記述言語：英語  

The etiology of Moyamoya disease (MMD) is still largely unclear, despite identification of RNF213 as the most significant susceptibility gene in East Asian patients. Following up our previous study confirming genetic heterogeneity in Japanese patients with MMD, we extensively surveyed novel candidate genes for a new perspective on the etiology of this disease. Two characteristic pedigrees without susceptibility variants in RNF213 were selected for whole-exome sequencing; 1 harbored 3 affected members, and the other included discordant monozygotic twins. In the former pedigree, 12 rare mutations in 12 genes were co-segregated with MMD. One of the most deleterious amino acid changes among these was p.T76_G80delinsPS in CCER2, which was also mutated in the latter pedigree (p.E242K), although the unaffected twin sister shared the same mutation reflecting reduced penetrance. These CCER2 mutations were predicted to promote aggregation or oligomerization of their protein product, using in silico functional analysis. Subsequent CCER2 re-sequencing in an additional 135 MMD probands identified 1 recurrent and an additional 2 in-frame insertion-deletion mutations, recurrent p.T76_G80delinsPS,

DOI： 10.1016/j.jstrokecerebrovasdis.2016.09.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The etiology of Moyamoya disease (MMD) is still largely unclear, despite identification of RNF213 as the most significant susceptibility gene in East Asian patients. Following up our previous study confirming genetic heterogeneity in Japanese patients with MMD, we extensively surveyed novel candidate genes for a new perspective on the etiology of this disease. Two characteristic pedigrees without susceptibility variants in RNF213 were selected for whole-exome sequencing; 1 harbored 3 affected members, and the other included discordant monozygotic twins. In the former pedigree, 12 rare mutations in 12 genes were co-segregated with MMD. One of the most deleterious amino acid changes among these was p.T76_G80delinsPS in CCER2, which was also mutated in the latter pedigree (p.E242K), although the unaffected twin sister shared the same mutation reflecting reduced penetrance. These CCER2 mutations were predicted to promote aggregation or oligomerization of their protein product, using in silico functional analysis. Subsequent CCER2 re-sequencing in an additional 135 MMD probands identified 1 recurrent and an additional 2 in-frame insertion-deletion mutations, recurrent p.T76_G80delinsPS, p.H218_H220del, and p.E299del. Although CCER2 molecular function is not well characterized, it is a secretory protein expressed in the brain; therefore, it constitutes a potential biomarker of MMD. (C) 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.09.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Autosomal dominant polycystic kidney disease (ADPKD) caused by deleterious mutations in PKD1 (16p13.3) and PKD2 (4q21) often coexists with intracranial aneurysms (IAs). In this study, we investigated whether IAs without obvious renal diseases were also associated with these ADPKD genes. Methods: We performed next-generation sequencing of the ADPKD genes in 150 Japanese familial IA patients and age- and sex-matched 150 non-IA controls without obvious renal diseases. Rare coding variants for the following association analysis were defined according to allelic frequencies of less than .5% either in our controls or in the 1000 genomes database. Association with IA was evaluated using burden and variance component methods: the weighted-sum statistic (WSS) and the sequence kernel association test (SKAT), respectively. Results: A total of 44 rare candidate variants were confirmed by Sanger sequencing; 26 were identified from 33 patients, whereas 21 were identified from 20 controls. The candidate variants were all missense variants, except for 1 patient's nonsense variant (p.Q924X) in PKD2, and showed consistent association with IA in both burden and variance component tests (odds ratio [ OR] = 1.80; WSS, P = .026; SKAT, P = .044). This association was largely derived from the variants found in the extracellular structural domains of PKD1 (OR = 2.06; WSS, P = .030; SKAT, P = .029). Conclusion: ADPKD genes are susceptibility genes for IA even in patients without ADPKD.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.08.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Automatic in vivo segmentation of multicontrast (multisequence) carotid magnetic resonance for plaque composition has been proposed as a substitute for manual review to save time and reduce inter-reader variability in large-scale or multicenter studies. Using serial images from a prospective longitudinal study, we sought to compare a semi-automatic approach versus expert human reading in analyzing carotid atherosclerosis progression. Baseline and 6-month follow-up multicontrast carotid images from 59 asymptomatic subjects with 16-79 % carotid stenosis were reviewed by both trained radiologists with 2-4 years of specialized experience in carotid plaque characterization with MRI and a previously reported automatic atherosclerotic plaque segmentation algorithm, referred to as morphology-enhanced probabilistic plaque segmentation (MEPPS). Agreement on measurements from individual time points, as well as on compositional changes, was assessed using the intraclass correlation coefficient (ICC). There was good agreement between manual and MEPPS reviews on individual time points for calcification (CA) (area: ICC; 0.85-0.91; volume: ICC; 0.92-0.95) and lipid-rich necrotic core (LRNC) (area: ICC; 0.78-0.82; volume: ICC; 0.84-0.86). For compositional changes, agreement was good for CA volume change (ICC; 0.78) and moderate for LRNC volume change (ICC; 0.49). Factors associated with LRNC progression as detected by MEPPS review included intraplaque hemorrhage (positive association) and reduction in low-density lipoprotein cholesterol (negative association), which were consistent with previous findings from manual review. Automatic classifier for plaque composition produced results similar to expert manual review in a prospective serial MRI study of carotid atherosclerosis progression. Such automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers.

