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Takamasa Kayama

Publications and source records attributed to Takamasa Kayama.

At least 19 recordsLinked to original sources
PubMed2006

The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease.

Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of alpha-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with alpha-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. Genetic association study revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of alpha-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.

Aged↗
PubMed2006

Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70.

BACKGROUND AND PURPOSE: Caspase-8 and caspase-9 are essential proteases of the extrinsic and intrinsic apoptotic pathways, respectively. We investigated whether neuroprotection associated with overexpression of heat-shock protein 70 (Hsp70), a natural cellular antiapoptotic protein, is mediated by caspase-8 and caspase-9 signaling in the neonatal mouse brain after hypoxia/ischemia (H/I) injury. METHODS: Postnatal day 7 transgenic mice overexpressing rat Hsp70 (Hsp70 Tg) and their wild-type (Wt) littermates underwent unilateral common carotid artery ligation followed by 30 minutes of exposure to 8% O2. The expression of apoptotic proteins was quantified by Western blot analysis, and the specific interaction between Hsp70 and apoptotic protease activating factor 1 (Apaf-1) was determined by coimmunoprecipitation. RESULTS: Hsp70 overexpression reduced cytosolic translocation of cytochrome c without affecting the levels of Apaf-1 and pro-caspase-9 24 hours after H/I. The expression of these apoptotic proteins in the naïve neonatal brains was also not affected by Hsp70 overexpression. Reduced caspase-9 cleavage occurred in Hsp70 Tg mice compared with Wt littermates 24 hours after H/I and correlated with increased binding of Hsp70 and Apaf-1. Increased cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) expression and decreased caspase-8 cleavage were also observed in Hsp70 Tg compared with Wt mice 24 hours after H/I. CONCLUSIONS: Our results suggest that the extrinsic and intrinsic apoptotic pathways mediate the neuroprotective effects of Hsp70 overexpression in neonatal H/I, specifically by upregulating FLIP and sequestering Apaf-1, leading to reduced cleavage of caspase-8 and caspase-9.

Animals↗
PubMed2006

Cardiovascular risk factors and retinal microvascular signs in an adult Japanese population: the Funagata Study.

OBJECTIVE: To describe the prevalence of retinal vascular signs and their association with cardiovascular risk factors in a Japanese population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Adult persons aged 35 years or older from Funagata, Yamagata Prefecture, Japan (n = 1481). METHODS: The Funagata Study is a Japanese population-based study of persons aged 35 years or older, and included 1961 nondiabetic participants (53.3% of 3676 eligible subjects). A nonmydriatic retinal photograph was taken of 1 eye to assess retinal microvascular signs. Retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex) and retinopathy were assessed in 1481 participants without diabetes (40.3% of eligible persons) using a standardized protocol. Using a computer-assisted method, retinal vessel diameters were measured in 921 participants with gradable retinal image (25.1% of eligible persons). MAIN OUTCOME MEASURES: Prevalence of retinal microvascular signs and their association with cardiovascular risk factors. RESULTS: Moderate or severe focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex, and retinopathy were found in 8.3%, 15.2%, 18.7%, and 9.0%, respectively, of the study population. Mean (+/-standard error) values for retinal arteriolar diameter were 178.6+/-21.0 mum, and mean values (+/-standard error) for venular diameter were 214.9+/-20.6 mum. Older persons were more likely to have retinal arteriolar wall signs, retinopathy, and narrower retinal vessel diameters. After adjusting for multiple factors, each 10-mmHg increase in mean arterial blood pressure was associated with a 20% to 40% increased likelihood of retinal arteriolar signs and a 2.8-mum reduction in arteriolar diameter. Retinopathy was associated with higher body mass index and both impaired glucose tolerance and impaired fasting glucose. CONCLUSIONS: In nondiabetic Japanese adults, retinal arteriolar wall signs were associated with older age and increased blood pressure, whereas retinopathy was associated with older age, higher body mass index, impaired glucose tolerance, and impaired fasting glucose. These findings are comparable with data from white populations.

Adult↗
PubMed2006

Diacylglycerol kinase zeta is involved in the process of cerebral infarction.

