Institution
Children's Hospital Oakland Research Institute
About: Children's Hospital Oakland Research Institute is a based out in . It is known for research contribution in the topics: Population & Human leukocyte antigen. The organization has 1568 authors who have published 2480 publications receiving 203418 citations.
Topics: Population, Human leukocyte antigen, Haplotype, Gene, Cholesterol
Papers published on a yearly basis
Papers
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TL;DR: These data support a novel mechanism of disease in which hemolysis contributes to reduced nitric oxide bioavailability and endothelial dysfunction via release of erythrocyte arginase, which limits arginine bioavailability, and release of ______ hemoglobin, which scavengesNitric oxide.
Abstract: ContextSickle cell disease is characterized by a state of nitric oxide resistance
and limited bioavailability of L-arginine, the substrate for
nitric oxide synthesis. We hypothesized that increased arginase activity and
dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary
hypertension, and patient outcomes.ObjectiveTo explore the role of arginase in sickle cell disease pathogenesis,
pulmonary hypertension, and mortality.DesignPlasma amino acid levels, plasma and erythrocyte arginase activities,
and pulmonary hypertension status as measured by Doppler echocardiogram were
prospectively obtained in outpatients with sickle cell disease. Patients were
followed up for survival up to 49 months.SettingUrban tertiary care center and community clinics in the United States
between February 2001 and March 2005.ParticipantsTwo hundred twenty-eight patients with sickle cell disease, aged 18
to 74 years, and 36 control participants.Main Outcome MeasuresPlasma amino acid levels, plasma and erythrocyte arginase activities,
diagnosis of pulmonary hypertension, and mortality.ResultsPlasma arginase activity was significantly elevated in patients with
sickle cell disease, with highest activity found in patients with secondary
pulmonary hypertension. Arginase activity correlated with the arginine-ornithine
ratio, and lower ratios were associated with greater severity of pulmonary
hypertension and with mortality in this population (risk ratio, 2.5; 95% confidence
interval [CI], 1.2-5.2; P = .006). Global
arginine bioavailability, characterized by the ratio of arginine to ornithine
plus citrulline, was also strongly associated with mortality (risk ratio,
3.6; 95% CI, 1.5-8.3; P<.001). Increased plasma
arginase activity was correlated with increased intravascular hemolytic rate
and, to a lesser extent, with markers of inflammation and soluble adhesion
molecule levels.ConclusionsThese data support a novel mechanism of disease in which hemolysis contributes
to reduced nitric oxide bioavailability and endothelial dysfunction via release
of erythrocyte arginase, which limits arginine bioavailability, and release
of erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine
to ornithine and arginine to ornithine plus citrulline are independently associated
with pulmonary hypertension and increased mortality in patients with sickle
cell disease.
652 citations
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Cincinnati Children's Hospital Medical Center1, Texas Scottish Rite Hospital for Children2, University of Alabama3, Children's Hospital Oakland Research Institute4, Heidelberg University5, University of Chicago6, University of California, Los Angeles7, University of Rome Tor Vergata8, University of Cape Town9, National Institutes of Health10, Novartis11
TL;DR: These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis and suggest it might represent a disease-modifying treatment for other aspects of tuberousclerosis.
650 citations
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TL;DR: The generation and analysis of over 12 megabases of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region.
Abstract: The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.
634 citations
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Virginia Mason Medical Center1, University of Konstanz2, Ontario Institute for Cancer Research3, University of Oxford4, Michigan State University5, University of Utah6, Hofstra University7, The Feinstein Institute for Medical Research8, Marine Biological Laboratory9, Icahn School of Medicine at Mount Sinai10, Stowers Institute for Medical Research11, University of Kansas12, University of New Hampshire13, University of Washington14, University of Toronto15, Emory University16, Harvard University17, Medical Research Council18, Wellcome Trust Sanger Institute19, California Institute of Technology20, University of Oklahoma21, Kalamazoo College22, University of Maryland, Baltimore23, University of Iowa24, Children's Hospital Oakland Research Institute25, Washington University in St. Louis26
TL;DR: Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages, and help define key evolutionary events within vertebrate lineages.
Abstract: Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.
596 citations
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TL;DR: In this article, the authors identify large variants in ∼2500 individuals by using Illumina SNP data, with an emphasis on “hotspots” prone to recurrent mutations, and find variants larger than 500 kb in 5%−10% of individuals and variants greater than 1 Mb in 1%−2%.
Abstract: Copy number variants (CNVs) contribute to human genetic and phenotypic diversity. However, the distribution of larger CNVs in the general population remains largely unexplored. We identify large variants in ∼2500 individuals by using Illumina SNP data, with an emphasis on “hotspots” prone to recurrent mutations. We find variants larger than 500 kb in 5%–10% of individuals and variants greater than 1 Mb in 1%–2%. In contrast to previous studies, we find limited evidence for stratification of CNVs in geographically distinct human populations. Importantly, our sample size permits a robust distinction between truly rare and polymorphic but low-frequency copy number variation. We find that a significant fraction of individual CNVs larger than 100 kb are rare and that both gene density and size are strongly anticorrelated with allele frequency. Thus, although large CNVs commonly exist in normal individuals, which suggests that size alone can not be used as a predictor of pathogenicity, such variation is generally deleterious. Considering these observations, we combine our data with published CNVs from more than 12,000 individuals contrasting control and neurological disease collections. This analysis identifies known disease loci and highlights additional CNVs (e.g., 3q29, 16p12, and 15q25.2) for further investigation. This study provides one of the first analyses of large, rare (0.1%–1%) CNVs in the general population, with insights relevant to future analyses of genetic disease.
585 citations
Authors
Showing all 1568 results
Name | H-index | Papers | Citations |
---|---|---|---|
Frank B. Hu | 250 | 1675 | 253464 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Bruce N. Ames | 158 | 506 | 129010 |
Rino Rappuoli | 132 | 816 | 64660 |
Robert S. Schwartz | 130 | 923 | 62624 |
Carlos López-Otín | 126 | 494 | 83933 |
Ronald M. Krauss | 120 | 438 | 77969 |
Robert S. Stern | 120 | 761 | 62834 |
Joan S. Brugge | 115 | 286 | 47965 |
Ewan Birney | 114 | 308 | 125382 |
Keith M. Sullivan | 105 | 447 | 39067 |
Bo Lönnerdal | 99 | 674 | 36297 |
Dennis E. Discher | 98 | 372 | 60060 |
Richard Reinhardt | 94 | 370 | 58076 |
Henry A. Erlich | 93 | 354 | 40295 |