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Biomedical subjects

Nobuo Hashimoto

Publications and source records attributed to Nobuo Hashimoto.

At least 19 recordsLinked to original sources

Evaluation of pituitary macroadenomas with multidetector-row CT (MDCT): comparison with MR imaging.

INTRODUCTION: It is important to have information on cavernous sinus extension and bony destruction in pituitary macroadenomas before surgery, but magnetic resonance (MR) imaging cannot always depict them. In the present study we sought to determine whether multidetector-row computed tomography (MDCT) could provide preoperative information in addition to that provided by MR imaging in pituitary macroadenoma. METHODS: The subjects comprised 33 consecutive patients (15 women, 18 men; mean age 50 years) with surgically proven macroadenoma. For MDCT, using the soft-tissue window and bone window, three orthogonal multiplanar reconstruction images were generated from venous-phase contrast-enhanced 0.5-mm isotropic voxel data. MDCT and MR images were evaluated with regard to: (1) clarity of tumor margins; (2) identification of the normal pituitary gland; (3) identification of erosion or destruction of the sellar floor; and (4) visualization of the adjacent optic pathways. RESULTS: MDCT more clearly demonstrated the lateral tumor margin than MR imaging (P = 0.002). No significant differences in visualization of the normal pituitary gland were noted between MDCT and dynamic MR imaging (P = 0.7). MDCT more clearly demonstrated sellar floor erosion or destruction at the sphenoid sinus than MR imaging (P < 0.001). MR imaging was superior to MDCT for visualizing the adjacent optic pathways (P < 0.001). CONCLUSION: MDCT is superior to MR imaging for assessing lateral tumor margin and the sellar floor at the sphenoid sinus. MDCT offers useful preoperative information in addition to that obtained from MR imaging.

Adenoma↗

Neuropoietin induces neuroepithelial cells to differentiate into astrocytes via activation of STAT3.

Neuropoietin (NP) is a recently identified member of the interleukin (IL)-6 family of cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, and is highly expressed in embryonic brain. In this study, we show that NP has the potential to induce neuroepithelial cells to differentiate into astrocytes. NP stimulation leads to promoter activation of the gene for an astrocyte marker, glial fibrillary acidic protein (GFAP), which is clearly inhibited by either expression of a dominant-negative form of a transcription factor, signal transducer and activator of transcription 3 (STAT3) or by a nucleotide-substitution in the STAT3-binding element within the gene promoter. We further show that NP induces binding of endogenous STAT3 to its cognate sequence within the gfap gene promoter in neuroepithelial cells. Moreover, like the other IL-6 cytokine family members, NP promotes astrocyte differentiation in a synergistic manner with bone-morphogenetic protein (BMP)-2. Taken together, our data indicate that NP can be considered as a new astrocyte-inducing cytokine in the developing brain.

Animals↗

Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats.

BACKGROUND AND PURPOSE: Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms. METHODS: Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9. RESULTS: Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model. CONCLUSIONS: These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.

Animals↗

Heterogeneous epileptogenicity and cortical function within malformations of cortical development: a case report.

The authors report a 24-year-old patient with intractable partial epilepsy and massive malformations of cortical development (MCD). Subdural EEG recordings of habitual seizures showed heterogeneous epileptogenicity, and visual evoked potential was recorded within the MCD just adjacent to the most active epileptogenic focus. Resection of the small cortical area presumably with core epileptogenicity, while sparing the cortical functional area, improved seizure outcome without any postoperative functional deficits.

Adult↗

Increased expression of aquaporin 1 in human hemangioblastomas and its correlation with cyst formation.