DOI： 10.1007/s10554-015-0704-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

As the recently developed medical treatments for asymptomatic cervical carotid artery stenosis (ACCAS) have shown excellent stroke prevention, carotid endarterectomy (CEA) should be carried out for more selected patients and with lower complication rates and better long-term outcomes. We have performed CEA for Japanese ACCAS patients with a uniform surgical technique and strict perioperative management. In this study, we retrospectively investigated the perioperative complications and long-term outcomes of our CEA series. A total of 147 CEAs were carried out in 139 Japanese ACCAS patients. All patients were routinely checked for their cardiac function and high risk coronary lesions were preferentially treated before CEA. All CEAs were performed under general anesthesia using a shunt system. The postoperative cerebral blood flow was routinely measured under continued sedation to prevent postoperative hyperperfusion. The 30-day perioperative morbidity rate was 2.04%, including a perioperative stroke rate of 0.68%. There were no perioperative deaths. With regard to the long-term outcomes of the 134 followed-up patients, 9 patients were dead and 5 patients suffered from strokes, including 2 patients with ipsilateral hemispheric ischemia. The annual rates of death, all stroke and ipsilateral ischemic stroke were 1.15%, 0.64%, and 0.25%, respectively. These results showed that the perioperative morbidity and mortality rates of our CEAs were lower than those in the previous large trials. Furthermore, the long-term outcomes of this series were favorable to those reported in the latest medical treatment trials for ACCAS patients. CEA may be useful for preventing ischemic stroke in Japanese ACCAS patients.

DOI： 10.2176/nmc.oa.2014-0398

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background-A founder variant of RNF213, p.R4810K (c. 14429G>A, rs112735431), was recently identified as a major genetic risk factor for moyamoya disease (MMD) in Japan. Although the association of p. R4810K was reported to be highly significant and reproducible, the disease susceptibility of other RNF213 variants remains largely unknown. In the present study, we systematically evaluated the coding variants detected in Japanese patients and controls for associations with MMD.
Methods and Results-To detect variants of RNF213, all coding exons were sequenced in 27 Japanese MMD patients without p. R4810K. We also validated all previously reported variants in our case-control samples and tested for associations in combination with previous Japanese study cohorts, including the 1000 Genomes Project data set, as population-based controls. Forty-six missense variants other than p. R4810K were identified among 370 combined patients and 279 combined controls in Japan. Sixteen of 46 variants were polymorphisms with minor allele frequency >1%, and, after conditioning on the p. R4810K genotype, were not associated with MMD. We conducted a variable threshold test using Combined Annotation-Dependent Depletion on the remaining 30 rare variants (minor allele frequency <1%), and the results showed that the frequency of potentially functional variants was significantly higher in patients than in controls (permutation, minimum P=0.045).
Conclusions-Not only p. 4810K but also other functional missense variants of RNF213 conferred susceptibility to MMD. Our analysis also revealed that approximate to 20% of Japanese MMD patients did not harbor susceptibility variants of RNF213, indicating the presence of other susceptibility genes for MMD.

DOI： 10.1161/JAHA.115.001862

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

In carotid endarterectomy (CEA), the traditional retractors are often difficult to use because they tend to obstruct surgical manipulations, especially in the deep operative field on the rostra! side. The authors have invented a new omnidirectional retractor-supporting ring (OD ring) to solve the problems of traditional retractors. The OD ring has an ellipsoid-shaped frame (major axis: 275 mm, minor axis: 192 mm) with 22 equally spaced outward protrusions. Rubber bands from which blunt mini-hooks are hung are twisted around the protrusions. The OD ring was placed on the operative area, and the. skin edges were retracted by mini-hooks placed symmetrically. The hooks were moved gradually from the shallow to the deep operative field as surgical dissection continued to expose the carotid bifurcation and distal internal carotid artery (ICA). The OD ring was used in 158 consecutive CEAs in the authors' institute between July 2010 and October 2013. The OD ring provided a flatter surgical field and was less obstructive than traditional retractors, thereby facilitating surgical manipulation in the deep operative field such as at the distal ICA. Furthermore, because of its simpler shape, angiorrhaphy could be conducted more smoothly, with less tangled thread during closure of the arteriotomy. There were no technical complications related to the OD ring. As a new retractor system for CEA, the OD ring is less obstructive and provides a flatter surgical field than traditional retractors, thereby facilitating surgical manipulations in the deep operative field around the distal ICA.

