A new family with an activating mutation (G431S) in the TSH receptor gene: a phenotype discussion and review of the literature

Germline nonautoimmune hyperthyroidism due to an activating mutation in the thyroid stimulating hormone receptor gene is an uncommon disease. To date 32 different mutations have been described. The severity of the hyperthyroid symptoms is variable and phenotype differences have been described in subjects harboring the same mutation. This paper describes a family with a mutation in codon 431 of the thyroid stimulating hormone receptor gene. This is the most common activating mutation in the thyroid stimulating hormone receptor gene with total of 13 patients harboring the mutation in four families. The similarities and differences among patients with the mutation in codon 431 are discussed. Furthermore all previously reported activating mutations in the thyroid stimulating hormone receptor gene are reviewed

Somatostatin is Only Partly Required for the Glucagonostatic Effect of Glucose but is Necessary for the Glucagonostatic Effect of KATP Channel Blockers

The mechanisms of control of glucagon secretion are largely unknown. In particular, the paracrine role of somatostatin is unclear. We studied its role in the control of glucagon secretion by glucose and KATP channel blockers, using perifused islets and the in situ perfused pancreas. The involvement of somatostatin was evaluated by comparing glucagon release of control tissue or tissue without paracrine influence of somatostatin (pertussis toxin-treated islets, or islets or pancreas from Sst-/- mice). We show that removal of the paracrine influence of somatostatin suppresses the ability of KATP channel blockers or KATP channel ablation to inhibit glucagon release, suggesting that, in control islets, the glucagonostatic effect of KATP channel blockers/ablation is fully mediated by somatostatin. By contrast, the glucagonostatic effect of glucose in control islets is mainly independent of somatostatin for low glucose concentrations (0-7 mmol/l) but starts to involve somatostatin for high concentrations of the sugar (15-30 mmol/l). This demonstrates that the glucagonostatic effect of glucose only partially depends on somatostatin. RT-qPCR and pharmacological experiments indicate that the glucagonostatic effect of somatostatin is mediated by two types of somatostatin receptors, SSTR2 and SSTR3. These results suggest that alterations of the paracrine influence of somatostatin will affect glucagon release

Expression of vascular endothelial growth factor, stromal cell-derived factor-1, and CXCR4 in human limb muscle with acute and chronic ischemia

OBJECTIVE: Vascular endothelial growth factor (VEGF)-induced stromal cell-derived factor-1 (SDF-1) has been implicated in angiogenesis in ischemic tissues by recruitment of CXCR4-positive bone marrow-derived circulating cells with paracrine functions in preclinical models. Here, evidence for this is provided in patients with peripheral artery disease. METHODS AND RESULTS: Expression patterns of VEGF, SDF-1, and CXCR4 were studied in amputated limbs of 16 patients. VEGF-A was expressed in vascular structures and myofibers. SDF-1 was expressed in endothelial and subendothelial cells, whereas CXCR4 was expressed in proximity to capillaries. VEGF-A, SDF-1, and CXCR4 expressions were generally decreased in ischemic muscle as compared with nonischemic muscle in patients with chronic ischemia (0.41-fold, 0.97-fold, and 0.54-fold induction [medians], respectively), whereas substantially increased in 2 patients with acute-on-chronic ischemia (3.5- to 65.8-fold, 3.9- to 19.0-fold, and 4.1- to 30.6-fold induction, respectively). Furthermore, these gene expressions strongly correlated with capillary area. Only acute ischemic tissue displayed a high percentage of hypoxia-inducible factor-1alpha-positive nuclei. CONCLUSIONS: These data suggest that VEGF and SDF-1 function as pro-angiogenic factors in patients with ischemic disease by perivascular retention of CXCR4-positive cells. Furthermore, these genes are downregulated in chronic ischemia as opposed to upregulated in more acute ischemia. The VEGF-SDF-1-CXCR4 pathway is a promising target to treat chronic ischemic diseas

Joint EANM/SIOPE/RAPNO practice guidelines/SNMMI procedure standards for imaging of paediatric gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0

Positron emission tomography (PET) has been widely used in paediatric oncology. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most commonly used radiopharmaceutical for PET imaging. For oncological brain imaging, different amino acid PET radiopharmaceuticals have been introduced in the last years. The purpose of this document is to provide imaging specialists and clinicians guidelines for indication, acquisition, and interpretation of [18F]FDG and radiolabelled amino acid PET in paediatric patients affected by brain gliomas. There is no high level of evidence for all recommendations suggested in this paper. These recommendations represent instead the consensus opinion of experienced leaders in the field. Further studies are needed to reach evidence-based recommendations for the applications of [18F]FDG and radiolabelled amino acid PET in paediatric neuro-oncology. These recommendations are not intended to be a substitute for national and international legal or regulatory provisions and should be considered in the context of good practice in nuclear medicine. The present guidelines/standards were developed collaboratively by the EANM and SNMMI with the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group and the Response Assessment in Paediatric Neuro-Oncology (RAPNO) working group. They summarize also the views of the Neuroimaging and Oncology and Theranostics Committees of the EANM and reflect recommendations for which the EANM and other societies cannot be held responsible.Keywords: DOPA; FDG; FET; Gliomas; MET; PET-CT; Paediatric PET; Paediatric brain imaging; Paediatric oncology