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Institution

Boston Children's Hospital

HealthcareBoston, Massachusetts, United States
About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.


Papers
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Journal ArticleDOI
TL;DR: The reduced severity of disease in patients without defined mutations suggests that many of these patients are mosaic for a TSC2 mutation and/or have TSC because of mutations in an as-yet-unidentified locus with a relatively mild clinical phenotype.
Abstract: Tuberous sclerosis (TSC) is a relatively common hamartoma syndrome caused by mutations in either of two genes, TSC1 and TSC2. Here we report comprehensive mutation analysis in 224 index patients with TSC and correlate mutation findings with clinical features. Denaturing high-performance liquid chromatography, long-range polymerase chain reaction (PCR), and quantitative PCR were used for mutation detection. Mutations were identified in 186 (83%) of 224 of cases, comprising 138 small TSC2 mutations, 20 large TSC2 mutations, and 28 small TSC1 mutations. A standardized clinical assessment instrument covering 16 TSC manifestations was used. Sporadic patients with TSC1 mutations had, on average, milder disease in comparison with patients with TSC2 mutations, despite being of similar age. They had a lower frequency of seizures and moderate-to-severe mental retardation, fewer subependymal nodules and cortical tubers, less-severe kidney involvement, no retinal hamartomas, and less-severe facial angiofibroma. Patients in whom no mutation was found also had disease that was milder, on average, than that in patients with TSC2 mutations and was somewhat distinct from patients with TSC1 mutations. Although there was overlap in the spectrum of many clinical features of patients with TSC1 versus TSC2 mutations, some features (grade 2–4 kidney cysts or angiomyolipomas, forehead plaques, retinal hamartomas, and liver angiomyolipomas) were very rare or not seen at all in TSC1 patients. Thus both germline and somatic mutations appear to be less common in TSC1 than in TSC2. The reduced severity of disease in patients without defined mutations suggests that many of these patients are mosaic for a TSC2 mutation and/or have TSC because of mutations in an as-yet-unidentified locus with a relatively mild clinical phenotype.

835 citations

Journal ArticleDOI
19 Oct 2006-Neuron
TL;DR: It is shown that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism, which controls the ability of Me CP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription.

835 citations

Journal ArticleDOI
TL;DR: Based on gene cloning, recombinant expression, mutagenesis studies, structural analysis of crystals and NMR studies, reaction mechanisms for the biosynthetic and recycling enzymes were proposed, and BH(4) deficiency due to autosomal recessive mutations in all enzymes (except sepiapterin reductase) have been described as a cause of hyperphenylalaninaemia.
Abstract: Tetrahydrobiopterin (BH % ) cofactor is essential for various processes, and is present in probably every cell or tissue of higher organisms. BH % is required for various enzyme activities, and for less defined functions at the cellular level. The pathway for the de noao biosynthesis of BH % from GTP involves GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase and sepiapterin reductase. Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and dihydropteridine reductase. Based on gene cloning, recombinant expression, mutagenesis studies, structural analysis of crystals and NMR studies, reaction mechanisms for the biosynthetic and recycling enzymes were proposed. With regard to the regulation of cofactor biosynthesis, the major controlling point is GTP cyclohydrolase I, the expression of which may be under the control of cytokine induction. In the liver at least, activity is inhibited by BH % , but stimulated by phenylalanine through the GTP cyclohydrolase I feedback regulatory protein. The enzymes that depend on BH % are the phenylalanine, tyrosine and tryptophan hydroxylases, the latter

835 citations

Journal ArticleDOI
TL;DR: It is illustrated how a better understanding of the mechanisms of effect by which poverty impacts children's mental, emotional, and behavioral health is valuable in designing effective preventive interventions for those in poverty.
Abstract: This article considers the implications for prevention science of recent advances in research on family poverty and children's mental, emotional, and behavioral health. First, we describe definitions of poverty and the conceptual and empirical challenges to estimating the causal effects of poverty on children's mental, emotional, and behavioral health. Second, we offer a conceptual framework that incorporates selection processes that affect who becomes poor as well as mechanisms through which poverty appears to influence child and youth mental health. Third, we use this conceptual framework to selectively review the growing literatures on the mechanisms through which family poverty influences the mental, emotional, and behavioral health of children. We illustrate how a better understanding of the mechanisms of effect by which poverty impacts children's mental, emotional, and behavioral health is valuable in designing effective preventive interventions for those in poverty. Fourth, we describe strategies to directly reduce poverty and the implications of these strategies for prevention. This article is one of three in a special section (see also Biglan, Flay, Embry, & Sandler, 2012; Munoz, Beardslee, & Leykin, 2012) representing an elaboration on a theme for prevention science developed by the 2009 report of the National Research Council and Institute of Medicine.

832 citations

Journal ArticleDOI
TL;DR: Grafted NSCs were genetically modified to produce neurotrophin-3, which significantly expanded NSC effects on host axons and confirmed that grafted stem cells expressed neurotrophic factor genes in vivo.

832 citations


Authors

Showing all 165661 results

NameH-indexPapersCitations
Walter C. Willett3342399413322
Frederick E. Shelton3271485295883
Robert Langer2812324326306
Graham A. Colditz2611542256034
Frank B. Hu2501675253464
George M. Whitesides2401739269833
Eugene Braunwald2301711264576
Ralph B. D'Agostino2261287229636
Mark J. Daly204763304452
Eric B. Rimm196988147119
Virginia M.-Y. Lee194993148820
Bernard Rosner1901162147661
Stuart H. Orkin186715112182
Mark Hallett1861170123741
Ralph Weissleder1841160142508
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202380
2022442
202119,543
202016,558
201913,868
201812,020