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association between human serum-induced crisis forms in cultured plasmodium falciparum and clinical immunity to malaria in sudan.clinical histories with regard to falciparum malaria were collected from adults living in holo-, hyper-, and hypoendemic areas of sudan and matched to serum samples which were assayed for antiparasitic activity in cultures of plasmodium falciparum. the adult population of the endemic areas could be divided into three groups based on oral histories: those who never experience falciparum malaria; those with a childhood history of malaria, who experience only mild occasional malaria as adults; and ...19836350183
production of human monoclonal antibodies against asexual erythrocytic stages of plasmodium falciparum. 19836134126
platelet secretory activities in acute malaria (plasmodium falciparum) infection.during acute plasmodium falciparum infection in man, plasma concentrations of platelet-specific proteins, beta-thromboglobulin (beta tg) and platelet factor 4 (pf4) were significantly elevated. for beta tg, the mean concentration was 136.24 +/- 71.58 ng/ml in patients, and 50.53 +/- 25.42 ng/ml in control subjects (t = 5.3794; p = 0.0001), while for pf4 mean values were, respectively, 75.35 +/- 23.09 and 18.64 +/- 13.42 ng/ml (t = -6.0897; p less than 0.0001). platelet ldh loss in vitro in respo ...19836192658
a comparison of epstein-barr virus-specific t-cell immunity in malaria-endemic and -nonendemic regions of papua new guinea.epstein-barr virus genome-positive burkitt's lymphoma is endemic in africa and papua new guinea and in both countries the tumour is restricted to regions with holoendemic malaria. the present work has compared groups of healthy indigenous individuals living in malarious and non-malarious regions of papua new guinea for epstein-barr virus-specific t-cell-mediated immunity using the in vitro regression assay. residents of the malarious region (55 tested), when compared with either residents of the ...19836305850
permselectivity changes in malaria (plasmodium falciparum) infected human red blood cell membranes.the development of the malaria parasite plasmodium falciparum in human red blood cells induces parasite-dependent perturbations in the permselectivity properties of the host cell membrane. the changes appear as parasites develop from ring to the trophozoite stage and persist during schizogony. in the present work we assessed the permeability changes of the infected cells to anionic substances by the use of radioactive and fluorescent probes. our data show that i) covalent binding probes, such as ...19836337170
antigens of the erythrocytes stages of the human malaria parasite plasmodium falciparum detected by monoclonal antibodies.a range of 22 mouse anti-p. falciparum monoclonal antibodies have been characterized by indirect immunofluorescence and immunoprecipitation. on the basis of these studies, 5 groups of antibodies and 6 classes of antigen were defined. group i antibodies give, bright, uniform, generalised staining of all blood stages including gametocytes. three of these antibodies precipitate a metabolically labelled molecule(s) of 35 kda. one precipitates a 50 kda antigen. group ii antibodies, which give strong ...19836350871
identification of surface and internal antigens from spontaneously released plasmodium falciparum merozoites by radio-iodination and metabolic labelling.spontaneously released merozoites from synchronous plasmodium falciparum cultures were isolated in the presence of protease blocker. 1-5 x 10(10) merozoites were obtained in each experiment. the isolated merozoites possessed a thick surface coat and about 80% were invasive to human erythrocytes although they did not subsequently develop into ring stages. tests using several analytical methods showed the merozoite preparations to be free of any erythrocyte contamination. six labelled proteins wer ...19836362252
plasma lipid changes in human malaria.lipid concentrations in human subjects during and after infection by plasmodium falciparum were determined. the increase in the concentration of phospholipids and triglycerides during infection was statistically significant (p less than 0.01 for moderate infection and p less than 0.001 for severe infection) when compared with concentration after infection. the increases in these lipid levels were almost two-fold in moderate infection and three fold in severe infection. there was no significant c ...19836356530
resistance of melanesian elliptocytes (ovalocytes) to invasion by plasmodium knowlesi and plasmodium falciparum malaria parasites in vitro.erythrocytes from humans with melanesian elliptocytosis are resistant to invasion by plasmodium falciparum in vitro and epidemiological evidence suggests they may be resistant to p. vivax and p. malariae. we have examined the ability of p. knowlesi merozoites to invade melanesian elliptocytes in vitro as a definitive means of examining these cells for resistance to invasion by malarial species with different receptor requirements. the melanesian elliptocytes were highly resistant to invasion by ...19836338046
phagocytosis of plasmodium falciparum-parasitized erythrocytes by human polymorphonuclear leukocytes.polymorphonuclear leukocytes (pmn) from normal blood donors phagocytosed p. falciparum-infected red blood cells (irbc) to a greater extent than normal rbc under in vitro culture condition. the phagocytic activity of pmn was greatly increased by the addition of sera from individuals living in areas endemic for malaria (immune sera) but not by sera from individuals recovering from a first acute p. falciparum infection. the enhancement of the phagocytic activity was associated with the purified igg ...19836338199
ineffective erythropoiesis in acute human p. falciparum malaria.an analysis of erythroblast cell kinetics utilizing quantitative 14c-autoradiography has been performed in five cases of acute plasmodium falciparum malaria prior to and, in four patients, 3 or 6 days after the onset of antimalarial therapy. associated with no or only moderate anemia were changes of erythroblast morphology, a considerable shift in the frequency of red and white blood cell precursors in the bone marrow, and a reduced rate of erythroblast proliferation. there was a marked loss of ...19836340761
