Biomedical subjects

Naoyuki Sato

Publications and source records attributed to Naoyuki Sato.

At least 19 recordsLinked to original sources

PubMed2006

Quantitative measurement of neurological deficit after mild (30 min) transient middle cerebral artery occlusion in rats.

Although 30-min transient middle cerebral artery occlusion (30-min tMCAo) causes reproducible subcortical infarction in rats, it is difficult to evaluate the resulting neurological deficit using common behavioral tests such as the rota-rod test, adhesive-removal test, or narrow beam test. Establishment of a method of quantitative evaluation would help to develop a novel therapeutic approach to treat cerebral infarction. To solve this problem, we examined whether the neurological deficit could be detected by the Montoya staircase test or methamphetamine-induced rotation, which are commonly used in a Parkinson disease model induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). From 10 to 14 days after tMCAo, the Montoya staircase test showed significant clumsiness in forelimb tasks contralateral to the lesion side, whereas sham-operated rats showed no significant clumsiness in both forelimbs. The number of ipsilateral rotations induced by methamphetamine was also increased in tMCAo-rats at 21 days after tMCAo. Although Pearson's correlations coefficient showed that the results of these tests were correlated with the infarction volume, there was no significant correlation between the results of these two tests. These findings imply that the neurological deficit detected by both tests might reflect the severity of ischemic injury, but each test might evaluate different aspects of neurological deficit. Thus, the Montoya staircase test and methamphetamine-induced rotation are useful to evaluate neurological deficit in the chronic stage of subcortical infarction induced by 30-min tMCAo.

Animals↗

PubMed2006

Gene transfer of hepatocyte growth factor gene improves learning and memory in the chronic stage of cerebral infarction.

There is no specific treatment to improve the functional recovery in the chronic stage of ischemic stroke. To provide the new therapeutic options, we examined the effect of overexpression of hepatocyte growth factor (HGF) in the chronic stage of cerebral infarction by transferring the HGF gene into the brain using hemagglutinating virus of Japan envelope vector. Sixty rats were exposed to permanent middle cerebral artery occlusion (day 1). Based on the sensorimotor deficits at day 7, the rats were divided equally into control vector or HGF-treated rats. At day 56, rats transfected with the HGF gene showed a significant recovery of learning and memory in Morris water maze tests (control vector 50+/-4 s; HGF 33+/-5 s; P<0.05) and passive avoidance task (control vector 132.4+/-37.5 s; HGF 214.8+/-26.5 s; P<0.05). Although the total volume of cerebral infarction was not related to the outcome, immunohistochemical analysis for Cdc42 and synaptophysin in the peri-infarct region revealed that HGF enhanced the neurite extension and increased synapses. Immunohistochemistry for glial fibriary acidic protein revealed that the formation of glial scar was also prevented by HGF gene treatment. Additionally, the number of the arteries was increased in the HGF group at day 56. These data demonstrated that HGF has a pivotal role for the functional recovery after cerebral infarction through neuritogenesis, improved microcirculation, and the prevention of gliosis. Our results also provide evidence for the feasibility of gene therapy in the chronic stage of cerebral infarction.

Animals↗

PubMed2006

Development of new screening system for Alzheimer disease, in vitro Abeta sink assay, to identify the dissociation of soluble Abeta from fibrils.

Abeta is one of the primary therapeutic targets for Alzheimer disease (AD). Abeta vaccination induces the disappearance of Abeta deposits. Since few reports have focused on the reverse phase of Abeta aggregation, we established a new screening system, the in vitro Abeta sink assay, to clarify the process of dissociation of soluble forms from fibrils. Abeta42 was more resistant to dissociation from fibrils to monomers and/or low molecular weight (LMW) soluble oligomers than Abeta40. We applied this system to find a potential therapy for AD. Ultrasound irradiation significantly enhanced the dissociation of soluble Abeta from fibrils, while ultrasound experiments also confirmed the difference between Abeta40 and Abeta42. We found that some compounds enhanced the dissociation of Abeta from fibrils. Here, we proposed that Abeta42 was more resistant to dissociation from fibrils to monomers and/or LMW soluble oligomers than Abeta40, and this system might be useful to identify dissociation of soluble Abeta from fibrils.

Alzheimer Disease↗

PubMed2006

HVJ-based non-viral gene transfer method: successful gene therapy using HGF and VEGF genes in experimental ischemia.