DOI： 10.3171/2014.9.JNS132856

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. METHODS: We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10 superficial temporal arteries with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns, using clustering methods. RESULTS: The clustering analysis identified 4 groups: superficial temporal arteries and unruptured IAs were aggregated into their own clusters, whereas RIAs segregated into 2 distinct subgroups (early and late RIAs). Comparing gene expression levels between early RIAs and unruptured IAs, we identified 430 upregulated and 617 downregulated genes in early RIAs. The upregulated genes were associated with inflammatory and immune responses and phagocytosis including S100/calgranulin genes (S100A8, S100A9, and S100A12). The downregulated genes suggest mechanical weakness of aneurysm walls. The expressions of Krüppel-like family of transcription factors (KLF2, KLF12, and KLF15), which were anti-inflammatory regulators, and CDKN2A, which was located on chromosome 9p21 that was the most consistently replicated locus in genome-wide association studies of IA, were also downregulated. CONCLUSIONS: We demonstrate that gene expression patterns of RIAs were different according to the age of patients. The results suggest that macrophage-mediated inflammation is a key biological pathway for IA rupture. The identified genes can be good candidates for molecular markers of rupture-prone IAs and therapeutic targets.

DOI： 10.1161/STROKEAHA.114.005851

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Moyamoya disease (MMD) and atherosclerotic cerebrovascular disease (ACVD) differ in angiographic appearance and probably hemodynamics. Pediatric MMD (PMMD) usually presents with cerebral ischemia, while intracranial hemorrhage is more common in adult MMD (AMMD), suggesting differences in cerebral hemodynamics. We analyzed the cortical flow velocity and direction of recipient arteries using micro-Doppler ultrasonography to evaluate the cortical circulation before and after anastomosis in MMD and ACVD. Twenty-eight patients with adult MMD (AMMD), 7 with pediatric MMD (PMMD), 16 with ACVD, and 12 control patients were studied. A micro-Doppler probe was applied on the cortical recipient artery (A4 or M4) before and after anastomosis. Systolic maximum flow velocity (V (max)) and blood flow direction were investigated at proximal and distal parts of anastomosed sites in recipient arteries. Pre- and postoperative regional cerebral blood flow was measured by cold xenon-computed tomography (Xe-CT). Before anastomosis, retrograde cortical flow was significantly more common in PMMD patients, and V (max) in cortical artery was significantly lower in AMMD patients. Bypass surgery changed the direction of blood flow from the anastomosis site to proximal and distal sites of the recipient artery in most patients, but pre-anastomosis flow direction was preserved more frequently in PMMD patients. The rate of V (max) increase after anastomosis was significantly higher in AMMD than in PMMD (11.6 +/- 9.8 vs. 3.9 +/- 1.8; P = 0.01). Micro-Doppler ultrasonography identified differences in cortical circulation among AMMD, PMMD, and ACVD. In AMMD, significantly low velocity in the cortical artery was observed before anastomosis, and bypass surgery reversed the flow and significantly increased flow velocity. The data of PMMD showed unique hemodynamics of the cortical artery before anastomosis, characterized by a higher frequency of retrograde flow and preserved velocity. The V (max) increase rate was significantly higher in patients with postoperative cerebral hyperperfusion on Xe-CT, and further study is warranted to validate the clinical use of intraoperative micro-Doppler monitoring to predict postoperative hyperperfusion.

DOI： 10.1007/s10143-012-0441-y

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DOI： 10.1007/s10143-012-0441-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Despite large efforts in researching the genesis of Moyamoya disease (MMD), the etiology of this rare disease remains widely unknown. In a previous publication we described two genetic variants in the first exon of transforming growth factor beta 1 (TGFB1) which were associated and showed a tendency toward significance, respectively. In this study we performed a follow-up analysis of TGFB1 by sequencing the complete exon 1 in European and by genotyping previously described positively associated single nucleotide polymorphisms (SNPs) in Japanese patients with MMD.
Methods: The complete first exon of TGFB1 was genotyped in 40 MMD patients and 68 healthy controls from central Europe. For verification, genotyping of the previously described SNPs rs1800470 and rs1800471 was performed in 45 Japanese MMD patients and 79 healthy controls. Analysis was performed by capillary sequencing with custom made primers.
Results: Sequencing of the first exon of TGFB1 in the European cohort did not reveal any new disease-associated nor other genetic variations. The previously described disease association of rs1800471 and tendency toward significance of rs1800470 could not be replicated in the Japanese cohort.
Conclusions: As no new genetic variants were uncovered in this study of the first exon of TGFB1 in European MMD patients and because of the negative association of rs1800470 and rs1800471 in Japanese MMD patients, a role of this exon of TGFB1 in the genesis of MMD is unlikely. Further analyses with even larger cohorts may be necessary to detect causal genetic factors that contribute to the genesis of this disease. (C) 2012 Elsevier Masson SAS. All rights reserved.

