Kotaro Miyashita

Publications (27)56.78 Total impact

• Article: Critical multi-organ emboli originating from collapsed, vulnerable caseous mitral annular calcification.

  Taka-aki Matsuyama, Hatsue Ishibashi-Ueda, Yoshihiko Ikeda, Kazuyuki Nagatsuka, Kotaro Miyashita, Makoto Amaki, Hideaki Kanzaki, Masafumi Kitakaze
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  ABSTRACT: Mitral annular calcification (MAC) is a generally asymptomatic abnormality found commonly in aged hearts. Some clinical studies have suggested that MAC should be considered an independent risk factor for stroke; however, whether the abnormality is indeed a risk factor remains controversial. We report a case in which debris from a vulnerable caseous MAC contributed to lethal embolisms in multiple organs. Postmortem examination revealed that caseous materials originating from a collapsed MAC were trapped in stenosed atherosclerotic cerebral and coronary arteries. Our findings support the notion at that subtle debris from collapsed vulnerable MACs can trigger major and even lethal embolic events in patients with severe atherosclerotic stenosis in vital organs.
  Pathology International 07/2012; 62(7):496-9. · 1.62 Impact Factor
• Article: [Response to the proposal].

  Hiroaki Naritomi, Kotaro Miyashita, Atsuo Koto
  Rinshō shinkeigaku = Clinical neurology. 01/2012; 52(7):513-4.
• Article: [Cell based therapy for patients after cerebral embolism].

  Akihiko Taguchi, Kozue Saito, Katsufumi Kajimoto, Hiroshi Moriwaki, Yukiko Kasahara, Hiroaki Naritomi, Kotaro Miyashita, Kazuyuki Nagatsuka
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  ABSTRACT: Neuronal stem cells are mobilized after cerebral infarction. We had shown that appropriate support of these stem cells, achieved by therapeutic angiogenesis, enhances neurological recovery in experimental stroke model. Based on these observations, we started cell based therapy using autologous bone marrow mononuclear cells for patients after cerebral embolism as phase 1/2a clinical trial. We have treated 6 patients in low dose group (harvest 25 ml of bone marrow cells) and none of them showed treatment-related adverse effects. We are now recruiting another 6 patients in high dose group (harvest 50 ml of bone marrow cells) and are planning to evaluate the effectiveness and safety of the therapy after obtaining the results of all 12 patients.
  Rinshō shinkeigaku = Clinical neurology. 11/2011; 51(11):1081-2.
• Article: A case of cortical infarction with isolated sensory disturbance in the c8 nerve root area.

  Arisa Umesaki, Hisakazu Uno, Hitoshi Niki, Takako Torii, Masahiro Higashi, Kotaro Miyashita, Hiroaki Naritomi
  European Neurology 07/2009; 62(2):124. · 1.81 Impact Factor
• Article: Severe hyperthermia caused by four-vessel occlusion of main cerebral arteries.

  Kuni Konaka, Kotaro Miyashita, Hatsue Ishibashi-Ueda, Hiroaki Naritomi
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  ABSTRACT: We present the case of a comatose patient with acute large infarction of posterior cerebral and cerebellar areas and severe hyperthermia (max. 40.4 degrees C). Angiography demonstrated four-vessel occlusion of the main cerebral arteries, suggesting the possibility that both internal carotid and left vertebral arteries were already occluded and he became unconscious following additional occlusion of the right vertebral artery. Autopsy findings revealed bilateral ischemic damage of the hypothalamus in addition to the above infarct areas. Sudden ischemic involvement of both hypothalamic regions may have caused the extremely high fever in this case.
  Internal Medicine 01/2009; 48(24):2137-40. · 0.94 Impact Factor
• Article: Genetic variations of CYP2C9 in 724 Japanese individuals and their impact on the antihypertensive effects of losartan.

