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Biomedical subjects

Atsushi Matsumoto

Publications and source records attributed to Atsushi Matsumoto.

At least 19 recordsLinked to original sources
PubMed2006

Volume of left amygdala subregion predicted temperamental trait of harm avoidance in female young subjects. A voxel-based morphometry study.

We investigated the relationship between temperamental predisposition and brain structure by using a standard questionnaire and high-resolution T1-weighted magnetic resonance image (MRI) in normal young volunteers. Fifty-six subjects completed the Japanese version of the Temperament and Character Inventory (TCI, 125 items) and underwent an MRI acquisition of the brain. The gray matter (GM) was extracted from the whole brain image of the subjects and normalized to the standard brain template using statistical parametric mapping and the optimized voxel-based morphometry (VBM) method. When the score on the harm avoidance (HA) subscale was used as a dependent variable, the multiple regression analysis revealed that the HA score positively correlated with the volume of the part of left amygdala. The region-of-interest analysis showed that the correlation was significant in the female subjects but not in the male subjects. The correlation was significant even after the effects of age, depression score, and total GM volume were taken into account. The differential correlation between the sexes may be caused by differences in hormonal condition and the vulnerability of women to socio-psychological stress. In addition, the novelty seeking (NS) score positively correlated with the GM of the left middle frontal gyrus. The volume of the tail of the right caudate nucleus positively correlated with the reward dependence (RD) score. With regard to the NS and RD scores, no significant sex difference was observed in the correlation. These results indicate that the temperamental traits measured using the questionnaire may have a morphological basis in the human brain.

Adult↗
PubMed2006

Restoration of natural IgM production from liver B cells by exogenous IL-18 improves the survival of burn-injured mice infected with Pseudomonas aeruginosa.

Pseudomonas aeruginosa is the most common bacterium of postburn infection. In the present study we investigated the immune mechanism of susceptibility to this type of postburn infection and also examined the efficacy of IL-18 treatment. C57BL/6 mice were challenged with P. aeruginosa on day 7 after burn injury. Although the burn-injured mice showed a poor survival rate after bacterial challenge, they retained their IFN-gamma production. The burned mice showed lower serum IgM levels and a poor IgM response following P. aeruginosa challenge in comparison with the sham mice, whereas IL-18 treatment after burn injury (alternate day injections for 1 wk) greatly improved the serum IgM levels, which are P. aeruginosa-independent natural IgM before bacterial challenge, thereby increasing the survival rate after the challenge. IL-18 treatment also induced specific IgM to P. aeruginosa in the sera 5 days after bacterial challenge in the burned mice. Interestingly, CD43(+)CD5(-)CD23(-)B220(dim) cells, namely B-1b cells, increased in the liver after the IL-18 treatment and were found to actively produce IgM in vitro without any additional stimulation. Furthermore, the IL-18 treatment up-regulated the neutrophil count and the C3a levels in the blood as a result of the increased IgM level, which may thus play a critical role in the opsonization and elimination of any invading bacteria. IL-18 treatment for the burned mice and their resultant natural IgM production were thus found to strengthen the host defense against P. aeruginosa infection.

Animals↗
PubMed2006

A critical role of CpG motifs in a murine peritonitis model by their binding to highly expressed toll-like receptor-9 on liver NKT cells.

BACKGROUND: Toll-like receptor (TLR)-9 plays a critical role in the recognition of the CpG motifs, which is frequently observed in bacterial DNA. To date, there have not been any reports regarding the role of bacterial DNA in the systemic circulation on the development of sepsis. METHODS: We examined the expression of TLR-9 in the liver and spleen in a murine peritonitis model (CLP mice). We also measured the cytokine response of mononuclear cells (MNCs) from normal and CLP mice to CpG oligodeoxynucleotides (ODN) in vitro and in vivo. RESULTS: TLR-9 expression on F4/80(+) and NK1.1(+)CD3epsilon(+) cells in the liver of CLP mice was elevated compared to sham-operated mice. With regard to cytokine production, we found that CpG ODN markedly stimulated the production of inflammatory cytokines by murine macrophages and liver MNCs. The intravenous injection of CpG ODN in mice that underwent CLP 12h earlier led to their increased cytokine production and their increased mortality. In addition, the depletion of NK/NKT cells contributed to improve their survival rate. CONCLUSIONS: Our results suggest that, in patients with overwhelming bacterial infection, bacterial DNA may induce liver toxicity that is mediated by liver NKT cells and macrophages that express high levels of TLR-9.

