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Biomedical subjects

Kenji Matsumoto

Publications and source records attributed to Kenji Matsumoto.

At least 37 records · Page 2Linked to original sources
PubMed2006

Young persimmon fruits prevent the rise in plasma lipids in a diet-induced murine obesity model.

The effect of young and mature persimmon fruits on lipid metabolism was investigated in a diet-induced murine obesity model. A commercially purchased high fat diet (Quick Fat, CLEA Japan) was used as the basal diet. Dried and powdered young and mature fruits of two breeds of persimmon, Fuyu-kaki and Hachiya-kaki, were added to the basal diet at a concentration of 10%, respectively. Male C57BL/6 mice (n=4) were divided into five groups and fed the basal diet or one of the persimmon-supplemented basal diets ad libitum for 14 weeks. Diets supplemented with both types of young fruit significantly reduced the rise in plasma lipids, including total cholesterol (p<0.005), triglyceride (p<0.05), and LDL cholesterol (p<0.05), and the effect was almost equal between the two breeds. Real-time RT-PCR revealed that both of these young fruit-supplemented diets equally up-regulated expression of the cholesterol 7 alpha-hydroxylase (CYP7A1) gene in the liver by about three-fold (p<0.05). CYP7A1 plays an important role in maintaining cholesterol homeostasis by regulating bile acid synthesis, suggesting that increased conversion of cholesterol to bile acids may have caused the cholesterol-lowering effect of the young fruits. The results indicate that young persimmon fruits are beneficial in the development of preventive and therapeutic agents against dyslipidemia.

Animals↗
PubMed2006

Gene expression profiling of human mast cell subtypes: an in silico study.

BACKGROUND: Human mast cells (MCs) were classified into at least two subtypes, i.e., tryptase- and chymase-positive MCs (MC(TC)) and tryptase-only-positive MCs (MC(T)). However, differences in global molecular expression between these subtypes are unknown. METHODS: We analyzed public microarray data of MC subtypes derived from various tissues and those of peripheral blood granulocytes by using hierarchical clustering methods to understand the global gene expression profiles. RESULTS: All the transcripts subjected to this clustering analysis were classified into two large clusters, i.e., MC-preferential or granulocyte-preferential. In the original works, MCs from tonsil, lung and skin had been cultured for more than several weeks to obtain highly viable and pure cell populations, and these MCs retained their typical profiles such as intensities of chymase protein expression. Most of the transcripts were commonly expressed by these MC subtypes. However, tonsil-derived MCs and skin-derived MCs but not lung-derived MCs expressed high levels of chymase (CMA1) as expected for the properties of MC(TC) and MC(T). These CMA1-high MCs and CMA1-low MCs respectively expressed distinct sets of transcripts as small gene clusters as well as CMA-1 even after being cultured in the absence of a tissue environment. CONCLUSIONS: The MC lineage seems to be far from the granulocyte lineages including basophils. CMA1-high MCs (MC(TC)) and CMA1-low MCs (MC(T)) can be regarded as differentiated MC subtypes. As such, importance of data analysis studies will be increasing along with the accumulation of global molecular data in the public database.

Cells, Cultured↗
PubMed2006

Human DEAD-box/RNA unwindase rck/p54 contributes to maintenance of cell growth by affecting cell cycle in cultured cells.

Understanding the control of gene expression in cancer cells requires defining the molecular and cellular basis of RNA metabolism compared with that in steady-state normal cells. Previously, we reported evidence that human RNA structure-modifying unwindase rck/p54, a member of the DEAD-box family, was highly expressed in most of the malignant cell lines tested and that this expression was linked to malignant transformation. Here, we show that rck/p54 positively affects cell growth, probably by modulating the gene expression at the translational level in cultured cells. In cell growth and differentiation induced by external stimuli, the level of rck/p54 expression was up-regulated during cell proliferation and down-regulated during differentiation. The down-regulation of rck/p54 in HeLa cells by RNAi induced cell growth inhibition through cell cycle arrest at S phase. Immunoprecipitation using anti-rck/p54 antibody in HeLa cells demonstrated the co-precipitation of rck/p54 with eIF4E, which is well-known to bind to the 5'cap-structure, resulting in initiation of translation. These data suggest that rck/p54 contributes to cell growth possibly by modulating translation-initiation control of the genes involved in the cell proliferation, which is a newly defined mechanism leading to carcinogenesis.

