Toshiyuki Okazaki

Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation.

ABSTRACT The N-terminal alpha-helix domain of the human immunodeficiency virus type 1 (HIV-1) Nef protein plays important roles in enhancement of viral infectivity, virion incorporation of Nef, and the down-regulation of major histocompatibility complex class I (MHC-I) expression on cell surfaces. In this study, we demonstrated that Met 20 in the alpha-helix domain was indispensable for the ability of Nef to modulate MHC-I expression but not for other events. We also showed that Met 20 was unnecessary for the down-regulation of CD4. These findings indicate that the region governing MHC-I down-regulation is proximate in the alpha-helix domain but is dissociated functionally from that determining enhancement of viral infectivity, virion incorporation of Nef, and CD4 down-regulation.

Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma

Interferon-beta (IFN-β) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-β, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN-β-induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.

Blocking of the interaction between Wnt proteins and their co- receptors contributes to the anti-tumor effects of adenovirus- mediated DKK3 in glioblastoma

The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.

The ratio of D-dimer to brain natriuretic peptide may help to differentiate between cerebral infarction with and without acute aortic dissection

BACKGROUND Previous studies reported that the plasma d-dimer level reflects the activity of thrombus formation in the left atrium of patients with acute cerebral infarction and acute aortic dissection (AAD). Brain natriuretic peptide (BNP) is considered to be a marker of chronic heart failure. The differential diagnosis in the emergency room between stroke due to cardioembolism and AAD is difficult but important for early treatment especially in patients requiring intravenous thrombolysis with a recombinant tissue-type plasminogen activator. We aimed to investigate the association between the plasma d-dimer and BNP levels in patients with cerebral infarction and AAD. METHODS We identified 115 consecutive patients with ischemic stroke who were admitted within 72 h of symptom onset and 15 consecutive patients with AAD and measured the level of plasma d-dimer and BNP and the d-dimer:BNP ratio. RESULTS In patients with AAD the d-dimer level was significantly higher than that in patients with any other stroke subtypes and their BNP level was significantly lower than that in patients with cardioembolic stroke. The d-dimer:BNP ratio was significantly higher in patients with AAD than in those with any other stroke subtype. Compared to patients with a cardioembolic stroke subtype they manifested significantly higher d-dimer levels and d-dimer:BNP ratios suggesting that this ratio may help to diagnose cerebral infarction due to AAD (sensitivity 80%, specificity 93.5%, cut-off 0.074). When the population was limited to patients within 6h of onset, the ratio had higher sensitivity and specificity at the same cut-off value (sensitivity 81.8%, specificity 96.4%). CONCLUSION We found that the d-dimer:BNP ratio may be helpful in distinguishing between cerebral infarction with and without AAD.

Surgical Strategies in Management of Cervical Spondylotic Myelopathy.

Regarding surgical approaches, 40% reported higher complication rates in posterior compared with 29% in anterior, and 30% believed the rates were the same. It is interesting to note that perceptions varied among regions. In detecting more prevalent complications following the anterior or posterior approach, 45% of European and North Americans chose posterior, while only 33% of respondents from Asia Pacific chose this option. Actually, 37% from Asia Pacific argued that complication rates were higher in the anterior approach.

Bone scintigraphy for the diagnosis of the responsible level of osteoporotic vertebral compression fractures in percutaneous balloon kyphoplasty

OBJECTIVES This study was to investigate the efficacy of bone scintigraphy in order to diagnose the correct level of vertebral compression fractures (VCF) for the severe back pain before balloon kyphoplasty (BKP) was performed. PATIENTS AND METHODS A total of 30 consecutive patients were treated with BKP for 38 times since May 2012. Eleven patients had acute multi-level VCFs. Bone scintigraphy was performed preoperatively except for the first case and the case with a chronic course and the level responsible for the pain was defined with bone scintigraphy. The responsible level of acute single level VCF was easily diagnosed with T1, T2, and fat sat T2 but the responsible level of acute multi-level VCFs was not easily determined. BKP was performed at the most accumulated level on bone scintigraphy and the preoperative and postoperative Visual analogue score (VAS) scores were researched with questionnaire postoperatively. RESULTS BKP was effective in relief of pain at the most accumulated level on bone scintigraphy. Preoperative VAS score (average 8.6) was significantly improved at post-ope day1 (average 3.9), at discharge (average 2.4) and at 1 month after discharge (average 2.1). New symptomatic VCFs after the first treatment occurred in 5 patients at an adjacent level in 3 and twice in 2 of 5 and additional BKP was effective in each patient. CONCLUSIONS The correct level of symptomatic VCF in the patients with acute multi-level VCFs should be diagnosed to achieve good clinical results. In this study, we showed that bone scintigraphy is very useful in diagnosing the proper level for BKP in addition to CT and MRI.