DOI： 10.1016/j.ejmg.2012.05.002

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central nervous system, usually affecting the optic nerves and the spinal cord. It is presumed to be an antibody-mediated disorder and the target antigen is the water channel aquaponn-4 (AQP4) on astrocyte cell membranes. NMO is a disease caused by astrocyte disorder and is distinct from multiple sclerosis (MS), which is a primarily demyelinating disease caused by oligodendrocyte disorder. In NMO, spinal MRI shows a T2-hyperintense, longitudinally extensive (≧3 vertebral segments) spinal cord lesion. The case, which has optic neuritis or transverse myelitis with the presence of AQP4 antibody, is called as NMO spectrum disorder. A 68 year-old woman with a history of hypertension and diabetes mellitus was brought to the former hospital by ambulance with acute onset of tetraparesis. She denied visual acuity disturbance. MRI revealed a T2-hyperintense lesion from C5 to T2 level. Laboratory examination showed the presence of AQP4 antibody and the absence of oligoclonal bands. Low-dose steroid treatment was started after establishing a diagnosis of NMO. She incompletely recovered from disability, although the T2-hyperintense lesion on MRI had almost disappeared six months after the onset. It is important to maintain a high index of suspicion for NMO in cases with a longitudinally extensive spinal cord lesion, because untreated NMO leads to severe disability.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

Three cases of extracranial carotid artery (ECA) aneurysm were treated with various surgical options. Two female patients (74 and 37-year-old women) presented with pulsatile masses in their necks, which were confirmed as ECA aneurysms. Another 65-year-old woman presented with a calcified mass in her neck caused by an ECA aneurysm. The first case was treated with aneurysmorrhaphy with primary closure, the second with replacement of the involved site with vascular prosthesis, and the third with a high flow bypass with proximal ligation of the internal carotid artery. All three different surgical techniques were successful. ECA aneurysms are rare and require careful selection of the surgical method according to etiology, shape, and location of the ECA aneurysm. Proficiency in various vascular reconstruction techniques is a desirable prerequisite for the surgeon in-charge.

DOI： 10.2176/nmc.52.208

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Cervical vertebral arteriovenous fistulas (AVFs) are very rare. The most frequent cause is trauma including iatrogenesis which result from vertebral artery penetration during central venous catheterization. Some endovascular techniques have been reported for this type of lesion. However, several potential problems exist, such as possibility of recurrence of AVFs and VA occlusion with endovascular treatment. In this article, we review two cases with iatrogenic vertebral AVFs which were successfully treated surgically and report the advantages of surgical treatment.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVE: Cerebral hyperperfusion syndrome is a major complication after carotid endarterectomy (CEA). We investigated whether our strategy of minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation prevented postoperative hyperperfusion.
METHODS: Eighty consecutive patients undergoing CEA were studied. A shunt was used in all patients during CEA. All patients were managed postoperatively under continuous sedation for as long as 48 hours on the basis of the regional cerebral blood flow (rCBF) measured immediately after CEA. Postoperative hyperperfusion was assessed, on the basis of the cerebral blood flow study under sedation (propofol) after CEA, either as a greater than 30% increase in rCBF compared with the contralateral side or a greater than 100% increase in the corrected rCBF (calculated from percentage reduction of the contralateral rCBF induced by propofol) compared with preoperative values.
RESULTS: No patient developed cerebral hyperperfusion syndrome. Postoperative hyperperfusion was found at very low rates (2.5% in the middle cerebral artery territory and 1.3% in the anterior cerebral artery territory by definition 1, and 0% in both territories by definition 2). Ratios of regional oxygen saturation after internal carotid artery clamping to preclamp baseline values were greater than 0.9 in 78 of 80 patients, indicating very mild intratoperative cerebral ischemia. Parameters related to cerebral ischemia during CEA, such as regional oxygen saturation, internal carotid artery cross-clamping duration, and Stump pressure (index), did not affect the incidence of postoperative hyperperfusion.
CONCLUSION: The present study suggests that minimizing intraoperative cerebral ischemia using a shunt, followed by strict postoperative blood pressure control under continuous sedation, can prevent post-CEA hyperperfusion.