Adjuvants, Immunologic↗
PubMed2006

Frontoparietal network involved in successful retrieval from episodic memory. Spatial and temporal analyses using fMRI and ERP.

The neural basis for successful recognition of previously studied items, referred to as "retrieval success," has been investigated using either neuroimaging or brain potentials; however, few studies have used both modalities. Our study combined event-related functional magnetic resonance imaging (fMRI) and event-related potential (ERP) in separate groups of subjects. The neural responses were measured while the subjects performed an old/new recognition task with pictures that had been previously studied in either a deep- or shallow-encoding condition. The fMRI experiment showed that among the frontoparietal regions involved in retrieval success, the inferior frontal gyrus and intraparietal sulcus were crucial to conscious recollection because the activity of these regions was influenced by the depth of memory at encoding. The activity of the right parietal region in response to a repeated item was modulated by the repetition lag, indicating that this area would be critical to familiarity-based judgment. The results of structural equation modeling revealed that the functional connectivity among the regions in the left hemisphere was more significant than that in the right hemisphere. The results of the ERP experiment and independent component analysis paralleled those of the fMRI experiment and demonstrated that the repeated item produced an earlier peak than the hit item by approximately 50 ms.

Brain Mapping↗
PubMed2006

Cooperative IFN-gamma production of mouse liver B cells and natural killer cells stimulated with lipopolysaccharide.

BACKGROUND/AIMS: Although mouse liver contains a large population of B cells, little is known about how hepatic B cells respond to bacterial lipopolysaccharide (LPS). METHODS: The cytokine and IgM productions of hepatic B cells were compared with those of splenic B cells. The effect of LPS-treated hepatic B cells on IFN-gamma production from co-cultured NK1.1+ cells was also examined by irradiation and transwell experiments. RESULTS: Hepatic B cells stimulated with LPS produced substantial amounts of IFN-gamma and IL-12 but a small amount of IgM, while splenic B cells did not produce any of these cytokines but produced a large amount of IgM. The hepatic B cells expressed surface markers similar to those on spleen B cells but expressed more C-X-C chemokine receptor 3 than spleen B cells. Notably, depletion of B220+ cells from liver MNCs (but not from spleen MNCs) greatly decreased LPS-induced IFN-gamma production. Furthermore, LPS-treated hepatic B cells stimulated liver NK1.1+ cells to produce a remarkable amount of IFN-gamma, not only through their soluble factors but also through direct cell-cell contact. CONCLUSIONS: Liver B cells may play an important role in the defense against gram-negative bacterial infections by inducing IFN-gamma production from liver NK cells.

Animals↗
PubMed2006

Hemodynamic and electrophysiological relationship involved in human face processing: evidence from a combined fMRI-ERP study.

Functional magnetic resonance imaging (fMRI) and event-related potential (ERP) experiments were conducted in the same group of subjects and with an identical task paradigm to investigate a possible relationship between hemodynamic and electrophysiological responses within the brain. The subjects were instructed to judge whether visually presented stimuli were faces or houses and then press the corresponding button. Functional MRI identified face- and house-related regions in the lateral and medial part of the fusiform gyrus, respectively, while ERP showed significantly greater N170 negativity for face than for house stimuli in the temporo-occipital electrodes. Correlation analysis between the BOLD signal in the fusiform gyrus and ERP parameters demonstrated a close relationship between the signal and both latency and amplitude of N170 across the subjects. These correlations may indicate that the variation in cognitive demand and hemodynamic responses during the face/house discrimination task is coupled with the variation of N170 peak latency/amplitude across the subjects. Thus, integrative analysis of spatial and temporal information obtained from the two experimental modalities may help in studying neural correlates involved in a particular cognitive task.

