J Imanishi

Meiji University of Oriental Medicine, Kioto, Kyōto, Japan

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Publications (333)1033.25 Total impact

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    ABSTRACT: To enhance the effect of anti-influenza-virus agent treatment, the effect of combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese traditional herbal medicine, HET) on early viral clearance was examined. Senescence-accelerated mice were given HET in drinking water for 2 weeks, followed by intranasal infection with influenza A virus strain PR8. After 4 hours of infection, oseltamivir was administered orally for 5 days. The viral loads in the lungs of the group receiving combined treatment were dramatically lower when compared with the viral loads in the lungs of the group receiving oseltamivir alone. HET significantly increased the induction of IL-1β and TNF-α in the lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From these results, we conclude that these functions may be responsible the increased effect on viral load reduction. Here, we show that the combined administration of oseltamivir and HET is very useful for influenza treatment in senescence-accelerated mice.
    Archives of Virology 08/2013; DOI:10.1007/s00705-013-1807-3 · 2.28 Impact Factor
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    ABSTRACT: Psycho-oncological care, including spiritual care, is essential for cancer patients. Integrated medicine, a therapy combining modern western medicine with various kinds of complementary and alternative medicine, can be appropriate for the spiritual care of cancer because of the multidimensional characteristics of the spirituality. In particular, therapies that enable patients to establish a deeper contact with nature, inspire feelings of life and growth of plants, and involve meditation may be useful for spiritual care as well as related aspects such as emotion. The purpose of the present study was to examine the effect of spiritual care of cancer patients by integrated medicine in a green environment. The present study involved 22 cancer patients. Integrated medicine consisted of forest therapy, horticultural therapy, yoga meditation, and support group therapy, and sessions were conducted once a week for 12 weeks. The spirituality (the Functional Assessment of Chronic Illness Therapy-Spiritual well-being), quality of life (Short Form-36 Health Survey Questionnaire), fatigue (Cancer Fatigue Scale), psychological state (Profile of Mood States, short form, and State-Trait Anxiety Inventory) and natural killer cell activity were assessed before and after intervention. In Functional Assessment of Chronic Illness Therapy-Spiritual well-being, there were significant differences in functional well-being and spiritual well-being pre- and postintervention. This program improved quality of life and reduced cancer-associated fatigue. Furthermore, some aspects of psychological state were improved and natural killer cell activity was increased. It is indicated that integrated medicine performed in a green environment is potentially useful for the emotional and spiritual well-being of cancer patients.
    EXPLORE The Journal of Science and Healing 03/2013; 9(2):87-90. DOI:10.1016/j.explore.2012.12.002 · 0.94 Impact Factor
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    ABSTRACT: In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPβ were involved in the positive regulation of C/EBPβ transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPβ transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPβ upregulation.
    PLoS ONE 01/2013; 8(1):e54862. DOI:10.1371/journal.pone.0054862 · 3.53 Impact Factor
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    ABSTRACT: Granulopoiesis is tightly regulated to meet host demands during both "steady-state" and "emergency" situations, such as infections. The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPβ is required are unknown. In this study, a novel flow cytometric method was developed that successfully dissected mouse bone marrow cells undergoing granulopoiesis into five distinct subpopulations (#1-5) according to their levels of c-Kit and Ly-6G expression. After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations. Upon infection, C/EBPβ was upregulated at the protein level in all the granulopoietic subpopulations. The rapid increase in immature subpopulations #1 and #2 observed in C/EBPβ knockout mice at 1 d postinfection was attenuated. Candidemia-induced cell cycle acceleration and proliferation of hematopoietic stem/progenitors were also impaired. Taken together, these data suggest that C/EBPβ is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.
