RESUMO
Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function caused by derangements in CD18 expression. The genetic and functional abnormalities in a lymphocyte cell line from a patient with LAD have been corrected by retrovirus-mediated transduction of a functional CD18 gene. Lymphocytes from patients with LAD were exposed to CD18-expressing retrovirus and enriched for cells that express CD11a and CD18 (LFA-1) on the cell surface. Molecular and functional analyses of these cells revealed (i) one copy of proviral sequence per cell, (ii) viral-directed CD18 RNA that exceeded normal endogenous levels, (iii) normal quantities of CD11a and CD18 protein on the cell surface, and (iv) reconstitution of LFA-1-dependent adhesive function.
Assuntos
Síndrome da Aderência Leucocítica Deficitária , Retroviridae/genética , Transfecção , Animais , Antígenos CD , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/imunologia , Antígenos CD18 , Agregação Celular , Linhagem Celular , Linhagem Celular Transformada , Expressão Gênica , Terapia Genética , Vetores Genéticos , Herpesvirus Humano 4 , Humanos , Antígeno-1 Associado à Função Linfocitária , Linfócitos/imunologia , Glicoproteínas de Membrana , Camundongos , Hibridização de Ácido Nucleico , Receptores de Adesão de Leucócito/genética , Receptores de Adesão de Leucócito/imunologia , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
OBJECTIVE: To investigate anecdotal reports that portal vein gas in necrotizing enterocolitis is no longer associated with a poor prognosis. PATIENTS AND METHODS: Twelve cases of neonatal necrotizing enterocolitis with portal vein gas from 1988 to 1994 were identified retrospectively from the radiology dictation system in a large university hospital. RESULTS: Two distinct groups of patients with portal vein gas in necrotizing enterocolitis were identified. In 3 of the 12 children, portal vein gas was identified on abdominal films after the diagnosis of necrotizing enterocolitis. These infants had no serious sequelae. By contrast, in 8 of the 9 infants with portal vein gas seen on the initial film at presentation, emergent surgery was required. Four of these infants died from complications of necrotizing enterocolitis and 2 died from sepsis related to total parenteral nutrition. The remaining 2 children have short bowel syndrome, 1 is dependent on total parenteral nutrition and 1 requires continuous gastrostomy tube feedings. CONCLUSION: The children with portal vein gas on the initial abdominal film continue to have a guarded prognosis.
Assuntos
Enterocolite Pseudomembranosa/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Feminino , Gases , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Radiografia Abdominal , Estudos RetrospectivosRESUMO
Genomic imprinting, or parental allele-specific expression of genes, has been demonstrated at the molecular level in insects and mice but not in man. Imprinting as a potential mechanism of human disease is suggested by paternal uniparental disomy of 11p15 in Beckwith-Wiedemann syndrome and by maternal uniparental disomy of 15q11-12 in Prader-Willi syndrome. Beckwith-Wiedemann syndrome is characterized by multiorgan overgrowth and predisposition to embryonal tumours such as Wilms' tumour of the kidney. A loss of heterozygosity of 11p15 is also frequently found in a wide variety of tumours, including Wilms' tumour and lung, bladder, ovarian, liver and breast cancers; 11p15 also directly suppresses tumour growth in vitro. Two genes in this band, H19 and insulin-like growth factor-II (IGF2) undergo reciprocal imprinting in the mouse, with maternal expression of H19 (ref. 13) and paternal expression of IGF2 (ref. 14). Here we find that both of these genes show monoallelic expression in human tissues and, as in mouse, H19 is expressed from the maternal allele and IGF2 from the paternal allele. In contrast, 69% of Wilms' tumours not undergoing loss of heterozygosity at 11p showed biallelic expression of one or both genes, suggesting that relaxation or loss of imprinting could represent a new epigenetic mutational mechanism in carcinogenesis.
Assuntos
Neoplasias/genética , Alelos , Sequência de Bases , DNA de Cadeia Simples , Mecanismo Genético de Compensação de Dose , Pai , Feminino , Feto , Humanos , Fator de Crescimento Insulin-Like II/genética , Neoplasias Renais/genética , Masculino , Dados de Sequência Molecular , Mães , Linhagem , Tumor de Wilms/genéticaRESUMO
Beckwith-Wiedemann syndrome (BWS), characterized by multiorgan developmental abnormalities and predisposition to cancer, usually occurs sporadically, but small apparently dominant pedigrees have been described. Since rare patients show varying karyotypic abnormalities on the short arm of chromosome 11, it has been suggested that BWS may be related to the Wilms tumor gene on 11p13 or, alternatively, to growth factor genes on 11p15. We performed genetic linkage analysis on two BWS kindreds, using RFLPs for loci on 11p. BWS was linked to the insulin gene (11p15.5), with an overall maximum lod score of 3.60 (recombination fraction = .00). Linkage to D11S16 (11p13) could be excluded for recombination fractions less than or equal to .03. These results suggest that BWS defines a tumor-predisposition gene on 11p15.