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Kazuyuki Nakagome

Publications and source records attributed to Kazuyuki Nakagome.

At least 19 recordsLinked to original sources
PubMed2006

Auditory P300 latency prolongation with age in schizophrenia: gender and subcomponent effects.

Previous studies showing prolongation of auditory P300b latency with increasing age provided support for post-onset progressive change in schizophrenia. We sought to extend the findings by evaluating the effects of gender and the subcomponents (P3b versus P3a) in schizophrenia (N=108) and controls (N=70). P3b latency significantly correlated with age in schizophrenia (Spearman's rho=0.214, P=0.026) and in male patients with schizophrenia (rho=0.260, P=0.049) whereas, it did not reach significance in female patients with schizophrenia (rho=0.174, P=0.23). P3a latency showed no correlation. Our findings may provide evidence for progressive change in the brain function in schizophrenia, and this change may be slower in female than male patients. P3b may serve as a more sensitive index for cognitive decline than P3a.

Adult↗
PubMed2006

Phonetic mismatch negativity predicts verbal memory deficits in schizophrenia.

Deficits in auditory sensory memory at the electrophysiological level as indexed by mismatch negativity and those in auditory verbal memory at the neuropsychological level have been independently demonstrated in previous studies of schizophrenia. We predicted a specific association between these indices in schizophrenia. Mismatch negativities elicited by change in tone duration and phoneme duration were recorded in 23 schizophrenia patients, who were also evaluated for auditory verbal memory and executive function. Lower amplitude of mismatch negativity under the phoneme-duration condition was significantly associated with worse verbal memory. Phoneme-duration mismatch negativity was not correlated with executive function, nor was tone-duration mismatch negativity correlated with verbal memory. These results suggest that electrophysiological auditory sensory memory dysfunction underlies the basis for neuropsychological auditory verbal memory deficits in schizophrenia.

Adult↗
PubMed2006

Splenic dendritic cells induced by oral antigen administration are important for the transfer of oral tolerance in an experimental model of asthma.

Peripheral tolerance can be induced after the feeding of Ag, which is referred to as oral tolerance. We demonstrated in this study that the oral administration of OVA induced tolerance in an experimental model of asthma in mice, and investigated which cells function as the regulatory cells in the transfer of this oral tolerance. In OVA-fed mice, the percentage of eosinophils in bronchoalveolar lavage fluid, serum IgE levels, airway hyperresponsiveness, and mRNA levels of IL-13 and eotaxin were significantly lower than found in nonfed mice. Histological examination of lung tissue showed a suppression of the accumulation of inflammatory cells in the peribronchial area of OVA-fed mice. Feeding after the first immunization or between the first and the second immunization suppressed these findings, whereas feeding just before the airway Ag challenge did not. The suppression of disease in OVA-fed mice was successfully transferred by injection of whole spleen cells of OVA-fed mice. When CD11c+ dendritic cells (DCs) were removed from splenocytes, this transfer of suppression was completely abolished. The injection of splenic DCs purified from OVA-fed mice alone transferred the suppression, whereas the injection of splenic DCs from naive mice that were cocultured with OVA in vitro did not. These data suggest that not only CD4+ T cells, but also CD11c+ DCs induced by Ag feeding are important for the active transfer of oral tolerance in this murine experimental model of asthma.

Administration, Oral↗
PubMed2006

Comparison between mismatch negativity amplitude and magnetic mismatch field strength in normal adults.

The auditory mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch field, MMF) has been widely used to assess the ability of stimulus-driven change detection process in humans. The authors evaluated the similarity of inter-individual variation of the response strength between MMN and MMF recordings. Three types of MMN or MMF were recorded in ten healthy subjects: change in duration of pure-tone stimuli, change in duration of the Japanese vowel /a/, and difference between the Japanese vowels /a/ and /o/. There was no significant correlation between MMN amplitude and MMF strength under any condition and in either hemisphere. These results suggest that widely used indices of MMN in the two technologies, i.e., EEG-amplitude and MEG-ECD may not be proportional in an individual. To further clarify the differential significance of recording MMN/MMF may be important to establish MMN/MMF as clinical indices of individual ability of preattentive stage of auditory processing.