Diacylglycerol kinase (DGK) is an enzyme that phosphorylates a second messenger diacylglycerol (DG) and is involved in a variety of pathophysiological cellular responses. We have previously reported that DGKzeta may be involved in the selective vulnerability of hippocampal CA1 neurons in transient forebrain ischemia. In this study we aimed to further elucidate functional implications of DGK isozymes in the cerebral cortex suffering from infarction using a focal ischemic model. In the early phase of 90 min of middle cerebral artery occlusion, DGKzeta-immunoreactivity is reduced rapidly in the nucleus of cortical neurons in the ischemic core, while DGKiota and other neuronal proteins such as MAP-2 and NeuN remain intact. This suggests that rapid disappearance of DGKzeta in ischemic neurons is a quite early event precedent to neuronal degeneration in response to ischemia. Furthermore, in the late inflammatory phase of infarction DGKzeta-immunoreactivity is detected in non-neuronal cells including factor VIII-positive endothelial cells and ED-1-positive phagocytic cells. The present study suggests that DGKzeta may play roles in various processes of ischemic brain damage including neuronal death and non-neuronal inflammatory response.

Animals↗
PubMed2006

Higher levels of serum fibrin-monomer reflect hypercoagulable state and thrombus formation in the left atrial appendage in patients with acute ischemic stroke.

BACKGROUND: It is sometimes difficult to make a diagnosis of cardioembolic stroke in the stroke care unit, because of the splashing and vanishing of the intracardiac source of the emboli on transesophageal echocardiography. Serum fibrin-monomer (FM) is a new marker for coagulation activity that is useful for identifying older individuals at increased risk of ischemic stroke. METHODS AND RESULTS: Two hundred and four patients with acute ischemic stroke were examined for serum coagulation and fibrinolytic activity on admission, and underwent transesophageal echocardiography within 7 days of onset. Serum levels of FM was significantly higher in patients with left atrial appendage (LAA) thrombus formation (n=24) than in those with no thrombus (88+/-52 vs 14+/-9 microg/ml, p<0.0001). On multivariate logistic regression analysis, FM was an independent predictor for LAA thrombus (RR 2.975, 95% confidence interval 1.114 to 4.820, p=0.0214). In patients with LAA thrombus negative group, cases with LAA emptying flow velocity at atrial systole that was absent or smaller than at early diastole had significantly higher FM levels as compared to cases with larger velocity (42+/-12 vs 8+/-5 microg/ml, p<0.0001). CONCLUSION: Higher levels of serum FM reflect LAA flow pattern alterations and thrombus formation in patients with acute ischemic stroke.

Aged↗
PubMed2006

Correlation between copper/zinc superoxide dismutase and the proliferation of neural stem cells in aging and following focal cerebral ischemia.

OBJECT: Neural stem cells (NSCs) have been demonstrated in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus (DG). Although aging rats manifest a decrease in NSCs, rats exposed to stress (for example, ischemia, epilepsy, radiation, and trauma) show an increase in these cells. In transgenic mice, the overexpression of human copper/zinc superoxide dismutase (SOD1), an endogenous antioxidant, has been reported to be a protective enzyme against transient focal cerebral ischemia. The authors investigated the correlation between SOD1 and the proliferation of NSCs in aging as chronic oxidative stress (Experiment 1) and acute oxidative stress induced by transient focal cerebral ischemia (Experiment 2) in mice. METHODS: Bromodeoxyuridine (BrdU) was used in the evaluation of NSCs. In Experiment 1, NSCs in the SVZ significantly increased in 16-month-old transgenic mice compared with wild-type mice (p = 0.0001). In Experiment 2, mice were subjected to 30-minute occlusions of the middle cerebral artery. The increase in NSCs in the DG in transgenic mice was significantly greater than that in wild-type mice (p < 0.05). CONCLUSIONS: Results in this study suggest that chronic and acute oxidative stress may inhibit the proliferation of NSCs and that SOD1 may play a key role in NSC proliferation.

Aging↗
PubMed2006

[Choroid plexus tumors: report of 7 cases in a single institution].