Amino Acid Sequence↗
PubMed2005

Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1 cells.

We investigated the antiproliferative effects of four structurally similar prenylated xanthones, alpha-mangostin, beta-mangostin, gamma-mangostin, and methoxy-beta-mangostin, in human colon cancer DLD-1 cells. These xanthones differ in the number of hydroxyl and methoxy groups. Except for methoxy-beta-mangostin, the other three xanthones strongly inhibited cell growth at 20 microM and their antitumor efficacy was correlated with the number of hydroxyl groups. Hoechst 33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that the antiproliferative effects of alpha- and gamma-mangostin, but not that of beta-mangostin, were associated with apoptosis. It was also shown that their antiproliferative effects were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest was by alpha-mangostin and beta-mangostin, and S arrest by gamma-mangostin. These findings provide a relevant basis for the development of xanthones as an agent for cancer prevention and combination therapy with anti-cancer drugs.

Apoptosis↗
PubMed2005

Synthesis, structure, spectroscopic properties, and photochemistry of homo- and heteropolynuclear copper(I) complexes bridged by the 2,5-bis(2-pyridyl)pyrazine ligand.

Cu(I)-Cu(I) and Cu(I)-Ru(II) dinuclear complexes bridged by the 2,5-bppz (2,5-bis(2-pyridyl)pyrazine) ligand have been prepared and characterized including the X-ray crystallographic study of the dinuclear [{CuI(PPh3)2}2(mu-2,5-bppz)](PF6)2)2CH3Cl complex: a = 13.974(2), b = 13.993(2), c = 13.537(2) A; alpha = 101.98(1), beta = 103.22(1), gamma = 113.90(1) degrees ; triclinic, P, Z = 1. The trinuclear [{(bpy)2RuII(mu-2,5-bppz)}2CuI](PF6)5 complex was also prepared, and the structure of the complex in solution was studied by spectrometric titration. The dinuclear Cu(I) complex and [(bpy)2RuII(mu-2,5-bppz)CuI(PPh3)2](PF6)5 show photoluminescence in the solid state, which should arise from MLCT states. Photochemical oxidation of the trinuclear RuII2CuI complex occurs in the presence of oxygen to give a RuII2CuII complex. The MLCT states and the redox reaction in the excited state are discussed.

Journal Article↗
PubMed2005

Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (HCE-2).

Twelve single nucleotide polymorphisms (SNPs) in the human CES2 gene, which encodes a carboxylesterase, hCE-2 [human carboxylesterase 2 (EC 3.1.1.1)], have been reported in the Japanese. In this report, we have examined functional alterations of three SNPs, a nonsynonymous SNP (100C>T, R34W), an SNP at the splice acceptor site in intron 8 (IVS8-2A>G), and one newly discovered nonsynonymous SNP (424G>A, V142M). For the two nonsynonymous SNPs, the corresponding variant cDNAs were expressed in COS-1 cells. Both the R34W and V142M variants showed little esterase activities toward the anticancer agent irinotecan and two typical carboxylesterase substrates, p-nitrophenol acetate and 4-methylumbelliferyl acetate, although increased levels of cDNA-mediated protein expression were observed by Western blotting as compared with the wild type. To investigate a possible splicing aberration in IVS8-2A>G, an in vitro splicing assay was utilized and transcripts derived from CES2 gene fragments of the wild type and IVS8-2A>G were compared. Sequence analysis of the cloned transcripts revealed that IVS8-2A>G yielded mostly aberrantly spliced transcripts, including a deleted exon or a 32-bp deletion proximal to the 5' end of exon 9, which resulted in truncated hCE-2 proteins. These results suggested that 100C>T (R34W), 424G>A (V142M), and IVS8-2A>G are functionally deficient SNPs.

Animals↗
PubMed2005

NR4A orphan nuclear receptor family in peripheral blood eosinophils from patients with atopic dermatitis and apoptotic eosinophils in vitro.

