| 1. |
- Chantzichristos, Dimitrios, 1976, et al.
(författare)
-
Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.
- 2021
-
Ingår i: eLife. - 2050-084X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.NCT02152553.
|
|
| 2. |
- Buendia, Rubén, et al.
(författare)
-
Robustness study of the different immittance spectra and frequency ranges in bioimpedance spectroscopy analysis for assessment of total body composition.
- 2014
-
Ingår i: Physiological measurement. - : IOP Publishing. - 1361-6579 .- 0967-3334. ; 35:7, s. 1373-95
-
Tidskriftsartikel (refereegranskat)abstract
- The estimation of body fluids is a useful and common practice for assessment of disease status and therapy outcomes. Electrical bioimpedance spectroscopy (EBIS) methods are noninvasive, inexpensive and efficient alternatives for determination of body fluids. One of the main source of errors in EBIS measurements in the estimation of body fluids is capacitive coupling. In this paper an analysis of capacitive coupling in EBIS measurements was performed and the robustness of the different immittance spectra against it tested. On simulations the conductance (G) spectrum presented the smallest overall error, among all immittance spectra, in the estimation of the impedance parameters used to estimate body fluids. Afterwards the frequency range of 10-500kHz showed to be the most robust band of the G spectrum. The accuracy of body fluid estimations from the resulting parameters that utilized G spectrum and parameters provided by the measuring device were tested on EBIS clinical measurements from growth hormone replacement therapy patients against estimations performed with dilution methods. Regarding extracellular fluid, the correlation between each EBIS method and dilution was 0.93 with limits of agreement of 1.06 ± 2.95 l for the device, 1.10 ± 2.94 l for G [10-500kHz] and 1.04 ± 2.94 l for G [5-1000kHz]. Regarding intracellular fluid, the correlation between dilution and the device was 0.91, same as for G [10-500kHz] and 0.92 for G [5-1000kHz]. Limits of agreement were 0.12 ± 4.46 l for the device, 0.09 ± 4.45 for G [10-500kHz] and 0.04 ± 4.58 for G [5-1000kHz]. Such close results between the EBIS methods validate the proposed approach of using G spectrum for initial Cole characterization and posterior clinical estimation of body fluids status.
|
|
| 3. |
- Glad, Camilla A M, 1981, et al.
(författare)
-
Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change.
- 2019
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:5, s. 1459-1470
-
Tidskriftsartikel (refereegranskat)abstract
- GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking.The aim of the present study was to investigate the gene expression patterns of GHR and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (JAK2, STAT3, STAT5A, and STAT5B) in human subcutaneous adipose tissue in relation to energy restriction and overfeeding.Tissue distribution was analyzed in a data set generated by RNA sequencing containing information on global expression in human tissues. Subcutaneous adipose tissue or adipocyte gene expression (measured by DNA microarrays) was investigated in the following settings: (i) individuals with obesity vs individuals with normal weight; (ii) energy restriction; and (iii) overfeeding.GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P < 0.001). It was increased in response to energy restriction and decreased in response to overfeeding (P = 0.015 and P = 0.030, respectively). STAT3 expression was increased in subjects with obesity (P < 0.001). It was decreased during energy restriction and increased during overfeeding (P = 0.004 and P = 0.006, respectively). STAT3-regulated genes showed an overall view of overexpression in obesity.The results of the present study have shown that GHR, STAT3, and STAT3-regulated genes are dynamically, and reciprocally, regulated at the tissue level in response to energy restriction and overfeeding, suggesting that GH signaling is perturbed in obesity.
|
|
| 4. |
- Nyström, Helena Filipsson, 1966, et al.
(författare)
-
Detection of genetic hypopituitarism in an adult population of idiopathic pituitary insufficiency patients with growth hormone deficiency.
- 2011
-
Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 14:3, s. 208-216
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pituitary insufficiency (IPI) is diagnosed in 10% of all hypopituitary patients. There are several known and unknown aetiologies within the IPI group. The aim of this study was to investigate an adult IPI population for genetic cause according a screening schedule. From files of 373 GH deficient (GHD) patients on GH replacement 50 cases with IPI were identified. Of the 39 patients that approved to the study, 25 patients were selected for genetic investigation according to phenotype and 14 patients were not further tested, as sporadic isolated GHD (n=9) and GHD with diabetes insipidus (n=5) have low probability for a known genetic cause. Genotyping of all coding exons of HESX1, LHX4, PROP1, POU1F1 and GH1 genes were performed according to a diagnostic algorithm based on clinical, hormonal and neuroradiological phenotype. Among the 25 patients, an overall rate of 8% of mutations was found, and a 50% rate in familial cases. Among two sibling pairs, one pair that presented with complete anterior pituitary insufficiency, had a compound heterozygous PROP1 gene mutation (codons 117 and 120: exon 3 p Phe 117 Ile (c349 T>A) and p Arg 120 Cys (c358 C>T)) with a phenotype of very late onset ACTH-insufficiency. In the other sibling pair and in the sporadic cases no mutation was identified. This study suggests that currently known genetic causes are rare in sporadic adult IPI patients, and that systematic genetic screening is not needed in adult-onset sporadic cases of IPI. Conversely, familial cases are highly suspect for genetic causes.
|
|
