The carboxy-terminal fragment of α1A calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease caused by a small polyglutamine (polyQ) expansion (control: 4–20Q; SCA6: 20–33Q) in the carboxyl(C)-terminal cytoplasmic domain of the α1A voltage-dependent calcium channel (Cav2.1). Although a 75–85-kDa Cav2.1 C-terminal fragment (CTF) is toxic in cultured cells, its existence in human brains and its role in SCA6 pathogenesis remains unknown. Here, we investigated whether the small polyQ expansion alters the expression pattern and intracellular distribution of Cav2.1 in human SCA6 brains. New antibodies against the Cav2.1 C-terminus were used in immunoblotting and immunohistochemistry. In the cerebella of six control individuals, the CTF was detected in sucrose- and SDS-soluble cytosolic fractions; in the cerebella of two SCA6 patients, it was additionally detected in SDS-insoluble cytosolic and sucrose-soluble nuclear fractions. In contrast, however, the CTF was not detected either in the nuclear fraction or in the SDS-insoluble cytosolic fraction of SCA6 extracerebellar tissues, indicating that the CTF being insoluble in the cytoplasm or mislocalized to the nucleus only in the SCA6 cerebellum. Immunohistochemistry revealed abundant aggregates in cell bodies and dendrites of SCA6 Purkinje cells (seven patients) but not in controls (n = 6). Recombinant CTF with a small polyQ expansion (rCTF-Q28) aggregated in cultured PC12 cells, but neither rCTF-Q13 (normal-length polyQ) nor full-length Cav2.1 with Q28 did. We conclude that SCA6 pathogenesis may be associated with the CTF, normally found in the cytoplasm, being aggregated in the cytoplasm and additionally distributed in the nucleus

Covered Stent of the Left Common Carotid and Subclavian Arteries Assist the Invasive Tumor Resection

Background. Some recent reports have described the usefulness of thoracic aortic stent grafts to facilitate en bloc resection of tumors invading the aortic wall. We report on malignant peripheral nerve sheath tumor resection in the left superior mediastinum of a 16-year-old man with neurofibromatosis type 1. The pathological margin was positive at the time of the first tumor resection, and radiation therapy was added to the same site. After that, a local recurrence occurred. The tumor was in wide contact with the left common carotid and subclavian arteries and was suspected of infiltration. After stent graft placement of these arteries to avoid fatal bleeding and cerebral ischemia by clamping these arteries and bypass procedure, we successfully resected the tumor without any complications. Conclusions. Here, we report the usefulness of the prior covered stent placement to aortic branch vessels for the resection of invasive tumor