  Tong Yin, Keiko Maekawa, Kei Kamide, Yoshiro Saito, Hironori Hanada, Kotaro Miyashita, Yoshihiro Kokubo, Yasuhisa Akaiwa, Ryoichi Otsubo, Kazuyuki Nagatsuka, Toshiho Otsuki, Takeshi Horio, Shin Takiuchi, Yuhei Kawano, Kazuo Minematsu, Hiroaki Naritomi, Hitonobu Tomoike, Jun-ichi Sawada, Toshiyuki Miyata
  [show abstract] [hide abstract]
  ABSTRACT: CYP2C9, a drug-metabolizing enzyme, converts the angiotensin II receptor blocker losartan to its active form, which is responsible for its antihypertensive effect. We resequenced CYP2C9 in 724 Japanese individuals, including 39 hypertensive patients under treatment with losartan. Of two novel missense mutations identified, the Arg132Gln variant showed a fivefold lower intrinsic clearance toward diclofenac when expressed in a baculovirus-insect cell system, while the Arg335Gln variant had no substantial effect. Several known missense variations were also found, and approximately 7% of the Japanese individuals (53 out of 724) carried one of the deleterious alleles (CYP2C9*3, *13, *14, *30, and Arg132Gln) as heterozygotes. After 3 months of losartan treatment, systolic blood pressure was not lowered in two patients with CYP2C9* 1/*30, suggesting that they exhibited impaired in vivo CYP2C9 activity. CYP2C9*30 might be associated with a diminished response to the antihypertensive effects of losartan.
  Hypertension Research 09/2008; 31(8):1549-57. · 2.58 Impact Factor
• Article: No association between vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) and the variability of warfarin dose requirement in a Japanese patient population.

  Tong Yin, Hironori Hanada, Kotaro Miyashita, Yoshihiro Kokubo, Yasuhisa Akaiwa, Ryoichi Otsubo, Kazuyuki Nagatsuka, Toshiho Otsuki, Akira Okayama, Kazuo Minematsu, Hiroaki Naritomi, Hitonobu Tomoike, Toshiyuki Miyata
  Thrombosis Research 02/2008; 122(2):179-84. · 2.44 Impact Factor
• Article: Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients.

  Rina Kimura, Kotaro Miyashita, Yoshihiro Kokubo, Yasuhisa Akaiwa, Ryoichi Otsubo, Kazuyuki Nagatsuka, Toshiho Otsuki, Akira Okayama, Kazuo Minematsu, Hiroaki Naritomi, Shigenori Honda, Hitonobu Tomoike, Toshiyuki Miyata
  [show abstract] [hide abstract]
  ABSTRACT: The dose required for the anticoagulant effect of warfarin exhibits large inter-individual variations. This study sought to determine the contribution of four genes, vitamin K epoxide reductase (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU), and cytochrome P450 2C9 (CYP2C9) to the warfarin maintenance dose required in Japanese patients following ischemic stroke. We recruited 93 patients on stable anticoagulation with a target International Normalized Ratio (INR) of 1.6-2.6. We genotyped eleven representative single nucleotide polymorphisms (SNPs) in the three genes involved in vitamin K cycle and the 42613A>C SNP in CYP2C9, known as CYP2C93, and then examined an association of these genotypes with warfarin maintenance doses (mean+/-SD=2.96+/-1.06 mg/day). We found an association of effective warfarin dose with the -1639G>A (p=0.004) and 3730G>A genotypes (p=0.006) in VKORC1, the 8016G>A genotype in GGCX (p=0.022), and the 42613A>C genotype in CYP2C9 (p=0.015). The model using the multiple regression analysis including age, sex, weight, and three genetic polymorphisms accounted for 33.3% of total variations in warfarin dose. The contribution to inter-individual variation in warfarin dose was 5.9% for VKORC1 -1639G>A, 5.2% for CYP2C9 42613A>C, and 4.6% for GGCX 8016G>A. In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients.
  Thrombosis Research 02/2007; 120(2):181-6. · 2.44 Impact Factor
• Article: [Clinicostatistical analysis of thalamic hemorrhage].

  Kotaro Miyashita, Hiroaki Naritomi
  Nippon rinsho. Japanese journal of clinical medicine 12/2006; 64 Suppl 8:390-4.
• Article: Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population.

  Rina Kimura, Yoshihiro Kokubo, Kotaro Miyashita, Ryoichi Otsubo, Kazuyuki Nagatsuka, Toshiho Otsuki, Toshiyuki Sakata, Junko Nagura, Akira Okayama, Kazuo Minematsu, Hiroaki Naritomi, Shigenori Honda, Kiyoshi Sato, Hitonobu Tomoike, Toshiyuki Miyata
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  ABSTRACT: gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K-dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G>A change leads to the substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.
  International Journal of Hematology 12/2006; 84(5):387-97. · 1.27 Impact Factor
• Article: Primary intracerebral hemorrhage during asleep period.

