Biomedical subjects

Masatoshi Itoh

Publications and source records attributed to Masatoshi Itoh.

At least 37 records · Page 2Linked to original sources

PubMed2003

Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease.

OBJECTIVES: Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D2 receptor density in Alzheimer's disease (AD). METHODS: Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [11C]raclopride (D2 antagonist). The uptake of [11C] raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg). RESULTS: There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients. CONCLUSIONS: Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD.

Aged↗

PubMed2003

FDG-PET imaging of lower extremity muscular activity during level walking.

We analyzed muscular activity of the lower extremities during level walking using positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG). We examined 17 healthy male subjects; 11 were assigned to a walking group and 6 to a resting group. After (18)F-FDG injection, the walking group subjects walked at a free speed for 15 min. A whole-body image was then obtained by a PET camera, and the standardized uptake ratio (SUR) was computed for each muscle. The SUR for each muscle of the walking group was compared with that for the corresponding muscles in the resting group. The level of muscular activity of all the muscles we examined were higher during level walking than when resting. The activity of the lower leg muscles was higher than that of the thigh muscles during level walking. The muscular activity of the soleus was highest among all the muscles examined. Among the gluteal muscles, the muscular activity of the gluteus minimus was higher than that of the gluteus maximus and gluteus medius. The concurrent validity of measuring muscular activity of the lower extremity during level walking by the PET method using (18)F-FDG was demonstrated.

Adult↗

PubMed2003

Imaging of central itch modulation in the human brain using positron emission tomography.

The unpleasantness of itching is reduced by cooling. Although previous research suggests the presence of a central itch modulation system, there is little documentation about the modulation system in the brain. In the present study, we investigated the modulating system of the itching sensation in human brains using positron emission tomography and H(2) (15)O. The significant increases of regional cerebral blood flow caused by histamine stimuli using iontophoresis were observed in the anterior cingulate cortex (BA24), the thalamus, the parietal cortex (BA40 and BA7), the dorsolateral prefrontal cortex (BA46) and the premotor cortex (BA6). We did not observe any changes in the secondary somatosensory cortex (S2) during the itching stimulus, corresponding to the previous imaging studies concerning itching. Activation in these areas related to itching stimuli was decreased by a simultaneous stimulation of itching and cold pain (the dual stimuli), as compared to itching alone. Interestingly, the midbrain, including periaqueductal gray matter (PAG), was only activated during the dual stimuli. PAG is well known to be a modulating noxious stimulus. Here we hypothesize that the activation of PAG may also be related to the itch modulation. These findings indicate that the modified brain activities in the PAG, the cingulate, the frontal and the parietal cortex might be associated with the itch modulation in the central nervous system and that the S2 might not be primarily involved in processing the itching perception in the brain since the activity of S2 was not observed in any concentration of itching stimuli.

Adult↗

PubMed2003

Analysis of numbers of repeated units in R2 region among varicella-zoster virus strains.

BACKGROUND: A variable region, R2, on the varicella-zoster virus (VZV) genome contains a repeated 42-bp unit. OBJECTIVE: The purpose of this study is the derivation of significance from tandem reiteration structure in the R2 region. METHODS: Fifty-two specimens were collected from 52 patients with herpes zoster in Osaka and Tokyo, Japan. After treatment of the specimens to release viral DNA, the samples were amplified directly by polymerase chain reaction. In addition, 14 samples were collected from 7 of these zoster patients after valaciclovir or aciclovir therapy. RESULTS: Analyses of the 52 specimens revealed that the number of repeats ranged from 4 to 13. Interestingly, the numbers of repeats among various VZV strains showed a normal distribution pattern, so that 6-9 repeats were found to be predominant in both Osaka (85%) and Tokyo (72%). The pre- and post-treatment strains taken from the same individuals showed the same numbers of repeats (7-9 in 6 cases and 11 in one). CONCLUSION: Our results suggest that the 6-9 repetitions of the 42-bp unit, with presumed stability, may offer these virus strains an advantage in virulence to human skin.

Acyclovir↗

PubMed2003

Thinking of the future and past: the roles of the frontal pole and the medial temporal lobes.