To identify novel genes related to the clinical signs of atopic dermatitis (AD), differentially expressed genes were sought in peripheral blood eosinophils from both AD patients and healthy volunteers. RNA was prepared from eosinophils, expression of various genes was monitored using the Affymetrix GeneChip, and expression was quantified by real-time RT-PCR. Two genes, Nur77 and NOR1, members of NR4A orphan nuclear receptor family, were expressed at a significantly higher level in AD patients than in healthy volunteers. Expression of another gene in the NR4A receptor family, Nurr1, was also higher in AD patients than in healthy volunteers. When peripheral blood leukocytes from healthy volunteers were fractionated, NOR1 expression was highest in eosinophils, but expression of Nur77 and Nurr1 genes was not eosinophil-specific. Extremely intense apoptosis was induced in both eosinophils and an eosinophil cell line, AML14.3D10, by treatment with antibody (Ab) to both CD30 and Fas. Rapid expression of the genes for the NR4A receptor family was observed with anti-CD30 Ab treatment but not with anti-Fas Ab. The NR4A orphan nuclear receptor family gene expression and the subsequent eosinophil apoptosis were downregulated by the MAPK inhibitor, U0126. These results suggest that the expression of the NR4A receptor family genes through CD30 signaling may regulate eosinophil apoptosis in allergic conditions such as AD.

Adolescent↗
PubMed2005

Infantile eczema at one month of age is associated with cord blood eosinophilia and subsequent development of atopic dermatitis and wheezing illness until two years of age.

BACKGROUND: Physiological and pathological skin eruptions are commonly encountered in neonates in our clinical practice. However, the types of skin eruptions that are associated with the subsequent development of atopic dermatitis and the mechanisms of these associations remain uncertain. METHODS: A total of 105 newborn babies with normal delivery were enrolled in this prospective cohort study. The cord blood eosinophil count was measured and the neonates were examined at 1 month of age and followed until 8 years of age. RESULTS: At 1 month of age, infantile eczema, seborrheic dermatitis, intertrigo and diaper dermatitis were diagnosed in a total of 29, 7, 14 and 24 neonates, respectively. No association was found among the prevalences of these eruptions. Neonates with infantile eczema had a significantly higher number and ratio of eosinophils in the cord blood (eosinophil count: 670.8 +/- 67.8 vs. 349.0 +/- 30.3/microl, p < 0.0001; eosinophil ratio: 5.12 +/- 0.53 vs. 2.61 +/- 0.22%, p < 0.0001, for the presence and the absence of infantile eczema, respectively). In contrast, no such tendency was found for any other skin eruptions. In neonates with infantile eczema at 1 month of age, the diagnosis of atopic dermatitis had been made significantly earlier and the prevalence of wheezing illness was significantly higher than in those without infantile eczema until 2 years of age. CONCLUSION: Infantile eczema, but not other skin eruptions, precedes the development of atopic dermatitis and wheezing illness during early infancy, presumably because of the activation of eosinophils before birth.

Cohort Studies↗
PubMed2005

Effects of immunosuppressants on induction of regulatory cells after intratracheal delivery of alloantigen.

BACKGROUND: We previously reported that intratracheal delivery (ITD) of alloantigen generated regulatory cells in mice. Here, we examined the effect of various doses of conventional immunosuppressants (FK506, cyclosporine A, azathioprine, mycophenolate mofetil, and rapamycin) on inducing regulatory cells in our model. METHODS: CBA mice (primary recipients) were given C57BL/6 splenocytes by ITD and either no additional treatment or various doses of an immunosuppressant. Seven days later, splenocytes from these mice were adoptively transferred into naive secondary CBA recipients that underwent C57BL/6 cardiac grafting the same day. RESULTS: Adoptive transfer from primary recipients given ITD of splenocytes alone induced prolonged allograft survival in secondary recipients (median survival time [MST], 50 days), suggesting that regulatory cells were generated. When ITD of alloantigen was combined with daily administration of 0.1 mg/kg FK506 or 0.2 mg/kg rapamycin, graft survival was similarly prolonged (MST 55 and 50 days, respectively). When combined with 20 or 40 mg/kg MMF or 0.4 mg/kg rapamycin, the majority of recipients demonstrated indefinite survival (MST, >100 days in all groups). When ITD of alloantigen was combined with 0.3, 0.5, or 1.0 mg/kg FK506; 5, 10, or 25 mg/kg cyclosporine A; or 1.0 or 2.0 mg/kg azathioprine, allografts were rejected acutely (MST 7-13 days). CONCLUSION: Generation of regulatory cells by ITD of alloantigen was facilitated by mycophenolate mofetil and high doses of rapamycin but abrogated by cyclosporine A, azathioprine, and high doses of FK506. Low doses of rapamycin and of FK506 did not interfere with generation of regulatory cells.

