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alterations of human serum proteins and other biochemical parameters after five to ten days of untreated acute falciparum malaria.untreated malaria for more than 4 days in eleven patients decreased significantly prealbumin, transferrin levels and increased sgot activity when compared with a control group and a group of 10 malaria patients who were admitted to the hospital at an earlier stage of the infection. total protein was significantly lower in the group of patients admitted after five to ten days to hospital compared with the control group. in all malaria patients independent of the duration of the acute infection th ...1977333673
separation of viable schizont-infected red cells of plasmodium falciparum from human blood. 1978350172
human parasitoses of the malili area, south sulawesi (celebes) province, indonesia.a biomedical survey was conducted in 9 villages in the malili area of south sulawesi, indonesia. blood specimens were examined for malaria and microfilariae; stool specimens were examined for intestinal parasites. malaria parasitemias were rare; plasmodium falciparum was detected in 10 and p. vivax in 11 of 985 blood smears. malayan filariasis was endemic to all villages surveyed. the overall prevalence of detectable microfilaremias was 15%, varying from 34% in kawata to 1% in nuha. microfilaria ...1978364674
in vitro production and partial purification of plasmodium falciparum antigen.a simple technique for achieving high yields of plasmodium falciparum parasites on a continuous basis is described. the technique is applicable in any laboratory. the culture apparatus is also simple and inexpensive and allows multiple cultures to be run simultaneously. a total of approximately 1-2 x 10(9) parasites can be harvested per culture flask per week requiring the use of only 40.0 ml of culture medium (rpmi 1640), 5.0 ml of human sera, and 2.0 ml of outdated human whole blood. p. falcip ...1979397010
invasion of erythrocytes by plasmodium falciparum in vitro.the erythrocytic stages of plasmodium falciparum from aotus trivirgatus were grown in mill hill medium. significant invasion of erythrocytes was obtained by a subculture technique. this invasion, by parasites grown in aotus erythrocytes, was greater when human erythrocytes were added to the cultures than when parasites were allowed to invade aotus erythrocytes. this difference appeared to be a function of the properties of the erythrocyte and was not serum dependent.1975812039
investigation of the evi antibody in parasitic diseases other than american trypanosomiasis. an anti-skeletal muscle antibody in leishmaniasis.the specificity of a circulating antibody observed in american trypanosomiasis and reacting with endocardium, blood vessels, and the interstitium of striated muscle (evi factor) was evaluated in the indirect fluorescent antibody test with 60 sera from patients with malaria, leishmaniasis, echinococcosis, amebiasis, african trypanosomiasis, toxoplasmosis, and trichinosis, collected from areas where chagas' disease is not endemic. two sera, 1 from a patient with plasmodium falciparum malaria and 1 ...19751089366
the rapid isolation from human blood of concentrated, white-cell-free preparations of plasmodium falciparum.the sucrose gradient centrifugation method has been applied to representative samples of human (gambian) blood infected with ring, trophozoite, schizont and gametocyte stages of p. falciparum in order to assess quantitatively the efficiency of recovery, white cell removal and the degree of enrichment of the infected cell fraction. maximal white cell removal was 90%. (a.v.) average infected cell recoveries varied with the level of white cell contamination, namely 47% (2-5% wbc), 34% (1-2% wbc) an ...19751096379
experimental infection of aotus monkeys with plasmodium falciparum light and electron microscopic changes.six splenectomized aotus owl monkeys were infected with p. falciparum. the animals were sacrificed when they became moribund and tissues were faken for light and electron microscopic studies. electron microscopy revealed marked structural changes in both the liver and the heart. in the liver there was glycogen depletion, lipid droplet infiltration mitochondrial disorganization with reduction in numbers and alterations of the microvilli in the sinusoidal pole and the bile canaliculi. in the heart ...1976817680
the release of antigens by plasmodium falciparum.antigens were released in vitro human red cells infected with plasmodium falciparum only when parasites reached a late stage of schizogony (probably at rupture of infected red cells during reinvasion). immune complexes formed if antibody was present. serum from immune aotus monkeys opsonized parasite debris from artificially disrupted infected aotus red cells.1975810759
evaluation of two phenanthrenemethanols for antimalarial activity in man: wr 122,455 and wr 171,669.two phenanthrenemethanols, wr 122,455 and wr 171,669, were tested in man for oral tolerance, toxicity, and efficacy against plasmodium falciparum. in healthy subjects, gastrointestinal symptoms limited single-day dosage of wr 122,455 to 800 mg and wr 171,669 to 1,260 mg. no laboratory abnormalities phototoxicity, or gastrointestinal blood loss were noted in the subjects receiving these drugs. in subjects infected with malaria, wr 122,455 cleared parasitemia when given for 1 day in doses from 440 ...1976795309
plasmodium falciparum invades human red cells via a parasite produced glycosidase.this report describes that p. falciparum produces a neuraminidase like activity on invasion into erythrocytes in culture on the basis of biochemical and immunological investigations. this activity in turn modifies the surface glycoprotein receptors of red cells and may be of help in the inhibition of further invasion by merozoites. the characterization of this enzyme activity may help elucidate the mechanism of cerebral malaria.19921284053
lung uptake of 99mtc-sulfur colloid in falciparum malaria: case report.increased lung uptake of 99mtc-sulfur colloid was seen during liver scanning in a patient with falciparum malaria. this finding was due to the enhanced activity of the phagocytic cells of the reticuloendothelial system in the liver, spleen, and lung found in human and experimental malaria. similar findings in other clinical situations and the relevant literature are reviewed.1976784917
human malaria parasites in continuous culture.plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees c in rpmi 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). the original parasite material, derived from an infected aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. the parasites continued to reproduce in their normal asexual cycle of approxima ...1976781840