The management of seven patients with choroid plexus tumors, 4 adults and 3 children (mean age 17.5 years) at our institution was reviewed. There were 4 cases of papilloma and 3 of carcinoma located in the lateral ventricle in 1 case, the third ventricle in 1 case, and the fourth ventricle in 5 cases. Total surgical excision was attempted in all patients. Total resection was achieved in three patients, resulting in no deficit in two and persistence of preoperative dysphagia in one. There was no recurrence after total resection. Subtotal resection was achieved in four patients, one of whom underwent second surgery resulting in total resection, and one patient died of respiratory disturbance after the third operation because of regrowth of the tumor. Complete excision could not be achieved in 3 of the 5 tumors located in the fourth ventricle because of extension to the brainstem. The median survival was 59.5 months for patients with papilloma, and 67.7 months for those with carcinoma. Adjuvant therapy was also required for carcinoma, one patient was treated by radiotherapy, and two by radiotherapy plus chemotherapy. Only one patient with papilloma was treated by radiotherapy plus chemotherapy postoperatively.

Adult↗
PubMed2006

[Trends in the incidence of stroke in Yamagata, Japan].

The purpose of this study was to clarify the incidence and features of acute cerebrovascular diseases in Yamagata Prefecture, by comparing with those in other prefectures reported in previous studies. Consecutive 13,639 cases of acute stroke were prospectively registered to Yamagata Society in Treatment for Cerebral Stroke (YSTCS) between January 1, 1998 and December 31, 2002. Cerebral infarction (CI), intracerebral hemorrhage (CH), subarachnoid hemorrhage (SAH) and transient ischemic attack (TIA) were observed in 58.4%, 25.8%, 11.4% and 4.4% of the patients, respectively. The frequencies of CH and SAH (37.2%) in Yamagata Prefecture were higher than those reported in other studies (p < 0.01). In addition, time from onset to admission in Yamagata Prefecture was longer than that reported in others(p< 0.01). This study was one of the largest stroke registration studies in Japan enrolling 13,639 patients. In addition, computed tomography (CT) and/or magnetic resonance image (MRI) was performed on admission in all patients. Diagnosis was made by a neurologist or a neurosurgeon based on CT and/or MRI findings. Our results might accurately reflect current status of stroke patients in Yamagata Prefecture.

Adult↗
PubMed2006

[Aneurysms of the anterior communicating artery and subclavian artery in association with congenital absence of unilateral internal carotid artery].

We encountered a rare case of unilateral internal carotid arterial defect complicated with anterior communicating aneurysm and subclavian artery aneurysm. The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA revealed defects in the right internal carotid artery and the right carotid canal, and an unruptured aneurysm in the anterior communicating artery. In addition, the patient was also found to have an unruptured aneurysm in the right subclavian artery. As both the aneurysms were considered to have a high risk of rupture and such subclavian aneurysms were likely to cause an embolism, radical surgery was performed for each aneurysm. The postoperative course was uneventful, and the patient was discharged without ambulatory limitations. Although the defect in the internal carotid artery is a relatively rare vascular deformity, the incidence of cerebral aneurysm is about 30% in such cases due to the marked hemodynamic stress involved. On the other hand, there have been only two previous case reports of internal carotid arterial defect complicated with a subclavian aneurysm. Moreover, there have been no previous reports of internal carotid arterial defect complicated with both an intracranial aneurysm and a subclavian aneurysm, as observed in the present case. Thus, this case was very rare and is reported here.

Aneurysm↗
PubMed2006

[Sacrococcygeal dermal sinus presented bacterial meningitis: a case report].

A rare case of sacrococcygeal dermal sinus suffering from relapsing meningitis is presented. In addition, deference of clinical figure and pathology between sacrococcygeal region and other regions are discussed. A 10 -month-old boy was suffering from relapsing meningitis. Spinal MRI was performed to find occult spinal dysraphism because he had a pit on his hip. The MRI revealed sacrococcygeal dermal sinus. He received surgical resection of dermal sinus based on this findings. Interestingly, different from other dermal sinuses, the dermal sinus runs to caudal direction, and was fused filum terminale with dermoid cyst. This interesting pathological feature of sacrococcygeal dermal sinus seems to come from developmental difference between sacrococcygeal dermal sinus and the other dermal sinuses. Only sacrococcygeal dermal sinus is related with caudal cell mass on its pathogenesis. Because filum terminale is also developed from caudal cell mass, sacrococcygeal dermal sinus seems to be related with filum terminale. Most important differential diagnosis is coccygeal pit that is found in 1 -4% of newborn baby. The clinical feature and pathology got from our case must be very helpful to distinguish sacrococcygeal dermal sinus from coccygeal pit.

