Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Ryu Matsuo Last modified date:2020.07.07

Associate Professor / Department of Health Care Administration and Management / Department of Basic Medicine / Faculty of Medical Sciences


Papers
1. Kuroda J, Matsuo R, Yamaguchi Y, Sato N, Kamouchi M, Hata J, Wakisaka Y, Ago T, Kitazono T; Fukuoka Stroke Registry Investigators., Poor glycemic control and posterior circulation ischemic stroke., Neurol Clin Pract., 2019.04.
2. yuji shono, Hiroshi Sugimori, ryu matsuo, Yoshihisa Fukushima, Yoshinobu Wakisaka, Junya Kuroda, Tetsuro Ago, Masahiro Kamouchi, Takanari Kitazono, Safety of antithrombotic therapy for patients with acute ischemic stroke harboring unruptured intracranial aneurysm, International Journal of Stroke, 10.1177/1747493018765263, 13, 7, 734-742, 2018.10, Background: The safety of antithrombotic therapy for patients with acute ischemic stroke harboring unruptured intracranial aneurysms remains unclear. Aims: This study was performed to determine whether treatment with antiplatelets, anticoagulants, or intravenous thrombolytic agents is safe for patients with acute ischemic stroke and unruptured intracranial aneurysms. Methods: Among 9149 patients with acute ischemic stroke enrolled in the Fukuoka Stroke Registry from June 2007 to December 2014, 8857 patients with data on cerebrovascular imaging and three-month outcomes were included in this study. The frequency of adverse events, including intracranial hemorrhage, symptomatic intracranial hemorrhage, and in-hospital mortality, was compared between patients with and without unruptured intracranial aneurysms. The risk of a poor functional outcome (modified Rankin scale score of ≥3) at three months after stroke onset was estimated after adjusting for confounding factors by logistic regression analysis. Results: Unruptured intracranial aneurysms were identified in 412 (4.7%) patients, and the mean diameter was 4.1 ± 3.2 mm. There was no significant difference in the frequency of any adverse events between patients with and without unruptured intracranial aneurysms among the overall patients or patients receiving antiplatelets, anticoagulants, or intravenous thrombolytic agents. The odds ratios of a poor functional outcome were not significantly higher in the presence of unruptured intracranial aneurysms, even in patients undergoing antiplatelet therapy, anticoagulation therapy, or intravenous thrombolysis. Conclusions: These findings suggest that unruptured intracranial aneurysms are not associated with increased risks of adverse events or poor functional outcomes even after antithrombotic therapy for acute ischemic stroke. However, accumulation of cases is required to verify these findings..
3. Kiyuna F, Sato N, Matsuo R, Kamouchi M, Hata J, Wakisaka Y, Kuroda J, Ago T, Kitazono T; for the Fukuoka Stroke Registry Investigators. , Association of Embolic Sources with Cause-Specific Functional Outcomes Among Adults with Cryptogenic Stroke. , JAMA Network Open., 2018.05.
4. Ago T, Matsuo R, Hata J, Wakisaka Y, Kuroda J, Kitazono T, Kamouchi M, Insulin resistance and clinical outcomes after acute ischemic stroke., NEUROLOGY, 90, 17, 1470-1477, 2018.04.
5. Satomi Mezuki, Kenji Fukuda, Tomonaga Matsushita, Yoshihisa Fukushima, ryu matsuo, Yu ichi Goto, Takehiro Yasukawa, Takeshi Uchiumi, Dongchon Kang, Takanari Kitazono, Tetsuro Ago, Isolated and repeated stroke-like episodes in a middle-aged man with a mitochondrial ND3 T10158C mutation
A case report, BMC neurology, 10.1186/s12883-017-1001-4, 17, 1, 2017.12, Background: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, is the most common phenotype of mitochondrial disease. It often develops in childhood or adolescence, usually before the age of 40, in a maternally-inherited manner. Mutations in mitochondrial DNA (mtDNA) are frequently responsible for MELAS. Case presentation: A 55-year-old man, who had no family or past history of mitochondrial disorders, suddenly developed bilateral visual field constriction and repeated stroke-like episodes. He ultimately presented with cortical blindness, recurrent epilepsy and severe cognitive impairment approximately 6 months after the first episode. Genetic analysis of biopsied biceps brachii muscle, but not of peripheral white blood cells, revealed a T10158C mutation in the mtDNA-encoded gene of NADH dehydrogenase subunit 3 (ND3), which has previously been thought to be associated with severe or fatal mitochondrial disorders that develop during the neonatal period or in infancy. Conclusion: A T10158C mutation in the ND3 gene can cause atypical adult-onset stroke-like episodes in a sporadic manner..
6. ryu matsuo, Yuko Yamaguchi, Tomonaga Matsushita, Jun Hata, Fumi Kiyuna, Kenji Fukuda, Yoshinobu Wakisaka, Junya Kuroda, Tetsuro Ago, Takanari Kitazono, Masahiro Kamouchi, Takao Ishitsuka, Setsuro Ibayashi, Kenji Kusuda, Kenichiro Fujii, Tetsuhiko Nagao, Yasushi Okada, Masahiro Yasaka, Hiroaki Ooboshi, Katsumi Irie, Tsuyoshi Omae, Kazunori Toyoda, Hiroshi Nakane, Hiroshi Sugimori, Shuji Arakawa, Jiro Kitayama, Shigeru Fujimoto, Shoji Arihiro, Yoshihisa Fukushima, Association between onset-to-door time and clinical outcomes after ischemic stroke, Stroke, 10.1161/STROKEAHA.117.018132, 48, 11, 3049-3056, 2017.11, Background and Purpose-The role of early hospital arrival in improving poststroke clinical outcomes in patients without reperfusion treatment remains unclear. This study aimed to determine whether early hospital arrival was associated with favorable outcomes in patients without reperfusion treatment or with minor stroke. Methods-This multicenter, hospital-based study included 6780 consecutive patients (aged, 69.9±12.2 years; 63.9% men) with ischemic stroke who were prospectively registered in Fukuoka, Japan, between July 2007 and December 2014. Onset-to-door time was categorized as T
0-1
, ≤1 hour; T
1-2
, >1 and ≤2 hours; T
2-3
, >2 and ≤3 hours; T
3-6
, >3 and ≤6 hours; T
6-12
, >6 and ≤12 hours; T
12-24
, >12 and ≤24 hours; and T
24
-, >24 hours. The main outcomes were neurological improvement (decrease in National Institutes of Health Stroke Scale score of ≥4 during hospitalization or 0 at discharge) and good functional outcome (3-month modified Rankin Scale score of 0-1). Associations between onset-to-door time and main outcomes were evaluated after adjusting for potential confounders using logistic regression analysis. Results-Odds ratios (95% confidence intervals) increased significantly with shorter onset-to-door times within 6 hours, for both neurological improvement (T
0-1
, 2.79 [2.28-3.42]; T
1-2
, 2.49 [2.0
2-3
.07]; T
2-3
, 1.52 [1.21-1.92]; T
3-6
, 1.72 [1.44-2.05], with reference to T
24
-) and good functional outcome (T
0-1
, 2.68 [2.05-3.49], T
1-2
2.10 [1.60-2.77], T
2-3
1.53 [1.15-2.03], T
3-6
1.31 [1.05-1.64], with reference to T
24-
), even after adjusting for potential confounding factors including reperfusion treatment and basal National Institutes of Health Stroke Scale. These associations were maintained in 6216 patients without reperfusion treatment and in 4793 patients with minor stroke (National Institutes of Health Stroke Scale ≤4 on hospital arrival). Conclusions-Early hospital arrival within 6 hours after stroke onset is associated with favorable outcomes after ischemic stroke, regardless of reperfusion treatment or stroke severity..
