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Biomedical subjects

T Menéndez

Publications and source records attributed to T Menéndez.

10 recordsLinked to original sources

Memory immune response generated in Cercopithecus aethiops against meningococcal polysaccharide serogroup C conjugate vaccine.

The chemical conjugation of bacterial polysaccharide to carrier proteins has proved to be an efficient tool to improve the immunological response against these bacterial antigens. In this study, we characterized the antibody response generated in a non-human primate model against the meningococcal capsular polysaccharide serogroup C (CCPS) conjugated to the P64k protein. Similar to licensed vaccines the CCPS conjugate is able to generate a good memory immune response with antibody titers threefold higher than the free CCPS. Three different ELISA protocols were used to measure the antibody response and the importance of the coating antigen was demonstrated. The ELISA using the derivatized CCPS showed the best results and had a high correlation with the bactericidal activity. The antibodies elicited showed a high protective capacity when assayed in the infant rat protection model.

Animals↗

Immunisation with phage-displayed variable region 2 from meningococcal PorA outer membrane protein induces bactericidal antibodies against Neisseria meningitidis.

The immunogenicity and functional activity of antibodies raised in mice against the cyclic disulphide peptide corresponding to the variable region 2 of PorA outer membrane protein from Neisseria meningitidis strain B385 (serosubtype P1.15), displayed on filamentous phage, were evaluated. The epitope, flanked either by cysteine or cysteine and three glycine residues, was expressed as a fusion to PVIII protein from M13. Immunisation of Balb/C mice with either phage generated antibody specific responses. Sera raised against the phage exposing the cyclic peptide through the three-glycine linker recognised the native protein better than those raised against the peptide with no linker. Only the phage displaying the cyclic peptide with linker was capable of inducing antibodies with bactericidal activity. These results indicate the possibility of using phage display for conformational peptide expression for immunisation to elicit functional antibody responses.

Adjuvants, Immunologic↗

Recombinant Opc protein from Neisseria meningitidis reconstituted into liposomes elicits opsonic antibodies following immunization.

The reconstitution of recombinant bacterial outer membrane proteins (OMPs) into their native conformations after purification has been the major problem in their use as effective vaccines. Liposomes have been shown to be an attractive approach, providing a native-like environment for these antigens. The meningococcal recombinant Opc (rOpc) protein, produced as inclusion bodies in Escherichia coli, was incorporated into phospholipid vesicles consisting of dipalmitoyl phosphatidylcholine and cholesterol. The incorporation of rOpc into the lipid bilayer was demonstrated, and the reconstitution of some native epitopes was tested using a set of monoclonal antibodies. Subcutaneous immunization of Balb/c mice with rOpc-containing vesicles resulted in the generation of a high level of specific antibodies. The elicited antibodies reacted with the native meningococcal protein and showed opsonic activity.

1,2-Dipalmitoylphosphatidylcholine↗

Fetal sinus bradycardia and the long QT syndrome.

OBJECTIVE: Recent evidence in literature shows that the long QT syndrome accounts for a fraction of the sudden infant death syndrome. Newborn infants with prolongation of the Q-T interval often show sinus bradycardia, which led us to test whether children who were diagnosed with long QT syndrome also show sinus bradycardia in the cardiotocogram before birth. STUDY DESIGN: We identified 18 children who were born from singleton pregnancies at or near term in whom long QT syndrome (corrected QT interval, >0.440 second) was diagnosed after birth or in childhood. Cardiograms during pregnancy and delivery were available from 17 of the 18 children. RESULTS: The cardiotocogram showed persistent fetal sinus bradycardia (baseline heart rate permanently below 120 beats/min) in 12 of 17 fetuses (71%) with long QT syndrome. Two fetuses had additional intermittent tachyarrhythmias. CONCLUSION: Sinus bradycardia in the cardiotocogram during delivery or in pregnancy may indicate long QT syndrome in the fetus. Postnatal electrocardiography should be performed in these children to rule out or confirm a prolongation of the Q-T interval.

Arrhythmia, Sinus↗

Prenatal diagnosis of QT prolongation by magnetocardiography.