VEGF and HGF are pleiotropic factors that regulate cell growth, cell motility, and morphogenesis of various types of cells. The receptors of these growth factors are expressed in neurons and endothelial cells, and are identified as neurotrophic, neuroprotective, and angiogenic factors. Indeed, gene therapy using viral vectors encoding the VEGF or HGF gene has been reported to be effective for preventing the expansion of ischemic injury. However, the safety issue of viral vectors is a major problem in clinical application. To overcome this problem, we have developed an HVJ-based non-viral vector, which achieves high-efficiency transfection rates of viral vectors with the safety of liposomes. This review discusses the feasibility of gene therapy using an HVJ-based non-viral vector containing the VEGF or HGF gene for cerebral ischemia.

Animals↗

PubMed2006

Study of association between hypertensive disorders of pregnancy and the human coagulation factor XI gene.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) are among the most common and serious complications of pregnancy. Persuasive evidence implicaties genetic factors in the genesis of HDP. The aim of the present study was to assess the association between single-nucleotide polymorphisms (SNPs) in the human coagulation factor XI (F11) gene and HDP, by conducting a haplotype-based case-control study. METHODS: We chose 3 SNPs (rs925453, rs925451, and rs12500151) in the human F11 gene as genetic markers. We then conducted an association study with 77 HDP patients and 154 age-matched non-HDP subjects. RESULTS: The frequency of rs925453 genotypes significantly differed between the two groups. The frequency of the T-G-G haplotype was significantly higher in the HDP group than in the non-HDP group (p = 0.0002). CONCLUSIONS: The T allele of rs925453 and the T-G-G haplotype appear to be useful genetic markers of HDP.

Adolescent↗

PubMed2006

Haplotypes of the plasminogen activator gene associated with ischemic stroke.

Ischemic stroke (IS) is thought to be a multifactorial disorder associated with genetic backgrounds and environmental factors. In the circulating plasma, tissue plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin. If there is a functional disability of tPA, induction of thrombosis and infarction disorders can occur. The aim of this study was to perform a haplotype-based case-control study using single nucleotide polymorphisms (SNPs) in the human tPA gene, and to assess the association between the tPA gene and IS. We genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five SNPs, a haplotype-based case control study was performed. There were seven SNP combinations that exhibited significant differences in the overall distribution between the IS and control groups. Linkage disequilibrium analysis showed that the combination of rs7007329 and rs8178750 was useful in identification of the susceptibility haplotype. The frequency of the G-T haplotype at rs7007329-rs8178750 was significantly higher in the IS group (1.2%) as compared to the control group (0.0%) (p = 0.003). Diplotype analysis also showed a significant association of the diplotype with the G-T haplotype at rs7007329-rs8178750 (OR:11.4, 95%CI:1.32-97.9, p = 0.013). These results suggest that the G-T haplotype at rs7007329-rs8178750 of the tPA gene is a genetic marker for IS, and that tPA or a neighboring gene is a susceptibility gene for IS.

Aged↗

PubMed2005

Genotype and haplotype association study of the STRK1 region on 5q12 among Japanese: a case-control study.

BACKGROUND AND PURPOSE: Cerebral infarction is thought to be a multifactorial disease that is affected by several environmental factors and genetic variants. Gretarsdottir et al identified a candidate locus (STRK1) for cerebral infarction with a significant logarithm of odds score at 5q12 in whites in 2002 and subsequently identified the PDE4D gene as a susceptibility gene at this locus in 2003. The aims of this haplotype-based case-control study were to confirm, using microsatellite markers and single-nucleotide polymorphisms (SNPs), whether PDE4D is also a susceptibility gene for cerebral infarction in Japanese subjects. METHODS: Cerebral infarction was defined as noncardiogenic ischemic stroke with signs and symptoms lasting >1 month in duration. We genotyped 208 Japanese cerebral infarction patients and 270 non-cerebral infarction controls for 31 SNPs, 3 dinucleotide microsatellites, and 1 tetranucleotide variable number of tandem repeat. Haplotypes were constructed and their frequencies compared between the cerebral infarction patients and the controls. RESULTS: The haplotype-based case-control study revealed that in addition to the region of the PDE4D gene (P=0.002), another region (P<0.001) also existed within the STRK1 locus. CONCLUSIONS: The region of the PDE4D gene and the other newly detected region within the STRK1 locus were associated with cerebral infarction.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Characterization of amorphous hydrogenated carbon formed by low-pressure inductively coupled plasma enhanced chemical vapor deposition using multiple low-inductance antenna units.

