Boston Children's Hospital

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 & Medicine. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.

Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty Liver Disease in Children and Adolescents: The TONIC Randomized Controlled Trial

Abstract: Context Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treatment has been established. Objective To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin. Design, Setting, and Patients Randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients (aged 8-17 years) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010. Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks. Main Outcome Measures The primary outcome was sustained reduction in alanine aminotransferase (ALT) defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures. Results Sustained reduction in ALT level was similar to placebo (10/58; 17%; 95% CI, 9% to 29%) in both the vitamin E (15/58; 26%; 95% CI, 15% to 39%; P = .26) and metformin treatment groups (9/57; 16%; 95% CI, 7% to 28%; P = .83). The mean change in ALT level from baseline to 96 weeks was −35.2 U/L (95% CI, −56.9 to −13.5) with placebo vs −48.3 U/L (95% CI, −66.8 to −29.8) with vitamin E (P = .07) and −41.7 U/L (95% CI, −62.9 to −20.5) with metformin (P = .40). The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo (95% CI, −0.2 to 0.3) vs −0.5 with vitamin E (95% CI, −0.8 to −0.3; P = .006) and −0.3 with metformin (95% CI, −0.6 to −0.0; P = .04); and in NAFLD activity score, −0.7 with placebo (95% CI, −1.3 to −0.2) vs −1.8 with vitamin E (95% CI, −2.4 to −1.2; P = .02) and −1.1 with metformin (95% CI, −1.7 to −0.5; P = .25). Among children with NASH, the proportion who resolved at 96 weeks was 28% with placebo (95% CI, 15% to 45%; 11/39) vs 58% with vitamin E (95% CI, 42% to 73%; 25/43; P = .006) and 41% with metformin (95% CI, 26% to 58%; 16/39; P = .23). Compared with placebo, neither therapy demonstrated significant improvements in other histological features. Conclusion Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD. Trial Registration clinicaltrials.gov Identifier: NCT00063635

Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n.

Abstract: The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)n. The sequence flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro.

The biology of nitrogen oxides in the airways.

Abstract: Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung. The relationship between the toxicities and the bioactivities of NOx must be understood in the context of their chemical interactions in the pulmonary microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system active in airway epithelial cells, macrophages, neutrophils, mast cells, autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells. The chemical products of NOS in the lung vary with disease states, and are involved in pulmonary neurotransmission, host defense, and airway and vascular smooth muscle relaxation. Further, certain patients with pulmonary hypertension, adult respiratory distress syndrome and asthma may experience physiologic improvement with NOx therapy, including inhalation of nitric oxide (NO.) gas. Both endogenous and exogenous NOx react readily with oxygen, superoxide, water, nucl...

Development of definitive endoderm from embryonic stem cells in culture

Abstract: The cellular and molecular events regulating the induction and tissue-specific differentiation of endoderm are central to our understanding of the development and function of many organ systems. To define and characterize key components in this process, we have investigated the potential of embryonic stem (ES) cells to generate endoderm following their differentiation to embryoid bodies (EBs) in culture. We found that endoderm can be induced in EBs, either by limited exposure to serum or by culturing in the presence of activin A (activin) under serum-free conditions. By using an ES cell line with the green fluorescent protein (GFP) cDNA targeted to the brachyury locus, we demonstrate that endoderm develops from a brachyury(+) population that also displays mesoderm potential. Transplantation of cells generated from activin-induced brachyury(+) cells to the kidney capsule of recipient mice resulted in the development of endoderm-derived structures. These findings demonstrate that ES cells can generate endoderm in culture and, as such, establish this differentiation system as a unique murine model for studying the development and specification of this germ layer.