    The Journal of Immunology 09/2012; 189(9):4546-55. DOI:10.4049/jimmunol.1103007 · 5.36 Impact Factor
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    ABSTRACT: Since it is supposed that the number of patients with dementia will increase as populations age in the near future, it is important to prevent dementia. In the present study, we examined whether acupuncture and life style improvements are able to enhance cognitive function.The subjects who worry about being forgetful were recruited and divided at random into two groups ; a group receiving acupuncture with transcutaneous electrical acupuncture-point stimulation (TEAS) and im provements in life style (20 subjects ; group A) and a group undergoing improvements in life style alone (20 subjects ; group B) for 12 weeks. The results showed that the cognitive functions assessed via a Mini-Mental State Examination (MMSE) and the Wechsler Memory Scale-Revised, sleep time, and sleep efficiency were improved in all subjects included in groups A and B after the interventions. There were significant pre-to post-intervention differences in MMSE and sleep efficiency in group A only. It was found that these interven tions increased NK cells, NK activity and B cell numbers, and decreased T cell and helper T cell numbers.Thus, acupuncture and improvement of life style could enhance cognitive function and may be useful for the prevention of dementia.
    Kampo Medicine 01/2012; 63(4):229-237. DOI:10.3937/kampomed.63.229
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    ABSTRACT: To understand the characteristics of peripheral immunity in patients with Parkinson's disease (PD), we investigated the natural killer (NK) cell activity and lymphocyte subpopulations including regulatory T (Treg) cells and type 17 helper T (Th17) cells. Peripheral blood was collected from 29 PD patients (mean age 70.4 years) and 30 healthy controls (mean age 68.9 years). NK cell activity was measured by a calcein acetoxymethyl ester release assay using NK-sensitive K562 cells, peripheral NK cells and lymphocytes subsets were analyzed using flow cytometry techniques. Comparison of the two groups demonstrated that the percentage of NK cells increased and that of helper T cells, particularly type 1 (Th1), decreased in patients with PD. There was no evidence of Th1/Th2 or Treg/Th17 cell predominance in PD. Moreover, the increase of NK cells and the decrease of Th1 cells correlated with Unified Parkinson's Disease Rating Scale scores and the heart-to-mediastinum ratios based on myocardial (123) I-metaiodobenzylguanidine uptake, both of which represent disease severity in patients with PD. Our investigation indicates that a certain proportion of NK cells and other lymphocytes in the peripheral blood of patients with PD and their association with disease severity may reflect the effect of innate immunity in patients with PD in addition to the effect of dopaminergic-related agents.
    Geriatrics & Gerontology International 09/2011; 12(1):102-7. DOI:10.1111/j.1447-0594.2011.00740.x · 1.58 Impact Factor
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    ABSTRACT: Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, including sleep and autonomic dysfunctions, controlled by circadian regulation. To evaluate the alteration of circadian rhythm in PD patients, we investigated both rest activities and autonomic functions. Twenty-seven patients with idiopathic PD and 30 age-matched control subjects were recruited. Group comparisons of controls (mean age: 68.93 years), early-PD patients classified as Hoehn-Yahr (HY) stage 1&2 (mean age: 70.78 years), and advanced-PD as HY 3&4 (mean age: 68.61 years) were conducted. Measurement of rest activities was performed using Actigraph for 7 continuous days, and included measuring rhythm patterns (activity patterns recorded in or out of bed) and circadian rhythm amplitudes (power of the cycle being closest to 24h). A power spectral analysis of heart rate variability (HRV) using 24-hour ambulatory ECG was also performed. The actigraphic measurements indicated that statistically PD patients have lower activity levels when out of bed and higher activity levels when in bed, and that, the circadian rest-activity rhythm in PD decreases with disease severity. The HRV analysis showed that the total frequency component and low frequency/high frequency ratio were low in PD patients, suggesting that autonomic activities and the circadian rhythm of the sympathetic nervous system are attenuated in PD. This study elucidated the disorganization in the rest activities and HRV of PD patients as well as the gradual alterations in the circadian rhythm. The circadian rhythm disturbances are important to consider the mechanism of non-motor symptoms that occur from early stage of PD.
