Takasaki, Japan
Takasaki, Japan

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Zhang Y.,Kansai Medical University | Zhang Y.,Nanfang Hospital | Hosaka N.,Kansai Medical University | Cui Y.,Kansai Medical University | And 3 more authors.
Stem Cells and Development | Year: 2011

We have recently shown that allogeneic intrabone marrow-bone marrow transplantation+adult thymus transplantation (TT) is effective for hosts with malignant tumors. However, since thymic and hematopoietic cell functions differ with age, the most effective age for such intervention needed to be determined. We performed hematopoietic stem cell transplantation (HSCT) using the intrabone marrow method with or without TT from fetal, newborn, and adult B6 mice (H-2b) into BALB/c mice (H-2d) bearing Meth-A sarcoma (H-2d). The mice treated with all types of HSCT+TT showed more pronounced regression and longer survival than those treated with HSCT alone in all age groups. Those treated with HSCT+TT showed increased numbers of CD4 + and CD8+ T cells but decreased numbers of Gr-1/Mac-1 myeloid suppressor cells and decreased percentages of FoxP3 cells in CD4 + T cells, compared with those treated with HSCT alone. In all mice, those treated with fetal liver cell (as fetal HSCs) transplantation+fetal TT or with newborn liver cell (as newborn HSCs) transplantation (NLT)+newborn TT (NTT) showed the most regression, and the latter showed the longest survival. The number of Gr-1/Mac-1 cells was the lowest, whereas the percentage of CD62L -CD44+ effector memory T cells and the production of interferon γ (IFN-γ) were highest in the mice treated with NLT+NTT. These findings indicate that, at any age, HSCT+TT is more effective against cancer than HSCT alone and that NLT+NTT is most effective. © Copyright 2011, Mary Ann Liebert, Inc. 2011.


Shi M.,Kansai Medical University | Adachi Y.,Kansai Medical University | Cui Y.,Kansai Medical University | Cui Y.,JIMRO Co. | And 7 more authors.
Stem Cells and Development | Year: 2011

The combination of allogeneic bone marrow transplantation (allo-BMT) and donor lymphocyte infusion (DLI) is a useful method for establishing donor chimerism and preventing a relapse of leukemia/lymphoma. However, there is a risk of inducing uncontrollable fatal graft-versus-host disease (GVHD). In fact, allo-BMT plus intravenous (IV)-DLI using donor splenocytes induces fatal GVHD in recipient mice. In this study, we examined the effects of the combination of intra-bone marrow (IBM)-BMT and the subcutaneous injection of donor splenocytes (SC-DLI) on the allo-BMT system. Recipient BALB/c mice were conditioned by sublethal irradiation (5 Gy), followed by IBM-BMT plus IV-DLI or SC-DLI in C57BL/6 mice. The IV-DLI group showed better engraftment of donor hemopoietic cells than the control group (without DLI) but showed fatal GVHD. The SC-DLI group, however, showed good reconstitution and mild GVHD. These results suggest that the combination of SC-DLI and IBM-BMT promotes the reconstitution of hemopoiesis and helps reduce the risk of GVHD. © Copyright 2011, Mary Ann Liebert, Inc.


Shi M.,Kansai Medical University | Shi M.,Guangdong Medical College | Li M.,Kansai Medical University | Cui Y.,Kansai Medical University | And 4 more authors.
PLoS ONE | Year: 2014

It has been shown that allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) plus thymus transplantation (TT) is effective in treating recipients with malignant tumors. Although TT increases the percentage of T cells in the early term after BMT, the myeloid-derived suppressor cells (MDSCs) are still the dominant population. We used the Gr-1 Ab to deplete the granulocytic MDSCs (G-MDSCs) in tumor-bearing mice that had received BMT+TT. Two weeks after the BMT, the mice injected with Gr-1 Ab showed smaller tumors than those in the control group. In addition, Gr-1 Ab significantly increased the percentages and numbers of CD4+ and CD8+ T cells, and decreased the percentages and numbers of MDSCs and G-MDSCs. No side effects of the Gr-1 Ab on recipient or donor thymus were observed. These findings indicate that Gr-1 Ab administered after BMT+TT may enhance the effectiveness of tumor suppression. © 2014 Shi et al.


Asao T.,Gunma University | Yazawa S.,Gunma University | Yazawa S.,Otsuka Pharmaceutical Factory Inc. | Nishimura T.,Otsuka Pharmaceutical Factory Inc. | And 4 more authors.
BioMed Research International | Year: 2013

Human plasma α1-acid glycoprotein (AGP) from cancer patients and healthy volunteers was purified by sequential application of ion-exchange columns, and N-linked glycans enzymatically released from AGP were labeled and applied to a mass spectrometer. Additionally, a novel software system for use in combination with a mass spectrometer to determine N-linked glycans in AGP was developed. A database with 607 glycans including 453 different glycan structures that were theoretically predicted to be present in AGP was prepared for designing the software called AGPAS. This AGPAS was applied to determine relative abundance of each glycan in the AGP molecules based on mass spectra. It was found that the relative abundance of fucosylated glycans in tri- and tetra-antennary structures (FUCAGP) was significantly higher in cancer patients as compared with the healthy group (P<0.001). Furthermore, extremely elevated levels of FUCAGP were found specifically in patients with a poor prognosis but not in patients with a good prognosis. In conclusion, the present software system allowed rapid determination of the primary structures of AGP glycans. The fucosylated glycans as novel tumor markers have clinical relevance in the diagnosis and assessment of cancer progression as well as patient prognosis. © 2013 Takayuki Asao et al.