Adult↗
PubMed2006

Noninvasive system for evaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis.

Until now there has been no method for physiologically evaluating nasal hypersensitivity in mice. Enhanced pause (Penh) has been used as an indicator that reflects changes in the lower airway. Recently, however, there is disagreement regarding the significance of the Penh system; this is because Penh is not essentially a physiological parameter, and it might not necessarily represent a change in the lower respiratory tract. The purpose of the present study is to investigate whether Penh could be applicable for analyzing nasal hypersensitivity in mice. BALB/c mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal injection and daily intranasal challenge in an awake condition. Penh was measured at each time point during sensitization, or a serial change in Penh value was followed after the final nasal challenge and the effect of treatment was assessed. Following sensitization and nasal challenge, the Penh value gradually increased and showed a significant difference on day 14. Changes in IgE, eosinophil infiltration into nasal mucosa, and OVA-induced symptoms all strongly correlated with the increase in Penh. On day 19, after OVA nasal provocation, Penh gradually increased and reached maximal values 25 min after the challenge. Pretreatment with dexamethasone or a histamine H1 blocker significantly suppressed this increase in Penh. We confirmed that intranasal OVA challenge did not induce bronchoconstriction by measuring airway resistance and bronchoalveolar lavage fluid, and through histological examination. These results clearly demonstrate that Penh could be a useful noninvasive indicator for studying nasal hypersensitivity.

Airway Resistance↗
PubMed2005

A novel role of hepatocyte growth factor as an immune regulator through suppressing dendritic cell function.

Hepatocyte growth factor (HGF) plays an important role in many biological events such as angiogenesis, cell proliferation, anti-fibrosis and antiapoptosis. It is well known that HGF promotes tumor progression and suppresses development of fibrosis after tissue injury. In contrast, its role in immune-mediated disorders has not been fully clarified. In the present study, we examined the role of HGF in Ag-specific immune response using in vitro studies and an experimental model of allergic airway inflammation. We first confirmed that dendritic cells (DCs) expressed the receptor for HGF, c-met, which was not expressed in T cells. Treatment with HGF both in vitro and in vivo potently suppressed DC functions such as Ag-presenting capacity, thus down-regulating Ag-induced Th1- and Th2-type immune responses. Exogenous administration of the HGF expression plasmid into Ag-primed mice markedly suppressed the development of airway eosinophilia and airway hyperresponsiveness, which was induced by Ag inhalation, with suppression of the Ag-presenting capacity of DCs in the lung. HGF exhibited these immunosuppressive effects without up-regulation of IL-10 or TGF-beta. We also found that expression of endogenous HGF in the lung significantly increased following Ag sensitization and inhalation challenges. Finally, neutralization of endogenous HGF in vivo significantly increased airway eosinophilia and airway hyperresponsiveness with up-regulation of the Ag-presenting capacity of DCs in the lung. These results demonstrated a novel, significant, and possibly therapeutic role of HGF as a potent regulator in immune-mediated disorders such as asthma.

Animals↗
PubMed2005

Left frontotemporal hyperperfusion in a patient with post-stroke mania.

A 78-year-old housewife with major depression developed a right-sided infarction in the territory of the middle cerebral arteries, followed by acute post-stroke mania. Comparison between pre- and post-stroke SPECT scans demonstrated a unique pattern of left orbitofrontal hyperperfusion with extensive right frontal hypoperfusion. A functional imbalance between right and left orbitofrontal cortices may be important in mania.

Aged↗
PubMed2005

In vivo IL-10 gene delivery suppresses airway eosinophilia and hyperreactivity by down-regulating APC functions and migration without impairing the antigen-specific systemic immune response in a mouse model of allergic airway inflammation.

