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- Parmar, A S, et al.
(författare)
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Association of celiac disease genes with inflammatory bowel disease in Finnish and Swedish patients
- 2012
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Ingår i: Genes and Immunity. - : Nature Publishing Group. - 1466-4879 .- 1476-5470. ; 13:6, s. 474-480
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Tidskriftsartikel (refereegranskat)abstract
- Some genetic loci may affect susceptibility to multiple immune system-related diseases. In the current study, we investigated whether the known susceptibility loci for celiac disease (CelD) also associate with Crohn's disease (CD) and/or ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), in Finnish patients. A total of 45 genetic markers were genotyped in a Finnish data set comprising 699 IBD patients and 2482 controls. Single-marker association with IBD and its subphenotypes was tested. A meta-analysis with a Swedish UC data set was also performed. A total of 12 single-nucleotide polymorphisms associated with CD and/or UC (P<0.05). In the subphenotype analysis, rs6974491-ELMO1 (P=0.0002, odds ratio (OR): 2.20) and rs2298428-UBE2L3 (P=5.44 × 10(-5), OR: 2.59) associated with pediatric UC and CD, respectively. In the meta-analysis, rs4819388-ICOSLG (P=0.00042, OR: 0.79) associated with UC. In the subphenotype meta-analysis, rs1738074-TAGAP (P=7.40 × 10(-5), OR: 0.61), rs6974491-ELMO1 (P=0.00052, OR: 1.73) and rs4819388-ICOSLG (P=0.00019, OR: 0.75) associated with familial UC, pediatric UC and sporadic UC, respectively. Multiple CelD risk loci also confer susceptibility for CD and/or UC in the Finnish and Swedish populations. Certain genetic risk variants may furthermore predispose an individual for developing a particular disease phenotype.
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| 4. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
- 2014
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:20, s. 9609-18
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Tidskriftsartikel (refereegranskat)abstract
- The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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| 7. |
- Einarsdottir, Ingibjörg, 1951, et al.
(författare)
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Occurrence of ghrelin-producing cells, the ghrelin receptor and Na+,K+-ATPase in tissues of Atlantic halibut
- 2011
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Ingår i: Cell and Tissue Resarch. - 0302-766X. ; 344:3, s. 481-498
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a pituitary growth hormone (GH)-secretagogue that also has metabolic, reproductive, proliferative, immunological and brain functions in mammals. Far less is known about its role in fish. We have therefore performed an immunohistochemical determination of its tissue distribution in the developing Atlantic halibut (Hippoglossus hippoglossus) to gain insights into its potential function. Ghrelin immunoreactivity was detected in first-feeding halibut larvae in the skin, urinary bladder, gastrointestinal (GI) tract and olfactory lobe of the brain. In subsequent stages up to metamorphosis, ghrelin immunoreactivity declined in the skin and became evident in the gills. When the stomach developed, ghrelin immunoreactivity declined throughout the GI tract with the exception of the stomach, which exhibited an intense signal. Immunoreactive ghrelin cells were also present in the olfactory lobe, nerve and epithelium and in occasional cells of the buccal cavity and oesophagus. Ghrelin immunoreactivity had an overlapping distribution with that for Na(+),K(+)-ATPase, colocalisation also being observed in some ionocytes of the gill. The co-expression of ghrelin and the GH-secretagogue receptor in the same tissue indicates that ghrelin can exert both endocrine and paracrine actions in the developing halibut. The presence of immunoreactive ghrelin in several osmoregulatory tissues, the GI tract and sensory tissue provides strong evidence that ghrelin has multiple functions during development and also suggests targets for future investigations.
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| 8. |
- Fuentes, EN, et al.
(författare)
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IGF-I/PI3K/Akt and IGF-I/MAPK/ERK pathways in vivo in skeletal muscle are regulated by nutrition and contribute to somatic growth in the fine flounder
- 2011
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Ingår i: American Journal of Physiology - Regulatory, Integrative. - 0363-6119. ; 300:6, s. 1532-1542
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Tidskriftsartikel (refereegranskat)abstract
- The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Nutrition also affects skeletal muscle growth, activating intracellular pathways and inducing protein synthesis and accretion. Thus, both hormonal and nutritional signaling regulate muscle mass. In this context, plasma IGF-I levels and the activation of both pathways in response to food were evaluated in the fine flounder using fasting and refeeding trials. The present study describes for the first time in a nonmammalian species that the MAPK/ERK and PI3K/Akt are activated by exogenous circulating IGF-I, as well as showing that the MAPK/ERK pathway activation is modulated by the nutritional status. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. Together, these results suggest that the nutritionally managed IGF-I could be regulating the activation of the MAPK/ERK and the PI3K/Akt signaling pathways differentially according to the nutritional status, triggering different effects in growth parameters and therefore contributing to somatic growth in fish. This study contributes to the understanding of the nutrient regulation of IGF-I and its signaling pathways in skeletal muscle growth in nonmammalian species, therefore providing insight concerning the events controlling somatic growth in vertebrates.