Aquaporins (AQPs) is a water channel family which facilitates the passage of water across cell membranes. Recently, expression of aquapporin 1 (AQP1) was found to be involved in not only water transport but also tumorigenesis. In present study, we analyzed the expression of AQP1 in 26 consecutive cases of human hemangioblastomas. Significant upregulation of AQP1 expression was found in hemangioblastomas compared with control brain (P=0.002). In hemangioblastomas, expression of AQP1 was predominantly localized on membranes of stromal cells. The expression level of AQP1 in cystic group of hemangioblastomas is much higher than that of solid group (P=0.021). Most hemangioblastomas showed a negative expression of AQP1 on endothelial cells. These results imply that increased expression of AQP1 in stromal cells may play a role in cyst formation and tumorigenesis of heman-gioblastomas.

Adult↗

Fibers from the dorsal premotor cortex elicit motor-evoked potential in a cortical dysplasia.

OBJECTIVE: To identify the fibers originating from the dorsal premotor cortex (dorsal PMC) that contribute to motor-evoked potentials (MEP), we have applied integrated functional neuronavigation and awake surgery during removal of an epileptic cortical dysplasia located in the right premotor cortex. METHODS: Chronic subdural electrodes were employed for functional mapping during a routine invasive evaluation for intractable epilepsy. After the fibers originating from the dorsal PMC were plotted into the tractography-integrated functional neuronavigation, subcortical MEPs and clinical symptoms were examined during resection of the epileptogenic dorsal PMC. RESULTS: During removal of the epileptogenic area, MEPs were elicited by electrical stimulation of the fibers originating from the dorsal PMC, which were separated from the pyramidal tracts from the precentral gyrus. Resection of the dorsal PMC and its fibers caused a transient dysmetric movement of the left toe without motor weakness. CONCLUSION: Functional corticospinal tract fibers originating from the dorsal PMC can be defined and removed safely under local anesthesia with the aid of integration of functional neuronavigation and subcortical electrical stimulation.

Adolescent↗

Low-frequency electric cortical stimulation decreases interictal and ictal activity in human epilepsy.

We previously reported that low-frequency electric cortical stimulation (LFECS) directly applied to the epileptic focus by means of subdural electrodes decreased the number of interictal epileptiform discharges in patients with intractable partial epilepsy. In the present study, LFECS was applied to the epileptic foci directly in four patients with medically intractable partial epilepsy through subdural electrodes and evaluated its effect on the number of interictal epileptiform discharges as well as simple partial seizures. We used alternating electric current of 0.3 ms duration presented at 0.9 Hz frequency for 250 s. LFECS did not induce seizures in any of the four patients. In one patient, the number of interictal epileptiform discharge decreased significantly by LFECS, which is in conformity with our previous report. In addition, LFECS applied to the seizure onset zone decreased the frequency of simple partial seizures in one patient. These results suggest that LFECS has an inhibitory effect not only on the interictal but also the ictal activities in patients with intractable partial epilepsy. Further study is required to determine the inhibitory effect of LFECS more in details.

Adolescent↗

Ipsilateral facial sensory and motor responses to basal fronto-temporal cortical stimulation: evidence suggesting direct activation of cranial nerves.

To clarify the generator mechanism of sensory and motor facial responses ipsilateral to electrical stimulation of the inferior fronto-temporal cortex in epilepsy patients. Out of 30 patients who have been evaluated with chronically implanted subdural electrodes for medically intractable partial seizure or brain tumor involving the basal frontal or temporal cortex, 4 patients (age ranging 24-57 years) showed sensory and motor responses in the ipsilateral face to high frequency electrical cortical stimulation of the inferior fronto-temporal cortex. We investigated motor evoked potentials (MEPs) in the facial muscle by single pulse stimulation in 2 out of 4 patients. Three patients showed both sensory symptoms and muscle contraction in the ipsilateral lower face when the orbitofrontal or basal temporal cortex was stimulated with 50 Hz electric current. One patient had only sensory symptoms in the lower face when ipsilateral basal temporal area was stimulated. MEPs at the left orbicularis oris muscle were constantly elicited with the onset latency of 7 ms throughout the stimulus rate of 2-30 Hz in 1 patient out of 2 patients was tested. In another patient, MEP onset latency was 3.0 ms with 11 Hz stimulation. With electrical stimulation of the basal fronto-temporal cortex, the ipsilateral facial twitch might occur through either the direct activation of the facial nerve by the current spread in the middle cranial fossa or through the mechanism similar to blink reflex.

