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how to select plasmodium falciparum pre-erythrocytic antigens in an expression library without defined probe.the restricted access to plasmodium falciparum liver stages has greatly limited the analysis of the antigenic content of that stage. due to the lack of material to perform immunochemical studies, of access to mrna, and of monoclonal probes, we decided to screen a genomic library with stage-restricted human antibodies. this strategy led to the identification of a large number of dna fragments encoding both sporozoite specific as well as liver-stage specific epitopes. following the initial charact ...19901709833
the circumsporozoite protein of plasmodium: a mechanism of immune evasion by the malaria parasite?sporozoites of malaria are covered with a repetitive surface antigen, the circumsporozoite (cs) protein. this antigen also appears to be a major target of the host immune response. the natural immunogenicity of the cs protein has led to attempts to develop the molecule as a vaccine candidate. it seems paradoxical, however, that a successful parasite should present to the host an immunogenic surface molecule which would induce protective immunity. in this paper we suggest that the cs protein is n ...19901709835
evidence implicating mhc genes in the immunological nonresponsiveness to the plasmodium falciparum cs protein.the circumsporozoite (cs) protein is a major candidate vaccine antigen for the sporozoite stage of malaria. both cytotoxic t cells (ctl) and antibody specific for the cs protein are thought to be important in protection. by examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (mhc) are important for immune responsiveness. f1 mice between high antibody responders and low antibody responders are high antibody responders, suggesti ...19901709836
an invariant, "universal" t-cell epitope in the p. falciparum circumsporozoite protein.although there are important obstacles to malaria vaccine development, we believe they might be overcome by a strategy of searching for conserved regions of a vaccine candidate that are recognized in association with many different hla molecules and, if necessary, deliberately modifying the conserved sequences to improve their immunogenicity for t cells. this approach is illustrated by work on the circumsporozoite (cs) protein of plasmodium falciparum, which covers the surface of the malaria spo ...19901709837
disruption of plasmodium falciparum-infected erythrocyte cytoadherence to human melanoma cells with inhibitors of glycoprotein processing.adherence of plasmodium falciparum-infected erythrocytes (ie) to the venular endothelium in brain and other organs is characteristic of cerebral malaria, an often fatal complication in infected individuals. it has been shown that cytoadherence may be mediated through interaction of ie with glycoproteins on host target cell surfaces, including cd36 (gpiv), intercellular adhesion molecule-1 (icam-1), and thrombospondin. inhibitors of glycoprotein synthesis and processing were tested for their abil ...19911710120
acridine orange detection of plasmodium falciparum malaria: relationship between sensitivity and optical configuration.blood samples collected from five volunteers participating in a p. falciparum infectivity trial were examined to determine the efficacy of the acridine orange technique. several lens configurations were tested for efficiency in the diagnosis of malaria using this system. there was no significant difference in the sensitivity for detecting positive specimens or number of parasites among three lens configurations: a 50x long working distance objective (0.34 mm) with either a 10x ocular (total magn ...19911710424
epithelial membrane glycoprotein pas-iv is related to platelet glycoprotein iiib binding to thrombospondin but not to malaria-infected erythrocytes.glycoprotein (gp) iiib (also termed gpiv or cd36) is an integral platelet membrane protein, and has been identified as a binding site for thrombospondin, collagen, and malaria-infected erythrocytes. pas-iv is an integral membrane protein found in lactating mammary epithelial cells and capillary endothelial cells. the n-terminal sequence of pas-iv is nearly identical to that of gpiiib and monospecific anti-pas-iv antibody reacts with gpiiib, indicating that pas-iv is structurally related to gpiii ...19911710515
failure of recombinant vaccinia viruses expressing plasmodium falciparum antigens to protect saimiri monkeys against malaria.saimiri sciurus monkeys were immunized at multiple sites with recombinant vaccinia viruses expressing plasmodium falciparum antigen genes and boosted 4 weeks later. control monkeys were immunized with a thymidine kinase-negative vaccinia virus mutant. two weeks later, all of the monkeys were challenged by intravenous inoculation of p. falciparum (indochina strain) parasites. a group of unimmunized monkeys was challenged in parallel. all of the monkeys that received vaccinia virus recombinants or ...19911711015
molecular basis of sequestration in severe and uncomplicated plasmodium falciparum malaria: differential adhesion of infected erythrocytes to cd36 and icam-1.the cd36 and icam-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for plasmodium falciparum-infected erythrocytes (irbc). adhesion of irbc from thai patients with uncomplicated and severe falciparum malaria to purified cd36 or icam-1 and to c32 melanoma cells was compared. all malaria isolates bound to solid phase-adsorbed cd36 and to fluid-phase 125i-labeled cd36. irbc adhesion to purified icam-1 varied widely, and no correlation with clinical sever ...19911711552
role of intrastructural/intermolecular help in immunization with peptide-phospholipid complexes.the design of effective subunit vaccines requires the inclusion of both b and t cell epitopes. the best mechanism for including both types of epitopes within an ag is dependent upon how the ag is processed by the apc for presentation to a responsive th cell. if it is more efficient to process a single molecule for both helper and primary epitopes, than covalent linkage of b cells and t cell epitopes for intramolecular presentation of help would be recommended. if however, separate peptides conta ...19911712806
definition of the epitope recognized by the plasmodium falciparum-reactive human monoclonal antibody 33g2.the human monoclonal antibody 33g2 has earlier been shown to inhibit merozoite reinvasion of red blood cells in plasmodium falciparum cultures in vitro and to inhibit cytoadherence of infected red blood cells to melanoma cells in vitro. 33g2 cross-reacts with a family of p. falciparum antigens, ag332, pf11.1 and pf155/resa, sharing a common feature of repeated sequences consisting of regularly spaced pairs of glutamic acid. peptides corresponding to residues 2-19 of the known amino acid sequence ...19911712912
