ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Males are at least four times more likely to develop autism than females. Among relatives with a broader autistic phenotype, males predominate too. Autism is a highly heritable disorder, yet genome scans have not revealed any predisposing loci on the sex chromosomes. A nongenetic explanation for male vulnerability, such as exposure to prenatal androgens, is unlikely for a variety of reasons. A novel genetic mechanism that resolves many of the outstanding difficulties is outlined here. The imprinted-X liability threshold model hypothesizes that the threshold for phenotypic expression of many autistic characteristics is influenced by an imprinted X-linked gene(s) that is protective in nature. Imprinted genes are known to play an important role in normal fetal and behavioral development. The gene is expressed only on the X-chromosome that is inherited from the father and raises the threshold for phenotypic expression. It is normally silenced when transmitted maternally. Because only females have a paternal X-chromosome, the threshold for phenotypic expression is higher in them than in males. Evidence for the existence of the genetic locus was found in a study of females with X-monosomy (Turner’s syndrome) in which females had either a single paternal or maternal X-chromosome. Identifying the sites of action of this X-linked gene could lead to the discovery of autosomal loci that confer more directly a predisposition to autism.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of cystinosis, is an autosomal recessive lysosomal storage disorder characterized by photophobia due to corneal cystine crystals but absence of renal disease. We determined the molecular basis for ocular cystinosis in four individuals. All had mutations in the cystinosis geneCTNS, indicating that ocular cystinosis is allelic with classic nephropathic cystinosis. The ocular cystinosis patients each had one severe mutation and one mild mutation, the latter consisting of either a 928 G→A (G197R) mutation or an IVS10–3 C→G splicing mutation resulting in the insertion of 182 bp of IVS10 into theCTNSmRNA. The mild mutations appear to allow for residualCTNSmRNA production, significant amounts of lysosomal cystine transport, and lower levels of cellular cystine compared with those in nephropathic cystinosis. The lack of kidney involvement in ocular cystinosis may be explained by two different mechanisms. On the one hand (e.g.the G197R mutation), significant residual cystinosin activity may be present in every tissue. On the other hand (e.g.the IVS10–3 C→G mutation), substantial cystinosin activity may exist in the kidney because of that tissue’s specific expression of factors that promote splicing of a normalCTNStranscript. Each of these mechanisms could result in minimally reduced lysosomal cystine transport in the kidneys.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited vascular disorder that is heterogeneous in terms of age of onset and clinical manifestations.Endoglinis the gene mutated in HHT1, which is associated with a higher prevalence of pulmonary arteriovenous malformations than HHT2, whereALK-1is the mutated gene. Endoglin is constitutively expressed on endothelial cells and inducible on peripheral blood activated monocytes so that protein levels can be measured by metabolic labeling and immunoprecipitation. We report the analysis of umbilical vein endothelial cells in 28 newborns from 24 families with a clinical diagnosis of HHT. Reduced levels of endoglin were observed in umbilical vein endothelial cells in 15/28 subjects and in activated monocytes of all clinically affected relatives tested, suggesting that these individuals had HHT1. No mutant protein was expressed at the cell surface in any of these cases, and a transient intracellular species was seen in samples of only two families, supporting a haploinsufficiency model. Quantitative multiplex PCR fragment analysis was established for theendoglingene and revealed six mutations that were confirmed by automated DNA sequencing. An additional 10 mutations were identified in newborns by sequencing all exons. Of the 16 mutations, 10 were novel, three had been independently identified in related families, and three were previously known. Our data confirm that endoglin levels correlate with the presence or absence of mutation in HHT1 families, allowing the early identification of affected newborns that should be screened clinically to avoid serious complications of this disorder, such as cerebral arteriovenous malformations.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

A prospective randomized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus. Infants were randomly assigned to three intravenous doses of either indomethacin (0.20–0.25 mg/kg, 12 hourly) or ibuprofen (5–10 mg/kg, 24 hourly) and also received a dose of saline. The primary end points of the study were the effects of the first dose on cerebral blood flow (CBF) and cerebral blood volume. Fifteen infants received indomethacin and 18 received ibuprofen. The group mean (SD) values for CBF (mL·100 g−1·min−1) before and after the first dose of indomethacin were 13.6 (4.1) and 8.3 (3.1), respectively, the change being significant (p< 0.001). In contrast, no significant changes in CBF were observed with the first dose of ibuprofen, the respective before and after values being 13.3 (3.2) and 14.9 (4.7) mL·100 g−1·min−1. The median (interquartile range) value for change in cerebral blood volume (mL/100 g) after the first dose in the indomethacin group was −0.4 (−0.3 to −0.6) and in the ibuprofen group was 0.0 (0.1 to −0.1), the difference between the two groups being significant (p< 0.001). Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group. Significant reductions in CBF, cerebral blood volume, and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin, but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen. The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78%, respectively. We conclude that ibuprofen, unlike indomethacin, has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The spectrum of clinical presentation of fatty acid oxidation defects (FAOD) continues to expand. One FAOD, L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been associated with liver disease in pregnancies involving a heterozygous mother carrying an affected fetus. Hepatic carnitine palmitoyltransferase (CPT I) deficiency typically presents as a Reye-like syndrome in children between 8 and 18 mo of age. We have investigated a family in which the mother developed liver disease consistent with acute fatty liver of pregnancy (AFLP) and hyperemesis gravidarum in her two successive pregnancies. Neither child nor their mother was found to carry the common LCHAD G1528C mutation. Both children were subsequently shown to have absent activity of CPT I. This is the first report of CPT I deficiency presenting as maternal illness in pregnancy.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID