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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
19 Jul 2001-Nature
TL;DR: Investigation of mother–child transmission in the setting of HLA-B27 expression suggests that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.
Abstract: Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.

566 citations

Journal ArticleDOI
30 Nov 2018-Science
TL;DR: Caspase-8 acts as a regulator of GSDMD-driven cell death and contributes to the NLRP3 inflammasome–dependent release of interleukin-1 β (IL-1β) and IL-18, establishing the importance of TAK1 and IKK activity in the control of G SDMD cleavage and cytotoxicity.
Abstract: Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8-dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome-dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.

566 citations

Journal ArticleDOI
TL;DR: A bioinspired, omniphobic coating is applied to tubing and catheters and it is shown that it completely repels blood and suppresses biofilm formation, which could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.
Abstract: Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.

565 citations

Journal ArticleDOI
TL;DR: Moderate or severe LV or RV systolic dysfunction, but not PR fraction or RV diastolic dimensions, is independently associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair.

565 citations

Journal ArticleDOI
TL;DR: The paracrine actions of a variety of polypeptide growth factors appear to be orchestrated in a complex sequence of steps that lead to the development of the adult vascular system.
Abstract: The vascular system forms through a combination of vasculogenesis and angiogenesis. In vasculogenesis, vessels form de novo via the assembly of endothelial precursors called angioblasts, whereas in angiogenesis new vessels arise by migration and proliferation of endothelial cells from preexisting vessels. Although the two processes are distinct in some respects, recent evidence suggests that they share a number of regulatory mechanisms. The identification of a number of defined growth factors, observations of genetically manipulated mice, and the recognition of the importance of cell-cell interactions have greatly expanded our understanding of the regulation of vascularization. The paracrine actions of a variety of polypeptide growth factors, including platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-beta, and the angiopoietins, appear to be orchestrated in a complex sequence of steps that lead to the development of the adult vascular system. Thus, communicati...

565 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