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Biomedical subjects

Kenji Matsumoto

Publications and source records attributed to Kenji Matsumoto.

At least 19 recordsLinked to original sources
PubMed2007

Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts.

What is it that defines a bone marrow-derived chondrocyte? We attempted to identify marrow-derived cells with chondrogenic nature and immortality without transformation, defining "immortality" simply as indefinite cell division. KUM5 mesenchymal cells, a marrow stromal cell line, generated hyaline cartilage in vivo and exhibited enchondral ossification at a later stage after implantation. Selection of KUM5 chondroblasts based on the activity of the chondrocyte-specific cis-regulatory element of the collagen alpha2(XI) gene resulted in enhancement of their chondrogenic nature. Gene chip analysis revealed that OP9 cells, another marrow stromal cell line, derived from macrophage colony-stimulating factor-deficient osteopetrotic mice and also known to be niche-constituting cells for hematopoietic stem cells expressed chondrocyte-specific or -associated genes such as type II collagen alpha1, Sox9, and cartilage oligomeric matrix protein at an extremely high level, as did KUM5 cells. After cultured OP9 micromasses exposed to TGF-beta3 and BMP2 were implanted in mice, they produced abundant metachromatic matrix with the toluidine blue stain and formed type II collagen-positive hyaline cartilage within 2 weeks in vivo. Hierarchical clustering and principal component analysis based on microarray data of the expression of cell surface markers and cell-type-specific genes resulted in grouping of KUM5 and OP9 cells into the same subcategory of "chondroblast," that is, a distinct cell type group. We here show that these two cell lines exhibit the unique characteristics of hyaline cartilage formation and enchondral ossification in vitro and in vivo.

Animals↗
PubMed2007

Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability.

Antimicrobial peptides human beta-defensins (hBD) are mainly produced by epithelia of several organs including skin, and participate in innate immunity by killing invading pathogens. Besides their microbicidal activities, hBD activate several inflammatory and immune cells. Since hBD are generated by tissues where mast cells are present, we hypothesized that these peptides could activate mast cells. In this study, we demonstrated that both hBD-3 and hBD-4 induced mast cell degranulation, prostaglandin D2 production, intracellular Ca2+ mobilization and chemotaxis. Furthermore, hBD-3- and hBD-4-induced activation of mast cells was suppressed by pertussis toxin and U-73122, inhibitors for G protein and phospholipase C, respectively. We further revealed that hBD-3 and hBD-4 increased vascular permeability in the skin, which was dependent on the presence of mast cells, because hBD-3 and hBD-4 failed to enhance vascular permeability in mast cell-deficient Ws/Ws rats. We also demonstrated that hBD-3 and hBD-4 induced phosphorylation of MAPK p38 and ERK1/2, which were further required for hBD-mediated mast cell activation, as evidenced by the inhibitory effects of p38 and ERK1/2 inhibitors on mast cell degranulation. Together, these findings suggest the key role of hBD in inflammatory responses by recruiting and activating mast cells, and increasing vascular permeability.

Animals↗
PubMed2006

Effects of novelty on activity of lateral and medial prefrontal neurons.

Detection of novel events is crucial for adapting to changing environments. The prefrontal cortex has been thought to be one of the areas involved in orienting attention to novel events. Here, we examined the effects of two components of novelty: context novelty, which purely happens when a familiar event occurs in an unpredicted situation or time and feature novelty, which happens by itself when an unfamiliar stimulus appears against the expectation of familiar ones. We trained monkeys on a task that included both novelty components and recorded the activity of neurons in the lateral and medial divisions of the prefrontal cortex. The responses of a substantial number of cells in both the lateral and medial divisions were enhanced when a familiar visual stimulus was presented in an unpredicted context. By contrast, enhancement of responses by the unfamiliarity of visual stimuli was observed mainly in cells in the lateral prefrontal cortex. These results suggest that the lateral and medial divisions of the prefrontal cortex are differentially involved in the control of attention triggered by novel sensory events.

Action Potentials↗
PubMed2006

Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism.

