RESUMO
Las causas de distrés respiratorio en el neonato son muy diversas: hay factores nutricionales e inflamatorios y trastornos del desarrollo embrionario que pueden contribuir al problema; pero en los últimos años ha cobrado importancia la consideración de los factores genéticos de riesgo. Entre las causas genéticas de distrés respiratorio, la mejor documentada es el déficit hereditario de la proteína del surfactante pulmonar SPB, que da lugar a un fracaso respiratorio agudo, crónico y potencialmente irreversible. La disponibilidad de marcadores genéticos de utilidad clínica para evaluar el riesgo de distrés respiratorio en el neonato permitirá el desarrollo de estrategias racionales para el tratamiento pulmonar y la posibilidad de ofrecer consejo genético a las familias de riesgo (AU)
Assuntos
Feminino , Masculino , Humanos , Recém-Nascido , Doenças Respiratórias/genética , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/terapia , Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/uso terapêutico , Fatores de Risco , Pulmão/patologia , Marcadores Genéticos/imunologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/uso terapêutico , Biologia Molecular/métodos , Biologia Molecular/tendências , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Ensaio de Imunoadsorção Enzimática/métodos , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da PolimeraseRESUMO
La esclerosis múltiple (EM) es una enfermedad que suele presentarse en la edad adulta, aunque algunos casos pueden debutar en la infancia. En niños, esta entidad resulta de especial interés por varias razones: en primer lugar, es relativamente infrecuente; en segundo lugar, los datos clínicos y los hallazgos de laboratorio son a menudo diferentes de los que se observan en la población adulta, y por último, dada la dificultad de la evaluación clínica, sobre todo en la edad preescolar, es muy importante la integración de todas las determinaciones paraclínicas para obtener un diagnóstico diferencial precoz y para el correcto tratamiento del paciente pediátrico (AU)
Assuntos
Feminino , Masculino , Criança , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Diagnóstico Diferencial , Espectroscopia de Ressonância MagnéticaRESUMO
A Tn5 insertion decreasing the production of microcin B17 was mapped to 50.2 min on the Escherichia coli chromosome map. Sequence analysis showed that the insertion disrupted hisT, the gene encoding pseudouridine synthase I, a tRNA-modifying enzyme. hisT::Tn5 mutant cells were also shown to be defective for the production of other antibiotic peptides, such as microcin C7, microcin H47, and colicin V.
Assuntos
Bacteriocinas/biossíntese , Colicinas/biossíntese , Elementos de DNA Transponíveis , Transferases Intramoleculares , Isomerases/genética , Mutação , Sequência de Aminoácidos , Sequência de Bases , DNA Bacteriano , Dados de Sequência Molecular , Mapeamento por RestriçãoRESUMO
Bacterial DNA gyrases are type II topoisomerases made up of two A subunits and two B subunits. Coumarins are carbohydrate-containing antibiotics that inhibit topoisomerases II by competing with ATP for binding to the enzymes. High resistance to coumarins is produced in bacterial species by mutations in gyrB, the gene encoding subunit B. We have found an unusual mechanism of resistance to coumarins in Escherichia coli. This mechanism is exhibited by cells containing the wild-type gyrB, or its 5' half, in high copy number. Since homologous mutant gyrB (coumermycin resistant) truncated genes did not confer drug resistance at all under the same conditions, we propose that this mechanism of resistance is due to drug sequestration by the overproduced wild-type GyrB polypeptides. A corollary of this is that the amino half of GyrB is required and sufficient to fashion the ATP-binding domain of DNA gyrase, a conclusion that was further supported by mapping three independent coumarin-resistant mutations at Arg-136 of GyrB. Just upstream of this residue there is a glycine-rich sequence highly conserved in all topoisomerases II, which seems to be a good candidate for the actual ATP-binding site.
Assuntos
DNA Topoisomerases Tipo II/fisiologia , Resistência Microbiana a Medicamentos , Escherichia coli/efeitos dos fármacos , Sequência de Aminoácidos , Aminocumarinas , Clonagem Molecular , Códon , Cumarínicos/farmacologia , Análise Mutacional de DNA , DNA Bacteriano/genética , Expressão Gênica , Genes Bacterianos , Dados de Sequência Molecular , Plasmídeos , Mapeamento por RestriçãoRESUMO
Microcin B17 (MccB17) is a peptide antibiotic produced by Escherichia coli strains harbouring plasmid pMccB17. We have isolated two mutations that strongly reduce the production of MccB17. These mutations, which map at 96 min on the E. coli chromosome, define a new gene that we have called pmbA. A chromosomal DNA fragment of about 13 kb, including the wild-type pmbA allele, was cloned into a mini-Mu plasmid vector. pmbA was located within the cloned DNA fragment by insertional mutagenesis and deletion analysis. The nucleotide sequence of a 1.7 kb DNA region containing the gene was determined. pmbA encodes a hydrophilic protein of 450-amino-acid residues with a predicted molecular size of 48375D, which was visualized in polyacrylamide gels. Protein profiles of cellular envelope and soluble fractions from cells with plasmids overproducing PmbA indicated that it is cytoplasmic. Physiological experiments suggested that pmbA mutants synthesize a molecule (pro-MccB17) able to inhibit DNA replication but unable to be released from cells. We propose that PmbA facilitates the secretion of the antibiotic by completing its maturation.