Adult↗
PubMed2006

Gamma band activity and its synchronization reflect the dysfunctional emotional processing in alexithymic persons.

In the present study, we investigated the gamma band response and its phase synchrony between electrodes in alexithymia, which is characterized by a disability in identifying and describing feelings. Individuals with high and low alexithymia scores were selected according to the scores on the 20-item Toronto Alexithymia Scale. EEG was recorded from alexithymic and nonalexithymic persons viewing emotionally negative or neutral stimuli. Nonalexithymic persons exhibited increased gamma band power and phase synchronization at the 400-450-ms time window when processing emotionally negative stimuli. Neither enhanced gamma band power nor phase synchronization was observed in alexithymic persons in the negative emotion condition. These results suggest that gamma band activity reflects emotional processing, and alexithymic persons may have a deficit in communication between brain regions or in the utilization of memory or emotional information during the processing of emotional stimuli.

Adult↗
PubMed2005

A variant C178T in the regulatory region of the serotonin receptor gene HTR3A modulates neural activation in the human amygdala.

Converging evidence in neurophysiological and neuroimaging studies has suggested that the limbic and prefrontal systems play important roles in emotion and cognition. These structures are activated when we see a human face, assuming that we automatically evaluate the biological significance of the stimuli. The serotonin (5-HT) system within the brain has been tied to various behaviors such as mood and anxiety and to the biology of neuropsychiatric disorders. To investigate the link between the 5-HT system and limbic/prefrontal activity, normal subjects (n = 26) who underwent functional magnetic resonance imaging and faced recognition tasks were genotyped for the single nucleotide polymorphism C178T in the regulatory region of the serotonin receptor type 3 gene (HTR3A). We found that the subjects with C/C alleles had greater activity in the amygdala and dorsal and medial prefrontal cortices than those with C/T alleles. The C/C group also showed a faster reaction time during the task than the C/T group. The temperamental predisposition of the subjects had a significant correlation with brain activity in the C/C group. The genotype effect in the right amygdala and prefrontal cortex was largest during the first run of the experiment. These results indicate that the C178T variation in the HTR3A has a critical influence on the amygdaloid activity and on human face processing, probably through regulation of the receptor expression. The present study may contribute to elucidating a possible link among genes, the brain, and behavior in normal populations and may help reveal the biological basis of neuropsychiatric disorders.

Adult↗
PubMed2005

Enhanced apoptosis and tumor regression induced by a direct agonist antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2.

PURPOSE: Substantial evidence indicates that supraoligomerization of the death receptors for Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is necessary for efficient activation of the apoptotic pathway. Bivalent IgG antibodies can induce the efficient apoptosis by mimicking the natural ligands but only after these antibodies are further oligomerized by cross-linking. In this study, we generated a novel agonist antibody to TRAIL receptor 2 (TRAIL-R2) capable of inducing apoptosis without cross-linking and elucidated its mode of action and efficacy. EXPERIMENTAL DESIGN: A fully human antibody to TRAIL-R2, KMTR2, was generated from KM Mouse immunized with TRAIL-R2 ectodomain. Apoptosis-inducing activities of unfractionated or purified monomeric IgG of KMTR2 was evaluated in the presence or absence of cross-linkers, secondary antibodies or Fc receptor-expressing effector cells, against human colorectal adenocarcinoma Colo205. Oligomerization of TRAIL-R2 was analyzed by size exclusion chromatography and confocal microscopy, and in vivo efficacy was examined in Colo205 xenograft model. RESULTS: KMTR2 specifically recognized TRAIL-R2 and induced apoptosis with or without cross-linking. Size exclusion chromatography showed that the apoptosis activity coeluted with monomeric IgG and was effective independent of secondary antibody or Fc receptor-expressing effector cells. The antibody formed supracomplexes with soluble recombinant and membrane-anchored TRAIL-R2 and enhanced clustering of TRAIL-R2 on cell surface without cross-linking. KMTR2 was dramatically efficacious in reducing established human tumor. CONCLUSION: Our findings indicate that novel agonist antibody KMTR2 can direct antibody-dependent oligomerization of TRAIL-R2 and initiates efficient apoptotic signaling and tumor regression independent of host effector function. Thus, the direct agonist would be a lead candidate for cancer therapeutics.