new permeability pathways induced in membranes of plasmodium falciparum infected erythrocytes.the permeability properties of the membrane of human erythrocytes infected with malaria parasites (plasmodium falciparum) were studied by the method of osmotic hemolysis. at the trophozoite stage, the host membrane becomes permeable to substrates such as sorbitol and glucose. the new permeability pathway is insensitive to most inhibitors of the glucose carrier, but is highly susceptible to the membrane dipole modifier phloretin. it is blocked by disaccharides and oligosaccharides, both of which ...19836348537
polymorphonuclear leucocytes defective in oxidative metabolism inhibit in vitro growth of plasmodium falciparum. evidence against an oxygen-dependent mechanism.this report presents evidence that polymorphonuclear leucocytes (pmn) from chronic granulomatous disease (cgd) patients, who are defective in oxidative metabolism, are capable of inhibiting in vitro multiplication of plasmodium falciparum. using a microtitre in vitro inhibition assay, we incubated various numbers of peripheral blood neutrophils from cgd patients and from normal individuals with p. falciparum isolate f32 in the in vitro culture system. inhibition of parasite growth by neutrophils ...19846379857
synthesis of adenosine nucleotides from hypoxanthine by human malaria parasites (plasmodium falciparum) in continuous erythrocyte culture: inhibition by hadacidin but not alanosine. 19846375681
hepatocytes as feeder-layers for in vitro cultivation of plasmodium falciparum blood-stages.to improve the in vitro growth of plasmodium falciparum we attempted to cultivate its erythrocytic stages on monolayers of functionally active hepatocytes. hepatocytes from swiss albino mice were isolated by perfusing the liver with a collagenase solution and were co-cultured with a liver epithelial cell type in rpmi 1640 medium supplemented with 10% human umbilical cord serum. the results show that the presence of hepatocytes improves both the multiplication rates of three strains of p. falcipa ...19846380021
altered red cell membrane fluidity during schizogonic development of malarial parasites (plasmodium falciparum and p. lophurae).the plasma membranes of human or duckling erythrocytes infected with malarial parasites (plasmodium falciparum and p. lophurae respectively) were stained by the fluorescent dye merocyanine 540 in the presence of serum. unparasitized erythrocytes from infected ducklings or from in vitro cultures remained unstained in the presence of serum. because merocyanine 540 has a greater affinity for fluid phased or disordered lipid bilayers the results suggest that upon infection of the red blood cell the ...19846390806
initial extracellular development in vitro of merozoites of plasmodium falciparum.late schizonts from continuous cultures of p. falciparum were concentrated over percoll, inoculated to various experimental media at the rate of about 20 x 10(6) per 0.5 ml of medium, and incubated in a candle jar at 37 degrees for 1 day. controls in standard culture medium showed a heavy invasion with young rings in the previously uninfected red cells introduced with the inoculum of schizonts. in a medium of high potassium content containing a 33% extract of human erythrocytes, this invasion wa ...19846392532
human antibodies to a mr 155,000 plasmodium falciparum antigen efficiently inhibit merozoite invasion.igg from a donor clinically immune to plasmodium falciparum malaria strongly inhibited reinvasion in vitro of human erythrocytes by the parasite. when added to monolayers of glutaraldehyde-fixed and air-dried erythrocytes infected with the parasite, this igg also displayed a characteristic immunofluorescence restricted to the surface of infected erythrocytes. elution of the igg adsorbed to such monolayers gave an antibody fraction that was 40 times more efficient in the reinvasion inhibition ass ...19846393131
hydrophobic interactions in plasmodium falciparum invasion into human erythrocytes.human glycophorins block in vitro invasion of plasmodium falciparum merozoites into human erythrocytes. a segment of glycophorin a which appears to be involved in the inhibition, is at, or adjacent to, the membrane-spanning domain of the molecule. to study the role of hydrophobic interactions in the inhibition, a series of proteins were derivatized with lipophilic side groups, and tested for inhibitory activity. glycophorin a became five times more inhibitory after derivatization with nitrobenzy ...19846384774
a role for rheumatoid factor enhancement of plasmodium falciparum schizont inhibition in vitro.studies were undertaken to determine whether rheumatoid factor (rf) was present in immune human and aotus trivirgatus monkey sera which inhibited plasmodium falciparum schizonts in vitro and to determine whether rf could be responsible for or contribute to merozoite agglutination in the parasite inhibition test. additional studies were conducted to determine the effect of exogenous rf on schizont inhibition when used alone or in conjunction with immune or normal sera. rf was not detected in any ...19846389357
the effects of aspirin-containing serum in the continuous culture of plasmodium falciparum.in vitro culture of plasmodium falciparum-infected human erythrocytes (rbc) has permitted systematic study of human host-parasite relations. in this study the effect of aspirin in the culture system was examined by using serum from blood of fasting, healthy male volunteers, before and after the ingestion of aspirin. the addition of aspirin-containing serum disturbed parasite growth and development: 0-1/2 dilutions of treated/control sera inhibited parasite development, with nuclear pyknosis, pyk ...19846389847
receptor mediated endocytosis of the malarial parasite by erythrocytes.malarial merozoites appear to interact with the major surface sialoglycoproteins, glycophorin a and glycophorin b, during entry into the human erythrocyte. intact merozoites bind 125i-glycophorin demonstrating directly that the parasites have glycophorin binding sites. a glycophorin containing fraction crosslinked to acrylamide beads provided a probe to identify merozoite molecules with an affinity for the erythrocyte surface. a fraction of merozoites, labeled with 3h-proline, and containing the ...19846390454
