electrophoretic identification of fusion proteins expressed in single recombinant lambda-bacteriophage plaques.sufficient fusion protein is present in single plaques produced by lytic, recombinant lambda bacteriophage to be detected by coomassie blue staining following electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. agar plugs containing single plaques can be loaded directly onto the stacking gel thus avoiding the need for extensive sample preparation.19862429583
[sickle cell anemia and malaria. current data]. 19862429629
the structure of human thrombospondin, an adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins.thrombospondin is one of a class of adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. we have used two monoclonal antibodies to isolate cdna clones of thrombospondin from a human endothelial cell cdna library and have determined the complete nucleotide sequence of the coding region. three regions of known amino acid sequence of human platelet thrombospondin confirm that the clones are authentic. three types of repeating amino acid sequence are present in thrombosp ...19862430973
two-color flow-cytometric analysis of the growth cycle of plasmodium falciparum in vitro: identification of cell cycle compartments.a previous study (hare jd, bahler dw: j histochem cytochem 34:215, 1986) has shown that the flow cytometric analysis of acridine-orange-stained plasmodium falciparum growing in vitro generates a complex two-color display, regions of which correlate with the major morphological stages. in this report, four cell cycle compartments (a-d) are defined by characteristic ratios of red and green fluorescence of cells distributed throughout the erythrocytic cycle as well as by the differential effects of ...19862431031
human t clones reactive to the sexual stages of plasmodium falciparum malaria. high frequency of gamete-reactive t cells in peripheral blood from nonexposed donors.malarial gametocytes, which are taken up by mosquitoes during a blood meal, develop in the gut of the mosquito into gametes. gametes and gametocytes contain the target antigens of transmission-blocking immunity. here, we show that the peripheral blood of nonexposed donors contains plasmodium falciparum gamete-reactive t cells at frequencies ranging from 1/300 to 1/4000. studies on long-term clones demonstrated that these cells often recognized antigens shared between gametes and asexual stage pa ...19872431058
detection of human antibodies against plasmodium falciparum sporozoites using synthetic peptides.a large peptide consisting of about 40 (asn-ala-asn-pro) repeats of plasmodium falciparum circumsporozoite protein, (nanp)40, was synthesized. it was recognized specifically by monoclonal antibodies produced against p. falciparum sporozoites. moreover, this peptide strongly inhibited the binding of such monoclonal antibodies to antigens present in a sporozoite extract. the (nanp)40 peptide was employed without any carrier to develop an enzyme-linked immunosorbent assay to detect sporozoite-speci ...19872432083
monoclonal antibody characterization of the 195-kilodalton major surface glycoprotein of plasmodium falciparum malaria schizonts and merozoites: identification of additional processed products and a serotype-restricted repetitive epitope.the gp195 from camp strain parasites was characterized with eight monoclonal antibodies (mab) that recognize different epitopes on gp195 and three of its merozoite-associated processed products. four mab (3h7, 3b10, 7f1, and 4g12) reacted with different epitopes on the 45-kda glycosylated product (gp45), shown by differences in their reactivities with soluble and immunoblotted gp45. one mab (7h10) reacted with a conformational epitope probably formed as a result of the interaction of gp45 with a ...19872433334
antigenic cross reactivity between p195 and a distinct protein of 100 kda in plasmodium falciparum.a monoclonal antibody raised against merozoites of plasmodium falciparum clone t9/96 was shown to react with an extremely strain specific epitope on a 195 kda protein synthesized only by late trophozoites and schizonts. this protein was shown to exhibit all of the characteristics attributed to the molecule known variously as merozoite surface protein precursor, polymorphic schizont antigen and p195. the monoclonal antibody also identified a cross-reactive epitope on a distinct protein of 100 kda ...19872433581
stage- and time-dependent effects of crisis form factor on plasmodium falciparum in vitro.to determine the stage- and time-dependent effects of crisis form factor (cff) on plasmodium falciparum metabolism in vitro, the parasite erythrocytic cycle was divided into sequential 8 hr time intervals, and highly synchronous parasites were exposed to cff for various lengths of time. hypoxanthine and phenylalanine incorporation into parasite nucleic acids and proteins, respectively, and glucose consumption by the parasites were compared in cultures grown in cff-containing or nonimmune sera. t ...19862434637
