排序方式: 共有72条查询结果,搜索用时 32 毫秒
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Sun Hee Ahn Ephraim L. Tsalik Derek D. Cyr Yurong Zhang Jennifer C. van Velkinburgh Raymond J. Langley Seth W. Glickman Charles B. Cairns Aimee K. Zaas Emanuel P. Rivers Ronny M. Otero Tim Veldman Stephen F. Kingsmore Joseph Lucas Christopher W. Woods Geoffrey S. Ginsburg Vance G. Fowler Jr 《PloS one》2013,8(1)
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host’s inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues. 相似文献
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David P. Dimmock Michelle M. Clark Mary Gaughran Julie A. Cakici Sara A. Caylor Christina Clarke Michele Feddock Shimul Chowdhury Lisa Salz Cynthia Cheung Lynne M. Bird Charlotte Hobbs Kristen Wigby Lauge Farnaes Cinnamon S. Bloss Stephen F. Kingsmore the RCIGM Investigators 《American journal of human genetics》2020,107(5):942
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Katherine A. Owen Andrew Price Hannah Ainsworth Bryce N. Aidukaitis Prathyusha Bachali Michelle D. Catalina James M. Dittman Timothy D. Howard Kathryn M. Kingsmore Adam C. Labonte Miranda C. Marion Robert D. Robl Kip D. Zimmerman Carl D. Langefeld Amrie C. Grammer Peter E. Lipsky 《American journal of human genetics》2020,107(5):864
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The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins 总被引:5,自引:0,他引:5
Tchernev VT Mansfield TA Giot L Kumar AM Nandabalan K Li Y Mishra VS Detter JC Rothberg JM Wallace MR Southwick FS Kingsmore SF 《Molecular medicine (Cambridge, Mass.)》2002,8(1):56-64
BACKGROUND:Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency disease characterized by giant lysosomes and impaired leukocyte degranulation. CHS results from mutations in the lysosomal trafficking regulator (LYST) gene, which encodes a 425-kD cytoplasmic protein of unknown function. The goal of this study was to identify proteins that interact with LYST as a first step in understanding how LYST modulates lysosomal exocytosis. MATERIALS AND METHODS: Fourteen cDNA fragments, covering the entire coding domain of LYST, were used as baits to screen five human cDNA libraries by a yeast two-hybrid method, modified to allow screening in the activation and the binding domain, three selectable markers, and more stringent confirmation procedures. Five of the interactions were confirmed by an in vitro binding assay. RESULTS: Twenty-one proteins that interact with LYST were identified in yeast two-hybrid screens. Four interactions, confirmed directly, were with proteins important in vesicular transport and signal transduction (the SNARE-complex protein HRS, 14-3-3, and casein kinase II). CONCLUSIONS:On the basis of protein interactions, LYST appears to function as an adapter protein that may juxtapose proteins that mediate intracellular membrane fusion reactions. The pathologic manifestations observed in CHS patients and in mice with the homologous mutation beige suggest that understanding the role of LYST may be relevant to the treatment of not only CHS but also of diseases such as asthma, urticaria, and lupus, as well as to the molecular dissection of the CHS-associated cancer predisposition. 相似文献
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Multiplexed protein profiling on antibody-based microarrays by rolling circle amplification 总被引:4,自引:0,他引:4
Multiplexed immunoassays on antibody-based protein microarrays are an attractive solution for analyzing biological responses in normal and diseased states. Recently, the feasibility and utility of these assays has been established as concerns about specificity and sensitivity are being overcome by careful quality control and amplification technologies such as rolling circle amplification (RCA). RCA-amplified protein chips can now profile up to 150 proteins in various substrates including serum, plasma, and supernatants with high sensitivity, broad dynamic range and good reproducibility. Diagnostic utility of RCA-amplified protein chips has been shown for multiplexed allergen testing. When allied with multivariate statistical analysis, RCA protein chips have the potential to identify multiplexed biomarker classifiers for disease diagnosis and drug response. 相似文献
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Carol Saunders Laurie Smith Flemming Wibrand Kirstine Ravn Peter Bross Isabelle Thiffault Mette Christensen Andrea Atherton Emily Farrow Neil Miller Stephen?F. Kingsmore Elsebet Ostergaard 《American journal of human genetics》2015,96(2):258-265
3-methylglutaconic aciduria (3-MGA-uria) is a nonspecific finding associated with mitochondrial dysfunction, including defects of oxidative phosphorylation. 3-MGA-uria is classified into five groups, of which one, type IV, is genetically heterogeneous. Here we report five children with a form of type IV 3-MGA-uria characterized by cataracts, severe psychomotor regression during febrile episodes, epilepsy, neutropenia with frequent infections, and death in early childhood. Four of the individuals were of Greenlandic descent, and one was North American, of Northern European and Asian descent. Through a combination of homozygosity mapping in the Greenlandic individuals and exome sequencing in the North American, we identified biallelic variants in the caseinolytic peptidase B homolog (CLPB). The causative variants included one missense variant, c.803C>T (p.Thr268Met), and two nonsense variants, c.961A>T (p.Lys321∗) and c.1249C>T (p.Arg417∗). The level of CLPB protein was markedly decreased in fibroblasts and liver of affected individuals. CLPB is proposed to function as a mitochondrial chaperone involved in disaggregation of misfolded proteins, resulting from stress such as heat denaturation. 相似文献
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