Diagnosis, Differential↗
PubMed2006

Ratio of peak early to late diastolic filling velocity of the left ventricular inflow is associated with left atrial appendage thrombus formation in elderly patients with acute ischemic stroke and sinus rhythm.

OBJECTIVES: To investigate the useful parameters of transthoracic echocardiography (TTE) for the diagnosis of stroke subtypes in patients with acute cerebral infarction. METHODS: One hundred and one acute ischemic stroke patients met all of the following criteria; > or = 50 years of age, normal sinus rhythm on admission, and transesophageal echocardiography (TEE) within 7 days from the onset. The clinical significance of the TTE parameters on admission was examined for identifying intracardiac thrombus formation as follows: left atrial dimension, left ventricular end-diastolic dimension, percentage fractional shortening, left ventricular mass index, ratio of the transmitral inflow velocities (E/A), and deceleration time of the E wave. RESULTS: There were 28 patients with E/A > or = 1.0(70 +/- 12 years old) and 73 with E/A < 1.0 (73 +/- 10 years old). No patient showed pulmonary congestion on chest radiography. There were no significant differences in age, TTE parameters, and plasma levels of brain natriuretic peptide between the two groups. Patients with E/A > or = 1.0 had higher incidence of left atrial appendage thrombus formation and/or spontaneous echographic contrast than those with < 1.0 (25% vs 5%, p = 0.0058). There was a significant relationship between E/A and emptying flow velocity of the left atrial appendage (r = -0.569, p < 0.0001). Multivariate logistic regression analysis showed E/A was an independent predictor for left atrial appendage thrombus (risk ratio 1.531 per 0.1 increase, 95% confidence interval 1.129-2.076, p = 0.0002). CONCLUSIONS: Increased level of E/A on admission was associated with the occurrence of left atrial appendage thrombus formation in patients with acute ischemic stroke.

Aged↗
PubMed2005

Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemia.

Enriched environment (EE) has been shown to increase neurogenesis in the adult brain. The aim of this study is to determine the effect of EE and spatial learning on neurogenesis following ischemic stroke. Male adult SD rats were subjected to sham surgery or distal middle cerebral artery occlusion (MCAO). MCAO induced a transient increase followed by a sustained depression of progenitor cell proliferation and neuroblast production below baseline level in both ipsilateral and contralateral DG compared to sham. Increased neuronal differentiation and neurogenesis in the DG were observed in both sham and MCAO rats following 8 weeks in the EE combined with spatial learning, compared to rats housed in the standard environment. EE/Learning also restored the total number of neuroblasts in the DG after MCAO compared to sham. Furthermore, EE/learning enhanced the density of NeuN positive cells in the ischemic penumbra, though no new neurons were detected in this region.

Animals↗
PubMed2005

Sequential changes of nitric oxide levels in the temporal lobes of kainic acid-treated mice following application of nitric oxide synthase inhibitors and phenobarbital.

Although studies have indicated a close relationship between nitric oxide (NO) and kainic acid (KA)-induced seizures, the role of NO in seizures is not fully understood. Here, we quantified NO levels in the brain of KA-treated mice using EPR spectrometry to elucidate the role of NO in KA-induced seizures. KA was administered to mice with or without pretreatment with one of the following: N(G)-nitro-l-arginine methyl ester (l-NAME), an NO synthase (NOS) inhibitor that acts on both endothelial NOS (eNOS) and neuronal NOS (nNOS); 7-nitroindazole (7-NI), which acts more selectively on nNOS in vivo; or the anti-epileptic drug, phenobarbital. To accurately assess NO production during seizure activity, we directly measured KA-induced NO levels in the temporal lobe using an electron paramagnetic resonance NO trapping technique. Our results revealed that the both dose- and time-dependent changes of NO levels in the temporal lobe of KA-treated mice were closely related to the development of seizure activity. l-NAME mediated suppression of the KA-induced NO generation led to enhanced severity of KA-induced seizures. In contrast, 7-NI induced only about 50% suppression and had little effect on seizure severity; while phenobarbital markedly reduced both NO production and seizure severity. These results show that KA-induced neuroexcitation leads to profound increases in NO release to the temporal lobe of KA-treated mice and that NO generation from eNOS exerts an anti-convulsant effect.