peripheral lymphocyte subpopulations in human falciparum malaria.the concentration of circulating t, b, and 'null' lymphocytes was determined in thirty children and three adults with plasmodium falciparum infections in west africa. during infection, both percentage as well as concentration of t cells were decreased as compared to levels following treatment. the percentage but not concentration of b cells was increased. both percentage and concentration of 'null' cells were increased in malaria. patients with splenomegaly had the most severe alterations in t-c ...1976780013
tetraethylthiuram disulfide (antabuse) inhibits the human malaria parasite plasmodium falciparum.plasmodium falciparum in culture grows optimally at 3% oxygen. oxygen levels down to 0.5% still support growth, but anaerobic conditions do not. these findings, and the absence of the krebs cycle in plasmodium, suggested that in this organism oxygen may not function in electron transport but rather may act through metalloprotein oxygenases. tetraethylthiuram disulfide (antabuse, disulfiram) and its reduction product diethyldithiocarbamate inhibit many metalloprotein oxygenases and have a lipid/h ...1979388434
studies on plasmodium falciparum in continuous cultivation. i. the effect of chloroquine and pyrimethamine on parasite growth and viability.recent advances in the in vitro study of human malaria have provided the knowledge to maintain plasmodium falciparum in continuous culture. using relatively cheap and easily obtainable materials it is now possible to study many parameters including parasite chemotherapy. the activity of two standard antimalarials, chloroquine and pyrimethamine, has been examined in vitro. the effect on the parasite is easily observed and can be measured not only as a decrease in parasite density, but also as the ...1979386970
changing patterns in the humoral immune response to malaria before, during, and after the application of control measures: a longitudinal study in the west african savanna.a longitudinal seroimmunological investigation of malaria was performed as part of the who research project conducted in the northern part of nigeria from 1970 to 1975. the project included a preintervention phase, an intervention phase with application of malaria control measures (spraying of residual insecticide and mass drug administration), and a postintervention phase. serological observations were made on the total population of eight villages consisting of approximately 3000 persons. six ...1978365386
plasmodium falciparum-infected erythrocytes bind icam-1 at a site distinct from lfa-1, mac-1, and human rhinovirus.the attachment of erythrocytes infected with p. falciparum to human venular endothelium is the primary step leading to complications from severe and cerebral malaria. intercellular adhesion molecule-1 (icam-1, cd54) has been implicated as a cytoadhesion receptor for p. falciparum-infected erythrocytes. characterization of domain deletion, human/murine chimeric icam-1 molecules, and amino acid substitution mutants localized the primary binding site for parasitized erythrocytes to the first amino- ...19921346257
chloroquine resistance produced in vitro in an african strain of human malaria.after condinous cultivation in the presence of chloroquine, an african strain of the malaria parasite, plasmodium falciparu, acquired resistance to the drug. the resistance was stable and comparable in vitro to that occurring naturally in a strain from southeast asia. this suggests that chloroquine resistance, absent until now in africa, might arise in the future.1978351801
structure and expression of the gene for pv200, a major blood-stage surface antigen of plasmodium vivax.molecular cloning and structure analysis of the gene encoding the pv200 protein of the sal-1 strain of plasmodium vivax revealed an overall identity of 34-37% when the deduced amino acid sequence was compared with the sequences of various major merozoite surface antigens of plasmodium falciparum, plasmodium yoelii and plasmodium chabaudi. when the sal-1 pv200 sequence was compared with the corresponding sequence from the belèm strain of p. vivax, it was found that the two merozoite surface antig ...19921371329
plasmodium falciparum-infected erythrocytes do not adhere well to c32 melanoma cells or cd36 unless rosettes with uninfected erythrocytes are first disrupted.plasmodium falciparum malaria parasites modify the human erythrocytes in which they grow so that some parasitized erythrocytes (pe) can cytoadhere (c+) to host vascular endothelial cells or adhere in rosettes (r+) to uninfected erythrocytes. these c+ and r+ adherence properties of pe appear to mediate much of the pathogenesis of severe malaria infections, in part by blocking blood flow in microvessels. from one parasite strain, pe were selected in vitro for c+ r+ or c+ r- adherence properties an ...19921371771
transcription mapping of a 100 kb locus of plasmodium falciparum identifies an intergenic region in which transcription terminates and reinitiates.we have mapped plasmodium falciparum erythrocytic stage transcription units on chromosome 10 in the vicinity of the gene encoding the glycophorin binding protein (gbp130) using yeast artificial chromosomes (yacs). three erythrocytic stage transcription units are clustered in a 40 kb region. two of these genes are closely linked, separated by less than 2 kb. nuclear run-on data demonstrate that transcription of these two genes, though unidirectional, is monocistronic. within this intergenic regio ...19921374714
invasion and growth of plasmodium falciparum in different types of human erythrocyte.the susceptibility of human red blood cells to invasion by plasmodium falciparum was investigated in microtissue cultures with different populations of erythrocytes containing fetal haemoglobin (hbf). preferential invasion of hbf-containing erythrocytes was observed with umbilical cord blood. the parasites showed no preference for hbf cells in blood from a subject with hereditary persistence of fetal haemoglobin (hpfh). by contrast, a significant preference for hba-containing erythrocytes was fo ...1977338178
[relations between malaria and burkitt's lymphoma].malaria, especially forest malaria, is the environmental factor which creates endemic conditions for the esptein-barr virus related burkitt's lymphoma. the plasmodium seems active through a mitogenic factor rather than through the so often invoked immunological depresssion.1977208788
factors affecting the in vitro culture of plasmodium falciparum and plasmodium knowlesi.plasmodium falciparum and plasmodium knowlesi have been established in continuous culture using the basic method of trager & jensen. various parameters of the culture system have been examined, namely, the gas requirements, serum and red cell requirements, frequency of medium replacement, and a comparison of static and agitated cultures made. the most important factors affecting growth in vitro seem to be the oxygen tension, red cell concentration, the frequency with which old medium is replaced ...1979120767