Human lesion data have indicated that the frontal polar area might be critically involved in having an insight into one's future. Retrospective memory mediated by medial temporal lobes and related structures, on the other hand, could be used to extract one's future prospects efficiently. In the present study, we investigated the roles of these two brain structures in thinking of the future and past by using positron emission tomography (PET) and a naturalistic task setting. We measured regional cerebral blood flow (rCBF) in healthy subjects while they were talking about their future prospects or past experiences, with regard to two different temporal windows (in years or days). Many areas in the frontal and the medial temporal lobes were activated during the future and past tasks compared with a control task requiring semantic retrieval. Among these, areas in anteromedial frontal pole showed greater activation during the future tasks than during the past tasks, showing significant effect of temporal distance from the present. Most areas in the medial temporal lobes showed greater or equivalent level of activations during the future tasks compared with the past tasks. The present results suggest that thinking of the future is closely related to retrospective memory, but that specific areas in the frontal pole and the medial temporal lobes are more involved with thinking of the future than that of the past.

Adult↗

PubMed2003

Difference spectra measurement of squid rhodopsin in the submillimeter wave region.

Theoretical studies by computer simulation have shown that vibrational modes, which depend on the subdomain motions of proteins, are located in the submillimeter wave region (i.e., 10-100 cm(-1)], 0.3-3 THz). We have successfully observed, by measuring the difference spectrum between squid rhodopsin and metarhodopsin to avoid water absorption, that squid rhodopsin shows its absorption features in this region. Our experimental results show that a native protein in solution indicates not only an absorbent property in this region but also an actual change of absorption with changes in protein conformation.

Animals↗

PubMed2003

Specific brain processing of facial expressions in people with alexithymia: an H2 15O-PET study.

Alexithymia is a personal trait characterized by a reduced ability to identify and describe one's own feelings and is known to contribute to a variety of physical and behavioural disorders. To elucidate the pathogenesis of stress-related disorders and the normal functions of emotion, it is important to investigate the neurobiology of alexithymia. Although several neurological models of alexithymia have been proposed, there is very little direct evidence for the neural correlates of alexithymia. Using PET, we studied brain activity in subjects with alexithymia when viewing a range of emotional face expressions. Twelve alexithymic and 12 non-alexithymic volunteers (all right-handed males) were selected from 247 applicants on the basis of the 20-item Toronto Alexithymia Scale (TAS-20). Regional cerebral blood flow (rCBF) was measured with H(2)(15)O-PET while the subjects looked at angry, sad and happy faces with varying emotional intensity, as well as neutral faces. Brain response in the subjects with alexithymia significantly differed from that in the subjects without alexithymia. The alexithymics exhibited lower rCBF in the inferior and middle frontal cortex, orbitofrontal cortex, inferior parietal cortex and occipital cortex in the right hemisphere than the non-alexithymics. Additionally, the alexithymics showed higher rCBF in the superior frontal cortex, inferior parietal cortex and cerebellum in the left hemisphere when compared with the non-alexithymics. A covariance analysis revealed that rCBF in the inferior and superior frontal cortex, orbitofrontal cortex and parietal cortex in the right hemisphere correlated negatively with individual TAS-20 scores when viewing angry and sad facial expressions, and that no rCBF correlated positively with TAS-20 scores. Moreover, the anterior cingulate cortex and insula were less activated in the alexithymics' response to angry faces than their response to neutral faces. These results suggest that people with alexithymia process facial expressions differently from people without alexithymia, and that this difference may account for the disorder of affect regulation and consequent peculiar behaviour in people with alexithymia.

Adult↗

PubMed2003

High social desirability and prefrontal cortical activity in cancer patients: a preliminary study.

