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Biomedical subjects

Hiroshi Matsuda

Publications and source records attributed to Hiroshi Matsuda.

At least 19 recordsLinked to original sources

Neural correlates for learning to read Roman numerals.

This study examined the neuronal correlates of reading Roman numerals and the changes that occur with extensive practice. Subjects were scanned by functional Magnetic Resonance Imaging (fMRI) three times the first day of the experiment and once following two to three months of practice. This allowed comparison of brain activations with varying levels of practice on the same day and across the two to three months of training. The results revealed that upon learning that the alphabetical symbols had numeric meaning subjects immediately activated a network of brain areas, many of which have been previously implicated in numerical processing. Subsequent practice led to a change in the pattern of neuronal activity in only a single region of the mid-dorsolateral prefrontal cortex in the left hemisphere. Implications of these findings are argued with regard to the prevalent neuronal model for the implementation of elementary numerical abilities.

Adult↗

A sensitive gait parameter for quantification of arthritis in rats.

Quantification of arthritis is helpful for investigating pain mechanisms of arthritis and for developing new drugs. We assessed and identified a feasible parameter for quantification of rat arthritis using a novel gait analyzing system. Knee-joint injection with small doses of lambda-carrageenan decreased swing time ratio (STR, swing time of the non-treated hindlimb/swing time of the lambda-carrageenan-injected hindlimb) in a dose-dependent manner. Intraperitoneal treatment with indomethacin restored the decreased STR dose-dependently. The arthritis could not be accurately quantified by swing time and swelling, common indices of arthritis. These results show that STR is a sensitive, reliable parameter for quantification of arthritis.

Animals↗

Empathy and judging other's pain: an fMRI study of alexithymia.

Because awareness of emotional states in the self is a prerequisite to recognizing such states in others, alexithymia (ALEX), difficulty in identifying and expressing one's own emotional states, should involve impairment in empathy. Using functional magnetic resonance imaging (fMRI), we compared an ALEX group (n = 16) and a non-alexithymia (non-ALEX) group (n = 14) for their regional hemodynamic responses to the visual perception of pictures depicting human hands and feet in painful situations. Subjective pain ratings of the pictures and empathy-related psychological scores were also compared between the 2 groups. The ALEX group showed less cerebral activation in the left dorsolateral prefrontal cortex (DLPFC), the dorsal pons, the cerebellum, and the left caudal anterior cingulate cortex (ACC) within the pain matrix. The ALEX group showed greater activation in the right insula and inferior frontal gyrus. Furthermore, alexithymic participants scored lower on the pain ratings and on the scores related to mature empathy. In conclusion, the hypofunction in the DLPFC, brain stem, cerebellum, and ACC and the lower pain-rating and empathy-related scores in ALEX are related to cognitive impairments, particularly executive and regulatory aspects, of emotional processing and support the importance of self-awareness in empathy.

Adult↗

Topical application with a new NF-kappaB inhibitor improves atopic dermatitis in NC/NgaTnd mice.

Growing evidence has demonstrated the crucial role of NF-kappaB activation on disease severity in allergic disorders. In this study, we examined the clinical relevance of a novel NF-kappaB inhibitor, IMD-0354, for atopic dermatitis (AD) by its topical application. To investigate the in vivo efficacy, 1% IMD-0354 ointment was applied daily to NC/NgaTnd mice with severe dermatitis, which served as a model for human AD. During 2 weeks of treatment, scratching behavior decreased and severity of dermatitis reduced in mice treated with IMD-0354 as well as FK506 without diverse effects. Based on histological examinations, the hyperplasia of keratinocytes and infiltration of inflammatory cells were significantly reduced in the skin of IMD-0354-treated mice. The expressions of T-helper 2 cytokines and tumor necrosis factor-alpha at the affected skin sites were downregulated in IMD-0354-treated mice. Furthermore, IMD-0354 suppressed the proliferation of various immunocompetent cells, neurite outgrowth of nerve growth factor-stimulated pheochromocytoma cells, IgE production from splenic B cells, and IgE-mediated activation of mast cells in vitro. IMD-0354 effectively reduced the allergic inflammation in NC/NgaTnd mice in vivo. Thus, a drug that interferes with NF-kappaB activity may provide an alternative therapeutic strategy for the treatment of AD.