Adult↗

Corticospinal tract localization: integration of diffusion-tensor tractography at 3-T MR imaging with intraoperative white matter stimulation mapping--preliminary results.

Institutional review board approval and written informed consent were obtained. The purpose of this study was to prospectively validate usefulness of diffusion-tensor (DT) fiber tractography of the corticospinal tract at 3-T magnetic resonance imaging, in combination with the subcortical motor-evoked potential (MEP) technique, as a tool for tractography-guided neurosurgery. DT imaging and corticospinal tractography were performed at 3 T in eight patients (four men, four women; mean age, 41 years; age range, 23-58 years) with intracranial space-occupying lesions. Tractography data were transferred to a neuronavigation system, and tractography-guided neurosurgery was performed. During lesion resection, subcortical MEPs were recorded. Positive MEP response was observed in four patients. No patients developed new motor weakness postoperatively. Complementary use of tractography and MEP may be useful for intraoperative depiction of corticospinal tracts.

Adult↗

Generators and temporal succession of giant somatosensory evoked potentials in cortical reflex myoclonus: epicortical recording from sensorimotor cortex.

OBJECTIVE: To clarify the generator mechanism of giant somatosensory evoked potentials (giant SEPs) and the hyperexcitability of primary somatosensory and motor cortices (SI and MI). METHODS: In a patient with intractable focal seizures manifesting cortical reflex myoclonus of the left foot, giant SEPs to left tibial nerve stimulation were epicortically recorded as a part of presurgical evaluation with subdural electrodes. RESULTS: In the single pulse SEPs, enlarged P1-N1 components were observed at the foot area of the SI and MI (86.5-258.8 microV, respectively), and the peak latencies were always shorter at SI than at MI by 6 ms. Similar findings were obtained for peroneal and sural nerve stimulation. In the paired pulse SEPs, the second response was less suppressed, as compared to other interstimulus intervals (ISIs), with ISIs of 40 and 200 ms both at SI and MI. CONCLUSIONS: In this particular patient, cortical hyperexcitability to somatosensory stimuli seems to originate from SI but subsequently both SI and MI are responsible for the generation of giant SEPs and cortical reflex myoclonus. SIGNIFICANCE: Somatosensory and primary motor cortices both generated enhanced early cortical components of SEPs, most likely by enhancing the latter by the former.

Adult↗

A dyad symmetry element in the fibroblast growth factor-2 gene promoter with different levels of activity in astrocytoma and hepatocelluar carcinoma cell lines.

Fibroblast growth factor-2 (FGF-2) gene expression is reported to be spatially and temporally regulated in the process of development, normal growth, and wound healing. We postulated that its constitutive expression in human malignant astrocytoma cells is due to loss of function of the regulatory mechanism of FGF-2 gene expression. Here, we report the characterization of a unique element in the FGF-2 gene promoter. We investigated the transcriptional regulation of the FGF-2 gene in a human malignant astrocytoma (U87MG) and a human hepatocellular carcinoma (HepG2) cell line. We found that a dyad symmetry element (DSE) in the FGF-2 gene promoter exhibited different promoter activities; in HepG2 cells it did, while in U87MG cells it did not, exhibit repressive activity. Examination of the relative promoter activities of the DSE in a thymidine kinase promoter revealed it exerted different activities, just as it did in the 2 cell lines studied. Gel shift assay demonstrated that 2 proteins bound to the DSE in nuclear extracts from HepG2 cells and that one protein was missing in nuclear extracts from U87MG cells. These results suggest that the DSE has a crucial role as a transcriptional regulatory element of FGF-2 gene expression.

Astrocytoma↗

Generation of graftable dopaminergic neuron progenitors from mouse ES cells by a combination of coculture and neurosphere methods.