  Yoshinari Nagakane, Kotaro Miyashita, Kazuyuki Nagatsuka, Takemori Yamawaki, Hiroaki Naritomi
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  ABSTRACT: The onset of intracerebral hemorrhage (ICH) has a circadian variation, with a lower risk during the asleep period. It is unclear, however, whether ICH during the asleep period differs from that during the awake period in pathophysiologic nature. The purpose of this study is to elucidate the incidences and clinical features of ICH during the asleep period. We studied 129 consecutive patients with primary ICH and classified them into two groups according to the circumstance of their stroke onset, either during the awake period (awake ICH group) or the asleep period (asleep ICH group). Demographic and clinical characteristics were then compared between the two groups. Of the patients, 19 (14.7%) had ICH during the asleep period. The mortality rate at 1 month after the stroke was significantly higher in the asleep ICH group than in the awake ICH group (21.1% v 4.9%, P = .0325). The hemorrhage volume in the asleep ICH group was also significantly larger than that in the awake ICH group (mean volume, 32.6 mL v 16.7 mL, P = .0122). Our findings indicate that ICH during the asleep period may be more detrimental compared with ICH during the awake period, causing larger hematoma and higher mortality rates.
  American Journal of Hypertension 05/2006; 19(4):403-6. · 3.18 Impact Factor
• Article: Interhemispheric neural conduction velocity estimated by auditory-evoked magnetic fields decreases correlating with the degree of depressive mood in elderly subjects

  Hiroshi Oe, Akihiko Kandori, Tsuyoshi Miyashita, Kuniomi Ogata, Kotaro Miyashita, Kuni Konaka, Keiji Tsukada, Hiroaki Naritomi
  Journal of Cerebral Blood Flow &#38 Metabolism 07/2005; · 5.01 Impact Factor
• Source

  Available from: Yusuke Yakushiji

  Article: "A girdle-like tightening sensation" misapprehended as abdominal splanchnopathy in a sarcoidosis patient.

  Yusuke Yakushiji, Kentaro Yamada, Kazuyuki Nagatsuka, Yukako Hashimoto, Kotaro Miyashita, Hiroaki Naritomi
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  ABSTRACT: We describe a 53-year-old man with the isolated manifestation of girdle-like tightening sensation of the trunk due to polyradiculopathy at the beginning of sarcoidosis which was first misapprehended as abdominal splanchnopathy. Late development of other neurological and systemic symptoms led to the final diagnosis of sarcoidosis. Segmental dysesthesia at the trunk in neurosarcoidosis is unique and may mimic a splanchnic pain. Such a dysesthesia may be solely manifested at the beginning of sarcoidosis and may continue for days without other symptoms. When patients complain of a girdle-like tightening with unknown etiology, sarcoidosis should be suspected as the possible cause.
  Internal Medicine 07/2005; 44(6):647-52. · 0.94 Impact Factor
• Article: Mechanisms of bihemispheric brain infarctions in the anterior circulation on diffusion-weighted images.

  Kozue Saito, Hiroshi Moriwaki, Hiroshi Oe, Kotaro Miyashita, Kazuyuki Nagatsuka, Satoshi Ueno, Hiroaki Naritomi
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  ABSTRACT: Multiple acute brain infarctions in both cerebral hemispheres usually suggest an embolic mechanism, particularly one of aortic or cardiac origin. The purpose of this study was to clarify the etiologic mechanisms and topographic features of bihemispheric infarctions depicted on diffusion-weighted imaging (DWI). Among 411 consecutive patients with ischemic stroke who underwent MR imaging in the acute phase, DWI showed bilateral infarctions in 19 (4.6%). In these patients, we analyzed the presence of carotid, aortic or cardiac embolic sources by using ultrasonography, cerebral angiography, and/or transesophageal echocardiography and evaluated the size and topographic distribution of the lesions. We assessed intracranial cross-flow through the anterior communicating artery, mainly on the basis of the anatomic information obtained from angiography or MR angiography. Bilateral lesions were derived from cardiac and/or aortic embolic sources in 16 (84%) of 19 patients and appeared to originate from unilateral carotid diseases in three (16%). In nine (82%) of 11 patients with cardiac embolic sources, at least one large territorial or subcortical lesion was found in either hemisphere, whereas in all eight patients without a cardiac embolic source, the lesions were small and disseminated bilaterally. Unilateral carotid lesions can cause bihemispheric infarctions through cross-flow in the anterior communicating artery. On DWI, small bihemispheric, disseminated lesions strongly suggest an artery-to-artery embolism. In such cases, aortic and carotid lesions should be assessed as potential embolic sources.
  American Journal of Neuroradiology 05/2005; 26(4):809-14. · 2.93 Impact Factor
• Article: [Multiple brain infarctions in a young patient with Buerger's disease. A case report of cerebral thromboangiitis obliterans].

