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Masatoshi Itoh

Publications and source records attributed to Masatoshi Itoh.

At least 19 recordsLinked to original sources

Reactivation of medial temporal lobe and occipital lobe during the retrieval of color information: A positron emission tomography study.

It is widely accepted that memory traces of an event include various types of information about the content of the event and about the circumstances in which the individual experienced it. However, how these various types of information are stored and later retrieved is poorly understood. One hypothesis postulates that the retrieval of specific event information reactivates regions that were active during the encoding of this information, with the aid of binding functions of the medial temporal lobe (MTL) structures. We used positron emission tomography to identify the brain regions related to the encoding and retrieval of color information. Specifically, we assessed whether overlapping activity was found in both the MTL structures and color-related cortical regions during the encoding and retrieval of color information attached with meaningless shapes. During the study, subjects were asked to encode colored (red or green) and achromatic random shapes. At subsequent testing, subjects were presented with only achromatic shapes, which had been presented with or without colors during encoding, and were engaged in retrieval tasks of shapes and colors. Overlapping activity was found in the MTL and occipital lobe (the lingual and inferior occipital gyri) in the right hemisphere during the encoding and retrieval of meaningless shapes with color information compared with those without color information. Although there are some limitations to be considered, the present findings seem to support the view that the retrieval of specific event information is associated with reactivation of both the MTL structures and the regions involved during encoding of the information.

Adult↗

Spontaneous scratching behavior in MRL/lpr mice, a possible model for pruritus in autoimmune diseases, and antipruritic activity of a novel kappa-opioid receptor agonist nalfurafine hydrochloride.

Pruritus is a common, distressing and difficult to manage complication of many autoimmune diseases. A suitable animal model of autoimmune disease associated pruritus would contribute to a better understanding of the pathophysiology of this symptom and lead to the development of safe and effective antipruritic agents. We noticed spontaneous scratching behavior in aged MRL/lpr mice, a model of autoimmune disease. This scratching behavior was observed in a specific pathogen-free environment and was more frequent in female mice. In contrast to animal models of dermatitis; NC/Nga mice, the serum IgE and IgG1 levels in MRL/lpr mice were not elevated. These features indicate that this scratching behavior is similar to human autoimmune disease associated pruritus. The antipruritic effects of an antihistamine (chlorpheniramine), an opioid receptor antagonist (naltrexone), and a novel kappa-opioid receptor agonist (nalfurafine hydrochloride [TRK-820]) were evaluated. The frequency of scratching was not reduced by oral administration of chlorpheniramine, suggesting that the behavior is antihistamine-resistant. The oral administration of nalfurafine and subcutaneously administered naltrexone inhibited the scratching behavior without causing gross behavioral changes. In conclusion, MRL/lpr mice scratching behavior is a suitable model of pruritus that occurs in autoimmune diseases, and nalfurafine was shown to be efficacious against this behavior suggesting that it may be beneficial in patients with autoimmune disease associated pruritus.

Age Factors↗

Dissociable roles of prefrontal and anterior cingulate cortices in deception.

Recent neuroimaging studies have shown the importance of the prefrontal and anterior cingulate cortices in deception. However, little is known about the role of each of these regions during deception. Using positron emission tomography (PET), we measured brain activation while participants told truths or lies about two types of real-world events: experienced and unexperienced. The imaging data revealed that activity of the dorsolateral, ventrolateral and medial prefrontal cortices was commonly associated with both types of deception (pretending to know and pretending not to know), whereas activity of the anterior cingulate cortex (ACC) was only associated with pretending not to know. Regional cerebral blood flow (rCBF) increase in the ACC was positively correlated with that in the dorsolateral prefrontal cortex only during pretending not to know. These results suggest that the lateral and medial prefrontal cortices have general roles in deception, whereas the ACC contributes specifically to pretending not to know.