plasmodium falciparum: protein antigens identified by analysis of serum samples from vaccinated aotus monkeys.serum samples from aotus trivirgatus subsp. griseimembra monkeys obtained at different stages of a vaccination experiment were analyzed for total antibody titer to plasmodium falciparum and were used for identifying protective antigens of the human malaria parasite. total malarial antibody titers were higher in serum samples from protected monkeys (vaccinated with antigen in an adjuvant) than in those from unprotected monkeys (vaccinated with either antigen or adjuvant only). parasite proteins w ...19846360901
long term cultivation of plasmodium falciparum in aotus trivirgatus erythrocytes.the erythrocytes of the colombian owl monkey aotus trivirgatus griseimembra can be used for the long-term in vitro cultivation of plasmodium falciparum employing a modified trager -jensen method. cultures are grown in hepes-buffered rpmi-1640 using a 4% suspension of monkey erythrocytes and 10% pooled heat-inactivated human ab serum, with initial parasitemias in a range between 0.2 and 0.5%. adaptation of new strains from human erythrocytes cultures can be performed by simply subculturing from h ...19846375405
prolonged incubation improves the micro-scale in-vitro test for drug sensitivity of plasmodium falciparum.in the standard micro-scale in-vitro test for detecting resistance of plasmodium falciparum to chloroquine, isolates are incubated for 24-28 h in medium that does not contain serum. the effect of prolonging incubation to 48 h and of adding human ab serum to the culture medium of p falciparum from irian jaya, indonesia was studied. addition of serum was not associated with any advantages or disadvantages. production of schizonts was increased when incubation was prolonged. this facilitated readin ...19846140392
human lymphocytes transformed with epstein-barr virus produce antibodies against sporozoite stage of plasmodium falciparum. 19846142241
identification of circumsporozoite proteins in individual malaria-infected mosquitoes by western blot analysis.circumsporozoite (cs) proteins of rodent (plasmodium berghei), simian (p. knowlesi), and human (p. falciparum) malaria parasites extracted from dead and dried mosquitoes have been identified by the western blot (immunoblot) technique. dried mosquitoes which were laboratory-reared and infected with plasmodium or freshly dissected sporozoites were triturated in sample reducing buffer and the extracts electrophoresed in a 10% sds-polyacrylamide gel. after transferring the proteins to nitrocellulose ...19846145742
killing of human malaria parasites by macrophage secretory products.the susceptibility of the human malaria parasite, plasmodium falciparum, to killing in vitro by macrophage secretory products was investigated. the effect of o2 radicals and tumor necrosis factor on parasite viability was assessed both morphologically and by following the uptake of [3h]hypoxanthine. h2o2 produced by the interaction of glucose and glucose oxidase was found to reduce viability; this effect was reversed by the addition of exogenous catalase. further studies indicated that the catal ...19846363296
the ring-infected erythrocyte surface antigen (resa) polypeptide of plasmodium falciparum contains two separate blocks of tandem repeats encoding antigenic epitopes that are naturally immunogenic in man.we showed previously that the ring-infected erythrocyte surface antigen (resa) of plasmodium falciparum contains a repetitive amino acid sequence. we have investigated here the sequence and antigenic relationships between resa from fc27, a papua new guinea isolate, and from nf7, a ghanaian isolate. the complete nucleotide sequences of eight different cdna clones demonstrate that resa from the two strains are closely homologous over the region that can be compared. a series of related eight, four ...19846085696
human antisera detect a plasmodium falciparum genomic clone encoding a nonapeptide repeat.plasmodium falciparum causes malaria infections in its human host. its wide distribution in tropical countries is a major world health problem. before a vaccine can be produced, the identification and characterization of parasite antigens is necessary. this can be achieved by the cloning and subsequent analysis of genes coding for parasite antigens. recently established cdna banks allow the expression of cdna derived from the simian parasite plasmodium knowlesi and p. falciparum in escherichia c ...19846090935
species- and stage-specific antigens in exoerythrocytic stages of plasmodium falciparum.numerous exoerythrocytic forms of plasmodium falciparum ( pfeef ) were obtained from the liver of the south american monkey, cebus apella, for analysis of the antigens on this stage. as antigen for the fluorescent assay, 5-micron sections of liver fragments collected on day 5 following sporozoite inoculation and fixed in carnoy's solution or kept in liquid nitrogen were used. two types of fluorescent labeling of the pfeef were identified: diffuse and peripheral. each of 23 sera from individuals ...19846203418
recognition and invasion of human erythrocytes by malarial parasites: contribution of sialoglycoproteins to attachment and host specificity.the receptivity of human erythrocytes to invasion by plasmodium falciparum merozoites can be decreased by neuraminidase or trypsin treatment, an observation that supports a role for the erythrocyte sialoglycoproteins (glycophorins) in invasion. we have found that alpha 1-acid glycoprotein (agp), added to in vitro cultures, can restore invasion of enzyme-treated human erythrocytes. agp is structurally different from the glycophorins although it does carry 12% sialic acid. its ability to restore r ...19846373782
lack of inhibitory effects of alpha 1-acid glycoprotein (orosomucoid) on plasmodium falciparum invasion of human erythrocytes.there has been controversy whether the plasma protein, alpha 1-acid glycoprotein (agp), is able to inhibit invasion of erythrocytes by p. falciparum merozoites. because agp resembles a typical cell membrane sialoglycoprotein, it has been proposed that it can inhibit the parasite from interacting with its sialoglycoprotein receptor on the erythrocyte surface. we therefore isolated and tested samples of agp obtained from a series of separate individuals. for comparative purposes, we also tested ag ...19853929633
