RESUMO
A newborn boy had meconium aspiration syndrome, hypospadias, a supernumerary digit on the left hand, hyperbilirubinemia, a fractured right clavicle, osteopenia, liver calcification, and mild pulmonary hyperplasia. Cytogenetic studies showed a chromosome 13 with additional material in 33% of the metaphases. The add(13) was considered to be a probable duplication of 13q12q22. The 13 paint probe hybridized to the add(13) from end to end. Fluorescence in situ hybridization (FISH) studies using retinoblastoma probe (RB)-1 that maps to 13q14 and D13S585 that maps to 13q32-q33 gave one signal for RB and three signals for D13S585. The pattern of the three signals from the 13q32q33 region and the G-banding pattern was best explained as a triplication of 13q22q33, with an inverted middle repeat resulting in tetrasomy for this segment. Mosaicism was confirmed by FISH using a D13S585 probe on a buccal smear. Three triplications detected in our laboratory were compared 13q22q33, 15q11q13, and 2q11.2q21. FISH was critical in identifying triplications 13q22q33 and 15q11q13. The hybridization pattern also indicated an inverted middle repeat. We conclude that intrachromosomal triplications may be more prevalent than previously assumed and they probably share a common mechanism in their formation. When the G-bands do not correspond exactly to a duplication or to a tandem triplication, an important consideration is that the majority of triplications have an inverted middle repeat. Triplications can be mistaken for duplications. Therefore, in assessing duplications, FISH confirmation is recommended.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos Par 13/genética , Análise Citogenética , Mosaicismo/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Aberrações Cromossômicas/diagnóstico , Bandeamento Cromossômico , Transtornos Cromossômicos , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 2/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Masculino , Gravidez , Diagnóstico Pré-NatalRESUMO
Increasing evidence indicates that cationic liposomes are capable of safely transferring foreign genes to pulmonary epithelium in vitro and in vivo. To transfer reporter genes and the cystic fibrosis transmembrane conductance regulator (CFTR) to mammalian respiratory epithelium we used two cationic lipid formulations: N-[1-(2,3-dioleoyloxy)propyl] N,N,N-triethylammonium chloride (DOTMA), and 1,2-dimyristyloxy-propyl-3-dimethylhydroxyethylammonium bromide (DMRIE) at a 1:1 molar ratio with dioleoyl phosphatidylethanolamine (DOPE). Lipid-DNA conjugates containing either CFTR or LacZ were instilled directly into the airways of Sprague-Dawley rats. Rats treated with LacZ cDNA in vivo demonstrated expression in 30-50% of the large and medium-sized airways, with some airways showing high efficiency gene transfer and expression (in the most proximal airways, 70-80% of surface epithelial cells were positive for expression of a nuclear targeted LacZ). While control and LacZ treated tracheas mounted in Ussing chambers showed minimal stimulation of transepithelial chloride (Cl)-currents by cAMP (suggesting low levels of endogenous rat CFTR activity), tracheas taken from animals receiving CFTR exhibited significant forskolin-stimulated currents at 72 h after gene transfer. Human CFTR gene expression was also detected by polymerase chain reaction (PCR) analysis of reverse transcribed lung RNA. These results, together with previous studies using lipid-mediated gene transfer in mice, help confirm the potential for cationic lipid-mediated gene transfer in the gene therapy of cystic fibrosis in humans.
Assuntos
Técnicas de Transferência de Genes , Terapia Genética/métodos , Lipídeos , Pulmão/metabolismo , Proteínas de Membrana/genética , Ácidos Mirísticos , Compostos de Amônio Quaternário , Animais , Sequência de Bases , Cloranfenicol O-Acetiltransferase/genética , Cloretos/metabolismo , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística , Epitélio/metabolismo , Expressão Gênica/genética , Genes Reporter/genética , Humanos , Óperon Lac/genética , Lipossomos , Proteínas de Membrana/biossíntese , Dados de Sequência Molecular , Fosfatidiletanolaminas , Coelhos , Ratos , Ratos Sprague-Dawley , Traqueia/metabolismoRESUMO
The interaction between tonic labyrinth or neck reflexes and the tonic vibration reflex acting on the medial head of triceps in the decerebrate cat is described. Medial triceps was isotonically loaded and reflex actions were measured as changes in muscle length. Natural stimulation of the receptors giving rise to tonic labyrinth or neck reflexes can either enhance or diminish the size of a pre-existing tonic vibration reflex. It is also shown that descending activity from either the labyrinth or neck reflex systems can completely suppress the tonic vibration reflex, whereas the tonic vibration reflex was never observed to suppress an established labyrinth or neck reflex.