Adolescent↗

Recruitment of fusiform face area associated with listening to degraded speech sounds in auditory-visual speech perception: a PET study.

For the fast and accurate cognition of external information, the human brain seems to integrate information from multi-sensory modalities. We used positron emission tomography (PET) to identify the brain areas related to auditory-visual speech perception. We measured the regional cerebral blood flow (rCBF) of young, normal volunteers during the presentation of dynamic facial movement at vocalization and during a visual control condition (visual noise), both under the two different auditory conditions of normal and degraded speech sounds. The subjects were instructed to listen carefully to the presented speech sound while keeping their eyes open and to say what they heard. The PET data showed that elevation of rCBF in the right fusiform gyrus (known as the "face area") was not significant when the subjects listened to normal speech sound accompanied by a dynamic image of the speaker's face, but was significant when degraded speech sound (filtered with a 500 Hz low-pass filter) was presented with the facial image. The results of the present study confirm the possible involvement of the fusiform face area (FFA) in auditory-visual speech perception, especially when auditory information is degraded, and suggest that visual information is interactively recruited to make up for insufficient auditory information.

Acoustic Stimulation↗

An experimental study on O-[18F]fluoromethyl-L-tyrosine for differentiation between tumor and inflammatory tissues.

OBJECTIVE: O-[18F]fluoromethyl-L-tyrosine (18F-FMT) is a recently developed tumor-detecting agent with simple preparation and high radiochemical yields. The aim of this study was to assess the potency of 18F-FMT for differentiating tumor and inflammatory tissues using an animal model with an implanted tumor and experimentally induced inflammatory foci. METHODS: An ascites hepatoma cell line, AH109A, turpentine oil and Staphylococcus aureus were inoculated subcutaneously into Donryu rats as a tumor model, aseptic inflammation model and bacterial infection model, respectively. The biodistribution of radioactivity was assessed in rats at 5, 10, 30, 60, and 120 min after injection with 18F-FMT. Dual tracer whole-body and macro autoradiographies were performed 60 min after injection with a mixture of 18F-FMT and 2-deoxy-D-[1-14C]glucose (14C-DG). RESULTS: Tumor uptake of 18F-FMT was on average 1.27% injected dose per gram of tissue (%ID/g) and 1.43% ID/g at 30 min and 60 min, respectively and significantly higher than that in other normal tissues, except the pancreas (3.48% ID/g at 60 min). The uptakes in the aseptic and bacterial inflammatory tissues were very low and were not different from those of the background tissues. Dual tracer whole-body and macro autoradiographic studies showed that tumor uptake of 18F-FMT was clearly higher than uptake by the other tissues, while 18F-FMT accumulated much less both in aseptic and bacterial inflammatory tissues. In contrast, the 14C-DG images showed high accumulations not only in tumors but also in aseptic and bacterial inflammatory tissues. CONCLUSION: 18F-FMT seems to be a promissing tracer for the differentiation between tumor and inflammation because of higher specificity to tumor.

Animals↗

Histamine H1 receptors in schizophrenic patients measured by positron emission tomography.

Increasing evidence has shown that the histaminergic neuron system is implicated in the pathophysiology of schizophrenia. The aim of this study was to compare the distribution of histamine H1 receptors between schizophrenics and normal human subjects in vivo using positron emission tomography (PET). H1 receptor binding was measured in 10 normal subjects and 10 medicated schizophrenic patients by PET and [11C] doxepin, a radioligand for the H1 receptor. The binding potential (BP=Bmax/K(D)) of [11C] doxepin for available brain H1 receptors was calculated by a graphical analysis on voxel-by-voxel basis and compared between schizophrenics and normal subjects using the regions of interest (ROIs) and the statistical parametrical mapping (SPM99). BP values for H1 receptors in the frontal and prefrontal cortices and the cingulate gyrus were significantly lower among the schizophrenic patients than among the control subjects. On the contrary, there were no areas of the brain where H1 receptors were significantly higher among the schizophrenic patients than the control subjects. The results of our study suggest that the central histaminergic neuron system could be involved in the pathophysiology of schizophrenia, although further studies are needed to confirm this hypothesis.