the pros and cons of modelling malaria transmission.the question is approached through three examples. ross's model, although very simple and formulated a priori, yielded important epidemiological insights: the existence of a threshold contact rate (vectorial capacity); the decreasing sensitivity of the endemic level to changes in the contact rate, as the latter gets larger; the return to the same equilibrium endemic level, as long as the contact rate remains the same; the progressively decreasing impact of a given reduction in the contact rate u ...19853914114
plasmodium falciparum malaria: band 3 as a possible receptor during invasion of human erythrocytes.human erythrocyte band 3, a major membrane-spanning protein, was purified and incorporated into liposomes. these liposomes, at nanomolar concentrations of protein, inhibited invasion of human erythrocytes in vitro by the malaria parasite plasmodium falciparum. liposomes containing human band 3 were ten times more effective in inhibiting invasion than those with pig band 3 and six times more effective than liposomes containing human erythrocyte glycophorin. liposomes alone or liposomes containing ...19853880920
different malaria control activities in an area of liberia--effects on malariometric parameters.the epidemiology of malaria was studied in a west african mining town (yekepa) and three surrounding zones defined as close, middle and far areas. malariometric parameters were investigated in children two to nine years of age at the end of the rainy season. in yekepa, vector control measures and intense suppression of malaria with drugs had created an almost hypoendemic situation with a spleen rate of 11%. in close area, vector control was applied to some extent and malaria drugs were frequentl ...19853896168
isolation and cultivation of plasmodium falciparum using adult bovine serum.rpmi 1640 medium supplemented with adult bovine serum and hypoxanthine was superior to human serum-supplemented medium for the isolation of new strains of plasmodium falciparum in sudan. similar observations in indonesia have since confirmed our results. the chloroquine sensitivity of new isolates was identical in either human or bovine serum. once acclimated to culture conditions p. falciparum strains grew better when using human serum. erythrocyte-specific antibody present in adult bovine seru ...19853897502
recent efforts in the development of a sporozoite vaccine against human malaria.nineteen monoclonal antibodies were produced against sporozoites of plasmodium falciparum. they have been characterized immunochemically, as well as by isotype, csp reactivity, and stage and species specificity. five of these monoclonal antibodies were used to screen a genomic library of p. falciparum in the expression vector lambda gt 11. aspects of the cloning and sequencing of the gene encoding for the cs protein of p. falciparum are described. the cs gene encodes for a sporozoite surface pro ...19853907309
the problem of drug resistance in malaria.the resistance in human malaria is mainly of practical importance in relation to plasmodium falciparum. strains resistant not only to chloroquine but also to dihydrofolate reductase inhibitors, and even to potentiating combinations of these with sulphonamides or sulphones, are appearing in an ever increasing geographical area which now includes tropical africa and india. few new drugs are available or foreseen for the near future, mefloquine and artemisinine being the leading contenders. it is v ...19853892439
human monocyte activation by supernatants from continuous cultures of plasmodium falciparum.when mononuclear cells derived from the blood of unsensitized adult caucasians are incubated for 22 hours with supernatants from cultures of plasmodium falciparum, there is a substantial stimulation of the phagocytic capacity of the adherent monocytes for anti-d sensitized red cells. this stimulatory effect is dependent on (i) a heat-stable factor in such supernatants, (ii) the presence of t lymphocytes in the mononuclear cell preparations and (iii) the occurrence of dna synthesis in the mononuc ...19853913068
role of carbohydrate residues in interaction of human erythrocytes with plasmodium falciparum merozoites--future prospects. 19853913699
the interferon compartment of the immune response in human malaria: ii. presence of serum-interferon gamma following the acute attack.the present study concerns the monitoring of serum-interferon (serum-ifn) levels among 189 patients followed after and sometimes during an acute episode of malaria due mainly to plasmodium falciparum (p. falciparum). of these patients, 110 known to have no other parasitic or infectious disease were followed in france; 79 were from thailand, among which 25 cases of neuromalaria were diagnosed. in a first four-month survey conducted in france, among 100 patients seen after the acute attack, serum- ...19853921628
specific proliferative response of human lymphocytes to purified soluble antigens from plasmodium falciparum in vitro cultures and to antigens from malaria patients' sera.antigens of plasmodium falciparum, in supernatants of in vitro cultures of the parasite were affinity purified on columns prepared with the igg fraction of the serum of an immune individual. the purified antigens induced proliferation of lymphocytes from persons who had recently had malaria. the responses were strongest with lymphocytes from individuals infected with falciparum and ovale malaria; vivax malaria infections induced a lower level of response and lymphocytes of unsensitized individua ...19853884198
expression of plasmodium falciparum surface antigens in escherichia coli.the asexual blood stages of the human malarial parasite plasmodium falciparum produce many antigens, only some of which are important for protective immunity. most of the putative protective antigens are believed to be expressed in schizonts and merozoites, the late stages of the asexual cycle. with the aim of cloning and characterizing genes for important parasite antigens, we used late-stage p. falciparum mrna to construct a library of cdna sequences inserted in the escherichia coli expression ...19853887406
monoclonal antibody okm5 inhibits the in vitro binding of plasmodium falciparum-infected erythrocytes to monocytes, endothelial, and c32 melanoma cells.plasmodium falciparum-infected erythrocytes bind in vitro to human endothelial cells, monocytes, and a certain melanoma cell line. evidence suggests that this interaction is mediated by similar mechanisms which lead to the sequestration of parasitized erythrocytes in vivo through their attachment to endothelial cells of small blood vessels. we show here that monoclonal antibody okm5, previously shown to react with the membranes of endothelial cells, monocytes, and platelets, also reacts with the ...19853900210