  Makiko Rai, Kotaro Miyashita, Hiroshi Oe, Kazuhiro Nishigami, Hiroaki Naritomi
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  ABSTRACT: We report a 46-year-old woman with Buerger's disease who presented vascular dementia. In her early thirties, she began to feel cold sensation and pain in the lower extremities and later developed Raynaud's phenomenon in the upper extremities. The diagnosis of Buerger's disease was established on the basis of angiographic findings which showed the obstruction of peripheral vessels in both anterior tibial arteries. She was admitted to our hospital because of a transient attack of left brachial monoparesis and two episodes of epileptic seizure with progressive cognitive impairment for preceding five years. Neurological examination revealed acalculia, constructional apraxia, recent memory disturbance, and hyperreflexia of the left limbs without motor disturbance. Brain MRI revealed multiple infarctions mainly located in the border zone territories of the major cerebral arteries. Conventional angiography failed to detect abnormalities of cerebral vessels. She had no cardiovascular abnormality or coagulopathy. Cerebrovascular complications, so-called cerebral thoromboangiitis obliterans (CTAO), occur approximately in 2% of patients with Buerger's disease. CTAO has two types. Type 1 is associated with large artery changes and type 2 is associated with medium and small artery changes. Patients with type 2 CTAO usually have multiple infarcts in the cerebral arterial border zones and may develop progressive cognitive decline without motor deficit. Her clinical features are compatible with type 2 CTAO. While CTAO is a relatively rare manifestation of Buerger's disease, it should be suspected in cases of Buerger's disease in association with cognitive impairment of unknown onset.
  Rinsho shinkeigaku = Clinical neurology 09/2004; 44(8):522-6.
• Article: Link between linear hyperintensity objects in cerebral white matter and hypertensive intracerebral hemorrhage.

  Masahiko Hiroki, Kotaro Miyashita, Hiroshi Oe, Shigetoshi Takaya, Shunsaku Hirai, Hidenao Fukuyama
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  ABSTRACT: We retrospectively studied the relationship between linear hyperintensity objects (LHOs) on T(2)-weighted magnetic resonance images (MRI) in the cerebral white matter and the occurrence of hypertensive intracerebral hemorrhage (HIH). Forty-nine hypertensive patients with a fixed imaging condition MRI were classified into three groups: HIH (n = 17), ischemic stroke due to hypertensive vasculopathy (n = 19), and hypertension only (n = 13). After assessing clinical and radiological background information among these groups and the reliability of LHO measurements, polynomial logistic regression analysis was used to identify the factors relating to HIH. HIH had a significantly higher LHO number (p = 0.002) and larger diameter (p = 0.007). The LHO number showed an excellent interrater (kappa = 0.91, 95% CI = 0.87-0.94, SEM = 6.2%) and intrarater reliability (kappa = 0.95, 95% CI= 0.92-0.97, SEM = 4.8%), and was the most significant independent indicator of HIH (OR = 1.29, 95% CI = 1.05-1.60, p = 0.017). The number of microbleeds was an additional indicator (OR = 3.73, 95% CI = 1.10-12.65, p = 0.034). LHOs are closely linked to HIH. A prospective, longitudinal study is needed to clarify whether LHOs can predict HIH.
  Cerebrovascular Diseases 02/2004; 18(2):166-73. · 2.72 Impact Factor
• Article: Reversible stenosis of major cerebral arteries demonstrated by MRA in thrombotic thrombocytopenic purpura.

  Kimito Kondo, Takemori Yamawaki, Kazuyuki Nagatsuka, Kotaro Miyashita, Hiroaki Naritomi
  Journal of Neurology 09/2003; 250(8):995-7. · 3.47 Impact Factor
• Article: Central retinal artery Doppler flow parameters reflect the severity of cerebral small-vessel disease.