antibody responses to plasmodium falciparum gametocyte antigens during and after malaria attacks in schoolchildren from madang, papua new guinea.sera from 49 school children in madang, papua new guinea with malaria and follow-up sera from 40 of these cases were tested by competitive elisa for antibodies capable of inhibiting binding of eight monoclonal antibodies (moabs) to plasmodium falciparum gametocytes. the proportion of sera inhibiting each moab ranged from 31.2% to 85.7%. at follow-up, the proportion of inhibitory sera decreased for 3 moabs, did not change significantly for 4 moabs and increased for one moab. when sera were groupe ...19911712931
conserved and variant epitopes of target antigens of transmission-blocking antibodies among isolates of plasmodium falciparum from malaysia.monoclonal antibodies (mabs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of plasmodium falciparum, pfs 25, pfs 230, and pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of p. falciparum from malaysia, using immunofluorescence microscopy (ifa). among 45 malaysian isolates, one epitope of pfs 25, designated region i, showed evidence of variable reactivity with mabs among different isolates; the pfs 25 e ...19911713424
plasmodium falciparum (human malaria)-induced modifications in human erythrocyte band 3 protein.a monoclonal antibody, 1c4, was produced which recognizes a 65 kda protein that is localized to the plasma membrane of human erythrocytes infected with plasmodium falciparum. by immunofluorescence the antigen was visualized as dots on the surface of the infected cell. the 65 kda protein was present in 4 strains of diverse geographical origin, and in erythrocytes infected with a knobless strain. the 65 kda protein was insoluble in non-ionic detergents, but was partly soluble in sds and some high ...19911714069
isotypic analysis, antigen specificity, and inhibitory function of maternally transmitted plasmodium falciparum-specific antibodies in gabonese newborns.an analysis of plasmodium falciparum-specific antibodies was performed in pairs of maternal and cord sera from gabon, a region endemic for malaria. all paired sera (n = 59) had p. falciparum-specific antibodies. immunofluorescence assays detected parasite-specific igg1, igg2, and igg3 in 100% of the tested pairs (n = 26) and igg4 in 42% of them. the titers of specific igg2 and igg3 were significantly lower in cord than in maternal sera. all maternal sera had specific igm. of the seven p. falcipa ...19911714245
immunity to sexual stages of human malaria parasites: immune modulation during natural infections, antigenic determinants, and the induction of transmission-blocking immunity.four antigens of plasmodium falciparum have so far been identified as targets of transmission-blocking antibodies; three of them (pfs 230, 48/45) are detectable in gametocytes and expressed on gametes, the fourth (pfs 25) appears only after fertilization. epitope analyses of each antigen were made with competitive immunoassays, and the extent of antigenic diversity determined amongst numerous isolates of p. falciparum. there was minimal variation within one of the two epitopes on pfs 230 both of ...19901714627
[antigenic diversity of asexual schizont antigen gp195 of plasmodium falciparum isolates from china].the antigenic diversity of asexual merozoite surface antigen precursor gp195 among 6 isolates of plasmodium falciparum from hainan and jiangsu provinces of china was investigated with a panel of murine anti-gp195 mcabs by indirect immunofluorescence assay and western blotting. the results show that all isolates express certain strain-common epitopes of gp195, and at the same time express or lack some strain-specific epitopes. the 6 isolates can be divided into two major gp195 serotypes according ...19911714800
direct access to serum macromolecules by intraerythrocytic malaria parasites.trafficking pathways in malaria-infected erythrocytes are complex because the internal parasite is separated from the serum by the erythrocyte and parasitophorous vacuolar membranes. intraerythrocytic plasmodium falciparum parasites can endocytose dextrans, protein a and an igg2a antibody. here we show that these macromolecules do not cross the erythrocyte or parasitophorous vacuolar membranes, but rather gain direct access to the aqueous space surrounding the parasite through a parasitophorous ...19911715521
generation of recombinant, carbohydrate-free intercellular adhesion molecule-1 (icam-1) and icam-1 fragments in escherichia coli and mapping of epitopes recognized by anti-icam-1 monoclonal antibodies.intercellular adhesion molecule-1 (icam-1) has been shown to interact with the integrin leukocyte function associated antigen-1 (lfa-1) in a variety of cell-cell adhesion phenomena. furthermore, it serves as a receptor for the majority of the rhinoviruses and for plasmodium falciparum-infected human erythrocytes. we generated recombinant, carbohydrate-free icam-1 and several icam-1 fragments by expression in escherichia coli using the fusion protein expression system puex1-3. in western blot and ...19911715847
[peptide synthesis--protein fragments from plasmodium falciparum and their conjugates with protein and synthetic carriers].to study coat proteins of plasmodium falciparum, seven putative antigenic-determinants of pmmsa, sharp, gbp and four known determinants of csp, cra and resa were synthesized. computerized methods for predicting protein antigenic determinants were employed to select the peptides. for immunochemical studies the peptides were conjugated to proteins and synthetic carriers by means of nonspecific and regiospecific heterobifunctional reagents.19911716102
[immunochemical study of antigenic determinants of surface protein s of the tropical malaria pathogen plasmodium falciparum using synthetic peptides].to develop new approaches to diagnostics and therapy of malaria, we carried out immunochemical study of the surface proteins of the tropical malaria parasite plasmodium falciparum with the use of synthetic peptides corresponding to the suggested antigenic determinants of the parasite proteins. rabbit antisera raised against the synthetic peptides bound to parasite proteins as shown by elisa and immunoblotting. affinity purified anti-peptide antibodies inhibited, in some cases, the parasite growt ...19911716103