the development and ultrastructure of plasmodium falciparum damaged in vitro by human "crisis" sera and by chloroquine.p. falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. intra-erythrocytic parasite damage was seen by light and electron microscopy. the significance of the results is discussed with relevance to non-specific immune mechanisms, and the damage induced by these mechanisms compared with that from chloroquine.19853893406
[entomological study on the transmission of human malaria in the senegal river basin (senegal)]. 19853907535
an improved technique for the cultivation of plasmodium falciparum in vitro without daily medium change.a simple method is described allowing growth of plasmodium falciparum in suspension cultures with 1% outdated human erythrocytes without the need for medium change for three to four days. depending on the initial parasitaemia, final parasitaemias of from 10% to 30% can be obtained. growth is exponential and asynchronous with a mean multiplication rate of 7.7 +/- 1.0 (n = 5) -fold per 48-hour cycle. the method is suitable for cultivation of a wide range of laboratory strains of p. falciparum, as ...19853907558
[distribution and ecology of anopheles lesteri, a human blood-sucking subspecies and its role in malaria transmission]. 19853912062
the interferon compartment of the immune response in human malaria: i. interferon inducers in plasmodium falciparum cultures.the present study concerns the interferon (ifn) compartment of the immune response in human malaria. it was undertaken with plasmodium falciparum parasitized human red blood cell culture supernatants (pf-rbcs). investigations were conducted in order to verify whether supernatants of such protozoa cultures had the capacity to induce gamma interferon previously identified in sera of p. falciparum infected patients and to verify whether a t-cell mitogen recently characterized in vitro could be corr ...19853921627
synthesis of small nuclear ribonucleoprotein particles by the malarial parasite plasmodium falciparum.sera from patients with autoimmune diseases have been used to identify small nuclear ribonucleoprotein particles (snrnps) present in higher eukaryotic cells and also in dinoflagellates. previously these sera have not detected crossreactive snrnp protein antigens of other lower eukaryotes such as yeast, tetrahymena, or dictyostelium. we report that anti-sm, anti-u1-rnp, and anti-la/ss-b human antisera react with specific snrnp protein antigens synthesized by the protozoan plasmodium falciparum, t ...19852582421
immunogenicity of synthetic peptides from circumsporozoite protein of plasmodium falciparum.in a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (cs) protein of plasmodium falciparum were found to be immunogenic for mice and rabbits. antibody to peptides from the repeating region of the cs protein recognized native cs protein and blocked sporozoite invasion of human hepatoma cells in vitro. antibodies to peptides from regions i and ii had no biologic activity, although antibody to region i recogniz ...19852988126
pathogenicity, stability, and immunogenicity of a knobless clone of plasmodium falciparum in colombian owl monkeys.the pathogenicity, immunogenicity, and morphological stability of a knobless clone of strain fcr-3 of the human malaria parasite plasmodium falciparum was investigated in aotus monkeys. an early knob-bearing (k+), wild-type isolate of strain fcr-3 and the d3 knobless (k-) clone were adapted to aotus monkey erythrocytes in continuous culture, establishing the parasites in aotus cells without exposure to in vivo cellular or humoral immune responses. all monkeys, intact or splenectomized, which wer ...19853882566
origin of proteinuria in human malaria.the prevalence and pathogenesis of renal involvement was investigated in 74 patients with malarial infections. a rise in proteinuria of 150 to 5,000 mg per day was seen in 12 out of 27 patients with plasmodium falciparum infections. sds-polyacrylamide gel electrophoresis revealed either an increase in albumin and high molecular weight proteins alone or an increase in low and high molecular weight proteins. serum creatinine and urea were increased in 5 patients. in p. vivax infections, 8 out of 4 ...19853890120
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
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
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
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
polymorphism of a high molecular weight schizont antigen of the human malaria parasite plasmodium falciparum.intraspecies antigenic diversity in the blood stages of the human malaria parasite plasmodium falciparum was investigated using a collection of murine monoclonal antibodies and clones of the parasite. the results were as follows: (a) the schizont and merozoite stages of the parasite express on their surface clonally restricted antigens detectable by strain-specific antibodies in indirect immunofluorescence tests. (b) these restricted antigens are phenotypically stable characteristics of clones g ...19852578540
malaria: the king is threatened.malaria received high priority at the xi international congress for tropical medicine held in the fall of 1984. 30 of the sessions focused on the malarial parasite and its "anopheles" mosquito vector. topics covered included genetics, epidemiology, chemotherapy, health care delivery, training, and vaccine development. dr. (sir) gustav nossal, director of the walter and eliza hall medical research institute, victoria, australia, set the theme with his statement: "vaccines are history's most c ...198512281239
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
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
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
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
[further discussion on human pseudo-haemogregarines]. 19863530086
