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Tetsuhito Murata

Publications and source records attributed to Tetsuhito Murata.

At least 19 recordsLinked to original sources
PubMed2006

Association between trait anxiety and endothelial function observed in elderly males but not in young males.

BACKGROUND AND OBJECTIVES: Endothelial function plays a key role in determining the clinical manifestations of atherosclerosis. Recent reports have shown that healthy elderly subjects with higher trait anxiety tend to have heightened risks of atherosclerotic lesions and cardiovascular disease. The present study was intended to examine whether an association exists between trait anxiety and endothelial function in healthy young and elderly subjects. METHODS: This study examined 26 young male and 30 elderly male subjects using brachial artery flow-mediated dilation (FMD) - a non-invasive ultrasound method - to evaluate endothelial function by measuring the dilation responses of vascular smooth muscle to the nitric oxide produced by endothelial cells following hyperemia. RESULTS: A significant negative correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and the percentage change of FMD (%FMD) in the elderly subjects, but not in the young subjects. The elderly subjects showed significantly lower %FMD than the young subjects. CONCLUSION: These results suggest the possibility that trait anxiety is a predisposing risk factor for cardiovascular damage that might, over a long period, induce atherosclerotic lesions.

Adult↗
PubMed2006

Effects of chlorpromazine on plasma membrane permeability and fluidity in the rat brain: a dynamic positron autoradiography and fluorescence polarization study.

Antipsychotic drugs have been widely used in psychiatry for the treatment of various mental disorders, but the underlying biochemical mechanisms of their actions still remain unclear. Although phenothiazine antipsychotic drugs have been reported to directly interact with the peripheral plasma membrane, it is not known whether these drugs actually affect plasma membrane integrity in the central nervous system. To clarify these issues, we investigated the effect of chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug, on plasma membrane permeability in fresh rat brain slices using a dynamic positron autoradiography technique and [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) as a tracer. Treatment with CPZ (> or =100 microM) resulted in the leakage of [(18)F]FDG-6-phosphate, but not [(18)F]FDG, suggesting that the [(18)F]FDG-6-phosphate efflux was not mediated by glucose transporters, but rather by plasma membrane permeabilization. The leakage of [(18)F]FDG-6-phosphate was followed by slower leakage of cytoplasmic lactate dehydrogenase, suggesting that CPZ could initially induce small membrane holes that enlarged with time. Furthermore, the addition of CPZ (> or =100 microM) caused a decrease in 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, which implies an increase in membrane fluidity. CPZ loading dose-dependently increased both membrane permeability and membrane fluidity, which suggested the involvement of a perturbation of membrane order in the mechanisms of membrane destabilization induced by antipsychotic drugs.

Animals↗
PubMed2006

A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain.

We compared the potency of the interaction of three antipsychotic drugs, i.e. chlorpromazine (CPZ), haloperidol (Hal) and sulpiride (Sul), with the plasma membrane in the rat brain. CPZ loading (> or = 100 microM) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concentration of Hal (1 mM) was required to observe these effects. However, Sul failed to change membrane permeability and fluidity even at a high concentration (1 mM). These results indicated the following ranking of the potency to interact with the membrane: CPZ>Hal>Sul. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side-effects such as parkinsonism and tardive dyskinesia.

Animals↗
PubMed2006

Multifractal analysis of deep white matter microstructural changes on MRI in relation to early-stage atherosclerosis.

Multifractal analysis based on generalized concepts of fractals has been applied to evaluate biological tissues composed of complex structures. This type of analysis can provide a precise quantitative description of a broad range of heterogeneous phenomena. Previously, we applied multifractal analysis to describe heterogeneity in white matter signal fluctuation on T2-weighted MR images as a new method of texture analysis and established Deltaalpha as the most suitable index for evaluating white matter structural complexity (Takahashi et al. J. Neurol. Sci., 2004; 225: 33-37). Considerable evidence suggests that pathophysiological processes occurring in deep white matter regions may be partly responsible for cognitive deterioration and dementia in elderly subjects. We carried out a multifractal analysis in a group of 36 healthy elderly subjects who showed no evidence of atherosclerotic risk factors to examine the microstructural changes of the deep white matter on T2-weighted MR images. We also performed conventional texture analysis, i.e., determined the standard deviation of signal intensity divided by mean signal intensity (SD/MSI) for comparison with multifractal analysis. Next, we examined the association between the findings of these two types of texture analysis and the ultrasonographically measured intima-media thickness (IMT) of the carotid arteries, a reliable indicator of early carotid atherosclerosis. The severity of carotid IMT was positively associated with Deltaalpha in the deep white matter region. In addition, this association remained significant after excluding 12 subjects with visually detectable deep white matter hyperintensities on MR images. However, there was no significant association between the severity of carotid IMT and SD/MSI. These results indicate the potential usefulness of applying multifractal analysis to conventional MR images as a new approach to detect the microstructural changes of apparently normal white matter during the early stages of atherosclerosis.