Activation of B cells in the airways is now believed to be of great importance in immunity to pathogens, and it participates in the pathogenesis of airway diseases. However, little is known about the mechanisms of local activation of B cells in airway mucosa. We investigated the expression of members of the B cell-activating TNF superfamily (B cell-activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL)) in resting and TLR ligand-treated BEAS-2B cells and primary human bronchial epithelial cells (PBEC). In unstimulated cells, expression of BAFF and APRIL was minimal. However, BAFF mRNA was significantly up-regulated by TLR3 ligand (dsRNA), but not by other TLR ligands, in both BEAS-2B cells (376-fold) and PBEC (224-fold). APRIL mRNA was up-regulated by dsRNA in PBEC (7-fold), but not in BEAS-2B cells. Membrane-bound BAFF protein was detectable after stimulation with dsRNA. Soluble BAFF protein was also induced by dsRNA (> 200 pg/ml). The biological activity of the epithelial cell-produced BAFF was verified using a B cell survival assay. BAFF was also strongly induced by IFN-beta, a cytokine induced by dsRNA. Induction of BAFF by dsRNA was dependent upon protein synthesis and IFN-alphabeta receptor-JAK-STAT signaling, as indicated by studies with cycloheximide, the JAK inhibitor I, and small interfering RNA against STAT1 and IFN-alphabeta receptor 2. These results suggest that BAFF is induced by dsRNA in airway epithelial cells and that the response results via an autocrine pathway involving IFN-beta. The production of BAFF and APRIL by epithelial cells may contribute to local accumulation, activation, class switch recombination, and Ig synthesis by B cells in the airways.

B-Cell Activating Factor↗
PubMed2006

Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma.

Suppressor of cytokine signaling (SOCS) 1 is an essential physiologic regulator of the IFN-gamma signaling that is crucial to lead appropriate immune responses, and impaired IFN-gamma production is considered a hallmark of atopic diseases. Recent study has shown that SOCS1 is also crucial in attenuating type 1 IFN signaling and in limiting the host response to viral infection. Clinical and experimental evidence suggest an important role for respiratory viral infections in the development of asthma. To assess genetic functional variants of SOCS1 related to susceptibility and clinical phenotypes in adult asthma in a Japanese population, we conducted association and haplotype analyses of 462 subjects with adult asthma and 639 control subjects. After screening for polymorphisms, we identified a total of 13 variants and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants were selected for genotyping with regard to the LD pattern, and we found a significant association between an SOCS1 promoter polymorphism -1478CA > del and adult asthma (P = 0.0063). The three-locus haplotype of SOCS1 using these three polymorphisms also showed a positive association with a haplotype T-C-del (-5388T, -3969C, and -1478 del; P = 0.0097). Furthermore, reporter gene analysis revealed that related promoter variant -1478 del enhanced the transcriptional level of SOCS1 in human lung epithelial cells, and induced higher levels of protein expression of SOCS1 and lower phosphorylation of STAT1 stimulated with IFN-beta. These findings suggest that the SOCS1 gene might be involved in the development of adult asthma through functional genetic polymorphism.

Adult↗
PubMed2006

Neuronal responses to object images in the macaque inferotemporal cortex at different stimulus discrimination levels.

We can discriminate visual objects at multiple levels, from coarse categorization to individual identification. It is not known how the brain adapts to the varying levels of discrimination required in different behavioral contexts. In the present study, we investigated whether the stimulus selectivity of neuronal responses in the monkey inferotemporal cortex, which is the final unimodal stage in the ventral visual pathway, changes with the varying levels of discrimination required for different task conditions. Responses of each inferotemporal cell to the same set of nine object images were examined in two different task conditions. The task alternated between coarse and fine discriminations in the first experiment, and the rule alternated between categorization and individual object identification in the second experiment. Despite these changes in the task requirements and the resulting differences in the monkeys' behavior, we found that the responses of inferotemporal cells were largely unchanged in both experiments. Our results suggest that representation of object images in the inferotemporal cortex is stable and rather insensitive to these kinds of shifts in behavioral context. Neuronal adaptations to behavioral context may occur downstream of the inferotemporal cortex.

Animals↗
PubMed2006

Goal-based action selection and utility-based action bias.