location of human cytotoxic t cell epitopes within a polymorphic domain of the plasmodium falciparum circumsporozoite protein.studies in mice have shown that cytotoxic t lymphocytes (ctl) specific for epitopes within the circumsporozoite (cs) protein of malaria sporozoites can prevent malaria probably by destroying infected hepatocytes. this has provided a model for the development of a sporozoite vaccine. it has not been shown whether humans can mount a ctl response to this protein nor what determinants on the protein could be considered as target epitopes for such cells and thus merit inclusion in a sporozoite vaccin ...19911716144
overcoming inhibition of antibody responses to a malaria recombinant vaccinia virus caused by prior exposure to wild type virus.pre-injection of mice with vaccinia virus inhibited the subsequent antibody response to a recombinant polypeptide expressed by vaccinia virus. the inhibition was overcome following additional challenges with recombinant vaccinia virus. this suggests that a potential disadvantage in vaccinia-immune individuals can be circumvented and may be outweighed by the advantages of the vector.19911716807
epitopes of the human malaria parasite p. falciparum carried on the surface of hbsag particles elicit an immune response against the parasite.the development of recombinant subunit vaccines against pathogenic organisms requires not only the identification of epitopes eliciting a protective immune response but also suitable carriers with adjuvant function. b- and t-cell epitopes of the malaria vaccine candidate gp190 were selected on the basis of a systematic search along the gp190 molecule and by computer prediction based on the amino acid sequence. using some of the epitopes identified, we have redesigned the surface of the hepatitis ...19911716808
model using a peptide with carrier function for vaccination against different pathogens.it has been shown that pre-immunization with a protein can inhibit the antibody response to a new b-cell sequence which is coupled to the protein (epitope-specific suppression). by utilizing a peptide with carrier function from the protein, rather than the entire protein, the antibody response to the new b-cell sequence is enhanced in protein-primed mice. the present results extend this observation by showing that mice which have been pre-immunized with a protein followed by a b-cell sequence li ...19911716809
human immune response in plasmodium falciparum malaria. synthetic peptides corresponding to known epitopes of the pf155/resa antigen induce production of parasite-specific antibodies in vitro.autologous cell mixtures containing t cells, b cells, and adherent accessory cells from individuals primed to the malaria parasite plasmodium falciparum by repeated natural infections were investigated for induction of ig and antibody secretion in vitro. in vitro activation of cell cultures with two synthetic peptides corresponding to immunodominant t cell epitopes of the merozoite ag ring-infected erythrocyte surface ag (mr 155,000) (pf155/resa), one from its carboxyl-terminal repeat and one fr ...19911717554
plasmodium falciparum reinfection in children from a holoendemic area in relation to seroreactivities against oligopeptides from different malaria antigens.the rate and densities of plasmodium falciparum reinfections were investigated in children five to 14 years old from one village in tanzania with a high transmission rate. initial parasitemias were eradicated by a curative treatment with quinine, a drug with a short elimination half-life, to minimize the effects of residual drug on reinfection. the seroreactivities to seven oligopeptides, representing t and b cell epitopes from the ring erythrocyte surface antigen (pf155/resa), the clustered arg ...19911718179
hla polymorphism and t cell recognition of a conserved region of p190, a malaria vaccine candidate.we have examined t cell recognition of a recombinant polypeptide (190l), corresponding to a 175-amino-acid-long conserved region of the major surface antigen (p190) of plasmodium falciparum merozoites. we show that 190l contains a variety of t cell epitopes, and can be recognized in association with many different mhc class ii molecules, including hla-dr, dp, and dq antigens. most of the epitope-containing peptides are able to bind to more than one dr, and a single dr molecule can bind to differ ...19911718405
a plasmodium falciparum malaria vaccine candidate which contains epitopes from the circumsporozoite protein and a blood stage antigen, 5.1.the previously described plasmodium falciparum blood stage antigen, 5.1 (also referred to as exp-1) was expressed at a high level in escherichia coli. saimiri monkeys immunised with purified recombinant antigen 5.1 were partially protected from p. falciparum blood stage parasite challenge. the gene coding for 5.1 was combined with dna coding for an (asn-ala-asn-pro)19 sequence (abbreviated (nanp)19 in the one-letter amino acid code). to facilitate purification of the recombinant protein, dna cod ...19911719416
population genetics of plasmodium falciparum within a malaria hyperendemic area.serotyping with monoclonal antibodies was used to estimate the number and frequencies of allelic variants of two merozoite surface proteins, msp1 and msp2, and an exported protein exp-1, in a sample of 344 clinical isolates of plasmodium falciparum from an urban region of the gambia. represented among the isolates were 36, 8 and 2 alleles of the msp1, msp2 and exp-1 loci respectively. relative frequencies of these alleles remained stable in the parasite population over the 2 years of the study. ...19911719468
[diseases observed after return from travels outside europe. 109 cases].we report a prospective study of travel-associated illnesses observed after their return in 109 french travellers, including 86 tourists. sixty-three were returning from africa and 84 percent had been abroad for less than 4 weeks. the percentages of travellers immunized against tetanus, poliomyelitis and typhoid fever were 70, 63 and 36 percent respectively. malaria prophylaxis was well adjusted to current recommendations in only 19 patients; for 9 patients it was a routine visit. one hundred pa ...19911719519
identification of a continuous and cross-reacting epitope for plasmodium falciparum transmission-blocking immunity.identification of continuous epitopes in the target antigens of plasmodium falciparum transmission-blocking antibodies is likely to facilitate the production of a subunit peptide vaccine. two such epitopes shared among several sexual-stage antigens were identified with murine monoclonal antibodies. an epitope recognized by four monoclonal antibodies capable of blocking infectivity of gametocytes in the mosquitoes is shared among three antigens (230, 48/45 doublet, and 27 kda). these antigens are ...19911719534
characterization of a plasmodium falciparum epitope recognized by a monoclonal antibody with broad isolate and species specificity. 19911719648
