Casein kinase 1δ/ε phosphorylates fused in sarcoma (FUS) and ameliorates FUS-mediated neurodegeneration.

Aberrant cytoplasmic accumulation of an RNA-binding protein, fused in sarcoma (FUS), characterizes the neuropathology of subtypes of ALS and frontotemporal lobar degeneration, although the effects of post-translational modifications of FUS, especially phosphorylation, on its neurotoxicity have not been fully characterized. Here, we show that casein kinase 1δ (CK1δ) phosphorylates FUS at 10 serine/threonine residues in vitro using mass spectrometric analyses. We also show that phosphorylation by CK1δ or CK1ε significantly increased the solubility of FUS in human embryonic kidney 293 cells. In transgenic Drosophila that overexpress wt or P525L ALS-mutant human FUS in the retina or in neurons, we found coexpression of human CK1δ or its Drosophila isologue Dco in the photoreceptor neurons significantly ameliorated the observed retinal degeneration, and neuronal coexpression of human CK1δ extended fly life span. Taken together, our data suggest a novel regulatory mechanism of the assembly and toxicity of FUS through CK1δ/CK1ε-mediated phosphorylation, which could represent a potential therapeutic target in FUS proteinopathies.

Elucidation of the intra- and inter-molecular electron transfer pathways of glucoside 3-dehydrogenase.

Glucoside 3­dehydrogenase (G3DH) is a flavin adenine dinucleotide (FAD)-containing oxidoreductase that catalyzes the oxidation of the hydroxy group on the C-3 position of pyranose and shows broad substrate specificity by oxidizing many saccharides. Due to unique site specificity and wide substrate specificity, G3DHs can be used for synthesis of sugar derivatives, anodic catalysis in biofuel cells, multi-sugar analysis using enzyme electrode, and for enzymatic detection of 1,5­anhydro­d­glucitol, a clinical marker for diabetes. However, few studies have focused on the fundamental biochemical properties of G3DH, including its electron transfer pathway. In this study, we isolated the G3DH gene from Rhizobium radiobacter, a homologue of marine bacterial G3DH, and reported that the isolated gene fragment contains the genes encoding the G3DH catalytic subunit (subunit I), G3DH hitch-hiker subunit (subunit II), and cytochrome c-like molecule (CYTc). Furthermore, we report the recombinant expression of G3DH from R. radiobacter in Escherichia coli, the characterization of recombinant G3DH and the investigation of the molecular electron pathway of G3DH. We first prepared the G3DH subunit I-II complex using a co-expression vector for both subunits. The G3DH subunit I-II complex showed dye-mediated G3DH activity toward methyl­α­d­glucoside (MαG). Electron paramagnetic resonance (EPR) and inductively coupled plasma optical emission spectroscopy (ICP-OES) analyses revealed that subunit I contains an iron-sulfur cluster. We, then, prepared recombinant CYTc and revealed that it is capable of accepting electrons from the catalytic subunit of G3DH by absorption spectrum analysis. These results suggested that R. radiobacter G3DH possesses an iron­sulfur cluster that may play an important role in the electron transfer from FAD to cytochrome c like molecule, which is an external electron acceptor of G3DH. Furthermore, we demonstrated that CYTc mediate the electron transfer from G3DH to electrode without the artificial electron mediator.

[Modified warden procedure for partial anomalous pulmonary venous connection in an adult].

A 46-year-old woman was admitted to our hospital because of congestive heart failure and atrial fibrillation. She had undergone atrial septal defect repair at the age of 7 years. Computed tomography( CT)scan revealed right upper pulmonary vein returned to superior vena cave and the left upper pulmonary vein returned to the innominate vein. Cardiac catheterization showed Qp/Qs of 2.6. Pulmonary venous drainage repair and right-sided maze procedure was planned. The right upper pulmonary vein was led to the left atrium using the modified Warden Procedure. The left upper pulmonary vein was divided and anastomosed to the left atrial appendage. Concomitantly right-sided maze procedure was performed. Postoperative course was uneventful and CT scan revealed no stenosis at anastomotic sites. Sinus rhythm was retained and she was discharged on postoperative day 30.

