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the c-terminal domain of rna polymerase ii of the malaria parasite plasmodium berghei.the c-terminal domain (ctd) of rna polymerase ii (rnap) has an essential function in the regulation of transcription. the ctd of the human malaria parasite, plasmodium falciparum, differs dramatically from that of higher eukaryotes. to determine whether this is a general feature of malarial parasites, we have analysed the ctd of the distantly related rodent malaria parasite p.berghei. the ctds of the two parasites enzymes are very similar in amino acid composition and contain the basic structure ...19911840489
[severe malaria in black africa].severe and complicated malaria is a fatal from a human plasmodium falciparum infection. in clinical practice cerebral malaria in children, with unrousable coma, hyperthermia, generalized convulsions, frequently hypoglycemia, is different of severe in non immunized adults resulting in multiple organ failure with degree of impaired consciousness less important. specific treatment requires quinine with loading dose: 16.7 mg/kg then 8.3 mg/kg every 8 hours for 7 days. symptomatic therapy, artificial ...19911842775
a stage specific gene expressed at the onset of gametocytogenesis in plasmodium falciparum.the gene encoding the gametocyte specific cytoplasmic protein pfg27/25 of the human malaria parasite plasmodium falciparum has been cloned. the gene encodes a highly hydrophilic non-repetitive protein which does not share obvious homologies with other polypeptides. the stage specificity of pfg27/25 is controlled at the stage of the production of stable mrna, which is detectable only in the sexual stages of the parasite, and contains long additional sequences outside the pfg27/25 coding region. a ...19911852178
clustering of malaria infections within an endemic population: risk of malaria associated with the type of housing construction.the occurrence of malaria infections due to plasmodium vivax and p. falciparum was monitored in a population of 3,023 people living in six contiguous villages in kataragama, an area of endemic malaria in southern sri lanka, over a period of 17 months. the annual incidence of malaria in this population during the study period was 25.8%. malaria attacks were clustered, occurring more frequently than expected in certain individuals and housing groups and less frequently than expected in others. in ...19911867350
anopheline ecology and malaria infection during the irrigation development of an area of the mahaweli project, sri lanka.a study on adult anopheline ecology and malaria vector incrimination was carried out from 1986 to 1989 during irrigation development in an area of the mahaweli project in eastern sri lanka. eleven potential vector species were collected resting indoors or by using human or bovid bait, and from light trap catches. overall, anopheles vagus (donitz), an. annularis (van der wulp), and an. subpictus (grassi) were the most prevalent, and an. culicifacies (giles) and an. barbirostris (van der wulp) wer ...19911877717
killing of plasmodium falciparum in vitro by nitric oxide derivatives.we have investigated the in vitro susceptibility of the human malaria parasite plasmodium falciparum to killing by nitric oxide and related molecules. a saturated solution of nitric oxide did not inhibit parasite growth, but two oxidation products of nitric oxide (nitrite and nitrate ions) were toxic to the parasite in millimolar concentrations. nitrosothiol derivatives of cysteine and glutathione were found to be about a thousand times more active (50% growth inhibitory concentration, approxima ...19911879941
interaction of the 140/130/110 kda rhoptry protein complex of plasmodium falciparum with the erythrocyte membrane and liposomes.during plasmodium falciparum merozoite invasion into human and mouse erythrocytes, a 110-kda rhoptry protein is secreted from the organelle into the erythrocyte membrane. in the present study our interest was to examine the interaction of rhoptry proteins of p. falciparum with the erythrocyte membrane. it was observed that the complex of rhoptry proteins of 140/130/110 kda bind directly to a trypsin sensitive site on intact mouse erythrocytes, and not human, saimiri, or other erythrocytes. howev ...19911889471
the role of t lymphocytes in immunity to plasmodium falciparum. enhancement of neutrophil-mediated parasite killing by lymphotoxin and ifn-gamma: comparisons with tumor necrosis factor effects.human neutrophils were treated with ifn-gamma or lymphotoxin and their interaction with the asexual blood forms of plasmodium falciparum was studied by a radiometric assay and microscopy. the results showed that human neutrophils inhibited the growth of p. falciparum and killed the parasite via a phagocytic mechanism. the cytokines significantly augmented the neutrophil-mediated killing of the parasite. when compared with the effects of tnf-alpha similar results were seen although ifn-gamma and ...19911898962
calcium and the malaria parasite: parasite maturation and the loss of red cell deformability.in the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. p. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. both parasite maturation and the loss of red cell defo ...19911902127
enhanced uptake and metabolism of riboflavin in erythrocytes infected with plasmodium falciparum.riboflavin deficiency inhibits the growth of malaria parasites both in vitro and in vivo in infected animals and humans. although the precise mechanisms underlying this inhibition are unknown, they may involve enhanced requirements for riboflavin by parasites. to investigate this possibility, the rate of uptake of [14c]riboflavin and the biosynthesis of fmn and fad from riboflavin were studied in infected (5-8% parasitemia) and uninfected human erythrocytes. all cells were incubated for 0-3 h at ...19911920146
peptide derivatives specific for a plasmodium falciparum proteinase inhibit the human erythrocyte invasion by merozoites.a specific proteinase of p. falciparum merozoites has been detected by using hydrosoluble fluorogenic peptidic substrates synthesized by classical peptide chemistry; their n-terminal end was acylated by a gluconoyl group that protects them from aminopeptidase degradation and increases their hydrosolubility, and their carboxylic end was substituted by a 3-amino-9-ethylcarbazole group. the sequence val-leu-gly-lys was found to be the most specific substrate. on this basis, reversible peptidic inhi ...19911920353
in vivo and in vitro derived palo alto lines of plasmodium falciparum are genetically unrelated.the uganda palo alto strain of plasmodium falciparum (fup) is routinely used as a reference isolate in a number of laboratories. it is one of the few p. falciparum strains that can both be propagated in vivo in monkeys and maintained in culture. the palo alto parasites have been characterized for several biochemical and molecular markers, but many of the data reported so far are contradictory. we have analyzed and compared by southern blotting, pcr and dna sequencing, several dna preparations ob ...19911944415