7. Toshiyasu Ogata, ryu matsuo, Fumi Kiyuna, Jun Hata, Tetsuro Ago, Yoshio Tsuboi, Takanari Kitazono, Masahiro Kamouchi, Takao Ishitsuka, Setsuro Ibayashi, Kenji Kusuda, Kenichiro Fujii, Tetsuhiko Nagao, Yasushi Okada, Masahiro Yasaka, Hiroaki Ooboshi, Katsumi Irie, Tsuyoshi Omae, Kazunori Toyoda, Hiroshi Nakane, Hiroshi Sugimori, Shuji Arakawa, Kenji Fukuda, Jiro Kitayama, Shigeru Fujimoto, Shoji Arihiro, Junya Kuroda, Yoshinobu Wakisaka, Yoshihisa Fukushima, Left atrial size and long-term risk of recurrent stroke after acute ischemic stroke in patients with nonvalvular atrial fibrillation, Journal of the American Heart Association, 10.1161/JAHA.117.006402, 6, 8, 2017.08, Background--Among patients with ischemic stroke and atrial fibrillation, which ones are at high risk of recurrent stroke is unclear. This study aimed to determine whether left atrial size was associated with long-term risk of stroke recurrence in patients with nonvalvular atrial fibrillation. Methods and Results--In this multicenter prospective cohort study, nonvalvular atrial fibrillation patients hospitalized for acute ischemic stroke were enrolled and followed up after discharge. Indexed-left atrial diameter was obtained by dividing left atrial diameter by body surface area. Cause-specific and subdistribution hazard ratios of recurrent stroke were estimated by Cox proportional hazards and Fine-Gray models, respectively. Risk prediction was evaluated by integrated discrimination improvement and net reclassification improvement. In total, 1611 patients (77.8±10.2 [mean±SD] years, 44.5% female) were included. During follow-up for 2.40±1.63 (mean±SD) years, 251 patients had recurrent stroke and 514 patients died. An increased indexed-left atrial diameter (per 1 cm/m
2
) was significantly associated with elevated risk of stroke recurrence (hazard ratio 1.60, 95% CI 1.30-1.98). The association was maintained when death was regarded as the competing risk and in 1464 patients who were treated with anticoagulants (hazard ratio 1.59, 95% CI 1.27-2.00). Risk prediction for recurrent stroke was significantly improved by adding indexed-left atrial diameter to the baseline model composed of the factors in the CHADS
2
score or those in the CHA
2
DS
2
-VASc score. Conclusion--These findings suggest that left atrial enlargement is associated with an increased risk of recurrent stroke in nonvalvular atrial fibrillation patients with ischemic stroke..
8. Yoshinobu Wakisaka, ryu matsuo, Jun Hata, Junya Kuroda, Takanari Kitazono, Masahiro Kamouchi, Tetsuro Ago, Adverse influence of pre-stroke dementia on short-term functional outcomes in patients with acute ischemic stroke
The Fukuoka stroke registry, Cerebrovascular Diseases, 10.1159/000453625, 43, 1-2, 82-89, 2017.02, Background: Dementia and stroke are major causes of disability in the elderly. However, the association between pre-stroke dementia and functional outcome after stoke remains unresolved. We aimed to determine this association in patients with acute ischemic stroke. Methods: Among patients registered in the Fukuoka Stroke Registry from June 2007 to May 2015, 4,237 patients with ischemic stroke within 24 h of onset, who were functionally independent before the onset, were enrolled in this study. Pre-stroke dementia was defined as any type of dementia that was present prior to the index stroke. Primary and secondary study outcomes were poor functional outcome (modified Rankin Scale 3-6) at 3 months after the stroke onset and neurological deterioration (≥2-point increases on the National Institutes of Health Stroke Scale score during hospitalization), respectively. For propensity score (PS)-matched cohort study to control confounding variables for pre-stroke dementia, 318 pairs of patients with and without pre-stroke dementia were also selected on the basis of 1:1 matching. Multivariable logistic regression models and conditional logistic regression analysis were used to quantify associations between pre-stroke dementia and study outcomes. Results: Of all 4,237 participants, 347 (8.2%) had pre-stroke dementia. The frequencies of neurological deterioration and poor functional outcome were significantly higher in patients with pre-stroke dementia than in those without pre-stroke dementia (neurological deterioration, 16.1 vs. 7.1%, p < 0.01; poor functional outcome, 63.7 vs. 27.1%, p < 0.01). Multivariable analysis showed that pre-stroke dementia was significantly associated with neurological deterioration (OR 1.67; 95% CI 1.14-2.41; p < 0.01) and poor functional outcome (OR 2.91; 95% CI 2.17-3.91; p < 0.01). In the PS-matched cohort study, the same trends were observed between the pre-stroke dementia and neurological deterioration (OR 2.60; 95% CI 1.17-5.78; p < 0.01) and between the dementia and poor functional outcome (OR 3.62; 95% CI 1.89-6.95; p < 0.01). Conclusions: Pre-stroke dementia was significantly associated with higher risks for poor functional outcome at 3 months after stroke onset as well as for neurological deterioration during hospitalization in patients with acute ischemic stroke..
9. ryu matsuo, Masahiro Kamouchi, Timing of anticoagulant therapy after acute ischemic stroke, Circulation Journal, 10.1253/circj.CJ-16-1287, 81, 2, 151-152, 2017.01.
10. ryu matsuo, Takehiro Michikawa, Kayo Ueda, Tetsuro Ago, Hiroshi Nitta, Takanari Kitazono, Masahiro Kamouchi, Short-Term Exposure to Fine Particulate Matter and Risk of Ischemic Stroke, Stroke, 10.1161/STROKEAHA.116.015303, 47, 12, 3032-3034, 2016.12, Background and Purpose - There is a strong association between ambient concentrations of particulate matter (PM) and cardiovascular disease. However, it remains unclear whether acute exposure to fine PM (PM 2.5) triggers ischemic stroke events and whether the timing of exposure is associated with stroke risk. We, therefore, examined the association between ambient PM 2.5 and occurrence of ischemic stroke. Methods - We analyzed data for 6885 ischemic stroke patients from a multicenter hospital-based stroke registry in Japan who were previously independent and hospitalized within 24 hours of stroke onset. Time of symptom onset was confirmed, and the association between PM (suspended PM and PM 2.5) and occurrence of ischemic stroke was analyzed by time-stratified case-crossover analysis. Results - Ambient PM 2.5 and suspended PM at lag days 0 to 1 were associated with subsequent occurrence of ischemic stroke (ambient temperature-adjusted odds ratio [95% confidence interval] per 10 μg/m 3: suspended PM, 1.02 [1.00-1.05]; PM 2.5, 1.03 [1.00-1.06]). In contrast, ambient suspended PM and PM 2.5 at lag days 2 to 3 or 4 to 6 showed no significant association with stroke occurrence. The association between PM 2.5 at lag days 0 to 1 and ischemic stroke was maintained after adjusting for other air pollutants (nitrogen dioxide, photochemical oxidants, or sulfur dioxide) or influenza epidemics and was evident in the cold season. Conclusions - These findings suggest that short-term exposure to PM 2.5 within 1 day before onset is associated with the subsequent occurrence of ischemic stroke..
