| 111. |
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| 112. |
- Suomalainen, Anu, et al.
(author)
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FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study.
- 2011
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In: Lancet neurology. - 1474-4465. ; 10:9, s. 806-818
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Journal article (peer-reviewed)abstract
- BACKGROUND: Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack of sensitive biomarkers in serum. Fibroblast growth factor 21 (FGF-21) is a growth factor with regulatory roles in lipid metabolism and the starvation response, and concentrations are raised in skeletal muscle and serum in mice with mitochondrial respiratory chain deficiencies. We investigated in a retrospective diagnostic study whether FGF-21 could be a biomarker for human mitochondrial disorders. METHODS: We assessed samples from adults and children with mitochondrial disorders or non-mitochondrial neurological disorders (disease controls) from seven study centres in Europe and the USA, and recruited healthy volunteers (healthy controls), matched for age where possible, from the same centres. We used ELISA to measure FGF-21 concentrations in serum or plasma samples (abnormal values were defined as >200 pg/mL). We compared these concentrations with values for lactate, pyruvate, lactate-to-pyruvate ratio, and creatine kinase in serum or plasma and calculated sensitivity, specificity, and positive and negative predictive values for all biomarkers. FINDINGS: We analysed serum or plasma from 67 patients (41 adults and 26 children) with mitochondrial disorders, 34 disease controls (22 adults and 12 children), and 74 healthy controls. Mean FGF-21 concentrations in serum were 820 (SD 1151) pg/mL in adult and 1983 (1550) pg/mL in child patients with respiratory chain deficiencies and 76 (58) pg/mL in healthy controls. FGF-21 concentrations were high in patients with mitochondrial disorders affecting skeletal muscle but not in disease controls, including those with dystrophies. In patients with abnormal FGF-21 concentrations in serum, the odds ratio of having a muscle-manifesting mitochondrial disease was 132·0 (95% CI 38·7-450·3). For the identification of muscle-manifesting mitochondrial disease, the sensitivity was 92·3% (95% CI 81·5-97·9%) and specificity was 91·7% (84·8-96·1%). The positive and negative predictive values for FGF-21 were 84·2% (95% CI 72·1-92·5%) and 96·1 (90·4-98·9%). The accuracy of FGF-21 to correctly identify muscle-manifesting respiratory chain disorders was better than that for all conventional biomarkers. The area under the receiver-operating-characteristic curve for FGF-21 was 0·95; by comparison, the values for other biomarkers were 0·83 lactate (p=0·037, 0·83 for pyruvate (p=0·015), 0·72 for the lactate-to-pyruvate ratio (p=0·0002), and 0·77 for creatine kinase (p=0·013). INTERPRETATION: Measurement of FGF-21 concentrations in serum identified primary muscle-manifesting respiratory chain deficiencies in adults and children and might be feasible as a first-line diagnostic test for these disorders to reduce the need for muscle biopsy. FUNDING: Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Molecular Medicine Institute of Finland, University of Helsinki, Helsinki University Central Hospital, Academy of Finland, Novo Nordisk, Arvo and Lea Ylppö Foundation.
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| 113. |
- Suviolahti, E, et al.
(author)
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The SLC6A14 gene shows evidence of association with obesity
- 2003
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In: Journal of Clinical Investigation. - 0021-9738. ; 112:11, s. 1762-1772
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Journal article (peer-reviewed)abstract
- In our previous genome-wide scan of Finnish nuclear families, obesity was linked to chromosome Xq24. Here we analyzed this 15-Mb region by genotyping 9 microsatellite markers and 36 single nucleotide polyp morphisms (SNPs) for 11 positional and functional candidate genes in an extended sample of 218 obese Finnish sibling pairs (sibpairs) (BMI > 30 kg/m(2)). Evidence of linkage emerged mainly from the obese male sibpairs, suggesting a gender-specific effect for the underlying gene. By constructing haplotypes among the obese male sibpairs, we restricted the region from 15 Mb to 4 Mb, between markers DXS8088 and DXS8067. Regional functional candidate genes were tested for association in an initial sample of 117 cases and 182 controls. Significant evidence was observed for association for an SNP in the 3'-untranslated region of the solute carrier family 6 member 14 (SLC6A14) gene (P = 0.0002) and for SNP haplotypes of the SLC6A14 gene (P = 0.0007-0.006). Furthermore, an independent replication study sample of 837 cases and 968 controls from Finland and Sweden also showed significant differences in allele frequencies between obese and non-obese individuals (P = 0.003). The SLC6A14 gene is an interesting novel candidate for obesity because it encodes an amino acid transporter, which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control.
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| 114. |
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| 115. |
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| 116. |
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| 117. |
- Visscher, T, et al.
(author)
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A break in the obesity epidemic? Explained by biases or misinterpretation of the data?
- 2015
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39:2, s. 189-198
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Journal article (peer-reviewed)abstract
- Recent epidemiologic papers are presenting prevalence data suggesting breaks and decreases in obesity rates. However, before concluding that the obesity epidemic is not increasing anymore, the validity of the presented data should be discussed more thoroughly. We had a closer look into the literature presented in recent reviews to address the major potential biases and distortions, and to develop insights about how to interpret the presented suggestions for a potential break in the obesity epidemic. Decreasing participation rates, the use of reported rather than measured data and small sample sizes, or lack of representativeness, did not seem to explain presented breaks in the obesity epidemic. Further, available evidence does not suggest that stabilization of obesity rates is seen in higher socioeconomic groups only, or that urbanization could explain a potential break in the obesity epidemic. However, follow-ups of short duration may, in part, explain the apparent break or decrease in the obesity epidemic. On the other hand, a single focus on body mass index (BMI) ⩾25 or ⩾30 kg m-2 is likely to mask a real increase in the obesity epidemic. And, in both children and adults, trends in waist circumferences were generally suggesting an increase, and were stronger than those reported for trends in BMI. Studies concluding that there is a recent break in the obesity epidemic need to be interpreted with caution. Reported studies presenting a break were mostly of short duration. Further, focusing on trends in waist circumference rather than BMI leads to a less optimistic conclusion: the public health problem of obesity is still increasing.International Journal of Obesity advance online publication, 22 July 2014; doi:10.1038/ijo.2014.98.
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| 118. |
- Warzok, Ulrike, et al.
(author)
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Surprising solvent-induced structural rearrangements in large [N center dot center dot center dot I+center dot center dot center dot N] halogen-bonded supramolecular capsules : an ion mobility-mass spectrometry study
- 2018
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In: Chemical Science. - : ROYAL SOC CHEMISTRY. - 2041-6520 .- 2041-6539. ; 9:44, s. 8343-8351
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Journal article (peer-reviewed)abstract
- Coordinative halogen bonds have recently gained interest for the assembly of supramolecular capsules. Ion mobility-mass spectrometry and theoretical calculations now reveal the well-defined gas-phase structures of dimeric and hexameric [NI+N] halogen-bonded capsules with counterions located inside their cavities as guests. The solution reactivity of the large hexameric capsule shows the intriguing solvent-dependent equilibrium between the hexamer and an unprecedented pentameric [NI+N] halogen-bonded capsule, when the solvent is changed from chloroform to dichloromethane. The intrinsic flexibility of the cavitands enables this novel structure to adopt a pseudo-trigonal bipyramidal geometry with nine [NI+N] bonds along the edges and two pyridine binding sites uncomplexed.
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| 119. |
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| 120. |
- Zhang, Fan, et al.
(author)
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VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
- 2009
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:15, s. 6152-6157
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Journal article (peer-reviewed)abstract
- VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
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