排序方式: 共有94条查询结果,搜索用时 15 毫秒
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Zaida Araujo Francesca Giampietro María de los Angeles Bochichio Andrea Palacios Jenifer Dinis Jaime Isern Jacobus Henry de Waard Elsa Rada Rafael Borges Carlos Fernández de Larrea Angel Villasmil Magnolia Vanegas Jose Antonio Enciso-Moreno Manuel Alfonso Patarroyo 《Memórias do Instituto Oswaldo Cruz》2013,108(2):131-139
The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection. 相似文献
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World distribution of the T833C/844INS68 CBS in cis double mutation: a reliable anthropological marker 总被引:4,自引:0,他引:4
Pepe G Vanegas OC Rickards O Giusti B Comeglio P Brunelli T Marcucci R Prisco D Gensini GF Abbate R 《Human genetics》1999,104(2):126-129
Mild hyperhomocysteinemia is associated to mutations either in cystathionine beta-synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In 1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common CBS mutation (T833C) detected in homocystinuric patients. Recently, this double mutation has been detected in Italian and North-American controls. Compared to a group of patients affected by coronary artery disease, North-American controls showed not statistically significant difference. Moreover, Italian controls displayed a microheterogeneity in the mutant allele frequency distribution depending on their geographical origin (North or South of Italy). Aim of our study was to evaluate the prevalence of the double in cis mutation in different populations. We studied 377 healthy subjects belonging to various human groups. Genomic DNA, extracted from peripheral blood samples, was amplified using specific primers; PCR fragments were digested with Bsr I restriction enzyme to detect the double mutation. Our data show a significant heterogeneity among the populations studied, therefore this mutation turned out to be a reliable anthropogenetic marker. The distribution of the double mutation will contribute, with other DNA polymorphisms, to evaluate the genetic admixture of mixed populations such as Afro-Americans. 相似文献
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1. The analgesic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is partly due to the fact that they act upon the periaqueductal gray matter (PAG) and the rostral ventromedial medulla of the brain stem and thus activate the descending pain-control system, which inhibits nociceptive transmission at the spinal dorsal horn.2. The analgesic action of dipyrone (metamizol) and of lysine-acetylsalicylate (LASA), two well-known NSAIDs, whether microinjected into the PAG or given systemically, can be reverted by naloxone. Repeated administration of dipyrone or LASA induces tolerance to their antinociceptive effect, with cross-tolerance to morphine, and a withdrawal syndrome upon naloxone administration. Dipyrone tolerance can be reverted by proglumide, a cholecystokinin antagonist.3. These findings reveal a close association between the central action of NSAIDs and endogenous opioids. 相似文献
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Puentes A García J Ocampo M Rodríguez L Vera R Curtidor H López R Suarez J Valbuena J Vanegas M Guzman F Tovar D Patarroyo ME 《Peptides》2003,24(7):1015-1023
This work determined Plasmodium falciparum merozoite surface protein-8 (MSP-8) regions specifically binding to membrane surface receptors on human erythrocytes. Five high activity binding peptides (HABPs), whose binding to erythrocytes became saturable and sensitive on being treated with neuraminidase and chymotrypsin were identified from the MSP-8 protein. Those amino acids directly involved in interaction with erythrocytes were also determined for each one of the HABPs. Some of them specifically recognized 28, 46, and 73 kDa erythrocyte membrane proteins. Some HABPs inhibited in vitro P. falciparum merozoite invasion of erythrocytes by up to 98%, suggesting the MSP-8 protein's possible role in the invasion process. 相似文献
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Magnolia Vanegas Adriana Bermúdez Yuly Andrea Guerrero Jesús Alfredo Cortes-Vecino Hernando Curtidor Manuel Elkin Patarroyo José Manuel Lozano 《Biochemical and biophysical research communications》2014
Developing novel generations of subunit-based antimalarial vaccines in the form of chemically-defined macromolecule systems for multiple antigen presentation represents a classical problem in the field of vaccine development. Many efforts involving synthesis strategies leading to macromolecule constructs have been based on dendrimer-like systems, the condensation of large building blocks and conventional asymmetric double dimer constructs, all based on lysine cores. 相似文献
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Carolina Vizcaíno Daniel Restrepo-Montoya Diana Rodríguez Luis F. Ni?o Marisol Ocampo Magnolia Vanegas María T. Reguero Nora L. Martínez Manuel E. Patarroyo Manuel A. Patarroyo 《PLoS computational biology》2010,6(6)