Animals↗
PubMed2005

Linking semantic priming effect in functional MRI and event-related potentials.

The aim of this study is to examine the neural substrates involved in semantic priming using a combined event-related functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) study. Twelve subjects were instructed to judge whether the presented target word was a real word or a nonword. Under the related condition, target words were preceded by a semantically related prime word. On the other hand, under the unrelated condition, prime words did not have semantic relatedness with the target word. The reaction time for reaching a judgment was longer under the unrelated condition than under the related condition, indicating that the recognition of target words is promoted by semantic priming under the related condition. In the fMRI results, we found reduced activity in the dorsal and ventral left inferior frontal gyrus, the anterior cingulate, and left superior temporal cortex for related versus unrelated conditions (i.e., the repetition suppression effect). ERP analysis revealed that the amplitude of the N400 component was reduced under the related condition compared with the unrelated condition (i.e., the N400 priming effect). Correlation analysis between the BOLD repetition suppression effect and the N400 priming effect decomposed by independent component analysis (ICA) across subjects showed significant correlation in the left superior temporal gyrus. This finding is consistent with the recent MEG data suggesting that the source of N400 is judged to be the bilateral superior temporal lobe. We discussed this finding herein in relation to the modulation of access to the phonological representation caused by semantic priming.

Adult↗
PubMed2005

Dissociation of conscious and unconscious repetition priming effect on event-related potentials.

Although the neural basis of the unconscious priming effect has previously been investigated, the results of these studies have possibly been contaminated by a conscious priming effect. The aim of the present study was to dissociate the effects of conscious and unconscious priming on event-related potential (ERP) by using the process-dissociation procedure. A prime word was presented briefly, followed by a word-stem, in each trial. Under the inclusion condition, subjects were instructed to complete the word-stem using the prime word, while under the exclusion condition subjects were asked to complete the word-stem with a word not seen as prime. The behavioral priming effect was obtained under both conditions, indicating that the prime words were processed unconsciously and influenced the word-stem completion task. We found that two ERP components were affected by repetition priming. First, the N400 amplitude was decreased by word repetition under the inclusion condition, but not under the exclusion condition. This result suggests that N400 would reflect conscious lexical processing, but not unconscious lexical activation. Second, the negativity at left front lateral region was enhanced by word repetition under the exclusion condition. We discuss this finding herein in relation to the activity of the left inferior prefrontal cortex with regard to word semantic processing.

Adolescent↗
PubMed2004

Expansion of human Valpha24+ NKT cells by repeated stimulation with KRN7000.

Changes in Valpha24+Vbeta11+ NKT cell number and function are associated with human autoimmune diseases and cancer. Restoration of this corresponding NKT cell population in mice or in vivo activation with alpha-galactosylceramide (KRN7000) can prevent or reduce tumor growth and autoimmunity. Although the therapeutic value of these natural killer T (NKT) cells in man remains to be determined, large numbers of functional antigen-specific NKT cells can be expanded in vitro. We show that Valpha24+Vbeta11+ human NKT cells are expanded by repeated stimulation with KRN7000, unfractionated donor peripheral blood mononuclear cells (PBMC), and recombinant human interleukin-2 (rhIL-2). NKT cells were expanded continuously for more than 2 months with a potential yield of >10(12) cells. The expanded NKT cells retained their CD4+ or CD4- phenotype after restimulation and were functional as shown by cytokine secretion, killing of antigen-pulsed target cells, and activation of NK cell cytotoxicity. This expansion method may be useful for proof-of-concept studies involving adoptive transfer of ex vivo-expanded NKT cells as a new therapeutic option for cancer and autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2004

Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment.