Administration, Topical↗

The tyrosine kinase inhibitor imatinib [STI571] induces regression of xenografted canine mast cell tumors in SCID mice.

Canine mast cell tumors (MCTs) are the most common cutaneous tumors in the dog. They have a wide range of behaviour, which can make these tumors challenging to treat. Recently, mutations in c-kit proto-oncogene have been identified in several canine MCTs. Imatinib is the first member of a new class of agents that act by inhibiting particular tyrosin kinase enzymes, including KIT which is a product of the c-kit. In this study the efficacy of imatinib to reduce or abolish canine MCT [CMC-1] using xenografted MCT in severe combined immunodeficient [SCID] mice was evaluated. Imatinib was administered at doses of 200mg/kg and 100mg/kg once a day for one week. The antitumor responses in SCID mice with CMC-1 xenografts following treatment with imatinib were observed. Significant tumor regression occurred with 100mg/kg on days 7, 10, 14 and 21, and 200mg/kg on all days. Our results indicate that imatinib is effective against canine mast cell tumor in mouse xenograft models. Canine MCTs might be a potential target for imatinib therapy.

Animals↗

Changes in cerebral glucose utilization in patients with panic disorder treated with cognitive-behavioral therapy.

Several neuroanatomical hypotheses of panic disorder have been proposed focusing on the significant role of the amygdala and PAG-related "panic neurocircuitry." Although cognitive-behavioral therapy is effective in patients with panic disorder, its therapeutic mechanism of action in the brain remains unclear. The present study was performed to investigate regional brain glucose metabolic changes associated with successful completion of cognitive-behavioral therapy in panic disorder patients. The regional glucose utilization in patients with panic disorder was compared before and after cognitive-behavioral therapy using positron emission tomography with (18)F-fluorodeoxyglucose. In 11 of 12 patients who showed improvement after cognitive-behavioral therapy, decreased glucose utilization was detected in the right hippocampus, left anterior cingulate, left cerebellum, and pons, whereas increased glucose utilization was seen in the bilateral medial prefrontal cortices. Significant correlations were found between the percent change relative to the pretreatment value of glucose utilization in the left medial prefrontal cortex and those of anxiety and agoraphobia-related subscale of the Panic Disorder Severity Scale, and between that of the midbrain and that of the number of panic attacks during the 4 weeks before each scan in all 12 patients. The completion of successful cognitive-behavioral therapy involved not only reduction of the baseline hyperactivity in several brain areas but also adaptive metabolic changes of the bilateral medial prefrontal cortices in panic disorder patients.

Adult↗

Impaired self-awareness and theory of mind: an fMRI study of mentalizing in alexithymia.

Alexithymic individuals have difficulty in recognizing and describing emotions in themselves. We investigated the neuronal basis of mentalizing in alexithymia to determine whether there is a common neuronal substrate associated with knowing the mental states of the self and others. Individuals high in alexithymia (n = 16) and low in alexithymia (n = 14) were selected from a pool of 310 college students using a combination of the Toronto Alexithymia Scale (TAS-20) and the Structured Interview version of the Beth Israel Questionnaire (SIBIQ). We compared the two groups on psychological measures, including ratings of mentalizing and the Interpersonal Reactivity Index (IRI), and regional brain activation using functional magnetic resonance imaging (fMRI) during a mentalizing animation task. The results for both groups showed activation in regions associated with mentalizing: medial prefrontal cortices (MPFC), temporo-parietal junctions (TPJ), and the temporal pole (TP). Alexithymics had lower mentalizing and IRI perspective-taking scores and less activation in the right MPFC. Activity in the MPFC was positively correlated with the mentalizing score and the IRI perspective-taking score. Although there were no group differences in cerebral activity in the TPJ and the TP, the activity in the right TP had a positive correlation with mentalizing and IRI personal distress scores. These results suggest that alexithymic individuals have an impairment in mentalizing associated with an inability to take the perspective of others. Thus, the skills involved in comprehending the self and others are inter-related and play an important role in emotion regulation.

