Rotational Vertebral Artery Syndrome (Bow Hunter's Syndrome): A Rare Differential Diagnosis in Patients With Syncope.

Syncope is a common symptom in clinical practice. Rotational vertebral artery occlusion syndrome, also referred to as Bow Hunter's syndrome (BHS), is a rare condition associated with syncope and is caused by mechanical occlusion or stenosis secondary to mechanical compression of the vertebral artery during head rotation. BHS is associated with a multifactorial etiology; however, in most cases, this condition is attributed to degenerative changes. A 53-year-old man visited our hospital for the evaluation of fainting and dizziness episodes that occurred when he turned his head. Evaluation as an outpatient in the Department of Neurology showed a positive result on the Frenzel goggle test. Transfemoral cerebral angiography performed at the Department of Neurosurgery revealed stenosis of the proximal right vertebral artery. Complete occlusion of the vertebral artery was observed, and the head was turned to the right. Decompression and fusion were performed, and the contributory lesion was completely removed. Postoperative imaging confirmed complete removal of the spur and sufficient vertebral artery decompression; the patient's symptoms resolved postoperatively.

Itch E3 ubiquitin ligase positively regulates TGF-ß signaling to EMT via Smad7 ubiquitination.

TGF-ß regulates pleiotropic cellular responses including cell growth, differentiation, migration, apoptosis, extracellular matrix production, and many other biological processes. Although non-Smad signaling pathways are being increasingly reported to play many roles in TGF-ß-mediated biological processes, Smads, especially receptor-regulated Smads (R-Smads), still play a central mediatory role in TGF-ß signaling for epithelial-mesenchymal transition. Thus, the biological activities of R-Smads are tightly regulated at multiple points. Inhibitory Smad (I-Smad also called Smad7) acts as a critical endogenous negative feedback regulator of Smad-signaling pathways by inhibiting R-Smad phosphorylation and by inducing activated type I TGF-ß receptor degradation. Roles played by Smad7 in health and disease are being increasingly reported, but the molecular mechanisms that regulate Smad7 are not well understood. In this study, we show that E3 ubiquitin ligase Itch acts as a positive regulator of TGF-ß signaling and of subsequent EMT-related gene expression. Interestingly, the Itch-mediated positive regulation of TGF-ß signaling was found to be dependent on Smad7 ubiquitination and its subsequent degradation. Further study revealed Itch acts as an E3 ubiquitin ligase for Smad7 polyubiquitination, and thus, that Itch is an important regulator of Smad7 activity and a positive regulator of TGF-ß signaling and of TGF-ß-mediated biological processes. Accordingly, the study uncovers a novel regulatory mechanism whereby Smad7 is controlled by Itch.