[Aortic valve replacement after percutaneous transcatheter aortic valvuloplasty for severe aortic stenosis].

BACKGROUND: Aortic valve replacement( AVR) is a definitive treatment in patients with severely calcified aortic stenosis (AS). However, elderly patients with multiple comorbidities are considered to be unsuitable for AVR. Percutaneous transcatheter aortic valvuloplasty( PTAV) has been performed as a palliative option to relieve symptoms or to be a bridge use toward definitive therapy. This study aimed to examine the effectiveness and clinical outcome of surgical AVR subsequent to PTAV. PATIENTS AND METHODS: Since 2010, 5 symptomatic patients have undergone AVR after PTAV in our institution. PTAV was performed as a bridge to definitive AVR in 2 patients. Other 2 patients developed symptomatic aortic valve restenosis during a follow-up, and required AVR. In the last patient,AVR was carried out after successful noncardiac surgery subsequent to PTAV. RESULTS: AVR improved cardiac hemodynamics in all patients. There was no operative death. Postoperative course was uneventful and all patients were discharged on foot except for 1 patient in whom metastatic liver tumor from advanced gastric cancer was noted. CONCLUSION: AVR might be performed safely even in high-risk patients with the history of PTAV. PTAV is useful as a palliation or a bridge to definitive therapy for treatment of patients with severe AS unsuitable for surgery.

[Aortopulmonary fistula caused by aortic arch aneurysm rupture presenting severe left to right shunt and congestive heart failure].

A 74-year-old female was admitted to our hospital due to hyperkinetic congestive heart failure. Noninvasive positive pressure ventilation, continuous hemodialysis and inotropic support were needed preoperatively. Computed tomography revealed saccular aortic arch aneurysm with aortopulmonary fistula toward the left pulmonary artery. Cardiac catheterization revealed severe left to right shunt with the pulmonary flow/systemic flow (Qp/Qs) ratio of 6.2.Emergency operation was performed under hypothermic circulatory arrest followed by selective cerebral perfusion and lower body perfusion. The aortopulmonary fistula was directly closed, reinforced with the aneurysmal wall, and total arch replacement was performed. Although the patient temporarily recovered by endoscopic suction of the blood from the lungs and continuous hemodialysis filtration, she died because of multiple organ failure due to mesenteric ischemia on postoperative day 34.

[Bilateral pulmonary artery banding for complex congenital heart disease in a patient with trisomy 13; report of a case].

We described a case of a neonate of 13 trisomy with hypoplastic aortic arch and multiple ventricular septal defect (VSD). The patient presented symptoms of congestive heart failure due to pulmonary high flow. Because of ductal patency without prostaglandin infusion, bilateral pulmonary artery banding was performed for regulation of pulmonary high flow. Surgical intervention improved the clinical symptoms of the patient and permitted the patient to be discharged. We concluded that palliative surgery for the patient contributes to improve the quality of life both the patient and the family. This is the 1st report of bilateral pulmonary artery banding for a patient with 13 trisomy.

[Effectiveness of simultaneous cardiac resynchronization therapy in surgical valvular patients with severe heart failure].