Animals↗
PubMed2005

Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury.

Apoptosis is implicated in neonatal hypoxic/ischemic (H/I) brain injury among various forms of cell death. Here we investigate whether overexpression of heat shock protein (Hsp) 70, an antiapoptotic protein, protects the neonatal brain from H/I injury and the pathways involved in the protection. Postnatal day 7 (P7) transgenic mice overexpressing rat Hsp70 (Tg) and their wild-type littermates (Wt) underwent unilateral common carotid artery ligation followed by 30 mins exposure to 8% O(2). Significant neuroprotection was observed in Tg versus Wt mice on both P12 and P21, correlating with a high level of constitutive but not inducible Hsp70 in the Tg. More prominent injury was observed in Wt and Tg mice on P21, suggesting its continuous evolution after P12. Western blot analysis showed that translocation of cytochrome c, but not the second mitochondria-derived activator of caspase (Smac)/DIABLO and apoptosis-inducing factor (AIF), from mitochondria into cytosol was significantly reduced in Tg 24 h after H/I compared with Wt mice. Coimmunoprecipitation detected more Hsp70 bound to AIF in Tg than Wt mice 24 h after H/I, inversely correlating with the amount of nuclear, but not cytosolic, AIF translocation. Our results suggest that interaction between Hsp70 and AIF might have reduced downstream events leading to cell death, including the reduction of nuclear AIF translocation in the neonatal brains of Hsp70 Tg mice after H/I.

Animals↗
PubMed2005

[A case of giant cell tumor in atlas].

We report a rare case of giant cell tumor in the atlas. A 50-year-old female presented with severe pain in her right neck and shoulder. The preoperative magnetic resonance images showed a tumor mixed with solid and cystic components in the right side of the atlas. CT scan showed that the anterior and posterior arches of the atlas were destroyed. Preoperative biopsy led to the pathological diagnosis of giant cell tumor with multinuclear giant cells and mononuclear stromal cells. A preoperative vertebral angiogram demonstrated tumor stain supplied from the muscular branches. To reduce intraoperative bleeding, the embolization of the right vertebral artery by GDC was performed before surgical removal. The tumor was subtotally removed following ligation of the right external carotid artery to reduce bleeding of tumor. We used the Olerud cervical system to prevent cervical instability after resection of the tumor. Although the symptoms disappeared completely after surgery, regrowth of tumor was observed in follow-up MRI 4 months after the operation. For this reason, local radiation therapy was performed (50 Gy). Then, the size of the tumor has not changed in the 1.5 years since the operation.

Cervical Atlas↗
PubMed2005

[An elderly case of craniopharyngioma: treatment by limited surgery and radiation therapy].

Craniopharyngioma accounts for approximately 3.5% of all intracranial neoplasm and may occur at any age. However craniopharyngioma in the elderly was rare. We report a rare case of craniopharyngioma in an elderly patient, who was treated by radical surgery successfully. An 80-year-old male was admitted to our hospital with a history of visual disturbance and bitemporal hemianopsia. CT scan of the brain revealed a hypodense cystic mass with calcification in the suprasellar area. MRI demonstrated the optic chiasm was displaced superiorly. Her symptom deteriorated day short time of her hospitalized life. We decided to removal tumor radically because of saving her visual function. Subtotal removal of the suprasellar lesion was performed, followed by radiotherapy to the residual lesion. A visual impairment was improved after surgery. No recurrences had been detected on MRI eighteen months after the initial operation. Based on previous report and the clinical course of our case, radical surgery is sometimes needed for saving visual function in spite of elderly patient. However, in this case, sparing hypothalamic and pituitary function is essential for good prognosis.

Aged, 80 and over↗