PubMed Health⌕ Search

Biomedical subjects

Shunichi Kato

Publications and source records attributed to Shunichi Kato.

At least 19 recordsLinked to original sources
PubMed2007

Allogeneic bone marrow transplantation from unrelated human T-cell leukemia virus-I-negative donors for adult T-cell leukemia/lymphoma: retrospective analysis of data from the Japan Marrow Donor Program.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-matched related donor has been suggested to improve the poor prognosis of adult T-cell leukemia/lymphoma (ATLL). However, the infusion of HTLV-I-infected cells from HTLV-I-positive related donors could lead to the development of donor-derived ATLL under immunosuppressive conditions. Although most ATLL patients lack a suitable HLA-matched related donor and require an HTLV-I-negative unrelated donor, little information is currently available regarding the outcome of unrelated bone marrow transplantation (UBMT) for ATLL. To evaluate the role of UBMT in treating ATLL, we retrospectively analyzed data from 33 patients with ATLL treated by UBMT through the Japan Marrow Donor Program (JMDP). Overall survival (OS), progression-free survival, and cumulative incidence of disease progression and progression-free mortality at 1 year after UBMT were 49.5%, 49.2%, 18.6%, and 32.3%, respectively. Multivariate analysis identified recipient age as an independent prognostic factor for OS (P = .044). Patients age >or=50 years who showed nonremission at transplantation tended to have higher rates of treatment-related mortality. Our observations suggest that UBMT could represent a feasible treatment option for ATLL patients and warrant further investigation based on these risk factors.

Adult↗
PubMed2006

Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells.

To elucidate the in vivo kinetics of human hematopoietic stem cells (HSCs), CD34+CD38- cells were infected with lentivirus vector and transplanted into immunodeficient mice. We analyzed the multilineage differentiation and self-renewal abilities of individual thymus-repopulating clones in primary recipients, and their descending clones in paired secondary recipients, by tracing lentivirus gene integration sites in each lymphomyeloid progeny using a linear amplification-mediated polymerase chain reaction (PCR) strategy. Our clonal analysis revealed that a single human thymus-repopulating cell had the ability to produce lymphoid and myeloid lineage cells in the primary recipient and each secondary recipient, indicating that individual human HSCs expand clonally by self-renewal division. Furthermore, we found that the proportion of HSC clones present in the CD34+ cell population decreased as HSCs replicated during extensive repopulation and also as the differentiation capacity of the HSC clones became limited. This indicates the restriction of the ability of individual HSCs despite the expansion of total HSC population. We also demonstrated that the extensive self-renewal potential was confined in the relatively small proportion of HSC clones. We conclude that our clonal tracking studies clearly demonstrated that heterogeneity in the self-renewal capacity of HSC clones underlies the differences in clonal longevity in the CD34+ stem cell pool.

ADP-ribosyl Cyclase 1↗
PubMed2006

Direct evidence for ex vivo expansion of human hematopoietic stem cells.

To characterize human hematopoietic stem cells (HSCs), xenotransplantation techniques such as the severe combined immunodeficiency (SCID) mouse repopulating cell (SRC) assay have proven the most reliable methods thus far. While SRC quantification by limiting dilution analysis (LDA) is the gold standard for measuring in vitro expansion of human HSCs, LDA is a statistical method and does not directly establish that a single HSC has self-renewed in vitro. This would require a direct clonal method and has not been done. By using lentiviral gene marking and direct intra-bone marrow injection of cultured CD34+ CB cells, we demonstrate here the first direct evidence for self-renewal of individual SRC clones in vitro. Of 74 clones analyzed, 20 clones (27%) divided and repopulated in more than 2 mice after serum-free and stroma-dependent culture. Some of the clones were secondary transplantable. This indicates symmetric self-renewal divisions in vitro. On the other hand, 54 clones (73%) present in only 1 mouse may result from asymmetric divisions in vitro. Our data demonstrate that current ex vivo expansion conditions result in reliable stem cell expansion and the clonal tracking we have employed is the only reliable method that can be used in the development of clinically appropriate expansion methods.

Animals↗
PubMed2006

Development of human-human hybridoma from anti-Her-2 peptide-producing B cells in immunized NOG mouse.

