Akira Shimizu

Massachusetts General Hospital, Boston, MA, United States

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Publications (449)2079.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis.
    Clinical and Experimental Nephrology 07/2014; · 1.25 Impact Factor
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    ABSTRACT: Aim This study aimed to carry out a case-control research study to assess occurrence of clicking of the temporo-mandibular joint (TMJ) in order to establish the relation-ship between TMJ clicking and the genotype of ''ANKH inorganic pyrophosphate transport regulator'' (ANKH) polymorphisms. Materials and Method A sample of 41 first-year dental residents was selected. Each was examined using standard clinical procedures and genotyping techniques. Results The participation rate was 91.8 %. The preva-lence of TMJ clicking was 51.2 % (95 % CI: 35.7–66.7 %). Occurrence of TMJ clicking was not related to age, gender and genotypes of ANKH-OR as well as ANKH-TR polymorphisms (p C 0.165). Conclusion A similar distribution of ANKH genotypes in TMJ clicking and asymptomatic individuals has been demonstrated by this study. A high percentage of TMJ clicking has been confirmed. Future investigations are indicated.
    Journal of Maxillofacial and Oral Surgery 05/2014;
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    ABSTRACT: Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (Cebpb) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in Cebpb deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of Cebpb, using a sample of Cebpb-/-, Cebpb+/- and Cebpb+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (muCT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with muCT. Masseter and temporal muscles were collected and weighed. Expression of Cebpb was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique.
    Journal of Biomedical Science 05/2014; 21(1):44. · 2.46 Impact Factor
  • Article: ERRATA.
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    ABSTRACT: While reviewing the manuscript entitled "Novel collagen/gelatin scaffold with sustained release of basic fibroblast growth factor: clinical trial for chronic skin ulcers" by Morimoto N, Yoshimura K, Niimi M, Ito T, Aya R, Fujitaka J, Tada H, Teramukai S, Murayama T, Toyooka C, Miura K, Takemoto S, Kanda N, Kawai K, Yokode M, Shimizu A, and Suzuki S, published in Tissue Engineering Part A (2013 Sep;19(17-18):1931-40), several numeric errors in the text and the figure legend were identified, as listed in errata below. The Figure 5 legend indicates the time course of the case of pressure ulcer (Case 3), whereas the numbers of the legend are transcribed from another case. These are transcription errors from our clinical study report and these errors do not change the conclusion of the paper. I would appreciate it very much if we could make these corrections in our article.
    Tissue Engineering Part A 05/2014; · 4.64 Impact Factor
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    ABSTRACT: The majority of patients with systemic sclerosis (SSc) have gastrointestinal (GI) tract involvement, but therapies using prokinetic agents are usually unsatisfactory. Ghrelin stimulates gastric motility in healthy human volunteers. In this study, we investigated whether ghrelin could improve gastric emptying in patients with gastrointestinal symptoms due to SSc. The study was performed in a randomized, double-blind, placebo-controlled crossover fashion on two occasions. Ten SSc patients with GI tract involvement received an infusion of either ghrelin (5.0 μg/kg) or saline, and gastric emptying rate was evaluated by (13)C-acetic acid breath test. Gastric emptying was significantly accelerated by ghrelin infusion in patients with SSc (ghrelin vs. saline: 43.3 ± 11.4 min vs. 53.4 ± 5.4 min, P≡0.03). No serious adverse effects were observed. Our results suggest that ghrelin might represent a new therapeutic approach for GI tract involvement in patients with SSc.
    Endocrine Journal 04/2014; · 2.23 Impact Factor
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    ABSTRACT: We previously reported life-supporting α1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b). Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention.
    Journal of the American Society of Nephrology 01/2014; · 8.99 Impact Factor
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    ABSTRACT: Bone morphogenetic proteins (BMPs) are highly conserved signaling molecules that are part of the transforming growth factor (TGF)-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1) suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.