Three-dimensional plasma enhanced chemical vapor deposition (CVD) of hydrogenated amorphous carbon (a-C:H) has been demonstrated using a new type high-density volumetric plasma source with multiple low-inductance antenna system. The plasma density in the volume of phi 200 mm x 100 mm is 5.1 x 10(10) cm(-3) within +/-5% in the lateral directions and 5.2 x 10(10)cm(-3) within +/-10% in the axial direction for argon plasma under the pressure of 0.1 Pa and the total power as low as 400 W. The uniformity of the thickness and refractive index is within +/-3.5% and +/-1%, respectively, for the a-C:H films deposited on the substrates placed on the six side walls, the top of the phi 60 mm x 80 mm hexagonal substrate holder in the pure toluene plasma under the pressure is as low as 0.04 Pa, and the total power is as low as 300 W. It is also found that precisely controlled ion bombardment by pulse biasing led to the explicit observation in Raman and IR spectra of the transition from polymer-like structure to diamond-like structure accompanied by dehydrogenation due to ion bombardment. Moreover, it is also concluded that the pulse biasing technique is effective for stress reduction without a significant degradation of hardness. The stress of 0.6 GPa and the hardness of 15 GPa have been obtained for 2.0 microm thick films deposited with the optimized deposition conditions. The films are durable for the tribology test with a high load of 20 N up to more than 20,000 cycles, showing the specific wear rate and the friction coefficient were 1.2 x 10(-7) mm3/Nm and 0.04, respectively.

Journal Article↗

PubMed2005

Online formation of a hierarchical cognitive map for object-place association by theta phase coding.

Object-place associative memory, the storage of object and place conjunctions based on a one-time experience, is hippocampal-dependent in humans. Theta phase precession, a type of neural dynamics observed in the rat hippocampus, has recently been suggested to serve a role in instantaneous memory formation based on a one-time experience, while its functional role in associating distinct types of information (object and place information) is unclear. In this study, we hypothesize that theta phase encoding with theta phase precession contributes to the storage of object-place associations. To examine this hypothesis, we propose a neural network model of the corticohippocampal system, including central-peripheral visual pathways and theta phase coding in the hippocampus. Memory storage computer experiments demonstrate that the hippocampal network successfully stores the object-place associations of a one-time experience. Interestingly, it is also found that a random visual input sequence results in a robust formation of asymmetric connections between objects and scenes instantaneously after a single trial. Furthermore, it is found that scene-object connections and scene-scene connections form a hierarchical network representing the spatial alignment of scenes and objects in the environment. Our findings indicate that the theta phase coding, as observed in the rat hippocampus, can facilitate the online memory storage of complex environments in humans as a hierarchical cognitive map.

Action Potentials↗

PubMed2005

Gene transfer into adult rat spinal cord using naked plasmid DNA and ultrasound microbubbles.

BACKGROUND: Although gene therapy might become a promising approach to treat spinal cord injury, the safety issue is a serious consideration in human gene therapy. Plasmid DNA transfer is safer than viral vectors, but the transfection efficiency is quite low. To overcome the problem, we applied the ultrasound microbubbles-mediated transfection method to the spinal cord in adult rats, since ultrasound microbubbles have been reported to be efficient to increase transfection efficiency in various tissues. METHODS: After exposing T9-10 spinal cord with a laminectomy, we injected a mixture of naked plasmid DNA and microbubbles into cerebrospinal fluid by lumbar puncture. Then, the T9-10 spinal cord was exposed to ultrasound. CONCLUSIONS: An ultrasound intensity of 0.4-0.5 W/cm2 significantly increased luciferase expression up to approximately 15-60-fold at the insonated level as compared to naked plasmid DNA alone. Luciferase activity could be detected at least up to 7 days after transfection, while the expression level was almost returned to undetectable level at 14 days after transfection. The transfected cells were mainly meningeal cells in the surface of insonated spinal cord. There was no obvious evidence of worsening of neurological deficits as compared to rats transfected with naked plasmid DNA alone or untransfected rats. Similarly, successful gene transfer was also achieved in the insonated T9-10 spinal cord after spinal cord injury. Overall, the present study demonstrated the feasibility of ultrasound microbubbles-mediated plasmid DNA transfer into the target level of the spinal cord.

Animals↗

PubMed2005

Association study of calcitonin-receptor-like receptor gene in essential hypertension.