BACKGROUND: Cardiac resynchronization therapy (CRT)has been accepted broadly as an alternative to medical treatment in managing severe heart failure patients. Despite advance in CRT, the presence of a significant valvular heart disease was currently specific exclusion criteria and a response to this therapy remains unclear. The purpose of this study was to determine the effectiveness of CRT in heart failure patients undergoing valvular operation simultaneously. PATIENTS AND METHODS: Between July 2010 and May 2012, 8 heart failure patients who underwent CRT in conjunction with valvular surgery were experienced. Right and left ventricular and atrial epicardial leads were implanted after completion of valvular procedures. In patients with chronic atrial fibrillation(Af),maze procedure was performed in order to eliminate Af. To evaluate the improvement of ventricular mechanical dyssynchrony, the echocardiographic assessment was repeated on admission and 1 month after the CRT implantation. RESULTS: There was no operative death. One patient of ischemic cardiomyopathy died of sustained ventricular tachycardia 2 months after the operation. Postoperative course of severe heart failure patients was uneventful and all patients except 1 discharged on foot with improved New York Heart Association (NYHA) class. Echocardiographic parameters of dyssynchrony did not reach to statistical significance, but several parameters, left ventricular( LV)-pre-ejectionperiod( PEP) and interventricular mechanical delay (IVMD) showing time delay of cardiac contraction, tended to be improve, suggesting contribution to satisfactory postoperative course. CONCLUSION: The acceptable outcome was demonstrated with our concept to recover the intraventricular and atrioventricular synchrony. Although it might be difficult to establish the patient selection criteria for concomitant CRT and valvular surgery, our strategy is considered to be a feasible procedure to improve the morbidity and mortality in patients with severe heart failure due to valvular disease.

[Pericardial defect incidentaly noticed during off-pump coronary artery bypass grafting; report of a case].

We experienced a rare case of congenital pericardial defect incidentally found during off-pump coronary artery bypass grafting (CABG)[OPCAB]. We performed off-pump for a 61-year-old man. He was asymptomatic but was noted to have an abnormal chest X-ray showing the enlarged heart. He had right ventricule lifting upward and apex shifting far to left side. Partial absence of the left pericardium was found. The surgery was technically more demanding than usual, because of heart rotation and inadequate pericardial stitch.

[Successful surgical treatment for aortic valve regurgitation and thoracoabdominal aortic aneurysm in a patient with homozygous familial hypercholesterolemia; report of a case].

A 46-year-old woman with homozygous familial hypercholesterolemia was referred due to aortic regurgitation. The patient was introduced selective low density lipoprotein cholesterol(LDL)apheresis 20 years ago. Echocardiogram revealed severe aortic regurgitation, and computed tomography revealed thoracoabdominal aortic aneurysm. We considered 2 staged operations were necessitated. Firstly, aortic valve replacement was performed. Emergent coronary artery bypass grafting was also done because intraoperative myocardial ischemia was strongly suspected from left ventricular hypokinesis. One year later, replacement of thoracoabdominal aorta was performed. Post-operative course was uneventful and the patient was discharged at post-operative day 21. The patients with homozygous familial hypercholesterolemia must be strictly followed up because systemic atherosclerosis frequently exacerbates despite selective LDL apheresis.

[Intraoperative cerebral malperfusion complicated with axillary artery cannulation].

To minimize the risk of malperfusion, axillary arterial cannulation which avoids retrograde flow, has been widely used in patients undergoing operations for various types of aortic pathologies. Despite several advantages of this technique, cerebral malperfusion is getting known and might be due to newly developed arterial damage or dissection. Eighty-four patients underwent cannulation of the axillary artery in recent 5 years. Malperfusion occurred in 3 patients with significant regional cerebral oxygen desaturation during operation. Axillary arterial perfusion was stopped and oxygen saturation was elevated immediately. The perfusion was switched to the femoral artery and following procedure was completed. Although axillary arterial cannulation is an attractive alternative, neither axillary nor femoral arterial perfusion is perfect to avoid the cerebral malperfusion. Whichever perfusion site is used, special care should be taken for intraoperative finding and appropriate use of each techniques.

[Re-do operation for coronary stenosis after Cabrol procedure; report of a case].

The Cabrol technique has been used to reimplant coronary arteries at the time of aortic root replacement. We describe a case of coronary stenosis after Cabrol procedure. A 42-year-old female with Marfan syndrome and chronic type B dissection who underwent aortic root replacement with Cabrol procedure complained of chest pain. Computed tomography( CT) showed extended thoraco-abdominal aortic aneurysm. Angiography revealed bilateral Cabrol limb stenosis at anastomotic sites. Re-do operation was performed under median re-sternotomy. Pannus around the coronary anastomosis was resected and patch extension using bovine pericardium was performed. Reconstruction of coronary arteries was completed by Piehler procedure and total arch replacement with elephant trunk technique was concomitantly performed. Post-operative course was uneventful. CT revealed the release from coronary stenosis.