    Autonomic neuroscience: basic & clinical 08/2011; 165(2):195-200. DOI:10.1016/j.autneu.2011.07.010 · 1.82 Impact Factor
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    ABSTRACT: Mechanical stress is known to be an important factor in the regulation of bone remodeling, and mandibular bone is continuously exposed to mechanical stressors such as occlusal force. Therefore, in this study, we investigated the effects of mechanical stress approaching occlusal force, to which mandible-derived osteoblasts (MDOB) are exposed, on cytokine expression and production using an original hydrostatic pressure apparatus. The levels of cytokine in MDOB were examined by real-time RT-PCR, ELISA, and western blotting. In addition, mitogen-activated protein kinase inhibitor for ERK1/2, JNK, and p-38 pathways was used to identify the signal transduction pathway. Hydrostatic pressure increased the expression of IL-6 and TNF-α mRNA in a magnitude- and time-dependent manner and also enhanced IL-6 and TNF-α protein production. Furthermore, hydrostatic pressure changed the RANKL/OPG ratio in favor of RANKL for both mRNA and protein levels. Specific inhibitor of p-38 pathway but not that of the ERK1/2 and JNK pathways suppressed the up-regulation of RANKL production induced by hydrostatic pressure loading. These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.
    Oral Diseases 06/2011; 17(7):712-9. DOI:10.1111/j.1601-0825.2011.01832.x · 2.40 Impact Factor
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    ABSTRACT: Although an association between periodontitis and cardiovascular diseases has been suggested, the role of Porphyromonas gingivalis in cardiovascular diseases is not clear. In this study, we examined whether experimental bacteremia of P. gingivalis causes cardiovascular diseases and investigated the mechanism of pathogenesis of cardiovascular diseases induced by P. gingivalis. C57BL/6 mice were intravenously inoculated with 2.0 × 10(8)CFU of P. gingivalis A7436 strain. Mice were sacrificed at specified days and their hearts were collected. The collected organs were divided into two halves and used for histological evaluation and cytokine analysis. IL-17A(-/-), IFN-γ(-/-) and TNF-α(-/-) mice were also intravenously inoculated and the histological changes of hearts in mice were examined. Myocarditis and/or myocardial infarction were observed in mice injected with P. gingivalis. The levels of IL1-β, IL-6, IL-17A, IL-18, TNF-α and IFN-γ mRNA increased significantly after P. gingivalis injection. In particular, high levels of IL-17A and IFN-γ mRNA expression were observed in hearts of mice after P. gingivalis injection in comparison with these levels before injection. Furthermore, the production of IL-17A was detected in hearts of wild-type mice after P. gingivalis injection. In wild-type, TNF-α(-/-) and IFN-γ(-/-) mice, moderate infiltration of neutrophils and monocytes was observed in hearts at 5 days after injection. In contrast, no inflammatory findings were observed in hearts of IL-17A(-/-) mice. We have demonstrated that an experimental bacteremia of P. gingivalis could induce myocarditis and/or myocardial infarction in mice, and IL-17A plays an important role in the pathogenesis of these diseases.
    Archives of oral biology 06/2011; 56(11):1290-8. DOI:10.1016/j.archoralbio.2011.05.012 · 1.65 Impact Factor
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    ABSTRACT: Interleukin-28B (IL-28B), also referred to as interferon-λ3, belongs to the type III interferon family. Earlier studies showed that IL-28B suppresses proliferation of some tumor cells in vitro. IL-28B gene transfection ex vivo also resulted in growth retardation of tumor cells in mice, through either direct antiproliferative action or induction of antitumor immunity. However, it has not been reported whether in vivo therapeutic administration of recombinant IL-28B can inhibit the growth of a pre-established tumor. Here, we found that repetitive subcutaneous administration of recombinant mouse IL-28B significantly induced tumor-specific cytotoxic T lymphocytes and augmented natural killer cytolytic activity, leading to moderate suppression of the growth of a murine head and neck squamous cell carcinoma (HNSCC) cell line that was completely resistant to the direct antiproliferative effect of IL-28B. Moreover, co-administration of recombinant mouse IL-28B and cisplatin (CDDP) more significantly inhibited in vivo growth of the tumor that had been established in syngenic mice and induced tumor-specific cytotoxic T lymphocytes. The CDDP treatment induced the expression of major histocompatibility complex class I and Fas molecules on the surface of HNSCC cells both in vitro and in vivo; this may be the mechanism underlying the synergistic tumor suppression activity of IL-28B and CDDP. Unlike type I interferon, IL-28B did not suppress growth of bone marrow cells in culture. Therefore, IL-28B may be useful as a tool for a novel multidisciplinary therapy against cancer, significantly potentiating innate and adaptive antitumor immune responses, especially when co-administrated with CDDP, which is currently the first choice chemotherapeutic agent against various tumors including HNSCCs.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 03/2011; 34(2):139-48. DOI:10.1097/CJI.0b013e318204ed70 · 3.20 Impact Factor