    PLoS ONE 01/2014; 9(5):e96938. · 3.73 Impact Factor
  • 01/2014; 81(3):120-1.
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    ABSTRACT: Neoadjuvant chemotherapy has been shown to have benefit in T1 high-grade or T2 bladder cancer. However, neoadjuvant chemotherapy fails in some patients. Careful patient selection for neoadjuvant chemotherapy is therefore needed. Several reports show that Snail is associated with resistance to chemotherapy. We hypothesized that Snail expression could predict survival in T1 high-grade and T2 bladder cancer patients treated with neoadjuvant chemotherapy. The participants were 44 patients with T1 high-grade and T2 bladder cancer receiving neoadjuvant chemotherapy. Immunohistochemical analysis was used to determine Snail expression in specimens of bladder cancer obtained by transurethral resection before neoadjuvant chemotherapy. The relationships between Snail expression and patients' outcomes were analyzed. Snail expression was positive in 15 of the 44 patients (34.1%) and negative in 29 (65.9%). Disease-free survival was significantly shorter for the Snail-positive group than for the Snail-negative group (p = 0.014). In addition, disease-specific survival was also significantly shorter for the Snail-positive group than for the Snail-negative group (p = 0.039). In multivariate analysis, Snail expression level was identified as an independent prognostic factor for disease-specific survival (p = 0.020). The results indicate that Snail expression may predict poor outcome in T1 high-grade and T2 bladder cancer patients treated with neoadjuvant chemotherapy.
    BMC Urology 12/2013; 13(1):73. · 1.69 Impact Factor
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    ABSTRACT: Sialic acids (Sias) are often conjugated to the termini of cellular glycans and are key mediators of cellular recognition. Sias are nine-carbon acidic sugars, and, in vertebrates, the major species are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), differing in structure at the C5 position. Previously, we described a positive feedback loop involving regulation of Neu5Gc expression in mouse B cells. In this context, Neu5Gc negatively regulated B-cell proliferation and Neu5Gc expression was suppressed upon activation. Similarly, resting mouse T cells expressed principally Neu5Gc, and Neu5Ac was induced upon activation. In the present work, we used various probes to examine sialoglycan expression by activated T cells in terms of the Sia species expressed and the linkages of Sias to glycans. Upon T-cell activation, sialoglycan expression shifted from Neu5Gc to Neu5Ac and the linkage from α2,6 to α2,3. These changes altered the expression levels of siglec (sialic acid-binding immunoglobulin-like lectins) ligands. Expression of sialoadhesin and Siglec-F ligands increased, and that of CD22 ligands decreased. Neu5Gc exerted a negative effect on T-cell activation, both in terms of the proliferative response and in the context of activation-marker expression. Suppression of Neu5Gc expression in mouse T and B cells prevented the development of nonspecific CD22-mediated T cell-B cell interactions. Our results suggest that an activation-dependent shift from Neu5Gc to Neu5Ac and replacement of α2,6 by α2,3 linkages, may regulate immune cell interactions at several levels.
    Journal of Biological Chemistry 12/2013; · 4.65 Impact Factor
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    ABSTRACT: We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC-matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs). Group 1 animals (n=3) received donor MHC-matched VCAs less than 70 days after primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched kidney transplant followed by a donor-matched VCA more than 200 days after primary KTx. Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of three recipients of VCAs in Group 2, accepted all components of the VCA, including epidermis (>200 days). The other two recipients lost only the epidermis on days 45 and 85, with survival of the remainder of the VCA long-term. All tissues of a VCA are accepted long-term on animals tolerant of class I-mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared with split-thickness skin grafts but not indefinite. Exposure of tolerant animals to second donor-matched kidneys before VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney.