Adult↗

Navigation ability dependent neural activation in the human brain: an fMRI study.

Visual-spatial navigation in familiar and unfamiliar environments is an essential requirement of daily life. Animal studies indicated the importance of the hippocampus for navigation. Neuroimaging studies demonstrated gender difference or strategies dependent difference of neural substrates for navigation. Using functional magnetic resonance imaging, we measured brain activity related to navigation in four groups of normal volunteers: good navigators (males and females) and poor navigators (males and females). In a whole group analysis, task related activity was noted in the hippocampus, parahippocampal gyrus, posterior cingulate cortex, precuneus, parietal association areas, and the visual association areas. In group comparisons, good navigators showed a stronger activation in the medial temporal area and precuneus than poor navigators. There was neither sex effect nor interaction effect between sex and navigation ability. The activity in the left medial temporal areas was positively correlated with task performance, whereas activity in the right parietal area was negatively correlated with task performance. Furthermore, the activity in the bilateral medial temporal areas was positively correlated with scores reflecting preferred navigation strategies, whereas activity in the bilateral superior parietal lobules was negatively correlated with them. Our data suggest that different brain activities related to navigation should reflect navigation skill and strategies.

Adult↗

Relationship between antisocial behavior and regional cerebral blood flow in frontotemporal dementia.

OBJECTIVE: To examine the relationship between antisocial behaviors and reduction of regional cerebral blood flow (rCBF) in patients with frontotemporal dementia (FTD). METHODS: Brain perfusion single photon emission computed tomography (SPECT) was performed in 22 patients with FTD and 76 age-matched healthy volunteers. The statistical analysis was conducted using the SPM99 software. The antisocial behavioral symptoms were assessed independently by three geriatric psychiatrists, who had not been given the information of the SPECT images. RESULTS: Compared with normal controls, FTD patients showed significant reduction of rCBF in the widespread frontal cortical areas. The correlation analysis showed that antisocial behavioral symptoms are associated with reduction of rCBF in the orbitofrontal cortex. CONCLUSION: The functional decline of orbitofrontal cortex is related to antisocial behavioral symptoms in patients with FTD.

Aged↗

Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer's disease.

PURPOSE: The aim of this study was to compare the diagnostic performance of( 18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM) on magnetic resonance imaging (MRI) in the same group of patients with very mild Alzheimer's disease (AD). METHODS: Thirty patients with very mild AD (age 67.0+/-5.8 years; MMSE score 25.5+/-1.2, range 24-28), 32 patients with mild AD (age 67.0+/-4.5 years, MMSE score 22.1+/-0.8, range 21-23) and 60 age- and sex-matched normal volunteers underwent both FDG-PET and three-dimensional spoiled gradient echo MRI. Statistical parametric mapping was used to conduct voxel by voxel analysis and Z score mapping. First, the region of interest (ROI) maps of significant reductions in glucose metabolism and grey matter density in the mild AD patients were defined. Secondly, analysis of receiver operating characteristic (ROC) curves for Z scores in the ROI maps discriminating very mild AD patients and normal controls was performed. RESULTS: In mild AD patients, FDG-PET indicated significant reductions in glucose metabolism in the bilateral posterior cingulate gyri and the right parietotemporal area, while VBM analysis showed a significant decrease in grey matter volume density in the bilateral amygdala/hippocampus complex, compared with the normal control group. ROC analysis showed that in very mild AD patients the accuracy of FDG-PET diagnosis was 89% and that of VBM-MRI diagnosis was 83%. The accuracy of the combination of FDG-PET and VBM-MRI diagnosis was 94%. CONCLUSION: In very mild AD, both FDG-PET and VBM-MRI had high accuracy for diagnosis, but FDG-PET showed slightly higher accuracy than VBM-MRI. Combination of the two techniques will yield a higher diagnostic accuracy in very mild AD by making full use of functional and morphological images.