The mycobacterial cell envelope has been implicated in the pathogenicity of tuberculosis and therefore has been a prime target for the identification and characterization of surface proteins with potential application in drug and vaccine development. In this study, the genome of Mycobacterium tuberculosis H37Rv was screened using Machine Learning tools that included feature-based predictors, general localizers and transmembrane topology predictors to identify proteins that are potentially secreted to the surface of M. tuberculosis, or to the extracellular milieu through different secretory pathways. The subcellular localization of a set of 8 hypothetically secreted/surface candidate proteins was experimentally assessed by cellular fractionation and immunoelectron microscopy (IEM) to determine the reliability of the computational methodology proposed here, using 4 secreted/surface proteins with experimental confirmation as positive controls and 2 cytoplasmic proteins as negative controls. Subcellular fractionation and IEM studies provided evidence that the candidate proteins Rv0403c, Rv3630, Rv1022, Rv0835, Rv0361 and Rv0178 are secreted either to the mycobacterial surface or to the extracellular milieu. Surface localization was also confirmed for the positive controls, whereas negative controls were located on the cytoplasm. Based on statistical learning methods, we obtained computational subcellular localization predictions that were experimentally assessed and allowed us to construct a computational protocol with experimental support that allowed us to identify a new set of secreted/surface proteins as potential vaccine candidates. 相似文献
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Espejo F Bermúdez A Vanegas M Rivera Z Torres E Salazar LM Patarroyo ME 《Journal of structural biology》2005,150(3):245-258
Plasmodium falciparum malaria protein peptides were synthesised in the search for more effective routes for inducing a protective immune response against this deadly parasite and this information has been associated with such molecules' three-dimensional structure. These peptides had high red blood cell binding activity and their carboxy- and amino-terminal extremes were elongated for determining their immunogenic and protection-inducing activity against this disease in the Aotus monkey experimental model. 1H-NMR was used for analysing their three-dimensional structure; FAST ELISA, immunofluorescence antibody test, and Western blot were used for identifying their antibody inducing capacity and these previously immunised Aotus were inoculated with a highly infective P. falciparum strain to determine whether these elongated peptides were able to induce protection. This was aimed at establishing an association or correlation between long peptides' three-dimensional structure and their immunogenic and protection-inducing response in these monkeys. Peptides 20026 (25 residue), 20028 (30 residue), and 20030 (35 residues) were synthesised based on elongating the amino-terminal region of the 10022 highly immunogenic and protection-inducing modified peptide. 1H-NMR studies revealed that the first three had Classical type III beta-turn structures, different from the 20-amino acid long modified peptide 10022 which had a distorted type III beta-turn. Humoral immune response analysis showed that even when some antibodies could be generated against the parasite, none of the immunised Aotus could be protected with elongated peptides suggesting that elongating them eliminated modified peptide 10022 immunogenic and protection-inducing capacity. 相似文献
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Plasmodium falciparum multi-stage proteins are involved in vital processes for parasite survival, which turns them into attractive targets for studies aimed at developing a fully effective antimalarial vaccine. MCP-1 and PfSPATR are both found in sporozoite and merozoite forms, and have been associated respectively with invasion of hepatocytes and red blood cells (RBCs). Binding assays with synthetic peptides derived from these two important proteins have enabled identifying those sequences binding with high specific activity (named High activity binding peptides-HABPs) to hepatoma-derived HepG2 cells and human RBCs. Twelve RBC HABPs were identified within the MCP-1 amino acid sequence, most of them in the C-terminal region. The MCP-1 HABPs 33387 and 33397 also presented high activity binding to HepG2 cells. PfSPATR presented four RBC HABPs and two HepG2 HABPs, but only one (32686) could bind to both cell types. RBC binding assays evidenced that binding of all HABPs was saturable and differentially affected by the enzymatic treatment of target cells. Moreover, all HABPs inhibited in vitro invasion of merozoites at 200 microM and had particular structural features when analyzed by circular dichroism. The results suggest that these synthetic peptides capable of binding to the two P. falciparum target cells could be potentially included in the design of a multi-stage, subunit-based, chemically synthesized antimalarial vaccine. 相似文献