renal disease in acute plasmodium falciparum infection in man. 1979119089
immunization against malaria with antigen from plasmodium falciparum cultivated in vitro.aotus monkeys, which are generally killed when infected with the human malaria parasite plasmodium falciparum, have been identified and grouped by karyotype. these animals were immunized with parasite material obtained from p. falciparum cultivated in vitro which had been maintained in culture for over a year. when sufficient amounts of this antigenic material were used with a synthetic muramyl dipeptide (mdp), protective immunity was induced without presenting the antigen in complete freund's a ...1978103100
vaccination of experimental monkeys against plasmodium falciparum: a possible safe adjuvant.owl monkeys (aotus trivirgatus griseimembra) were effectively immunized against a human malaria parasite, plasmodium falciparum. two injections of antigen, primarily mature segmenters with fully developed merozoites, mixed with adjuvant (6-o-stearoyl-n-acetylmuramyl-l-alanyl-d-isoglutamine and liposomes) were administered intramuscularly at a 4-week interval. approximately 2 weeks after the second vaccination, the monkeys were challenged with the homologous strain of p. falciparum. all immunized ...197899814
plasmodium falciparum and plasmodium vivax infections in the owl monkey (aotus trivirgatus). i. the courses of untreated infections.this study, the first of three designed to determine the feasibility of using owl monkeys infected with human plasmodia in the search for new, more broadly active antimalarial drugs, dealt with the characteristics of untreated infections with eight strains of plasmodium falciparum and two strains of p. vivax. such infections, induced by standardized inocula of these strains in 1,733 monkeys, all aotus trivirgatus griseimembra, were followed from day of inoculation to death of self-cure. the viru ...197899055
antimalarial activities of various 4-quinolonemethanols with special attention to wr-142,490 (mefloquine).pilot appraisals of the activities of a selected group of 4-quinolinemethanols against acute plasmodium falciparum infections in owl monkeys indicated that compounds of this class are equally active against infections with chloroquine-resistant and chloroquine-susceptible strains and that this efficacy is not compromised by concomitant resistance to pyrimethamine, and in addition, identified three derivatives with outstanding activity (wr-226,253; wr-142,490; and wr-184,806). wr-142,490, the sec ...197898104
recent advances in applied malaria immunology.our present knowledge of cellular and humoral factors which are involved in immunity to plasmodial infections are discussed. immunization against plasmodial infection has been achieved in birds, rodents, simians, and humans. avian hosts have been immunized against gametocytes which resulted in inhibition of gametocytes within the mosquito vector. immunization of humans against plasmodial gametocytes would indirectly protect them against malaria by blocking mosquito transmission to other suscepti ...197993828
cultured plasmodium falciparum used as antigen in a malaria indirect fluorescent antibody test.human sera obtained from persons infected with plasmodium falciparum were tested by a standard indirect fluorescent antibody (ifa) technique using antigen obtained from long term in vitro cultures of two strains of p. falciparum, and antibody in high titer was reproducibly detected. sera from uninfected persons had undetectable or very low titers of antibody. the use of cultured parasites offers a convenient, stable source of antigens from different p. falciparum strains without requiring their ...197882407
occurrence of s-antigens in serum in plasmodium falciparum infections in man.gambians with severe plasmodium falciparum infections frequently have malarial s-antigens in their serum or plasma. detection of these with the available antisera which are from immune adults is complicated because there are many different s-antigens and none of the antisera contains antibodies to them all. despite this we found s-antigens in about 60% of a large series of malarious children and demonstrated that this was a considerable underestimate of the true incidence. we also showed that th ...197559433
evaluation of in vitro drug sensitivity of human plasmodium falciparum by incorporation of radioactive isoleucine. 19751107459
[demonstration of chloroquine diphosphate resistance in plasmodium falciparum strains naturally infecting man in an area of the bolivar state, venezuela]. 19751091958
human monoclonal antibodies against plasmodium falciparum: production, stabilization and characterization.nine human monoclonal antibodies (moabs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite p. falciparum (pf) were produced by epstein-barr virus transformed b-cell lines (ebv-tcl) with or without fusion to the lymphoblastoid cell line kr4. the peripheral blood b-lymphocytes were obtained from 8 gambian donors immune to pf malaria. two of the ebv-tcl could be expanded and maintained for more than 6 months but neither one could be cloned. six additional e ...19921279503
distribution of repetitive and non-repetitive circumsporozoite protein epitopes on plasmodium falciparum sporozoites and immunochemical characterization of human malaria antisera.the presence and distribution of circumsporozoite protein (csp) epitopes located in the repetitive and non-repetitive regions were studied in three plasmodium falciparum strains, nf54, ifa5 and ifa6. it was found by immunofluorescence, western blotting and immunoelectron microscopy that mabs to epitopes of the repetitive domaine bound similarly to the csp of all three strains. mabs to epitopes of the flanking regions yielded either some strain differences (mabs to the c-terminal end), or reacted ...19921279961
detection of circulating plasmodial antigens in human sera by sandwich elisa with monoclonal antibodies.two monoclonal antibodies (mabs), one produced against plasmodium falciparum (pf-ig8) and the other against p. cynomolgi (pc-ie12) schizont antigens were used in a sandwich elisa for the detection of circulating plasmodial antigens in sera of patients infected with either p. falciparum, p. vivax or p. malariae. the mean +/- sd optical density (od) values for the normal control group using pf-108 and pc-1e12 were 0.351 +/- 0.036 and 0.205 +/- 0.044, respectively. mean od values for the three infe ...19921298082
method to test inhibitory antibodies in human sera to wild populations of plasmodium falciparum. 1976787801