DOI： 10.1227/01.NEU.0000339110.73385.8A

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記述言語：日本語  

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm (IA) is a devastating condition with high mortality and morbidity. Genetic as well as environment factors play important roles in the pathogenesis of SAH and IAs. We review the present knowledge on the genetic factors responsible for SAH or IAs. Linkage analysis and association study are used for genetic dissection. Genome-wide linkage analyses have specified several genetic loci for IAs and 6 loci (1p34-36, 7q11, 11q24-25, 14q22-31, 19q13, and Xp22) have been replicated in different populations. Numerous functional and/or positional candidate genes for IAs have been investigated by case-control association studies. The results of genetic association studies are modest because of small sample sizes. To date, no specific genes have been identified as responsible for IA development or rupture. Recent, large-scale genome-wide association (GWA) studies have revealed consistent and replicable genetic markers of several complex diseases such as coronary artery disease and type 2 diabetes. Although, thus far, no GWA studies have been performed for IAs, such a study may accomplish the breakthrough of genetic dissection of IAs. The identification of susceptible genes might lead to the understanding of the mechanism of IA formation or rupture and to novel therapeutic strategies.

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DOI： 10.1016/j.neuroscience.2008.04.049

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その他リンク： http://orcid.org/0000-0001-6808-5491

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

The rupture of an intracranial aneurysm (IA) results in subarachnoid hemorrhage, a catastrophic neurological condition with high morbidity and mortality. Following-up on our previous genome-wide linkage study in Japanese population, we extensively analyzed a 4.6 Mb linkage region around D7S2472 on 7q11 by genotyping 168 single nucleotide polymorphisms (SNPs). SNP association and window scan haplotype-based association studies revealed a susceptibility locus for IA on a single LD block covering the 3 '-untranslated region (3 '-UTR) of ELN and the entire region of LIMK1. An association study with 404 IA patients and 458 non-IA controls revealed that the ELN 3 '-UTR G(+659)C SNP has the strongest association to IA (P=0.000002) and constitutes a tag-SNP for an at-risk haplotype, which contains two functional SNPs, the ELN 3 '-UTR (+502) A insertion and the LIMK1 promoter C(-187)T SNP. These allelic and haplotype-based associations were confirmed in a Korean population. Ex vivo and in vitro analyses demonstrate that the functional impact of both SNPs is the decrease of transcript levels, either through accelerated ELN mRNA degradation or through decreased LIMK1 promoter activity. Elastin and LIMK1 protein are involved in the same actin depolymerization signaling pathway; therefore, these lines of evidence suggest a combined effect of the SNPs in the at-risk haplotype possibly by weakening the vascular wall and promoting the development of IA.

DOI： 10.1093/hmg/ddl096

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

A linkage region on chromosome 17cen has previously been found in 29 Japanese families with a history of familial intracranial aneurysms (IA). To investigate whether there is evidence of linkage in affected Japanese sib-pairs we performed nonparametric and parametric linkage analysis of a total of 253 familial aneurysm cases including 111 affected sib-pairs (ASP). Ten microsatellite markers covering a 17.7 cM region were chosen, in accordance with previous work in which nominal P had been below 0.05. Statistical analysis was performed by use of Genehunter and Sibpal software. After calculation of the logarithm of the odds (LOD) and nonparametric linkage analysis (NPL) scores our study did not show any linkage in the region analyzed. Our conclusion did not change even after only ASP were analyzed. In contrast with a previous study examining multigenerational Japanese families with IA, most Japanese ASP may not have a genetic linkage to chromosome 17 cen.

DOI： 10.1007/s10038-006-0379-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations-Japanese and Korean.
Methods. The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with IAs and 214 Japanese and 191 Korean control volunteers. Differences in genotype frequencies among the various aneurysm sizes were evaluated using the Fisher exact test.
There was no significant difference in heterozygous (T/C) eNOS T-786C SNP between aneurysms 5 mm or smaller and those from 6 to 9 mm, and between lesions 5 mm or smaller and those 10 mm or larger in 336 Japanese patients harboring aneurysms-220 with ruptured and 116 with unruptured lesions-and in 191 Korean patients with ruptured aneurysms.
Conclusion. The eNOS T-786C SNP genotype does not influence the size of aneurysms.