OBJECTIVE: Numerous monoclonal antibodies have been developed for the purpose of medical treatments, including cancer treatment. For clinical application, the most useful are human-derived antibodies. In this study, we tried to prepare designed antigen-specific antibodies of completely human origin using immunodeficient mouse. METHODS: Nonobese diabetic/severe combined immunodeficient/IL-2 receptor gamma null mouse (NOG) mouse was used to reconstitute the human immune system with umbilical cord blood hematopoietic stem cells (CB-NOG mouse) and to prepare human-derived Her-2-epitope-specific antibodies. Hybridoma lines were prepared by fusing the human myeloma cell line Karpas707H. RESULTS: Serum of immunized NOG mouse contained human-derived immunoglobulin M (IgM) antibodies specific for a short peptide sequence of 20 amino acids, including the epitope peptide of apoptotic Her-2 antibody CH401. Hybridoma lines were successfully prepared with spleen B cells obtained from the immunized CB-NOG mouse. One of these cell lines produced human IgM against the epitope peptide that can recognize surface Her-2 molecule. CONCLUSION: We could produce human-derived IgM antibody against Her-2 epitope peptide in CB-NOG mouse, succeeding in generation of human hybridoma-secreting IgM against a given peptide.

Animals↗
PubMed2006

Allogeneic haematopoietic cell transplantation from alternative donors with a conditioning regimen of low-dose irradiation, fludarabine and cyclophosphamide in Fanconi anaemia.

A pilot study was undertaken using a fludarabine-based conditioning regimen to improve haematopoietic cell transplantation (HCT) from alternative donors in 27 Fanconi anaemia (FA) patients. Patients were conditioned with 150-180 mg/m2 of fludarabine, 40 mg/kg of cyclophosphamide, 5-10 mg/kg of antithymocyte globulin, and 300-450 cGy of thoracoabdominal/total body irradiation. One patient who received unrelated cord blood transplantation failed to engraft, another patient died of sepsis. The 1-year overall survival was 96.3% (95% CI, 89-100). This conditioning regimen exerted an immunosuppressive effect that enabled durable engraftment in alternative donor HCT without severe toxicity.

Child↗
PubMed2006

Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan.

A total of 57 patients with Wiskott-Aldrich syndrome (WAS) were studied after undergoing stem cell transplantation (SCT) in Japan between January 1985 and December 2004. Eleven patients received transplants from human leucocyte antigen (HLA)-matched related donors, 10 from HLA-mismatched related donors, 21 from unrelated bone marrow donors, and 15 from unrelated cord blood donors. Nine of the 57 patients rejected the initial graft. The overall 5-year survival rate was 73.7% and the 5-year failure-free survival rate was 65.7% (failure was defined as rejection or death). The overall 5-year survival rates for patients receiving bone marrow and cord blood from unrelated donors were both 80.0%. Based on univariate analysis, the factors associated with poor survival were: transplantation from an HLA-mismatched related donor, patient age of more than 5 years at the time of transplantation, and a conditioning regimen other than busulfan and cyclophosphamide (BU-CY) or busulfan, cyclophosphamide and antithymocyte globulin (BU-CY-ATG). In a multivariate analysis, a conditioning regimen other than BU-CY and BU-CY-ATG was the only independent factor associated with transplantation failure. Given the improved outcome for WAS patients following transplantation from an unrelated donor, we conclude that patients with WAS should receive SCT as soon as possible after diagnosis.

Adolescent↗
PubMed2006

Current status of hematopoietic cell transplantation for adult patients with hematologic diseases and solid tumors in Japan.

A nationwide survey of hematopoietic cell transplantation (HCT) was started in Japan in 1991, and the analyzed survey data have been presented as the annual report of the Japan Society for Hematopoietic Cell Transplantation. The 10-year overall survival (OS) rates after HCT for each disease are as follows: acute myelogenous leukemia, 44.2%; acute lymphocytic leukemia, 33.7%; adult T-cell leukemia, 24.6%; chronic myelogenous leukemia, 53.3%; myelodysplastic syndrome, 37.3%; non-Hodgkin's lymphoma, 41.5%; Hodgkin's lymphoma, 50.8%; aplastic anemia, 72.5%; breast cancer, 37.1%; germ cell tumor, 52.6%; and ovarian cancer, 44.2%. The 5-year OS rates for multiple myeloma and lung cancer were 40.6% and 23.6%, respectively. Except in cord blood transplantation, engraftment was accomplished in more than 90% of patients. The respective frequencies of acute graft-versus-host disease (GVHD) and chronic GVHD were 41.1% and 34.9% for related bone marrow transplantation (BMT), 66.8% and 34.5% for unrelated BMT, 52.9% and 36.0% for allogeneic peripheral blood stem cell transplantation, and 53.3% and 32.1% for allogeneic cord blood transplantation. OS for each disease was analyzed by patient age, stem cell source, donor type, disease status, and disease type. These data provide objective and valuable information for hematologists as well as for patients who need HCT.