The cytokine thrombopoietin (TPO), the ligand for the hematopoietic receptor c-Mpl, acts as a primary regulator of megakaryocytopoiesis and platelet production. We have determined the crystal structure of the receptor-binding domain of human TPO (hTPO(163)) to a 2.5-A resolution by complexation with a neutralizing Fab fragment. The backbone structure of hTPO(163) has an antiparallel four-helix bundle fold. The neutralizing Fab mainly recognizes the C-D crossover loop containing the species invariant residue Q111. Titration calorimetric experiments show that hTPO(163) interacts with soluble c-Mpl containing the extracellular cytokine receptor homology domains with 1:2 stoichiometry with the binding constants of 3.3 x 10(9) M(-1) and 1.1 x 10(6) M(-1). The presence of the neutralizing Fab did not inhibit binding of hTPO(163) to soluble c-Mpl fragments, but the lower-affinity binding disappeared. Together with prior genetic data, these define the structure-function relationships in TPO and the activation scheme of c-Mpl.

Amino Acid Sequence↗
PubMed2004

Modulation of human leukocyte antigen-DR on monocytes and CD16 on granulocytes in patients with septic shock using hemoperfusion with polymyxin B-immobilized fiber.

BACKGROUND: Hemoperfusion with PMX-F (polymyxin B covalently immobilized on fibers) has been reported to be safe and effective for patients with septic shock. However, the molecular mechanism of this usefulness is not yet clear. The purpose of this study was to evaluate whether the expression of CD14, human leukocyte antigen (HLA)-DR on monocytes, and the expression of CD16, CD11b/CD18 on neutrophils, are altered in septic patients according to the severity, and whether PMX-F treatment affects the clinical parameters and the expression of leukocyte surface antigen expression. PATIENTS AND METHODS: Thirty-four patients who were taken to the National Defense Medical College hospital at emergency, and who had an identified focus of infections, were enrolled in this study. The patients were divided into three groups: non-systemic inflammatory response syndrome [SIRS]) group, sepsis group, and septic shock group. Peripheral blood samples were collected at the time of admission to our hospital. The CD14, HLA-DR expression on monocytes and the CD11b/CD18, CD16 expression on granulocytes were evaluated using flowcytometry, and the serum interleukin (IL)-6 and IL-10 levels were measured using enzyme-linked immunosorbent assay. Treatment with a PMX-F column was performed in 10 patients with septic shock. RESULTS: The HLA-DR expression on monocytes and the CD16 intensity on granulocytes in patients with septic shock were significantly lower than those in patients with sepsis. The serum IL-6 and 10 levels in patients with septic shock were significantly higher than those in patients with sepsis. The mean systolic blood pressure in patients with septic shock was significantly increased after the PMX-F treatment; furthermore, the HLA-DR expression on monocytes and the CD16 intensity on granulocytes were significantly increased after the PMX-F treatment. The serum IL-10 levels were significantly decreased after the PMX-F treatment. CONCLUSIONS: We showed that the surface antigens, HLA-DR on monocytes and CD16 on granulocytes, are extremely decreased in patients with septic shock, and that PMX-F treatment is effective for beneficially increasing the surface antigen expression on leukocytes. This therapy might be a new strategy for helping patients recover from immunoparalysis in septic conditions.

Aged↗
PubMed2003

Interleukin-12 and -18 induce severe liver injury in mice recovered from peritonitis after sublethal endotoxin challenge.

BACKGROUND: Postoperative intraabdominal abscess is the major complication after abdominal surgery, and additional infection is often observed and becomes the leading cause of death in septic patients who survive initial resuscitation. Sepsis is initiated and perpetuated by the overzealous systemic production of proinflammatory cytokines-such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-12, and IL-18-sometimes resulting in excessive tissue injury and death. The purpose of this study was to assess the correlation between liver and spleen innate cytokine responses and organ dysfunction in sepsis syndrome. METHODS: Peritonitis was induced by cecal ligation and puncture (CLP). All CLP mice survived more than 7 days after the procedure, and serum cytokine (TNF-alpha, IL-12, IL-18, and IL-10) levels peaked 12 hours after CLP; thereafter, they returned to basal levels 7 days after CLP. The mice were injected with a sublethal dose of lipopolysaccharide (LPS) 7 days after CLP. Survival rates, tissue damage, serum cytokine levels, and cytokine production of liver or spleen mononuclear cells (MNCs) were evaluated. RESULTS: All CLP mice died within 6 hours from liver injury 7 days after LPS challenge, but all sham mice survived. IL-12, IL-18, and IFN-gamma levels in supernatants of the liver MNCs stimulated with LPS in CLP mice were significantly higher than those in sham mice 7 days after the procedure. Furthermore, serum IL-12 and IL-18 levels and liver MNCs IL-12, IL-18, and IFN-gamma production were significantly increased in CLP mice compared with sham mice after LPS challenge. Thereafter, effects of anti-IL-12 and/or anti-IL-18 antibody were evaluated in LPS-injected CLP mice. The survival rate of LPS-injected CLP mice treated with both anti-IL-12 and anti-IL-18 antibody was significantly better than that of untreated mice. Furthermore, liver damage was improved. CONCLUSION: Mice recovered from mild peritonitis died of severe liver injury by subsequent injection of a sublethal dose of LPS, and this liver injury was related to the collaborating production of IL-12 and IL-18 by liver MNCs.