Yazawa S.,Gunma University | Yazawa S.,Otsuka Pharmaceutical Factory Inc. | Yokobori T.,Gunma University | Ueta G.,Nagaoka University of Technology | And 14 more authors.
PLoS ONE | Year: 2014

Blood group-related glycans determining ABO and Lewis blood groups are known to function as attachment factors for most of the norovirus (NoV) strains. To identify binding specificity of each NoV, recombinant norovirus-like particles (VLPs) and human saliva samples with different ABO, Lewis phenotypes and secretor status have been commonly applied. When binding specificities of VLPs prepared from 16 different genotypes of NoVs in GI and GII genogroups were characterized in samples of human gastric mucosa compared to human saliva based on blood group phenotypes, considerable differences were observed for several strains. Novel binding specificities determined by an ELISA using preparations from human gastric mucosa were also ascertained by immunohistochemical analyses using human jejunal mucosa, widely believed to be susceptible to NoV infection. Further, A, B and O(H) blood group substances prepared from porcine and squid tissues were found to be effective for preventing ABO blood group-specific binding of VLPs to both saliva and mucosa samples. Therefore, these blood group substances might have potential for the prevention and treatment of NoV infection. © 2014 Yazawa et al.


PubMed | Inflammatory Bowel Disease Center, Fukuoka University, The University of Shimane, Saga Medical School and 22 more.
Type: | Journal: BMC gastroenterology | Year: 2015

Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohns disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD.In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level).Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 5.3 days in the weekly GMA and 21.7 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/L to 6950/L (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern.In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.


PubMed | JIMRO Co., Nihon University, University of Nantes, Otsuka Pharmaceutical Factory Inc. and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2014

Blood group-related glycans determining ABO and Lewis blood groups are known to function as attachment factors for most of the norovirus (NoV) strains. To identify binding specificity of each NoV, recombinant norovirus-like particles (VLPs) and human saliva samples with different ABO, Lewis phenotypes and secretor status have been commonly applied. When binding specificities of VLPs prepared from 16 different genotypes of NoVs in GI and GII genogroups were characterized in samples of human gastric mucosa compared to human saliva based on blood group phenotypes, considerable differences were observed for several strains. Novel binding specificities determined by an ELISA using preparations from human gastric mucosa were also ascertained by immunohistochemical analyses using human jejunal mucosa, widely believed to be susceptible to NoV infection. Further, A, B and O(H) blood group substances prepared from porcine and squid tissues were found to be effective for preventing ABO blood group-specific binding of VLPs to both saliva and mucosa samples. Therefore, these blood group substances might have potential for the prevention and treatment of NoV infection.


Patent
Jms Co. and Jimro Co. | Date: 2014-08-21

A blood reservoir (20) for storing blood includes a first storage section (21), a second storage section (22), and a third storage section (23) that is provided between the first storage section and the second storage section, and communicates with the first storage section and the second storage section. A volume of the blood reservoir (20) can be adjusted by changing the amount of expansion or contraction of a bellows structure (28) using a bellows adjustment mechanism (83, 93).


Ansary M.M.U.,The University of Shimane | Ishihara S.,The University of Shimane | Oka A.,The University of Shimane | Kusunoki R.,The University of Shimane | And 6 more authors.
Inflammatory Bowel Diseases | Year: 2014

Apoptosis is a programmed physiological death of unwanted cells, and handling of apoptotic cells (ACs) is thought to have profound effects on immune-mediated disorders. However, there is scant information regarding the role of ACs in intestinal inflammation, in which immune homeostasis is a major concern. To investigate this, we injected ACs into a severe combined immunodeficiency adoptive transfer model of chronic colitis in the presence and absence of cotransferred whole B or regulatory B cell (Breg)-depleted B cells. We also injected syngeneic ACs into AKR/N mice as a control and into milk fat globule-epidermal growth factor 8 knockout mice deficient of phagocytic function. Chronic colitis severity was significantly reduced in the AC as opposed to the phosphate-buffered saline group with cotransferred whole B cells. The AC-mediated effect was lost in the absence of B cells or presence of Breg-depleted B cells. In addition, ACs induced splenic B cells to secrete significantly increased levels of interleukin 10 in AKR/N mice but not milk fat globule-epidermal growth factor 8 knockout mice. Apoptotic leukocytes were induced by reactive oxygen species during granulocyte/monocyte apheresis therapy in rabbits and H2O2-induced apoptotic neutrophils ameliorated mice colitis. Our results indicate that ACs are protective only in the presence of B cells and phagocytosis of ACs induced interleukin 10 producing Bregs. Thus, the ameliorative effect seen in this study might have been exerted by ACinduced Bregs through increased production of the immunosuppressive cytokine interleukin 10, whereas an AC-mediated effect may contribute to the antiinflammatory effect of granulocyte/monocyte apheresis as a novel therapeutic mechanism for inflammatory bowel disease. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

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