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    ABSTRACT: Malignant melanoma is a malignant neoplasm originating from the melanocyte lineage. Microphthalmia-associated transcription factor (Mitf) is crucially involved in the melanin synthesis as well as proliferation and survival of melanocyte and melanoma. We previously showed that short interfering RNA (siRNA) that is specific for the Mitf gene (Mitf-siRNA) significantly inhibited growth of B16 melanoma after electro-transfected in vivo into preestablished tumor in mice. Here we assessed efficacy of electroporation-mediated co-transfection of Mitf-siRNA and IL-12 gene in the treatment of murine melanoma. As results, the tumor growth was more strongly inhibited by intratumor co-transfection with Mitf-siRNA and IL-12-encoding plasmid DNA than by transfection with either of the molecules alone. The co-transfection induced intratumor infiltration of CD4+ and CD8+ T cells, and hampered neoangiogenesis in the tumor. The findings suggest that the RNAi/cytokine gene combination therapy by means of electroporation may become a novel and efficacious therapeutic modality to treat neoplasms including melanoma.
    International immunopharmacology 04/2010; 10(4):540-5. DOI:10.1016/j.intimp.2009.12.015 · 2.21 Impact Factor
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    ABSTRACT: The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.
    European Journal of Clinical Microbiology 03/2010; 29(6):633-41. DOI:10.1007/s10096-010-0905-3 · 3.02 Impact Factor
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    ABSTRACT: The efficacy and specificity of small interfering RNAs (siRNAs) are largely dependent on the siRNA sequence. Since only empirical strategies are currently available for predicting these parameters, simple and accurate methods for evaluating siRNAs are needed. To simplify such experiments, target genes are often tagged with reporters for easier readout. Here, we used a bicistronic vector expressing a target gene and green fluorescent protein (GFP) to create a system in which the effect of an siRNA sequence was reflected in the GFP expression level. Cells were transduced with the bicistronic vector, expression vectors for siRNA and red fluorescent protein (RFP). Flow cytometric analysis of the transduced cells revealed that siRNAs for the target gene silenced GFP from the bicistronic vector, but did not silence GFP transcribed without the target gene sequence. In addition, the mean fluorescence intensities of GFP on RFP-expressing cells correlated well with the target gene mRNA and protein levels. These results suggest that this flow cytometry-based method enables us to quantitatively evaluate the efficacy and specificity of siRNAs. Because of its simplicity and effectiveness, this method will facilitate the screening of effective siRNA target sequences, even in high-throughput applications.
    Biochemical and Biophysical Research Communications 02/2010; 393(3):498-503. DOI:10.1016/j.bbrc.2010.02.033 · 2.28 Impact Factor
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    ABSTRACT: Goblet cells, which contribute to mucosal defense and repair in the intestinal epithelium, are depleted in human and rodent colitis. The Notch signal pathway regulates the differentiation of intestinal stem cells into epithelial cells and inhibits the differentiation of secretory lineages, including goblet cells. The aim of our study was to clarify whether the blocking of the Notch pathway at an early stage of colitis would preserve goblet cells and facilitate the healing process in dextran sulfate sodium (DSS)-induced colitis in mice. DSS was orally administered to C57/BL6 mice for 7 days, and dibenzazepine (DBZ), a Notch pathway blocker, was administered for 5 consecutive days, beginning on the first day of DSS treatment. Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. The expression of the goblet cell-associated genes Math1 and MUC2 and proinflammatory cytokines was evaluated by real-time reverse-transcriptase-PCR, with the expression of Math1 and MUC2 also visualized by immunohistochemical examination. The administration of DBZ at 4 mumol/kg significantly reduced the severity of the colitis. Compared with the DSS only-treated intestine, the number of goblet cells was relatively sustained, and the expression of Math1 and MUC2 was also elevated in the DSS/DBZ-treated intestine. DBZ treatment suppressed the mRNA levels for interleukin-1beta and -6, and matrix metalloproteinases-3 and -9 in the DSS-treated intestine. Early-stage blocking of Notch signaling may ameliorate acute DSS colitis by preventing reduction in the number of goblet cells.