DOI： 10.3171/jns.2005.102.1.0068

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background and Purpose-A possible association has been proposed for the formation of intracranial aneurysm (IA) and deficiency alleles (S and Z) of the alpha(1)-antitrypsin (AAT) gene. We extensively screened this gene in Japanese and Korean patients with aneurysmal subarachnoid hemorrhage.
Methods-Seven allelic variants, including S and Z alleles, were genotyped by direct sequencing of genomic DNA obtained from 195 and 189 ruptured IA patients and 195 and 94 controls in Japanese and Koreans, respectively. The haplotype in phase-unknown samples was constructed with the expectation-maximization method. Differences in allelic frequencies between patients and controls were evaluated by Fisher exact test.
Results-No significant differences in allelic frequencies were observed at all 7 variants between ruptured IA patients and controls. We could not detect the S and Z alleles of the AAT gene in Japanese and Korean populations.
Conclusions-AAT deficiency may not be a common genetic risk factor for aneurysmal subarachnoid hemorrhage in Japanese and Koreans.

DOI： 10.1161/01.STR.0000147966.81215.be

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background and Purpose - The collagen alpha2(I) gene (COL1A2) on chromosome 7q22.1, a positional and functional candidate for intracranial aneurysm (IA), was extensively screened for susceptibility in Japanese IA patients.
Methods - Twenty-one single nucleotide polymorphisms (SNPs) of COL1A2 were genotyped in genomic DNA from 260 IA patients (including 115 familial cases) (mean age, 59.9 years) and 293 controls (mean age, 61.6 years). Differences in allelic and genotypic frequencies between the patients and controls were evaluated with the chi(2) test. Circular dichroism spectrometry was monitored with collagen-related peptides that mimic triple-helical models of type I collagen with Ala-459 and Pro-459 to estimate the conformation and stability of alterations.
Results - Significant genotypic association in the dominant model was observed between an exonic SNP of COL1A2 and familial IA patients (chi(2)=11.08; df=1 ; P=0.00087; odds ratio=3.19; 95% CI, 2.22 to 6.50). This SNP induces Ala to Pro substitution at amino acid 459, located on a triple-helical domain. Circular dichroism spectra showed that the Pro-459 peptide had a higher thermal stability than the Ala-459 peptide.
Conclusions - The variant of COL1A2 could be a genetic risk factor for IA patients with family history.

DOI： 10.1161/01.STR.0000110788.45858.DC

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background and Purpose-A 6-base insertion (6bINS) polymorphism in intron 7 of the endoglin gene (ENG), which codes for a component of the transforming growth factor-beta receptor complex, was reported to be associated with intracranial aneurysm (IA) in a Japanese population. A recent report using a white population could not replicate the association. We tested for this association with high statistical power in our independent Japanese subjects and evaluated the linkage between markers on chromosome 9, which contains ENG, and IA.
Methods-The sample for the linkage study comprised 179 individuals with IA in 85 nuclear families, with 104 possible affected sibpairs. For the association study of the 6bINS polymorphism and 4 single nucleotide polymorphisms (SNPs) in ENG, 172 Japanese patients with IA and 192 control subjects were examined.
Results-There was no evidence of linkage in the vicinity of ENG by analysis of affected sibpairs. The allele frequency of the 6bINS polymorphism was 104 of 344 (30.2%) in the total IA group and 122 of 382 (31.9%) in the control group. The statistical difference in allele frequency between the 2 groups was not significant (chi(2)=0.245, df=1, P=0.620). The power of the present association study was 98.3% at a significance level of 0.05 on the basis of the allele frequencies in the previous study. In addition, no associations between the 4 SNPs in ENG and IA were detected.
Conclusions-We provide evidence that there is no association between the 6bINS polymorphism or 4 SNPs in ENG and IA and that there is no linkage between the ENG locus and IA, indicating that ENG is not a major susceptibility gene for IA in Japanese.

DOI： 10.1161/01.STR.0000075770.70554.99

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background and Purpose-Maintenance of an adequate intravascular volume is important in the management of patients with subarachnoid hemorrhage (SAH). The purpose of this study was to investigate the circulating blood volume (CBV) after SAH with the use of indocyanine green pulse spectrophotometry.
Methods-CBV and plasma hormones related to stress and fluid regulation were measured 4 times: day 2 to 3, day 4 to 5, day 7 to 8, and day 14 in 50 consecutive patients with SAH surgically treated within 48 hours.
Results-The mean value of CBV was 64 mL/kg on day 2 to 3, which gradually increased to 69 mL/kg on day 4 to 5, 71 mL/kg on day 7 to 8, and 70 mL/kg on day 14 (P=0.005) (control, 72 mL/kg). The clinical grades and plasma corticotropin levels were higher in patients with <60 mL/kg of CBV on day 2 to 3 (P<0.05 for both). There were no significant differences in other physiological and laboratory parameters such as time for surgery, estimated blood loss, levels of plasma noradrenaline, brain natriuretic peptide, serum sodium, and hematocrit. When CBV was decreased >10% of the former level, there were decreases in hematocrit (P<0.05), serum sodium (P<0.01), and serum albumin (P<0.05) and an increase in urinary sodium (P<0.05).
Conclusions-A significant reduction of CBV, especially in patients with poor clinical grades, was noted after SAH and early surgery, which could not be detected by routine examinations. Anemia, central salt wasting, and hypoalbuminemia may be related to a decrease in CBV from the former level. Indocyanine green pulse spectrophotometry may be a powerful tool for the management of patients with SAH.