high seasonal malaria transmission rates in the intermediate rainfall zone of sri lanka.malaria transmission was studied at nikawehera, a long-established farming village, located in the intermediate rainfall zone of sri lanka. observations were made over a 12-month period (october-september) that included the main rainy season which occurred during the north-east monsoon in november-january. anolpheles culicifacies, the recognized vector of malaria in sri lanka, was the predominant anopheline mosquito collected by human night baiting at nikawehera. high entomological inoculation r ...19921304700
missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus.molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in lesch-nyhan and gout patients, and somatic mutation in 6-thioguanine resistant t-lymphocytes from healthy individuals. the pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites schistosoma m ...19921306134
human peripheral blood gamma delta t cells respond to antigens of plasmodium falciparum.peripheral blood lymphocytes from donors previously unexposed to malaria parasites proliferate in vitro when stimulated with whole parasitized red blood cells of several different strains of plasmodium falciparum. here we show that both cells enriched for both memory (cd45r0+) and naïve (cd45r0-) phenotype can respond. cells involved in these responses occur at frequencies similar to those observed for recall antigens such as tetanus toxoid but at lower frequencies than observed for the superant ...19921531764
construction of a genomic dna library of the toxoplasma gondii zs2 strain, screening of specific clones, and dna diagnosis of toxoplasmosis.we have constructed a genomic dna library of the toxoplasma gondii zs2 strain and isolated a specific cloned dna sequence from this organism. the restriction map of this cloned 1.1-kb dna fragment was analyzed. southern and dot-blot analyses showed that the 32p-labeled dna fragment hybridized to parasite dna, to dnas from peripheral blood leukocytes and the thymus of baby pigs that were artificially infected with t. gondii, and to dnas of t. gondii-positive anencephalic and hydrocephalic fetuses ...19921536384
incorporation of free fatty acids can explain alterations in the molecular species composition of phosphatidylcholine and phosphatidylethanolamine in human erythrocytes as induced by plasmodium falciparum.phosphatidylcholine (pc) and phosphatidylethanolamine (pe) species composition of human erythrocytes changes upon intraerythrocytic development of plasmodium falciparum. though the activity of the phosphotransferases which catalyze the last step of the kennedy pathway for the synthesis of pc and pe is dependent of the species on diacylglycerol, it appeared that this cannot, by itself, explain the alterations found in pc and pe molecular species composition. when the incorporation of radiolabeled ...19921327542
[malarial encephalopathy and disseminated intravascular coagulation (author's transl)].clinical and anatomical studies of a case of malarial encephalopathy are described in a 51 year old man. in view of the typical symptomatology it was important to ascertain an period even brief of stay in an endemic area. only when this was confirmed the appropriate investigations could be planned (in thic case thick blood drop test) to identify the parassite. the physiopathological mechanisms through which the malarial infection causes the parenchymal lesions are considered. such lesions accord ...1975778999
cytokines and dysregulation of the immune response in human malaria.the dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. in spite of the important role interleukin-1 (il-1) plays on the immunoregulation, and its ability to mimic various features of clinical malaria, reports on il-1 in malaria are lacking. we found that only 2 out of 35 subjects with acute malaria showed increased levels of serum il-1 alpha by enzyme immunoassay. to assess whether il-1 could interfer ...19921343709
antiparasitic agents.in recent years, introduction of new and more effective agents has improved the overall therapy for parasitic infections. this field, however, is still plagued by numerous problems, including the development of resistance to antimicrobial agents (especially with malaria), unavailability of agents in the united states or lack of approval by the food and drug administration, and major toxicities or lack of experience in pregnant women and children, which limits use in these groups of patients. wid ...19921545596
transcription of the gene for the merozoite surface antigen msa2 of the human malaria parasite plasmodium falciparum during the asexual cycle.the transcription of the plasmodium falciparum gene for the msa2 antigen has been studied throughout the parasite's asexual growth cycle. for this purpose poly(a)+ rna from different times of the cycle was tested for the presence of the mrna encoding msa2 by in vitro translation and subsequent analysis of the translation products by immunoprecipitation with an antibody against msa2. the results revealed that this mrna is present in trophozoites, reaches the highest concentration during the trans ...19921547892
human igg responses against the n-terminal region of the merozoite surface protein 1 of plasmodium vivax.the complete primary structure of the gene encoding the merozoite surface protein 1 of plasmodium vivax (pvmsp-1) revealed the existence of interspecies conserved regions among the analogous proteins of other plasmodia species. here, three dna recombinant clones expressing 50, 200 and 500 amino acids from the n-terminal region of the pvmsp-1 protein were used on elisa and protein immunoblotting assays to look at the igg antibody responses of malaria patients from the brazilian amazon region of r ...19921343729
protection against malaria in aotus monkeys immunized with a recombinant blood-stage antigen fused to a universal t-cell epitope: correlation of serum gamma interferon levels with protection.the major surface antigen p190 of the human malaria parasite plasmodium falciparum contains nonpolymorphic, immunogenic stretches of amino acids which are attractive components for a subunit vaccine against malaria. one such polypeptide, termed 190l, is contained in the 80-kda processing product of p190, which constitutes the major coat component of mature merozoites. we report here that immunization of aotus monkeys with 190l gives only poor protection against p. falciparum challenge. however, ...19921370271
the increased k+ leak of malaria-infected erythrocytes is not via a ca(2+)-activated k+ channel.charybdotoxin and nitrendipine both inhibited k+(86rb+) influx via the ca(2+)-activated channel of uninfected erythrocytes but had no effect on k+(86rb+) transport in malaria-infected cells. activation of the channel in uninfected cells in which the cytoplasmic [na+]/[k+] ratio was adjusted to be comparable with that of late-stage malaria-infected erythrocytes resulted in a large (nitrendipine-sensitive) increase in k+(86rb+) influx. these results suggest that the endogenous ca(2+)-activated k+ ...19921375512