    Transplantation 09/2013; · 3.78 Impact Factor
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    ABSTRACT: We have previously shown that tolerance of kidney allografts across a full major histocompatibility complex (MHC) barrier can be induced in miniature swine by a 12-day course of high-dose tacrolimus. However, that treatment did not prolong survival of heart allografts across the same barrier. We have now tested the effect of cotransplanting an allogeneic heart and kidney from the same MHC-mismatched donor using the same treatment regimen. Heart allografts (n = 3) or heart plus kidney allografts (n = 5) were transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. As expected, all isolated heart allografts rejected by postoperative day 40. In contrast, heart and kidney allografts survived for >200 days with no evidence of rejection on serial cardiac biopsies. Heart/kidney recipients lost donor-specific responsiveness in cell-mediated lympholysis and mixed-lymphocyte reaction assays, were free of alloantibody and exhibited prolonged survival of donor, but not third-party skin grafts. Late (>100 days) removal of the kidney allografts did not cause acute rejection of the heart allografts (n = 2) and did not abrogate donor-specific unresponsiveness in vitro. While kidney-induced cardiac allograft tolerance (KICAT) has previously been demonstrated across a Class I disparity, these data demonstrate that this phenomenon can also be observed across the more clinically relevant full MHC mismatch. Elucidating the renal element(s) responsible for KICAT could provide mechanistic information relevant to the induction of tolerance in recipients of isolated heart allografts as well as other tolerance-resistant organs.
    American Journal of Transplantation 08/2013; · 6.19 Impact Factor
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    ABSTRACT: In addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets after allogeneic islet cell transplantation. Using our previously described islet-kidney (IK) transplantation model in miniature swine, we studied whether an islet-toxic triple-drug immunosuppressive regimen (cyclosporine+azathioprine+prednisone) affects the islet engraftment process and thus long-term islet function. Donor animals underwent partial pancreatectomy, autologous islet preparation, and injection of these islets under the autologous kidney capsule to prepare an IK. Experimental animals received daily triple-drug immunosuppression during the islet engraftment period. Control animals did not receive any immunosuppression during this period. Four to 8 weeks later, these engrafted IK were transplanted across a minor histocompatibility mismatched barrier into pancreatectomized, nephrectomized recipient animals at an islet dose of approximately 4500 islet equivalents/kg recipient weight. Cyclosporine was administered for 12 days to the recipients to induce tolerance of the IK grafts and the animals were followed long-term. Diabetes was corrected by IK transplantation in all pancreatectomized recipients on both the control arm (n=3) and the experimental arm (n=4) of the study and all animals showed normal glucose regulation over the follow-up period. Intravenous glucose tolerance tests performed at 1, 2, and 3 or more months after IK transplantation showed essentially equivalent glycemic control in both control and experimental animals. In this preclinical in vivo large animal model of islet transplantation, the effect of triple-drug immunosuppression on islet function does not negatively affect islet engraftment as assessed by the long-term function of engrafted islets.
    Transplantation 07/2013; · 3.78 Impact Factor
  • Human pathology 06/2013; 44(6):1193-1194. · 3.03 Impact Factor
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    ABSTRACT: Hepatic artery (HA) reconstruction is performed in the clinical liver transplantation. We assessed the importance of HA reconstruction in the success of liver transplantation. Orthotopic liver transplantation was performed without immunosspression from Lewis (RT1l) to Lewis rats (syngeneic transplantation) as well as Lewis to BN (RT1n) rats (allogeneic transplantation) with or without HA reconstruction. We examined graft function, pathology, and mRNA levels using DNA arrays in both arterialized and nonarterialized liver grafts. In Lewis-to-Lewis syngeneic grafts, both the arterialized and nonarterialized grafts survived >120 days with normal graft function. lnfiltration of CD3(+) T cells and CD68(+) macrophages, marked bile duct proliferation with apoptotic epithelial cells, and expansion and increasing fibrosis of portal areas were evident in the nonarterialized grafts at day 120, although preservation of architecture was noted in the arterialized grafts. DNA array analysis of nonarterialized syngeneic grafts demonstrated the upregulation of mRNA of cell death-related proteins, cell cycle-related proteins, and inflammation-related proteins than those in arterialized grafts. Moreover, the arterialized Lewis-to-BN allogeneic grafts could survive for a long time with less severe graft dysfunction than those in non-arterialized allogeneic grafts. HA reconstruction in liver transplantation inhibited hypoxic injury and subsequent inflammation and bile duct proliferation, prevented the augmentation of T-cell-and antibody-mediated rejection, and mediated long-term graft acceptance. HA reconstruction is essential factor in the success of liver transplantation.