immunization of owl monkeys with a recombinant protein containing repeated epitopes of a plasmodium falciparum glycophorin-binding protein.a plasmodium falciparum glycophorin binding protein (gbp-130) has been implicated in protective immunity to malaria. the gene for gbp-130 encodes a protein containing 11 tandemly repetitive 50 amino acid units. we report an immunization trial in aotus monkeys using a recombinant dna protein containing three of these 50 amino acid repeats. when administered with aluminum hydroxide, this antigen induced low levels of antibodies that reacted with the recombinant protein by elisa and with parasite a ...19911719834
congenital malaria with chloroquine resistance.a preterm infant with possible congenital clinical malaria is described. the infant developed persistent pyrexia, hyperbilirubinaemia, anaemia, increasing gastric residuals and hepatosplenomegaly from the 7th day of life. thick and thin smears of the infant's blood were heavily loaded with various asexual stages of plasmodium falciparum. the parasite exhibited r1 resistance. there was no satisfactory response to chloroquine, but response to intravenous quinine therapy was achieved on day 15. the ...19911719926
adhesive functions of platelets lacking glycoprotein iv (cd36).glycoprotein iv (gpiv; cd36 or gpiiib) is a cell surface glycoprotein that has been proposed as mediating a number of physiologically important processes such as the adhesion of platelets to thrombospondin (tsp) and collagen, the cytoadherence of plasmodium falciparum-infected erythrocytes, and the tsp-dependent interaction of monocytes with platelets and macrophages. because platelets of the naka-negative phenotype have recently been shown to lack detectable gpiv, their availability offered the ...19911720035
plasmodium falciparum: intragenic recombination and nonrandom associations between polymorphic domains of the precursor to the major merozoite surface antigens.extensive allelic polymorphism in the plasmodium falciparum major merozoite antigen precursor (msp1/pmmsa) is partly due to intragenic recombination events within a short region near the 5' end of the gene. newly described allelic sequences from this region of the gene are compared to those previously published, revealing additional sites of intragenic recombination. epitopes recognised by monoclonal antibodies on the protein have been assigned on the basis of correlations between serology and a ...19911720396
world malaria situation in 1989. part ii. 19911720650
persistence of cellular and humoral response to synthetic peptides from defined plasmodium falciparum antigens.the cellular and humoral immune responses to synthetic peptides reproducing the repeat sequences of two major vaccine candidates (circumsporozoite protein and pfl55/resa) were investigated in two groups of african subjects according to the length of their stay outside endemic areas. the relation between the lymphoproliferative response and the antibody levels to these antigens was studied. the results confirm the existence of t-cell epitopes within the repeat sequences of the cs protein and the ...19911720947
immunogenicity of multiple antigen peptides (map) containing t and b cell epitopes of the repeat region of the p. falciparum circumsporozoite protein.the immunogenicity of multiple antigen peptides (map) constructs containing t and b cell epitopes of the repeat region of the p. falciparum circumsporozoite (cs) protein was examined in vitro, using a human t cell clone, and in vivo, using four different strains of mice. all the map constructs that contained the t cell epitope, (dpnanpnvdpnanpnv), stimulated proliferation and interferon-gamma production by a human t cell clone specific for this epitope which is located in the 5' end of the repea ...19911721025
towards the design of heterovalent anti-malaria vaccines: a hybrid immunogen capable of eliciting immune responses to epitopes of circumsporozoite antigens from two different species of the malaria parasite, plasmodium.the peptide cs.t3, corresponding to residues 378-398 of the plasmodium falciparum (pf) circumsporozoite (cs) protein sequence (except with cysteines 384 and 389 replaced by alanines), has been found to be almost universally recognized by human and mouse t lymphocytes. when colinearly linked to the repetitive b-lymphocyte-specific epitope (asn-ala-asn-pro)n of pf cs protein, cs.t3 induces t-helper activity for an anti-(asn-ala-asn-pro)n antibody response in mice of different haplotypes. we constr ...19911721043
failure to detect mhc class ii associations of the human immune response induced by repeated malaria infections to the plasmodium falciparum antigen pf155/resa.available evidence suggests that human t and b cell responses to a major plasmodium falciparum malaria antigen (pf155/resa) in individuals primed by repeated infections are genetically regulated. in the present study we have attempted to establish whether these regulations reflect genetic restrictions imposed on the immune response by class ii molecules of the donor's mhc system. t cell activation (proliferation and ifn-gamma release in vitro) and antibody activity (elisa) were assayed with synt ...19911721833
cytotoxic cd4+ t cells from a sporozoite-immunized volunteer recognize the plasmodium falciparum cs protein.the present data provide the first evidence that a protozoan parasite, plasmodium falciparum, can induce cd4+ cytotoxic t cells in man. the cd4+ cytotoxic t lymphocytes (ctl) were derived from a sporozoite-immunized volunteer who was protected against challenge with p. falciparum sporozoites. these t cells recognize an epitope within the circumsporozoite (cs) protein, an immunodominant sporozoite surface antigen, present also in liver stages of the parasite, which has been investigated as a vacc ...19911721837
selection of t cell epitopes and vaccine engineering. 19911722274
stage-specific expression of plasmodial proteins containing an antigenic marker of the intraerythrocytic cisternae.a monoclonal antibody, lwli, recognized 3 proteins of 45, 50 and 102 kda in plasmodium falciparum-infected erythrocytes. the 45- and 50-kda proteins were parasite-encoded and displayed markedly different peptide maps, indicating that they were distinct plasmodial polypeptides with a common antigenic epitope rather than differentially processed forms of a primary translational product. the 45-kda protein was present throughout intraerythrocytic growth, while the 50-kda molecule was not detected e ...19911723147