Aged↗
PubMed2006

Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy.

Adiponectin, an adipose tissue-specific plasma protein, is involved in insulin sensitization and has anti-atherosclerotic properties, whereas tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory protein, plays important roles in inflammatory endothelial injury and atherosclerotic changes. It has been reported that adiponectin and TNF-alpha inhibit each other's expression and production in adipocytes. Several in vitro studies indicated that antidepressant medications decreased the production of pro-inflammatory cytokines including TNF-alpha, but the effect of antidepressants on the expression of adiponectin is still unknown. We examined the plasma levels of TNF-alpha and adiponectin in patients with remitted depression receiving maintenance antidepressant therapy for longer than half a year, and compared the levels with those in healthy controls. The plasma levels of TNF-alpha and adiponectin in the remitted depression group were significantly lower and higher than those in the control group, respectively. This preliminary cross-sectional study suggests the possibility that maintenance antidepressant therapy may have anti-inflammatory effects and prevent the development of atherosclerosis.

Adiponectin↗
PubMed2006

Interactions among higher trait anxiety, sympathetic activity, and endothelial function in the elderly.

Negative psychological characteristics have been recognized as independent risk factors of cardiovascular disease (CVD). The purpose of this study was to evaluate the influence of depression and anxiety on cardiac autonomic function and endothelial function in healthy elderly subjects. Forty-six healthy elderly volunteers (mean age 60.8 years) were enrolled in this study. Cardiac autonomic function was assessed by spectral analysis of heart rate variability (HRV) with the head-up tilt test. Brachial artery endothelium-dependent flow-mediated dilation (FMD) was measured using high-resolution ultrasound. A significant positive correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and HRV sympathetic modulation in the supine position (baseline), and a significant negative correlation between this score and the head-up-induced HRV sympathetic response from the baseline. The STAI-trait score also showed a significant negative correlation with the percent change of FMD (%FMD). Analysis using structural equation modeling showed that higher trait anxiety reduced %FMD via abnormalities of sympathetic activity. On the other hand, psychometric parameters of depression were not associated with any HRV component or %FMD. These results suggest that there are specific interactions among higher trait anxiety, abnormalities of sympathetic activity, and endothelial dysfunction. This finding may be useful in clarifying the pathophysiological mechanism by which anxiety is associated with increased risks for atherosclerosis and CVD.

Aged↗
PubMed2006

White coat phenomenon, anxiety and endothelial function in healthy normotensive elderly subjects.

OBJECTIVE: The white coat phenomenon (WCP) is a blood pressure (BP) elevation specifically observed in the clinical setting. Though WCP has been suggested to associate with emotional responses such as anxiety or with cardiovascular complications, its pathogenesis and clinical significance are unclear. We studied the possible association between WCP and anxiety or vascular function in normotensive elderly subjects without major cardiovascular risk factors. METHODS: As a parameter of anxiety, the State and Trait Anxiety Inventory (STAI) was used. WCP was evaluated by calculating the difference between the clinic BP and mean daytime ambulatory BP. As parameters of vascular function, brachial artery endothelium-dependent flow-mediated dilation (FMD) and the endothelium-independent dilation response to sublingual glyceryl trinitrate (GTN) were measured using high-resolution ultrasound. RESULTS: Using confounding factors as covariates, no association was observed between WCP and the STAI-trait or STAI-state score. There was a significant negative association between WCP and the percent change of FMD but no association between WCP and the percent change of GTN. CONCLUSION: WCP in the healthy normotensive elderly subjects may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than anxiety.

Aged↗
PubMed2006

Depressive psychosis: clinical usefulness of MR spectroscopy data in predicting prognosis.