    Transplantation Proceedings 06/2013; 45(5):1748-53. · 0.95 Impact Factor
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    ABSTRACT: The category of chronic antibody-mediated rejection (AMR) is not included in Banff schema for liver allograft rejection. In the present study, we examined the pathology of chronic rejection using rat liver transplantation. Orthotopic liver transplantation from Lewis to BN rats was performed without immunosuppression, and with or without HA reconstruction. We studied grafts at day 120 for arterialized and day 39 for nonarterialized transplants focusing on the immunoglobulin G (IgG) deposition and the pathologic characteristics of rejection. About 20% of arterialized grafts survived more than 120 days. Between day 7 and day 120, T-cell infiltration to arterialized grafts was accompanied by IgG deposition in portal veins, hepatic arteries, and bile ducts in portal areas, sinusoids and hepatocytes. At day 120, arterialized grafts were morphologically characterized by late chronic rejection with IgG deposition, intraluminal portal veins fibrosis, intimal fibrous thickening of hepatic arteries, diffuse sinusoidal fibrosis, as well as injury and loss of bile ducts due to fibrosis. The severities of T cell-mediated rejection and AMR were higher in nonarterialized than arterialized grafts. Nonarterialized Lewis liver grafts in BN rats were rejected by day 39, as characterized by late chronic rejection with IgG deposition and cellular infiltration. In conclusion, chronic AMR may be involved in chronic rejection of liver transplantations. When chronic AMR was involved in chronic liver graft rejection, typical late morphological changes emerged within a short period.
    Transplantation Proceedings 06/2013; 45(5):1743-7. · 0.95 Impact Factor
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    ABSTRACT: BACKGROUND: Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. METHOD AND RESULTS: In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an α-1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). CONCLUSIONS: These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice.
    Xenotransplantation 04/2013; · 2.57 Impact Factor
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    ABSTRACT: Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in healthcare. We have developed a novel artificial dermis, collagen/gelatin sponge (CGS), which is capable of the sustained release of basic fibroblast growth factor (bFGF) for more than 10 days. The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. Patients with chronic skin ulcers that had not healed in at least four weeks were treated with CGS impregnated with bFGF at 7 μg/cm2 or 14 μg/cm2 after debridement, and the wound bed improvement was assessed 14 days after application. Wound bed improvement was defined as a granulated and epithelialized area on Day 14 with a proportion to the baseline wound area after debridement of 50% or higher. The wound area, the wound area on Day 14, and the granulation area on Day 14 were independently measured by blinded reviewers in a central review using digital images of wounds taken with a calibrator. Patients were followed up until 28 days after application to observe the adverse reactions related to the application of CGS. From May 2010 to June 2011, 17 patients were enrolled and, in 16 patients, the wound bed improved. Among the randomized patients in step 2, no significant difference was seen between the low-dose group and the high-dose group. No serious adverse reactions were observed. Adverse reactions with a clear causal relationship to the study treatment were mild and recovered from quickly. This study is the first-in-man clinical trial of CGS and showed the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. This combination therapy could be a promising therapy for chronic skin ulcers.