    Journal of Gastroenterology 02/2010; 45(6):608-17. DOI:10.1007/s00535-010-0210-z · 4.02 Impact Factor
  • Japanese Journal of Complementary and Alternative Medicine 01/2010; 7(2):87-93. DOI:10.1625/jcam.7.87
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    ABSTRACT: To clarify the significance of subchondral bone and osteophytes in the pathology of osteoarthritis (OA), we investigated the expression of asporin (ASPN), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, TGF-beta3, and runt-related transcription factor-2 (Runx2) genes involved in bone metabolism. Osteoblasts were isolated from 19 patients diagnosed with knee OA and from 4 patients diagnosed with femoral neck fracture. Osteoblast expression of mRNA encoding ASPN, TGF-beta1, TGF-beta2, TGF-beta3, and Runx2 was analyzed using real-time RT-PCR. Expression of ASPN, TGF-beta1, and TGF-beta3 mRNA in the subchondral bone and osteophytes of OA patients increased compared with that of non-OA patients. The ratio of ASPN to TGF-beta1 mRNA in patients with severe cartilage damage was higher than that in patients with mild cartilage damage. The increased ratio of ASPN mRNA to TGF-beta1 mRNA in patients with severe relative to mild cartilage damage indicates that increased ASPN mRNA expression was significantly associated with the severity of cartilage degeneration. This finding suggests that ASPN may regulate TGF-beta1-mediated factors in the development of OA, which may provide clues as to the underlying pathology of OA.
    Journal of Orthopaedic Science 11/2009; 14(6):738-47. DOI:10.1007/s00776-009-1401-4 · 1.01 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the influence of hydrostatic pressure (HP) on the gene expression of cartilage matrix, cytokines, and apoptosis-associated factors in chondrocytes in which the cartilage was in extracellular matrix (ECM)-rich or ECM-poor condition. Chondrocytes were isolated from rabbit joints and cultured in alginate beads. Immediately after embedding (0W group) or after 2 weeks culture (2W group), the amounts of glycosaminoglycan (GAG) in the alginate beads were quantified. Both groups were exposed to continuous HP of 10 or 50 MPa for 12 h. The expression of inflammatory cytokines, proteases, and apoptosis-related factors were examined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of proteoglycan core protein (PG) and collagen type II were quantified by real-time RT-PCR. All of the GAG components in alginate beads markedly increased in the 2W group. The expression of PG and collagen type II increased after exposure to 10 MPa in both groups. In the 0W group, these levels decreased after exposure to 50 MPa of HP. The expression of interleukins IL-6 and IL-8 increased after exposure to HP in the 0W group. HP at 50 MPa induced mRNA expression of ADAMTS-5 in the 0W group but not in the 2W group. The expression of Fas increased after exposure to HP in the 0W group. These findings suggested that nonphysiological, excessive HP on chondrocytes with the ECM in poor condition reduced matrix gene expression and increased expression of the genes associated with apoptosis and catabolism of the cartilage matrix. These results might therefore be associated with the pathogenesis of osteoarthritis.