Adoptive Transfer↗
PubMed2005

Expression of rck/p54, a DEAD-box RNA helicase, in gametogenesis and early embryogenesis of mice.

rck/p54 is a DEAD-box RNA helicase protein with ATP-dependent RNA-unwinding activity. Its ortholog is required for sexual reproduction in yeast and for oocyte survival and sperm fertility in Caenorhabditis elegans. In the current study, we investigated the expression of rck/p54 in mouse gametogenesis and early embryogenesis. Western blot analysis revealed that rck/p54 was highly expressed in both the ovary and testis. In the ovary, maturing oocytes strongly expressed rck/p54 in their cytoplasm. In contrast, in the testis, spermatogonia and primary spermatocytes highly expressed rck/p54 in their cytoplasm, but its expression decreased in the spermatids. Interestingly, rck/p54 was concentrated in the heads of spermatozoa; and then its expression gradually decreased as these cells matured along the epididymal duct. After fertilization, rck/p54 protein and its mRNA remained present in the pronucleus phase; and then their expression levels slightly but definitely decreased in morulae and blastocytes. The injection of a CMV-based rck/p54 expression vector into the pronuclei of fertilized eggs caused a delay in early embryogenesis. In generating RCK transgenic mice, the birth rate of the mice was significantly lower than those of other gene transgenic mice. These findings indicate that rck/p54 may play an important role in gametogenesis and early embryogenesis in mammals.

Animals↗
PubMed2005

Allergy-related genes in microarray: an update review.

Microarrays have attracted tremendous interest among biologists. However, questions have been raised regarding the reproducibility between experiments performed in different laboratories using different platforms. Here, we discuss these problems and reach the following conclusions. First, the reproducibility between different platforms of arrays is low, but bioinformatics may permit compensation at least among oligonucleotide microarrays. Second, it is hard to interpret microarray results generated using mixed cell populations. Hierarchical clustering may be applied to identify whether upregulated transcripts in an inflammatory tissue were caused simply by an increased number of inflammatory cells.

Animals↗
PubMed2005

Distinct gene expression profiles characterize cellular phenotypes of follicle-associated epithelium and M cells.

Follicle-associated epithelium (FAE) covering Peyer's patches contains specialized epithelial M cells that take up ingested macromolecules and microorganisms from the lumen of the gut by transcytosis. Using high-density oligonucleotide microarrays, we analyzed the gene expression profiles of FAE and M cells in order to characterize their cellular phenotypes. The microarray data revealed that, among approximately 14,000 genes, 409 were expressed in FAE at twofold or higher levels compared to the intestinal epithelial cells (IECs) of the villi. These included genes involved in membrane traffic, host defense and transcriptional regulation, as well as uncharacterized genes. Real-time PCR and in situ hybridization analyses identified three molecules, ubiquitin D (Ub-D), tumor necrosis factor receptor superfamily 12a (TNFRsf12a), and transmembrane 4 superfamily 4 (Tm4sf4), which were predominantly distributed throughout FAE, but were expressed little, if at all, in IECs. By contrast, transcripts of secretory granule neuroendocrine protein 1 (Sgne-1) were scattered in FAE, and were co-localized with Ulex europaeus agglutinin-1 (UEA-1)-positive cells. This clearly suggests that expression of Sgne-1 in the gut is specific to M cells. Such a unique pattern of gene expression distinguishes FAE and M cells from IECs, and may reflect their cellular phenotype(s) associated with specific functional features.

Animals↗
PubMed2005

Prostaglandin D2 induces chemotaxis in eosinophils via its receptor CRTH2 and eosinophils may cause severe ocular inflammation in patients with allergic conjunctivitis.

PURPOSE: Eosinophils are known to have important roles in the pathogenesis of allergic conjunctivitis. Prostaglandin (PG) D2, which has been implicated as a factor in allergic diseases, is known to have chemotactic activity for eosinophils. Its receptor, chemoattractant receptor homologous molecule expressed on TH2 (CRTH2), serves as a receptor for PGD2 and has been reported to mediate PGD2-dependent migration of eosinophils. In the present study, both eosinophil toxic activity for corneal epithelial cells and chemotaxis induced by PGD2 in normal volunteers were investigated. Expression of CRTH2 in normal subjects was also measured. METHODS: Primary cultured corneal epithelial cells and eosinophils in serum from normal volunteers were used and a human corneal epithelial cell line was established. Studies were performed with/without amniotic membrane. CRTH2 expression on eosinophils was assessed by flow cytometry. Chemotaxis experiments were performed using a modified Boyden chamber technique. RESULTS: Corneal epithelial cells cultured with eosinophils showed higher floating epithelial cells and epithelial defect than those cultured in the absence of eosinophils. Flow cytometry analysis revealed that eosinophils expressed CRTH2. PGD2 induced chemotaxis of eosinophils. CONCLUSIONS: Corneal epithelial damage might be caused by eosinophils, which are recruited by PGD2 secretion via CRTH2 expressed on eosinophils.