processing of the plasmodium falciparum major merozoite surface protein-1: identification of a 33-kilodalton secondary processing product which is shed prior to erythrocyte invasion.we have previously shown that only a single 19-kda fragment of the plasmodium falciparum major merozoite surface protein (msp1) is carried with an invading merozoite into the infected red cell. this fragment (msp1(19] is derived from the c-terminal membrane-bound end of a major product, msp1(42), of the primary stage of msp1 proteolytic processing. using a monoclonal antibody mapped to an epitope within the n-terminal region of msp1(42), we have shown that a soluble 33-kda polypeptide (msp1(33) ...19911723148
identification of a common plasmodium epitope (cpe) recognised by a pan-specific inhibitory monoclonal antibody.a plasmodium falciparum genomic expression library was screened with a monoclonal antibody produced from mice infected with plasmodium yoelii. eleven unique clones were isolated all of which contained the sequence nknd, iknd or kknd. this sequence was confirmed as the epitope of m26-32 by testing a series of overlapping peptides and the allowable substitutions determined by testing the binding of m26-32 to peptides containing all possible single amino acid replacements of nknd. potential epitope ...19911723149
[use of synthetic carriers and adjuvants for increasing the immunogenicity of a synthetic peptide from the cs-protein of plasmodium falciparum].in order to increase immunogenicity of the peptide (nanp)3, we have prepared a large set of fully synthetic constructions based on the peptide, glycopeptide adjuvant gmdp and some synthetic carriers. immunogenicity of these constructions was tested on mice (line c57b1/6) responding to the peptide polymer (nanp)40 without carrier and on mice (line balb/c) not responding to this antigen. immunogenic constructions based on synthetic polytuftsin induced as high titres of anti-(nanp)3 antibodies as t ...19911723268
detection of different developmental stages of malaria parasites by non-radioactive dna in situ hybridization.a highly sensitive non-radioactive dna in situ hybridization procedure is described that enables detection and unequivocal identification of various developmental stages of human and rodent malaria parasites. using biotinylated species-specific dna probes, erythrocytic parasites can be specifically stained in blood smears. similarly exoerythrocytic stages can be visualized in cell culture and in sections of paraffin-embedded liver. in blood smears, the hybridization procedure provides a rapid de ...19911723723
antigenic analysis of plasmodium yoelii liver stages by fluorescence antibody assays.little is known about the immune response against liver stage antigens which were first described for plasmodium falciparum. in order to provide a basis for experimental studies, we analysed antigenically the liver stages of plasmodium yoelii using sera of restricted specificity. several distinct fluorescence patterns could be described in maturing liver forms. one pattern was identified as corresponding to antigens specific to the liver phase which are also species specific. another pattern cor ...19911724570
peptide immunization can elicit malaria protein-specific memory helper but not proliferative t cells.we have studied the proliferative and helper t cell responses in mice to a malaria sporozoite vaccine candidate currently undergoing human trials. following immunization of b10 (i-ab) mice with the purified recombinant baculovirus-expressed plasmodium falciparum circumsporozoite protein, draining lymph node cells were challenged in vitro with a series of overlapping synthetic peptides which span the construct. surprisingly, only a single peptide from the protein was immunodominant in that it cou ...19901724615
[applications of q beta replicase for diagnostic purposes]. 19911724730
epitopes of the plasmodium falciparum clustered-asparagine-rich protein (carp) recognized by human t-cells and antibodies.linear b- and t-cell epitopes have been identified in the plasmodium falciparum clustered-asparagine-rich-protein (carp). twenty-six synthetic peptides, 15-25 amino acids in length, were assayed for their ability to stimulate purified, human t-cells primed to p.falciparum by natural infection to proliferate and/or secrete gamma-interferon (ifn gamma). the plasma of malaria exposed individuals were tested for antibody reactivity with peptides coupled to bovine serum albumin in a semiquantitative ...19911725821
cross-reacting epitopes shared between plasmodium falciparum and its host: the origin of autoreactive antibodies? 19911726272
heat shock proteins as "super"-carriers for sporozoite peptide vaccines? 19911726273
protective immunization with invariant peptides of the plasmodium falciparum antigen msa2.three octapeptides from the n and c terminal c regions of the merozoite surface ag 2 (msa2) of plasmodium falciparum elicit anti-msa2 antibody when given as diphtheria toxoid conjugates. these antibodies also bind to the msa2 homolog from the rodent malaria plasmodium berghei. all mice vaccinated with these conjugates and challenged with an otherwise lethal inoculum of p. berghei showed substantial protection with most surviving. there was a inverse correlation between the development of the par ...19921727867
malaria. how chloroquine works. 19921729645
inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites.the incidence of human malaria has increased during the past 20 years; 270 million people are now estimated to be infected with the parasite. an important contribution to this increase has been the appearance of malaria organisms resistant to quinoline-containing antimalarials such as chloroquine and quinine. these drugs accumulate in the acid food vacuoles of the intraerythrocytic-stage malaria parasite, although the mechanism of their specific toxicity in this organelle is uncertain. the prima ...19921729651
liposomal malaria vaccine in humans: a safe and potent adjuvant strategy.this study describes the safety and immunogenicity of a liposome-based vaccine injected into human subjects. thirty healthy adult male volunteers were immunized with a liposome-encapsulated recombinant protein (r32ns181) containing epitopes from the repeat region of the circumsporozoite protein of plasmodium falciparum. this antigen had previously been found to be poorly immunogenic in humans when it was adsorbed with al(oh)3. in the present study, r32ns181 was encapsulated in liposomes containi ...19921729706
iron chelation with desferrioxamine b in adults with asymptomatic plasmodium falciparum parasitemia.to determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine b in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic plasmodium falciparum infection in a randomized, double-blind, placebo-controlled crossover trial. peripheral blood concentrations of p falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine b + ferrioxamine (the ir ...19921730079
