Search results for "610 Medicine & health"

IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice

2009

The clear association of Th17 cells with autoimmune pathogenicity implicates Th17 cytokines as critical mediators of chronic autoimmune diseases such as EAE. To study the impact of IL-17A on CNS inflammation, we generated transgenic mice in which high levels of expression of IL-17A could be initiated after Cre-mediated recombination. Although ubiquitous overexpression of IL-17A led to skin inflammation and granulocytosis, T cell–specific IL-17A overexpression did not have a perceptible impact on the development and health of the mice. In the context of EAE, neither the T cell–driven overexpression of IL-17A nor its complete loss had a major impact on the development of clinical disease. Sin…

Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.

2019

Abstract Background Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used. The objective of this study was to fully describe adverse events from the COLUMBUS study evaluating the most recent BRAF/MEK inhibitor combination encorafenib+binimetinib. Patients and methods Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg on…

Fundamentals of Paleoimaging Techniques: Bridging the Gap Between Physicists and Paleopathologists

2011

Connected pathway relative permeability from pore-scale imaging of imbibition

2016

Abstract Pore-scale images obtained from a synchrotron-based X-ray computed micro-tomography (µCT) imbibition experiment in sandstone rock were used to conduct Navier–Stokes flow simulations on the connected pathways of water and oil phases. The resulting relative permeability was compared with steady-state Darcy-scale imbibition experiments on 5 cm large twin samples from the same outcrop sandstone material. While the relative permeability curves display a large degree of similarity, the endpoint saturations for the µCT data are 10% in saturation units higher than the experimental data. However, the two datasets match well when normalizing to the mobile saturation range. The agreement is p…

Isolation and characterization of a cDNA encoding rat liver cytosolic epoxide hydrolase and its functional expression in Escherichia coli.

1993

A cDNA of 1992 base pairs encoding the complete rat liver cytosolic epoxide hydrolase has been isolated using a polymerase chain reaction-derived DNA fragment (Arand, M., Knehr, M., Thomas, H., Zeller, H. D., and Oesch, F. (1991) FEBS Lett. 294, 19-22) known to represent the 3'-end of the cytosolic epoxide hydrolase mRNA. Sequence analysis revealed an open reading frame of 1662 nucleotides corresponding to 554 amino acids (M(r) = 62,268). The DNA sequence obtained did not display significant homology to the sequences of microsomal epoxide hydrolase or leukotriene A4 hydrolase or to any other DNA included in the EMBL Data Bank (release 32). On Northern blotting of rat liver RNA, a single mRN…

Xenobiotic metabolizing enzyme activities and viability are well preserved in EDTA-isolated rat liver parenchymal cells after cryopreservation

1995

Rat liver parenchymal cells (PC) were isolated by EDTA perfusion and were purified by a subsequent Percoll centrifugation. The isolated PC had a viability of 95%, as judged by trypan blue exclusion. Freshly isolated PC were cryopreserved with an optimized protocol in a computer-controlled freezer. After thawing, the PC still retained a viability of 89%. The activities of representative xenobiotic metabolizing enzymes were compared between freshly isolated and cryopreserved PC after thawing. The cytochrome P450 content and the cytochrome P450 2C11 isoenzyme activity, determined by hydroxylation of testosterone in intact cells, were not affected by the cryopreservation. The following phase II…

The telltale structures of epoxide hydrolases.

2003

Traditionally, epoxide hydrolases (EH) have been regarded as xenobiotic-metabolizing enzymes implicated in the detoxification of foreign compounds. They are known to play a key role in the control of potentially genotoxic epoxides that arise during metabolism of many lipophilic compounds. Although this is apparently the main function for the mammalian microsomal epoxide hydrolase (mEH), evidence is now accumulating that the mammalian soluble epoxide hydrolase (sEH), despite its proven role in xenobiotic metabolism, also has a central role in the formation and breakdown of physiological signaling molecules. In addition, a certain class of microbial epoxide hydrolases has recently been identi…

Sequestration of biological reactive intermediates by trapping as covalent enzyme-intermediate complex

2001

One important class of biological reactive intermediates arising in the course of human xenobiotic metabolism are arene and alkene oxides. The major safeguard against the potential genotoxic effects of these compounds is the microsomal epoxide hydrolase (mEH). This enzyme has a broad substrate specificity but--on the first sight--seems to be inadequately suited for this protection task due to its low turnover number with most of its substrates. The recent progress in the understanding of the mechanism of enzymatic epoxide hydrolysis has shed new light on this apparent dilemma: Epoxide hydrolases convert their substrates via the intermediate formation of a covalent enzyme-substrate complex, …

Detection of primary DNA damage: applicability to biomonitoring of genotoxic occupational exposure and in clinical therapy

1995

The biological effect of putative genotoxic chemicals in the work place environment was monitored in peripheral mononuclear blood cells of exposed workers. DNA strand breaks, alkali-labile sites of DNA and DNA cross-links were measured using the alkaline filter elution method. A dose dependent increase in DNA damage was found in sterilization workers exposed to ethylene oxide and metal workers with exposure towards N-nitrosodiethanolamine. Two subpopulations with different response to the external exposure were found in nonsmoking sterilization workers. Nurses handling antineo-plastic agents without adequate safety provisions showed a statistically significantly higher rate of DNA strand br…

Viewing patterns regarding panoramic radiographs with different pathological lesions: an eye-tracking study.

2021

Objective: The aim of this study was to examine how dental students vary their viewing patterns of panoramic radiographs during different levels of dental education. Methods: Two groups of students (total number = 48, n = 24) in different grades (second and fifth clinical semester) were compared. The second clinical semester participated twice, as during the second clinical semester a specific lecture on dental radiology and diagnosis is held. The first viewing took place at the beginning of the semester (2a), the second at the end of it (2e). The fifth semester (5e) represents students shortly before graduation. While viewing 20 panoramic radiographs showing specific pathologies, the eye m…