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| 9. |
- Fuentes, E. N., et al.
(författare)
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Inherent Growth Hormone Resistance in the Skeletal Muscle of the Fine Flounder Is Modulated by Nutritional Status and Is Characterized by High Contents of Truncated GHR, Impairment in the JAK2/STAT5 Signaling Pathway, and Low IGF-I Expression
- 2012
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 153:1, s. 283-294
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Tidskriftsartikel (refereegranskat)abstract
- A detailed understanding of how the GH and IGF-I regulate muscle growth, especially in early vertebrates, is still lacking. The fine flounder is a flatfish species exhibiting remarkably slow growth, representing an intriguing model for elucidating growth regulatory mechanisms. Key components of the GH system were examined in groups of fish during periods of feeding, fasting, and refeeding. Under feeding conditions, there is an inherent systemic and local (muscle) GH resistance, characterized by higher levels of plasma GH than of IGF-I, skeletal muscle with a greater content of the truncated GH receptor (GHRt) than of full-length GHR (GHRfl), an impaired activation of the Janus kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) signaling pathway, and low IGF-I expression. Fasting leads to further elevation of plasma GH levels concomitant with suppressed IGF-I levels. The ratio of GHRfl to GHRt in muscle decreases during fasting, causing an inactivation of the JAK2/STAT5 signaling pathway and suppressed IGF-I expression, further impairing growth. When fish are returned to nutritionally favorable conditions, plasma GH levels decrease, and the ratio of GHRfl to GHRt in muscle increases, triggering JAK2/STAT5 reactivation and local IGF-I expression, concomitant with increased growth. The study suggests that systemic IGF-I is supporting basal slow growth in this species, without ruling out that local IGF-I is participating in muscle growth. These results reveal for the first time a unique model of inherent GH resistance in the skeletal muscle of a nonmammalian species and contribute to novel insights of the endocrine and molecular basis of growth regulation in earlier vertebrates. (Endocrinology 153:283-294, 2012)
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| 10. |
- Fuentes, E. N., et al.
(författare)
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Plasma leptin and growth hormone levels in the fine flounder (Paralichthys adspersus) increase gradually during fasting and decline rapidly after refeeding
- 2012
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480. ; 177:1, s. 120-127
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Tidskriftsartikel (refereegranskat)abstract
- In fish, recent studies have indicated an anorexigenic role of leptin and thus its possible involvement in regulation of energy balance and growth. In the present study, the effects of fasting and refeeding periods on plasma leptin levels were studied in the fine flounder, a flatfish with remarkably slow growth. To further assess the endocrine status of the fish during periods of catabolism and anabolism, plasma growth hormone (GH) levels were also analyzed. Under normal feeding condition, plasma leptin and CH levels remained stable and relatively high in comparison with other teleost species. For the three separate groups of fish, fasted for 2, 3, and 4 weeks, respectively, plasma leptin levels increase gradually, becoming significantly elevated after 3 weeks, and reaching highest levels after 4-week fasting. Plasma GH levels were significantly elevated after 2-week fasting. At the onset of refeeding, following a single meal, leptin levels decline rapidly to lower than initial levels within 2 h, irrespective of the length of fasting. Plasma GH also decline, the decrease being significant after 4, 24 and 2 h for the 2, 3 and 4-week fasted groups, respectively. This study shows that plasma leptin levels in the fine flounder are strongly linked to nutritional status and suggests that leptin secretion is regulated by fast-acting mechanisms. Elevated leptin levels in fasted fish may contribute to a passive survival strategy of species which experience natural food shortage periods by lowering appetite and limiting physical foraging activity. (C) 2012 Elsevier Inc. All rights reserved.
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