Adult↗

Attenuation of fluctuating striatal synaptic dopamine levels in patients with Parkinson disease in response to subthalamic nucleus stimulation: a positron emission tomography study.

OBJECT: The "wearing-off" phenomenon often hampers the treatment of Parkinson disease (PD). Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to ameliorate the wearing-off phenomenon, the mechanism by which it does this remains unclear. As part of an inquiry into the mechanism of STN DBS, the authors measured synaptic dopamine levels in the striatum by performing positron emission tomography (PET) with [11C]raclopride. METHODS: Three patients with PD who were experiencing the wearing-off phenomenon underwent PET scanning before and after DBS of the STN. The clinical features in these patients were evaluated by applying the Hoehn and Yahr, United Parkinson's Disease Rating, and Schwab and England Activities of Daily Living Scales. Before and after surgery, PET scans were obtained using [11C]raclopride prior to and 1 hour following an oral administration of levodopa. Regions of interest for the [11C]raclopride binding potential (RacloBP) were set in the bilateral putamen and the caudate nucleus. All clinical scores were dramatically improved postoperatively. Deep brain stimulation of the STN reduced the baseline RacloBP in both the putamen and caudate nucleus, but the differences between the pre- and postoperative levels were insignificant. Before DBS of the STN, the levodopa administration significantly reduced RacloBP in the putamen (p < 0.0001). Postoperatively the drug-induced reduction in RacloBP became statistically insignificant. The drug-induced increase in synaptic dopamine concentrations in the putamen preoperatively was estimated to be approximately four times higher than that after surgery (p < 0.01). The drug-induced RacloBP change in the caudate nucleus was similar to that in the putamen, although the magnitude of the change was lower (p < 0.005). The drug-induced increase in the caudate nucleus was also reduced postoperatively (p < 0.05). CONCLUSIONS: Deep brain stimulation of the STN induces the stabilization of synaptic dopamine concentrations in the striatum and may attribute to the alleviation of levodopa-related motor fluctuations.

Aged↗

The neural correlates of driving performance identified using positron emission tomography.

Driving is a complex behavior involving multiple cognitive domains. To identify neural correlates of driving performance, [15O]H2O positron emission tomography was performed using a simulated driving task. Compared with the resting condition, simulated driving increased regional cerebral blood flow (rCBF) in the cerebellum, occipital, and parietal cortices. Correlations between rCBF and measurements of driving performance were evaluated during simulated driving. Interestingly, rCBF in the thalamus, midbrain, and cerebellum were positively correlated with time required to complete the course and rCBF in the posterior cingulate gyrus was positively correlated with number of crashes during the task. These brain regions may thus play roles in the maintenance of driving performance.

Adult↗

FDG-PET delayed imaging for the detection of head and neck cancer recurrence after radio-chemotherapy: comparison with MRI/CT.