IL-10 is an immunosuppressive cytokine. Although previous studies have reported that exogenous delivery of IL-10 reduced airway inflammation in experimental allergic airway inflammation, the mechanism of action has not been fully clarified. In this report, we elucidated a mechanism of action of IL-10 in vivo. BALB/c mice were immunized and aerosol challenged with OVA-Ag. We delivered the IL-10 gene to the mice before systemic sensitization or during aerosol Ag challenge by administering an IL-10-producing plasmid vector. Not only presensitization delivery of IL-10, as reported, but also delivery during inflammation strongly suppressed the development of airway eosinophilia and hyperreactivity. Presensitization delivery suppressed the Ag-specific Th2-type immune response in both the lung and spleen. In contrast, delivery in the effector phase suppressed the Th2 response only in the lung, whereas that in the spleen was not affected. IL-10 gene delivery did not induce the development of a regulatory phenotype of T cells or dendritic cells; rather, it suppressed the overall functions of CD11c(+) APCs of the lung such as Ag-presenting capacity, cytokine production, and transportation of OVA-Ag to lymph nodes, thus attenuating Th2-mediated allergic airway inflammation. Further, IL-10 revealed a distinct immunosuppressive effect in the presence of Ag and APCs. These results suggest that suppression of APC function in the lung, the site of immune response, played a critical role in the IL-10-mediated suppression of Ag-induced airway inflammation and hyperreactivity. Therefore, if delivered selectively, IL-10 could site specifically suppress the Ag-specific immune response without affecting systemic immune responses.

Aerosols↗
PubMed2005

Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting.

BACKGROUND: Airway hyperresponsiveness (AHR) is one of the most prominent features of asthma, however, precise mechanisms for its induction have not been fully elucidated. We previously reported that systemic antigen sensitization alone directly induces AHR before development of eosinophilic airway inflammation in a mouse model of allergic airway inflammation, which suggests a critical role of antigen-specific systemic immune response itself in the induction of AHR. In the present study, we examined this possibility by cell transfer experiment, and then analyzed which cell source was essential for this process. METHODS: BALB/c mice were immunized with ovalbumin (OVA) twice. Spleen cells were obtained from the mice and were transferred in naive mice. Four days later, AHR was assessed. We carried out bronchoalveolar lavage (BAL) to analyze inflammation and cytokine production in the lung. Fluorescence and immunohistochemical studies were performed to identify T cells recruiting and proliferating in the lung or in the gut of the recipient. To determine the essential phenotype, spleen cells were column purified by antibody-coated microbeads with negative or positive selection, and transferred. Then, AHR was assessed. RESULTS: Transfer of spleen cells obtained from OVA-sensitized mice induced a moderate, but significant, AHR without airway antigen challenge in naive mice without airway eosinophilia. Immunization with T helper (Th) 1 elicited antigen (OVA with complete Freund's adjuvant) did not induce the AHR. Transferred cells distributed among organs, and the cells proliferated in an antigen free setting for at least three days in the lung. This transfer-induced AHR persisted for one week. Interleukin-4 and 5 in the BAL fluid increased in the transferred mice. Immunoglobulin E was not involved in this transfer-induced AHR. Transfer of in vitro polarized CD4+ Th2 cells, but not Th1 cells, induced AHR. We finally clarified that CD4+CD62Llow memory/effector T cells recruited in the lung and proliferated, thus induced AHR. CONCLUSION: These results suggest that antigen-sensitized memory/effector Th2 cells themselves play an important role for induction of basal AHR in an antigen free, eosinophil-independent setting. Therefore, regulation of CD4+ T cell-mediated immune response itself could be a critical therapeutic target for allergic asthma.

Animals↗
PubMed2005

Delayed automatic detection of change in speech sounds in adults with autism: a magnetoencephalographic study.