localisation of hypoxanthine phosphoribosyl transferase in the malaria parasite plasmodium falciparum.the enzyme hypoxanthine phosphoribosyl transferase of the human malaria parasite plasmodium falciparum has been located in parasites and parasite-infected erythrocytes by antibody probing. the probe was a polyclonal rabbit antiserum made against the parasite enzyme made in escherichia coli. the enzyme is associated with membrane-bound compartments in merozoites and asexual blood parasites. in particular, indirect immunofluorescence studies reveal the enzyme localized in vesicle-like structures w ...19921730267
involvement of pf155/resa and cross-reactive antigens in plasmodium falciparum merozoite invasion in vitro.lines of plasmodium falciparum fcr3 either expressing or not expressing the blood-stage antigen pf155/resa were used to analyze the possible involvement of this antigen in the merozoite invasion process in vitro. antibodies from human sera, affinity purified on synthetic peptides corresponding to c-terminal repeated sequences in pf155/resa, were shown to inhibit merozoite invasion of both types of parasites with similar efficiency. reversal of the invasion inhibition by fusion proteins containin ...19921730474
geographically restricted heterogeneity of the plasmodium falciparum circumsporozoite protein: relevance for vaccine development.the design of a subunit vaccine against the malaria parasite relies on the epitopes recognized by t cells being identified and polymorphisms therein being defined. here we present the analysis of a 354-bp fragment of the circumsporozoite (cs) protein encompassing defined proliferative and cytotoxic t-cell recognition regions. we reveal that the polymorphism of cs protein t-cell sites appears to be very limited among plasmodium falciparum isolates prevalent in certain geographical regions, in par ...19921730503
biological activities of peptides and peptide analogues derived from common sequences present in thrombospondin, properdin, and malarial proteins.thrombospondin (tsp), a major platelet-secreted protein, has recently been shown to have activity in tumor cell metastasis, cell adhesion, and platelet aggregation. the type 1 repeats of tsp contain two copies of csvtcg and one copy of cstscg, per each of the three polypeptide chains of tsp and show homology with peptide sequences found in a number of other proteins including properdin, malarial circumsporozoite, and a blood-stage antigen of plasmodium falciparum. to investigate whether these co ...19921730745
cloning and characterization of a highly conserved hmg-like protein (pf16) gene from plasmodium falciparum.a novel gene encoding a protein of 147 amino acids (pf16) has been cloned from plasmodium falciparum and expressed in e. coli. the protein contains 19 methionines, all of which are localized in the nh2-terminal 35 amino acid residues, and it is also rich in lysine. pf16 is highly basic, contains a polyacidic domain consisting of aspartic acid and is related to the non-histone high mobility group proteins of higher eukaryotes. the gene is conserved among eight different species of plasmodium so f ...19921731798
rheological analysis of the adhesive interactions of red blood cells parasitized by plasmodium falciparum.adhesion of parasitized red blood cells (rbcs) to vascular endothelium is thought to be a key factor in the pathology of falciparum malaria. however, quantitative analyses of the intercellular forces and of the effects of flow on adhesion have been lacking. we have characterized cytoadhesion of rbcs parasitized by the strains ito4 (which can bind to receptors icam-1 or cd36) and fcr3a2 (which can bind to cd36 only) using micropipette manipulation and flow chamber techniques. target cells were un ...19921732018
shortened cecropin a-melittin hybrids. significant size reduction retains potent antibiotic activity.we have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin a (ca) and melittin (m). we now report a substantial reduction in size at the c-terminal section of the highly active hybrid ca(1-8)m(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule. in particular, the 15-residue hybrids ca(1-7)m(2-9), ca(1-7)m(4-11) and ca(1-7)m(5-12) are the shortest cecropin-based peptide antibiotics ...19921733777
quinoline-containing antimalarials--mode of action, drug resistance and its reversal. an update with unresolved puzzles.malaria constitutes one of the major health threats in the tropical and sub-tropical areas of the world. yet, few advances were made in recent years in revealing the mode of action of the common and most economically affordable antimalarial drugs, the schizontocidal 4-aminoquinolines. data presented indubitably repudiate the previous notions that these drugs act by either halting the feeding of the parasite on its host erythrocyte cytosol or repressing nucleic acid synthesis due to intercalation ...19921734899
single or multiple localization of adp/atp transporter in human malarial plasmodium falciparum. 19921734900
analysis of cpg suppression in methylated and nonmethylated species.the development of nearest-neighbor analysis led to the finding that the frequency of the dinucleotide cpg is markedly depressed in vertebrates. one explanation of this suppression is that methylation of cpg found in vertebrates represents a mutational hot spot through deamination of methylcytidine to thymidine. we have examined the role of methylated cpg as a factor in cpg suppression by comparing cpg distributions in coding regions of 121 genes from six species, three with methylated dna and t ...19921736311
prolonged recrudescence of plasmodium falciparum. 19921738899
malaria mimicry with tumor necrosis factor. contrasts between species of murine malaria and plasmodium falciparum.because plasmodium berghei anka induces cerebral malaria and p. vinckei does not, the former has often been studied as a model for human falciparum malaria. it lacks, however, many of the systemic changes seen in the human disease. because both of these murine models and the human disease have now been defined in terms of excess tumor necrosis factor (tnf) production, the authors have more closely examined the two murine models in this light to see which provides the better overall model for fal ...19921739126
a novel 40-kda membrane-associated ef-hand calcium-binding protein in plasmodium falciparum.a 40-kda sexual stage radiolabeled surface protein of plasmodium falciparum, pfs40, was previously identified as a potential target antigen of transmission blocking immunity by an immunogenetic approach. synthetic oligonucleotide "guessmers," based on microsequenced tryptic peptides of pfs40 purified by two-dimensional gel electrophoresis, were used to clone the full length cdna and genomic dna encoding pfs40. the deduced amino acid sequence predicted an integral membrane protein containing five ...19921740445
