| 1. |
- Chaillou, Thomas, 1985-, et al.
(författare)
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Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth
- 2015
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Ingår i: Journal of applied physiology. - Bethesda, USA : American Physiological Society. - 8750-7587 .- 1522-1601. ; 118, s. 86-97
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading.
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| 2. |
- Holmes, Alice E., et al.
(författare)
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Perceived hearing status and attitudes toward noise in young adults
- 2007
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Ingår i: American Journal of Audiology. - Rockville, USA : American Speech Language Hearing Association. - 1059-0889 .- 1558-9137. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To estimate the prevalence of perceived hearing loss, tinnitus, and temporary threshold shift (TTS) in community college students and to see whether those students' attitudes toward noise affected their perception of their own possible hearing loss, tinnitus, and TTS. Method: Young adults (N = 245; age 18-27) completed 3 questionnaires: the Hearing Symptom Description, Youth Attitude to Noise Scale, and Adolescents' Habits and Hearing Protection Use. Results: Perceived TTS and pain associated with loud noise were the most common hearing related factors, followed by perceived tinnitus and hearing loss. The students' attitudes toward noise in their daily environment showed the most negative response, whereas attitudes toward noise and concentration indicated a more positive, or less harmful, response. Chi-square analysis indicated a significant correlation between perceived hearing loss and respondents' overall attitudes toward noise exposure. Hearing protection use was limited for all participants, with the majority reporting never having used hearing protection. Conclusion: Approximately 6% of respondents reported perceived hearing loss, and 13.5% reported prolonged tinnitus. In general, participants had neutral attitudes toward noise. Over 20% of participants reported ear pain, tinnitus, and/or TTS after noise exposure at least sometimes. Coincidentally, few participants reported consistent use of hearing protection. © American Speech-Language-Hearing Association.
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| 3. |
- Escher, Sylvia E., et al.
(författare)
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Integrate mechanistic evidence from new approach methodologies (NAMs) into a read-across assessment to characterise trends in shared mode of action
- 2022
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Ingår i: Toxicology in Vitro. - : Elsevier. - 0887-2333 .- 1879-3177. ; 79
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Tidskriftsartikel (refereegranskat)abstract
- Read-across approaches often remain inconclusive as they do not provide sufficient evidence on a common mode of action across the category members. This read-across case study on thirteen, structurally similar, branched aliphatic carboxylic acids investigates the concept of using human-based new approach methods, such as in vitro and in silico models, to demonstrate biological similarity.Five out of the thirteen analogues have preclinical in vivo studies. Three out of them induced lipid accumulation or hypertrophy in preclinical studies with repeated exposure, which leads to the read-across hypothesis that the analogues can potentially induce hepatic steatosis.To confirm the selection of analogues, the expression patterns of the induced differentially expressed genes (DEGs) were analysed in a human liver model. With increasing dose, the expression pattern within the tested analogues got more similar, which serves as a first indication of a common mode of action and suggests differences in the potency of the analogues.Hepatic steatosis is a well-known adverse outcome, for which over 55 adverse outcome pathways have been identified. The resulting adverse outcome pathway (AOP) network, comprised a total 43 MIEs/KEs and enabled the design of an in vitro testing battery. From the AOP network, ten MIEs, early and late KEs were tested to systematically investigate a common mode of action among the grouped compounds.The targeted testing of AOP specific MIE/KEs shows that biological activity in the category decreases with side chain length. A similar trend was evident in measuring liver alterations in zebra fish embryos. However, activation of single MIEs or early KEs at in vivo relevant doses did not necessarily progress to the late KE “lipid accumulation”. KEs not related to the read-across hypothesis, testing for example general mitochondrial stress responses in liver cells, showed no trend or biological similarity.Testing scope is a key issue in the design of in vitro test batteries. The Dempster-Shafer decision theory predicted those analogues with in vivo reference data correctly using one human liver model or the CALUX reporter assays.The case study shows that the read-across hypothesis is the key element to designing the testing strategy. In the case of a good mechanistic understanding, an AOP facilitates the selection of reliable human in vitro models to demonstrate a common mode of action. Testing DEGs, MIEs and early KEs served to show biological similarity, whereas the late KEs become important for confirmation, as progression from MIEs to AO is not always guaranteed.