DOI： 10.1161/01.STR.0000064321.10700.63

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG TOKYO  

We previously performed a genome-wide linkage study of intracranial aneurysm (IA) and found positive evidence of linkage at chromosomes 5q22-31, 7q11, and 14q22. In the present study, we focus on 5q31, where three candidate genes, fibroblast growth factor I (FGF1), fibrillin 2 (FBN2), and lysyl oxidase gene (LOA) lie, and evaluate associations with IA. Genomic DNAs were obtained from 172 IA patients and 192 controls. Association analysis was performed with ten, five, and four single-nucleotide polymorphisms (SNPs) identified in FGF1, FBN2, and LOX, respectively. A difference in allelic frequency was observed for only the SNP at intron 4 in FGF1 (chi(2) = 4.44, df = 1, P = 0.035). Although a haplotype association was observed with the combination of ten SNPs in FGF1 (chi(2) = 16.04, df = 1, P = 0.00006), significant haplotype associations were not observed when haplotypes were constructed with the three, two, and four SNPs in FGF1 according to the linkage disequilibrium structure. No associations of FBN2 and LOX with IA were detected in the present study.

DOI： 10.1007/s10038-003-0030-6

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DOI： 10.1086/323614

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記述言語：日本語   出版者・発行元：IGAKU-SHOIN LTD  

We report three patients (a 36-year-old man, a 41-year-old woman, and a 22-year-old man) with lymphoplasmacyte-rich meningioma who manifested characteristics on radiological and blood examinations. Two were hospitalized with gradual deterioration of hemiparesis and one with general convulsive seizure. Radiological examination revealed typical meningiomas of convexity in two and that of falx in one. Two of the patients showed large perifocal edema. Anemia was found in one patient and an elevated level in the zinc sulfate turbidity test was noted in all cases. Abnormal findings in laboratory examination improved quickly, whereas perifocal edema remained for six months after tumor removal. The tumors were histologically confirmed to be meningioma with massive infiltrates of plasma cells and lymphocytes. Seventeen cases of lymphoplasmacyte-rich meningioma that have been reported to date including our three cases were reviewed.

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記述言語：日本語   出版者・発行元：(株)医学書院  

77歳女。突然の頭痛にて近医を受診し、頭部CTでくも膜下出血(SAH)を認め、紹介搬送された。CT angiographyでは右内頸動脈瘤を認め、緊急で開頭クリッピング術を行ったが、術中、動脈瘤と反対側の動脈壁が突然lacerationをきたし、解離性動脈瘤が疑われた。SAHとしての経過は比較的良好であったが、第6病日にヘモグロビン値が急激に低下し、第8病日に突然心停止をきたして死亡した。剖検所見では上腸間膜動脈の破裂、多量の腹腔内出血がみられ、病理所見では腹腔動脈本幹、脾動脈の解離、ならびに筋層内の空胞変性と中膜の一部残存を認めたほか、内頸動脈、脳底動脈筋層内にも同様の所見が確認され、segmental arterial mediolysisによる頭蓋内および腹腔内動脈瘤と診断した。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01228&link_issn=&doc_id=20190531140009&doc_link_id=10.11477%2Fmf.1436203979&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436203979&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

今回、我々はbranch atheromatous disease(BAD)の初診時のCT灌流画像の平均通過時間における梗塞巣の左右差ならびにMRIによる梗塞巣のサイズ、危険因子について検討を行った。その結果、レンズ核線条体動脈領域の梗塞については、症状の増悪は梗塞巣のサイズによらず、症状の増悪例は全例MTTにて左右差を認めており、このような症例は症状の増悪に備えた治療が必要であると考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01786&link_issn=&doc_id=20180802420001&doc_link_id=%2Fdh3strok%2F2018%2F004004%2F001%2F0243-0248%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh3strok%2F2018%2F004004%2F001%2F0243-0248%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

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記述言語：日本語   出版者・発行元：東京女子医科大学学会  

CiNii Books

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その他リンク： http://hdl.handle.net/10470/31540

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：KARGER  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：KARGER  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：KARGER  

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記述言語：日本語   出版者・発行元：スパズム・シンポジウム事務局  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

DOI： 10.3995/jstroke.30.886

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

DOI： 10.3995/jstroke.30.886

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記述言語：日本語   出版者・発行元：東京女子医科大学学会  