Cell Line↗
PubMed2005

Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential.

Murine bone marrow stromal cells differentiate not only into mesodermal derivatives, such as osteocytes, chondrocytes, adipocytes, skeletal myocytes, and cardiomyocytes, but also into neuroectodermal cells in vitro. Human bone marrow stromal cells are easy to isolate but difficult to study because of their limited life span. To overcome this problem, we attempted to prolong the life span of bone marrow stromal cells and investigated whether bone marrow stromal cells modified with bmi-1, hTERT, E6, and E7 retained their differentiated capability, or multipotency. In this study, we demonstrated that the life span of bone marrow stromal cells derived from a 91-year-old donor could be extended and that the stromal cells with an extended life span differentiated into neuronal cells in vitro. We examined the neuronally differentiated cells morphologically, physiologically, and biologically and compared the gene profiles of undifferentiated and differentiated cells. The neuronally differentiated cells exhibited characteristics similar to those of midbrain neuronal progenitors. Thus, the results of this study support the possible use of autologous-cell graft systems to treat central nervous system diseases in geriatric patients.

Aged↗
PubMed2005

The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy.

OBJECTIVE: The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)-4 and/or tumor necrosis factor (TNF)-alpha stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS: Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-alpha, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS: Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-alpha. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-alpha, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS: Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-alpha. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.

Cell Adhesion↗
PubMed2005

A new method for predicting functional recovery of stroke patients with hemiplegia: logarithmic modelling.

OBJECTIVE: To examine the validity and applicability of logarithmic modelling for predicting functional recovery of stroke patients with hemiplegia. DESIGN: Longitudinal postal survey. SUBJECTS: Stroke patients with hemiplegia staying in a long-term rehabilitation facility, who had been referred from acute medical service 30-60 days after onset. METHODS: Functional Independence Measure (FIM) scores were periodically assessed during hospitalization. For each individual, a logarithmic formula that was scaled by an interval increase in FIM scores during the initial 2-6 weeks was used for predicting functional recovery. RESULTS: For the study, we recruited 18 patients who showed a wide variety of disability levels on admission (FIM scores 25-107). For each patient, the predicted FIM scores derived from the logarithmic formula matched the actual change in FIM scores. The changes predicted the recovery of motor rather than cognitive functions. Regression analysis showed a close fit between logarithmic modelling and actual FIM scores (across-subject R2 = 0.945). CONCLUSIONS: Provided with two initial time-point samplings, logarithmic modelling allows accurate prediction of functional recovery for individuals. Because the modelling is mathematically simple, it can be widely applied in daily clinical practice.

Adult↗
PubMed2005

Prostaglandin A2 acts as a transactivator for NOR1 (NR4A3) within the nuclear receptor superfamily.

Within the nuclear receptor superfamily, Nur77, Nurr1, and NOR1 constitute the nuclear receptor subfamily 4 group A. Modulation of NOR1 function would be therapeutic potential for diseases related to dysfunction of NOR1, including extraskeletal myxoid chondrosarcoma and autoimmune diseases. By screening arachidonate metabolites for their capacity of transcriptional activation, we have identified prostaglandin (PG) A2 as a transactivator for NOR1. PGA2 acted as a potent activator of NOR1-dependent transcription through the GAL4-based reporter system. The putative ligand-binding domain (LBD) of the receptor directly bound PGA2, and LBD-deleted receptor showed little transcriptional activation by PGA2. Primary cultured spleen cells derived from transgenic mice overexpressing NOR1, showed higher sensitivity to PGA2 compared to those from wild-type mice. These observations suggest that PGA2 can serve as a transactivator of NOR1, and thus suggest a possibility of pharmacological modulation of the NOR1 pathways by PGA2-related compounds.

Animals↗