BACKGROUND: Social desirability is sometimes associated with poor prognosis in cancer patients. Psycho-neuro-immune interaction has been hypothesized as an underlying mechanism of the negative clinical outcome. Purpose of this study was to examine possible effects of high social desirability on the regional brain activity in patients with malignant diseases. MATERIAL/METHODS: Brain metabolism of 16 patients with various malignant diseases was measured by PET with 18F-fluorodeoxyglucose (FDG). Patients were divided into 2 groups using median split on Marlowe & Crown's Social Desirability Scale (MC), controlling for age, gender, and for severity of depression and anxiety, the possible two major influential factors. A group comparison of the regional cerebral activity was calculated on a voxel-by-voxel basis using statistical parametric mapping (SPM). RESULTS: The subgroup comparison showed that the high social desirability was associated with relatively increased metabolism in the cortical regions in the prefrontal, temporal and occipital lobes as well as in the anterior cingulate gyrus. CONCLUSIONS: High social desirability seems to be associated with increased activity in the prefrontal and other cortical areas. The finding is in an accordance with previous studies that demonstrated an association between prefrontal damage and anti-social behavior. Functional neuroimaging seems to be useful not only for psychiatric evaluation of major factors such as depression and anxiety but also for further psychosocial factors in cancer patients.

Adult↗

PubMed2002

Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain.

Brain histamine is involved in a wide range of physiological functions such as regulation of the sleep-wake cycle, arousal, cognition, and memory mainly through interactions with histamine H1 receptors (H1Rs). Neurons producing histamine, histaminergic neurons, are exclusively located in the posterior hypothalamus and transmit histamine to almost all regions of the brain. Histamine H1 antagonists, or antihistamines, often prescribed for treatment of allergic disorders, sometimes induce sleepiness and cognitive deficits. It is understood that the mechanism of such CNS side effects is that antihistamine blocks H1Rs in the brain. The purpose of the present study was to compare the CNS side effects of different antihistamines. Subjective sleepiness was measured using the Stanford Sleepiness Scale (SSS) and psychomotor performance was examined by a tachistoscope testing system in healthy, young, Japanese volunteers (16 males, 20-28 yrs.) before and after oral administration of antihistamines such as fexofenadine (FEX) and cetirizine (CET). Additionally, H1R occupancy by antihistamines was examined by PET with 11C-doxepin in 8 volunteers. The results of SSS and psychomotor tests demonstrated that FEX tended to be less sedative than CET though the difference was not statistically significant. PET measurements revealed that no H1Rs in the cerebral cortex were occupied by FEX while about 30% of H1Rs were occupied by CET. In summary, it was confirmed that histamine and H1Rs are involved in maintaining arousal and cognition in humans, and that the severity of clinical symptoms is correlated to the amount of antihistamine that penetrated into the brain.

Adult↗

PubMed2002

Time-dependent contribution of the hippocampal complex when remembering the past: a PET study.

Previous studies of brain-damaged patients and functional neuro-imaging have consistently shown the importance of the hippocampal complex, i.e. the hippocampus and parahippocampal gyrus, in episodic memory retrieval. We wished to determine whether patterns of brain activation during memory retrieval as measured by PET are same or different when the oldness of a to-be-retrieved episode is manipulated. Using cue words, subjects remembered related episodes from three periods of their life, childhood, adolescence and recent period. The results showed an increase of parahippocampal activities during recall of episodes from childhood and recent period, but not from adolescence. These data suggest a possibility of time-dependent hippocampal contribution in episodic recall, which cannot be understood in simple terms of recent remote memory dichotomy.

Adolescent↗

PubMed2002

The effects of a sedative antihistamine, d-chlorpheniramine, on visuomotor spatial discrimination and regional brain activity as measured by positron emission tomography (PET).

Although most people taking antihistamines have experienced sedation and impaired performance, the neural correlates of these sedative properties are not well understood in man. Brain imaging can be used to demonstrate how regional brain activities are altered during such sedative effects. The aim of this study was to visualize the brain mechanism of impaired visuomotor spatial cognition with orally administered d-chlorpheniramine, a first-generation sedative antihistamine, using H(2) (15)O and positron emission tomography (PET). Normal subjects were randomly assigned to two groups (chlorpheniramine and placebo) and performed a spatial discrimination task after the oral administration of 6 mg d-chlorpheniramine or a placebo. The administration of d-chlorpheniramine impaired visuomotor spatial discrimination and altered cortical and subcortical activity. Decreased and increased activities were observed in the right parietal cortex (BA 40) which is related to visuomotor spatial cognition and the posterior cingulate cortex which constitutes the attention system of the brain, respectively. In particular, the brain activities of BA 40 were negatively and positively correlated to those of bilateral caudate nuclei and the dorsolateral prefrontal cortex, respectively. These findings clearly suggest that the alteration in the cortical and subcortical activity contributes to impaired spatial cognition caused by treatment with d-chlorpheniramine.