    Tissue Engineering Part A 03/2013; · 4.64 Impact Factor
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    ABSTRACT: BACKGROUND: Nanoparticle of Lactosome, which is composed of poly(l-Lactic acid)-base depsipeptide with diameter of 35 nm, accumulates in solid tumors by the enhanced permeability and retention (EPR) effect. However, a pharmacokinetic alteration of Lactosome was observed when Lactosome was repeatedly administered. This phenomenon is named as the Lactosome accelerated blood clearance (ABC) phenomenon. In this study, the effect of Lactosome dose on the ABC phenomenon was examined and discussed in terms of immune tolerance. METHODS: To tumor transplanted mice, Lactosome (0-350 mg/kg) was administrated. At 7 days after the first administration, indocyanine green (ICG)-labeled Lactosome (ICG-Lactosome, 0-350 mg/kg) was injected. Near-infrared fluorescence imaging was performed, and biodistribution of ICG-Lactosome was evaluated. Further, the produced amounts of anti-Lactosome IgM were determined by ELISA. RESULTS: ICG-Lactosome accumulated in the tumor region when the first Lactosome dose exceeded over 150 mg/kg. The amounts of anti-Lactosome IgM were inversely correlated with the first Lactosome doses. Even after establishment of the Lactosome ABC phenomenon with the first Lactosome dose as low as 5.0 mg/kg, the Lactosome ABC phenomenon can be evaded apparently by dosing ICG-Lactosome over 50 mg/kg regardless of anti-Lactosome IgM production. CONCLUSIONS: There are two different mechanisms for evasion from the Lactosome ABC phenomenon before and after its establishment. In either mechanism, however, the Lactosome ABC phenomenon can be evaded by excessive administration of Lactosome. GENERAL SIGNIFICANCE: Lactosome is a potential nanocarrier for drug and/or imaging agent delivery, which can be used for frequent administrations without significant pharmacokinetic alterations.
    Biochimica et Biophysica Acta 03/2013; · 4.66 Impact Factor

Publication Stats

9k Citations
2,079.59 Total Impact Points

Institutions

  • 1997–2013
    • Massachusetts General Hospital
      • • Transplantation Biology Research Center
      • • Department of Surgery
      • • Department of Pathology
      Boston, MA, United States
  • 1993–2013
    • Nippon Medical School
      • • Department of Analytic Human Pathology
      • • Department of Internal Medicine
      • • Department of Pathology
      Tokyo, Tokyo-to, Japan
  • 1985–2012
    • Kyoto University
      • • Department of Oral and Maxillofacial Surgery
      • • Department of Experimental Therapeutics
      • • Graduate School of Biostudies
      • • Institute for Frontier Medical Sciences
      • • Department of Biophysics
      • • Department of Medical Chemistry
      • • Graduate School of Medicine / Faculty of Medicine
      Kyoto, Kyoto-fu, Japan
  • 1988–2011
    • Harvard Medical School
      • • Department of Pathology
      • • Department of Genetics
      Boston, Massachusetts, United States
    • Howard Hughes Medical Institute
      Maryland, United States
  • 2010
    • Iwate Medical University
      Morioka, Iwate, Japan
  • 2009–2010
    • Kagoshima University
      Kagosima, Kagoshima, Japan
  • 1993–2009
    • Osaka Medical College
      • • First Department of Internal Medicine
      • • Department of Otolaryngology
      • • Central Research Laboratory
      Takatuki, Ōsaka, Japan
  • 2008
    • Kansai Medical University
      • Institute of Biomedical Science
      Moriguchi, Ōsaka, Japan
  • 2002–2006
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 2005
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
    • Tokyo Women's Medical University
      • Kidney Center
      Edo, Tōkyō, Japan
    • University of Fukui
      • Division of Molecular Genetics
      Hukui, Fukui, Japan
    • Kobe Tokiwa University
      Kōbe, Hyōgo, Japan
  • 2003–2004
    • Universitätsklinikum Freiburg
      Freiburg an der Elbe, Lower Saxony, Germany
    • Aichi Prefectural Institute of Public Health
      Nagoya, Aichi, Japan
  • 1989
    • Dokkyo Medical University
      Totigi, Tochigi, Japan
  • 1980
    • National Institute of Child Health and Human Development
      Maryland, United States
    • The University of Tokyo
      Edo, Tōkyō, Japan