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Noboru Sakai

Publications and source records attributed to Noboru Sakai.

At least 19 recordsLinked to original sources
PubMed2005

Culture method for the induction of neurospheres from mouse embryonic stem cells by coculture with PA6 stromal cells.

Embryonic stem (ES) cells proliferate and maintain their pluripotency for over 1 year in vitro and may therefore provide a sufficient source for cell therapies. However, most of the previously reported methods for obtaining a source for cell therapies have not been simple. We describe here a novel method for induction of neurospheres from mouse ES cells by coculturing on PA6 cells instead of the formation of embryoid bodies. The ES cells cocultured with the PA6 stromal cell line for at least 3 days were capable of differentiating into spheres. The cells in the spheres were all green fluorescent protein (GFP) positive, showing that they were derived from GFP-expressing D3-ES cells. The spheres contained nestin-positive cells. The number of spheres increased when they were cocultured with PA6 for a longer period. Sphere formation was observed even after 10 mechanical dissociations and subculturings, showing its self-renewal ability. The cells differentiated into microtubule-associated protein-2 (MAP2)-positive neuronal cells and glial fibrillary acidic protein (GFAP)-positive glial cells. gamma-Aminobutyric acid-positive cells and tyrosine hydroxylase-positive cells were also observed in the spheres. The percentages of the MAP2- or GFAP-positive cells in the sphere changed according to the period of coculture on PA6 cells. At an early stage of coculture, more neurons were generated and, at a later period, more glial cells were generated. These results suggested that neurosphere could be generated from ES cells by coculturing with PA6, and that these cells resembled neural stem cells derived from mouse fetal brain tissue.

Animals↗
PubMed2005

Hemangioblastomatosis of the central nervous system without von Hippel-Lindau disease: a case report.

We report a very rare case of hemangioblastomatosis in a patient without von Hippel-Lindau disease (VHL). A 50-year-old woman had a history of surgical procedures for total removal of a cerebellar hemangioblastoma (HB). Twenty-one years after the last operation, she developed communicating hydrocephalus; computed tomographic (CT) scans of the brain showed no recurrence of HB in the posterior fossa. Subsequently, she underwent placement of a ventriculo-peritoneal shunt. One year later, she was readmitted because of progressive numbness and pain in the left lower limb. Magnetic resonance imaging (MRI) showed multiple Gd-enhancing tumors around the brain stem, in the cerebellum, and in the cervical and thoracolumbar regions of the spine. She underwent surgical removal of the tumors in the cerebellum and spinal cord. Although the extirpated tissues were histopathologically verified HB with less than 1% MIB-1 labeling index, surgery was followed by external beam radiation therapy with doses of 40 Gy to the whole brain, 10 Gy to the posterior fossa and 30 Gy to the whole spine. However, she subsequently developed quadriparesis and became bedridden.

Central Nervous System Neoplasms↗
PubMed2005

Two cases of dissecting aneurysm of the distal posterior inferior cerebellar artery: possible involvement of segmental mediolytic arteriopathy in the pathogenesis.

BACKGROUND: Dissecting aneurysm of the posterior inferior cerebellar artery (PICA) uninvolved with the vertebral artery is rare. The exact pathohistological diagnosis might result in 'unknown' because the underlying pathoanatomical features are, for a variety of reasons, not always identified. CASE DESCRIPTION: We report herein two cases of dissecting aneurysm harbored in different segments of the distal posterior inferior cerebellar artery. In our cases, after trapping the PICA at both just proximal and distal to the aneurysm, the abnormal portion was successfully resected with/without an end-to-end anastomosis. The first patient made a good recovery, while the other died 2 days after the surgery. Although its pathogenetic etiology was unidentified in the second case, the formation of dissecting aneurysm had resulted from a segmental mediolytic arteriopathy in the first case. CONCLUSION: This is the first report of a segmental mediolytic arteriopathy possibly being identified as causing an isolated dissecting aneurysm at this site.

Aortic Dissection↗
PubMed2005

Thrombosed unruptured cerebral aneurysm causing brain infarction followed by subarachnoid hemorrhage--case report--.