[Our technical modification of aortic valve sparing operation focused on standardization and reproducibility].

BACKGROUND: The aortic valve-sparing operation has been accepted as an ideal procedure for the treatment of aortic root aneurysm, especially in young patients. However, this operation is thought to be technically difficult due to lack of conceptual understanding of the procedure for many surgeons. In order to overcome the surgical problem, we have developed a simple valve-sparing aortic root replacement focused on standardization and reproducibility. METHODS: Seven consecutive patients underwent the aortic valve-sparing operation in our institution.Our surgical strategy to restore valvular competency is based on the concept of inserting a dilated aortic annulus into small sized graft. Regardless of annular diameter, the Valvalva graft of 26 mm was used in all patients. Proximal end of the graft is secured on the outside of the left ventricular outflow tract with 12 mattress sutures. The 3 commissures are suspended upward inside the graft as possible. The remnants of aortic sinuses are sutured to the graft in U-shaped manner using continuous suture line. If necessary, aortic cusp repair was performed. Coronary arteries are reconstructed by Piehler's method. RESULTS: There was no operative death. Valve-sparing procedure was completed without conversion to valve replacement and no significant postoperative aortic insufficiency was noted. CONCLUSIONS: The excellent outcome was demonstrated with our simple modification. Although we recommend this technique of the aortic valve-sparing procedure which is reproducible and technically less demanding, close observation would be mandatory concerning with valvular durability in this particular circumstance.

[Right atrial rupture associated with left hemothorax].

A 71-year-old female fell down the stairs, hit the right chest and was admitted to our hospital with right chest pain. Computed tomography revealed cardiac effusion and left hemothorax due to traumatic cardiac injury. She underwent emergency operation. Median sternotomy revealed a lot of clot and no acute bleeding. However, severe bleeding started as soon as the clot was removed. The right atrium was teared by 7 cm at the site parallel to the right coronary artery. While the cardiac injury was covered with the operator's hand, cardiopulmonary bypass was established. The injury was sutured with an aid of the heart positioner to achieve complete hemostasis. Successful repair of rupture of the right atrium was reported.

[Emergent surgical treatment for purulent pericarditis associated with cardiac tamponade; report of a case].

We describe a case of purulent pericarditis presented with cardiac tamponade. A 65-year-old man was admitted to our hospital with shock by cardiac tamponade and high grade fever. Transthoracic echocardiography revealed a large amount of pericardial effusion. Surgical drainage via median sternotomy was carried out in an emergent manner. Because culture of pericardial effusion showed positive for methicillin sensitive Staphylococcus aureus and thick white purulence covering over all pericardium, purulent pericarditis was diagnosed. Postoperative course was uneventful and discharged in a good condition. Special care should be taken of purulent pericaditis in differential diagnosis of cardiac tamponade.

A novel neural network with Non-Recursive IIR Filters on EEG Artifacts Elimination.

The artifacts caused by various factors, EOG (electrooculogram), blink and EMG (electromyogram), in EEG (Electroencephalogram) signals increase the difficulty in analyzing them. In addition, EEG signals containing artifacts often cannot be used in analyzing them. So, it is useful and indispensable to eliminate the artifacts from EEG signals. In this paper, a neural network with non-recursive IIR (Infinite Impulse Response) filters are used to eliminate the artifacts from EEG signals. The proposed method is a new approach that is respect to slotting a non-recursive IIR filter into individual neurons of a neural network. First of all, in order to investigate the usefulness of the proposed method in eliminating the artifacts from EEG signals, we apply it to the artificial EEG signals that are weakly stationary process. As the result, the artifacts can be eliminated from EEG signals almost exactly using the proposed method, and it is suggested the proposed method should be useful in eliminating the artifacts from EEG signals.