BACKGROUND: Plasma adrenomedullin (ADM) concentrations increase in patients with hypertension, renal failure, heart failure, essential pulmonary hypertension, myocardial infarction, endotoxin shock, and many other conditions. The ADM receptor is a complex molecule that consists of calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2). Because CRLR determines the binding specificity of ADM, the CRLR gene is thought to be a susceptibility gene of hypertension. However, studies have not yet defined the relationship between the CRLR gene and hypertension. The aim of the present study was to investigate relationships between single-nucleotide polymorphisms (SNP) in the human CRLR gene and essential hypertension (EH) in a Japanese population. METHODS: We selected four SNP in the human CRLR gene (rs3771073, rs696574, rs698590, and rs1528233), and we performed a genetic association study in 209 EH patients and 216 age-matched normotensive (NT) individuals. RESULTS: There was no significant difference in overall distribution of genotypes or alleles of any of the SNP between the EH and NT groups. However, among women, the T allele of the SNP rs696574 (C --> T, in intron 6) was significantly more frequent in EH subjects than in NT subjects (P = .032). CONCLUSION: Our findings suggest that rs696574 can be used as a genetic marker of EH in women.

Adult↗

PubMed2005

Haplotype-based case-control study revealing an association between the adrenomedullin gene and proteinuria in subjects with essential hypertension.

Adrenomedullin (AM) has various physiological actions on the cardiovascular system, including vasodilatation, diuresis, natriuresis, inhibition of aldosterone secretion, and increases of the cardiac output, all of which cause hypotension. Since AM plays a role in the pathophysiology of vascular diseases, genes controlling AM might be involved in the development and etiology of essential hypertension (EH). However, there have been few studies examining the relationship between the AM gene and hypertension. The aims of this study were to genotype some of the genetic markers for the human AM gene in Japanese subjects, and via a haplotype-based case-control study, assess the association between and the AM gene and EH or its risk factors, such as hyperlipidemia, renal damage, and proteinuria. We genotyped 205 EH patients and 210 age-matched normotensive (NT) individuals for two single nucleotide polymorphisms of rs4399321, rs7944706 and a microsatellite polymorphism located approximately 5,400 base pairs downstream of the 3' end of the human AM gene. The overall distribution in each variant and haplotype did not significantly differ between the two groups. However, after dividing the groups into those subjects with and without proteinuria, the haplotype analysis revealed a positive association. In conclusion, a possible mutation linked to the haplotype may indicate a genetic predisposition for proteinuria in EH.

Adrenomedullin↗

PubMed2005

Recent progress in cerebrovascular gene therapy.

Gene therapy provides a potential strategy for the treatment of cardiovascular disease such as peripheral arterial disease, myocardial infarction, restenosis after angioplasty, and vascular bypass graft occlusion. Currently, more than 20 clinical studies of gene therapy for cardiovascular disease are in progress. Although cerebrovascular gene therapy has not proceeded to clinical trials, in contrast to cardiovascular gene therapy, there have been several trials in experimental models. Three major potential targets for cerebrovascular gene therapy are vasospasm after subarachnoid hemorrhage (SAH), ischemic cerebrovascular disease, and restenosis after angioplasty, for which current therapy is often inadequate. In experimental SAH models, strategies using genes encoding a vasodilating protein or decoy oligodeoxynucleotides have been reported to be effective against vasospasm after SAH. In experimental ischemic cerebrovascular disease, gene therapy using growth factors, such as Brain-derived neurotrophic factor (BDNF), Fibroblast growth factor-2 (FGF-2), or Hepatocyte growth factor (HGF), has been reported to be effective for neuroprotection and angiogenesis. Nevertheless, cerebrovascular gene therapy for clinical human treatment still has some problems, such as transfection efficiency and the safety of vectors. Development of an effective and safe delivery system for a target gene will make human cerebrovascular gene therapy possible.

Cardiovascular Diseases↗

PubMed2005

[Residues of total mercury and methyl mercury in eel products].

Fifty-two samples of broiled eels and broiled eel liver were analyzed for total mercury (total Hg) and methyl mercury. The mean concentrations of total Hg in broiled eels and broiled eel liver were 0.21 ppm and 0.10 ppm, respectively. Meanwhile, the mean concentrations of methyl mercury in broiled eels and broiled eel liver were 0.085 ppm and 0.039 ppm, respectively. The rate of methyl mercury to total Hg mainly ranged from 60 to 80% in broiled eels and from 35 to 65% in broiled eel liver. The total Hg concentrations of 2 samples of broiled eels and one sample of broiled eel liver exceeded the provisional regulation limit (0.4 ppm) of total Hg in fish in Japan. In these samples, the rates of methyl mercury to total Hg were lower than 20%. The muscles and the skin of broiled eels were measured separately. The ratios of skin to muscle concentration of total Hg and methyl mercury were mainly in the range from 1/10 to 1/4. The mean intakes of total Hg from broiled eels and broiled eel liver per individual were 24.6 microg and 3.1 microg, respectively. The mean intakes of methyl mercury from broiled eels and broiled eel liver per individual were 10.4 microg and 1.2 microg, respectively.