a plasmodium falciparum exo-antigen alters erythrocyte membrane deformability.here we describe a reduced membrane deformability of human erythrocytes when aspirated into 0.6 microns diameter in polycarbonate sieves, after exposure of uninfected cells to spent parasite-culture supernatant. this, taken in concert with a previous observation that intra-erythrocytic development of the parasite p. falciparum decreases host localised membrane deformability, may indicate a biological role for such parasite-induced changes in the rheological properties of the erythrocyte.19911959636
specific killing of cytotoxic t cells and antigen-presenting cells by cd4+ cytotoxic t cell clones. a novel potentially immunoregulatory t-t cell interaction in man.mycobacterial antigens not only stimulate th cells that produce macrophage-activating factors, but also cd4+ and cd8+ ctl that lyse human macrophages. the mycobacterial recombinant 65-kd hsp was previously found to be an important target antigen for polyclonal cd4+ ctl. because of the major role of 65-kd hsp in the immune response to mycobacterial as well as autoantigens, we have studied ctl activity to this protein at the clonal level. hla-dr or hla-dq restricted, cd4+cd8- t cell clones that re ...19901972178
human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies.plasmodium falciparum isolates from 24 gambian children with cerebral malaria and 57 children with mild forms of the disease were assessed for their ability to form erythrocyte rosettes. all isolates from the children with cerebral malaria were able to form rosettes, whereas those from children with mild forms of the disease did not form rosettes, or had a significantly lower rosetting rate. plasma of children with cerebral malaria lacked anti-rosetting activity, whereas plasma of children with ...19901979090
metabolism of glutamine in erythrocytes infected with the human malaria parasite: plasmodium falciparum.the metabolism of glutamine was studied in erythrocytes infected with plasmodium falciparum, comparatively to normal cells, in presence or not of don (6-diazo-5-oxo-l-norleucine) or acivicin, two glutamine antagonists which have been shown to inhibit the growth of p. falciparum in vitro. extracellular glutamine was partially converted into glutamate using two routes corresponding to gamma-glutamyl transpeptidase (ggt) and glutaminase activities. in cells infected with mature trophozoites, the ob ...19901982204
lipid traffic between high density lipoproteins and plasmodium falciparum-infected red blood cells.several intraerythrocytic growth cycles of plasmodium falciparum could be achieved in vitro using a serum free medium supplemented only with a human high density lipoprotein (hdl) fraction (d = 1.063-1.210). the parasitemia obtained was similar to that in standard culture medium containing human serum. the parasite development was incomplete with the low density lipoprotein (ldl) fraction and did not occur with the vldl fraction. the lipid traffic from hdl to the infected erythrocytes was demons ...19911988461
isolation and characterization of a soluble antigen complex of plasmodium falciparum with pyrogenic properties.a soluble antigen complex, previously designated antigen no. 7 (ag7) on the basis of the pattern obtained by crossed immunoelectrophoresis of culture supernatants of p. falciparum, was isolated by affinity chromatography. it was shown to be synthesized at the schizont stage of the parasite growth cycle and to be located on the surface of the schizonts. antibodies to ag7 did not inhibit the growth of the parasite in vitro. ag7 is recognized by immune human sera from many parts of the world and it ...19911993114
human antibody response to the major merozoite surface antigen of plasmodium falciparum is strain specific and short-lived.the precursor of the major merozoite antigen of plasmodium falciparum, gp190, is considered a candidate for inclusion in a malaria vaccine. this protein, which consists of conserved, dimorphic, and polymorphic sequences, is very immunogenic in humans. in a longitudinal study carried out with 94 inhabitants of a rural community in mali, west africa, we show that in this endemic area naturally acquired gp190-specific antibodies are predominantly directed against the dimorphic parts of one of the m ...19912004813
a circular dna in malaria parasites encodes an rna polymerase like that of prokaryotes and chloroplasts.a 3.5-kb sau3ai fragment was cloned from a circular dna molecule isolated from the human malaria parasite plasmodium falciparum and found to contain two contiguous open reading frames. these encode portions of beta and beta' subunits of an rna polymerase similar to prokaryotic and chloroplast rna polymerases, and contain highly conserved structural elements. the plasmodium genes are arranged in a polycistronic transcription unit, as in both escherichia coli and chloroplast genomes, and are trans ...19912011147
synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives.a series of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives has been synthesized and evaluated for antimalarial activity in vitro against the human malaria parasite, plasmodium falciparum (vietnam smith strain, chloroquine-resistant at the r3 level). the most active compounds, 2-aziridinyl-1,4-naphthoquinon-5-yl p-ethylbenzenesulfonate (13), 2-aziridinyl-1,4-naphthoquinon-5-yl p-tert-butylbenzenesulfonate (48), and 2-aziridinyl-5-hydroxy-1,4-naphthoqui ...19912033589
antibody responses to a synthetic peptide-based malaria vaccine candidate: influence of sequence variants of the peptide.a synthetic peptide (asn-ala-asn-pro)3, representing a protective sequence from the sporozoite stage of plasmodium falciparum, conjugated to tetanus toxoid has undergone clinical testing. although some protection was obtained, anti-parasite responses were generally low. in attempting to improve the anti-parasite protein antibody response, we evaluated the efficacy of tetanus toxoid conjugates containing seven sequence variants of the peptide. most of the conjugates tested in both mice and monkey ...19912044658
identification of plasma membrane proteins involved in the hepatocyte invasion of plasmodium falciparum sporozoites.to determine whether surface proteins of hepatocytes might be involved in the sporozoite invasion, plasma membrane proteins were prepared from human livers with chaps (3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate) and radiolabelled with 125i (iodogen; 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril). the labelled proteins were incubated with plasmodium falciparum sporozoites and cross-linked with dsp (dithio-bis-succinimidylpropionate). radiolabelled proteins released by re ...19912052023