molecular cloning, stage-specific expression and cellular distribution of a putative protein kinase from plasmodium falciparum.a putative protein kinase gene (pfpk2) has been isolated from the human parasite plasmodium falciparum by using a mixed oligonucleotide pool which corresponds to a highly conserved region of serine/threonine protein kinases. the complete nucleotide sequence of 5 kb suggests the existence of a second transcriptional unit besides that of the pfpk2 gene, separated by a highly (a+t)-rich region and transcribed in a different orientation. no intron sequence exists in pfpk2. the predicted amino acid s ...19921378403
human vascular endothelial cell adhesion receptors for plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1.the clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, plasmodium falciparum. we now report that a primary p. falciparum-infected erythrocyte (parasitized red blood cell [prbc]) isolate from a patient with severe complicated malaria binds to cytokine-induced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leuko ...19921383378
plasmodium falciparum: cytoadherence of malaria-infected erythrocytes to human brain capillary and umbilical vein endothelial cells--a comparative study of adhesive ligands.the cytoadherence of plasmodium falciparum-infected erythrocytes (fcr-3 line) to human brain capillary endothelial cells (hbec), c32 amelanotic melanoma cells, and human umbilical vein endothelial cells (huvec) was studied. the adhesion of infected red cells was hbec > amelanotic melanoma > huvec. the presence or absence of the adhesive ligands icam-1 (cd54 or intercellular adhesion molecule 1), icam-2, and cd36 (= glycoprotein iv) was determined for each of these cells by indirect immunofluores ...19921385207
effect of heat-shock on plasmodium falciparum viability, growth and expression of the heat-shock protein 'pfhsp70-i' gene.cultures of the human malaria parasite plasmodium falciparum were subjected to heat-shock for varying times and temperatures and then tested for their viability, growth and expression of heat-shock protein. results show that the majority of parasites remained viable after heat-shock but their growth was affected. however, the expression of the heat-shock protein 'pfhsp70-i' gene was enhanced after heat-shock. we conclude that malarial parasites are able to survive in vivo during fever probably d ...19921385215
mhc and malaria: the relationship between hla class ii alleles and immune responses to plasmodium falciparum.in mice, immune responses to subunits of defined malaria antigens are regulated by genes mapping within the mhc and it has been suggested that such genetic restriction will be a major obstacle in the development of a human malaria vaccine. the relationship between class ii human leukocyte antigen (hla) genes and immune recognition of three candidate antigens for a vaccine against plasmodium falciparum malaria has been investigated in a human population living in a malaria endemic area of west af ...19921390436
[chemical synthesis and cloning of plasmodium falciparum 45 peptide antigen gene].we have synthesized a 162 bp gene of human plasmodium falciparum hybrid peptide antigen by the solid-phase phosphoramidite method with abi 381a dna synthesizer. the gene encodes three fragments of the relative molecules 83 kda, 55 kda and 35 kda merozoite-specific proteins and two cs repeats or four peptides. the gene with the designed two cohesive ends was divided into 8 fragments to be synthesized. all synthetic fragments were annealed and ligated with t4 dna ligase to form double dna chain. t ...19921394913
detection of human antibodies against plasmodium falciparum antigens in blood meals of anopheline mosquitoes.human igg antibodies against plasmodium falciparum asexual stages, gametocytes and sporozoites were detected by indirect fluorescent antibody (ifa) techniques in the blood meals of anopheles gambiae s.l. from a malaria-endemic area of western kenya. field-collected mosquitoes, which had been stored dry for over 2 years, were screened first for human igg by elisa. in 141 blood meal samples from human-fed mosquitoes, the prevalence of stage-specific antibodies was 87.9% for asexual-stage parasites ...19921402862
human immune response directed against plasmodium falciparum heat shock-related proteins.heat shock-related stress proteins present in all eucaryotes and procaryotes have been shown to be immune targets in a broad range of infections. we have analyzed sera from people exposed primarily to plasmodium falciparum for specific antibodies against two heat shock-related proteins (proteins similar to the heat shock protein with a molecular weight of 75,000 [pfhsp] and a glucose-regulated protein with a molecular weight of 72,000 [pfgrp]). in an immunoprecipitation analysis with metabolical ...19901691147
evidence for diversity of plasmodium falciparum sporozoite surface antigens derived from analysis of antibodies elicited in humans.we have compared the reactivities of antibodies developed by individuals frequently exposed to plasmodium falciparum infections with the epitopes contained within the repeats of the circumsporozoite (cs) protein and their reactivities with the epitopes of a native molecule(s) accessible on the sporozoite surface. results of direct-binding assays and competition assays between artificial and native molecules or between human antibodies and anti-cs monoclonal antibodies suggest that humans respond ...19901696936
characterization of yeast artificial chromosomes from plasmodium falciparum: construction of a stable, representative library and cloning of telomeric dna fragments.molecular genetic studies of the human malaria parasite plasmodium falciparum have been hampered in part due to difficulties in stably cloning and propagating parasite genomic dna in bacteria. this is thought to be a result of the unusual a+t bias (>80%) in the parasite's dna. pulsed-field gel electrophoretic separation of p. falciparum chromosomes has shown that large chromosomal polymorphisms, resulting from the deletion of dna from chromosome ends, frequently occur. understanding the biologic ...19921427849
the characterization of two monoclonal antibodies which react with high molecular weight antigens of asexual plasmodium falciparum.we prepared rat monoclonal antibodies (mab) specific for very large plasmodium falciparum proteins to assist in their characterization. hybridomas prepared from rats immunized with parasitized erythrocyte (pe) proteins of greater than 200 kda exhibited two patterns of western blot reactivity with pe sds extracts: one represented by clone 41e11 (igm, kappa), the other by clone 12c11 (igm, lambda). mab 41e11 reacted by western blotting with at least 15 antigens, most of which comigrated with antig ...19921435861