11. Hiromi Ishikawa, Yoshinobu Wakisaka, ryu matsuo, Noriko Makihara, Jun Hata, Junya Kuroda, Tetsuro Ago, Jiro Kitayama, Hiroshi Nakane, Masahiro Kamouchi, Takanari Kitazono, Influence of Statin Pretreatment on Initial Neurological Severity and Short-Term Functional Outcome in Acute Ischemic Stroke Patients
The Fukuoka Stroke Registry, Cerebrovascular Diseases, 10.1159/000447718, 42, 5-6, 395-403, 2016.11, Background: Statins have neuroprotective effects against ischemic stroke. However, associations between pre-stroke statin treatment and initial stroke severity and between the treatment and functional outcome remain controversial. This study aimed at determining these associations in ischemic stroke patients. Methods: Among patients registered in the Fukuoka Stroke Registry from June 2007 to October 2014, 3,848 patients with ischemic stroke within 24 h of onset, who had been functionally independent before onset, were enrolled in this study. Ischemic stroke was classified as cardioembolic or non-cardioembolic infarction. Primary and secondary study outcomes were mild neurological symptoms defined as a National Institutes of Health Stroke Scale score of ≤4 on admission and favorable functional outcome defined as a modified Rankin Scale score of ≤2 at discharge, respectively. Multivariable logistic regression models were used to quantify associations between pre-stroke statin treatment and study outcomes. Results: Of all 3,848 participants, 697 (18.1%) were taking statins prior to the stroke. The frequency of mild neurological symptoms was significantly higher in patients with pre-stroke statin treatment (64.1%) than in those without the treatment (58.3%, p < 0.01). Multivariable analysis showed that pre-stroke statin treatment was significantly associated with mild neurological symptoms (OR 1.31; 95% CI 1.04-1.65; p < 0.01). Sensitivity analysis in patients with dyslipidemia (n = 1,998) also showed the same trend between pre-stroke statin treatment and mild neurological symptoms (multivariable-adjusted OR 1.26; 95% CI 0.99-1.62; p = 0.06). In contrast, the frequency of favorable functional outcome was not different between patients with (67.0%) and without (65.3%) the treatment (p = 0.40). Multivariable analysis also showed no significant association between pre-stroke statin treatment and favorable functional outcome (OR 1.21; 95% CI 0.91-1.60; p = 0.19). Continuation of statin treatment, however, was significantly associated with favorable functional outcome among patients with pre-stroke statin treatment (multivariable-adjusted OR 2.17; 95% CI 1.16-4.00; p = 0.02). Conclusions: Pre-stroke statin treatment in ischemic stroke patients was significantly associated with mild neurological symptoms within 24 h of onset. Pre-stroke statin treatment per se did not significantly influence the short-term functional outcome; however, continuation of statin treatment during the acute stage of stroke seems to relate with favorable functional outcome for patients with pre-stroke statin treatment..
12. Asako Nakamura, Junya Kuroda, Tetsuro Ago, Jun Hata, ryu matsuo, Shuji Arakawa, Takahiro Kuwashiro, Masahiro Yasaka, Yasushi Okada, Takanari Kitazono, Masahiro Kamouchi, Causes of ischemic stroke in patients with non-valvular atrial fibrillation, Cerebrovascular Diseases, 10.1159/000445723, 42, 3-4, 196-204, 2016.07, Background: Oral anticoagulants (OACs) reduce the incidence of embolic events associated with non-valvular atrial fibrillation (NVAF); however, ischemic stroke can still occur in such patients. Although there are various causes of ischemic stroke in patients with NVAF, their medication status at onset has scarcely been studied. This retrospective study aimed to determine the underlying causes of ischemic stroke in patients with NVAF in relation to pre-stroke anticoagulation. Methods: Among Japanese patients with acute ischemic stroke enrolled in the Fukuoka Stroke Registry from June 2007 to May 2013, 1,302 patients with NVAF who had been hospitalized within 24 h of onset were included in this study, and their backgrounds, pre-stroke use of OACs and prothrombin time-international normalized ratio (PT-INR) on admission were investigated. Strokes were regarded as being non-cardioembolic (CE) type when causes other than NVAF had been identified. The sub-therapeutic range (TR) for warfarin was defined according to Japanese guidelines for pharmacotherapy of atrial fibrillation. Results: Atrial fibrillation had been diagnosed prior to onset of stroke in 704 of 1,302 patients (54%). However, it had not been detected before or on admission, but identified later during hospitalization in 270 patients (21%). Of the patients who had atrial fibrillation on admission but had not been diagnosed as having it, 108 (8%) had not received any medication before onset of stroke and 220 (17%) had received medications other than OACs. OACs had been administered to 415 (59%) of the patients with known atrial fibrillation. The proportion of pre-stroke CHADS2 or CHA2DS2-VASc scores ≥1 ranged from 93 to 99% depending on whether atrial fibrillation had been diagnosed or anticoagulation therapy administered before stroke onset. The PT-INR was in the sub-TR on admission in 283 of 399 patients (71%) receiving warfarin. Male sex, smoking and previous stroke were more prevalent in patients with values within or over the TR of PT-INR than in those in the sub-TR. Non-CE stroke was more prevalent in patients with values above the lower therapeutic limit of the recommended PT-INR than in those in the sub-TR (p < 0.001). The number of CE strokes was much smaller in patients with high admission PT-INR values; this was not observed for non-CE ischemic strokes (p < 0.001). Conclusions: In the clinical setting, under-diagnosis, underuse and sub-therapeutic doses of OACs are major causes of ischemic stroke in patients with NVAF. However, non-CE ischemic strokes may develop in patients receiving therapeutic doses of warfarin..
13. Ryu matsuo, Tetsuro Ago, Jun Hata, Yoshinobu Wakisaka, Junya Kuroda, Takahiro Kuwashiro, Takanari Kitazono, Masahiro Kamouchi, Plasma C-reactive protein and clinical outcomes after acute ischemic stroke
A prospective observational study, PloS one, 10.1371/journal.pone.0156790, 11, 6, 2016.06, Background and Purpose: Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke. Methods: We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale ≥3 at 3 months), were investigated using a logistic regression analysis. Results: Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65-0.97] for neurological improvement, 1.72 [1.26-2.34] for neurological deterioration, and 2.03 [1.55-2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged <70 years (Pheterogeneity = 0.001). Conclusions: High plasma hsCRP is independently associated with unfavorable clinical outcomes after acute ischemic stroke..
14. Tomoya Shibahara, Tomonaga Matsushita, ryu matsuo, Yoshihisa Fukushima, Kenji Fukuda, Hiroshi Sugimori, Masahiro Kamouchi, Takanari Kitazono, Tetsuro Ago, Anti-Cyclic Citrullinated Peptide Antibody-Positive Meningoencephalitis in the Preclinical Period of Rheumatoid Arthritis, Case Reports in Neurology, 10.1159/000447627, 8, 2, 156-160, 2016.01, Rheumatoid meningoencephalitis (RM) is a rare complication of rheumatoid arthritis (RA). This report describes a 63-year-old man with complaints of high-grade fever, headache, and vomiting for several days before admission. Both his serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor, and contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (MRI) showed abnormal gadolinium enhancement of the meninges and high-intensity lesions in the subarachnoid spaces. The patient was diagnosed with RM despite lack of signs suggesting RA. His symptoms drastically improved with intravenous infusion of high-dose methylprednisolone. Two months later, he developed RA. The findings in this patient suggest that RM could develop prior to the onset of RA. Anti-CCP antibody and MRI findings may be useful for the diagnosis of RM, regardless of RA history..
15. Shinichi Wada, ryu matsuo, Tomonaga Matsushita, Yoshihisa Fukushima, Tetsuro Ago, Takanari Kitazono, Intravascular large B cell lymphoma with cauda equina syndrome
A case report and review of the literature authors, Brain and Nerve, 68, 1, 97-101, 2016.01, A 62-year-old man complained of gait disturbance, bladder and bowel dysfunction and paresthesia of both legs one month before admission. His symptoms were suggestive of cauda equina syndrome. After admission, he developed rapid progressive numbness and weakness of both legs and a disturbance of consciousness. A random skin biopsy was performed and a histological diagnosis of intravascular large B cell lymphoma (IVLBCL) was reached. His symptoms were improved after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy..