plasmodium falciparum: protease inhibitors and inhibition of erythrocyte invasion.invasion of human red blood cells by plasmodium falciparum is inhibited by the protease inhibitors, leupeptin and chymostatin. the efficacy of chymostatin was reduced if the cells were first treated with chymotrypsin. on the other hand, exposure of fresh cells to the supernatant from a synchronous culture at the reinvasion stage showed no such effect. this suggests that a proteolytic step occurs in the course of invasion and may be confined to the region of contact between the invading parasite ...19863536568
effects of red blood cell potassium and hypertonicity on the growth of plasmodium falciparum in culture.malarial parasites reproduce asexually inside the erythrocytes of their vertebrate host. relatively little is known about the interaction between host cell and parasite metabolism. in the present study the effect of host cell cation composition and osmotic shrinkage on in vitro growth and propagation of plasmodium falciparum in human erythrocytes was investigated. it is shown that throughout the parasite cell cycle, infected cells lose potassium and gain sodium. compartment analysis of infected ...19863518266
[intravector anti-plasmodium activity of a pyrethrinoid: deltamethrin].in vitro tests, deltamethrin reduced the parasitemic index of plasmodium falciparum on human red blood corpuscles. in vivo tests, at sublethal doses, deltamethrin limited the development of the sporogonic cycle of plasmodium yoelii yoelii in anopheles stephensi. this novel type of antiplasmodic activity involve an intravectorial route and gives an explanation about surprising antimalaria effects observed several months after treatment.19863096513
perturbation of red cell membrane structure during intracellular maturation of plasmodium falciparum.an experimental approach, which in this study was applied to the malarial system, can be used to analyze the molecular structure and organization of individual phospholipids in a wide variety of biological membranes. electron spin resonance spectroscopy was used to investigate the structural modifications of the major red cell phospholipids that occur in erythrocyte membranes infected with the human malarial parasite, plasmodium falciparum. these modifications were correlated with the intracellu ...19863006251
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
antimalarial activity of selected aromatic chelators. iv. cation uptake by plasmodium falciparum in the presence of oxines and siderochromes.the growth of plasmodium falciparum, a human malaria parasite, is sensitive to inhibition by chelators of several types. the alkylthiocarbamates and 8-hydroxyquinoline at pharmacologic doses selectively inhibit glycolysis within 6 hr in parasitized erythrocytes. the mechanism attributed to these agents is through the extracellular formation of lipid-soluble 2:1 metal complexes which enter susceptible cells and liberate a lethal 1:1 complex. this study further supports this mechanism since the up ...19862945090
plasmodium falciparum: regional differences in lectin and cationized ferritin binding to the surface of the malaria-infected human erythrocyte.the distribution of anionic residues on the surface of erythrocytes infected with plasmodium falciparum was studied using cationized ferritin (cf) and transmission electron microscopy. cf staining of uninfected erythrocytes or erythrocytes infected with a knobless variant resulted in a dense and uniform distribution of ferritin particles; however, when red cells infected with a knob-inducing variant were exposed to cf, aggregates of ferritin particles were observed in the region of membrane elev ...19863528994
effectiveness of liposomes as potential carriers of vaccines: applications to cholera toxin and human malaria sporozoite antigen.two antigens, cholera toxin (ct) and a synthetic albumin-conjugated 16-residue peptide derived from the circumsporozoite (cs) protein of plasmodium falciparum sporozoites, were tested as immunogens in rabbits. the malaria peptide-albumin conjugate by itself was completely nonimmunogenic, and although cholera toxin was immunogenic it also expressed considerable native toxicity. after attachment of ct to liposomes containing ganglioside gm1, toxicity of ct was completely eliminated and antigenicit ...19863532603
role of immune serum and complement in stimulation of the metabolic burst of human neutrophils by plasmodium falciparum.interaction between human neutrophils (polymorphonuclear leukocytes [pmn]) and plasmodium falciparum in the natural defense of the host remains to be elucidated. in patients with acute malaria, oxygen consumption (qo2) of pmn at rest and after stimulation by zymosan was significantly increased compared with that in the controls. with 10% immune serum, both qo2 and chemiluminescence of normal pmn were significantly increased after stimulation by a p. falciparum erythrocyte culture. this activatio ...19863512435
effects of mitochondrial inhibitors on intraerythrocytic plasmodium falciparum in in vitro cultures.malarial parasites infecting mammalian hosts are considered to be homolactate fermentors at their asexual intraerythrocytic developmental stage; however, existing ultrastructural and biochemical evidence suggest that their acristate mitochondria could be involved in energy metabolism. in the present study, inhibitors of mitochondrial function including compounds which act on nadh and succinate dehydrogenases, electron transport and mitochondrial atpase, as well as uncouplers, were found to inhib ...19863514901
potential vectors of malaria and their different susceptibility to plasmodium falciparum and plasmodium vivax in northern brazil identified by immunoassay.during the period from may 1983 to july 1985 we conducted an epidemiological study to determine potential vectors of malaria in 6 districts in the state of pará in northern brazil. the examination of random human blood smears, prepared at the time of mosquito capture, indicated overall human infection rates of 16.7% and 10.9% for plasmodium falciparum and p. vivax, respectively. two immunoassays, the immunoradiometric assay (irma) and the enzyme-linked immunosorbent assay (elisa), based on the u ...19863532844
[elisa test in sero-epidemiologic studies of human malaria. evaluation of an antigen prepared from erythrocytes of saimiri sciureus experimentally infected with plasmodium falciparum].a soluble antigen was prepared from squirrel monkeys (saimiri sciureus) infected with blood-passaged plasmodium falciparum, and evaluated in an enzyme-linked immunosorbent assay (elisa) as a potent antigen for malaria diagnostic. the specificity, reproducibility and sensibility of the test showed the suitability of our antigenic preparation in detecting antibodies, igg and igm, in patients with p. falciparum infections. thus, the saimiri monkey represents an interesting alternative to the classi ...19863516425
