Triple A Syndrome is an autosomal recessive neurodegenerative disorder characterised by central and peripheral nervous system disturbances, autonomic dysfunction, alacrima, achalasia, and ACTH-resistant adrenal insufficiency (1). It results from mutations in the AAAS gene located on 12q13 which encodes the WD-repeat protein ALADIN (2) (ALacrima Achalasia aDrenal Insufficiency Neurologic disorde...

The tumor suppressor Rb is thought to control cell proliferation, survival and differentiation. We recently showed that differentiating Rb-deficient mouse myoblasts can fuse to form short myotubes that quickly collapse through a mechanism involving autophagy, and that autophagy inhibitors or hypoxia could rescue the defect leading to long, twitching myotubes. Here we determined the contribution...

Metastasis is the most significant cause of cancer-associated morbidity and mortality but remains poorly understood. Recent work revealed that metastasis of aggressive triple-negative breast cancers is suppressed by Sharp1, a factor that promotes degradation of hypoxia-inducible factors (HIF) and blunts HIF-induced malignant cell behavior.

In order to investigate positive and negative regulatory elements of the erythropoietin (Epo) gene, synthetic oligonucleotides were designed to control Epo transcription by means of an antigen strategy. We devised a new method for detecting regulatory elements of genes that have a weak promoter. Synthetic oligonucleotides were incubated with Hep3B cells in the presence or absence of CoCl2 or hy...

macrophages accumulate in poorly vascularised and hypoxic sites including solid tumours, wounds and sites of infection and inflammation where they can be exposed to low levels of oxygen for long periods. up to date, different studies have shown that a number of transcription factors are activated by hypoxia which in turn activate a broad array of mitogenic, pro-invasive, pro-angiogenic, and pro...

fat embolism syndrome refers to a constellation of symptoms secondary to the presence of fat globules in the lung parenchyma and/or peripheral blood circulation. the syndrome is most often seen in association with long bone or pelvic fractures and can cause significant morbidity and mortality. the present randomized double blind placebo-controlled trial was conducted to evaluate the efficacy of...

Fat embolism syndrome refers to a constellation of symptoms secondary to the presence of fat globules in the lung parenchyma and/or peripheral blood circulation. The syndrome is most often seen in association with long bone or pelvic fractures and can cause significant morbidity and mortality. The present randomized double blind placebo-controlled trial was conducted to evaluate the efficacy of...

Triple A (Allgrove) syndrome was first described by Allgrove in 1978 in two pairs of siblings. Since then, about 100 cases have been reported, all of them displaying an autosomal recessive pattern of inheritance. Clinical picture is characterized by achalasia, alacrimia and ACTH-resistant adrenal failure. A progressive neurological syndrome including central, peripheral and autonomic nervous sy...

Mutations in the AAAS gene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. Triple A patients present with a characteristic phenotype including alacrima, achalasia and adrenal insufficiency. Patient fibroblasts show increased levels of oxidative stress, and several in vitro studies have demonstrated that the nucleoporin ALADIN is inv...

OBJECTIVE ACTH resistance syndromes are rare, autosomal, and genetically heterogeneous diseases that include familial glucocorticoid deficiency (FGD) and triple A syndrome. FGD has been shown to segregate with mutations in the gene coding for ACTH receptor (MC2R) or melanocortin 2 receptor accessory protein (MRAP), whereas mutations in the triple A syndrome (AAAS, Allgrove syndrome) gene have b...