Proper regulation of intracellular protein levels is essential in maintaining cellular homeostasis. The ubiquitin-proteasome system plays a central role in this regulation by degrading ubiquitinated-substrates in a target-specific manner. The abnormal enhancement of proteasomal activity in cancer tissues is closely related to cancer cell proliferation or survival. Therefore, it is important that we elucidate the underlying mechanism as a basis for cancer treatments with proteasome inhibitors. Here, we focused on the proteasomal regulator UBE3C and UBE3B, another highly homologous protein. Although these factors have been hypothesized to contribute to cell proliferation through proteasome regulation, their exact roles are largely unclear. In this report, we showed that UBE3B is required for cell proliferation. Although the cellular function of UBE3B is not known thus far, it is now clear that UBE3B co-localizes with the proteasome component in the nucleus and represses the aggregation or accumulation of ubiquitinated substrates. These results suggest that proper proteasomal regulation by UBE3B contributes to cell proliferation. In addition, UBE3B co-localizes with UBE3C, and the decreased proliferation of depleted UBE3B was slightly canceled by the depletion of both proteins. Taken together, UBE3C may modulate the function of UBE3B in cell proliferation.
Going forward, it is imperative that we clarify the relationship between the expression pattern of these factors and proteasomal function. This will help to ascertain the role of these factors as potential proteasome inhibitors in cancer therapy.

Objectives: The purpose of this study is to evaluate the operative outcomes of conventional total aortic arch repair and hybrid arch repair.
Methods: Between July 2009 and October 2014, 48 consecutive patients underwent aortic arch repair (excluding hemiarch or partial arch reconstruction ) at St. Marianna university hospital. We categorized 38 total aortic arch repair with antegrade cerebral perfusion under circulatory arrest as T group and 10 hybrid aortic arch repair with thoracic endovascular aortic repair as H group. Then, we compared early outcomes between T and H groups.
Results: Preoperatively, patient ages and Japan risk scores for mortality and major complications were significantly higher in H group than in T group (69.2±9.9 years vs 77.9±4.2 years; P. .0003 and 21.3±12.0 vs 37.8±16.2; P. <0.001). There were no significant differences in 30-day and in-hospital deaths between the T and H groups (0% [0/38] vs 0% [0/10]; P. >.99 and 2.6% [1/38] vs 10.0% [1/10]; P. .2995). Although there were no significant differences in the incidences of other major complications, low output syndrome and spinal infarction were observed more frequently in H group (0% [0/38] vs 10.0% [1/10]; P. .0049 and 0% [0/38] vs 10.0% [1/10]; P. .0049) compared with T group.
Conclusions: Although there were more high risk patients in H group than in T group, early operative mortalities were equivalent in both groups.

Spinal epidural abscess (SEA) is known to cause paralytic symptoms during follow-up. Although SEA and spinal epidural hematoma (SEH) both involve epidural lesions, some physicians believe that SEA results in less improvement of paralysis. We investigated the causes of paralytic symptoms in patients with epidural abscess.
The subjects comprised 20 patients diagnosed as having acute SEA for which the pathogenic bacteria could be identified. Patients showing clear muscle weakness and bladder and rectal disturbances during treatment follow-up were assigned to the paralytic group and those with no neurological disorders were assigned to the non- paralytic group. The most common pathogenic bacteria were Staphylococcus aureus (13/20 cases, 65%), which accounted for 11 of 12 cases (92%) in the paralytic group and 2 of 8 cases (25%) in the non-paralytic group. Thus, the percentage of cases involving S.aureus was significantly higher in the paralytic group (P=0.004). Moreover, all 3 patients with the solitary occurrence of SEA (all caused by S.aureus) were in the paralytic group.
Because cases of SEA due to S.aureus involve ischemic changes to neural tissue and bacteria-induced histological damage in addition to direct compression of neural tissue by the tumor, less improvement in paralysis may be seen than in cases of SEH. Moreover, SEA due to S.aureus is thought to be more likely to result in neuropathy than SEA caused by other bacteria. Because the SEA in the 3 patients with solitary occurrence was due to S.aureus, it developed rapidly, caused paralytic symptoms and required surgical treatment. Going forward, the type of pathogenic bacteria should be taken into consideration when determining treatment strategy.