synthetic gene construct expressing a repeated and highly immunogenic epitope of the plasmodium falciparum antigen pf155.the plasmodium falciparum-derived antigen pf155 contains two blocks of tandemly repeated amino acid sequences. a pair of complementary oligonucleotides, encoding the c-terminally located repeat val-glu-his-asp-ala-glu-glu-asn, were synthesized. the oligonucleotides were polymerized by ligation, and the resulting multimers were cloned into an expression vector. one construct that contained four copies of the repeat was expressed in escherichia coli. the product, a fusion protein, was soluble and ...19872434955
construction of synthetic immunogen: use of new t-helper epitope on malaria circumsporozoite protein.the circumsporozoite (cs) protein of plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. localization of sites for t-cell recognition on this molecule is critical for vaccine design. by using an algorithm designed to predict t-cell sites and a large panel of h-2 congenic mice, a major nonrepetitive t-cell site was located. when a synthetic peptide corresponding to this site was covalently linked to the major b-cell site on the molecule, an immunoge ...19872434994
antibodies to the repetitive epitope of plasmodium falciparum circumsporozoite protein in a rural tanzanian community: a longitudinal study of 132 children.an elisa employing a novel synthetic peptide consisting of 40 (asn-ala-asn-pro) repeats of plasmodium falciparum circumsporozoite protein, (nanp)40, was used to detect antibodies against p. falciparum circumsporozoite protein in 132 children, 1 month to 15 years old, from a rural community (kikwawila village) of tanzania, a region where malaria is hyperendemic. the children were surveyed comprehensively over 3 consecutive years for clinical, parasitological, and serological parameters. entomolog ...19872435181
the basis of antimalarial action: non-weak base effects of chloroquine on acid vesicle ph.biologically active concentrations of chloroquine increase the ph of the parasite's acid vesicles within 3-5 min. this increase in ph results from two mechanisms, one of which is markedly reduced in chloroquine-resistant parasites. because chloroquine is a weak base, it increases vesicle ph by that mechanism in chloroquine-susceptible and resistant parasites and mammalian cells (based on its two pks and on the delta ph between the acid vesicle and the extracellular environment). in chloroquine-s ...19872435182
kinetic constraints on the development of a malaria vaccine. 19872436129
transport of an mr approximately 300,000 plasmodium falciparum protein (pf emp 2) from the intraerythrocytic asexual parasite to the cytoplasmic face of the host cell membrane.the profound changes in the morphology, antigenicity, and functional properties of the host erythrocyte membrane induced by intraerythrocytic parasites of the human malaria plasmodium falciparum are poorly understood at the molecular level. we have used mouse mabs to identify a very large malarial protein (mr approximately 300,000) that is exported from the parasite and deposited on the cytoplasmic face of the erythrocyte membrane. this protein is denoted p. falciparum erythrocyte membrane prote ...19872437128
fragments of the polymorphic mr 185,000 glycoprotein from the surface of isolated plasmodium falciparum merozoites form an antigenic complex.merozoites of the human malaria parasite plasmodium falciparum express on their surface several antigens derived from a polymorphic glycoprotein precursor of mr 185,000 synthesised earlier on by trophozoites and schizonts. a panel of 18 monoclonal antibodies against a range of different specificities of the precursor was used to characterise its mature products in spontaneously released merozoites. merozoites released by [35s]methionine or [14c]glucosamine-labelled schizonts, or surface 125i-lab ...19872437453
a malaria protein exported into a new compartment within the host erythrocyte.a plasmodium falciparum protein which is exported into a new compartment in the host erythrocyte has been located. this protein, exp-1, has a variable region recognized by a monoclonal antibody. naturally occurring mutants of this region have been characterized. all mutants studied so far have the same a----g transition abolishing the target for the antibody. the exp-1 gene has a complex structure containing two introns. it is highly conserved in five independent, genetically defined parasite li ...19872438130
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