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Doctoral Thesis
DOI
10.11606/T.42.2002.tde-02022005-145755
Document
Author
Full name
Karin Kirchgatter
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2001
Supervisor
Committee
Obando, Hernando Antonio Del Portillo (President)
Boulos, Marcos
Segurado, Aluisio Augusto Cotrim
Wunderlich, Gerhard
Yoshida, Nobuko
Title in Portuguese
Análise de seqüências var de populações naturais de Plasmodium falciparum da Amazônia Brasileira
Keywords in Portuguese
DBL1alfa
Genes var
Malária
Malária grave
Plasmodium falciparum
Proteína PfEMP1
Abstract in Portuguese
Os genes var de Plasmodium falciparum codificam a proteína PfEMP1 expressa na superfície de eritrócitos infectados e que medeia os fenômenos de citoaderência e "rosetting". Ambos os fenômenos estão diretamente associados à malária grave, e seu domínio mais N-terminal, DBL1alfa, media especificamente "rosetting". Análise de seqüências DBL1alfa de isolados brasileiros e de outros países revelou que a similaridade entre elas não pode predizer origem geográfica. Com o objetivo de determinar se existem seqüências DBL1alfa associadas à malária grave, analisamos as seqüências DBL1alfa expressas em parasitas obtidos de pacientes brasileiros com esta manifestação clínica e encontramos que as seqüências predominantemente expressas apresentavam uma ou duas deleções de cisteínas. Significativamente, apesar de freqüentes no genoma de parasitas de pacientes com malária não grave, essas seqüências foram raramente expressas. Esses dados demonstram a primeira associação de seqüências PfEMP1 expressas e malária grave em pacientes da Amazônia Brasileira.
Title in English
Analysis of var sequences from natural parasite populations of Plasmodium falciparum in the Brazilian Amazon
Keywords in English
DBL1alfa
Malaria
PfEMP1
Plasmodium falciparum
severe malaria
var genes
Abstract in English
Plasmodium falciparum var genes code for PfEMP1, a protein expressed on the surface of infected erythrocytes, and which mediates cytoadherence and rosetting. Both phenomena are directly associated with severe malaria and the most N-terminal domain, DBL1alfa, specifically mediates rosetting. DBL1alfa sequence analysis from Brazilian and worldwide isolates revealed that sequence similarities cannot predict geographical origin. To determine whether there are DBL1alfa sequences associated with severe malaria, we examined expressed var DBL1alfa sequences in patients with severe malaria from the Brazilian Amazon and found that the predominantly expressed DBL1alfa sequences from these parasites lacked 1-2 cysteine residues. Significantly, these sequences were amply found on the genomic repertoire of parasites from patients with mild malaria and yet they were rarely expressed. These data demonstrate the first association of particular PfEMP1 expressed sequences and severe malaria in patients from the Brazilian Amazon.
 
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TESE_KARIN.pdf (12.72 Mbytes)
Publishing Date
2005-04-05
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • KIRCHGATTER, K. Plasmodium falciparum : DBL-1 Var Sequence Analysis in Field Isolates from Central Brazil [doi:10.1006/expr.2000.4520]. Experimental Parasitology [online], 2000, vol. 95, n. 2, p. 154-157.
  • KIRCHGATTER, Karin, and DEL PORTILLO, Hernando A. Association of severe noncerebral Plasmodium falciparum malaria in Brazil with expressed PfEMP1 DBL1 alpha sequences lacking cysteine residues. Molecular Medicine [online], 2002, vol. 8, n. 1, p. 16-23. [cited 2016-08-14]. Available from : <http://www.ncbi.nlm.nih.gov/pubmed/11984002>
  • KIRCHGATTER, Karin, and DEL PORTILLO, Hernando A. Clinical and molecular aspects of severe malaria [doi:10.1590/S0001-37652005000300008]. Anais da Academia Brasileira de Ciências [online], 2005, vol. 77, n. 3, p. 455-475.
All rights of the thesis/dissertation are from the authors
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