plasmodium falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in kinshasa, zaire. a prospective, longitudinal cohort study of 587 children.it is uncertain whether plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (hiv-1) infection and whether p. falciparum infection accelerates the progression of hiv-related disease.19912052043
fine specificities of monoclonal antibodies against the plasmodium falciparum circumsporozoite protein: recognition of both repetitive and non-repetitive regions.the fine specificities of 6 monoclonal antibodies (moabs) raised against the circumsporozoite (cs) protein of the human malaria parasite, plasmodium falciparum, were defined by their binding to a series of overlapping octapeptides corresponding to the 7g8 variant of the cs protein. the precise specificities of the moabs to the immunodominant nanp repeat region were elucidated by their binding to all possible 4, 5, 6, 7 and 8 amino acid peptides in this region. all 6 moabs recognized the nanp rep ...19912052404
chloroquine inhibits heme-dependent protein synthesis in plasmodium falciparum.a cell-free protein-synthesizing system has been reconstituted using the s-30 fraction or ribosomes and the s-100 fraction from plasmodium falciparum. addition of heme in vitro stimulates cell-free protein synthesis strikingly. chloroquine inhibits the heme-dependent protein synthesis in the parasite lysate. the drug has also been found to inhibit parasite protein synthesis in situ at therapeutic concentrations soon after addition to parasite cultures. ribosomes as well as the s-100 fraction iso ...19912052558
periodic and chaotic host-parasite interactions in human malaria.it has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. malaria fever is related to the parasite growth cycle in erythrocytes. after a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. simultaneous rupture of a large number of schizonts stimulates a host fever response. febrile temperatures are damaging to plasmodium ...19912052590
[molecular recognition between glycophorin a and plasmodium falciparum merozoites].by using purified human erythrocyte membrane glycophorin a (gpa) and glycopeptide of gpa, antibodies against gpa and against gpa-glycopeptide, and spa-colloidal gold, plasmodium falciparum fcc-1/hn merozoites were immunolabeled. the labeled samples were observed under transmission electron microscope (tem). the tem pictures showed that colloidal gold pellets were distributed over all of the merozoite surface. this is the first report on the direct experimental evidence of molecular recognition a ...19912065445
the tubulin genes of the human malaria parasite plasmodium falciparum, their chromosomal location and sequence analysis of the alpha-tubulin ii gene.we report the isolation and sequencing of genomic clones encompassing the entire alpha-tubulin ii gene from the human malaria parasite plasmodium falciparum. this gene is closely related to, but significant different from the alpha-tubulin i gene that we have described previously. these two genes represent the entire complement of alpha-tubulin sequences in this organism and are expressed in a stage-specific manner. the alpha-ii gene is present as a single copy and encodes a tubulin molecule wit ...19902090947
human studies with synthetic peptide sporozoite vaccine (nanp)3-tt and immunization with irradiated sporozoites.the synthetic peptide plasmodium falciparum circumsporozoite (cs) protein conjugate vaccine (nanp)3-tt was safe when given parenterally to 202 volunteers. however, with a few notable exceptions, antibody responses were low and could not be boosted. vaccinees' lymphocytes did not proliferate when exposed in vitro to (nanp)3. the tetanus toxoid (tt) carrier immunomodulated the response to the cs peptide in that both epitopic suppression and immune enhancement were demonstrated during the course of ...19902094588
[construction of a genomic dna library of toxoplasma gondii (zs2 strain), screening of specific clone and dna diagnosis of toxoplasmosis].we have constructed a genomic dna library of toxoplasma gondii (zs2 strain) and screened out a specific dna sequence for t. gondii. the restriction map of the cloned dna fragment (1.1kb) was analysed. the southern and dot-blot analyses showed that the 32p-labeled cloned dna fragment hybridized to the parasite dna, dnas from peripheral white blood cells and thymus of baby pigs artificially infected with t. gondii and dnas of t. gondii- positive anencephalus and hydrocephalus, but did not hybridiz ...19902095993
[in vitro cultivation of plasmodium falciparum with umbilical cord erythrocyte].plasmodium falciparum was cultivated with umbilical cord erythrocytes or with erythrocytes from human adults for 33 days and 50 days respectively. the erythrocyte infection rate increased eightfold to eighteenfold at intervals of three to four days, the highest erythrocyte infection rate being more than 20%. furthermore, the infection rate of umbilical cord erythrocytes was higher than that of adult erythrocytes at 48, 72 and 96 hours of cultivation, respectively (p less than 0.01). the results ...19902099258
anopheles pharoensis and transmission of plasmodium falciparum in the senegal river delta, west africa.1. anopheles pharoensis theobald was found to be the prevalent man-biting anopheline mosquito in the central area of the senegal river delta. 2. blood-fed females of an. pharoensis were obtained during september-december 1987 from mosquito bednets in the village of souhloul, near the boundoum dam, 70 km ne of st louis. 3. dried mosquito specimens were identified morphologically and each thorax processed using monoclonal antibody against the circumsporozoite protein of plasmodium falciparum. 4. f ...19902133009
[erythrocytes infected by plasmodium falciparum activate human platelets].blood platelets are involved in plasmodium falciparum malaria pathology as shown by thrombocytopenia and increased plasma level of two alpha granule proteins: beta thromboglobulin (beta tg) and platelet factor 4 (pf4). in this study we demonstrate that plasmodium falciparum parasitized erythrocytes activate directly the secretion of beta tg and pf4 by human platelets. this secretion is related to parasitemia and occurs immediately after contact. treatment of parasited erythrocytes by trypsin and ...19902142012
ion metabolism in malaria-infected erythrocytes.malaria parasites of the genus plasmodium spend much of their asexual life cycle inside the erythrocytes of their vertebrate hosts. parasites presumably have to exploit metabolic and transport mechanisms to adapt themselves to the host erythrocyte's physicochemical environment. this review surveys the metabolism and transport of ca2+, alkali cations, and h+ in malaria-infected erythrocytes. the ca2+ content of plasmodium-infected erythrocytes increases as the parasite matures. an increase in the ...19902175223