Adult↗

PubMed2002

The role of the basal forebrain in episodic memory retrieval: a positron emission tomography study.

Human lesion data indicate that the basal forebrain or orbitofrontal cortex, or both, as well as medial temporal and diencephalic structures, is important for normal memory and that its disruption causes the pure amnesic syndrome, in which episodic memory is grossly impaired while other kinds of memory remain preserved. Among these critical areas, functional imaging studies have so far failed to detect activation of the basal forebrain, although activation in the nearby orbitofrontal cortex has been reported during episodic memory retrieval. We employed positron emission tomography to elucidate the neural basis of episodic memory recall utilizing two types of time cues and successfully detected activity in the basal forebrain for the first time. Specifically, recall of previously memorized words from temporal cues was associated with activity in the basal forebrain, right middle frontal gyrus, right superior temporal gyrus, and posterior cingulate gyrus, whereas their recall from person cues was associated with activity in the left insula, right middle frontal gyrus, and posterior cingulate gyrus. Furthermore, percentage increases of regional blood flow in the basal forebrain were correlated with behavioral data of successful recall. Our results provide clear evidence that the human basal forebrain has a specific role in episodic memory recall, especially that from time-contextual information.

Adult↗

PubMed2002

Encoding-related brain activity during deep processing of verbal materials: a PET study.

The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.

Adult↗

PubMed2002

Neuroanatomical correlates of low body weight in Alzheimer's disease: a PET study.

Weight loss is a common problem in patients with Alzheimer's disease (AD) and this might be associated with an increased risk for mortality. Recent evidences have suggested that certain brain dysfunctions may result in impaired nutritional status in AD patients. However, the mechanism of body weight loss in AD remains enigmatic. To investigate a possible association between low body weight and regional brain dysfunction, the authors conducted the correlational analysis of body mass index (BMI) with regional brain glucose metabolism using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Twenty-seven patients with probable AD were divided into two groups: the low BMI group and the normal BMI group. Regional brain glucose metabolic ratios were calculated using the cerebellar hemisphere as a reference region. Comparisons were made of regional brain metabolic ratios between the low BMI group and the normal BMI group. Correlations of the glucose metabolic ratio with BMI were also assessed in all patients with AD. In the comparison between the two groups, glucose metabolic ratio in the anterior cingulate cortex (ACC) was significantly lower in the low BMI group, whereas no significant differences were found in all the other brain regions. Furthermore, regional glucose metabolism in the ACC had a significant and positive correlation with BMI (r=.450, P=.018). After adjustment for age, gender and disease duration, regional glucose metabolism in the ACC was independently associated with BMI. Our findings suggest that the ACC may be preferentially involved in the regulation of nutritional status in AD patients, and provides a new insight into developing strategies for prevention and treatment of undernutritional demented patients.

Age Factors↗

PubMed2002

A novel bisphosphonate inhibits inflammatory bone resorption in a rat osteolysis model with continuous infusion of polyethylene particles.

This study examined the inhibitory effect of a new bisphosphonate (TRK-530) on wear debris-mediated bone resorption in a rat osteolysis model involving continuous infusion of high density polyethylene (HDPE) particles. TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Forty Wistar rats were randomized to two groups (n = 20 each). In each rat, a Kirshner (K) wire was inserted into the femur and HDPE particles were continuously infused into the knee joint. Thereafter, the animals were subcutaneously injected with saline (control group) or 1 mg/kg of TRK (TRK group) every second day, and were sacrificed at 4 or 8 weeks after surgery. Radiographs obtained at the time of sacrifice were evaluated for periprosthetic osteolysis. We also examined the thickness of the reactive membrane as well as the number of osteoclast-like cells around the K-wire. In addition, we examined the expression of genes for bone-resorbing cytokines in the reactive membrane. Radiographic peri-implant osteolysis was more frequent in the control group compared with the TRK group at each time of assessment (p < 0.01). The interfacial membrane was significantly thinner in the TRK group compared with the control group (p < 0.01) and the average number of osteoclast-like cells around the K-wire was significantly fewer in the TRK group (p < 0.01). In addition, the expression of interleukin 1-alpha messenger ribonucleic acid (IL-1alpha mRNA) and TNF-alpha mRNA was suppressed in the TRK group at each time of assessment. We conclude that the TRK can inhibit the formation of inflammatory peri-implant osteolysis induced by HDPE particles.