suppression of plasmodium falciparum infections during concomitant measles or influenza but not during pertussis.in tropical countries, concomitant infections are a continuous problem. in the rufiji delta, an area of tanzania that is holoendemic for malaria, there were outbreaks of influenza a, measles, and pertussis in 1986 and 1987. significantly lower parasitic prevalences and mean densities of malaria parasites were found in children up to nine years of age who had measles or influenza than in asymptomatic control children. in contrast, children with pertussis had a higher prevalence and mean density t ...19921449208
how to select plasmodium falciparum pre-erythrocytic antigens in an expression library without defined probe.the restricted access to plasmodium falciparum liver stages has greatly limited the analysis of the antigenic content of that stage. due to the lack of material to perform immunochemical studies, of access to mrna, and of monoclonal probes, we decided to screen a genomic library with stage-restricted human antibodies. this strategy led to the identification of a large number of dna fragments encoding both sporozoite specific as well as liver-stage specific epitopes. following the initial charact ...19901709833
intravenous immunoglobulin in the treatment of paediatric cerebral malaria.hyperimmune globulin can inhibit and reverse the cytoadherence between plasmodium falciparum-infected erythrocytes and melanoma cells in vitro. cytoadherence is believed to mediate disease in cerebral malaria. therefore we studied the efficacy of i.v. immunoglobulin, purified from the plasma of local semi-immune blood donors, as an adjunct to standard treatment for cerebral malaria in malawian children. the immunoglobulin preparation (ifat antimalarial antibody titre 1:5120) recognized erythrocy ...19921458672
antigenic diversity amongst ten geographic isolates of plasmodium falciparum defined by merozoite invasion inhibition assay.the extent to which human antibodies involved in functional immunity react with antigenic determinants varying between different isolates or strains of human malaria parasite plasmodium falciparum will influence the design of vaccine against malaria. in this study, in vitro inhibition of merozoite invasion in erythrocytes by an immune human serum was used to define the antigenic differences in 10 isolates of p. falciparum from three endemic areas, i.e. africa, south america and southeast asia. t ...19921459296
origins of the parasitophorous vacuole membrane of the malaria parasite, plasmodium falciparum, in human red blood cells.we have attempted to determine whether the parasitophorous vacuole membrane, in which the malaria parasite (merozoite) encapsulates itself when it enters a red blood cell, is derived from the host cell plasma membrane, as the appearance of the invasion process in the electron microscope has been taken to suggest, or from lipid material stored in the merozoite. we have incorporated into the red cell membrane a haptenic phospholipid, phosphatidylethanolamine, containing an nbd (n-(7-nitrobenz-2-ox ...19921506432
identification of anti-plasmodium falciparum antibodies in human breast milk.malarial infections are rarely observed in neonates. it has been postulated that some immunity may be passively transferred during nursing, but anti-malarial antibodies (abs) have not been detected in human milk. in this study, milk samples, collected 2-14 days after parturition from women at the central maternity hospital, yaounde, were evaluated for total igg and iga antibody levels by radial diffusion, protein composition by sds-page, anti-malarial antibodies using an isotype-specific immunof ...19921514035
continuous cultivation and drug susceptibility testing of plasmodium falciparum in a malaria endemic area.isolates (uch-23 and om) and cloned strains of plasmodium falciparum (clones w-2 and d-6) were maintained in continuous culture for 28 to 150 days using culture media supplemented with 10% (v/v) heat inactivated semi-immune human plasma. microscopic appearance and growth rates (r) of the parasites in media supplemented with semi-immune human plasma [r = 1.13 (w-2), 0.92 (d-6), 0.75 (om) and 0.84 (uch-23)] were comparable to those of parallel cultures maintained in media supplemented with 10% (v/ ...19921522542
antimalarial activities of oligodeoxynucleotide phosphorothioates in chloroquine-resistant plasmodium falciparum.synthetic oligonucleotides and their chemical modifications have been shown to inhibit viral and cellular gene expression by sequence-specific antisense hybridization to target mrnas. we now report that oligodeoxynucleotide phosphorothioates and their nuclease-resistant modifications are effective in micromolar and submicromolar concentrations against the growth of both chloroquine-resistant and chloroquine-sensitive strains of plasmodium falciparum in vitro. parasitized human erythrocytes were ...19921528864
intraspecific chromosomal polymorphism in the anopheles gambiae complex as a factor affecting malaria transmission in the kisumu area of kenya.the paracentric inversion polymorphisms of anopheles gambiae and an. arabiensis populations in the kisumu area of western kenya were studied in relation to parameters of plasmodium falciparum transmission. anopheles gambiae (n = 1,387) was polymorphic for inversions b on chromosomal arm 2r and a on arm 2l, with frequencies of the inverted arrangements of 17% and 43%, respectively. anopheles arabiensis (n = 484) was polymorphic for inversion b on chromosomal arm 2r and a on 3r, with frequencies o ...19921539757
dictyostelium discoideum as an expression host for the circumsporozoite protein of plasmodium falciparum.we have used the cellular slime mold, dictyostelium discoideum (dd), to express the plasmodium falciparum circumsporozoite protein (cs), a potential component of a subunit vaccine against malaria. this was accomplished via an expression vector based on the discoidin i-encoding gene promoter, in which we linked a sequence coding for a dd leader peptide to the almost complete cs coding region (pedii-cs). cs production at both the mrna and protein levels is induced by starving cells in a simple pho ...19921541397
the pf332 gene of plasmodium falciparum codes for a giant protein that is translocated from the parasite to the membrane of infected erythrocytes.we studied the gene structure of the plasmodium falciparum antigen 332 (ag332). the gene size was estimated to be approx. 20 kb based on the large size of both the transcript found in mature asexual blood stage parasites and mung bean nuclease fragment generated from genomic dna. sequence analysis of genomic and cdna clones representing different regions of the pf332 locus showed that the gene product contains a large number of highly degenerated glutamic acid (glu)-rich repeats (32% glu). the g ...19921544579