Parkinson's disease is characterized by a loss of midbrain dopamine (DA) neurons and is generally viewed as a potential target for stem cell therapy. Although several studies have reported the generation of postmitotic DA neurons from embryonic stem (ES) cells, it is unknown whether the proliferative progenitors of DA neurons can be isolated in vitro. To investigate this possibility, we have developed a combined approach in which ES cells are cocultured with PA6 stromal cells to expose them to stromal cell-derived inducing activity (SDIA) and are then cultured as neurospheres. Mouse ES cell colonies were detached from PA6 feeder cells after 8 days of SDIA treatment and then expanded as spheres for another 4 days in serum-free medium supplemented with fibroblast growth factor-2. The spheres exhibited neural stem cell characteristics and contained few DA neurons at this stage of culture. After being induced to differentiate on polyornithine/laminin-coated dishes for 7 days, these spheres generated DA neurons in vitro at a relatively low frequency. Intriguingly, addition of PA6 cell conditioned medium to the sphere culture medium significantly increased the percentage of DA neurons to 25-30% of the total number of neurons. Transplantation of conditioned medium-treated day 4 spheres, which contained DA neuron progenitors, into the mouse striatum resulted in the generation of a significant number of graft-derived DA neurons. These findings suggest that progenitors of DA neurons are generated and can proliferate in ES cell-derived neurospheres induced by serial SDIA and PA6 conditioned medium treatment.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm: a preliminary study.

BACKGROUND: Our previous studies have shown a significant linkage of intracranial aneurysms (IAs) to chromosome 17. METHODS AND RESULTS: Nine genes (TNFRSF13B, M-RIP, COPS3, RAI1, SREBF1, GRAP, MAPK7, MFAP4, and AKAP10) were selected from 108 genes that are located between D17S1857 and D17S1871 by excluding 99 genes that were pseudogenes, hypothetical genes, or well-characterized genes but not likely associated with IA. Direct sequencing of all coding and regulatory regions in 58 cases (29 pedigree probands and 29 unrelated nonpedigree cases) was performed. Deleterious changes were found only in TNFRSF13B, K154X, and c.585 to 586insA in exon4. The association of IA with TNFRSF13B was further studied in 304 unrelated cases and 332 control subjects. Rare nonsynonymous changes, a splicing acceptor site change and a frame shift, were found in unrelated cases (2.3%; 14 of 608) more frequently than in control subjects (0.8%; 5 of 664; P=0.035). The association study using single-nucleotide polymorphisms in an unrelated case-control cohort revealed a protective haplotype (odds ratio 0.69, 95% confidence interval 0.52 to 0.92, P=0.012) compared with the major haplotype after adjustment for covariates. CONCLUSIONS: We propose that TNFRSF13B is one of the susceptibility genes for IA.

Adult↗

Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm.

BACKGROUND AND PURPOSE: Previous studies have shown positive evidence of linkage of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22. These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A), apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are considered to be promising candidate genes for IA. We aimed to examine the association of single-nucleotide polymorphisms (SNPs) with IA in these candidate genes. METHODS: To identify polymorphisms in NOS2A and ACE2, all exons and exon-intron boundaries were screened by direct sequencing in 30 randomly selected controls. The program tagSNPs was used to select an optimal set of haplotype-tagging SNPs. For ELN and APOE, SNPs were selected from previous reports. These selected SNPs were then genotyped in 362 cases with IA and 332 residential area matched controls. THESIAS software was used to investigate the association of alleles and haplotypes with IA by adjusting with covariates. RESULTS: We genotyped 8 SNPs in ELN, 8 SNPs in NOS2A, 3 epsilon alleles in APOE and 1 SNP in ACE2. No alleles or haplotypes of 4 candidate genes revealed any significant association with IA. CONCLUSIONS: Investigated polymorphisms in this study were not associated with IA.

Adult↗

A step-by-step resection guided by electrocorticography for nonmalignant brain tumors associated with long-term intractable epilepsy.