    Journal of Orthopaedic Science 11/2009; 14(6):776-83. DOI:10.1007/s00776-009-1393-0 · 1.01 Impact Factor
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    British Journal of Haematology 09/2009; 147(4):585-7. DOI:10.1111/j.1365-2141.2009.07858.x · 4.94 Impact Factor
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    ABSTRACT: The angiotensin II (Ang II) type 1 (AT(1)) receptor is expressed in bone marrow (BM) cells, whereas it remains poorly defined how Ang II regulates differentiation/proliferation of monocyte-lineage cells to exert proatherogenic actions. We generated BM chimeric apoE(-/-) mice repopulated with AT(1)-deficient (Agtr1(-/-)) or wild-type (Agtr1(+/+)) BM cells. The atherosclerotic development was significantly reduced in apoE(-/-)/BM-Agtr1(-/-) mice compared with apoE(-/-)/BM-Agtr1(+/+) mice, accompanied by decreased numbers of BM granulocyte/macrophage progenitors (GMP:c-Kit(+)Sca-1(-)Lin(-)CD34(+)CD16/32(+)) and peripheral blood monocytes. Macrophage-colony-stimulating factor (M-CSF)-induced differentiation from hematopoietic stem cells (HSCs:c-Kit(+)Sca-1(+)Lin(-)) to promonocytes (CD11b(high)Ly-6G(low)) was markedly reduced in HSCs from Agtr1(-/-) mice. The expression of M-CSF receptor c-Fms was decreased in HSCs/promonocytes from Agtr1(-/-) mice, accompanied by a marked inhibition in M-CSF-induced phosphorylation of PKC-delta and JAK2. c-Fms expression in HSCs/promonocytes was mainly regulated by TNF-alpha derived from BM CD45(-)CD34(-) stromal cells, and Ang II specifically regulated the TNF-alpha synthesis and release from BM stromal cells. Ang II regulates the expression of c-Fms in HSCs and monocyte-lineage cells through BM stromal cell-derived TNF-alpha to promote M-CSF-induced differentiation/proliferation of monocyte-lineage cells and contributes to the proatherogenic action.
    Arteriosclerosis Thrombosis and Vascular Biology 08/2009; 29(10):1529-36. DOI:10.1161/ATVBAHA.109.187732 · 6.34 Impact Factor
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    ABSTRACT: The circadian rhythm and immune system are thought to be associated with the pathological state of diabetes. The aim of this study was to examine the correlation of circadian rhythm disturbance including sleep disturbance with the immune state in patients with type 2 diabetes compared to healthy controls. Nineteen patients with type 2 diabetes (11 males and 8 females; aged 46-85 years) and 19 healthy controls (7 males and 12 males; aged 45-85 years) were recruited, and the presence of circadian rhythm disturbance including sleep disturbance was examined using an actigraph. Immunological parameters were also measured. Sleep and circadian rhythm disturbances were more frequently noted in diabetic patients than in healthy controls. Higher fasting plasma glucose and hemoglobin A1c levels were correlated with stronger sleep and circadian rhythm disturbances. The levels of B lymphocytes, helper T lymphocytes, natural killer cells, natural killer activity, and several cytokines were increased in diabetic patients compared to healthy controls. Correlations were shown among sleep disturbance (circadian rhythm disturbance), immunological measures, and diabetic indices. The exacerbation of diabetes was related to the level of sleep disturbance, circadian rhythm disturbance, and activation of the immune system.
    Diabetes research and clinical practice 08/2009; 85(3):286-92. DOI:10.1016/j.diabres.2009.07.001 · 2.74 Impact Factor

Publication Stats

6k Citations
1,033.25 Total Impact Points


  • 2011–2013
    • Meiji University of Oriental Medicine
      Kioto, Kyōto, Japan
    • Kyoto Sangyo University
      • Faculty of Life Sciences
      Kyoto, Kyoto-fu, Japan
  • 1977–2012
    • Kyoto Prefectural University of Medicine
      • • Department of Microbiology
      • • Graduate School of Medical Science
      • • Department of Ophthalmology
      • • Department of Cell Biology
      • • Department of Pediatrics
      Kioto, Kyōto, Japan
  • 1995–2009
    • Kyoto Prefectural University
      Kioto, Kyōto, Japan
  • 1991–2004
    • Kyoto University
      • Department of Urology
      Kioto, Kyōto, Japan
  • 1993
    • Kyoto Biken Laboratories
      Uji-chō, Kyōto, Japan