PURPOSE: To prospectively assess the usefulness of magnetic resonance (MR) spectroscopy data acquired before the initiation of medical therapy in predicting prognosis in patients with depressive psychosis. MATERIALS AND METHODS: All subjects gave written informed consent to an institutional committee for clinical research-approved study protocol. The clinical course after medication in 52 patients with depressive psychosis (age range, 52-78 years; 21 men, 31 women) was investigated. In all patients, MR spectroscopy was performed with a 1.5-T MR imaging unit before the initiation of medical therapy. Cerebrovascular lesions (CVLs), which appear as high-signal-intensity areas on T2-weighted MR images, were evaluated by using the Fazekas rating scale. Patients were classified into two groups on the basis of the ratio of N-acetylaspartate (NAA) to creatine and phosphocreatine (Cr): Patients in group A had an NAA/Cr ratio greater than 1.91, and patients in group B had an NAA/Cr ratio of 1.91 or less. To assess the response of the patients to medication, standard psychiatric tests--the Verbal Associative Fluency Test (VAFT), the Digit Symbol Test (DST), the Mini-Mental State Examination (MMSE), and the Hamilton Depression Rating Scale (HAM-D)--were administered before and after medical therapy was initiated. Mean test scores before and after medication were compared with paired t testing. P < .05 was considered to indicate a significant difference. RESULTS: There were 25 patients in group A and 27 in group B. In group A, the mean VAFT and DST scores increased and the mean HAM-D score decreased after medication. There was no significant difference in mean MMSE scores before and after medication (P = .945 for group A and P = .934 for group B). In group B, there were no significant differences in any of the psychiatric test scores before and after medication. The high-signal-intensity area score in group B was significantly higher than that in group A (P = .004). CONCLUSION: MR spectroscopy data obtained before the initiation of medical therapy were useful in predicting prognosis in patients with depressive psychosis; this suggests that the combined burden of all CVLs may affect the response to antidepressant medication.

Aged↗
PubMed2006

[Changes in autonomic function and EEG power during mental arithmetic task and their mutual relationship].

Meditation is a specific consciousness state in which deep relaxation and increased internalized attention coexist. Autonomic nervous activity during meditation was reported to be characterized by decreased sympathetic activity and increased parasympathetic activity. And concerning EEG power, slow alpha power and fast theta power increased during meditation. On the other hand, mental arithmetic (MA) tasks have been reported to induce an increase in blood pressure and heart rate with enhanced sympathetic activity. However, changes in autonomic nervous activity and EEG power during MA tasks and their mutual relationship have not been adequately studied. In the present study, we quantitatively analyzed the changes in autonomic nervous activity using heart rate variability (HRV) and EEG power during MA task in 30 healthy volunteers. MA task induced significant increases in normalized LF, LF/HF ratio (as a sympathetic index), and a decrease in normalized HF (as a parasympathetic index). On the other hand, significant decrease in EEG power (slow theta: 4-6 Hz and fast alpha: 10-13 Hz in the posterior region and fast theta: 6-8 Hz and slow alpha: 8-10 Hz in all the regions) were induced by MA task. Further evaluation of these changes showed a negative correlation between the change rates (with the control resting condition as the baseline) in fast alpha power and that in LF/HF. These results suggest that specific correlated relationships exist between the change in autonomic nervous activity and EEG power depending on the difference in mental task (i.e., meditation or MA).

Adult↗
PubMed2005

Changes in EEG and autonomic nervous activity during meditation and their association with personality traits.

Meditation is the attainment of a restful yet fully alert physical and mental state practiced by many as a self-regulatory approach to emotion management, but the psychophysiological properties and personality traits that characterize this meditative state have not been adequately studied. We quantitatively analyzed changes in psychophysiological parameters during Zen meditation in 20 normal adults, and evaluated the results in association with personality traits assessed by Cloninger's Temperament and Character Inventory (TCI). During meditation, increases were observed in fast theta power and slow alpha power on EEG predominantly in the frontal area, whereas an increase in the normalized unit of high-frequency (nuHF) power (as a parasympathetic index) and decreases in the normalized unit of low-frequency (nuLF) power and LF/HF (as sympathetic indices) were observed through analyses of heart rate variability. We analyzed the possible correlations among these changes in terms of the percent change during meditation using the control condition as the baseline. The percent change in slow alpha EEG power in the frontal area, reflecting enhanced internalized attention, was negatively correlated with that in nuLF as well as in LF/HF and was positively correlated with the novelty seeking score (which has been suggested to be associated with dopaminergic activity). The percent change in fast theta power in the frontal area, reflecting enhanced mindfulness, was positively correlated with that in nuHF and also with the harm avoidance score (which has been suggested to be associated with serotonergic activity). These results suggest that internalized attention and mindfulness as two major core factors of behaviors of mind during meditation are characterized by different combinations of psychophysiological properties and personality traits.