thymidylate synthase-dihydrofolate reductase in protozoa.in protozoa, thymidylate synthase (ts) and dihydrofolate reductase (dhfr) exist on the same polypeptide. the dhfr domain is on the amino terminus, ts is on the carboxy terminus, and the domains are separated by a junction peptide of varying size depending on the source. the native protein is a dimer of two such subunits and is 110-140 kda. most studies of bifunctional ts-dhfr have been performed with the protein from anti-folate resistant strains of leishmania major, which show amplification of ...19902178951
fatal plasmodium falciparum malaria after an inadequate response to quinine treatment.a 24-year-old man with severe plasmodium falciparum malaria died after 77 h of treatment with full parenteral doses of quinine. his peripheral parasitemia at death exceeded the level on admission. plasma concentrations of quinine were abnormally low throughout. this case emphasizes the importance of pharmacokinetic factors in determining the therapeutic response in severe p. falciparum malaria.19902179427
immunogenicity and antigenicity in rabbits of a repeated sequence of plasmodium falciparum antigen pf155/resa fused to two immunoglobulin g-binding domains of staphylococcal protein a.a synthetic gene encoding a tetramer of the repeated subunit eenvehda of the plasmodium falciparum antigen pf155/resa was expressed in a dual-expression system. the resulting fusion proteins, designated zz-m1 and bb-m1, comprised the eenvehda repeats and either two immunoglobulin g-binding domains from staphylococcal protein a or the human serum albumin-binding domains from streptococcal protein g, respectively. the soluble fusion proteins were affinity purified to homogeneity in one-step proced ...19902180822
antimalarial action of flavin analogues seems not be due to inhibition of glutathione reductase of host erythrocytes.a series of 10-(4'-chlorophenyl)-3-substituted flavins (1a-f) were examined with respect to their antimalarial properties. they were tested against plasmodium falciparum in vitro and plasmodium vinckei vinckei in vivo. the proposition that they might act through glutathione reductase (gr) (ec 1.6.4.2) inhibition has been studied. inhibition of p. falciparum in vitro by these compounds shows only slight variation between analogues; in contrast, inhibition of human erythrocyte gr by members of the ...19902182031
use of a tuberculin purified protein derivative--asn-ala-asn-pro conjugate in bacillus calmette-guérin primed mice overcomes h-2 restriction of the antibody response and avoids the need for adjuvants.because of its immunodominancy, and because it is conserved in different geographical isolates of plasmodium falciparum, the repetitive sequence of the circumsporozoite protein, (asn-ala-asn-pro)n [(nanp)n], has been envisaged for the development of an anti-falciparum malaria subunit vaccine. however, the murine immune response to (nanp)n peptides, either carrier-free or coupled to carrier proteins, was shown to be inducible only by using strong (e.g., freund's) adjuvants. furthermore, response ...19902183219
increased nicotinamide adenine dinucleotide content and synthesis in plasmodium falciparum-infected human erythrocytes.plasmodium falciparum-infected red blood cells (rbcs) are characterized by increases in the activity of glycolytic enzymes. because nicotinamide adenine dinucleotide (nad) and nad phosphate (nadp) are cofactors in the reactions of glycolysis and pentose phosphate shunt, we have examined nad and nadp content in p. falciparum-infected rbcs. although nadp content was not significantly altered, nad content was increased approximately 10-fold in infected rbcs (66% parasitemia) compared with uninfecte ...19902183889
falciparum malaria parasitized erythrocytes bind to a carboxy-terminal thrombospondin fragment and not the amino-terminal heparin-binding region.we investigated plasmodium falciparum parasitized erythrocyte binding to proteolytic fragments of thrombospondin and the effects of anti-thrombospondin monoclonal antibodies on this binding. purified human platelet thrombospondin was cleaved by trypsin, chymotrypsin or thrombin. fragments were separated by heparin-agarose affinity chromatography, removing the amino-terminal heparin-binding region. trypsin at 5.0 micrograms ml-1 of thrombospondin cleaved thrombospondin to reduced 140 and 120 kda ...19902194122
water and urea transport in human erythrocytes infected with the malaria parasite plasmodium falciparum.the permeability properties of the human red cell membrane to various solutes are altered by malarial infection. in the present work we show that the permeability of the red cell membrane to water is also affected by the intraerythrocytic growth of the malaria parasite plasmodium falciparum, whereas urea permeability appears unchanged. the data from infected cells show decreases in membrane surface area, cell volume, the osmotically active water fraction (weff), and osmotic water permeability (p ...19902194124
evidence for a switching mechanism in the invasion of erythrocytes by plasmodium falciparum.the human malaria parasite plasmodium falciparum demonstrates variability in its dependence upon erythrocyte sialic acid residues for invasion. some lines of p. falciparum invade neuraminidase-treated or glycophorin-deficient red blood cells poorly, or not at all, while other lines invade such cells at substantial rates. to explore the molecular basis of non-sialic acid dependent invasion, we selected parasite lines from a clone (dd2) that initially exhibited low invasion of neuraminidase-treate ...19902200806
a multiple antigen peptide from the repetitive sequence of the plasmodium malariae circumsporozoite protein induces a specific antibody response in mice of various h-2 haplotypes.the major repetitive epitopes of the surface circumsporozoite (cs) protein of malaria sporozoites represent candidates for the development of subunit vaccines against malaria. however, previous experimental work has shown that repetitive peptides from the cs proteins of plasmodium falciparum, p. vivax, p. yoelii and p. berghei are immunogenic only in mice with the h-2b or h-2k haplotype. this led to the conclusion that strong t helper epitopes from the non-repetitive cs sequences were required i ...19902201549
malaria transmission and vector biology in manarintsoa, high plateaux of madagascar.to evaluate the factors which determine the transmission level of falciparum malaria, entomological and parasitological surveys were conducted from october 1988 to february 1990 in manarintsoa in the central highland plateaux of madagascar. mosquitoes were collected for 928 man-nights in pit shelters and indoor resting sites. malaria vectors were anopheles arabiensis and an. funestus, with no evidence of the presence of an. gambiae sensu stricto. vectors were mainly exophilic and zoophilic. the ...19902202220