Animals↗
PubMed2002

Role of macrophage inflammatory protein 2 in acute lung injury in murine peritonitis.

BACKGROUND: Acute lung injury is a frequent extraabdominal complication of bacterial peritonitis, and neutrophil plays an important role in this lung damage. Macrophage inflammatory protein 2 (MIP-2) serves the same chemotactic function as IL-8 which is a potent neutrophil chemotactic factor in humans, and we investigated the role of MIP-2 associated with neutrophil recruitment in the lung of murine peritonitis. METHODS: Cecal ligation and puncture (CLP) were performed on mice. MIP-2 levels in blood and lung tissue, MIP-2 mRNA expression in lung tissue and bronchoalveolar lavage fluid (BALF), and CD11b expression on peripheral blood neutrophil and BALF cells were determined after CLP. In addition, we investigated the effect of anti-MIP-2 antibody on the lung injury associated with peritonitis. RESULTS: MIP-2 mRNA expression was observed in lung tissue after CLP and numerous neutrophils were accumulated in the lung under those conditions. Anti-MIP-2 antibody contributed to the inhibition of the CD11b expression and chemotaxis of pulmonary neutrophils, lung edema, and thus the reduction in peritonitis-related mortality. CONCLUSIONS: MIP-2 plays a pivotal role in neutrophil recruitment in the lung following peritonitis, and control of neutrophil accumulation in the lung by neutralizing MIP-2 is recommended as a new therapeutic approach to the lung damage associated with peritonitis.

Acute Disease↗
PubMed2002

Sequence-dependent motions of DNA: a normal mode analysis at the base-pair level.

Computer simulation of the dynamic structure of DNA can be carried out at various levels of resolution. Detailed high resolution information about the motions of DNA is typically collected for the atoms in a few turns of double helix. At low resolution, by contrast, the sequence-dependence features of DNA are usually neglected and molecules with thousands of base pairs are treated as ideal elastic rods. The present normal mode analysis of DNA in terms of six base-pair "step" parameters per chain residue addresses the dynamic structure of the double helix at intermediate resolution, i.e., the mesoscopic level of a few hundred base pairs. Sequence-dependent effects are incorporated into the calculations by taking advantage of "knowledge-based" harmonic energy functions deduced from the mean values and dispersion of the base-pair "step" parameters in high-resolution DNA crystal structures. Spatial arrangements sampled along the dominant low frequency modes have end-to-end distances comparable to those of exact polymer models which incorporate all possible chain configurations. The normal mode analysis accounts for the overall bending, i.e., persistence length, of the double helix and shows how known discrepancies in the measured twisting constants of long DNA molecules could originate in the deformability of neighboring base-pair steps. The calculations also reveal how the natural coupling of local conformational variables affects the global motions of DNA. Successful correspondence of the computed stretching modulus with experimental data requires that the DNA base pairs be inclined with respect to the direction of stretching, with chain extension effected by low energy transverse motions that preserve the strong van der Waals' attractions of neighboring base-pair planes. The calculations further show how one can "engineer" the macroscopic properties of DNA in terms of dimer deformability so that polymers which are intrinsically straight in the equilibrium state exhibit the mesoscopic bending anisotropy essential to DNA curvature and loop formation.

Anisotropy↗