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Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We report the isolation of cDNA clones for a Plasmodium falciparum gene that encodes the complete amino acid sequence of a previously identified exported blood stage antigen. The Mr of this antigen protein had been determined by sodium dodecylsulphate-polyacrylamide gel electrophoresis analysis, by different workers, to be 113,000, 126,000, and 140,000. We show, by cDNA nucleotide sequence analysis, that this antigen gene encodes a 989 amino acid protein (111 kDa) that contains a potential signal peptide, but not a membrane anchor domain. In the FCR3 strain the serine content of the protein was 11%, of which 57% of the serine residues were localized within a 201 amino acid sequence that included 35 consecutive serine residues. The protein also contained three possible N-linked glycosylation sites and numerous possible O-linked glycosylation sites. The mRNA was abundant during late trophozoite-schizont parasite stages. We propose to identity this antigen, which had been called
p126
, by the acronym SERA, serine-repeat antigen, based on its complete structure. The usefulness of the cloned cDNA as a source of a possible
malaria
vaccine is considered in view of the previously demonstrated ability of the antigen to induce parasite-inhibitory antibodies and a protective immune response in Saimiri monkeys.
...
PMID:Amino acid sequence of the serine-repeat antigen (SERA) of Plasmodium falciparum determined from cloned cDNA. 284 41
In Brazil, no study has been done concerning the detection of
malaria
parasites by polymerase chain reaction (PCR) related to the diagnosis of Plasmodium falciparum malaria. In the present report we describe a highly sensitive methodology for
malaria
diagnosis using a nested PCR method based on amplification of the
p126
P. falciparum gene detected by simple ethidium bromide staining. The P. falciparum Palo Alto strain (culture samples) was serially diluted in blood from an uninfected donor to a final level of parasitemia corresponding to 10(-8)% and was processed for PCR amplification. In each of these dilutions a parasitological examination was performed to compare the sensitivity with that of PCR amplification. Blood samples (field samples) were obtained from 51 malarious patients with positive thick blood smears (TBS) who were living in endemic regions of the Brazilian Amazon. They corresponded to 42 P. falciparum and 9 P. vivax cases, with parasitemia levels ranging from only 16 to 20,200 parasites/microliter for P. falciparum disease and from 114 to 11,000 parasites/microliter for P. vivax
malaria
. We demonstrate that the use of nested PCR allows the detection of 0.005 parasites/microliter without the use of radioactive material. The use of a 1-ml sample volume and the organic DNA extraction method should be suitable in blood banks and for the evaluation of patients during and after drug treatment.
...
PMID:Malaria diagnosis: standardization of a polymerase chain reaction for the detection of Plasmodium falciparum parasites in individuals with low-grade parasitemia. 887 68
We compared the antigenicity of
p126
Plasmodium falciparum peptides with predicted antigenic regions identified using the methods described by Garnier et al. (1978) and Chou & Fasman (1974). For this purpose nine different P. falciparum peptides were synthesized in accordance with the deduced amino acid sequence of the
p126
gene, and their reactivity was tested using an enzyme linked immunosorbent assay against sera from individuals with a natural
malaria
infection. Both predictive methods gave similar antigenic-index scores, however, a comparison of these predictive results with data obtained by ELISA showed that the probability of a correct prediction was only around 45% for both cases. Thus, in our view computer software could not be used in isolation for screening purposes, and other parameters must also be taken into account when using such software to assess antigenicity.
...
PMID:Can software be used to predict antigenic regions in Plasmodium falciparum peptides? 922 70
A parasitophorous vacuole protein of Plasmodium falciparum,
p126
, is a potential candidate for a
malaria
vaccine. Its N-terminal region, composed of six repeats of eight amino acids, appears to be involved in the induction of protective immunity against P. falciparum challenge in monkeys. This study evaluated the immune response to
p126
and to its N-terminal region (Nt47) in patients (n = 45) living in a
malaria
-endemic area of Brazil (Colina, Porto Velho, Rondonia). Cellular proliferative responses against Nt47 were low and infrequent. The study of the humoral immune response demonstrated that 95% of the patients had detectable anti-
p126
antibodies and 77% had anti-Nt47 antibodies. Analysis of the antibody isotypes specific for Nt47 revealed that all four IgG subclasses were present and individuals with higher levels of anti-Nt47 cytophilic IgG antibody (IgG1 + IgG3/IgG2 + IgG4) had significantly lower parasitemia levels, suggesting that antibodies to the N-terminal region of the
p126
protein may contribute to acquisition of immunity to P. falciparum
malaria
.
...
PMID:Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans. 966 Apr 61
We investigated the relationships between class II human leukocyte antigens (HLA) and the antibody response to Plasmodium falciparum
p126
protein and to its amino-terminal portion (Nt47) in 2
malaria
-endemic villages in Brazil, Colina and Ribeirinha. All people from the endemic areas had anti-
p126
antibodies, and the frequencies of anti-Nt47 antibodies were similar in both communities (66% for Colina and 75% for Ribeirinha). Typing of HLA showed that Colina and Ribeirinha groups had no significant differences in HLA antigen frequencies. However, in both groups, significant associations between positive response to anti-Nt47 and presence of HLA-DR4, as well as between absence of response and presence of HLA-DR15, were observed. The predominance of positive responses to Nt47 among HLA-DR4 people was independent of the presence of any particular allele. There was no evidence for association between HLA-DQB1 alleles and antibody response to Nt47. Thus, naturally exposed people with different HLA class II antigens seem to respond differently to Nt47, indicating that the choice of relevant peptide sequences may have important consequences for subunit vaccine development.
...
PMID:Human leukocyte antigen class II control of the immune response to p126-derived amino terminal peptide from Plasmodium falciparum. 1220 84