According to artificial intelligence studies, goal-based and utility-based agents can select an action to attain a desired outcome. The goal-based agent sets a specific goal regardless of its utility at first, and selects the action that leads to that goal (goal-based action selection). The utility-based agent compares the utilities of different possible outcomes, and selects the action that causes the outcome with the highest utility (utility-based action bias). The medial prefrontal cortex is involved in implementing the goal-based action selection and the striatum is involved in implementing the utility-based action bias. Goal-based action selection may be temporarily dominant over the utility-based action bias in a new environment, whereas the utility-based action bias becomes dominant after acquisition of action utilities in the environment. This transition of dominance between the two decision systems may be enhanced by a reference-point shift based on the goal-setting process during goal-based action selection.

Animals↗
PubMed2006

CpG oligodeoxynucleotide prolongs eosinophil survival through activation of contaminating B cells and plasmacytoid dendritic cells in vitro.

BACKGROUND: In our previous study, oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) significantly prolonged eosinophil survival without inducing active release of eosinophil-derived neurotoxin or interleukin 8. In addition, this survival-promoting activity was nuclear factor-kappaB dependent. However, some eosinophil preparations from different donors hardly responded to CpG ODNs at all. To clarify why CpG ODN-induced nuclear factor-kB activation in eosinophils does not cause eosinophil-derived neurotoxin or interleukin 8 release and why the survival-promoting activity of CpG ODNs was not found in some eosinophil preparations, we determined the effect of extensive removal of contaminating B cells and plasmacytoid dendritic cells from human eosinophil preparations. METHODS: Eosinophils were purified from the peripheral blood of healthy or slightly allergic donors by gradient sedimentation and negative selection with anti-CD16 alone or a combination of anti-CD16, anti-CD19 and anti-blood dendritic cell antigen 4 (BDCA4) immunomagnetic beads. Eosinophil survival was measured with FITC-conjugated annexin V and propidium iodide by FACS after incubation with synthetic CpG 2006(CpG-B), CpG 2216 (CpG-A) or their GpC control ODNs for 24 h. RESULTS: The addition of anti-CD19 and anti-BDCA4 immunomagnetic beads reduced the number of contaminating CD19+ cells and CD123+ BDCA2+ cells in eosinophil preparations. CpG 2006 and CpG 2216, but not their GpC control ODNs, significantly prolonged survival of eosinophils purified with anti-CD16 immunomagnetic beads alone but not eosinophils purified with a combination of anti-CD16, anti-CD19 and anti-BDCA4 beads. CONCLUSIONS: These results strongly suggest that contaminating B cells or plasmacytoid dendritic cells in eosinophil preparations critically regulate CpG ODN-mediated prolongation of eosinophil survival and that CpG ODNs do not activate eosinophils directly.

Adjuvants, Immunologic↗
PubMed2006

A functional polymorphism in MMP-9 is associated with childhood atopic asthma.

Although MMP-9 has been suggested to be important in inflammation and in the connective tissue remodeling associated with asthma, the genetic influences of the polymorphisms of MMP-9 are unclear. To examine whether polymorphisms in MMP-9 are associated with childhood atopic asthma, we identified a total of 17 polymorphisms and conducted an association study with asthma (n = 290) and controls (n = 638). 2127G>T and 5546G>A (R668Q) were significantly associated with the risk of childhood atopic asthma (p = 0.0032 and 0.0016, respectively). In haplotype analysis, we also found a positive association with a haplotype (p = 0.0053). MMP-9 was expressed in cultured human bronchial epithelial cells, and the mRNA expression level was upregulated by dsRNA. Furthermore, the promoter SNP -1590C>T, in strong linkage disequilibrium with 2127G>T, enhanced the transcriptional level of MMP-9. Thus, the MMP-9 gene might be involved in the development of asthma through functional genetic polymorphisms.

5' Flanking Region↗
PubMed2006

JNK (c-Jun NH2 terminal kinase) and p38 during ischemia reperfusion injury in the small intestine.

