[Fundamental surgical techniques for cerebral arteriovenous malformations].
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Adult↗
Biomedical subjects
Nobuo Hashimoto
Publications and source records attributed to Nobuo Hashimoto.
Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.
Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.
Animals↗
Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis.
Chicken B lymphocyte precursors and DT40 cells diversify their immunoglobulin-variable (IgV) genes through homologous recombination (HR)-mediated Ig gene conversion. To identify DNA polymerases that are involved in Ig gene conversion, we created DT40 clones deficient in DNA polymerase eta (poleta), which, in humans, is defective in the variant form of xeroderma pigmentosum (XP-V). Poleta is an error-prone translesion DNA synthesis polymerase that can bypass UV damage-induced lesions and is involved in IgV hypermutation. Like XP-V cells, poleta-disrupted (poleta) clones exhibited hypersensitivity to UV. Remarkably, poleta cells showed a significant decrease in the frequency of both Ig gene conversion and double-strand break-induced HR when compared to wild-type cells, and these defects were reversed by complementation with human poleta. Our findings identify a DNA polymerase that carries out DNA synthesis for physiological HR and provides evidence that a single DNA polymerase can play multiple cellular roles.
Animals↗
Evidence for a wide distribution of negative motor areas in the perirolandic cortex.
OBJECTIVE: The perirolandic regions were studied by extensive electrical stimulation to clarify the topography and somatotopic distribution of negative motor areas (NMAs) and examine the clinical significance of these areas. METHODS: We evaluated the cortical function elicited by electrical stimulation in 30 patients with tumors or intractable epilepsy. The somatotopic distribution of NMAs was examined by localizing these regions using Talairach's bicommissural reference system. NMAs within the lesions of two patients were removed under local anesthesia. RESULTS: We obtained negative motor responses following the stimulation of 30 electrodes in 15 patients. On the lateral brain surface, the majority of NMAs for the upper extremities were distributed broadly throughout the premotor cortex, while NMAs for the tongue were only found in the inferior frontal gyrus of the dominant hemisphere. During removal of the NMAs within the lesions of two patients, we documented transient hand clumsiness in one patient. CONCLUSIONS: NMAs were widely distributed throughout the perirolandic area, as well as the previously reported regions in the inferior frontal gyrus. These areas likely function in the control of skilled movements; dysfunction of such movements transiently follows resection of these regions, but is subsequently well compensated for after surgery. SIGNIFICANCE: The localization and consequences of resection of NMAs suggests their clinical significance in motor control.
Adolescent↗
Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation.
The differentiation of dopaminergic (DA) neurons from mouse embryonic stem cells (ESCs) can be efficiently induced, making these neurons a potential source for transplantation as a treatment for Parkinson's disease, a condition characterized by the gradual loss of midbrain DA neurons. One of the major persistent obstacles to the successful implementation of therapeutic ESC transplantation is the propensity of ESC-derived grafts to form tumors in vivo. To address this problem, we used fluorescence-activated cell sorting to purify mouse ESC-derived neural precursors expressing the neural precursor marker Sox1. ESC-derived, Sox1+ cells began to express neuronal cell markers and differentiated into DA neurons upon transplantation into mouse brains but did not generate tumors in this site. In contrast, Sox1- cells that expressed ESC markers frequently formed tumors in vivo. These results indicate that Sox1-based cell sorting of neural precursors prevents graft-derived tumor formation after transplantation, providing a promising strategy for cell transplantation therapy of neurodegenerative disorders.
Animals↗
Surgical resection of an epileptogenic cortical dysplasia in the deep foot sensorimotor area.
Epileptogenic foci in the foot/leg motor area of cortex are rarely resected, due to the risks of the surgical procedures. A 31-year-old right-handed man with cortical dysplasia deep in the central sulcus suffered from disturbances in walking due to frequent daily seizures. Following subdural electrode implantation to define the epileptogenic area and assess cortical function, limited regions of cortex were removed from the foot/leg primary motor and sensory areas under local anesthesia until the epileptiform discharges disappeared. Postoperative motor weakness and sensory disturbances completely resolved within 2 weeks and 2 months, respectively; the patient has been free from seizures for more than a year and a half postsurgery. Intraoperative examination demonstrated that small and moderate cortical dysplasia in the depths of the central sulcus exhibits both intrinsic epileptogenicity and function. Focused resection of the lower extremity of the sensorimotor area may be a surgical strategy for intractable epilepsy if resolution of clinical symptoms with minimal dysfunction due to the limited size of the resection is expected to follow surgery.