uptake of [3h]chloroquine by drug-sensitive and -resistant strains of the human malaria parasite plasmodium falciparum.chloroquine accumulation by human erythrocytes infected with nine different strains of the malarial parasite plasmodium falciparum, which varied by greater than or equal to 20-fold sensitivity to the drug, was measured as a function of time and drug concentration. although the kinetics of uptake were clearly quite complex in this system, at least two general phases were observed, an extremely rapid short phase (less than 30 sec), followed by a slower phase leading to steady state within 60 min. ...19863535803
inhibition of malarial invasion by intracellular antibodies against intrinsic membrane proteins in the red cell.it has previously been shown that antibodies against the transmembrane proteins, band 3 and glycophorin a, inhibit entry of the merozoite into the red cell and, in the case of band 3, it was established that attachment of the parasite to the cell is not prevented. we have found that antibodies against the cytoplasmic domains of band 3 and of glycophorin a, when present in the interior of resealed ghosts of human red cells, also inhibit invasion by p. falciparum. it is inferred that attachment of ...19863540816
14c-desferrioxamine b: uptake into erythrocytes infected with plasmodium falciparum.plasmodium falciparum-infected human erythrocytes (early trophozoite stages) and non-infected erythrocytes were incubated in 1.7 mm 14c-desferrioxamine b (specific activity 1 microci/2.6 mg desferrioxamine b). after 270 min the cells were washed and the radioactivity was measured in the cell pellet and, after lysis, in cytoplasm and membranes. the results indicate that desferrioxamine b can the red blood cell and pass through the parasite membrane and that the parasites are killed by the intrace ...19863541423
suppression of blood monocyte and neutrophil chemotaxis in acute human malaria.the host response to plasmodia includes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. in addition, the neutrophil chemotaxis was measured in 12 patients. before the initiation of antimalarial tre ...19863808753
plasmodium falciparum-specific human t cell clones: recognition of different parasite antigens.t lymphocyte clones specific for malarial (plasmodium falciparum) blood stage antigens were obtained from acutely infected patients or from donors living in a malaria-endemic area of west africa. thirty-four clones carrying the cd4 antigen, and one cd8+ clone, were tested in a proliferation assay for their capacity to recognize p. falciparum isolates of different geographical origins. only one clone distinguished between different parasite isolates (it failed to react with a parasite isolate ori ...19873549326
ultrastructural localization of the 150/130 kd antigens in sexual and asexual blood stages of plasmodium falciparum-infected human erythrocytes.the subcellular localization of the 150/130 kd antigen in plasmodium falciparum-infected erythrocytes was determined by electron microscopy using monoclonal antibody 9b11 and immuno-gold labeling. we now find that this antigen may be associated with the membrane of newly-infected human erythrocytes and the cytoplasm of ring stage parasites. during differentiation of the parasite to the trophozoite stage, the antigens are no longer detectable on the erythrocyte membrane, while gold particles beco ...19873555137
human and primate malarial sera inhibit fc receptor-mediated phagocytosis.sera obtained from humans in p. falciparum-endemic regions and from p. vivax-infected saimiri sciureus were assayed for their ability to inhibit fc receptor-mediated phagocytosis. some sera of humans exposed to p. falciparum from the gambia, sudan, and thailand inhibited ingestion via the fc receptor by normal human monocytes. in addition, sera from infected monkeys and a high molecular weight fraction of infected monkey serum inhibited ingestion of eigg by normal monkey spleen macrophages. gene ...19873548450
toxicity of certain products of lipid peroxidation to the human malaria parasite plasmodium falciparum.aldehydes generated during radical-induced lipid peroxidation, in particular 4-hydroxynonenal, are known to inhibit growth of certain cells. to extend our arguments that free radicals might be involved in the host response against malaria parasites we tested 26 carbonyls (n-alkanals, c6-c11; 2-alkenals, c3-c9; 2,4-alkadienals, c7, c9, c10; 4-oh-2-alkenals, c6, c8, c9; 2-alkanones, c3-c9; and malonyldialdehyde) against plasmodium falciparum in vitro. we had previously detected many of these subst ...19873548730
human cerebral malaria: a pathological study.the following report using light and electron microscopic and immunological techniques is based on a series of 19 burmese patients who died of cerebral malaria. the principal change was blockage of cerebral capillaries by plasmodium falciparum-infected erythrocytes. ring hemorrhages and segmental necrosis of cerebral capillaries were common. cerebral edema was variable in these cases. electron-dense knobs, 40 x 80 nm in size, which protruded from the membrane of infected erythrocytes, formed foc ...19873546601
purification of the bifunctional thymidylate synthase-dihydrofolate reductase complex from the human malaria parasite plasmodium falciparum.the bifunctional thymidylate synthase-dihydrofolate reductase complex from the human malaria parasite plasmodium falciparum has been purified to homogeneity using a sequence of separation steps including phenyl-superose, gel filtration, dye affinity matrix, hydroxyapatite, and anion exchange chromatography. the specific activity of dihydrofolate reductase increased approximately 24,000-fold from 3.3 units mg-1 protein to 79,000 units mg-1 protein after five successive chromatographic steps with ...19873320742