くも膜下出血は致死性の高い疾患であり、原因となる脳動脈瘤の成因には環境要因とともに遺伝要因の関与が想定されている。我々は世界に先駆けて、脳動脈瘤罹患同胞104対を用いてゲノム全域にわたり連鎖解析を行った。結果、第5番染色体(5q22-31)、第7番染色体(7q11)、第14番染色体(14q22)に疾患との連鎖を認めた。その後、フインランド人の解析では第19番染色体(19q13.3)、日本人の他の解析では、第17番染色体(17cen)、19番染色体(19q13)、X染色体(Xp22)、その他、第1番染色体(1p34.3-36.13)、第2番染色体(2p13)などに連鎖を認めた報告がある。現在、2つの領域(7qと19q)で日本人と白人の両集団で連鎖が確認されており、罹患同胞対と大家系を用いた解析で両領域はそれぞれ連鎖が確認されている。我々は連鎖解析の結果に基づき、最も疾患との連鎖が強い第7番染色体にあるマーカー(D7S2472)近傍、4.6Mbに渡り、168ヶ所のSNP(single nucleotide polymorphism;一塩基多型)を利用して関連解析およびハプロタイプ解析を行った。これにより、ELNの3'UTRからLIMK1全域にかけてのLD block内に疾患感受性領域があることが判明した。さらにELNの3'UTR内に疾患と有意に関連するSNP(G(+639)C)を同定できた。このSNPは、ELNとLIMK1の転写量に影響を及ぼす2ヶ所の機能的SNPを含むat-risk haplotypeのtag SNPであった。その他いろいろな候補遺伝子が、多様な集団において関連解析されているが、未だ確定的な疾患遺伝子は同定されていない。今後は、より大きな集団を利用した遺伝解析や機能解析による原因究明が待たれる。(著者抄録)

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記述言語：日本語   出版者・発行元：東京女子医科大学  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

インドシアニングリーン(ICG)を静脈注射した後,循環血液中のICGの濃度変化をpulse spectrophotometryにより測定することで計算される循環血液量変化法を用いて,くも膜下出血患者50症例の循環血液量について検討を行った.循環血液量の平均値は発症間もない時期に最も低く,徐々に増加し,7-8日目にはほぼ正常になることが明らかになった.手術後2〜3日においては循環血液量の差が大きく,原因について検討した結果,60ml/kg以下のグループには重症例が多く,corticotropinが有意に高かった.また,中心静脈圧を8cm以上に保つべく,電解質輸液の他に5%アルブミン液250mlを2時間毎に輸注し,中心静脈圧を5cm以上に保つ群と比較した.点滴投与群はhypervolemic治療群が常に多かったが,循環血液量,脳循環血液量に差はなく,虚血症状の発症率にも差はなかった

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記述言語：日本語   出版者・発行元：(株)先端医学社  

脳動脈瘤が合併する代表疾患である,常染色体優性の多発性嚢胞腎の原因遺伝子は,第16番染色体短腕に存在するPKD1遺伝子(全体の約85%)と,第4番染色体長腕に存在するPKD2である.遺伝性疾患に合併しないほとんどの脳動脈瘤は,単一ではない遺伝要因と環境要因が複雑に絡む生活習慣病(多因子疾患)に属すと考えられ,遺伝解析は容易ではない.罹患同胞を多数集めておこなう罹患同胞対連鎖解析の結果,感受性遺伝子座は,第5番,7番,14番,19番染色体長腕に存在した.現在,候補遺伝子の探索がおこなわれている(著者抄録)

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

Intracranial aneurysm (IA) is a common disorder with a prevalence of 3-6% as shown by angiographic and autopsy studies and rupture of IA causes subarachnoid hemorrhage (SAH). It is well known that IA has a substantial genetic component, however, there has been little attention to the genetic determinants. We performed a genome-wide linkage study of IA in 104 Japanese affected sib-pairs using SIBPAL and GENEHUNTER programs. Evidence of linkage at chromosome 5q22-31 (MLS = 2.24), 7q11 (MLS = 3.22), and 14q22 (MLS = 2.31) was found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for the disease. Fourteen distinct single nucleotide polymorphisms (SNPs) are identified in ELN, and no obvious allelic association between IA and each SNP was observed. A haplotype between the intron 20/23 polymorphism of ELN is strongly associated with IA (P = 3.81 x 10(-6)), and homozygote patients are at high risk with an odds ratio of 4.39. (C) 2003 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0531-5131(03)00102-X

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：UNIV CHICAGO PRESS  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳神経外科学会  

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開催年月日： 2017年2月

記述言語：日本語  

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開催年月日： 2007年10月

記述言語：日本語  

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開催年月日： 2000年10月

記述言語：日本語  

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