Animals↗

PubMed2002

Differential cognitive effects of ebastine and (+)-chlorpheniramine in healthy subjects: correlation between cognitive impairment and plasma drug concentration.

AIMS: It has been widely recognized that classical antihistamines induce sedation as an adverse effect, while second-generation antihistamines have few if any sedative effects. In order to evaluate the sedative properties of ebastine, a second-generation antihistamine, its effect on cognitive performance in healthy subjects was compared with placebo and (+)-chlorpheniramine. METHODS: Twelve healthy male subjects were instructed to perform six types of attention-demanding cognitive tasks, and objective measurements of reaction times and accuracy was made before and after drug administration. Their sleepiness levels were also monitored. Test drugs were ebastine 10 mg, placebo and two doses of (+)-chlorpheniramine 2 mg and 6 mg, as positive controls. Plasma drug concentrations at the end of the study were analysed. RESULTS: After treatments with (+)-chlorpheniramine, the reaction times of the tasks were significantly prolonged (e.g. ratios of after/before dosing: placebo (0.998 +/- 0.113) vs (+)-chlorpheniramine 2 mg (1.103 +/- 0.083; P<0.05) or (+)-chlorpheniramine 6 mg (1.170 +/- 0.139; P<0.001) in a 7 ms visual discrimination time task) and the accuracy was significantly decreased (e.g. ratios: placebo (1.038 +/- 0.158) vs (+)-chlorpheniramine 2 mg (0.792 +/- 0.202; P<0.01) or (+)-chlorpheniramine 6 mg (0.837 +/- 0.222; P<0.05) in a 7 ms task). On the other hand, performance was not affected by ebastine or placebo treatment (e.g. ebastine 10 mg (reaction time ratio; 1.014 +/- 0.067 and accuracy ratio; 0.990 +/- 0.146) in a 7 ms task). Subjective sleepiness was also not affected by ebastine but (+)-chlorpheniramine significantly increased sedation. With respect to the relationship between plasma drug concentrations and task performance, the latter deteriorated with an increase in plasma (+)-chlorpheniramine concentration (e.g. r=0.439 (P=0.007) in a 5 ms and r = 0.352 (P=0.039) in a 7 ms task), but it did not correlate with the plasma concentration of carebastine, an active metabolite of ebastine. CONCLUSIONS: Ebastine 10 mg did not cause any cognitive impairment or subjective sleepiness. On the other hand, (+)-chlorpheniramine impaired cognitive function and induced sleepiness even at 2 mg, the recommended dose in over-the-counter medication. In addition, impaired CNS performance was significantly correlated with plasma (+)-chlorpheniramine concentration.

Administration, Oral↗

PubMed2002

Schnitzler's syndrome with IgG kappa gammopathy.

A seventy-year-old man with a variant type of Schnitzler's syndrome is reported. Physical examination showed pruritic urticarial lesions on the extremities, arthralgia of knee joints, and intermittent fever. Laboratory investigations revealed a high level of IgG, an increased enythrocyte sedimentation rate, urinary Bence-Jones protein, and an M-bow in serum protein electrophoresis, which was shown to be a monoclonal IgG kappa type. Histological examination showed perivascular neutrophil and lymphocytic infiltration into the upper dermis and diffuse neutrophilic infiltration in the middle dermis. One of the clinical features of typical Schnitzler's syndrome is IgM macroglobulinemia, and this is a very rare case of this syndrome with IgG gammopathy.

Aged↗

PubMed2002

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease.

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.

Aged↗