Animals↗

PubMed2004

Novel therapeutic strategy to treat brain ischemia: overexpression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat model.

BACKGROUND: Although cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. An ideal therapeutic approach to treat ischemia might have both aspects of enhancement of collateral formation and prevention of neuronal death. Hepatocyte growth factor (HGF) is a potent angiogenic factor that also acts as a neurotrophic factor. Thus, in this study, we examined the therapeutic effects of HGF on brain injury in a rat permanent middle cerebral artery occlusion model. METHODS AND RESULTS: Gene transfer into the brain was performed by injection of human HGF gene with hemagglutinating virus of Japan-envelope vector into the cerebrospinal fluid via the cisterna magna. Overexpression of the HGF gene resulted in a significant decrease in the infarcted brain area as assessed by triphenyltetrazolium chloride staining, whereas rats transfected with control vector exhibited a wide area of brain death after 24 hours of ischemia. Consistently, the decrease in neurological deficit was significantly attenuated in rats transfected with the HGF gene at 24 hours after the ischemic event. Stimulation of angiogenesis was also detected in rats transfected with the HGF gene compared with controls. Of importance, no cerebral edema or destruction of the blood-brain barrier was observed in rats transfected with the HGF gene. CONCLUSIONS: Overall, the present study demonstrated that overexpression of the HGF gene attenuated brain ischemic injury in a rat model, without cerebral edema, through angiogenic and neuroprotective actions. In particular, the reduction of brain injury by HGF may provide a new therapeutic option to treat cerebrovascular disease.

Animals↗

PubMed2004

An association study in essential hypertension using functional polymorphisms in lymphotoxin-alpha gene.

BACKGROUND: Lymphotoxin-alpha (LTA), a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The substance LTA mediates a wide variety of inflammatory, immunostimulatory, and antiviral responses. In 2002, LTA was identified as a major risk factor for myocardial infarction (MI) in Japanese individuals, in a large-scale case-control study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers in the whole human genome. Essential hypertension (EH) is thought to be a multifactorial disorder involved in endothelial dysfunction and atherosclerosis. Although hypertension is one of the greatest risk factors for MI, there have been no reports estimating the association between EH and LTA. The aim of the present study was to evaluate the association between EH and the LTA gene. METHODS: In the present study, we assessed the association between EH and SNP and haplotypes of the LTA gene in a case-control study of 202 EH patients and 217 age-matched normotensive control subjects. RESULTS: The overall distribution of genotypes for each SNP did not significantly differ between the two groups. Furthermore, the haplotype analysis revealed no association between the EH and normotensive groups. CONCLUSIONS: Polymorphisms of the LTA gene were not associated with EH. This finding suggests differences in genetic backgrounds between EH and MI.

Case-Control Studies↗

PubMed2004

Synchronization of neural oscillations as a possible mechanism underlying episodic memory: a study of theta rhythm in the hippocampus.

Rat hippocampal cells exhibit characteristic phase-dependent firings when oscillation in frequency range around 8Hz is present. Based on the hypothesis that theta phase coding is generated by synchronization of neural activities, an autoassociative network model of the hippocampus and the entorhinal cortex was analyzed to explore mechanisms underlying episodic memory. Phase coding in theta rhythm enables instantaneous acquisition of experienced events including temporal and spatial contents. Further comparison with electrophysiological data from both rodents and primates suggests a possible role of theta oscillations in memory encoding and online processing of episodic events.

Action Potentials↗

PubMed2004

Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia.

The pathophysiology of preeclampsia (PE) remains uncertain despite many research efforts. Actual hypotheses seek to explain the vascular damage that characterizes the disease. Recently, it was reported that the mouse disrupted estrogen receptor beta (ESR2) gene was associated with abnormal vascular function and hypertension. Moreover, some investigators have reported that subjects with a family history of hypertension have a statistically significant increased risk for PE. Thus, it is thought that the pathophysiology of PE overlaps that for hypertension. The aim of the present study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the human ESR2 gene and PE in Japanese subjects, and to assess the involvement of a family history of hypertension in these relationships. Based on a database search on the web site of the National Center of Biotechnology Information (NCBI), we chose four SNPs in the human ESR2 gene, and performed an association study in 84 PE patients and 160 age-matched non-PE subjects. The overall distribution in each SNP did not differ significantly between the two groups. However, after dividing the groups into subjects with and without a family history of hypertension, the allelic distribution of one of the SNPs (rs928554) revealed a positive association. Thus, a possible mutation linked to a SNP may prescribe a genetic predisposition for patients with a family history of hypertension in PE.

Adolescent↗