Radiotherapy is one of the first-line strategies for cancer treatment. However, radioresistance remains a major obstacle against effective radiotherapy. Recent advances in cancer research have underlined several intrinsic mechanisms that render cancer cells radioresistant. Additionally, cross-talk between tumor and myeloid cells in the tumor microenvironment (TME) comprises an important extrinsic mechanism that effects tumorigenicity and therapeutic resistance. Thus, factors affecting the biology of myeloid cells are expected to contribute to radioresistance and may serve as novel therapeutic targets to overcome radioresistance. Interleukin-34 (IL-34) is a hematopoietic cytokine that acts as a second ligand of CSF1R, in addition to the previously well-known ligand M-CSF. Both M-CSF and IL-34 regulate survival, proliferation and differentiation of myeloid lineage cells including monocytes, macrophages and osteoclasts. Importantly, IL-34 can be induced upon cellular stress and contributes to the pathogenicity of various diseases. In this study, we examined whether IL-34 expression could be induced in radiation-stressed cancer cells. In prostate and colon cancer cells, both M-CSF and IL-34 expressions were induced upon exposure to radiation. M-CSF expression showed a tendency to increase during the early phases (24-48 h), whereas IL-34 expression increased at later phases (72-96 h). Using various pharmacological inhibitors, we found that M-CSF and IL-34 expressions were regulated differentially by Abl and NF-kB, respectively. Repeated radiation exposure results in induced expression of both M-CSF and IL-34, with the expression of IL-34 stronger than that of M-CSF, consistent with its relation to chronic inflammatory conditions. Taken together, our results show that both M-CSF and IL-34 can be induced in radiation-stressed cancer cells, with a tendency for IL-34 to dominate upon repeated radiation exposure, which suggests important roles for IL-34 in radioresistance. Future work will focus on the impact of IL-34 on radiation-treated TME and the therapeutic potential of IL-34 targeting when accompanied by anti-cancer radiotherapy.

Quinolone antibacterial agents have been reported to induce articular cartilage damage in juvenile animals, and therefore, their therapeutic use in pediatric and adolescent patients is restricted. However, the exact mechanism of quinolone-induced chondrotoxicity remains unclear. The aim of this study was to investigate the molecular mechanism of chondrotoxicity induced by ciprofloxacin, a second-generation quinolone. Ciprofloxacin (1,200 mg/kg once daily) was orally administered on 10 consecutive days to 3-week-old rats. After treatment, the thickness of the cartilage decreased, and dilated cisternae of rough endoplasmic reticulum were observed. A shotgun proteomics analysis of ciprofloxacin-treated and -untreated rat chondrocytes was subsequently performed. As a result, 78 kD glucose-regulated protein (GRP78), an endoplasmic reticulum (ER) stress-related protein, was identified. To investigate whether ER stress is involved in ciprofloxacin-induced chondrotoxicity, we examined the protein expression of GRP78 and C/EBP homologous protein (CHOP), which is well known to promote cell death. Western blot analysis showed a significant 2.2-fold increase (p < 0.01) in CHOP, but not in GRP78, protein expression in ciprofloxacin-treated rat chondrocytes compared to those in untreated rats. These results suggested that the ciprofloxacin-induced chondrotoxicity was caused by induced ER stress-mediated apoptosis in juvenile rat chondrocytes.

Oxidative stress is implicated in the pathogenesis of schizophrenia. Although atypical antipsychotic drugs have been reported to have antioxidant effects, the pathophysiologic mechanism of schizophrenia with various clinical symptoms and the effect of antipsychotics on neurons are entirely unknown. The aim of this study was to investigate the mechanism of aripiprazole, an atypical antipsychotic drug, on neurons. A shotgun proteomics analysis of aripiprazole-treated human neuroblastoma SH-SY5Y cells was performed. As a result, peroxiredoxin (Prx) 1 and 6, antioxidant enzymes, were identified in aripiprazole-treated SH-SY5Y cells. Subsequently, we examined the change in protein expression of antioxidant enzymes by aripiprazole. We observed a significant increase in Prx6 and superoxide dismutase (SOD) 1 protein expression in aripiprazole-treated SH-SY5Y cells compared to control SH-SY5Y cells. In contrast, there was no change in the expression of Prx1, SOD2, catalase and glutathione peroxidase. These results suggested that aripiprazole has an antioxidant effect on neurons via increased expression of Prx6 and SOD1.

Background: The relation between corticosteroids and thrombosis continues to remain uncertain. We investigated the effects of methylprednisolone (m-PSL) treatment on coagulation factors in patients before and after pulse steroid therapy for immune thrombocytopenia (ITP) and studied the m-PSL-induced changes in mRNA expression of various coagulation factor genes using HepG2 cells.
Materials and Methods: m-PSL (30 mg/kg/dose) was administered intravenously for 3 days to patients with ITP (n=3). The changes in fibrinogen levels and activities of prothrombin, FV, FVII, FVIII, FIX, FX, FXI, and FXII before treatment and one day after the end of treatment were analyzed. Furthermore, the mRNA expression of coagulation factor genes in the cultured HepG2 cell treated with m-PSL (100μM) was also analyzed by RT-PCR.
Results: An increase in FVIII: C (p=.00064) was observed in the patients with ITP after the m-PSL pulse therapy. However, in the experiments in which cultured HepG2 cells were treated with m-PSL, there was no increase in the expression of the coagulation factor genes, including the FVIII gene. However, the expression of FXI mRNA alone was decreased significantly (p=.044).
Discussion: The results of the increased FVIII: C after m-PSL treatment suggested the induction of the hypercoagulable state and supported finding of previous reports. However, the relation of the coagulation factors between the activity changes of the patients with ITP and the mRNA expression in HepG2 cells was inconsistent. Further investigations to clarify the mechanism underlying the hypercoagulable state after m-PSL treatment is necessary.