In advanced head and neck cancer, an organ-sparing approach comprising radiation therapy combined with intra-arterial chemotherapy has become an important technique. However, the high incidence of residual masses after therapy remains a problem. In this study, we prospectively evaluated the use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) delayed imaging for the detection of recurrence of head and neck cancer after radio-chemotherapy, and compared the FDG-PET results with those of magnetic resonance imaging (MRI) or computed tomography (CT). Forty-three lesions from 36 patients with head and neck cancer suspected to represent recurrence after radio-chemotherapy (median interval from therapy, 4 months) were studied. PET was performed at 2 h after FDG injection, and evaluated. The results were compared to those of contrast studies with MRI or CT performed within 2 weeks of the PET study, and to histological diagnosis (in all patients suspected of having recurrence) or clinical diagnosis. The lesion-based sensitivity (visual interpretation) and negative predictive value of FDG-PET (88% and 91%, respectively) were higher than those of MRI/CT (75% and 67% respectively). The specificity, accuracy and positive predictive value of FDG-PET (78%, 81% and 70%, respectively) were significantly ( P<0.05) higher than those of MRI/CT (30%, 47% and 39% respectively). Three of six patients with false positive findings had post-therapy inflammation. Receiver operating characteristic (ROC) analysis showed that retrospective evaluation with the standardised uptake ratio yielded the best results (sensitivity 87.5%, specificity 81.5%), followed by visual interpretation and then the tumour/neck muscle ratio. An FDG-PET delayed imaging protocol yielded significantly better results for the detection of recurrence of head and neck cancer after radio-chemotherapy than MRI/CT. Because of the high negative predictive value of FDG-PET (91.3%), if PET is negative, further invasive procedures may be unnecessary.

Adult↗

Target dependency of brain mechanism involved in dispositional inference: a PET study.

The cognitive mechanism for inference of personal dispositions, such as personality traits and abilities, is postulated to be dependent on the amount of episodic memory concerning target persons. To examine whether there is such target dependency in the brain mechanism during dispositional inference, we measured brain activity of normal volunteers while they were performing seven dispositional inference tasks, each for a target person in different categories, using positron emission tomography (PET). Effect of the target-person category on activation was significant in the posterodorsal, polar, and ventral subdivisions of medial prefrontal cortex, right orbitoinsular junction, left temporal pole and superior temporal sulcus, cerebellum, and thalamus, suggesting the existence of target dependency in activation during dispositional inference. The amount of episodic memory concerning a target person measured using the self-evaluative questionnaire was positively correlated with the activation in the polar subdivision of the medial prefrontal cortex, and negatively with that in a region in the left superior temporal sulcus. Together with the available knowledge on the functional roles of these regions and the proposed cognitive model in social psychology, our results suggest that these two regions play roles supplementary to each other in dispositional inference; a region in the superior temporal sulcus is involved in the processing of relevant episodic exemplar and the polar subdivision of the medial prefrontal cortex in the processing of summarized value information about the target person.

Adolescent↗

Neural correlates of context memory with real-world events.

There has been little evidence for the difference in the retrieval processes of when and where something happened, one of the important factors in understanding episodic memory. We used positron emission tomography (PET) to identify the neural networks associated with temporal and spatial context memory of events experienced under experimental conditions similar to those of everyday life. Before PET, subjects experienced 36 events. The events were divided into four groups of nine each. The subjects experienced the first two groups of events before a 15-min recess and the other two after the recess; they experienced the first and last groups of events in one room, took a recess in another room, and experienced the second and third groups in a different room. During PET, the subjects were scanned under three different retrieval tasks: a time-retrieval task, a place-retrieval task, and a simple recognition task. The results showed that the retrieval of time and space, compared with the simple recognition, was associated with activity in substantially different regions as well as a common region: time retrieval with the posterior part of the right orbitofrontal cortex and left inferior parietal lobule, place retrieval with two regions in right parietal association cortex, right posterior cingulate gyrus, left precentral gyrus, and right cerebellum, and both with the right inferior frontal gyrus. These findings indicate that there are unique areas, in addition to a common area, for retrieving temporal and spatial context.

Adult↗

Decreased histamine H1 receptor binding in the brain of depressed patients.