OBJECTIVE: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones. METHODS: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded. RESULTS: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity. CONCLUSIONS: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism. SIGNIFICANCE: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

Acoustic Stimulation↗
PubMed2005

Electrophysiological indices associated with social functioning outcome in schizophrenia: a 5-year follow-up study.

We previously demonstrated that event-related potentials (ERPs), such as N1/N2b amplitudes in an auditory selective attention task, were significantly associated with communication skills of schizophrenia. The present study investigated the relationship between N1/N2b amplitudes and the quality of life (QOL) 5 years after ERP measurement. QOL of 15 patients with schizophrenia was assessed using the quality of life scale (QLS). Correlational analyses revealed a significant relationship between N2b, but not N1, amplitude and specific domains of QOL. N2b amplitude, an electrophysiological index of orienting response, may be associated with longitudinal social functioning outcome in schizophrenia.

Acoustic Stimulation↗
PubMed2004

Association between lower P300 amplitude and smaller anterior cingulate cortex volume in patients with posttraumatic stress disorder: a study of victims of Tokyo subway sarin attack.

Previous investigations of auditory P300 event-related potentials have provided electrophysiological evidence for attentional problems in patients with posttraumatic stress disorder (PTSD). The present study sought to evaluate the relationship between P300 deficits and underlying brain morphological abnormalities in never-treated, comorbidity-free patients with PTSD following the Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and 13 victims without PTSD were identified. Correlational analyses were performed between auditory P300 amplitude at Pz electrode site elicited in an oddball task and anterior cingulate gray matter volume that was shown to be reduced in our previous study using voxel-based morphometry on magnetic resonance imaging. Victims with PTSD showed significantly lower amplitudes of P300 compared with victims without PTSD, and the lower P300 amplitudes at Pz were significantly associated with higher avoidance/numbing scores in the PTSD group. Furthermore, in the PTSD group only, the P300 amplitudes showed a trend toward significant positive correlation with voxel densities of the anterior cingulate cortex gray matter. These results provide the first evidence that electrophysiological deficits of controlled attention observed in patients with PTSD may be linked to underlying brain morphological abnormalities.

Adult↗
PubMed2004

A novel role of cysteinyl leukotrienes to promote dendritic cell activation in the antigen-induced immune responses in the lung.

Although the critical role of cysteinyl leukotrienes (cysLTs) in the inflammation, especially eosinophilic lung inflammation, in asthma has been well documented, their role in the early stage of Ag-specific immune response has not been completely clarified. In the present study, with a mouse model of asthma and in vitro studies we demonstrated that cysLTs potentiated dendritic cell (DC) functions such as Ag-presenting capacity and cytokine production. The cysLT-1 receptor antagonist (LTRA) strongly suppressed the activation of these DC functions and led to inhibition of subsequent not only Th2, but also Th1, responses in the early stage of immune response. Moreover, treatment with LTRA during the early stage of the immune response potently suppressed the development of Ag inhalation-induced eosinophilic airway inflammation, mucus production, and airway hyper-reactivity in vivo. Treatment with LTRA significantly increased PGE(2) production in the lung, and treatment with the cyclooxygenase inhibitor indomethacin abolished LTRA's suppressive effect on DCs and deteriorated the Th2 and Th1 responses and airway inflammation. With in vitro studies, we also confirmed that cysLTs production by DCs increased with LPS stimulation, and that LTRA directly suppressed the alloantigen-presenting capacity of DCs. These results suggested that cysLTs potentiate DC functions both in vivo and in vitro, and that LTRA could be beneficial to suppress the initial immune response in many immune-mediated disorders beyond asthma.

Adjuvants, Immunologic↗
PubMed2004

Brain electric activity for active inhibition of auditory irrelevant information.