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| 4. |
- Johansen, Jeanne D., et al.
(författare)
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European Society of Contact Dermatitis guideline for diagnostic patch testing : recommendations on best practice
- 2015
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 73:4, s. 195-221
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Forskningsöversikt (refereegranskat)abstract
- The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
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| 5. |
- Kimberling, William J., et al.
(författare)
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Usher syndrome : clinical findings and gene localization studies
- 1989
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Ingår i: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 99:1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an indepth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.
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| 6. |
- Ruoqing, Chen, 1985-, et al.
(författare)
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No association between hair cortisol or cortisone and brain morphology in children
- 2016
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Ingår i: Psychoneuroendocrinology. - : Pergamon Press. - 0306-4530 .- 1873-3360. ; 74:101, s. 101-110
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the relationship between the long-term hypothalamic-pituitary-adrenal (HPA) axis functioning and brain structure in children. Glucocorticoid in hair has emerged as an important biomarker of HPA activity. In this study, we investigated the associations of hair cortisol and cortisone concentrations with brain morphology in young children. We included 219 children aged 6-10 years from the Generation R Study in Rotterdam, the Netherlands. We examined cortisol and cortisone concentrations by hair analysis using liquid chromatography-tandem mass spectrometry, and assessed brain morphometric measures with structural magnetic resonance imaging. The relationships of hair cortisol and cortisone concentrations with brain volumetrics, cortical thickness, cortical surface area and gyrification were analyzed separately after adjustment for several potential confounding factors. We observed a positive association between cortisol concentrations and cortical surface area in the parietal lobe, positive associations of cortisone concentrations with thalamus volume, occipital lobe volume and cortical surface area in the parietal lobe, and a negative association between cortisone concentrations and cortical surface area in the temporal lobe in the regions of interest analyses. A negative association between cortisol or cortisone concentrations and hippocampal volume was observed in children with behavioral problems. The whole brain vertex-wise analyses did however not show any association between cortisol or cortisone concentration and brain morphometric measures after correction for multiple testing. Although some associations are noted in region of interest analyses, we do not observe clear association of hair cortisol or cortisone with brain morphometric measures in typically developing young children.
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| 7. |
- Syed, Akheel A, et al.
(författare)
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A common intron 2 polymorphism of the glucocorticoid receptor gene is associated with insulin resistance in men
- 2008
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Ingår i: Clinical Endocrinology. - : Wiley-Blackwell Publishing Inc.. - 0300-0664 .- 1365-2265. ; 68:6, s. 879-884
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Clinical similarities between the metabolic syndrome and Cushing's syndrome have led to speculation of genetic association between them. The Bcl1 polymorphism in intron 2 of the glucocorticoid receptor (GR) gene has been associated with insulin resistance/hyperinsulinaemia. Our objective was to test the association of rs2918419, a T-->C single nucleotide change in intron 2 downstream of the Bcl1 locus, with components of the metabolic syndrome and its interaction with the Bcl1 locus.DESIGN AND METHODS: We genotyped a subsample of 325 White subjects (116 men) in the Newcastle Heart Project (NHP), a population-based study in north-east England. Gender-specific statistical analysis by stepwise backward multiple regression was performed to test the association of allele status with adiposity, glucose and insulin responses to oral glucose tolerance test (OGTT), fasting lipids and blood pressure.RESULTS: Minor allele frequency was 0.14 for rs2918419 and 0.39 for the Bcl1 polymorphism. rs2918419 was associated with higher fasting insulin concentration and insulin resistance in men but not in women. Contrary to earlier studies, the Bcl1 polymorphism on its own was not associated with insulin resistance/hyperinsulinaemia in either gender. Subjects carrying variant rs2918419 alleles also had variant alleles at the Bcl1 locus. In men, but not women, Bcl1 variant alleles on a background of rs2918419 wild-type alleles associated with lower fasting insulin compared to wild-type alleles at both loci or variant alleles at both loci.CONCLUSIONS: We report that rs2918419 was linked with hyperinsulinaemia and insulin resistance in men. Carrying Bcl1 variant alleles without rs2918419 was not associated with hyperinsulinaemia/insulin resistance. Previous reports of the association of Bcl1 polymorphism with obesity-related characteristics may reflect linkage disequilibrium with rs2918419.
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