To delineate a surgical strategy for long-term intractable epilepsy associated with nonmalignant brain tumor, we developed a protocol for 25 patients whereby removal of tumor alone and additional irritative peritumoral tissue between sulci (gyrectomy), as well as further resectioning, was performed based on intraoperative electrocorticogram results. In five patients, no irritative zones were observed that required resectioning following complete removal of tumors. Additional gyrectomy was indicated in 18 patients who demonstrated gliosis or cortical dysplasia in the peritumoral residual irritative zone. Remote irritative zone observed in two patients was correlated with long-term and frequent seizures. During a follow-up period of at least 5 years, seizure outcome was Engel category I in 92%, and all patients have remained tumor-free. Peritumoral gyrectomy as a means of removing likely epileptic tissue following tumor resection appears to be a useful method for treating long-term intractable tumoral epilepsy. Further resectioning of remote tissue should be considered in patients with severely intractable seizures.

Adolescent↗

Comparison of 3.0- and 1.5-T three-dimensional time-of-flight MR angiography in moyamoya disease: preliminary experience.

PURPOSE: To prospectively compare 3.0- and 1.5-T three-dimensional (3D) time-of-flight (TOF) magnetic resonance (MR) angiography in patients with moyamoya disease, with special emphasis on the visualization of abnormal netlike vessels (moyamoya vessels). MATERIALS AND METHODS: Study protocols were approved by the local ethics committee; written informed consent was obtained from all patients. The study included 24 consecutive patients with moyamoya disease (four male and 20 female patients). Patients ranged in age from 17 to 66 years (mean age, 41 years). Moyamoya disease had been diagnosed in all patients before they were entered into the study. All patients underwent 3D TOF MR angiography at both 3.0 and 1.5 T; imaging examinations were performed within 14 days of each other. Maximum intensity projections (MIPs) obtained with MR angiography performed at both 3.0 and 1.5 T were evaluated by two neuroradiologists; the visualization of moyamoya vessels was graded according to a 4-point scale. For both 3.0- and 1.5-T imaging, the number of high-signal-intensity areas and the summation of cross-sectional areas of high signal intensity on source images obtained at the same level of MR angiography were compared quantitatively by using the Wilcoxon matched-pair signed-rank test. RESULTS: Moyamoya vessels were better visualized on MIPs obtained with 3.0-T imaging than on MIPs obtained with 1.5-T imaging (P < .001). At the identical level of the source image, 3.0-T imaging depicted more high-signal-intensity areas than did 1.5-T imaging. Wider cross-sectional areas of moyamoya vessels were visualized with 3.0-T imaging than with 1.5-T imaging (P < .001). CONCLUSION: Moyamoya vessels are better depicted with MR angiography at 3.0 T than at 1.5 T.

Adolescent↗

Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage caused by cerebral aneurysm rupture remains a life-threatening emergency despite advances in treatment. However, the mechanisms underlying aneurysm initiation, progression, and rupture remain unclear. We developed a method to induce experimental cerebral aneurysms in rats, monkeys, and mice. Interleukin-1beta (IL-1beta) is a key inflammatory mediator, and it is thought to be a promising target for the treatment of inflammatory diseases. In the present study, we examined the role of IL-1beta in cerebral aneurysm development. METHODS: Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1beta gene-deficient (IL-1beta-/-) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically. RESULTS: IL-1beta was expressed in vascular media in mice at an early stage of aneurysmal models' cerebral arteries. No differences were seen in the rate of aneurysm development between IL-1beta-/- and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1beta-/- mice, increased caspase-1 expression was seen compared with wild-type animals. Additionally, the number of apoptotic cells assessed by single-stranded DNA immunoreactivity and TUNEL was significantly reduced in IL-1beta-/- mice compared with wild-type animals. CONCLUSIONS: IL-1beta is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1beta gene results in the reduced incidence of mature experimental cerebral aneurysms.

Aneurysm↗