secondary processing of the plasmodium falciparum merozoite surface protein-1 (msp1) by a calcium-dependent membrane-bound serine protease: shedding of msp133 as a noncovalently associated complex with other fragments of the msp1.merozoites of the malaria parasite plasmodium falciparum possess on their surface proteolytically processed fragments of the merozoite surface protein-1 (msp1). secondary processing of one of these fragments, msp1(42), always occurs prior to, or at the point of successful erythrocyte reinvasion. it is shown that a product of this secondary processing, msp1(33), is shed in the form of a noncovalently-associated complex with a number of other proteins, including the msp1-derived species msp1(38) a ...19921741018
the role of calcium in the invasion of human erythrocytes by plasmodium falciparum.the role of calcium in the invasion of human erythrocytes by plasmodium falciparum merozoites has been investigated using a variety of techniques. it has been demonstrated using calcium-depleted medium that invasion is dependent upon the presence of calcium and that neither magnesium, manganese or zinc may substitute for it, suggesting that the effect is calcium specific and not dependent upon a non-specific, charge-based mechanism. using resealed erythrocyte ghosts and altering the internal and ...19921741019
repeat structures in a plasmodium falciparum protein (mesa) that binds human erythrocyte protein 4.1.the mature-parasite-infected erythrocyte surface antigen (mesa, also known as pfemp-2 and pp300) of plasmodium falciparum is a phosphoprotein of approx. 250-300 kda that is exported from the parasite to the erythrocyte membrane skeleton where it binds to protein 4.1. determination of the primary sequence of mesa reveals that it is encoded by 2 exons, a structure common to other exported proteins of p. falciparum. the mesa protein is heavily charged and contains 7 distinct repeat regions that com ...19921741020
sequence of a 16-kilodalton sexual stage and sporozoite surface antigen of plasmodium reichenowi and comparison with pfs16 of plasmodium falciparum. 19921741021
a simple method for the purification of mitochondrial dna from plasmodium falciparum.mitochondrial dna (mtdna) from plasmodium falciparum was isolated by conventional differential centrifugation in an ss34 rotor, a simpler method than csc1 centrifugation of total dna as employed by other workers. the nature of the sample was verified by sequencing a polymerase chain reaction (pcr) product obtained using oligonucleotide primers derived from known malarial mtdna sequence.19911743858
an in vitro study on mefloquine/quinine in plasmodium falciparum malaria.an in vitro designed for determining sensitivity of plasmodium falciparum strains isolated from kanchanaburi province, to mefloquine/quinine combination, was carried out. the mic values of mefloquine/quinine for the p.falciparum strains were found to be 0.075/3.75 to 0.225/11.15 nm/ml. the changes observed following the drug treatment were an enlargement of the space between the outer and the inner limiting membrane of the parasitophorous vacuole. these changes were followed by cytoplasmic degen ...19911744537
west african malaria.plasmodium falciparum malaria poses an increasing risk to travellers to west africa. the development of chloroquine resistant in west africa has further compounded the risk. two cases of falciparum malaria from sierra leone are presented. one represents the classic missed case and the other a probable case of chloroquine resistant (ri vide infra) falciparum malaria. these cases highlight the danger of the missed or late diagnosis; the need for chemoprophylaxis, even in emigrants; the threat pose ...19911744827
sero-epidemiological survey of malaria by immunofluorescence in pakistan (district gujranwala-punjab).indirect immunofluorescence antibody (ifa) technique was employed, for field detection of malarial parasite. the technique involved application of homologous antigen slides of plasmodium falciparum and p. vivax prepared in the field conditions. serological study, simultaneously using p. falciparum and p. vivax antigens, brought out a clearer picture of distribution and role of the parasite species in the epidemiology of the disease in the area studied. the survey supported the contention of pers ...19911744969
imported malaria in australia.to obtain information on imported malaria in australia.19911745165
transmission and epidemiology of newly transmitted falciparum malaria in the central highland plateaux of madagascar.the recent reappearance of plasmodium falciparum in the central highland plateaux of madagascar has led to an important increase in both morbidity and mortality in the population. to understand the phenomena that originated this outbreak, and to evaluate the clinical and biological reactions of the population, we conducted entomological surveys during the whole malaria transmission season of 1988. in parallel, 41 individuals presenting with a malaria attack in january were given a curative antim ...19911746977
plasmodium falciparum: recombinant baculoviruses direct the expression of circumsporozoite proteins in spodoptera frugiperda cell cultures.the dna coding for the circumsporozoite protein (cps) of plasmodium falciparum has been cloned into the baculovirus expression vector pacym1 and expressed in spodoptera frugiperda (sf9) insect cells. three dna constructs have been made: the first one directs the synthesis of the complete csp (aa 1-412), the second leads to the production of a species devoid of the anchor domain (aa 1-391) and the third one to a molecule lacking both signal and membrane anchor sequences (aa 18-391). all three rec ...19911749376
prevalence of malaria in native and transmigrant populations. effects of age and history of exposure.a malaria prevalence study was performed in a village in irian jaya, indonesia, that contains a population of people who have been exposed lifelong to hyperendemic malaria and another population of people who had arrived 18 months previously from areas of very low endemicity. mean spleen sizes correlated positively with prevalence of malaria, not resistance to it. prevalence of sexual and asexual blood stage parasites was higher in transmigrants than in the natives. the data also show that clini ...19911750095
transfusion associated malaria in endemic areas. 19911752686