The central histaminergic neuron system modulates the wakefulness, sleep-awake cycle, appetite control, learning and memory, and emotion. Previous studies have reported changes in neuronal histamine release and its metabolism under stress conditions in the mammalian brain. In this study, we examined, using positron emission tomography (PET) and [(11)C]-doxepin, whether the histaminergic neuron system is involved in human depression. Cerebral histamine H1 receptor (H(1)R) binding was measured in 10 patients with major depression and in 10 normal age-matched subjects using PET and [(11)C]-doxepin. Data were calculated by a graphical analysis on voxel-by-voxel and ROI (region of interests) basis. Binding potential (BP) values for [(11)C]-doxepin binding in the frontal and prefrontal cortices, and cingulate gyrus were significantly lower in the depressed patients than those in the normal control subjects. There was no area of the brain where [(11)C]-doxepin binding was significantly higher in the depressed patients than in the controls. ROI-based analysis also revealed that BP values for [(11)C]-doxepin binding in the frontal cortex and cingulate gyrus decreased in proportion to self-rating depressive scales scores. The results of this study demonstrate that depressed patients have decreased brain H(1)R binding and that this decrease correlates with the severity of depression symptoms. It is therefore suggested that the histaminergic neuron system plays an important role in the pathophysiology of depression and that its modulation may prove to be useful in the treatment of depression.

Adult↗

Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography.

Histamine H1-receptor (H1R) antagonists, or antihistamines, often induce sedative side effects when used for the treatment of allergic disorders. This study compared the sedative profiles of the second-generation antihistamines, fexofenadine and cetirizine, using 3 different criteria: subjective sleepiness evaluated by the Stanford Sleepiness Scale, objective psychomotor tests (simple and choice reaction time tests and visual discrimination tests at 4 different exposure durations), and measurement of histamine H1-receptor occupancy (H1RO) in the brain. Subjective sleepiness and psychomotor performance were measured in 20 healthy Japanese volunteers at baseline and 90 min after administration of fexofenadine 120 mg or cetirizine 20 mg in a double-blind, placebo-controlled crossover study. Hydroxyzine 30 mg was included as a positive control. H1RO was measured using positron emission tomography (PET) with (11)C-doxepin in 12 of the 20 subjects, and a further 11 volunteers were recruited to act as controls. In psychomotor tests, fexofenadine was not significantly different from placebo and significantly less impairing than cetirizine on some tasks, as well as significantly less impairing than hydroxyzine on all tasks. For subjective sleepiness, fexofenadine was not significantly different from placebo, whereas cetirizine showed a trend toward increased sleepiness compared with fexofenadine and placebo. H1RO was negligible with fexofenadine (-0.1%) but moderately high with cetirizine (26.0%). In conclusion, fexofenadine 120 mg is distinguishable from cetirizine 20 mg, as assessed by H1RO and psychomotor testing.

Adult↗

Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease.

Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer's disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone.

Aged↗

Inhibitory effect of a novel bisphosphonate, TRK-530, on dental calculus formation in rats.

BACKGROUND: A newly developed bisphosphonate, TRK-530 (disodium dihydrogen[4-(methylthio)phenylthio]methanebisphosphonate), has recently been reported to show anti-inflammatory and anti-bone-resorbing activity. Since bisphosphonates have been shown to inhibit the formation of calcium-phosphate crystals in vitro, TRK-530 may inhibit the formation of dental calculus. Therefore, the present study was performed to examine whether this compound has such an effect. METHODS: Three groups of Wistar rats fed a calculogenic diet (RC16) were treated with TRK-530 in drinking water at concentrations of 0 (control group), 0.75, and 1.5 mM. Another group received a daily subcutaneous injection of TRK-530 at a dose of 2.25 micromoles/rat, which was assumed to correspond to the maximum amount of this compound absorbed from the intestine when rats received 1.5 mM TRK-530 in drinking water. Rat dental calculus formation was evaluated. The crystalline nature of dental calculus was studied by x-ray diffraction analysis. Finally, the effects of TRK-530 on the precipitation of calcium-phosphate from solution were tested in vitro. RESULTS: TRK-530 in drinking water inhibited dental calculus formation dose-dependently. However, subcutaneous injection of TRK-530 did not have any significant effect, suggesting that the anticalculus effect of TRK-530 in drinking water was topical, not systemic. The calculus that formed in both the control and experimental groups was primarily hydroxyapatite, a main constituent of human dental calculus. TRK-530 inhibited the precipitation of calcium-phosphate from solution in vitro. CONCLUSIONS: TRK-530 inhibited the formation of dental calculus in a dose-dependent fashion via a local effect. Inhibition of the precipitation of calcium-phosphate from solution might be involved in the anticalculogenic mechanism of this drug.