susceptibility of owl monkeys to plasmodium falciparum in relation to hemoglobin and karyotype.humans with inherited abnormalities of hemoglobin (hb) synthesis have less frequent and less severe infections of malaria. this study sought to determine if karyotypic variation in the owl monkey was expressed as differences in hb moieties and if it offered a selective advantage in susceptibility to malaria. five karyotypes of owl monkey were evaluated on the basis of the electrophoretic mobility of their major and minor hb components. the results of 40 owl monkeys of different karyotypes demons ...19921558276
binding of plasmodium falciparum 175-kilodalton erythrocyte binding antigen and invasion of murine erythrocytes requires n-acetylneuraminic acid but not its o-acetylated form.sialic acid on human erythrocytes is involved in invasion by the human malaria parasite, plasmodium falciparum. mouse erythrocytes were used as a reagent to explore the question of whether erythrocyte sialic acid functions as a nonspecific negative charge or whether the sialic acid is a necessary structural part of the receptor for merozoites. human erythrocytes contain n-acetylneuraminic acid (neu5ac), whereas mouse erythrocytes, which are also invaded by p. falciparum merozoites, contain 9-o-a ...19921565137
[spontaneous splenic rupture in acute malaria tropica].a 44-year-old man developed bouts of fever (up to 40 degrees c) seven days after returning from a holiday in kenya. malaria prophylaxis with chloroquine had been correctly undertaken. concentrations of lactate dehydrogenase and total bilirubin were raised (493 u/l and 3.55 mg/dl, respectively). blood smear revealed the ring forms of plasmodium falciparum. thereupon the patient was given mefloquine in decreasing doses (750/500/250 mg) at intervals of 8 hours. the following night he had a circulat ...19921597109
segregation analysis detects a major gene controlling blood infection levels in human malaria.the profound influence that the genetic makeup of the host has on resistance to malaria infection has been established in numerous animal studies. this genetic heterogeneity is one of the main causes of the difficulties in developing an effective malaria vaccine. segregation analysis is the first step in identifying the nature of genetic factors involved in the expression of human complex diseases, as infectious diseases. to assess the role of host genes in human malaria, we performed segregatio ...19921598911
ultrastructural analysis of fresh plasmodium falciparum-infected erythrocytes and their cytoadherence to human leukocytes.sixty fresh plasmodium falciparum isolates obtained from gambian children with mild or cerebral malaria were investigated by transmission electron microscopy for the expression of knob-like protrusions (k+) on the surface of the infected erythrocytes. more than six-hundred infected erythrocytes were analyzed. knob-forming parasites were present in all 60 isolates. although knobless parasites (k-) were found in 25 (42%) of the isolates, only 39 were k-, while 577 were k+. nine of the 39 k- infect ...19921599044
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
isolation of skeleton-associated knobs from human red blood cells infected with malaria parasite plasmodium falciparum. 19921620167
calcium transport and compartment analysis of free and exchangeable calcium in plasmodium falciparum-infected red blood cells.calcium (ca2+) is indispensable for normal development of the various stages of the asexual erythrocytic cycle of malaria parasites. however, the mechanisms involved in ca2+ uptake, compartmentalization and cellular regulation are poorly understood. to clarify some of these issues, we have measured total, exchangeable, and free ca2+ in normal red cells (rbcs) and plasmodium falciparum (fcr-3)-infected cells (irbcs) as a function of parasite development. all three forms of ca2+ were found to be s ...19911667934
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
circulating epstein-barr virus-carrying b cells in acute malaria.epstein-barr virus (ebv) infection and plasmodium falciparum malaria are two known cofactors in the aetiology of endemic burkitt's lymphoma. to assess the relation between these factors, limiting dilution analysis was used to assess the number of ebv-carrying b cells in the circulation of gambian children during and after acute malaria. numbers of virus-carrying cells were five times higher in acute malaria patients and in uk patients with infectious mononucleosis than in convalescent malaria pa ...19911672968
in vivo platelet aggregation in acute malaria.thirteen patients suffering from acute malaria attack and thirteen apparently healthy human volunteers (control) were used for the study. platelet aggregation was determined by platelet count ratio technique in which a reduction in platelet count ratio signified an increase in platelet aggregation. platelet count ratio in acute malaria patients was 0.75 +/- 0.03 (sem). platelet count ratio in subjects used as control was 0.88 +/- 0.02. this value was significantly higher than the former (p less ...19911685303
polyclonal in vitro proliferative responses from nonimmune donors to plasmodium falciparum malaria antigens require uchl1+ (memory) t cells.the in vitro polyclonal proliferative responses of peripheral blood mononuclear cells to whole blood stage parasites or fractionated antigens from the human malaria parasite plasmodium falciparum were studied. cells from healthy laboratory donors who had never been exposed to malaria antigens in vivo consistently proliferated to p. falciparum antigens, as did cord blood mononuclear cells. this response was only observed in sheep rosette-positive cells in the presence of adherent cells and was in ...19901690132
[malaria in the dunkerque hospital center from december 1979 to december 1990].seventy-one cases of malaria were diagnosed in the hospital of dunkerque from 1979 to 1990. forty-five patients have been infected in the comores islands. among the 24 other imported cases, 17 (71%) have been contaminated in western or central africa. one case of congenital malaria and one of malaria acquired by blood transfusion are also reported. plasmodium falciparum was detected in 84.5% of the patients. the four human species were found among the comorians. two cases with abnormal forms of ...19921443798
agglutination of plasmodium falciparum-infected erythrocytes from east and west african isolates by human sera from distant geographic regions.plasmodium falciparum-infected erythrocytes (pfe) were collected from acutely infected children in the gambia and tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. sera collected from these countries, other african countries, asia, and south america were used in the pfe microagglutination test to determine whether pfe from east and west africa share surface antigens. from the patterns of agglutination reactivity, we identified extensive antigenic diversity i ...19921449203