A 71-year-old man presented with right hemiparesis and aphasia due to cerebral infarction in the frontal lobe. Computed tomography (CT) revealed a high-density mass, 12 mm in diameter, in the stem of the left sylvian fissure. Carotid angiography demonstrated occlusion of the left ascending frontal artery complex and retention of contrast medium at the bifurcation of the left middle cerebral artery (MCA). The diagnosis was cerebral infarction caused by occlusion of the ascending frontal artery complex resulting from thrombosed left MCA aneurysm. The patient was managed conservatively and his neurological symptoms gradually improved. One month later, he lapsed into a coma. CT revealed subarachnoid hemorrhage. Carotid angiography showed a large left MCA aneurysm with branch occlusion of the left ascending frontal artery complex. A left frontotemporal craniotomy was performed. The MCA aneurysm was opened and the intramural thrombi removed, and finally neck clipping was performed. The patient made a good postoperative recovery.

Aged↗
PubMed2005

Isolated central nervous system hemophagocytic lymphohistiocytosis: case report.

OBJECTIVE AND IMPORTANCE: The first case of histologically proven hemophagocytic lymphohistiocytosis (HLH) isolated to the central nervous system (CNS) is reported. HLH affecting the CNS mimics several neurological disorders and may be misdiagnosed. The diagnostic and therapeutic problems of this disease are discussed. CLINICAL PRESENTATION: We report a case of a 5-year-old girl with a 2-month history of right hemiparesis. The initial magnetic resonance imaging scan mimicked the appearance of malignant glioma or cerebral infarction. By use of neuroimaging alone, it was extremely difficult to reach an appropriate diagnosis. INTERVENTION: Pathological examination of a surgical specimen of the lesion revealed histological characteristics typical of HLH. Because of the absence of both physical and blood chemical findings of systemic HLH, the patient was diagnosed as having HLH isolated in the CNS without systemic HLH. Radiotherapy with corticosteroid administration led to complete resolution of the CNS lesions, but the duration of remission was only 3 months. The patient died secondary to refractory progression of the CNS lesion. CONCLUSION: Radiotherapy with corticosteroid administration led to a complete resolution of the lesions, although for only a transitory remission. Although HLH is extremely rare, the existence of this disease isolated in the CNS should be documented, and further case accumulation and therapeutic investigations are needed to clarify the pathophysiological characteristics of this disease.

Brain Diseases↗
PubMed2004

A non-infantile case of desmoplastic infantile astrocytoma.

CASE REPORT: We describe a very rare non-infantile case of desmoplastic infantile astrocytoma (DIA). A 9-year-old boy presented with motor weakness and sensory disturbance in his right upper and lower limbs. CT and MRI showed a contrast-enhanced large cystic tumor in the left sensorimotor area. We successfully resected the entire tumor. Its histopathological features were typical of DIA. OUTCOME: The patient's neurological symptoms improved postoperatively. Neither radiotherapy nor chemotherapy was used postoperatively. The patient developed normally and had been doing well for 12 months after surgery without tumor recurrence.

Astrocytoma↗
PubMed2004

Hepatocyte growth factor promotes neuronal differentiation of neural stem cells derived from embryonic stem cells.

We previously reported that hepatocyte growth factor (HGF) promoted proliferation of neurospheres and neuronal differentiation of neural stem cells (NSCs) derived from mouse embryonic brain. In this study, spheres from mouse embryonic stem (ES) cells were generated by floating culture following co-culture on PA6 stromal cells. In contrast to the behavior of the neurospheres derived from embryonic brain, addition of HGF to the growth medium of the floating cultures decreased the number of spheres derived from ES cells. When spheres were stained using a MAP-2 antibody, more MAP-2-positive cells were observed in spheres cultured with HGF. When HGF was added to the growth and/or differentiation medium, more MAP-2-positive cells were also obtained. These results suggest that HGF promotes neuronal differentiation of NSCs derived from ES cells.

Animals↗
PubMed2004

Neuronal protein NP25 interacts with F-actin.