Administration, Topical↗

The role of sigma-receptors in levodopa-induced dyskinesia in patients with advanced Parkinson disease: a positron emission tomography study.

OBJECT: Levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD) mimics acute dystonic reactions induced by antipsychotic agents, possibly mediated by sigma-receptors; however, there are few reports in which the relationship between sigma-receptors and LID in advanced PD is investigated. The binding potential of cerebellar sigma-receptors before and after a pallidal surgery for dyskinesia in patients with advanced PD is assessed. METHODS: Six patients with advanced PD (male/female ratio 3:3, age 56.7 +/- 9.8 years) underwent stereotactic pallidal surgery (two posteroventral pallidotomy procedures and four deep brain stimulation of the globus pallidus internus, including one bilateral case). Clinical features of patients with PD were assessed using Hoehn and Yahr (H & Y) stages, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Schwab and England Activities of Daily Life Scale (S & E). The LID was evaluated by LID severity score. The binding potential of cerebellar sigma-receptors was determined before and after the surgery by 11C-nemonapride positron emission tomoraphy, a specific radioligand for sigma-receptors in the cerebellum. All clinical scores, especially the LID severity score, were dramatically improved after the surgery (p < 0.05). Preoperatively, contralateral cerebellar binding potential was significantly elevated (p < 0.01), and it was reduced after the surgery, but it was still higher than that of healthy volunteers (p < 0.05). The ipsilateral cerebellar binding potential remained unchanged after the surgery. The level of binding potential did not correlate with H & Y stage, UPDRS, or S & E score, but a strong positive correlation was seen between the binding potential and the preoperative LID severity score when the patients were receiving medication (r = 0.893, p < 0.05). CONCLUSIONS: Cerebellar sigma-receptors may potentially involve the genesis of LID in advanced PD.

Aged↗

[Changes in food allergen sensitization rates of Japanese allergic children during the last 15 years].

In order to evaluate the changes in food allergen sensitization rates of allergic children, serum samples from 85 patients about 15 years ago (past group) and those from 90 current patients (present group) were randomly selected, and the specific IgE for six food allergens (wheat, peanuts, sesame, mackerel, ovomucoid, and kiwi) were measured with the CAP-RAST system. Sensitivity rates (class 2 or higher) for wheat and peanuts were significantly higher in the present than in the past group. Although there was no statistical difference in sensitivity rates (class 2 or higher) for kiwi between the groups, sensitivity rates (class 1 or higher) of the present group were significantly higher than those of the past group, indicating that the number of cases mildly sensitized to kiwi has been increasing. This trend was especially marked among children aged 6 or younger, and there was no statistical difference in sensitivity rates among those aged 7 or older. For the management of food allergy, special attention should therefore be paid not only to an increase in the number of patients, but also to changes in the kinds of causative foods.

Allergens↗

[Changes in Japanese cedar sensitization rates of Japanese allergic children during the last 15 years].

In order to evaluate the changes in Japanese Cedar (JC) sensitization rates of allergic children, serum samples from 88 patients about 15 years ago (past group) and those from 91 current patients (present group) were randomly selected, and their JC specific IgE were measured with the CAP-RAST system. Sensitivity rate (class 2 or more) for JC of the present group was 65.9%, which was significantly higher than that of the past group, which was 46.6%. However, there was no significant difference between these two groups for children aged 6 or younger. For children aged 7 or older, the sensitivity rate of the present group was significantly higher than that of the past group. Thus, protection against JC sensitization, especially during early childhood, should be given serious attention.

Allergens↗