We applied high resolution event-related potentials (ERPs) to assess brain activities associated with inhibition of irrelevant information processing during auditory selective attention. Ten healthy subjects performed an auditory selective attention task. ERPs in response to standard stimuli delivered to the unattended ear (irrelevant stimuli) and those delivered to the attended ear (relevant stimuli) were evaluated using temporally sequential scalp current density (SCD) mappings. For the irrelevant stimuli, current sources were located in the mid-frontal regions at 140-220 ms post-stimuli, and these SCD values were significantly larger than those for the relevant stimuli. These results suggest that auditory selective attention process involves not only focusing attention on relevant information, but also inhibitory processing of irrelevant information mediated by the frontal cortex.

Adult↗
PubMed2004

Effects of corollary discharge on event-related potentials during selective attention task in healthy men and women.

Corollary discharge is a brain electrical activity associated with self-monitoring, which distinguishes self from others in thoughts or behaviors. Corollary discharge can be non-invasively assessed using event-related potential (ERP) recordings in humans. Previous studies have revealed that the amplitude of the N100 component elicited during an "odd-ball" task is reduced while a healthy subject is vocalizing, which may index the effect of corollary discharge on auditory ERPs. In this study, we attempted to assess the effect of vocalization on ERP components including N100, mismatch negativity (MMN), negative difference wave (Nd), and P300 during a selective attention task in 22 healthy adults. We also evaluated the possible contribution of gender to these effects. N100 amplitudes elicited by unattended standard stimuli were reduced under the vocalization condition compared with those under the baseline condition. However, there were no significant effects of vocalization on MMN, Nd or P300. Moreover, there was no significant effect of gender to the corollary discharge. These results suggest that the effect of corollary discharge on auditory ERPs is limited to the perceptual stage of information processing in healthy men and women.

Acoustic Stimulation↗
PubMed2004

Executive and prefrontal dysfunction in unipolar depression: a review of neuropsychological and imaging evidence.

This paper reviews recent empirical findings related to prefrontal and executive function in unipolar depression. While a number of reviews have dealt with either the neuropsychological literature or findings from imaging studies, the present review addresses both, as well as findings from studies that have combined brain-imaging techniques with neuropsychological measures. This combined approach is of great interest as the performance of a structured task may act to load the areas of interest and reduce variance, thus making the imaging evidence more valuable; while the use of imaging provides a check that the neuropsychological tasks are indeed engaging the structures whose performance they are intended to assess. Prominent models of the neurobiology of depression implicate involvement of the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). The evidence from combined imaging and neuropsychological studies supports the involvement of the ACC, but is less clear in the case of the DLPFC. However, the limited number of such studies conducted to date means that conclusions must be tentative and further studies employing this combined approach may be of great value.

Animals↗
PubMed2003

Neuromagnetic correlates of impaired automatic categorical perception of speech sounds in schizophrenia.

Schizophrenia is associated with dysfunction in language processing. At the earliest stage of language processing, dysfunction of categorical perception of speech sounds in schizophrenia has been demonstrated in a behavioral task. The aim of this study was to assess automatic categorical perception of speech sounds as reflected by event-related changes in magnetic field power in schizophrenia. Using a whole-head magnetoencephalographic recording, the magnetic counterpart of mismatch negativity (MMNm) elicited by a phonetic change was evaluated in 16 right-handed patients with chronic schizophrenia and in 19 age-, sex-, and parental socioeconomic status-matched normal control subjects. Three types of MMNm (MMNm in response to a duration decrement of pure-tone stimuli; a vowel within-category change [duration decrement of Japanese vowel /a/]; vowel across-category change [Japanese vowel /a/ versus /o/]) were recorded. While the schizophrenia group showed an overall reduction in magnetic field power of MMNm, a trend was found toward more distinct abnormalities under the condition of vowel across-category change than under that of duration decrement of a vowel or tone. The patient group did not show abnormal asymmetries of MMNm power under any of the conditions. This study provides physiological evidence for impaired categorical perception of speech sounds in the bilateral auditory cortex in schizophrenia. The language-related dysfunction in schizophrenic patients may be present at the early stage of auditory processing of relatively simple stimuli such as phonemes, and not just at stages involving higher order semantic processes.

Adult↗