studies on glycoproteins in the human malaria parasite plasmodium falciparum--lectin binding properties and the possible carbohydrate-protein linkage.several glycoproteins of the human malarial parasite plasmodium falciparum are shown to bind to the lectins concanavalin a, wheat germ agglutinin, ricinus communis 120 lectin and bandeirea simplicifolia lectin. there was reduced binding of [125i]-concanavalin a to several red blood cell glycoproteins, including the anion transport protein, in parasitised cells. the carbohydrates of parasite glycoproteins are not typical n-linked oligosaccharides since the enzyme peptide: n-glyconase f fails to c ...19873301641
doxycycline prophylaxis for falciparum malaria.188 schoolchildren aged 10-15 living in a malaria endemic area along the thai-burmese border were matched for age, splenomegaly, and weight and were then randomly assigned to receive either doxycycline (adult equivalent of 100 mg daily) or chloroquine (adult equivalent of 300 mg base weekly). all drugs were administered by the investigators and blood smears were done weekly. in 95 subjects taking doxycycline for 597 man-weeks there were 5 cases of falciparum malaria and in the 93 controls taking ...19872883488
safety and efficacy of a recombinant dna plasmodium falciparum sporozoite vaccine.a recombinant dna plasmodium falciparum sporozoite vaccine produced in escherichia coli (fsv-1) was tested in doses of 10 micrograms to 800 micrograms protein in fifteen volunteers. no serious adverse reactions occurred. antibodies that reacted with p falciparum sporozoite antigens by enzyme-linked immunoassay developed in twelve of the volunteers. the highest antibody titres induced were similar to those resulting from lifelong natural exposure to sporozoite-infected mosquitoes. postimmunizatio ...19872884410
globin gene-associated restriction-fragment-length polymorphisms in southern african peoples.the combination of polymorphic restriction-enzyme sites in the 3' region of the beta-globin gene cluster shows very little variation in southern-african bantu-speaking black and kalahari !kung san populations. the sites of the 5' region, on the other hand, show marked variation, and two common haplotypes are present--the "negro" type (- - - - +) and the "san" type (- + - - +)--in frequencies of .404 and .106, respectively, in the bantu-speakers and .262 and .405, respectively, in the san. twenty ...19872891298
plasmodium falciparum-specific human t cell clones: evidence for helper and cytotoxic activities.this report describes the isolation, and the phenotypic and functional characterization of plasmodium falciparum-specific human t lymphocyte clones (tlc) obtained from 2 acutely infected and 4 clinically immune donors. approximately one third of the tlc obtained from the acutely infected patients had the phenotype cd8+/cd4-. no such clones were obtained from the clinically immune donors. p. falciparum-specific, major histocompatibility complex-restricted cd8+ clones can lyse unrelated tumor cell ...19873030767
generation of reactive oxygen radicals by human phagocytic cells activated by plasmodium falciparum.the role of monocytes, macrophages and neutrophils in killing malaria parasites is well documented, and their involvement in malaria pathology has been suggested. however, the underlying mechanisms are not clear. the present study reports on the role of p. falciparum-parasitized erythrocytes, free merozoites, and culture supernatant antigens in the generation of reactive oxygen radicals by human peripheral blood monocytes and neutrophils. blood neutrophils and monocytes obtained from healthy ind ...19873033817
inhibition of human lymphocyte proliferative response by serum from plasmodium falciparum infected patients.malaria infection has been shown to induce alterations in immune reactivity. this report describes the effect of serum obtained from plasmodium falciparum infected patients on in vitro proliferation of human blood mononuclear cells (bmnc) isolated from healthy individuals. serum obtained before initiation of treatment suppressed the in vitro lymphocyte proliferative response to both plasmodium-derived antigens and an unrelated antigen (ppd-tuberculin). the suppressive effect was lost if the seru ...19873327360
genetic analysis of the human malaria parasite plasmodium falciparum.malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. the parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. a cross was made between two clones of plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. parasites showing recombination between the parent clone mark ...19873299700
naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications.the first human vaccines against the malaria parasite have been designed to elicit antibodies to the circumsporozoite protein of plasmodium falciparum. however, it is not known whether any level of naturally acquired antibodies to the circumsporozoite protein can predict resistance to plasmodium falciparum malaria. in this study, 83 adults in a malaria-endemic region of kenya were tested for circumsporozoite antibodies and then treated for malaria. they were monitored for the development of new ...19873299709
experimental infections of simians with human malaria: attempts to infect callithrix penicillata with plasmodium falciparum.after reviewing the use of non-human primates of the old and new worlds for human malaria research, we concluded that another experimental animal which is easily available to use and possible to rear indoors is needed. thus, we studied the susceptibility of the marmoset callithrix penicillata to plasmodium falciparum erythrocytic infections. the marmosets received various p. falciparum human isolates, directly from a patient and from continuous cultures. the palo alto strain, which has been adap ...19873149726
frequency of human leukocyte antigen (hla) in patients with malaria and in the general population of humaitá county, amazonas state, brazil. 19873333875
invasion of mouse erythrocytes by the human malaria parasite, plasmodium falciparum.plasmodium falciparum malaria merozoites require erythrocyte sialic acid for optimal invasion of human erythrocytes. since mouse erythrocytes have the form of sialic acid found on human erythrocytes (n-acetyl neuraminic acid), mouse erythrocytes were tested for invasion in vitro. the camp and 7g8 strains of p. falciparum invaded mouse erythrocytes at 17-45% of the invasion rate of human erythrocytes. newly invaded mouse erythrocytes morphologically resembled parasitized human erythrocytes as sho ...19873295109
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