Adult↗
Quantitative analysis of topoisomerase IIalpha to rapidly evaluate cell proliferation in brain tumors.
Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase IIalpha (topo IIalpha), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo IIalpha mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo IIalpha mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo IIalpha mRNA was significantly correlated with its immuno-staining index (p<0.0001, r=0.9077). Furthermore, it sharply detected that topo IIalpha mRNA decreased in growth-inhibited glioma cell. These results support that topo IIalpha mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors.
Antigens, Neoplasm↗
Electric cortical stimulation suppresses epileptic and background activities in neocortical epilepsy and mesial temporal lobe epilepsy.
OBJECTIVE: To evaluate the suppressive effect of electric cortical stimulation upon the seizure onset zone and the non-epileptic cortex covered by subdural electrodes in patients with neocortical epilepsy and mesial temporal lobe epilepsy (MTLE). METHODS: Four patients with medically intractable focal epilepsy had implanted subdural electrodes for preoperative evaluation. Cortical functional mapping was performed by intermittently repeating bursts of electric stimulation, which consisted of 50 Hz alternating square pulse of 0.3 ms duration, 1-15 mA, within 5 s. The effect of this stimulation on the seizure onset zones and on the non-epileptic areas was evaluated by comparing spike frequency and electrocorticogram (ECoG) power spectra before and after stimulation. A similar comparison was performed in stimulation of 0.9 Hz of the seizure onset zones for 15 min. RESULTS: When the seizure onset zone was stimulated with high frequency, spike frequency decreased by 24.7%. Logarithmic ECoG power spectra recorded at stimulated electrode significantly decreased in 10-32 Hz band by high frequency stimulation of the seizure onset zone, and in 14-32 Hz band by high frequency stimulation of the non-epileptic area. Low frequency stimulation of the seizure onset zone produced 18.5% spike reduction and slight power decrease in 12-14 Hz. CONCLUSIONS: Both high and low frequency electric cortical stimulation of the seizure onset zone have a suppressive effect on epileptogenicity. Reduction of ECoG fast activities after electric cortical stimulation suggests the augmentation of inhibitory mechanisms in human cortex.
Adult↗
Processing of Japanese morphogram and syllabogram in the left basal temporal area: electrical cortical stimulation studies.
Language functions in the left basal temporal area (LBTA) were investigated using electrical cortical stimulation during functional mapping in six Japanese patients with refractory epilepsy. This study provides the first direct evidence that kana (Japanese syllabogram) is processed in the LBTA. Electrical stimulation of some areas within LBTA induced disturbance in overt reading of kana words only in the first trials, with no errors in the subsequent trials. By contrast, stimulation of the same area caused obvious disturbance in kana non-word reading in all trials. Since a kana word carries both meaning and sound while a kana non-word carries only sounds of a letter string, the contrasting results of partial and complete disturbance imply a possibility that there are two distinct pathways for kana reading: one dealing with both phonological and semantic aspects of the words and the other dealing only with phonological aspect. Kanji words (Japanese morphogram) and objects/pictures were found to be processed in an area different from the area for the kana non-word processing. Furthermore, the present study also identified the common area for processing kanji reading and object/picture naming. There were no errors in matching pictures with kanji words, indicating that concepts of pictures and meanings of kanji words were not interfered by the electrical stimulation of that area. The new insight provides a clue for partial description of processing pathways for language-related visual information in LBTA. Three types of information (morphological, phonological, and semantic) are conveyed together at some stages and are separated into different routes at some other stages.
Acoustic Stimulation↗
Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells.