Objective: Frozen-thawed ovarian tissue transplantation is a 20-year-old technology. We are currently developing a closed device for ovarian tissue cryopreservation and are using transmission electron microscopy rather than hormone values to physiologically evaluate the ovarian tissue following freezing, thawing and transplantation of ovaries preserved by our device.
Methods: Ovaries of cynomolgus monkeys were resected by laparotomy, and these tissues were cryopreserved in liquid nitrogen for more than 3 hours in a closed-type vitrification device. After these tissues were thawed, they were transplanted to the omentum and the mesosalpinx, and ovarian stimulation was started after confirmation of the recovery of the menstrual cycle following transplantation. Oocytes were collected from the transplanted ovarian tissue, and a portion of the ovarian tissues resected by laparotomy were evaluated with a transmission electron microscope.
Results: Ovarian tissues were evaluated by transmission electron microscopy immediately after they were thawed and after transplantation to the omentum and mesosalpinx. Immediately after thawing, gaps were observed in the interstitial portions of the ovarian tissue. Moreover, as time elapsed following transplantation, changes in the ovarian tissue such as vacuolar degeneration were confirmed. Oocytes could not be acquired from ovarian tissue transplanted into the mesosalpinx in which the cellular components could not be confirmed with the transmission electron microscope.
Conclusion: Tissue evaluation after ovarian tissue cryopreservation by transmission electron microscopy suggested the effectiveness of a newly developed closed device for ovarian tissue preservation.

Acute sinusitis can lead to intracranial complications, such as brain abscess, subdural or epidural empyema, meningitis, and cavernous sinus thrombosis, and to orbital complications, such as orbital cellulitis and orbital subperiosteal abscess. We encountered a case of bacterial meningitis that arose from frontal sinusitis. The patient was a 13-year-old-girl who presented with fever, headache, diplopia, and some neck stiffness and right upper limb numbness. She was referred to our department when blood tests revealed C-reactive protein elevation. Head computed tomography and cerebrospinal fluid examination were performed, and the results led a diagnosis of bacterial meningitis and subdural abscess; staining of the cerebrospinal fluid revealed gram-positive cocci. We began treatment by administering ceftriaxone and vancomycin, but when Streptococcus pneumoniae was isolated from the spinal fluid and blood, we switched to ampicillin because of the sensitivity of S. pneumoniae to this antimicrobial agent. Head magnetic resonance imaging was performed, and a semicircular subdural abscess around the fornix was seen. Because the patient’s numbness seemed to result from pressure caused by this abscess, we performed burr-hole drainage. The antibiotics were administered for a total of 6 weeks, and the patient improved without sequela. Pneumococcal serotype 20 was identified in the final culture. Intracranial complications of acute sinusitis may result in neurologic sequela or be fatal; hence, early diagnosis and treatment are critical.

In recent years, narrowing of the root of the celiac artery has drawn attention as a cause of pancreaticoduodenal artery aneurysm. The median arcuate ligament (MAL) is formed by connecting the left crus of the diaphragm and the right crus anterior to the vertebral body, and vascular compression at this level can alter the hemodynamics of the celiac artery root resulting in aneurysms. We present the case of a 61-year-old man, who presented with abdominal pain. Abdominal aneurysms were found by CT, and transcatheter arterial embolization (TAE) was performed in the emergency department. The patient’s post-TAE course was uneventful and he was subsequently referred to our hospital for a surgical cure. We performed laparoscopic median arcuate ligamentectomy. Intraoperatively, strong binding connective tissue was found on the anterior surface of the celiac artery, which was dissected away. Antegrade hemodynamic flow was observed in the common hepatic artery on the CT image obtained on the seventh postoperative day. Anterior hemodynamic flow was also observed in the common hepatic artery, and the narrowing at the root of the celiac artery improved as well. In cases where selective TAE is successful, laparoscopic MAL resection may be an effective radical procedure.

Cementifying fibroma is a relatively rare benign tumor. The incidence of this disease is estimated to be approximately 2% of all odontogenic tumors. We report a rare case of cementifying fibroma of the mandible in a 55-year-old woman with complete edentulism. She noted a mass on her right mandibular gingiva and was referred to our department in July 2014. Plain computed tomography revealed a tumor within the right mandibular body. The tumor was subsequently resected with the patient under general anesthesia. The histopathological examination showed that the tumor consisted of fibrous connective tissue with particles suggestive of cementicles. There have been no signs of recurrence over 1 year of follow-up after surgery.