BACKGROUND: In small intestinal ischemia reperfusion injury, we investigated the pathophysiological role of c-Jun NH2 terminal kinase (JNK) and p38 in order to determine whether the dual inhibition of JNK and p38 was beneficial. METHODS: Ischemia reperfusion injury was induced by clamping the superior mesenteric artery for 30 min in Wistar male rats. The inhibition of JNK and p38 was achieved with LL-Z1640-2 as a novel JNK and p38 dual inhibitor in vivo. Between the non-treatment group (Control group) and the LL-Z1640-2 treatment group (LL-Z group), the following findings were compared; histological damage by hematoxylin and eosin (H. E.) staining, JNK and p38 activation by a kinase assay, the localization of apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, the localization of activated JNK and activated p38 based on immunohistochemistry. RESULTS: The activation of JNK and p38 increased remarkably after reperfusion according to a kinase assay. In immunohistochemistry for activated JNK and activated p38, a remarkable degree of positive staining was revealed in the nucleus of the detached epithelial cells from the tip of villi after reperfusion. In addition, many TUNEL positive cells were observed in the detached epithelial cells where JNK and p38 were activated. Pretreatment of LL-Z1640-2 inhibited the activation of JNK and p38, and also significantly improved the histological damage. CONCLUSIONS: These results suggest that JNK and p38 both play a key role during small intestinal ischemia reperfusion injury through a proapoptotic action on the tip of villi.

Animals↗
PubMed2006

Prefrontal cell activities related to monkeys' success and failure in adapting to rule changes in a Wisconsin Card Sorting Test analog.

The cognitive flexibility to select appropriate rules in a changing environment is essential for survival and is assumed to depend on the integrity of prefrontal cortex (PFC). To explore the contribution of the dorsolateral PFC to flexible rule-based behavior, we recorded the activity of cells in this region of monkeys performing a Wisconsin Card Sorting Test (WCST) analog. The monkey had to match a sample to one of three test items by either color or shape. Liquid reward and a discrete visual signal (error signal) were given as feedback to correct and incorrect target selections, respectively. The relevant rule and its frequent changes were not cued, and the monkeys could find it only by interpreting the feedback. In one-third of cells, cellular activity was modulated by the relevant rule, both throughout the trial and between trials. The magnitude of the modulation correlated with the number of errors that the monkeys committed after each rule change in the course of reestablishing high performance. Activity of other cells differed between correct and error trials independently from the rule-related modulation. This difference appeared during actual responses and before the monkeys faced the problems. Many PFC cells responded to the error-signal presentation, and, in some of them, the magnitude of response depended on the relevant rule. These results suggest that the dorsolateral PFC contributes to WCST performance by maintaining the relevant rule across trials, assessing behavioral outcomes, and monitoring the processes that could lead to success and failure in individual trials.

Action Potentials↗
PubMed2006

An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway.

Although associations between endotoxin exposure or respiratory infection and asthma have been recognized, the genetic effects in these conditions are unclear. Toll-like receptors (TLRs) play an essential role in innate host defense and in the control of adaptive immune responses. IL-1R-associated kinase-M (IRAK-M) and single immunoglobulin IL-1R-related molecule (SIGIRR) negatively regulate TLR-signaling pathways. To investigate whether polymorphisms in these genes were associated with asthma or asthma-related phenotypes, we screened these genes for polymorphisms by direct sequencing of 24 asthmatics and identified 19 variants in IRAK-M and 12 variants in SIGIRR. We next conducted linkage disequilibrium mapping of the genes, and examined the association of polymorphisms and haplotypes using 391 child patients with asthma, 462 adult patients with asthma, and 639 controls. None of the alleles or haplotypes of IRAK-M and SIGIRR were associated with asthma susceptibility or asthma-related phenotype. Our results indicate that polymorphisms in IRAK-M and SIGIRR are not likely to be associated with the development of asthma in the Japanese population.

Adolescent↗
PubMed2006

Quantitative study of changes in oxidative metabolism during visual stimulation using absolute relaxation rates.

