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: An overview of the process to establish consensus definitions of the most frequently occurring complications of Sickle Cell Disease is provided and use of these definitions will support greater accuracy in genotype–phenotype studies, thereby achieving a better understanding of SCD pathophysiology.
Abstract: Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype-phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed.
346 citations
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TL;DR: De novo hepatic lipogenesis is a quantitatively minor pathway, consistent with gas exchange estimates; fatty acid futile cycling (oxidation/resynthesis) is not thermogenically significant; and synthesis rates of different nonessential fatty acids by human liver are not identical in nonoverfed normal men.
Abstract: Direct measurement of de novo lipogenesis has not previously been possible in humans. We measured de novo hepatic lipogenesis in normal men by means of stable isotopes and by combining the acetylated-xenobiotic probe technique with mass isotopomer analysis of secreted very low density lipoprotein-fatty acids (VLDL-FA). Sulfamethoxazole (SMX) was administered with [13C]acetate during an overnight fast followed by refeeding with intravenous glucose (7-10 mg/kg of weight per min), oral Ensure (7-10 mg of carbohydrate/kg of weight per min), or a high-carbohydrate mixed-meal breakfast (3.5 g of carbohydrate/kg of weight). Respiratory quotients remained less than 1.0. High-performance liquid chromatography/mass spectrometry-determined enrichments in SMX-acetate attained stable plateau values, and hepatic acetyl-coenzyme A (CoA) dilution rate did not increase with refeeding (approximately 0.024 mmol/kg per min). The fraction of VLDL-palmitate derived from de novo lipogenesis was only 0.91 +/- 0.27% (fasted) and 1.64-1.97% (fed). For stearate, this was 0.37 +/- 0.08% and 0.47-0.64%. Precursor enrichments predicted from isotopomer ratios were close to measured SMX-acetate enrichments, indicating that SMX-acetate samples the true lipogenic acetyl-CoA pool. Stearate synthesis was less than palmitate and the two did not move in parallel. Estimated total VLDL-FA synthesis is less than 500 mg/day. Thus, de novo hepatic lipogenesis is a quantitatively minor pathway, consistent with gas exchange estimates; fatty acid futile cycling (oxidation/resynthesis) is not thermogenically significant; and synthesis rates of different nonessential fatty acids by human liver are not identical in nonoverfed normal men. The contribution and regulation of de novo lipogenesis in other settings can be studied using this technique.
346 citations
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Charles N. Rotimi1, Akin Abayomi2, Alash'le Abimiku3, Victoria Adabayeri4 +242 more•Institutions (82)
TL;DR: If the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent.
Abstract: H3Africa is developing capacity for health-related genomics research in Africa Our understanding of genome biology, genomics, and disease, and even human history, has advanced tremendously with the completion of the Human Genome Project. Technological advances coupled with significant cost reductions in genomic research have yielded novel insights into disease etiology, diagnosis, and therapy for some of the world's most intractable and devastating diseases—including malaria, HIV/AIDS, tuberculosis, cancer, and diabetes. Yet, despite the burden of infectious diseases and, more recently, noncommunicable diseases (NCDs) in Africa, Africans have only participated minimally in genomics research. Of the thousands of genome-wide association studies (GWASs) that have been conducted globally, only seven (for HIV susceptibility, malaria, tuberculosis, and podoconiosis) have been conducted exclusively on African participants; four others (for prostate cancer, obsessive compulsive disorder, and anthropometry) included some African participants (www.genome.gov/gwastudies/). As discussed in 2011 (www.h3africa.org), if the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent.
344 citations
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TL;DR: In this article, the authors show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL cases.
341 citations
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Children's Hospital Oakland Research Institute1, University of Tennessee Health Science Center2, University of Cincinnati3, Kenya Medical Research Institute4, Cairo University5, Alexandria University6, Brigham and Women's Hospital7, Sultan Qaboos University8, Emory University9, Columbia University10, Queen Mary University of London11, University of Illinois at Chicago12, University of Alabama at Birmingham13, American University of Beirut14, Guy's and St Thomas' NHS Foundation Trust15
TL;DR: Voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis in this phase 3 randomized, placebo-controlled trial involving participants with sickle cell disease, consistent with inhibition of HbS polymerization and indicate a disease-modifying potential.
Abstract: Background Deoxygenated sickle hemoglobin (HbS) polymerization drives the pathophysiology of sickle cell disease. Therefore, direct inhibition of HbS polymerization has potential to favora...
340 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 |