  Masahiko Hiroki, Kotaro Miyashita, Hiroshi Yoshida, Shunsaku Hirai, Hidenao Fukuyama
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  ABSTRACT: We investigated the usefulness of central retinal artery (CRA) Doppler flowmetry in patients with cerebral small-vessel disease (SVD). CRA Doppler flowmetry was performed in 103 SVD patients who underwent MRI. Sixty-four adjusted control subjects were also registered. We assessed average CRA flow parameter values for both eyes with the clinical and MRI findings. Each Doppler flowmetry was performed within 5 minutes. Patients with SVD had significantly lower end-diastolic and mean velocities of the CRA than control subjects; they also had higher pulsatility and resistive indexes. Multivariate analysis showed that the number of small infarcts was an independent predictor of peak systolic and mean velocities. Grade of periventricular hyperintensities was an additional independent predictor of peak systolic and mean velocities, whereas the number of small infarcts was predictive of end-diastolic velocity. Flow parameters may be useful for the quantitative assessment of SVD severity.
  Stroke 08/2003; 34(7):e92-4. · 5.73 Impact Factor
• Article: Magneto-encephalographic measurement of neural activity during period of vertigo induced by cold caloric stimulation.

  Akihiko Kandori, Hiroshi Oe, Kotaro Miyashita, Shinji Ohira, Hiroaki Naritomi, Yoshihide Chiba, Kuniomi Ogata, Masahiro Murakami, Tsuyoshi Miyashita, Keiji Tsukada
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  ABSTRACT: The aim of this study was to investigate neural activity during period of vertiginous sensation, induced by caloric stimulation. After caloric vestibular stimulation (CVS) by cold water of five volunteers (n=5, age: 30+/-10), auditory evoked magnetic fields (AEFs) during the subsequent period of vertiginous sensations were measured by magnetoencephalography (MEG). Current-arrow maps (CAMs) were produced to estimate the spatial current distribution of the AEF responses, and a rotation value (dI(rot)) was calculated from the CAM. The worth of the dI(rot) values as indicators of vertigo was evaluated by comparing them with earlier reported values for elderly control (n=11, age: 67+/-5) and chronic dizziness (CD) (n=27, age: 68+/-8) groups (obtained from AEF responses with no the CVS). Although all volunteers felt vertigo during the AEF measurements, the AEF waveforms and CAM pattern only showed slight changes. While the dI(rot) values (1.43+/-0.73) just after CVS were not significantly different from those (1.59+/-0.46) for the elderly controls, they were significantly different from those (3.54+/-1.34) for the CD patients. These findings suggest that (i) the new parameter (dI(rot)) is more sensitively indicates dizziness (non-rotatory sensation) than vertigo (ii) the auditory cortical region may play an important role in body-balance perception of floating sensations.
  Neuroscience Research 08/2003; 46(3):281-8. · 2.25 Impact Factor
• Article: Cerebral hemodynamic evaluation using perfusion-weighted magnetic resonance imaging: comparison with positron emission tomography values in chronic occlusive carotid disease.

  Katsufumi Kajimoto, Hiroshi Moriwaki, Naoaki Yamada, Kohei Hayashida, Junya Kobayashi, Kotaro Miyashita, Hiroaki Naritomi
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  ABSTRACT: Perfusion-weighted magnetic resonance imaging (PWI) is a reliable and semiquantitative method for estimating cerebral hemodynamics. We sought to evaluate the potential of PWI for assessing cerebral blood flow (CBF) and metabolism compared with positron emission tomography (PET) in patients with chronic occlusive carotid disease. In 24 patients with chronic unilateral occlusive carotid disease, time-to-peak (TTP) delay (TTP-D) measured by PWI was compared with CBF, cerebral blood volume (CBV), and oxygen extraction fraction (OEF) obtained by PET. TTP indicates the time from the start of PWI to the bolus peak. TTP-D indicates the difference in TTP values between the occlusive and contralateral hemispheres. TTP-D was compared between patients with normal and reduced CBF/CBV and also between patients with normal and elevated OEF. TTP-D in patients with reduced CBF/CBV was significantly longer than that in patients with normal CBF/CBV (3.4+/-1.8 versus 1.4+/-0.7 seconds; P<0.001). In the patients with reduced CBF/CBV, TTP-D correlated with OEF significantly (r=0.710, P<0.0001). TTP-D in patients with elevated OEF was significantly longer than that in patients with normal OEF (4.8+/-2.2 versus 2.0+/-0.9 seconds; P<0.01). In all 5 patients with TTP-D >or=4 seconds, OEF was elevated markedly. TTP-D >or=4 seconds is considered to indicate a high risk of hemodynamic failure. The measurement of TTP-D by PWI appears to provide important clinical information for evaluating cerebral hemodynamics in chronic occlusive carotid disease.
  Stroke 07/2003; 34(7):1662-6. · 5.73 Impact Factor