Institution
University of Utah
Education•Salt Lake City, Utah, United States•
About: University of Utah is a education organization based out in Salt Lake City, Utah, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 52894 authors who have published 124076 publications receiving 5265834 citations. The organization is also known as: The U & The University of Utah.
Topics: Population, Medicine, Poison control, Health care, Cancer
Papers published on a yearly basis
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TL;DR: A multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study.
Abstract: We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR](common) 0.64, combined P [Pcomb]=7.85x10(-10)). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (OR(common) 1.40, Pcomb=8.11x10(-9)) and a less frequent protective haplotype (OR(common) 0.58, Pcomb=5.65x10(-12)), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (OR(common) 1.44, Pcomb=3.13x10(-6)). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (OR(common) 1.66, Pcomb=1.33x10(-8)). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis pathogenesis.
1,078 citations
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University of California, Irvine1, New York Medical College2, Loma Linda University3, University of North Carolina at Chapel Hill4, University of Chicago5, University of Washington6, Johns Hopkins University7, Yeshiva University8, University of Texas Health Science Center at San Antonio9, University of Pennsylvania10, University of Pittsburgh11, University of Utah12, Brown University13, University of Colorado Denver14, Vanderbilt University15, University of Miami16, Yale University17
TL;DR: This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those atrisk for any type of atypical development, and to identify those specifically at risk for autism.
Abstract: Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.
1,077 citations
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St. Jude Children's Research Hospital1, University of New Mexico2, University of Washington3, Washington University in St. Louis4, National Institutes of Health5, University of Florida6, Ohio State University7, New York University8, University of Alabama at Birmingham9, University of Texas Southwestern Medical Center10, University of Pennsylvania11, Royal Children's Hospital12, University of Toronto13, Texas A&M University14, University of Utah15, Emory University16, Mayo Clinic17, University of Chicago18, University of Texas Health Science Center at San Antonio19, University of Texas MD Anderson Cancer Center20, Yeshiva University21, University of California, San Francisco22, University of Colorado Denver23
TL;DR: Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors.
Abstract: BACKGROUND Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR–ABL1–positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. METHODS We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL. We examined the functional effects of fusion proteins and the efficacy of tyrosine kinase inhibitors in mouse pre-B cells and xenografts of human Ph-like ALL. RESULTS Ph-like ALL increased in frequency from 10% among children with standard-risk ALL to 27% among young adults with ALL and was associated with a poor outcome. Kinase-activating alterations were identified in 91% of patients with Ph-like ALL; rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations involving FLT3, IL7R, or SH2B3 were most common. Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent proliferation and activation of phosphorylated STAT5. Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6–NTRK3 fusion was sensitive to crizotinib. CONCLUSIONS Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors. Trials identifying Ph-like ALL are needed to assess whether adding tyrosine kinase inhibitors to current therapy will improve the survival of patients with this type of leukemia. (Funded by the American Lebanese Syrian Associated Charities and others.)
1,077 citations
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TL;DR: This review examines the colon cancer syndromes, their genetics and management, and also the common familial colon cancers with current genetic advances and screening guidelines.
1,076 citations
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TL;DR: Evidence suggests that NF1 encodes a cytoplasmic GAP-like protein that may be involved in the control of cell growth by interacting with proteins such as the RAS gene product.
1,073 citations
Authors
Showing all 53431 results
Name | H-index | Papers | Citations |
---|---|---|---|
Bert Vogelstein | 247 | 757 | 332094 |
George M. Whitesides | 240 | 1739 | 269833 |
Hongjie Dai | 197 | 570 | 182579 |
Robert M. Califf | 196 | 1561 | 167961 |
Frank E. Speizer | 193 | 636 | 135891 |
Yusuke Nakamura | 179 | 2076 | 160313 |
David L. Kaplan | 177 | 1944 | 146082 |
Marc G. Caron | 173 | 674 | 99802 |
George M. Church | 172 | 900 | 120514 |
Steven P. Gygi | 172 | 704 | 129173 |
Lily Yeh Jan | 162 | 467 | 73655 |
Tobin J. Marks | 159 | 1621 | 111604 |
David W. Bates | 159 | 1239 | 116698 |
Alfred L. Goldberg | 156 | 474 | 88296 |
Charles M. Perou | 156 | 573 | 202951 |