16. Noriko Makihara, Koichi Arimura, Tetsuro Ago, Masaki Tachibana, ataru nishimura, Kuniyuki Nakamura, ryu matsuo, Yoshinobu Wakisaka, Junya Kuroda, Hiroshi Sugimori, Masahiro Kamouchi, Takanari Kitazono, Involvement of platelet-derived growth factor receptor β in fibrosis through extracellular matrix protein production after ischemic stroke, Experimental Neurology, 10.1016/j.expneurol.2014.12.007, 264, 127-134, 2015.02, Fibrosis is concomitant with repair processes following injuries in the central nervous system (CNS). Pericytes are considered as an origin of fibrosis-forming cells in the CNS. Here, we examined whether platelet-derived growth factor receptor β (PDGFRβ), a well-known indispensable molecule for migration, proliferation, and survival of pericytes, was involved in the production of extracellular matrix proteins, fibronectin and collagen type I, which is crucial for fibrosis after ischemic stroke. Immunohistochemistry demonstrated induction of PDGFRβ expression in vascular cells of peri-infarct areas at 3-7. days in a mouse stroke model. The PDGFRβ-expressing cells extended from peri-infarct areas toward the ischemic core after day 7 while expressing fibronectin and collagen type I in the infarct areas. In contrast, desmin and α-smooth muscle actin, markers of pericytes, were only expressed in vascular cells. In PDGFRβ heterozygous knockout mice, the expression of fibronectin and collagen type I was attenuated at both mRNA and protein levels with an enlargement of the infarct volume after ischemic stroke compared with that in wild-type littermates. In cultured brain pericytes, the expression of PDGF-B, PDGFRβ, fibronectin, and collagen type I, but not desmin, was significantly increased by serum depletion (SD). The SD-induced upregulation of fibronectin and collagen type I was suppressed by SU11652, an inhibitor of PDGFRβ, while PDGF-B further increased the SD-induced upregulation. In conclusion, the expression level of PDGFRβ may be a crucial determinant of fibrosis after ischemic stroke. Moreover, PDGFRβ signaling participates in the production of fibronectin and collagen type I after ischemic stroke..
17. Fumi Irie, Masahiro Kamouchi, Jun Hata, ryu matsuo, Yoshinobu Wakisaka, Junya Kuroda, Tetsuro Ago, Takanari Kitazono, Takao Ishitsuka, Shigeru Fujimoto, Setsuro Ibayashi, Kenji Kusuda, Shuji Arakawa, Kinya Tamaki, Seizo Sadoshima, Katsumi Irie, Kenichiro Fujii, Yasushi Okada, Masahiro Yasaka, Tetsuhiko Nagao, Hiroaki Ooboshi, Tsuyoshi Omae, Kazunori Toyoda, Hiroshi Nakane, Hiroshi Sugimori, Kenji Fukuda, Yoshihisa Fukushima, Sex differences in short-term outcomes after acute ischemic stroke
The fukuoka stroke registry, Stroke, 10.1161/STROKEAHA.114.006739, 46, 2, 471-476, 2015.02, BACKGROUND AND PURPOSE - : Variable sex differences in clinical outcomes after stroke have been reported worldwide. This study aimed to elucidate whether sex is an independent risk factor of poor functional outcome after acute ischemic stroke. METHODS - : Using the database of patients with acute stroke registered in the Fukuoka Stroke Registry in Japan from 1999 to 2013, 6236 previously independent patients with first-ever ischemic stroke who were admitted within 24 hours of onset were included in this study. Baseline characteristics were assessed on admission. Study outcomes included neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin Scale score, 3-6 at discharge). Logistic regression analyses were performed to evaluate the association between sex and clinical outcomes. RESULTS - : Overall, 2398 patients (38.5%) were women. Severe stroke (National Institutes of Health Stroke Scale score, ≥8) on admission was more prevalent in women than in men. The frequency of neurological improvement or deterioration during hospitalization was not different between the sexes. After adjusting for possible confounders, including age, stroke subtype and severity, risk factors, and poststroke treatments, it was found that female sex was independently associated with poor functional outcome at discharge (odds ratio, 1.30; 95% confidence interval, 1.08-1.57). There was heterogeneity of the association between sex and poor outcome according to age: women had higher risk of poor outcome than men among patients aged ≥70 years, but no clear sex difference was found in patients aged <70 years. CONCLUSIONS - : Female sex was associated with the risk of poor functional outcome at discharge after acute ischemic stroke..
18. Matsuo R, Kamouchi M, Fukuda H, Hata J, Wakisaka Y, Kuroda J, Ago T, Kitazono T, Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator for Ischemic Stroke Patients over 80 Years Old: The Fukuoka Stroke Registry, PLOS ONE, 10.1371/journal.pone.0110444, 9, 10, 2014.10.
19. Matsuo R, Kamouchi M, Ago T, Hata J, Shono Y, Kuroda J, Wakisaka Y, Sugimori H, Kitazono T, Thrombolytic therapy with intravenous recombinant tissue plasminogen activator in Japanese older patients with acute ischemic stroke: Fukuoka Stroke Registry, GERIATRICS & GERONTOLOGY INTERNATIONAL, 10.1111/ggi.12205, 14, 4, 954-959, 2014.10.
20. Matsuo R, Ago T, Hata J, Kuroda J, Wakisaka Y, Sugimori H, Kitazono T, Kamouchi M, Impact of the 1425G/A Polymorphism of PRKCH on the Recurrence of Ischemic Stroke: Fukuoka Stroke Registry, JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, 10.1016/j.jstrokecerebrovasdis.2013.11.011, 23, 6, 1356-1361, 2014.07.
21. Yoshinobu Wakisaka, Tetsuro Ago, Masahiro Kamouchi, Junya Kuroda, ryu matsuo, Jun Hata, Seiji Gotoh, Tetsu Isomura, Hideto Awano, Kazuo Suzuki, Kenji Fukuda, Yasushi Okada, Yutaka Kiyohara, Hiroaki Ooboshi, Takanari Kitazono, Plasma S100A12 is associated with functional outcome after ischemic stroke
Research for Biomarkers in Ischemic Stroke, Journal of the Neurological Sciences, 10.1016/j.jns.2014.02.031, 340, 1-2, 75-79, 2014.05, Background Ischemic stroke is accompanied by an inflammatory response, which exacerbates brain injury and deteriorates functional outcome. S100A12 is expressed abundantly in granulocytes, and has been implicated to play an important role on inflammatory reactions in various disease states. We aimed to determine the association between plasma S100A12 levels and a functional outcome in patients with acute ischemic stroke. Methods We prospectively included 171 patients with acute ischemic stroke within 24 h after onset in this study. Plasma samples were collected for the measurement of S100A12 levels. Poor functional outcome was defined as a modified Rankin Scale of 2-6 at day 90 after stroke onset. Results Of 171 patients, 74 (43.3%) had a poor functional outcome at day 90 after stroke onset. Plasma S100A12 levels on admission were significantly higher in patients with a poor functional outcome (2.1 [1.2-5.1] ng/mL, median [interquartile]) than in those with a favorable outcome (1.1 [0.5-2.0] ng/mL; p < 0.001). Multivariate analysis showed that the highest quartile of plasma S100A12 levels on admission showed a significantly higher risk for a poor functional outcome (odds ratio, 4.01; 95% confidence interval, 1.09-16.10; p = 0.03) than the lowest quartile. Conclusions High plasma S100A12 levels on admission are associated with a poor functional outcome in patients with acute ischemic stroke..