effect of polyamines on the activity of malarial alpha-like dna polymerase.dna polymerase from the malarial parasite plasmodium falciparum required mg2+ for activity, putrescine (1 mm) caused a twofold increase in enzyme activity in the presence of a suboptimal concentration of mgcl2 (2 mm). spermidine (1.5-2.0 mm) or spermine (0.1-0.3 mm) increased the activity of malarial dna polymerase, in the presence of 2 mm mgcl2, by factors of 6 and 3-5, respectively. the activity of dna polymerase from calf thymus or from nih 3t3 cells transformed by the ras oncogene were not s ...19902202598
[ecological factors in the renewed outbreak of malaria in madagascar].the new epidemic of malaria which spread on the madagascar high plateau in 1986-1987 is due to the combination of several factors (some of which are analysed by the authors, especially those related to anopheles, parasite and man). the authors compare the situations on the high plateau and on st mary island, on the east madagascar coast, where the malaria is stable. concerning the vector, the most interesting fact is the come-back of anopheles funestus on the high plateau from which it had disap ...19902208464
structural diversity of plasmodium falciparum gp200 is detected by t cells.t lymphocyte clones (tlc) specific for p. falciparum gp200 (a glycoprotein precursor of the main merozoite surface component) were obtained from two individuals with past exposure to malaria. the 25 established tlc carried the cd4 antigen and proliferated in the presence of immunopurified gp200, crude lysate of the parasite and intact infected red blood cells. they were further tested in proliferation assays for their capacity to recognize the structural diversity displayed by gp200. the stimula ...19902209687
geographical distribution of plasmodium falciparum erythrocyte rosetting and frequency of rosetting antibodies in human sera.uninfected erythrocytes bind spontaneously to those infected with certain strains of plasmodium falciparum. this is known as spontaneous erythrocyte rosetting. we have studied the occurrence and frequency of rosetting in 75 fresh patient isolates and have identified rosetting strains from africa, south america, and asia. rosetting was present in 49% of the isolates tested; the frequency of rosetting red blood cells (rbc) in individual isolates was 0-75% when scored during the first cycle of in v ...19902240361
biochemical characterization, localization and immunostimulating properties of a soluble glycoprotein, ag1, isolated from in vitro cultures of plasmodium falciparum.the soluble amphiphilic glycoprotein, ag1 (gp60), purified from supernatants of in vitro cultures of plasmodium falciparum has a molecular mass of 60 kda and did not exhibit size variation in the different p. falciparum isolates tested by immunoblotting. ag1 was shown to interact with the lectin erythrina christagalli agglutinin, which is specific for carbohydrates bearing beta-d-galactose(1-4)-d-n-acetylglucosamine. indirect immunofluorescence studies showed that ag1 is located on the surface o ...19902251241
role of calcium and erythrocyte cytoskeleton phosphorylation in the invasion of plasmodium falciparum.the role of calcium in the invasion of the human erythrocyte by the parasite plasmodium falciparum was studied. the intraerythrocytic and intraparasitic concentrations of ca2+ were modified using calcium-ionophore a23187 and the chelator egta. the ca2+ inside the parasite appeared to be necessary for the normal completion of invasion. we determined that in recently invaded erythrocytes (2 h), the ca2+ concentration increased about 10 times. merozoite invasion produced a decrease in beta-spectrin ...19902251243
innate resistance to malaria: the intraerythrocytic cycle.the human innate resistance to p. falciparum malaria is based on genetic features that affect several stages of the intraerythrocytic cycle of the plasmodia. hbs, hbe and alpha and beta thalassemia (in addition to g-6pd deficiency) are protective to the carriers, because they inhibit the intraerythrocytic growth period, and in the case of as red cells, in addition, parasitosis make them detectable expeditiously by the spleen. blood group polymorphisms can interfere with red cell invasion by plas ...19902257317
purines and pyrimidines in malarial parasites.in order for the plasmodium malarial parasite to replicate in the human erythrocyte it requires metabolic pathways which are not operative in the host erythrocyte. thus, the malarial parasite not only synthesizes enzymes for purine salvage and interconversion, for the pyrimidine biosynthetic pathway de novo, and for the folate cycle, but it also alters the host erythrocyte membrane in respect to the transport of purines. several of the plasmodium enzymes from these pathways have been cloned and ...19902257323
biochemical characterization of plasmodium falciparum hemozoin.hemozoin, the pigment granule which develops within the blood stage food vacuole of the malaria parasite plasmodium falciparum, was biochemically characterized. hemozoin was found to be composed of 65% protein, 16% ferriprotoporphyrin-ix (hematin), 6% carbohydrate, and trace amounts of lipid and nucleic acids. the overwhelming majority of the protein component is a mixture of native and denatured human globin non-covalently associated with the metalloporphyrin. immunoelectron microscopy, employi ...19902267961
hyperendemic malaria in a thai village: dependence of year-round transmission on focal and seasonally circumscribed mosquito (diptera: culicidae) habitats.in a longitudinal study of hyperendemic malaria in a village in eastern thailand (from october 1985 to november 1987), man-biting anopheline mosquitoes were collected for 16 man-nights per month in 22 of 26 mo. mosquitoes were separated according to collection sites (inner, central, more populated; outer, peripheral, more forested), biting period, and parity, and then they were tested for sporozoite antigen using an enzyme-linked immunosorbent assay (elisa). abundance of anopheles dirus peyton & ...19902280385
human cerebral malaria in thailand: a clinico-pathological correlation.based on the cerebral malaria coma scale, 39 falciparum malaria autopsy cases from the hospital for tropical diseases, mahidol university, bangkok, thailand were divided into two groups of patients that had either cerebral malaria or non-cerebral malaria. we then studied significant pathological differences, such as parasitized erythrocyte (prbc) sequestration, ring hemorrhages and cerebral edema, between these two groups in order to investigate the correlation between the clinical coma scale an ...19902283150