xanthine oxidase inhibits growth of plasmodium falciparum in human erythrocytes in vitro.malaria parasites, unable to synthesize purine de novo, use host-derived hypoxanthine preferentially as purine source. in a previous study (1990. j. biol. chem. 265:6562-6568), we noted that xanthine oxidase rapidly and completely depleted hypoxanthine in human erythrocytes, not by crossing the erythrocyte membrane, but rather by creating a concentration gradient which facilitated hypoxanthine efflux. we therefore investigated the ability of xanthine oxidase to inhibit growth of fcr-3, a chloroq ...19911752946
association between immune recognition of the malaria vaccine candidate antigen pf155/resa and resistance to clinical disease: a prospective study in a malaria-endemic region of west africa.we have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen pf155/resa in a longitudinal, prospective study of clinical immunity to plasmodium falciparum malaria in a cohort of 354 gambian children aged 3-8 years. a significant association was observed between presence of antibodies to the 3' repeat region peptide (eenv)6 and resistance to clinical malaria. the prevalence of protective antipeptide antibodies va ...19911755042
paraphimosis apparently associated with plasmodium falciparum infection. 19911755043
a case of plasmodium falciparum malaria sensitive to chloroquine but resistant to pyrimethamine/sulfadoxine in sennar, sudan. 19911755045
potentiation of monodesethylamodiaquine and amopyroquine with desipramine against plasmodium falciparum in vitro. 19911755046
genetic evidence for the importance of interrupted feeding by mosquitoes in the transmission of malaria.plasmodium falciparum isolates were obtained from 17 pairs of gambian children, each pair living in the same house and presenting with malaria at the same time. frequencies of allelic serotypes of 3 polymorphic blood stage proteins (msp1, msp2, and exp-1) were previously determined from a large number of isolates from patients in the local area, and the probability of a random pair of isolates containing an identical genotype was calculated to be less than 0.01. however, 3 of 8 household pairs i ...19911755049
heat shock response of babesia divergens and identification of the hsp70 as an immunodominant early antigen during ox, gerbil and human babesiosis.using antisera (alpha-r and alpha-c7ag) directed against the conserved gly-gly-met-pro-epitope of the hsp70 family, a single antigen was identified in the human babesia divergens rouen 1987 isolate by western immunoblotting and immunoprecipitation experiments. this b divergens hsp70 is highly conserved as shown by the analysis of five other geographical b divergens isolates from different hosts (human and bovine). indirect immunofluorescence assay performed on the asexual intraerythrocytic stage ...19911756315
protection by alpha-thalassaemia against plasmodium falciparum malaria: modified surface antigen expression rather than impaired growth or cytoadherence.we have attempted to determine the cellular mechanism by which alpha-thalassaemia may protect against plasmodium falciparum malaria. invasion and development of p. falciparum in the microcytic red cells of two-gene deletion forms of alpha-thalassaemia when measured morphologically or by [3h]hypoxanthine incorporation were normal compared to controls. normal invasion rates were also observed following schizogony in thalassaemic red cells. neither the addition of the oxidant menadione, 30% oxygen, ...19911757109
identification of plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria.plasmodium falciparum histidine-rich protein 2 (pfhrp-2) is a water-soluble protein released from parasitized erythrocytes into in vitro culture supernatants. this study sought to determine whether pfhrp-2 could be detected in the plasma of humans with p. falciparum malaria. a monoclonal antibody (1e1) is described that binds to pfhrp-2. by using monoclonal antibody 1e1, pfhrp-2 was identified by western blot (immunoblot) analysis in the plasma of 37 of 39 (95%) patients experiencing either a fi ...19911761684
sequence of the knob protein of plasmodium falciparum recognized by a monoclonal antibody. 19911762632
dna polymerase delta: gene sequences from plasmodium falciparum indicate that this enzyme is more highly conserved than dna polymerase alpha.genes encoding proteins homologous to the catalytic subunits of dna polymerase alpha and delta have been cloned from the human malaria parasite plasmodium falciparum. these are among the first cellular replicative dna polymerase genes to be cloned and their sequences allow us to make new statements about the relative degrees of conservation of these two enzymes. the most important finding was that p. falciparum pol delta showed considerable homology to the only other pol delta enzyme for which p ...19911762904
quinine treatment of severe falciparum malaria in african children: a randomized comparison of three regimens.the pharmacokinetics and effectiveness of three dosage regimens of quinine were studied in a group of 59 children with severe malaria. the children were randomized to receive high-dose intravenous or intramuscular quinine (20 mg salt/kg loading, then 10 mg salt/kg every 12 hr), or low-dose intravenous quinine (10 mg salt/kg loading, then 5 mg salt/kg every 12 hr). in the group receiving the high-dose intravenous regimen, mean high and low quinine concentrations were consistently greater than 10 ...19911763797
[clinical presentation of non-pernicious malaria attacks in patients hospitalized in brazzaville (congo) in 1989].the clinical manifestations observed in 102 malaria patients (parasitaemia of over 8,000 plasmodium falciparum/mm3) hospitalized in 1989 in brazzaville (congo) were analyzed after ruling out the cases of pernicious malaria. the clinical picture was fever, stomach upset with headache and musculo-articular pain as in classical cases. in children these manifestations were frequently associated with convulsions. diarrhoea was not uncommon in young children. vomiting was frequent in both children and ...19911764754
[malaria in the republic of são tomé and principe. epidemiologic evaluation and chemoresistance of p. falciparum].the authors report the results of a valuation of paludometric indices during mai 1990 in democratic são tomé e príncipe republic (rdstp). these investigations (parasitic index and spleen index) suggest that malaria is mesoendemic in these area. plasmodium susceptibility to chloroquine at posology of 25 mg/kg per os was evaluated (who standard 7 days field test). among 58 children, ranging from 5 to 11 years old, resistance at level r i was observed in 9% of cases, at level r ii in 14%. among 10 ...19911764755
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