22. Yuka Kanazawa, Noriko Hagiwara, ryu matsuo, Shuji Arakawa, Tetsuro Ago, Takanari Kitazono, A case of intravascular large B-cell lymphoma (IVLBCL) with central nervous system symptoms diagnosed by renal biopsy, Clinical Neurology, 10.5692/clinicalneurol.54.484, 54, 6, 484-488, 2014.01, A 60-year-old man was admitted to our hospital complaining of fever, headache and vertigo. Neurological examination on admission showed mild ataxic gait. Brain magnetic resonance imaging showed linear high intensity in the left parietal lobe on diffusion-weighted imaging (DWI) and laboratory data revealed elevated serum lactate dehydrogenase and soluble interleukin-2 receptor. Although intravascular lymphoma was suspected from these findings, bone marrow and skin biopsies were negative. Two months later, he presented with sensory disturbance of the left upper limb, and new lesions in the right frontal and bilateral parietal lobes were detected on DWI. A systemic evaluation showed multiple low-density lesions in the bilateral kidneys on computed tomography. Based on the results of a renal biopsy, we made a histological diagnosis of intravascular large B-cell lymphoma (IVLBCL). As IVLBCL is quite rare and often has a poor prognosis, a systemic evaluation to determine the proper biopsy site is needed for early diagnosis..
23. Koji Ishitsuka, Masahiro Kamouchi, Jun Hata, Kenji Fukuda, ryu matsuo, Junya Kuroda, Tetsuro Ago, Takahiro Kuwashiro, Hiroshi Sugimori, Hiroshi Nakane, Takanari Kitazono, High blood pressure after acute ischemic stroke is associated with poor clinical outcomes
Fukuoka stroke registry, Hypertension, 10.1161/HYPERTENSIONAHA.113.02189, 63, 1, 54-60, 2014.01, The relationship between the poststroke blood pressure (BP) and functional outcomes in patients with acute ischemic stroke is still controversial. The aim of the present study was to elucidate the impact of the poststroke BP on the clinical outcomes of acute ischemic stroke. Among the patients in the Fukuoka Stroke Registry, 1874 patients with first-ever acute ischemic stroke (within 24 hours of onset) who had been functionally independent before onset were prospectively enrolled in the present study. The poststroke BP levels were defined as the average values during the 48 hours after onset. The study outcomes were a good neurological recovery, neurological deterioration, and a poor functional outcome. The higher poststroke BP levels were significantly associated with a lower probability of a good neurological recovery and elevated risks of neurological deterioration and a poor functional outcome after adjusting for potential confounding factors. The multivariate-adjusted odds ratios (95% confidence interval) in the highest quintile of systolic BP (versus the lowest quintile as a reference) were 0.51 (0.37-0.71) for a good neurological recovery, 1.92 (1.15-3.27) for neurological deterioration, and 2.51 (1.69-3.74) for a poor functional outcome. Similar associations were observed when we applied the poststroke diastolic BP or pulse pressure. No evidence of the J-curve phenomenon was observed for each association. These results suggest that a high poststroke BP was significantly associated with unfavorable clinical outcomes in patients with acute ischemic stroke. There was no evidence of the J-curve phenomenon between the poststroke BP levels and the clinical outcomes..
24. ryu matsuo, Masahiro Kamouchi, Shuji Arakawa, Yoshihiko Furuta, Yuka Kanazawa, Takanari Kitazono, Magnetic resonance imaging in breath-hold divers with cerebral decompression sickness, Case Reports in Neurology, 10.1159/000357169, 6, 1, 23-27, 2014.01, The mechanism of cerebral decompression sickness (DCS) is still unclear. We report 2 cases of breath-hold divers with cerebral DCS in whom magnetic resonance imaging (MRI) demonstrated distinctive characteristics. One case presented right hemiparesthesia, diplopia, and gait disturbance after breath-hold diving into the sea at a depth of 20 m. Brain MRI with fluid-attenuated inversion recovery (FLAIR) sequence revealed multiple hyperintense lesions in the right frontal lobe, bilateral thalamus, pons, and right cerebellar hemisphere. The second case presented visual and gait disturbance after repetitive breath-hold diving into the sea. FLAIR imaging showed hyperintense areas in the bilateral occipito-parietal lobes. In both cases, diffusion-weighted imaging and apparent diffusion coefficient mapping revealed hyperintense areas in the lesions identified by FLAIR. Moreover, follow-up MRI showed attenuation of the FLAIR signal abnormalities. These findings are suggestive of transient hyperpermeability in the microvasculature as a possible cause of cerebral DCS..
25. Junya Kuroda, Tetsuro Ago, ataru nishimura, Kuniyuki Nakamura, ryu matsuo, Yoshinobu Wakisaka, Masahiro Kamouchi, Takanari Kitazono, Nox4 is a major source of superoxide production in human brain pericytes, Journal of Vascular Research, 10.1159/000369930, 51, 6, 429-438, 2014.01, Background: Pericytes are multifunctional cells surrounding capillaries and postcapillary venules. In brain microvasculature, pericytes play a pivotal role under physiological and pathological conditions by producing reactive oxygen species (ROS). The aims of this study were to elucidate the source of ROS and its regulation in human brain pericytes. Methods: The expression of Nox enzymes in the cells was evaluated using RT-PCR and western blot. Superoxide production was determined by superoxide dismutase-inhibitable chemiluminescence. Silencing of Nox4 was performed using RNAi, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results: Nox4 was predominant among the Nox family in human brain pericytes. Membrane fractions of cells produced superoxide in the presence of NAD(P)H. Superoxide production was almost abolished with diphenileneiodonium, a Nox inhibitor; however, inhibitors of other possible superoxide-producing enzymes had no effect on NAD(P)H-dependent superoxide production. Pericytes expressed angiotensin II (Ang II) receptors, and Ang II upregulated Nox4 expression. Hypoxic conditions also increased the Nox4 expression. Silencing of Nox4 significantly reduced ROS production and attenuated cell proliferation. Conclusion: Our study showed that Nox4 is a major superoxide-producing enzyme and that its expression is regulated by Ang II and hypoxic stress in human brain pericytes. In addition, Nox4 may promote cell growth..
26. Takahiro Kuwashiro, Tetsuro Ago, Masahiro Kamouchi, ryu matsuo, Jun Hata, Junya Kuroda, Kenji Fukuda, Hiroshi Sugimori, Masayo Fukuhara, Hideto Awano, Tetsu Isomura, Kazuo Suzuki, Masahiro Yasaka, Yasushi Okada, Yutaka Kiyohara, Takanari Kitazono, Significance of plasma adiponectin for diagnosis, neurological severity and functional outcome in ischemic stroke - Research for Biomarkers in Ischemic Stroke (REBIOS), Metabolism: Clinical and Experimental, 10.1016/j.metabol.2014.04.012, 63, 9, 1093-1103, 2014.01, Objective Although adiponectin is a major adipocytokine that affects the pathogenesis of various cardiovascular diseases, its clinical significance in stroke remains controversial. We investigated the clinical significance of plasma adiponectin for the diagnosis, neurological severity and functional outcomes of patients with ischemic stroke. Methods We prospectively enrolled 171 patients with ischemic stroke and 171 age- and sex-matched healthy controls. Blood samples and clinical information were obtained at day 0, 3, 7, 14 and 90 after stroke onset. Results Average adiponectin values at day 0 did not significantly differ between the controls and the patients, but were significantly lower and higher in patients with atherothrombotic brain (ATBI) (p = 0.047) and cardioembolic (CE) (p = 0.008) infarction, respectively, than in the controls. Multivariate logistic regression analyses showed that the adiponectin value at day 0 could predict ATBI (odds ratio, 0.75; 95% confidence interval, 0.58 to 0.91, p = 0.009, per 1-μg/mL increase). Adiponectin values at day 0 were positively associated with neurological severity as evaluated by the National Institute of Health Stroke Scale upon admission (r = 0.420, p = 0.003) and were higher in the groups with poor outcomes (modified Rankin Scale (mRS) ≥ 3 on day 90) than in those with good ones (mRS ≤ 2) in all stroke subtypes, with statistical significance in ATBI (p = 0.015). Conclusions Plasma adiponectin values may help to classify stroke subtypes and predict neurological severity and functional outcome in ischemic stroke patients..