Aged↗

A new IkappaB kinase beta inhibitor prevents human breast cancer progression through negative regulation of cell cycle transition.

Constitutive nuclear factor-kappaB (NF-kappaB) activity plays a crucial role in the development and progression of lymphoma, leukemia, and some epithelial cancers. Given the contribution of NF-kappaB in carcinogenesis, a novel approach that interferes with its activity might have therapeutic potential against cancers that respond poorly to conventional treatments. Here, we have shown that a new IkappaB kinase beta inhibitor, IMD-0354, suppressed the growth of human breast cancer cells, MDA-MB-231, HMC1-8, and MCF-7, by arresting cell cycle and inducing apoptosis. In an electrophoretic mobility shift assay and a reporter assay, IMD-0354 abolished the NF-kappaB activity in MDA-MB-231 cells in a dose-dependent manner. In the cells incubated with IMD-0354, cell cycle arrested at the G0-G1 phase and apoptotic cells were increased. The expression of some cell cycle regulatory molecules and antiapoptotic molecules was suppressed in cells treated with IMD-0354. On the other hand, cyclin-dependent kinase suppressor p27Kip1 was up-regulated by the addition of IMD-0354. Daily administration of IMD-0354 inhibited tumor expansion in immunodeficient mice into which MDA-MB-231 cells were transplanted. These results indicate that NF-kappaB may contribute to cell proliferation through up-regulation of cell cycle progression; accordingly, inhibition of NF-kappaB activity might have a therapeutic ability in the treatment of human breast cancers.

Animals↗

Food antigen causes TH2-dependent enteropathy followed by tissue repair in T-cell receptor transgenic mice.

BACKGROUND: Clarification of the mechanisms underlying the development of food-sensitive intestinal inflammation will provide an important clue to combating food allergies. OBJECTIVE: To establish a model of intestinal inflammation caused by oral administration of antigen without additional treatments, we focused on the ovalbumin (OVA) 23-3 T-cell receptor transgenic mouse, which had been reported to have high serum antigen-specific IgE responses to the feeding of an egg white diet. METHODS: Changes in body weight of mice fed an egg white diet were monitored throughout the 28-day experimental period. After the 28-day feeding, intestinal tissues were harvested for histologic examination. Endogenous production of cytokines and histamine in the jejunum, and production of cytokines secreted by OVA-specific CD4+ T cells purified from mesenteric lymph nodes, were analyzed. RESULTS: Egg white diet-fed OVA23-3 mice developed weight loss and inflammation with villous atrophy and goblet cell hyperplasia, especially in the jejunum. A further characteristic feature was evidence of weight recovery and tissue repair. Jejunal inflammation was also observed in egg white diet-fed recombination activating gene (RAG)-2-deficient OVA23-3 mice. In addition, tissue sections revealed significant infiltration of specific IgE-positive cells and IgE-positive degranulating mast cells. Higher levels of IL-4 and significant levels of histamine were detected in the tissues. In the supernatant of OVA-stimulated T cells, IL-10 levels were also markedly elevated. CONCLUSION: We report that high-dose and continuous intake of primitive OVA alone induces enteropathy containing regions under repair in OVA23-3 mice. Antigen-specific T cells and inflammatory cells primed by T(H)2 responses play important roles in regulation of development and improvement of the disease. CLINICAL IMPLICATIONS: Long-term antigen intake causes T(H)2-dependent and food-sensitive enteropathy followed by tissue repair.

Animals↗

Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography.