To investigate the effect of estrogen on neuronal differentiation, especially on dopaminergic (DA) neurons, human neural stem cells (NSCs) were differentiated in the presence of 17beta-estradiol. NSCs gave rise to tyrosine hydroxylase (TH)-positive neurons in vitro, the proportion of which was increased by 17beta-estradiol. Increase in TH-positive neurons was abrogated by an estrogen receptor (ER) antagonist, ICI182780, suggesting ERs play a role in differentiation of DA neurons. The observation that ERs were expressed in both proliferating NSCs and postmitotic DA neurons suggested that increase in TH-positive neurons was due to induction and support of DA neurons. 17beta-Estradiol also increased the number of DA neurons derived from human NSCs in vivo when the cells were grafted into mouse brains. These results support a possible role for estrogen in the transplantation of NSCs for Parkinson's disease.
Animals↗
An adult case of moyamoya syndrome that developed dural sinus thrombosis associated with protein C deficiency: case report and literature review.
We describe a 54-year-old woman exhibiting MMS who developed delayed dural sinus thrombosis associated with PCD. Angiographic findings of the patient were so unusual that bilateral internal carotid arteries were occluded between their origin and the carotid fork with extensive development of collateral circulation via the external carotid arteries and the posterior cerebral arteries instead of moyamoya vessels at the base of the brain. Seven years after bilateral cerebral revascularization surgery, intracerebral hemorrhage occurred caused by dural sinus thrombosis. In the treatment for the patient with MMS associated with PCD, risk of sinus thrombosis should be taken into account.
Age Factors↗
Effects of trans-sylvian approach to basal forebrain projection fibers: verbal memory decline after selective amygdalohippocampectomy.
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Amygdala↗
In vivo epileptogenicity of focal cortical dysplasia: a direct cortical paired stimulation study.
PURPOSE: Alternation of the intracortical inhibitory and excitatory mechanisms in focal cortical dysplasia (FCD) has not been well elucidated in vivo in humans. We investigated in vivo alternation of these mechanisms in epileptogenesis of FCD by means of paired-pulse direct cortical electrical stimulation. METHODS: A 31-year-old man with FCD at the left foot primary somatosensory (SI) and motor areas who underwent invasive monitoring with subdural electrodes was studied. By means of subdural electrodes, paired-pulse electrical stimulation was performed at the epileptic focus (foot SI) and control cortex (hand SI) with interstimulus interval (ISI) of 1-100 ms. Instead of using motor evoked potentials to investigate the degree of cortical excitability in response to motor cortex stimulation, we evaluated the size change of corticocortical evoked potentials (CCEPs), which are elicited at the adjacent cortex by direct cortical stimulation via fiber projection and thus reflect direct and indirect excitation of corticocortical projection neurons at the site of stimulation. RESULTS: During the interictal state, paired-pulse stimulation of the focus revealed abnormally enhanced intracortical inhibition at ISI of 1-10 ms (maximum, 22%) compared with control stimulation of the hand SI (ISI of 1-2 ms; maximum, 18%) (p < 0.01). While the patient was having the somatosensory aura that later evolved into the left-leg clonic seizure, single and paired stimulation at the focus showed increased cortical excitability (enlarged CCEP) and decreased intracortical inhibition, respectively. CONCLUSIONS: During the aura, interictally enhanced intracortical inhibition at the focus was replaced by increased cortical excitability and decreased intracortical inhibition, suggesting increased net intrinsic epileptogenicity during seizure generation in this patient with FCD.
Cerebral Cortex↗
Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.
Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Techniques for passing the PercuSurge Guardwire system through severe and tortuous stenotic lesions.
Distal embolism is one of the major causes of morbidity and mortality associated with treating stenotic lesions by endovascular procedures, such as percutaneous angioplasty and stenting. Many devices have been designed and used to prevent this complication. The PercuSurge Guardwire system is recognized as the best system available to prevent distal embolism during stenting. However, this system is sometimes hard to pass through severe stenotic, tortuous lesions because of the poor selectivity and support. The PercuSurge device was safely introduced into two cases of severe stenotic and tortuous lesions with a triple coaxial system and the buddy wire technique, and stenting was performed successfully. These techniques are very helpful for introducing and maintaining this system in the correct position across stenoses with unfavorable configurations.
Aged↗
Large paraclinoid aneurysm with a calcified neck treated by tailored multimodality procedures.