27. Noriko Makihara, Masahiro Kamouchi, Jun Hata, ryu matsuo, Tetsuro Ago, Junya Kuroda, Takahiro Kuwashiro, Hiroshi Sugimori, Takanari Kitazono, Takao Ishitsuka, Shigeru Fujimoto, Setsuro Ibayashi, Kenji Kusuda, Shuji Arakawa, Katsumi Irie, Kenichiro Fujii, Yoshiyuki Wakugawa, Yasushi Okada, Masahiro Yasaka, Tetsuhiko Nagao, Hiroaki Ooboshi, Tsuyoshi Omae, Kazunori Toyoda, Hiroshi Nakane, Kenji Fukuda, Yoshihisa Fukushima, Kinya Tamaki, Seizo Sadoshima, Statins and the risks of stroke recurrence and death after ischemic stroke
The Fukuoka Stroke Registry, Atherosclerosis, 10.1016/j.atherosclerosis.2013.09.017, 231, 2, 211-215, 2013.12, Background and purpose: The findings of recent clinical trials suggest that treatment with high-dose statins reduces the risk of stroke recurrence. However, the doses approved in Japan are much lower than those in the previous studies. This study aimed to elucidate whether prescribed doses of statins reduce the risks of cerebrovascular events (CVEs: stroke recurrence or transient ischemic attack) and all-cause mortality in a cohort of Japanese patients with first-ever ischemic stroke. Methods: The 2822 eligible patients registered in the Fukuoka Stroke Registry with first-ever acute ischemic stroke from June 2007 to February 2011 were classified into statin users (n=993) and non-users (n=1829) at discharge, and followed up until March 2012. We assessed the cumulative risks of CVE and all-cause mortality by the Kaplan-Meier method, and calculated hazard ratios (HRs) and 95% confidential intervals (CIs) using the Cox proportional hazards model. Results: During the follow-up time (median, 2.0 years), 305 patients had CVEs and 345 died. The cumulative risks of CVE and death after 4 years were significantly lower in statin users than in non-users (13.8% versus 19.5%, P=0.005 for CVE; 11.8% versus 21.7%, P<0.001 for death). After adjusting for multiple confounding factors, statin treatment significantly reduced the risks of CVE (HR, 0.70; 95% CI, 0.53 to 0.92; P=0.011) and all-cause mortality (HR, 0.67; 95% CI, 0.50 to 0.89; P=0.006). Conclusions: Our findings suggest that low-dose statin may reduce the risks of CVE and death in Japanese patients with acute ischemic stroke..
28. Asako Nakamura, Tetsuro Ago, Masahiro Kamouchi, Jun Hata, ryu matsuo, Junya Kuroda, Takahiro Kuwashiro, Hiroshi Sugimori, Takanari Kitazono, Intensity of anticoagulation and clinical outcomes in acute cardioembolic stroke the Fukuoka stroke Registry, Stroke, 10.1161/STROKEAHA.113.002523, 44, 11, 3239-3242, 2013.11, Background and Purpose: The relationship between the intensity of anticoagulation at the onset of acute cardioembolic stroke and clinical outcome after stroke is unclear. Here, we elucidated the relationship between prothrombin time-international normalized ratio (PT-INR) values on admission and clinical outcomes in patients with acute cardioembolic stroke. Methods: A total of 602 patients from the Fukuoka Stroke Registry in Japan who had been treated with warfarin but developed cardioembolic stroke were enrolled. The patients were classified into 3 groups according to their PT-INR values on admission: PT-INR <1.50, 411 patients; PT-INR 1.50 to 1.99, 146 patients; and PT-INR ≥2.00, 45 patients. The associations between PT-INR categories and severe neurological deficits (National Institutes of Health Stroke Scale ≥10) on admission and poor functional outcome (modified Rankin scale 4-6) at discharge were investigated using a logistic regression analysis. Results: Neurological deficits on admission were less severe, and functional outcome at discharge was more favorable as the PT-INR level on admission increased. The multivariate analysis revealed that severe neurological deficits were inversely associated with PT-INR on admission (PT-INR 1.50-1.99: odds ratio, 0.66;95% confidence interval, 0.43-1.00; PT-INR ≥2.00: odds ratio, 0.41;95% confidence interval, 0.20-0.83; compared with a reference group of PT-INR <1.50). Poor functional outcome was less likely in patients with PT-INR ≥2.00 (odds ratio, 0.20;95% confidence interval, 0.06-0.55) after adjustment for confounders. Conclusions: Prestroke PT-INR ≥2.0 is associated with favorable clinical outcomes after acute cardioembolic stroke..
29. Yuka Kanazawa, ryu matsuo, Yoshihisa Fukushima, Kenji Fukuda, Masahiro Kamouchi, Takanari Kitazono, Progression of right internal carotid artery stenosis in ischemic stroke patient with autoimmune polyglandular syndrome
A case report, Clinical Neurology, 10.5692/clinicalneurol.53.531, 53, 7, 531-535, 2013.08, A 40-year-old man who presented with left hemiparesis was admitted to our hospital. He had tachycardia and a fever. He had a 25-year history of insulin therapy for diabetes mellitus. Brain magnetic resonance (MR) images showed fresh infarction in the right hemisphere, and carotid ultrasonography showed stenosis of the right internal carotid artery (ICA). We determined that atherothrombotic brain infarction had likely occurred. After admission, the right ICA became narrow and finally occluded. Computed tomography revealed the presence of a thrombus in the right ICA, and gadoliniumenhanced MRA showed vasculitis of the ICA. In laboratory tests, his thyroid hormones were elevated. He was diagnosed with hyperthyroidism. After treatment, the tachycardia and high fever were improved. Because of a positive antiglutamic acid decarboxylase antibody test result, he was diagnosed with insulin-dependent diabetes mellitus. We found that he had anti-phospholipid antibody syndrome because he was positive for anti-beta-glycoprotein I antibody. These findings suggested that his condition was autoimmune polyglandular syndrome type 3. He received prednisolone and warfarin. After 3 months, his neurological findings were improved; however, occlusion of the ICA remained. Autoimmunity was considered to be the cause of ICA occlusion. Ischemic stroke with autoimmune polyglandular syndrome is very rare and is associated with progressive carotid lesions in juvenile patients. It is necessary to diagnose and treat this condition as soon as possible..
30. Matsuo R, Ago T, Kamouchi M, Kuroda J, Kuwashiro T, Hata J, Sugimori H, Fukuda K, Gotoh S, Makihara N, Fukuhara M, Awano H, Isomura T, Suzuki K, Yasaka M, Okada Y, Kiyohara Y, Kitazono T, Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study, BMC NEUROLOGY, 10.1186/1471-2377-13-32, 13, 2013.04.