generation of recombinant, carbohydrate-free intercellular adhesion molecule-1 (icam-1) and icam-1 fragments in escherichia coli and mapping of epitopes recognized by anti-icam-1 monoclonal antibodies.intercellular adhesion molecule-1 (icam-1) has been shown to interact with the integrin leukocyte function associated antigen-1 (lfa-1) in a variety of cell-cell adhesion phenomena. furthermore, it serves as a receptor for the majority of the rhinoviruses and for plasmodium falciparum-infected human erythrocytes. we generated recombinant, carbohydrate-free icam-1 and several icam-1 fragments by expression in escherichia coli using the fusion protein expression system puex1-3. in western blot and ...19911715847
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
[immunochemical study of antigenic determinants of surface protein s of the tropical malaria pathogen plasmodium falciparum using synthetic peptides].to develop new approaches to diagnostics and therapy of malaria, we carried out immunochemical study of the surface proteins of the tropical malaria parasite plasmodium falciparum with the use of synthetic peptides corresponding to the suggested antigenic determinants of the parasite proteins. rabbit antisera raised against the synthetic peptides bound to parasite proteins as shown by elisa and immunoblotting. affinity purified anti-peptide antibodies inhibited, in some cases, the parasite growt ...19911716103
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
human immune response in plasmodium falciparum malaria. synthetic peptides corresponding to known epitopes of the pf155/resa antigen induce production of parasite-specific antibodies in vitro.autologous cell mixtures containing t cells, b cells, and adherent accessory cells from individuals primed to the malaria parasite plasmodium falciparum by repeated natural infections were investigated for induction of ig and antibody secretion in vitro. in vitro activation of cell cultures with two synthetic peptides corresponding to immunodominant t cell epitopes of the merozoite ag ring-infected erythrocyte surface ag (mr 155,000) (pf155/resa), one from its carboxyl-terminal repeat and one fr ...19911717554
towards the design of heterovalent anti-malaria vaccines: a hybrid immunogen capable of eliciting immune responses to epitopes of circumsporozoite antigens from two different species of the malaria parasite, plasmodium.the peptide cs.t3, corresponding to residues 378-398 of the plasmodium falciparum (pf) circumsporozoite (cs) protein sequence (except with cysteines 384 and 389 replaced by alanines), has been found to be almost universally recognized by human and mouse t lymphocytes. when colinearly linked to the repetitive b-lymphocyte-specific epitope (asn-ala-asn-pro)n of pf cs protein, cs.t3 induces t-helper activity for an anti-(asn-ala-asn-pro)n antibody response in mice of different haplotypes. we constr ...19911721043
epitopes of the plasmodium falciparum clustered-asparagine-rich protein (carp) recognized by human t-cells and antibodies.linear b- and t-cell epitopes have been identified in the plasmodium falciparum clustered-asparagine-rich-protein (carp). twenty-six synthetic peptides, 15-25 amino acids in length, were assayed for their ability to stimulate purified, human t-cells primed to p.falciparum by natural infection to proliferate and/or secrete gamma-interferon (ifn gamma). the plasma of malaria exposed individuals were tested for antibody reactivity with peptides coupled to bovine serum albumin in a semiquantitative ...19911725821
inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites.the incidence of human malaria has increased during the past 20 years; 270 million people are now estimated to be infected with the parasite. an important contribution to this increase has been the appearance of malaria organisms resistant to quinoline-containing antimalarials such as chloroquine and quinine. these drugs accumulate in the acid food vacuoles of the intraerythrocytic-stage malaria parasite, although the mechanism of their specific toxicity in this organelle is uncertain. the prima ...19921729651
dna polymerase delta: gene sequences from plasmodium falciparum indicate that this enzyme is more highly conserved than dna polymerase alpha.genes encoding proteins homologous to the catalytic subunits of dna polymerase alpha and delta have been cloned from the human malaria parasite plasmodium falciparum. these are among the first cellular replicative dna polymerase genes to be cloned and their sequences allow us to make new statements about the relative degrees of conservation of these two enzymes. the most important finding was that p. falciparum pol delta showed considerable homology to the only other pol delta enzyme for which p ...19911762904
prospects for malaria control in urban and rural kinshasa.malaria is a major cause of paediatric illness and death in kinshasa, and all 3 million inhabitants are at risk. in view of the increasing chloroquine-resistance of plasmodium falciparum, the early treatment of fever cases as the sole malaria control measure is no longer acceptable. the prospects for vector control are determined by the effectiveness, the acceptability and the practicability of the various methods in the local conditions of kinshasa. pronounced differences in the level of endemi ...19911793262
cytotoxic and antimalarial constituents of the roots of eurycoma longifolia.by bioactivity-directed fractionation, five cytotoxic constituents have been characterized from the roots of eurycoma longifolia collected in kalimantan, indonesia. four canthin-6-one alkaloids, namely, 9-methoxycanthin-6-one, 9-methoxycanthin-6-one-n-oxide, 9-hydroxycanthin-6-one, and 9-hydroxycanthin-6-one-n-oxide, and one quassinoid, eurycomanone, were found to be cytotoxic principles. each of these compounds was evaluated against a panel of cell lines comprising a number of human cancer cell ...19911800638
an original method for rapid serial determination of phospholipid biosynthesis. applications to mammalian lymphocytic cells and a lower eucaryote, plasmodium falciparum.a rapid, convenient, and efficient method is presented to measure phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol biosynthesis from [3h]choline, [3h]ethanolamine, and [3h]inositol, respectively. after incubation of the cells in 96-multi-well dishes with the appropriate radioactive precursor, cells were lysed with water and the water-insoluble materials, particularly cellular membranes which contain the bulk of phospholipids, were serially collected on glass-fiber papers u ...19911812785
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
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