Search PubMed⌕ Search

Biomedical subjects

Julie Cook

Publications and source records attributed to Julie Cook.

5 recordsLinked to original sources
PubMed2005

Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development.

Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization. Although it is known that Gli transcription factors are key effectors of hedgehog signaling, it has not been established which Gli protein mediates Ihh activity in skeletal development. Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and maturation of chondrocytes, but only partially rescued the defects in osteoblast development and cartilage vascularization. Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization promoted osteoblast development in perichondrial progenitor cells. Our results not only establish Gli3 as a critical effector for Ihh activity in the developing skeleton, but also identify an osteogenic role for a vasculature-derived signal, which integrates with Ihh and Wnt signals to determine the osteoblast versus chondrocyte fate in the mesenchymal progenitors.

Animals↗
PubMed2005

Latex-enhanced immunoassay d-dimer and blood gases can exclude pulmonary embolism in low-risk patients presenting to an acute care setting.

BACKGROUND: Pulmonary embolism (PE) is common, and diagnosis is often difficult. Investigation has traditionally required expensive imaging procedures that are frequently nondiagnostic. Consequently, current practice favors noninvasive diagnosis of PE using algorithms combining risk assessment and d-dimer. Despite the proven safety of this approach, concern persists about such strategies to exclude PE, largely due to variable d-dimer sensitivity. The aim of this study was to prospectively assess the safety of a new algorithm combining a novel, rapid d-dimer test (IL Test; Instrumentation Laboratory; Lexington, MA), Pa(O2) measurement, and risk factor assessment in excluding PE in subjects presenting to an acute care setting. METHODS: All patients aged 18 to 60 years presenting to the emergency department of Christchurch Hospital with suspected PE underwent measurement of d-dimer (IL Test latex-enhanced immunoassay) and Pa(O2), and were assessed for the presence of major clinical risk factors. Those with no risk factors, normal d-dimer findings, and Pa(O2) > or = 80 mm Hg (study arm A) were discharged and followed up by telephone questionnaires over 12 months. Those with elevated d-dimer levels, Pa(O2) < 80 mm Hg, or one or more risk factors (study arm B) were managed as per hospital guidelines. Outcome data were collected on these patients. Our primary outcome was incidence of PE in group A during the first 3-month follow-up period. RESULTS: Three hundred twenty-eight patients were enrolled, of whom 149 were assigned to group A and 179 were assigned to group B. In none of the group A patients was PE diagnosed over the subsequent 3-month period (0%; 95% confidence interval, 0 to 2.1%). PE was diagnosed in 37 group A patients (21%). CONCLUSIONS: The latex-enhanced immunoassay d-dimer and normal arterial oxygen pressure levels can safely exclude PE in a low-risk population presenting to an acute care setting. While these results cannot be extrapolated to all patients with suspected PE, they do confirm the safety of this approach in a population with a low underlying risk of PE.

Blood Gas Analysis↗
PubMed2004

Specific and covalent targeting of conjugating and deconjugating enzymes of ubiquitin-like proteins.

Modification of proteins by ubiquitin (Ub)-like proteins (UBLs) plays an important role in many cellular processes, including cell cycle progression, nuclear transport, and autophagy. Protein modification occurs via UBL-conjugating and -deconjugating enzymes, which presumably exert a regulatory function by determining the conjugation status of the substrate proteins. To target and identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUMO-1 in Escherichia coli and equipped them with a C-terminal electrophilic trap (vinyl sulfone [VS]) via an intein-based method. These C-terminally modified UBL probes reacted with purified UBL-activating (E1), -conjugating (E2), and -deconjugating enzymes in a covalent fashion. Modified UBLs were radioiodinated and incubated with cell lysates prepared from mouse cell lines and tissues to allow visualization of polypeptides reactive with individual UBL probes. The cell type- and tissue-specific labeling patterns observed for the UBL probes reflect distinct expression profiles of active enzymes, indicating tissue-specific functions of UBLs. We identify Ub C-terminal hydrolase L1 (UCH-L1) and DEN1/NEDP1/SENP8, in addition to UCH-L3, as proteases with specificity for Nedd8. The Ub-specific protease isopeptidase T/USP5 is shown to react with ISG15-VS. Furthermore, we demonstrate that the desumoylation enzyme SuPr-1 can be modified by SUMO-1-VS, a modification that is dependent on the SuPr-1 active-site cysteine. The UBL probes described here will be valuable tools for the further characterization of the enzymatic pathways that govern modification by UBLs.

Animals↗
PubMedDate not supplied

Breathing space.

Explore the source record for details and available documents.

Dyspnea↗