31. ryu matsuo, Shuji Arakawa, Yoshihiko Furuta, Yuka Kanazawa, Masahiro Kamouchi, Takanari Kitazono, Neurological decompression illness in a Japanese breath-hold diver
A case report, Clinical Neurology, 10.5692/clinicalneurol.52.757, 52, 10, 757-761, 2012.10, We report a Japanese breath-hold diver (Ama) who presented neurological disorders after diving. He repeated diving into 25-30 meters depth in the sea for 6 hours. After diving, he felt dizziness and unsteady gait. Neurological examination showed left quadrant hemianopia, bilateral limb ataxia and ataxic gait. Head CT revealed gas bubbles in the left parietal lobe. In CT scan on 3 days after onset, gas bubbles disappeared and low density areas were observed in the bilateral parietal lobes. Brain imaging (DWI, T2WI and FLAIR) demonstrated high intensity in the parietooccipital lobes. Neither pulmonary barotrauma nor intracardiac shunt was detected. He was diagnosed as having neurological decompression illness and therefore underwent hyperbaric oxygen therapy. The pathogenesis of this case was considered to be microbubbles induced by decompression. The present case suggests that repetitive rapid surfacing from the deep sea causes neurological decompression illness even in the breath-hold diver..
32. Kuniyuki Nakamura, Masahiro Kamouchi, Takanari Kitazono, Junya Kuroda, ryu matsuo, Noriko Hagiwara, Eiichi Ishikawa, Hiroaki Ooboshi, Setsuro Ibayashi, Mitsuo Iida, Role of NHE1 in calcium signaling and cell proliferation in human CNS pericytes, American Journal of Physiology - Heart and Circulatory Physiology, 10.1152/ajpheart.01203.2007, 294, 4, 2008.04, The central nervous system (CNS) pericytes play an important role in brain microcirculation. Na+/H+ exchanger isoform 1 (NHE1) has been suggested to regulate the proliferation of nonvascular cells through the regulation of intracellular pH, Na+, and cell volume; however, the relationship between NHE1 and intracellular Ca2+, an essential signal of cell growth, is still not known. The aim of the present study was to elucidate the role of NHE1 in Ca2+ signaling and the proliferation of human CNS pericytes. The intracellular Ca2+ concentration was measured by fura 2 in cultured human CNS pericytes. The cells showed spontaneous Ca2+ oscillation under quasi-physiological ionic conditions. A decrease in extracellular pH or Na+ evoked a transient Ca 2+ rise followed by Ca2+ oscillation, whereas an increase in pH or Na+ did not induce the Ca2+ responses. The Ca2+ oscillation was inhibited by an inhibitor of NHE in a dose-dependent manner and by knockdown of NHE1 by using RNA interference. The Ca2+ oscillation was completely abolished by thapsigargin. The proliferation of pericytes was attenuated by inhibition of NHE1. These results demonstrate that NHE1 regulates Ca2+ signaling via the modulation of Ca2+ release from the endoplasmic reticulum, thus contributing to the regulation of proliferation in CNS pericytes..
33. Kuniyuki Nakamura, Masahiro Kamouchi, Takanari Kitazono, Junya Kuroda, ryu matsuo, Noriko Hagiwara, Hiroaki Ooboshi, Setsuro Ibayashi, Mitsuo Iida, Role of NHE1 in calcium oscillation and cell proliferation in human CNS pericytes, Journal of Cerebral Blood Flow and Metabolism, 27, SUPPL. 1, 2007.11, Background and aims: Central nervous system (CNS) pericytes located at the abluminal side of microvessels, such as arterioles, venules, and particularly capillaries, appear to play an important role in angiogenesis, regulation of blood flow, immune responses, and maintenance of blood-brain barrier (BBB). Na+/H+ exchanger isoform 1 (NHE1) ubiquitously expressed in plasma membrane has been implicated to have a role in proliferation of non-vascular cells through regulation of intracellular pH, Na+ and cell volume; however, the relationship between NHE1 and pericyte growth is not known. Thus, the aim of the present study was to elucidate the role of NHE1 in the proliferation of human CNS pericytes. We have found on intracellular Ca2+ change, an essential signal of cell growth. Methods: Human brain microvascular pericytes were cultured and cytosolic Ca2+ concentration and pH were measured by fluorescent indicators, fura-2 and 2', 7'-bis-2-carboxyethyl-5-(6)-carboxyfluorescein (BCECF), respectively. Reverse transcription and polymerase chain reaction (RT-PCR) was used to examine expression level of each mRNA. Knockdown of NHE1 mRNA was done by RNA interference (RNAi) with the double-strand siRNAs targeting NHE1 specifically. Cell proliferation was evaluated by cell count. Results: Human microvascular pericytes showed spontaneous Ca2+ oscillation in the presence of extracellular Na+ (132mM). A decrease in extracellular Na+ (0-99mM) evoked transient Ca2+ rise followed by Ca2+ plateau or Ca2+ oscillation, whereas increase in extracellular Na+ to 166mM eliminated the Ca2+ responses. A decrease in extracellular pH to 6.5 induced similar cytosolic Ca2+ change as that by low extracellular Na+. Low Na+-induced Ca2+ oscillation was inhibited by hexamethylene amiloride (HMA, an inhibitor of Na+/H+ exchanger) dosedependently (5-50μM). The Ca2+ oscillation was also inhibited by amiloride (50μM) or benzamil (50μM). Nicardipine (1μM), Gd3+ (100μM), La3+ (100μM) or omission of external Ca2+ did not affect the Ca2+ oscillation. KB-R7943 (10μM; a selective inhibitor of Na+/Ca2+ exchanger), carbonyl cyanide p-trifluoro-methoxyphenylhydrazone (1μM; FCCP, the mitochondrial uncoupler), or changes in the external osmolarity did not affect the Ca2+ oscillation. On the other side, the Ca2+ oscillation was completely abolished by pretreatment with thapsigargin (1μM; an inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase), suggesting that Ca2+ oscillation was originated from endoplasmic reticulum. RT-PCR revealed that human CNS pericytes expressed NHE1 and NHE7. Low extracellular Na+ could not induce the Ca2+ oscillation in the cells transfected with specific siRNA targeting NHE1. Proliferation of the pericytes was significantly attenuated by addition of HMA (5μM) to the medium. Knockdown of NHE1 by transfecting mRNA also inhibited the proliferation of pericytes. Conclusions: These results indicate that NHE1 plays an important role in Ca2+ signaling via modulation of endoplasmic reticulum and thereby contributes to the regulation of proliferation in CNS pericytes. This novel role of NHE1 in the pericytes may have pathophysiological relevance to angiogenesis or BBB disruption in the cerebral ischemia..
34. Masahiro Kamouchi, Yoko Wakugawa, Yasushi Okada, Kazuhiro Kishikawa, ryu matsuo, Kazunori Toyoda, Kotaro Yasumori, Tooru Inoue, Setsuro Ibayashi, Mitsuo Iida, Venous infarction secondary to septic cavernous sinus thrombosis, Internal Medicine, 10.2169/internalmedicine.45.1430, 45, 1, 25-27, 2006.02, A 65-year-old woman with poorly controlled diabetes presented bilateral miosis, bilateral abducens nerve palsy, and left hemiparesis. On MRI, cavernous sinus thrombosis, subdural empyema and hemorrhagic infarction in the frontotemporal lobe were detected. Cerebral angiogram revealed filling defect in the cavernous sinus with venous congestion but no involvement of internal carotid artery. Postmortem examination demonstrated hemorrhagic infarction in the right frontotemporal lobe as well as hemorrhagic necrosis of the pituitary gland. It should be noted that venous congestion due to cavernous sinus thrombosis may cause these complications..