OBJECTIVE: The cause of the reduced regional cerebral blood flow (rCBF) in the posterior cingulate cortex in the early stage of Alzheimer's disease has not been clarified. In Alzheimer's disease, the posterior cingulate cortex itself shows little neuropathologic degeneration, and a hypothesis explaining such a discrepancy is that the functional impairment in the posterior cingulate cortex reflects remote effects caused by degeneration in distant but connected areas, such as the entorhinal cortex. To test the hypothesis, we investigated the functional connectivity between the entorhinal cortex and posterior cingulate cortex. METHODS: Sixty-one patients with probable Alzheimer's disease at a very early stage and 61 age-matched healthy controls underwent both brain structural magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Voxel-based morphometry was performed on MRI data to identify clusters of significantly reduced grey matter concentration in patients with Alzheimer's disease relative to controls, which were set as volumes of interest (VOIs) for correlation analyses of SPECT images. We then used adjusted rCBF values in the VOIs as covariates of interest in statistical parametric mapping. RESULTS: Voxel-based morphometry demonstrated a significant reduction in grey matter concentration in the bilateral entorhinal cortex in Alzheimer's disease. A positive correlation between rCBF in the entorhinal cortex as VOI and that in the limbic and paralimbic systems, including the posterior cingulate cortex, anterior cingulate cortex, lingual gyri and left middle temporal gyrus (P<0.001), was observed in Alzheimer's disease. Control subjects also showed a similar correlation in the limbic and paralimbic systems, but not in the posterior cingulate cortex. CONCLUSION: These results indicate that rCBF changes in the posterior cingulate cortex may be closely related to those in the entorhinal cortex in patients with Alzheimer's disease, thereby supporting the 'remote effect' hypothesis.

Aged↗

[The 27th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (the 30th survey in 2004)].

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals and defect products in FY2004 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 968 institutions among 1,220 to which the questionnaire had been sent. Sixteen cases of adverse reactions were reported. A total of 1,277,906 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 1.3. Eight cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.6.

Adverse Drug Reaction Reporting Systems↗

Regional brain cerebral glucose metabolism and temperament: a positron emission tomography study.

Personality, and in particular temperament, is thought to have a biological basis. In the present study, the relationships between regional brain glucose metabolism and temperament have been investigated. Regional brain glucose metabolism was measured using [18F] fluorodeoxyglucose positron emission tomography in 31 healthy subjects. Temperament was assessed using the Temperament and Character Inventory. Temperament dimensions were observed to be significantly correlated with specific brain regions. In particular, novelty seeking was significantly correlated with the superior temporal gyrus, inferior parietal lobule, and the precuneus, which have been reported to be related with impulsiveness, while reward dependence was significantly correlated with the caudate head, which has been shown to be associated with reward processing. The various aspects of temperament may have biological bases in the specific brain regions. The accumulation of results from studies of this kind should provide further evidence connecting personality traits with their biological bases.

Adult↗

An hour after immunization peritoneal B-1 cells are activated to migrate to lymphoid organs where within 1 day they produce IgM antibodies that initiate elicitation of contact sensitivity.

Elicitation of contact sensitivity (CS), a classic example of T cell-mediated immunity, requires Ag-specific IgM Abs to trigger an initiation process. This early process leads to local recruitment of CS-effector T cells after secondary Ag challenge. These Abs are produced by the B-1 subset of B cells within 1 day after primary skin immunization. In this study we report the surprising observation that B-1 cells in the peritoneal cavity are activated as early as 1 h after naive mice are painted with a contact-sensitizing Ag on the skin of the trunk and feet to begin the initiation of CS. B-1 cells in the spleen and draining lymph nodes produce the initiating Abs by 1 day after immunization, when we found increased numbers of Ag-specific IgM Ab-producing cells in these tissues by ELISPOT assay. Importantly, we show that contact-activated peritoneal B-1 cells migrate to these lymphoid tissues and then differentiate into Ag-specific IgM Ab-producing cells, resulting in specific CS-initiating IgM Abs in the serum by 1 day. Furthermore, pertussis toxin, which is known to inhibit signaling via G protein-coupled chemokines, inhibited the migration of contact-activated peritoneal B-1 cells to the lymphoid tissues, probably due to BLR-1 (Burkitt lymphoma receptor-1). These findings indicate that within 1 h after contact skin immunization, B-1 cells in the peritoneal cavity are activated to migrate to the lymphoid tissues by chemokine-dependent mechanisms to produce serum Ag-specific IgM Abs within 1 day after immunization, leading to local recruitment of CS-effector T cells.

Animals↗