Sequence analysis of the apical membrane antigen I (AMA-1) of Plasmodium vivax.
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Amino Acid Sequence↗
Biomedical subjects
A Saul
Publications and source records attributed to A Saul.
DNA probes for identifying the members of the Anopheles punctulatus complex in Papua New Guinea.
Genomic DNA probes were made for five members of the Anopheles punctulatus complex of mosquitoes found in Papua New Guinea. Specific DNA probes were developed for An. punctulatus, An. koliensis, and three sibling species, An. farauti No. 4, An. farauti No. 5, and An. farauti No. 6, by differentially screening total genomic DNA libraries of individual species and sibling species with homologous DNA against heterologous DNA labeled with 32P. Probes ranged from 273 to 630 bp. Identification of species can be made from squash or dot blots using only a segment of the mosquito (i.e, head, thorax, abdomen, or even legs), allowing for concurrent analysis of the remainder of the mosquito for other epidemiologic characteristics.
Animals↗
Rhesus D genotyping using polymerase chain reaction.
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Base Sequence↗
Minimal efficacy requirements for malarial vaccines to significantly lower transmission in epidemic or seasonal malaria.
The effect of vaccines against the pre-erythrocytic, the erythrocytic and the sexual stages of malaria on the transmission of malaria was examined using a simulation model of seasonal or epidemic transmission. The primary outcome of the model was the number of cases of malaria present at the end of the transmission season. A range of efficacy for the vaccine, or of coverage of the population and of vectorial capacities were tested for each vaccine type. For a similar level of efficacy or coverage under conditions simulating hypo or mesoendemic malaria, all types of vaccines gave similar decreases in the number of people infected. Although all vaccine types gave significant reductions in malaria incidence at efficacy or coverage levels considerably lower than that required to completely block transmission, this reduction in case numbers was highly dependent on the vectorial capacity. The simulation model is equally applicable to other transmission blocking measures such as insecticide treated bed nets.
Animals↗
Polymorphism in Plasmodium vivax MSA1 gene--the result of intragenic recombinations?
The diversity in a 925 bp portion of the Plasmodium vivax MSA1 gene in isolates from the Philippines, China, the Solomon Islands and Papua New Guinea was investigated. A total of 74 base pair changes was found in the amplified fragment from 18 isolates. Most of these changes were single or double base pair substitutions. In several regions, these point changes were tightly linked with one set always present or always absent in the different isolates. Seven such blocks were identified. These blocks were present in different combinations in the different isolates indicating that extensive intragenic recombination has occurred.
Amino Acid Sequence↗
Mice immunized with a synthetic peptide construct corresponding to an epitope present on a Plasmodium falciparum antigen are protected against Plasmodium chabaudi challenge.
Inhibitory monoclonal antibody (MoAb) 8E7/55 recognizes a parasitophorous vacuole membrane (PVM) antigen in Plasmodium falciparum. Previous studies have identified the epitope, DNNLVSGP, recognized by the MoAb. A synthetic peptide containing this sequence was synthesized and coupled to diphtheria toxoid (DT) and was found capable of generating antibodies when used as an immunogen in mice which recognize the native antigen exp-1. In this study we demonstrate the ability of the MoAb and antisera generated against the peptide construct to recognize a 54 kD PVM antigen in Plasmodium chabaudi. The P. chabaudi antigen is synthesized in trophozoites and released to the surrounding culture media outside the parasitized erythrocyte. Mice immunized with the peptide conjugate are protected when challenged with a lethal strain of P. chabaudi. Protection in the mice correlated with the antibody titre prior to challenge. If the PVM antigen from P. chabaudi is a homologue of exp-1 from P. falciparum, then these experiments may provide a guide to the antibody titres required in human trials before antibody mediated protection could be expected. The discovery that a PVM localized antigen is secreted into the surrounding in vitro culture media provides us with a valuable model system for further investigation of protein trafficking pathways in malaria-infected erythrocytes.
Amino Acid Sequence↗
Amoxicillin and clavulanic acid in the treatment of actinomycetoma.
BACKGROUND: Mycetoma is a relatively frequent disease in tropical countries. Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement. The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro. METHODS: We have used this combination in two cases of mycetoma caused by N. brasiliensis, both with bone involvement and resistance to the drugs usually used. A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid). RESULTS: Clinical and mycologic amelioration was observed in the two cases after completing the treatment. There were no side effects or relapses after 3 to 6 months of follow-up after treatment. CONCLUSIONS: We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease.
Amoxicillin↗
Protective immunization with invariant peptides of the Plasmodium falciparum antigen MSA2.
Three octapeptides from the N and C terminal C regions of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum elicit anti-MSA2 antibody when given as diphtheria toxoid conjugates. These antibodies also bind to the MSA2 homolog from the rodent malaria Plasmodium berghei. All mice vaccinated with these conjugates and challenged with an otherwise lethal inoculum of P. berghei showed substantial protection with most surviving. There was a inverse correlation between the development of the parasitemia and the antibody titer, with alum, algammulin, and CFA giving comparable results. These observations show that the conserved region of MSA2 could form the basis of a malaria vaccine when presented in a suitably immunogenic form, thus avoiding the problems of antigenic diversity [corrected].