tumor necrosis factor production by human macrophages stimulated in vitro by plasmodium falciparum.production of tumor necrosis factor by human macrophages may be induced in vitro by cytoadherent and noncytoadherent strains of plasmodium falciparum, with an optimal ratio of one to three parasitized erythrocytes per macrophage. centrifuged and heated crude culture supernatants have the same effect, thus showing the existence of a thermostable soluble factor able to induce this expression. in vitro kinetic experiments have shown that the secretion of tumor necrosis factor appears early, with a ...19902403531
flavin analogs with antimalarial activity as glutathione reductase inhibitors.10-(4'-chlorophenyl)-3-methylflavin has antimalarial activity in vitro and in vivo (cowden et al., j med chem 31: 799, 1988). this flavin analog and two of its derivatives were found to inhibit the antioxidant flavoenzyme glutathione reductase from human erythrocytes in its isolated form as well as in hemolysates. the mixed-type inhibition was completely reversible, the ki-values being of the order of 1 microm. surprisingly, the drugs were not competitive with fad, but with gssg, one of the enzy ...19902404494
specificity and inhibitory activity of antibodies to plasmodium falciparum aldolase.the multiplication of plasmodium falciparum within rbc is energy-dependent and the glucose consumption of infected rbc is increased more than 50 times over the consumption of normal rbc. high levels of glycolytic enzymes such as fructose-1,6-diphosphate aldolase (p41) have been detected in infected rbc. expression of the cloned aldolase gene of p. falciparum in escherichia coli resulted in an enzymatically active polypeptide with a high sp. act. and the recombinant p41 aldolase was used for enzy ...19902406342
quinine-induced hearing loss.sensorineural hearing loss due to quinine therapy for malaria has frequently been mentioned in the literature but has not been a subject of research during the last decades. the global spreading of chloroquine-resistant falciparum malaria brings about an increasing use of quinine. the ototoxicity of quinine can accurately be studied with ultrahigh frequency audiometry (up to 20 khz). the case of a 29-year-old man suffering from falciparum malaria disease who got a reversible hearing loss from qu ...19902406680
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
thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence.plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. knobs appear on infected erythrocytes and are the points of attachment to endothelium. sequestration may protect the parasite from splenic destruction and may play a role in the pathogenesis of cerebral malaria. correlates of sequestration have been developed in vitro using cultured human endothelium and a ...19852414670
circumsporozoite protein of plasmodium vivax: gene cloning and characterization of the immunodominant epitope.the gene encoding the circumsporozoite (cs) protein of the human malaria parasite plasmodium vivax has been cloned. the deduced sequence of the protein consists of 373 amino acids with a central region of 19 tandem repeats of the nonapeptide asp-arg-ala-asp/ala-gly-gln-pro-ala-gly. a synthetic 18-amino acid peptide containing two tandem repeats binds to a monoclonal antibody directed to the cs protein of plasmodium vivax and inhibits the interaction of this antibody with the native protein in sp ...19852414847
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
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
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
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
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
synthetic gene construct expressing a repeated and highly immunogenic epitope of the plasmodium falciparum antigen pf155.the plasmodium falciparum-derived antigen pf155 contains two blocks of tandemly repeated amino acid sequences. a pair of complementary oligonucleotides, encoding the c-terminally located repeat val-glu-his-asp-ala-glu-glu-asn, were synthesized. the oligonucleotides were polymerized by ligation, and the resulting multimers were cloned into an expression vector. one construct that contained four copies of the repeat was expressed in escherichia coli. the product, a fusion protein, was soluble and ...19872434955
sequence variation in putative functional domains of the circumsporozoite protein of plasmodium falciparum. implications for vaccine development.sequences of the circumsporozoite protein gene from five isolates of the human malaria parasite plasmodium falciparum are compared, and the extent of sequence variability within putative functional domains is assessed in terms relating to vaccine efficacy. nucleotide substitutions were observed outside of the immunodominant domain. of the substitutions observed outside of the repeat domain, none were silent. the substitutions correlated with biologically functional regions, such as a helper t ce ...19872442154
a synthetic vaccine protects humans against challenge with asexual blood stages of plasmodium falciparum malaria.we have previously shown that a mixture of three synthetic peptides (83.1, 55.1, 35.1), corresponding to fragments of the relative molecular mass 83,000 (83k), 55k and 35k plasmodium falciparum merozoite-specific proteins, induces protection in aotus triviroatus monkeys experimentally infected with p. falciparum. here we describe two polymeric synthetic hybrid proteins based on these peptides that delay or suppress the development of parasitaemia in immunized human volunteers.19882450281
neonatal exposure to immunogenic peptides. differential susceptibility to tolerance induction of helper t cells and b cells reactive to malarial circumsporozoite peptide epitopes.the effects of neonatal administration of immunogenic peptides on subsequent t and b cell function were tested using defined t and b cell peptide epitopes from the circumsporozoite (cs) protein of the human malaria parasite, plasmodium falciparum. we observed that neonatal exposure of responder strain mice to either of the two major murine t sites on the cs protein resulted in specific tolerance of both helper and proliferating t cells. one of these t sites, (nanp)n, is also the immunodominant b ...19882452193
epitopes recognized by human t lymphocytes on malaria circumsporozoite protein.the circumsporozoite protein of the malaria parasite plasmodium falciparum contains regions of nonrepetitive sequences which are predicted to be t cell recognition sites. we synthesized peptides corresponding to three of these regions, and tested their ability to stimulate proliferation of peripheral blood lymphocytes from donors living in a malaria-endemic area, or from nonimmune donors. cells from 15 out of 22 donors (including 4 of 6 nonimmune individuals) were stimulated by one or more of th ...19882452748