Magnetocardiography constitutes a new tool for monitoring fetal cardiac activity. The fetal magnetocardiogram (FMCG) recorded noninvasively over the maternal abdomen is detectable with high temporal resolution and permits analysis of all parts of the PQRST waveform. In this way measurements of cardiac time intervals, including the QT interval, become possible. The following article constitutes the first report of antenatal detection of QT prolongation in two fetuses by FMCG.

Adult↗

Characterisation of the lpdA gene from Neisseria meningitidis by polymerase chain reaction, restriction fragment length polymorphism and sequencing.

P64k protein from Neisseria meningitidis is well recognised in sera from individuals convalescent from meningococcal disease or vaccinated with the Cuban antimeningococcal vaccine VA-MENGOC-BC. The presence of the protein in more than 80 meningococcal strains has also been verified. It is immunogenic in animal models and the antibodies elicited show bactericidal activity against meningococci. To further investigate at the molecular level whether lpdA, the gene coding for P64k protein, is conserved among different N. meningitidis strains, a total of 20 strains isolated from different geographic areas were differentiated on the basis of restriction fragment length polymorphism (RFLP) patterns after polymerase chain reaction (PCR) amplification of the lpdA gene and restriction endonuclease digestion with HpaII. Although a total of five different PCR-RFLP patterns were present, nucleotide sequence determination showed that identity levels were as high as 93-99% among the N. meningitidis strains analysed.

Amino Acid Sequence↗

Antigenic and genetic characterization of a putative hybrid transferrin-binding protein B from Neisseria meningitidis.

The transferrin-binding protein Bs (TbpBs) from the bacterium Neisseria meningitidis have been divided into two families according to genetic and antigenic features. TbpB from meningococcal strain B385 showed a molecular mass similar to that exhibited by TbpBs belonging to the high molecular mass family of TbpBs. TbpB was recognized by immunoassay using a specific serum directed against the TbpB of the reference strain for this family (strain M982). It was also recognized by a serum elicited against the TbpB of the reference strain for the low molecular mass family (strain B16B6). The tbpB gene from strain B385 was cloned and sequenced. The highest degree of sequence homology was found to be with the TbpBs belonging to the high molecular mass family, although a region of 14 amino acids that is only present in the TbpB from strain B16B6 was also found. This report illustrates a TbpB that shows hybrid antigenic and genetic behaviour.

Amino Acid Sequence↗

[Prenatal recording of fetal heart action with magnetocardiography].

Fetal magnetocardiography (fMCG) registers the magnetic field generated by the fetal heart. In contrast to the fetal electrocardiogram, fECG permits non-invasive registration of fetal heart activity and documentation of all parts of the PQRST-wave-forms from the second trimenon onwards. This facilitates the determination of cardiac time intervals and establishment of reference values for different stages of pregnancy. We examined 53 women in 104 recordings from the 10th week of gestation onwards (1 to 10 recordings per individual). The fMCG (37 magnetic channels, sampling rate 1024 Hz, bandwidth 1-200 Hz) was recorded non-invasively over the mother's abdomen in a magnetically shielded room. Registration of fetal heart beats was generally successful from the 20/21th week of gestation onwards. In a few cases, fetal heart beats could be registered as early as in the 16th week. Cardiac time intervals and amplitudes of fMCG increased concordantly with fetal growth. Mean P wave duration increased from 31 to 49 ms (p < 0.05), PQ interval from 95 to 107 ms (n.s.) and QRS duration from 36 to 52 ms (p < 0.01). The mean amplitudes of the P and R waves also increased. FMCG, furthermore permits a prenatal diagnosis of fetal cardiac arrhythmias. We recorded fetal arrhythmias in 20 cases (26-38th week), including episodes of ventricular and supraventricular arrhythmias or atrioventricular blockings. Due to its high resolution, fMCG offers new information on the development of fetal cardiac activity which cannot be achieved by conventional methods like cardiotocography or dopplerultrasound. Therefore, fMCG could become a new diagnostic instrument for monitoring fetal wellbeing during pregnancy.

Adult↗