A 68-year-old woman presented with a large paraclinoid aneurysm with a calcified neck causing visual symptoms. Direct clipping was hazardous because of severe calcification of the neck. Endovascular internal trapping was difficult because of the short distance between the neck and the origin of the posterior communicating artery. Proximal occlusion was likely to be less effective because of large collateral back flow to the aneurysm via the ophthalmic artery (OphA). The aneurysm was successfully treated by a combination of a high-flow bypass, intraoperative coil embolization of the parent artery including the origin of the OphA, and clipping of the internal carotid artery distal to the aneurysm. Paraclinoid aneurysms may be difficult to treat by the simple application of direct clipping, endovascular coiling, or trapping. Multimodality procedures can be tailored to treat such aneurysms.
Aged↗
Asymptomatic microbleeds in moyamoya disease: T2*-weighted gradient-echo magnetic resonance imaging study.
OBJECT: The aim of this study was to investigate the incidence of asymptomatic microbleeds (MBs) in patients with moyamoya disease (MMD) by using a 3-tesla magnetic resonance (MR) imaging unit. METHODS: Data on 63 patients hospitalized with MMD between 1999 and 2004 were retrospectively examined to determine the incidence of asymptomatic MBs. Gradient-echo T2*-weighted MR imaging studies obtained using 3- and 1.5-tesla units were available in 25 patients. These patients consisted of five men and 20 women, ranging in age from 17 to 66 years (mean age 41 +/- 14 years). Ischemic MMD was diagnosed in 18 patients, and hemorrhagic MMD in seven. The incidence of MBs was also evaluated using the same 3-tesla MR imaging unit in 34 healthy volunteers including seven men and 27 women, ranging in age from 18 to 71 years (mean age 33 +/- 12 years). Using the 3-tesla MR unit, asymptomatic MBs were demonstrated in 11 patients (44%); they were detected in seven patients (28%) by using the 1.5-tesla unit. In the 3-tesla MR studies in healthy individuals, MBs were found in two patients (5.8%). Based on 3-tesla MR studies, the incidence of MBs was significantly higher in patients with MMD compared with that in healthy individuals. Asymptomatic MBs were demonstrated in eight (44%) of 18 patients with ischemic MMD and three (43%) of seven patients with hemorrhagic MMD. CONCLUSIONS: Microbleeds are significantly more common in patients with MMD than in healthy individuals regardless of the disease type. The evaluation of MBs with T2*-weighted 3-tesla MR imaging might contribute to the treatment of MMD.
Adolescent↗
Long-term outcome in patients harboring intracranial ependymoma.
OBJECT: The prognostic significance of tumor grade and resection and the efficacy of prophylactic radiation remain controversial in the management of intracranial ependymoma. The outcomes in patients with intracranial ependymoma treated at the Kyoto University Hospital were reviewed retrospectively, and prognostic significance was analyzed. METHODS: Between 1972 and 2002, 29 patients were seen at the authors' institution. Eighteen cases involved a Grade II lesion according to the World Health Organization classification of ependymoma and 11 involved a Grade III lesion. Postoperative radiation was applied in 24 cases and chemotherapy was administered in nine. Overall survival and progression-free survival rates were significantly higher in patients with Grade II ependymoma (p = 0.006 and 0.004, respectively) and in patients who had undergone gross-total resection of the tumor (p = 0.002 and 0.04, respectively). Fourteen patients relapsed from 10 to 120 months (median 39 months) after diagnosis. In nine patients the ependymoma recurred only at the original tumor site. Three patients experienced both local and distant relapse, whereas two others had only a distant relapse. All relapses of the Grade II ependymoma initially occurred at the primary tumor site. Histological grade and extent of resection were significantly associated with tumor dissemination (p = 0.0034 and 0.0011, respectively). The field of postoperative radiation had no impact on patient survival or lesion recurrence. CONCLUSIONS: Tumor grade and resection are the two important prognostic factors with respect to patient survival, tumor recurrence, and tumor dissemination. Considering that relapses were predominantly local and that there was no apparent benefit from prophylactic radiation, the authors concluded that postoperative radiation should be focused on local control, especially for Grade II ependymomas.
Adolescent↗