Neuronal protein NP25 is a neuron-specific protein present in highly differentiated neural cells, but its functional properties have not been well characterized. NP25 shows high amino acid sequence homology with the smooth muscle cell cytoskeleton-associated proteins, SM22, mp20, and calponin. To gain an insight into the biological functions of NP25, we first examined its subcellular localization in the human neuroblastoma cell line, SK-N-SH. NP25 diffusely distributed in the cytoplasm and fiber-like staining was also observed. It showed that NP25 co-localized with F-actin on stress fibers. A co-sedimentation assay demonstrated that NP25 bound to filamentous actin. Further investigations using fluorescence resonance energy transfer (FRET) technique revealed intracellular binding of NP25 and actin. The significance of the interaction between NP25 and F-actin is discussed.

Actins↗
PubMed2004

Surgery for carotid dural ring aneurysms.

BACKGROUND: Carotid aneurysms of the paraclinoid segment are usually located in the intradural space, but can infrequently straddle the intra- and extradural space. CASE DESCRIPTION: We present 2 cases of unruptured carotid dural ring aneurysms with an aneurysmal sac that straddled the distal dural ring. Each paraclinoid aneurysm projected superiorly from the anterior surface of the internal carotid artery with a relatively flattened dome and central indentation on angiography. The aneurysmal domes were circumscribed by the distal dural ring and straddled the intra- and extradural space. After broad opening of the distal dural ring, aneurysms were successfully obliterated by clip application in parallel with the internal carotid artery. CONCLUSION: These cases underscore the significance of an aneurysmal dome indentation on angiographic images as a reflection of aneurysmal circumscription by the distal dural ring. Aneurysms that straddle the intra- and extradural space may require broad opening of the distal dural ring for adequate control and clipping.

Aged↗
PubMed2004

Prognostic factors and therapeutic problems of primary intracranial choriocarcinoma/germ-cell tumors with high levels of HCG.

OBJECTIVE: Primary intracranial choriocarcinoma (PICCC)/germ-cell tumors (GCTs) with high levels of human chorionic gonadotropin (HCG) (PICCC/GCTs with HL-HCG) are rare and malignant. The goal of this study was to report our 3 cases of PICCC/GCTs with HL-HCG and to review the literature to elucidate the clinical problems and prognostic factors and to discuss the therapeutic modalities of this rare tumor. METHODS: Survival was analyzed in 66 previously reported PICCC/GCTs with HL-HCG including our 3 cases, of which the clinical results have been described in the literature since 1975. In the 66 cases (mean age: 12.1 years; male/female: 45/21), 35 were verified histologically as pure choriocarcinoma, 23 were as mixed GCTs with choriocarcinoma element, and 8 were not verified as including choriocarcinoma element histologically but with very high HCG levels. Significance of the differences among survival curves concerning each parameter (age, sex, tumor location, serum HCG/beta-HCG level, precocious puberty, extent of surgery, radiotherapy, chemotherapy, mixture of other non-germinomatous GCT elements and extraneural metastasis) was tested using univariate and multivariate analyses. RESULTS: The median survival time and the 1- and 2-year survival rates were 22 months, 61.2% and 49.8%, respectively. In univariate analysis, male, subtotal removal or more, radiotherapy and chemotherapy were revealed to be significantly good prognostic factors. However, suprasellar region and tumor hemorrhage were poor prognostic factors. Multivariate analysis showed that extent of surgery, radiotherapy and chemotherapy were independent prognostic factors. CONCLUSIONS: Although, we should mind the limitations of this study design because of case selection bias, different treatment protocols and incomplete follow-up of patients, this study led the following results and suggestive conclusions. Tumor hemorrhage and progressive extraneural and cerebrospinal fluid metastasis were characteristic clinical problems of PICCC/GCTs with HL-HCG. In the cases with extremely elevated levels of HCG, biopsy for histological diagnosis may be no longer needed. Initial biopsy and radiotherapy may lead to tumor hemorrhage. To prevent tumor hemorrhage, gross tumor removal followed by radiotherapy and chemotherapy should be aimed for. A few courses of chemotherapy before surgery may prevent metastasis. Stereotactic radiotherapy and high dose chemotherapy may be promising options for treatment.

