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.

Evolution of HLA class II molecules: Allelic and amino acid site variability across populations.

Abstract: Analysis of the highly polymorphic beta1 domains of the HLA class II molecules encoded by the DRB1, DQB1, and DPB1 loci reveals contrasting levels of diversity at the allele and amino acid site levels. Statistics of allele frequency distributions, based on Watterson's homozygosity statistic F, reveal distinct evolutionary patterns for these loci in ethnically diverse samples (26 populations for DQB1 and DRB1 and 14 for DPB1). When examined over all populations, the DQB1 locus allelic variation exhibits striking balanced polymorphism (P < 10(-4)), DRB1 shows some evidence of balancing selection (P < 0.06), and while there is overall very little evidence for selection of DPB1 allele frequencies, there is a trend in the direction of balancing selection (P < 0.08). In contrast, at the amino acid level all three loci show strong evidence of balancing selection at some sites. Averaged over polymorphic amino acid sites, DQB1 and DPB1 show similar deviation from neutrality expectations, and both exhibit more balanced polymorphic amino acid sites than DRB1. Across ethnic groups, polymorphisms at many codons show evidence for balancing selection, yet data consistent with directional selection were observed at other codons. Both antigen-binding pocket- and non-pocket-forming amino acid sites show overall deviation from neutrality for all three loci. Only in the case of DRB1 was there a significant difference between pocket- and non-pocket-forming amino acid sites. Our findings indicate that balancing selection at the MHC occurs at the level of polymorphic amino acid residues, and that in many cases this selection is consistent across populations.

Children's Hospital Association consensus statements for comorbidities of childhood obesity.

Abstract: Background: Childhood obesity and overweight affect approximately 30% of US children. Many of these children have obesity-related comorbidities, such as hypertension, dyslipidemia, fatty liver disease, diabetes, polycystic ovary syndrome (PCOS), sleep apnea, psychosocial problems, and others. These children need routine screening and, in many cases, treatment for these conditions. However, because primary care pediatric providers (PCPs) often are underequipped to deal with these comorbidities, they frequently refer these patients to subspecialists. However, as a result of the US pediatric subspecialist shortage and considering that 12.5 million children are obese, access to care by subspecialists is limited. The aim of this article is to provide accessible, user-friendly clinical consensus statements to facilitate the screening, interpretation of results, and early treatment for some of the most common childhood obesity comorbidities. Methods: Members of the Children's Hospital Association (formerly NACHRI) FOCUS on a Fitter Future II (FFFII), a collaboration of 25 US pediatric obesity centers, used a combination of the best available evidence and collective clinical experience to develop consensus statements for pediatric obesity-related comorbidities. FFFII also surveyed the participating pediatric obesity centers regarding their current practices. Results: The work group developed consensus statements for use in the evaluation and treatment of lipids, liver enzymes, and blood pressure abnormalities and PCOS in the child with overweight and obesity. The results of the FFFII survey illustrated the variability in the approach for initial evaluation and treatment as well as pattern of referrals to subspecialists among programs. Conclusions: The consensus statements presented in this article can be a useful tool for PCPs in the management and overall care of children with overweight and obesity.

Intravenously injected human apolipoprotein A-I rapidly enters the central nervous system via the choroid plexus.

Abstract: Background-—Brain lipoprotein metabolism is dependent on lipoprotein particles that resemble plasma high-density lipoproteins but that contain apolipoprotein (apo) E rather than apoA-I as their primary protein component. Astrocytes and microglia secrete apoE but not apoA-I; however, apoA-I is detectable in both cerebrospinal fluid and brain tissue lysates. The route by which plasma apoA-I enters the central nervous system is unknown. Methods and Results-—Steady-state levels of murine apoA-I in cerebrospinal fluid and interstitial fluid are 0.664 and 0.120 lg/ mL, respectively, whereas brain tissue apoA-I is � 10% to 15% of its levels in liver. Recombinant, fluorescently tagged human apoA-I injected intravenously into mice localizes to the choroid plexus within 30 minutes and accumulates in a saturable, dose-dependent manner in the brain. Recombinant, fluorescently tagged human apoA-I accumulates in the brain for 2 hours, after which it is eliminated with a half-life of 10.3 hours. In vitro, human apoA-I is specifically bound, internalized, and transported across confluent monolayers of primary human choroid plexus epithelial cells and brain microvascular endothelial cells. Conclusions-—Following intravenous injection, recombinant human apoA-I rapidly localizes predominantly to the choroid plexus. Because apoA-I mRNA is undetectable in murine brain, our results suggest that plasma apoA-I, which is secreted from the liver and intestine, gains access to the central nervous system primarily by crossing the blood–cerebrospinal fluid barrier via specific cellular mediated transport, although transport across the blood–brain barrier may also contribute to a lesser extent. (J Am Heart Assoc. 2014;3:e001156 doi: 10.1161/JAHA.114.001156)