35. ryu matsuo, Hiroyuki Kubota, Tohru Obata, Keiji Kito, Kazuhisa Ota, Takanari Kitazono, Setsuro Ibayashi, Takuma Sasaki, Mitsuo Iida, Takashi Ito, The yeast eIF4E-associated protein Eap1p attenuates GCN4 translation upon TOR-inactivation, FEBS Letters, 10.1016/j.febslet.2005.03.043, 579, 11, 2433-2438, 2005.04, Amino acid-starved yeast activates the eIF2α kinase Gcn2p to suppress general translation and to selectively derepress the transcription factor Gcn4p, which induces various biosynthetic genes to elicit general amino acid control (GAAC). Well-fed yeast activates the target of rapamycin (TOR) to stimulate translation via the eIF4F complex. A crosstalk was demonstrated between the pathways for GAAC and TOR signaling: the TOR-specific inhibitor rapamycin activates Gcn2p. Here we demonstrate that, upon TOR-inactivation, the putative TOR-regulated eIF4E-associated protein Eap1p likely functions downstream of Gcn2p to attenuate GCN4 translation via a mechanism independent of eIF4E-binding, thereby constituting another interface between the two pathways..
36. Masahiro Kamouchi, Kazuhiro Kishikawa, ryu matsuo, Kotaro Yasumori, Tooru Inoue, Yasushi Okada, Setsuro Ibayashi, Ultrasonographic detection of extracranial vertebral artery compression in bow hunter's brain ischemia caused by neck rotation, Cerebrovascular Diseases, 10.1159/000071134, 16, 3, 303-305, 2003.08.
37. Shigeri Fujimoto, Tooru Inoue, Masahiro Kamouchi, ryu matsuo, Tsuyoshi Imamura, Takao Yonekura, Ken Uda, Tsutomu Hitotsumatsu, Kazunori Toyoda, Kotaro Yasumori, Yasushi Okada, Detection of intracranial aneurysm using transcranial color-coded duplex sonography with echo contrast agent, Japanese Journal of Neurosurgery, 10.7887/jcns.12.179, 12, 3, 179-184, 2003.03, Purpose: It has been suggested that intracranial aneurysms could be observed using transcranial color-coded duplex sonography (TCDS). We investigated the sensitivity of TCDS studies for detecting unruptured aneurysms both with and without an echo contrast agent. Methods: We studied 39 patients (44 aneurysms) who were diagnosed as having unruptured intracranial aneurysms by cerebral angiography (36 patients) or MRA (3 patients). We performed TCDS both with and without echo contrast agents in all patients. In 7 patients who underwent endovascular treatment for unruptured intracranial aneurysms, enhanced TCDS studies were done both before and after the treatment. Results: Because of an insufficient transtemporal bone window, intracranial cerebral arteries were not visible with TCDS in 3 patients, despite enhancement by echo contrast agents. Among the 36 patients (38 aneurysms) whose intracranial cerebral arteries could be evaluated by TCDS, 13 cerebral aneurysms were detected (34%) without the aid at echo contrast agents. After echo contrast agents were administered, 9 additional aneurysms were observed by TCDS studies and the sensitivity of the test resulted in 58%. The sensitivity of enhanced TCDS for detecting cerebral aneurysms in the internal carotid artery, middle cerebral artery, anterior cerebral artery or anterior communicating artery, and basilar artery was 46%, 80%, 17%, and 67%, respectively. The frequency of larger aneurysms detection (>5 mm) was significantly higher (78%) than that of smaller ones (<5 mm; 40%). In all the patients who underwent endovascular treatment, cerebral aneurysms that had been observed by enhanced TCDS were not detected after the treatment. Conclusions: TCDS may be suitable for the detection as well as follow-up study of intracranial aneurysms. The sensitivity of this noninvasive study is drastically improved by contrast agents..
38. ryu matsuo, Masahiro Kamouchi, Tooru Inoue, Yasushi Okada, Setsuro Ibayashi, Cerebral infarction due to carotid occlusion caused by cervical vagal neurilemmoma, Stroke, 10.1161/01.STR.0000015241.40071.99, 33, 5, 1428-1431, 2002.05, Background - We report a case of a 71-year-old woman with cerebral infarction due to occlusion of the internal carotid artery (ICA) caused by a neck tumor. Case Description - In 1998, the patient complained of mild hoarseness, and a diagnostic workup showed a cervical mass that was considered a benign neck tumor. In September 2000, she developed right-sided weakness. Diffusion-weighted MRI showed a high-intensity area in the territory of the left middle cerebral artery. Carotid angiography and ultrasonography revealed occlusion of the left ICA, which was due to compression by the neck tumor. Superficial temporal artery-middle cerebral artery anastomosis was performed to prevent critical reduction of cerebral blood flow in the left ICA territory; this was followed by tumor resection. The occluded ICA recanalized after tumor resection. Microscopic examination showed that the tumor was a vagal neurilemmoma. Conclusions - This is the first case of cerebral infarction due to left ICA occlusion by a cervical neurilemmoma. Even when the neck tumor is benign, it may occlude the ICA and thereby cause cerebral infarction..
39. ryu matsuo, Hisanobu Ogata, H. Tsuji, Takanari Kitazono, M. Shimada, K. Taguchi, M. Fujishima, Spontaneous regression of hepatocellular carcinoma - A case report, Hepato-Gastroenterology, 48, 42, 1740-1742, 2001.12, We report a 72-year-old man with hepatocellular carcinoma, which showed spontaneous regression. He was diagnosed as having chronic hepatitis type C five years before admission. In January 1998, a liver mass was found by ultrasonography. In February, computed tomography showed a low-density mass, 3.5cm in diameter in the S5 region. Although liver biopsy was not performed, findings obtained by computed tomography and ultrasonography indicated that the tumor was hepatocellular carcinoma. The levels of α-fetoprotein and PIVKA (protein induced by vitamin K antagonist)-II were increased to 1000ng/mL and 2000mAU/mL, respectively. The patient was admitted to our hospital in March 1998. At the time, the size of liver mass was reduced to 2.5cm in diameter on computed tomography, and the tumor markers, α-fetoprotein and PIVKA-II, spontaneously decreased to the normal range. We considered that hepatocellular carcinoma of this patient regressed spontaneously. Because it was hard to exclude the possibility that the mass contained residual malignant cells, we resected the mass on April 28, 1998. Microscopically, the resected mass did not contain any malignant cells. The parenchyma surrounding tumor necrosis, which is reflected by severe inflammatory infiltration with lymphocytes, indicates spontaneous regression. Although the precise mechanism regarding spontaneous regression of hepatocellular carcinoma is not fully understood, either ischemia due to rapid growth of the tumor or some inflammatory mechanism may be involved in regression of hepatocellular carcinoma..
40. ryu matsuo, Yuko Ohta, Yusuke Ohya, Takanari Kitazono, Hiroyuki Irie, Tatsuru Shikata, Isao Abe, Masatoshi Fujishima, Isolated dissection of the celiac artery
A case report, Angiology, 10.1177/000331970005100710, 51, 7, 603-607, 2000.01, Isolated arterial dissection, which occurs with the absence of aortic dissection, has been reported in carotid and renal arteries but rarely in visceral arteries. A case of isolated celiac artery dissection is reported here. A healthy 58-year-old man experienced sudden upper abdominal pain, which continued for several days. A body computed tomogram (CT) showed a multiple low-density wedge-shaped area in the spleen, which was diagnosed as splenic infarction, and an aneurysm with thrombus in the celiac artery. A selective angiogram showed dilatation of the celiac artery with wall irregularity, and proximal occlusion of the hepatic artery. The distal hepatic artery was fed by collateral arteries from the superior mesenteric artery. Splenic infarction was probably due to the embolism from the thrombus in the dissected celiac artery. The absence of other vascular lesions and causes or risks for the arterial dissection would suggest the occurrence of spontaneous dissection. The dissection of visceral arteries should be considered in diagnosing acute abdominal pain..