characterization of antibodies to sporozoites in plasmodium falciparum malaria and correlation with protection.the antibody response to sporozoites of plasmodium falciparum and the role of these antibodies in protection against malaria have not been systematically investigated. an understanding of antisporozoite antibodies in natural infection is, however, important to the development of a human malaria vaccine. in a prospective study in thailand, an antibody response to sporozoites was observed only in individuals who developed parasitemia. antibodies were detected against an epitope in the repeat regio ...19882454941
characterization of a plasmodium falciparum polypeptide associated with membrane vesicles in the infected erythrocytes.a plasmodium falciparum polypeptide (46 kda) associated with the infected erythrocytes of all asexual stages as well as immature gametocytes was identified by the monoclonal antibody (mab) 30b8.3. the expression of this protein was not dependent upon the knobby phenotype and was detected in parasites grown either in human or aotus erythrocytes. the antigen was heatstable, did not label with [14c]glucosamine, and was not sensitive to periodate oxidation. immunofluorescent staining patterns of mab ...19882457806
mature liver stages of cloned plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages.the liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. in addition, only a low proportion of cells are obtained in vivo, the parasites from cebus and aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by conta ...19882457864
identification of t epitopes within a potential plasmodium falciparum vaccine antigen. a study of human lymphocyte responses to repeat and nonrepeat regions of pf155/resa.pbmc from melanesians who had high antibody reactivities to fusion proteins encompassing the 3' and the 5' repeat regions of the ring infected e surface antigen (pf155/resa), were tested for their ability to respond to synthetic and recombinant peptides representing regions of pf155/resa. the aim was to identify t cell epitopes within the ag. most of the synthetic peptides from the nonrepeat regions of pf155/resa were selected for study on the basis of their tendency to form amphipathic alpha-he ...19882459246
a malaria t-cell epitope recognized in association with most mouse and human mhc class ii molecules.an ideal vaccine should elicit a long lasting immune response against the natural parasite, both at the t- and b-cell level. the immune response should occur in all individuals and be directed against determinants that do not vary in the natural parasite population. a major problem in designing synthetic peptide vaccines is that t cells generally recognize peptide antigens only in association with one or a few of the many variants of major histocompatibility complex (mhc) antigens. during the ch ...19882462673
human and murine cd4 t cell epitopes map to the same region of the malaria circumsporozoite protein: limited immunogenicity of sporozoites and circumsporozoite protein.the circumsporozoite (cs) protein is a candidate vaccine antigen for the sporozoite stage in the life cycle of the malaria parasite. using cs protein purified from recombinant baculovirus-infected cells and a panel of h-2 congenic mice, we are able to demonstrate that this protein is poorly immunogenic in terms of antibody production as a result of ir gene control. the immune response to the protein is also restricted following immunization with a cs-recombinant vaccinia virus or with sporozoite ...19882468986
effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults.a plasmodium falciparum sporozoite vaccine, composed of a synthetic dodecapeptide (nanp)3 coupled to tetanus toxoid (tt), was injected, at weeks 0 and 8, into non-immune volunteers in two randomized double-blind placebo-controlled trials. in the first trial, 37 volunteers received the vaccine simultaneously with placebo (group 1), 0.5 x 10(6-) (group 2), or 1.5 x 10(6) u (group 3) of recombinant human interferon-alpha (= ifn-alpha). in the second trial, 35 other volunteers received the vaccine w ...19892479187
a heat shock-like protein from the human malaria parasite plasmodium falciparum induces autoantibodies.the humoral immune response to a 72-kda heat shock-like protein of plasmodium falciparum has been analyzed using mouse monoclonal antibodies (mab) and human immune sera. three regions of the molecule containing b cell epitopes were identified by screening a sublibrary encoding the cooh-terminal half of the antigen with the mab. one b cell epitope mapped to a region poorly conserved between the parasite 72-kda polypeptide and mammalian heat-shock proteins (hsp 70). another mab, g10c9, reacted wit ...19892479563
conserved repetitive epitope recognized by cd4+ clones from a malaria-immunized volunteer.t cell clones obtained from a human volunteer immunized with plasmodium falciparum sporozoites specifically recognized the native circumsporozoite (cs) antigen expressed on p. falciparum sporozoites, as well as bacteria- and yeast-derived recombinant falciparum cs proteins. the response of these cd4+ cd8- cells was species-specific, since the clones did not proliferate or secrete gamma interferon when challenged with sporozoites or recombinant cs proteins of other human, simian, or rodent malari ...19892480642
dissection of the human antibody response to the malaria antigen pf155/resa into epitope specific components.the development of vaccines is presently receiving major attention in malaria research. as it is not possible to base malaria vaccines on the use of killed or attenuated organisms, the vaccines which are being developed are subunit vaccines in which the immunogens consist of defined parasite antigens or antigenic fragments. since protective immunity to malaria involves both antibody-dependent and antibody-independent mechanisms, the immunogens in a subunit vaccine must have the capacity to induc ...19892481640
phosphocholine epitopes on helminth and protozoal parasites and their presence in the circulation of infected human patients.antigens containing phosphocholine (pc) circulate in the blood during chronic filarial infection. because of the wide occurrence of such pc epitopes, we examined their specificity by evaluating 10 common parasites of humans for the presence of pc epitopes, and sera from patients infected with these parasites for circulating antigens containing pc. immunoblot analysis of extracts from various parasites using an anti-pc monoclonal antibody (ca101) demonstrated the presence of pc epitopes on the pr ...19892482559