Successful Emergency Carotid Endarterectomy after Thrombolysis with Intravenous Recombinant Tissue-Type Plasminogen Activator.

Acute internal carotid artery (ICA) occlusion may result in severe disability or death. Revascularization by carotid artery stenting after treatment with intravenous (iv) recombinant tissue-type plasminogen activator (rt-PA) has been documented. However, there are few reports on emergency carotid endarterectomy (CEA) within 24 hours after the iv administration of rt-PA. We treated a 58-year-old man with right ICA occlusion with iv rt-PA. Although partial recanalization of the ICA was obtained, severe stenosis at the origin of the ICA persisted and he developed fluctuating neurological deficits. To prevent progressive stroke he underwent CEA 10.5 hours after rt-PA treatment. Thereafter his blood pressure was strictly controlled under sedation. During and after CEA there were no hemorrhagic complications. Our findings suggest that emergency CEA may be an option to address symptomatic severe residual ICA stenosis even after iv rt-PA therapy delivered in the acute stage. J. Med. Invest. 63: 300-304, August, 2016.

Coloring Technique of Magnetic Resonance Angiography for Superficial Temporal Artery to Middle Cerebral Artery Bypass Surgery

OBJECTIVE Superficial temporal artery (STA)-to-middle cerebral artery (MCA) bypass is an established surgical technique for achieving revascularization. It is important to select the proper recipient artery of the MCA. Three-dimensional computed tomographic angiography (3D-CTA) and conventional angiography are useful in the selection process but need contrast agents. The authors have designed a coloring MRA technique that needs no agents to visualize the recipient artery. Retrospective evaluation of the efficacy and limitation for selection of the recipient artery and decision of the place and size of the craniotomy were carried out. METHODS The authors performed the coloring MRA before operation since January 2013. Ninety-two patients underwent STA-MCA bypass for atherosclerotic stenosis or occlusion of internal carotid artery (ICA), MCA with reference to the coloring MRA. To evaluate the efficacy of coloring MRA, the control group consisted of 75 patients who underwent STA-MCA bypass between January 2012 to November 2013 with reference to 3D-CTA. The size of craniotomy was retrospectively calculated and compared. RESULTS Neither additional craniotomy nor wrong selection of the recipient artery was done in either group. There was no significant difference in size between the 2 groups in both single and double bypass. CONCLUSIONS The coloring MRA technique was not inferior to 3D-CTA with respect to the size of craniotomy. This novel technique was found to be very helpful not only for the virtual identification of the proper recipient artery but also for preoperative simulation such as decisions about length of donor artery, location, and size of craniotomy.

Posttraumatic Cerebrospinal Fluid Leak Associated with an Upper Cervical Meningeal Diverticulum

BACKGROUND Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear. CASE DESCRIPTION We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved. CONCLUSIONS Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak.

Microdiscectomy and Foraminotomy in Cervical Spondylotic Myelopathy and Radiculopathy

This study was to assess the efficacy of microdiscectomy, cage fixation, and right tranuncal foramintomy for the patients suffering from right radiulo-myelopathy. Anterior cervical foraminotomy was reported to be an effective option for the treatment of cervical degenerative radiculopathy but with the problem of recurrence. Since Hakuba reported the method of trans-unco-discal approach in 1976, it was designed as keyhole foraminotomy which was called transuncal approach, transpedicular approach or transvertebral approach. In the anterior approach, we usually use the right-sided approach because most of us are right-handed surgeons. We retrospectively investigated our patients who had the right foraminal stenosis causing radiculopathy and were treated with microdiscectomy, cage fixation, and right keyhole transuncal foraminotomy. Since 2011, 23 patients were treated with the manner. All of the 23 patients who had central canal stenosis and among the 23 patients, 8 patients showed only right radiculopathy and 15 patients showed radiculo-myelopathy. In all patients, the radiculopathy disappeared or significantly improved without any complications postoperatively. The average of VAS scores was 7.6 ± 2.2 in preoperative state, 2.8 ± 2.2 at discharge, and 1.1 ± 1.6 in 1 month after surgery. The average of follow-up time was 38.3 months and they had no recurrence of radiculopathy. We showed that this manner is effective and one option for the combined disease of right foraminal and canal stenosis and we believe that this manner is not complex and safe if we can understand the anatomy.