Adult↗
PubMed2005

Understanding of cerebral energy metabolism by dynamic living brain slice imaging system with [18F]FDG.

Recently, lactate has been receiving great attention as an energy substrate in the brain. In this study, the role of lactate was evaluated by "bioradiography" system with 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), which is a positron emitting radiotracer for glucose uptake quantification. "Bioradiography" is the dynamic living tissue slice imaging system for positron-emitter labeled compounds. We investigated the brain energy metabolism under resting state and neural activated conditions induced by KCl addition. The monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), had no effect on [(18)F]FDG uptake rate in rat brain slices before KCl addition. On the other hand, addition of 4-CIN induced larger [(18)F]FDG uptake rates under the activated condition in comparison with the control condition. Because neurons cannot utilize lactate under the 4-CIN loaded conditions, this indicates that activated neurons consume lactate as an energy substrate. The lactate concentration in the incubation medium was increased with KCl treatment in both groups and the extent was slightly greater in 4-CIN group. These results suggested that: (1) the brain mainly uses glucose, not lactate, as an energy substrate in resting state; (2) when neuron is stimulated, excess amounts of lactate might be produced in astrocytes and the lactate is mobilized as an energy substrate.

Animals↗
PubMed2004

Quantitative evaluation of age-related white matter microstructural changes on MRI by multifractal analysis.

Multifractal analysis has been applied to evaluate biological tissues, which are composed of complex structures. We carried out multifractal analyses in a group of healthy young and elderly subjects to examine age-related white matter microstructural changes on T2-weighted MR images without any visible abnormal intensity, and to correlate such changes with age-related cognitive decline. Comparison between the two age groups showed that Deltaalpha (established as the most suitable index of heterogeneity in our previous report) in the frontal region was significantly higher in the elderly group, but no significant group difference was found in Deltaalpha in the parieto-occipital region. The Trail-Making Test score (a measure of executive dysfunction) was significantly higher in the elderly group. In the elderly group, the Trail-Making Test score was positively correlated with Deltaalpha in the frontal region, but not in the parieto-occipital region. These results suggest that microstructural changes in the white matter preferentially occur in the frontal region with normal aging, and these changes are associated with executive cognitive decline reflective of frontal-subcortical dysfunction.

Adult↗
PubMed2004

Role of lactate in the brain energy metabolism: revealed by Bioradiography.

To elucidate the role of lactate in the brain, we used a novel method, 'Bioradiography', in which the dynamic process could be followed in living slices by use of positron-emitter-labeled compounds and imaging plates. We studied the incorporation of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) into rat brain slices incubated in oxygenated Krebs-Ringer solution. Under the glucose-free condition, [18F]FDG uptake rate in the cerebral cortex decreased with time and plateaued within 350 min but the addition of 5 mM lactate made the [18F]FDG uptake linear. When an inhibitor of the lactate transporter, 0.5 mM alpha-cyano-4-hydroxycinnamate (4-CIN) was applied to the glucose-free solution, the uptake rate decreased. Under the normal glucose condition, [18F]FDG uptake linearly increased for 6 h, but when 10 mM lactate was applied, the uptake rate decreased. In contrast, when 0.5 mM 4-CIN was applied to the normal glucose solution, [18F]FDG uptake rate increased. These results suggest that exogenous and endogenous lactate can substitute for glucose in the brain.

Animals↗
PubMed2003

Different mechanisms of hypoxic injury on white matter and gray matter as revealed by dynamic changes in glucose metabolism in rats.

Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and the fractional rate constant (=k3*) of [18F]FDG proportional to the cerebral glucose metabolic rate in white matter and gray matter was investigated with positron autoradiography. In both white matter and gray matter, the k3* value with > or = 20 min hypoxia was markedly lower than the unloaded control value, indicating irreversible hypoxic injury. Next, the neuroprotective effect against hypoxia induced by the addition of an N-methyl-D-aspartate receptor antagonist or a free radical scavenger was assessed by determining whether a decrease in the k3* value after hypoxia loading was prevented. In gray matter, both agents exhibited a neuroprotective effect against 20 min hypoxia. In white matter, however, only the free radical scavenger was effective. These results suggest a similarity in the degree of vulnerability to hypoxia between white matter and gray matter as well as a difference in the developmental mechanism of hypoxic injury, i.e. the involvement of both glutamate and free radicals in gray matter, and the more selective involvement of free radicals in white matter.

Animals↗
PubMed2002

Hypoxic tolerance induction in rat brain slices following hypoxic preconditioning due to expression of neuroprotective proteins as revealed by dynamic changes in glucose metabolism.

We prepared rat brain slices following sublethal hypoxic pretreatment (preconditioning) and untreated (control) rats, and measured the cerebral glucose metabolic rate (CMRglc) by dynamic positron autoradiography with [18F]2-fluoro-2-deoxy-D-glucose before and after originally lethal 20-min hypoxic loading. In the regions of interest such as the frontal cortex, the CMRglc before hypoxic loading did not differ between the preconditioning and control groups. The CMRglc after reoxygenation was markedly lower than that before hypoxic loading in the control group but did not significantly differ from the preloading value in the preconditioning group. Thus, hypoxic tolerance induction by preconditioning was demonstrated using the maintenance of CMRglc as a neuronal viability index. In addition, profiling of gene expression using an Atlas Rat Stress Array suggested the involvement of the expression of genes such as stress protein in hypoxic tolerance induction.

Animals↗
PubMed2002

Hypoxic tolerance induction in rat brain slices following 3-nitropropionic acid pretreatment as revealed by dynamic changes in glucose metabolism.

Pretreatment with 3-nitropropionic acid (3-NPA) has been shown to induce tolerance to ischemic/hypoxic brain damage. However, regional differences in tolerance induction by 3-NPA and the degree to which impaired glucose metabolism due to 3-NPA pretreatment itself is directly involved remain unknown. To evaluate these issues using dynamic positron autoradiography with [(18)F]2-fluoro-2-deoxy-D-glucose, the cerebral glucose metabolic rate (CMRglc) was serially measured before and after hypoxia-loading in rat brain slices pretreated with 3-NPA. CMRglc before hypoxia did not significantly differ between the 3-NPA pretreatment group and control group. The 3-NPA-associated recovery of CMRglc after reoxygenation was observed in the frontal cortex, hippocampus, and cerebellum, but not in the striatum and thalamus. Thus, we demonstrated the induction of region-specific hypoxic tolerance after 3-NPA pretreatment using CMRglc maintenance as an index of neuronal viability, and it is unlikely that this induction is associated with the persistence of impaired glucose metabolism due to 3-NPA pretreatment.

Animals↗
PubMed2002

Age-related differences in the medial temporal lobe responses to emotional faces as revealed by fMRI.

Age-related differences involved in the neural substrates of emotional face perception were investigated in young and old healthy volunteers. The subjects were scanned using functional magnetic resonance imaging while they were judging the gender of faces with negative, positive, or neutral emotional valence. The results showed that both the predominant activation in young subjects and reduced activity in old subjects contributed to a significant age difference in the left amygdala during the perception of negative faces. Activity in the right parahippocampal gyrus during the perception of positive faces diminished with advancing age. Neural activity in the angular gyrus and lingual gyrus of the right hemisphere was reduced in the old subjects during the perception of positive faces. There was no region where old subjects had greater activity than young subjects during the task. In old subjects, the overall activity in the right hippocampus during the task correlated negatively with age, whereas the activity in the right parahippocampal gyrus correlated positively with neuropsychological performance. There was no significant correlation between subjects' characteristics and signal change in young subjects. These results indicate the age-associated vulnerability of the medial temporal lobe structures including the amygdala, hippocampus, and parahippocampal gyrus during face perception. The dissociation with reduced activity in the left amygdala and the right parahippocampal gyrus may suggest that aging differentially affects neural responses to faces with negative or positive emotional valence. The parieto-occipital lobe, which has been found to be involved in face processing, also showed a functional decline associated with aging.

Adult↗