Adjuvants, Immunologic↗
The 42-kilodalton rhoptry-associated protein of Plasmodium falciparum.
The gene coding for a 42-kDa rhoptry protein of Plasmodium falciparum has been cloned. On the basis of prior monkey vaccination studies, this protein is regarded as an important vaccine candidate, but its identity has been the subject of considerable uncertainty. Analysis of the cloned sequence shows that it is a basic, hydrophobic protein, without repetitive elements, unrelated to any of the previously postulated gene products and shows minimal sequence diversity. The availability of the corresponding recombinant protein will enable studies of its efficacy in human vaccine trials to be undertaken.
Amino Acid Sequence↗
Parasite-induced changes to localized erythrocyte membrane deformability in Plasmodium falciparum cultures.
The effect of intra-erythrocyte development of the Plasmodium falciparum parasite on local deformability of human erythrocyte membranes was studied by aspiration of cells into 0.56 micron diameter pores in polycarbonate filters and examination, after fixing, with a scanning electron microscope. As the aspiration pressure increased, the erythrocyte membrane was extruded into the filter pores. The pressure dependence of the protrusion length and the minimum pressure required to produce any deformation provided measures of the membrane shear and the bending moduli, respectively. At the trophozoite and, to a greater extent, schizont stage of development, host cell membrane deformability was significantly decreased. There was no appreciable difference between uninfected and ring-infected erythrocytes.
Animals↗
Conservation of repeating structures in the PfEMP2/MESA protein of Plasmodium falciparum.
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Amino Acid Sequence↗
Cloning and characterization of a novel multicopy, repetitive sequence of Plasmodium falciparum, REP51.
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Animals↗
Towards a malaria vaccine: riding the rollercoaster between unrealistic optimism and lethal pessimism.
Activity in many laboratories over the past decade has resulted in many vaccine candidates nearing clinical trials. These include several antigens from the sporozoite stage; merozoite surface antigens MSA1 and MSA2, RESA, the rhoptry proteins RAP-1 and RAP-2 from the asexual blood stage; the pfs25, pfg45 and pfg230 from the ookinete and gamete stages. This progress in the identification of potential vaccine candidates now highlights a series of scientific, developmental, economic and operational problems the solutions to which will be as critical to the development of a vaccine as the cloning and expression of parasite genes.
Animals↗
Antibody detection ELISAS for malaria diagnosis.
Parasite extracts of Plasmodium falciparum and P. chabaudi and three synthetic peptides from the P. falciparum MSA2 merozoite antigen were tested for suitability as antigens in an antibody detection ELISA using sera from malaria patients in Brisbane. The P. chabaudi extract was superior to P. falciparum extract for detecting P. vivax cases, while for P. falciparum cases the two parasite extracts were equivalent. Single peptide antigens were generally less sensitive than parasite extracts; however, peptides G3 and G7 were more sensitive than parasite extracts in detecting first attacks of P. vivax. Examination of isotype specific responses demonstrated that this may be explained by higher IgG responses to these peptides in first than in subsequent P. vivax attacks. Because of the differing antibody specificities in primary and secondary P. falciparum and P. vivax cases, the best sensitivity was achieved by using the combined results of assays with three antigens: P. chabaudi, peptide G3 and peptide G7. The combined sensitivity was 77.1% for P. falciparum and 88.6% for P. vivax acute cases with 91.1% specificity.
Amino Acid Sequence↗
Molecular cloning of Plasmodium falciparum blood stage antigens and application of the recombinant proteins in serodiagnosis.
A Plasmodium falciparum genomic DNA library was established in the expression vector lambda gt11, cloned in Escherichia coli. The library was screened with human hyperimmune sera by in situ hybridization. Twenty clones expressing P. falciparum sequences as polypeptides fused to beta-galactosidase were identified. One, CD3A/9025/60, reacted with all immune sera and expressed polypeptides that were larger than beta-galactosidase as well as reacting with antibodies to beta-galactosidase and to P. falciparum. When the fusion proteins were used as target antigens to diagnose malaria antibodies, a result was obtained which correlated well with indirect fluorescence assay.
Animals↗
BLT esterase activity as an alternative to chromium release in cytotoxic T cell assays.
Granules released by cytotoxic T cells (CTL), during recognition and killing of target cells, contain granule enzyme A. This serine protease has an esterase activity, which is easily measured using the substrate benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT). BLT activity, routinely used as an assay for granule release, provides an alternative to the standard chromium release assay as a measure of CTL-mediated killing. The two methods were highly comparable when either exogenous synthetic peptide or endogenously produced epitopes were used as targets and human CTL clones acted as effectors. The advantages of the BLT assay are that it uses inexpensive non-radioactive reagents, the assay can be run over any period between 4 and 30 h and can be performed with as few as 10(4) CTLs if synthetic peptide epitopes are used.
Amino Acid Sequence↗
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.
Animals↗