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Background: Deep vein thrombosis and its progression to pulmonary thromboembolism is a major source of mortality in patients with neuromuscular disease. Furthermore, ventilator use poses a high risk of DVT to patients. Methods: Hospitalized patients with neuromuscular disease who underwent tracheotomy with positive pressure ventilation (TPPV) had DVT evaluated in the lower extremities by ongoing whole leg venous ultrasonography. Patients who were diagnosed with DVT underwent a second ultrasonography 1 month later. The attending physicians decided on therapeutic measures. All patients were followed during the study period. Results: Eight of 33 patients had DVT. The site of DVT formation was the iliac veins in three cases, femoral veins in two cases, and calf veins in three cases. All of the patients with DVT were asymptomatic. There was no difference in the clinical future between patients with DVT and those without DVT. Progression of DVT was not observed in the second ultrasonographic examination 1 month later. All patients with DVT had an excellent prognosis after a follow‐up period of 9 months. Conclusion: The prevalence of DVT in patients with neuromuscular disease who undergo TPPV might be high. Further large studies on this issue are required because the clinical significance of this DVT is uncertain. [ABSTRACT FROM AUTHOR]

Abstract: Hypoxia-inducible factor-1α (HIF-1α) has a central role in neuroprotective responses to hypoxia in the brain. Hydroxylation of HIF-1α by prolyl-hydroxylase PHD and aspargynyl-hydroxylase FIH (factor inhibiting HIF-1α) causes proteasomal degradation and transcriptional inhibition of HIF-1α. Siah ubiquitin ligases regulate the abundance of PHD via targeting for proteasomal degradation. The present study identified Siah-1 as a binding partner for another hydroxylase FIH. Siah-1 and FIH coimmunoprecipitated each other in mammalian cells. Siah-1 was found both to interact with the JmjC domain of FIH through its substrate-binding domain and to specifically ubiquitinate FIH via its RING finger domain. Siah-1 facilitated FIH degradation via the ubiquitin-proteasome pathway under hypoxic conditions. Such findings suggest that Siah ubiquitin ligases might play a role as up-stream regulators of both hydroxylases for HIF-1α, i.e., PHD and FIH, by targeting them for proteasomal degradation, leading to increased HIF-1α abundance, and transcriptional activity in hypoxia. [Copyright &y& Elsevier]

Abstract: Synphilin-1 represents a cytoplasmic protein that interacts with α-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson''s disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear. In the present study, we generated transgenic mice expressing human synphilin-1 under the prion protein promoter. Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed. In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble. Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments. [Copyright &y& Elsevier]