Adolescent↗
PubMed2004

[Therapeutic neurogenesis for CNS disorders].

Although neurogenesis is observed in the human adult brain, its regulation and role are unknown. Among lots of factors promoting neurogenesis, we focused on fibroblast growth factor-2 (FGF-2), because it is known to be an important factor for neural stem cell culture. In our study, neurogenesis was upregulated in the dentate gyrus (DG) following cerebral ischemia and kainic acid-induced seizure in wild type animals, but it was reduced in FGF-2-/- mice. When FGF-2 was overexpressed using gene transfer technique with herpes virus vector, neurogenesis was upregulated, and, furthermore, degenerative changes of the hippocampus after traumatic brain injury were also reduced. These results suggested that FGF-2 is a critical factor to regulate neurogenesis in the DG after brain injury. Administration of growth factors after brain injury may provide a strategy for repair of the brain following neuronal injury and other CNS disorders.

Animals↗
PubMed2004

Interleukin-2 activated microglia engulf tumor infiltrating T cells in the central nervous system.

Interleukin-2 (IL-2) has been utilized to treat cancer patient. However, recent studies disclosed that IL-2 induces T cell death. To clarify IL-2 induced T cell apoptosis at tumor sites in the central nervous system (CNS), we utilized an intracranial implantation of IL-2 cDNA transduced murine tumor cells and examined freshly recovered tumor infiltrating T lymphocytes (TIL) with a magnetic beads separation method. CD8(+) TIL recovered from the IL-2 therapy model had three times more apoptosis than a control group, tumor weights at day 12 decreased (0.016 versus 0.041 g/mouse) and the number of TIL per gram of tumor tissue increase more than six times by IL-2 therapy (5.69x10(6) versus 33.7x10(7) cells per mouse). In addition, both activation marker expressions (CD25 and CD69) and cytokine message levels (interferon gamma, and tumor necrosis factor alpha) on CD8(+) TIL decrease in the IL-2 therapy model. Moreover, we detected higher CD8beta message levels in purified tumors associated with F4/80(+) cells from the IL-2 model than the control by a one-step RT-PCR method. Finally, we observed many CD8beta(+) TIL surrounded by numerous infiltrating F4/80(+) cells in the tumor tissues of the IL-2 therapy model by immuno-fluorescence microscopic analysis. Our data show that IL-2 sensitization of apoptosis induction for CD8(+) TIL occurred and the apoptotic T cells were eliminated by F4/80(+) microglia in the CNS. Moreover, this is the first report describing in situ elimination of TIL by F4/80(+) phagocytic cells in the CNS.

Animals↗
PubMed2004

Prediction of neurologic deterioration in patients with lacunar infarction in the territory of the lenticulostriate artery using perfusion CT.

BACKGROUND AND PURPOSE: A significant proportion of patients with lacunar infarctions experience neurologic deterioration after onset. However, no clinical examination has been established for prediction of the progress of symptoms. To determine the hemodynamic predictors of such progression, we performed perfusion CT to quantitatively assess cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) of patients with lacunar infarctions in the territory of the lenticulostriate artery. METHODS: We performed MR imaging and perfusion CT of 26 patients with lacunar infarction within 24 hr after onset. On the CBF map on perfusion CT scans, a round small region of interest was set at the region, with decreased CBF in the territory of the lenticulostriate artery (region of interest 1). Another region of interest was set in the mirror position to region of interest 1 in the contralateral hemisphere (region of interest 2). Using these two regions of interest, CBF, CBV, and MTT were measured. All patients underwent neurologic and MR imaging follow-up while receiving equivalent medical treatment. RESULTS: Neurologic deterioration after onset was shown in 13 patients (progress group), whereas no neurologic deterioration was shown in the other 13 patients (control group). In the progress group, lacunar infarctions were enlarged on follow-up MR images. The ratio of region of interest 1/region of interest 2 showed significantly lower CBF and higher MTT in the progress group than in the control group. CONCLUSIONS: These results suggest that progressive lacunar infarction in the territory of the lenticulostriate artery could be predicted with a higher MTT ratio (>1.26) and a lower CBF ratio (<0.76) on perfusion CT scans obtained within 24 hr after onset.