erythrocyte invasion by two plasmodium falciparum isolates differing in sialic acid dependency in the presence of glycophorin a antibodies.merozoites of plasmodium falciparum depend on glycophorins for invasion into human erythrocytes, although this dependency varies between different geographic isolates of the species. the fcr-3 (gambia) isolate appears to be fully dependent on the n-acetylneuraminic acid (neunac) residues of the o-linked tetrasaccharide of glycophorin for invasion. invasion of the cdc-1 (honduras) isolate into neuraminidase treated erythrocytes is 50% of that into normal erythrocytes. this and additional results ...19892539023
interactions of cd4+ and cd8+ human t lymphocytes from malaria-unprimed donors with plasmodium falciparum schizont stage.during plasmodium falciparum malaria, a wide spectrum of parasite-encoded blood-stage proteins is presented to the immune system of the host. to explore their multiple interactions with t cells from donors who have had no previous exposure to the parasite, whole schizont extract was used in vitro. both cd4+ and cd8+ lymphocytes from all individuals tested were stimulated to proliferate. the responses were dependent on the presence of accessory cells and were only partially replaced by recombinan ...19892572603
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
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
c-reactive protein protects against preerythrocytic stages of malaria.we previously reported that low doses of interleukin-1 strongly inhibited in vitro development of the hepatic stages of plasmodium falciparum and p. yoelii. among several hypotheses, we considered the role of c-reactive protein (crp), a major acute-phase reactant whose concentration increases markedly in infectious disorders. we demonstrated that human hepatocytes cultured in the presence of interleukin-1 released, as early as 30 min after stimulation, an increased amount of crp. we then establi ...19892642467
restricted or absent immune responses in human populations to plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies.we have studied the antibodies to sexual stage antigens of plasmodium falciparum in human sera from papua new guinea where intense transmission of p. falciparum occurs as well as the less prevalent p. malariae and p. vivax. in extracts of gametes of p. falciparum we have studied the reactivity of serum antibodies with antigens labeled with 125i on the surface of the gametes as well as intracellular gamete antigens. a prominent 27-kd sexual stage-specific intracellular protein was recognized more ...19892642527
characterization of a modified red cell membrane protein expressed on erythrocytes infected with the human malaria parasite plasmodium falciparum: possible role as a cytoadherent mediating protein.infections with the human malaria plasmodium falciparum are characterized by the retention of parasitized erythrocytes in tissue capillaries and venules. erythrocytes containing trophozoites and schizonts attach to the endothelial cells that line these vessels by means of structurally identifiable excrescences present on the surface of the infected cell. such excrescences, commonly called knobs, are visible by means of scanning or transmission electron microscopy. the biochemical mechanisms resp ...19892642911
uninfected erythrocytes form "rosettes" around plasmodium falciparum infected erythrocytes.the human malaria parasite, p. falciparum, exhibits cytoadherence properties whereby infected erythrocytes containing mature parasite stages bind to endothelial cells both in vivo and in vitro. another property of cytoadherence, "rosetting," or the binding of uninfected erythrocytes around an infected erythrocyte, has been demonstrated with a simian malaria parasite p. fragile which is sequestered in vivo in its natural host, macaca sinica. in the present study we demonstrate that rosetting occu ...19892645800
cytoadherence in human falciparum malaria as a cause of respiratory distress.the ultrastructure of three cases of fatal human falciparum malaria was studied in order to identify the cytoadherence of the endothelial cells in relation to parasitized red blood cells and septal interstitial changes which could be related to respiratory distress. two cases showed marked endothelial oedema narrowing the capillary lumen with areas of adherence preferentially related to knobs, accompanied by septal interstitial oedema. one case showed no endothelial cells oedema, no knobs in par ...19892651687
antimalarial action of nitrobenzylthioinosine in combination with purine nucleoside antimetabolites.the infection of human erythrocytes by two strains of the human malarial parasite, plasmodium falciparum (fcq-27 or the multi-drug-resistant strain k-1), markedly changed the transport characteristics of the nucleosides, adenosine and tubercidin, compared to uninfected erythrocytes. a component of the transport of these nucleosides was insensitive to the classical mammalian nucleoside transport inhibitor nitrobenzylthioinosine (nbmpr). in vitro studies with tubercidin demonstrated id50 values of ...19892651920
high-performance liquid chromatographic assay for thymidylate synthase from the human malaria parasite, plasmodium falciparum.a rapid and highly sensitive high-performance liquid chromatographic assay for thymidylate synthase activity is described. the assay is based on the separation of the substrate, deoxyuridylate (dump), and its product, deoxythymidylate (dtmp), on a lichrosorb rp-8 reversed-phase column with 44 mm triethylammonium phosphate (ph 7.0) as mobile phase and a flow-rate of 1.0 ml/min. in addition, using a mu bondapak c18 reversed-phase column with 10 mm potassium phosphate (ph 4.0) and a gradient of 0-2 ...19892654157
the use of 5-fluorocytosine and ketoconazole in the culture of the erythrocytic stages of plasmodium falciparum and some tumor cell lines.in vitro culture systems are often contaminated by bacteria and fungi. it is therefore often necessary to supplement culture media with agents such as penicillin/streptomycin, gentamycin or amphotericin b. the latter cannot be used in the in vitro culture of erythrocytic stages of p. falciparum, and thus anti-fungal agents have not been regularly used in this system. we describe the prophylactic use of 5-fluorocytosine (5-fc) and ketoconazole (ktz) in tissue cultures at concentrations up to 300 ...19892656288
diagnosis of falciparum malaria delayed by long incubation period and misleading presenting symptoms: life-saving role of manual leucocyte differential count.in countries where malaria is not endemic the diagnosis of the disease is often delayed or overlooked, particularly if the clinical symptoms are atypical and if automated cell analyzers are used instead of blood films for leucocyte differential counts. we report 2 cases of severe plasmodium falciparum malaria with unusual clinical features: a 46-year-old man with an exceptionally long incubation period and a 22-year-old woman with presenting symptoms suggesting viral hepatitis. in both cases the ...19892658017
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