In the context of quantitative functional MRI (fMRI), deoxyhemoglobin (dHb) content is the essential physiological parameter for calibrating the blood oxygenation level-dependent (BOLD) signal. In studies on humans, the baseline dHb content or its equivalent has been evaluated indirectly by means of carbon dioxide breathing as a physiological reference condition. In this study with normal volunteers, quantitative mapping of baseline dHb content was performed in a direct manner by measuring the reversible contribution of the effective transverse relaxation rate. The BOLD signal change in the visual cortex during 8 Hz flicker visual stimulation was calibrated based on the quantitative map of baseline dHb content. The calibrated relaxation rate change that represents the stimulation-induced fractional change of dHb content decreased by 14% within the activated visual cortex. Simultaneous measurement of cerebral blood flow (CBF) with BOLD showed an increase of 59%. From the calibrated relaxation rate and CBF changes, the cerebral metabolic rate of oxygen (CMRO2) was calculated to increase by 19-28% within the activated visual cortex. The ratio of the CBF increase to the CMRO2 increase was 2-3:1, which agreed well with results of similar quantitative fMRI studies for humans. The method proposed here for quantitative evaluation of the BOLD signal may be applicable not only to fMRI for normal human subjects, but also to physiologically altered or diseased states, because it requires no physiological perturbation.

Adult↗
PubMed2006

Reconstructive surgery for segmental arterial mediolysis involving both the internal carotid artery and visceral arteries.

Segmental arterial mediolysis (SAM) is a rare, nonatherosclerotic, noninflammatory arteriopathy. A 52-year-old man with sudden hemiparesis of the right side was found to have an aneurysm of the left internal carotid artery and concomitant multiple aneurysms of the extrahepatic, celiac, and superior mesenteric arteries. Reconstructive operations using autologous vein graft were performed to treat the aneurysms. The histopathology analyses of resected arterial and aneurysmal specimens showed characteristics consistent with SAM. To our knowledge, a successfully treated case of SAM affecting both the carotid artery and visceral arteries has not previously been described.

Aneurysm↗
PubMed2006

Large renal artery aneurysm in Takayasu arteritis.

Takayasu arteritis (TA), a primary arteritis of unknown cause, commonly affects the aorta and its main branches. Most patients with TA have stenotic or occlusive changes; aneurysmal degeneration is relatively rare, and renal artery aneurysms are extremely rare. We observed a fusiform, 7-cm renal artery aneurysm in a 57-year-old man with TA who had been followed up for 17 years. The patient underwent nephrectomy and resection of the aneurysm. Histologic examinations of resected specimens of the lesion showed characteristics typical of TA.

Aneurysm↗
PubMed2006

Relationships between independence level of single motor-FIM items and FIM-motor scores in patients with hemiplegia after stroke: an ordinal logistic modelling study.

OBJECTIVE: To assess the relationships between independence levels of single motor-related Functional Independence Measure (FIM) items and summed FIM-motor scores of patients with hemiplegia after stroke. DESIGN: For each patient FIM scores were assessed 4 times during hospitalization. Ordinal logistic analyses were performed on group data. SUBJECTS: Fifty patients with hemiplegia after stroke staying in a long-term rehabilitation facility. RESULTS: Analyses revealed that FIM-motor scores accounted for much of the variability of independence levels for most of the single FIM items, including dressing upper body, and transfers to bed/chair/wheelchair and to toilet. For these items, the independence levels were proportionally associated with FIM-motor scores. For eating, higher FIM-motor scores (>60) were associated with modified independence and lower FIM-motor scores (<40) correlated with attainment of supervision/set-up levels. For dressing lower body, greater independence was apparent when FIM-motor scores were higher (>60). CONCLUSION: For single FIM items, relative difficulty was comparable with results from previous literatures using Rasch analyses. Moreover, our results revealed that relative difficulty for single items varied greatly between independence levels. With regard to disability task targets, probability of independence evaluated from logistic modelling is an aid to efficient rehabilitation scheduling.

Activities of Daily Living↗
PubMed2006

Growth inhibition of stilbenoids in Welwitschiaceae and Gnetaceae through induction of apoptosis in human leukemia HL60 cells.

Fifty-six stilbenoids isolated from the families of Welwitschiaceae and Gnetaceae were screened for growth inhibitory activity against HL60 cells, and two compounds (gnemonol G and gnetin I) among them exhibited a strong activity with IC(50) of 10.0 microM and 12.2 microM at 48 h incubation, respectively. The growth suppression by gnemonol G and gnetin I was found to be in part due to apoptosis which was assessed by morphological findings such as nuclear condensation and fragmentation, and DNA ladder formation in human leukemia HL60 cells.

Apoptosis↗