Aged↗
PubMed2004

Ceramide triggers caspase activation during gamma-radiation-induced apoptosis of human glioma cells lacking functional p53.

We have previously shown that treatment of human glioma U87-MG cells expressing wild-type p53 with a DNA topoisomerase II inhibitor, etoposide resulted in ceramide-dependent apoptotic cell death. However, U87-W E6 cells lacking functional p53 due to the expression of human papilloma virus type 16 (HPV-16) E6 oncoprotein were resistant to etoposide. In order to gain insight into the roles of p53 and ceramide in gamma-radiation-induced glioma cell death, we used U87-W E6 and vector-infected U87-LXSN cells. U87-LXSN glioma cells expressing wild-type p53 were relatively resistant to gamma-radiation. U87-W E6 cells, which lost functional p53, became susceptible to radiation-induced apoptosis. Activation of caspase-3, and formation of ceramide by acid sphingomyelinase, but not by neutral sphingomyelinase, were associated with p53-independent apoptosis. Radiation-induced caspase activation and apoptotic death in U87-W E6 cells were modified by the agents which affected ceramide metabolism. SR33557, an inhibitor of acid sphingomyelinase, suppressed radiation-induced caspase activation and then apoptotic cell death. In contrast, N-oleoylethanolamine (OE) and D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), which inhibit ceramidase and UDP-glucose:ceramide glucosyltransferase-1, respectively, and then augment ceramide formation, enhanced radiation-induced caspase activation. These results indicate that glioma cells with functional p53 were relatively resistant to gamma-radiation, and that ceramide may play an important role in caspase activation during gamma-radiation-induced apoptosis of glioma cells lacking functional p53.

Apoptosis↗
PubMed2003

Preoperative construction of an extracranial arterial shunt for resection of an aortic arch aneurysm with occluded left carotid artery.

A 68-year-old man with aortic arch aneurysm was referred to our department. Preoperative carotid echography and magnetic resonance angiography revealed occlusion of the left internal carotid artery. Single-photon emission computed tomography scanning indicated that cerebral blood flow was decreased and reactivity to acetazolamide was reduced in the left temporal lobe. A successful superficial temporal artery-middle cerebral artery anastomosis was first made by neurosurgeons. A postoperative single-photon emission computed tomography scan showed that cerebral blood flow and reactivity to acetazolamide were remarkably improved. Two months after the anastomosis, the aortic arch aneurysm was successfully repaired.

Acetazolamide↗
PubMed2003

Cell permeable ROS scavengers, Tiron and Tempol, rescue PC12 cell death caused by pyrogallol or hypoxia/reoxygenation.

The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2003

Hepatocyte growth factor promotes proliferation and neuronal differentiation of neural stem cells from mouse embryos.

Hepatocyte growth factor (HGF), originally cloned as a hepatocyte mitogen, has recently been reported to exhibit neurotrophic activity in addition to being expressed in different parts of the nervous system. At present, the effects of HGF on neural stem cells (NSCs) are not known. In this study, we first report the promoting effect of HGF on the proliferation of neurospheres and neuronal differentiation of NSCs. Medium containing only HGF was capable of inducing neurosphere formation. Addition of HGF to medium containing fibroblast growth factor 2 or epidermal growth factor increased both the size and number of newly formed neurospheres. More neurons were also obtained when HGF was added in differentiation medium. In contrast, neurosphere numbers were reduced after repeated subculture by mechanical dissociation, suggesting that HGF-formed neurospheres comprised predominantly progenitor cells committed to neuronal or glial lines. Together, these results suggest that HGF promotes proliferation of neurospheres and neuronal differentiation of NSCs derived from mouse embyos.

Animals↗