Adolescent↗
PubMed2005

Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment.

Hematopoiesis is maintained by specific interactions between both hematopoietic and nonhematopoietic cells. Whereas hematopoietic stem cells (HSCs) have been extensively studied both in vitro and in vivo, little is known about the in vivo characteristics of stem cells of the nonhematopoietic component, known as mesenchymal stem cells (MSCs). Here we have visualized and characterized human MSCs in vivo following intramedullary transplantation of enhanced green fluorescent protein-marked human MSCs (eGFP-MSCs) into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Between 4 to 10 weeks after transplantation, eGFP-MSCs that engrafted in murine BM integrated into the hematopoietic microenvironment (HME) of the host mouse. They differentiated into pericytes, myofibroblasts, BM stromal cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells, which constituted the functional components of the BM HME. The presence of human MSCs in murine BM resulted in an increase in functionally and phenotypically primitive human hematopoietic cells. Human MSC-derived cells that reconstituted the HME appeared to contribute to the maintenance of human hematopoiesis by actively interacting with primitive human hematopoietic cells.

Animals↗
PubMed2005

Effect of conditioning regimen on the outcome of bone marrow transplantation from an unrelated donor.

Little information is available regarding the effect of the conditioning regimen on the outcome of bone marrow transplantation (BMT) from an unrelated donor. Therefore, we retrospectively compared the outcome after a cyclophosphamide/total body irradiation (Cy-TBI) regimen, an intensified Cy-TBI regimen (Cy-TBI+), a busulfan and cyclophosphamide (Bu-Cy) regimen, and a Bu-Cy regimen with total lymphoid irradiation (Bu-Cy-TLI). Clinical data of 1875 adult patients who underwent unmanipulated unrelated BMT for leukemia or myelodysplastic syndrome by using 1 of the 4 regimens between 1993 and 2002 were extracted from the database of the Japan Marrow Donor Program. The effect of the conditioning regimen was adjusted for other independent significant factors by multivariate analyses. The Cy-TBI regimen was significantly better than the Bu-Cy regimen with regard to the incidence of engraftment failure (odds ratio, 2.49; P = .046) and overall survival (relative risk [RR], 1.31; P = .050). The Bu-Cy-TLI regimen decreased relapse (RR, 0.13; P = .039) but increased nonrelapse mortality (RR, 1.89; P = .0061). The Cy-TBI+ regimen resulted in increased nonrelapse mortality (RR, 1.48; P = .0003) and inferior survival (RR, 1.45; P < .0001). The results of this retrospective study suggested that the Cy-TBI regimen was superior to other regimens in unrelated BMT.

Adolescent↗
PubMed2005

Natural history of X-linked adrenoleukodystrophy in Japan.

The natural history of X-linked adrenoleukodystrophy (ALD) was investigated, using a nation-wide retrospective study based on a questionnaire survey. The data on 145 patients, including 46 patients with the childhood cerebral form, 39 with adrenomyeloneuropathy (AMN), 33 with the adult cerebral form, 14 with the adolescent form and 13 with the olivo-ponto-cerebellar (OPC) form, were analyzed. Initial symptoms of the childhood cerebral form were intellectual (n=16) and visual (n=11) disturbances, whereas those of AMN were gait (n=37) and sensory (n=3) disturbances; the adult cerebral form, psychic (n=19) and gait (n=11) disturbances; the adolescent form, visual n=5) and gait (n=4) disturbances; and the OPC form, gait (n=9) disturbance. Patients with onset under the age of 8 years progressed more rapidly than those over 8 years old. Visual, hearing, gait and swallowing disturbances progressed more slowly in the older group. About half of AMN patients showed cerebral involvement about 10 years after onset. Patients with the OPC form also showed a similar progression. A Kaplan-Meier plot clarified the characteristic pattern of progression of neurological symptoms in each phenotype. These finding will improve the understanding of the natural history of X-linked ALD and will provide a basis for the evaluation of specific treatment for X-linked ALD.

Adolescent↗
PubMed2005

Potential and origin of the hematopoietic population in human skeletal muscle.

While mononuclear cells isolated from murine skeletal muscle were shown to be capable of hematopoietic activity, similar hematopoietic cells (HC) recently were reported to exist in primate muscle. We investigated muscle-derived HC from young and adult human subjects. Although hematopoietic stem cells were rare in muscle, their frequency nonetheless was approximately four times greater than in peripheral blood. These cells in muscle appeared to originate from CD45(+) bone marrow cells. Our results suggested an additional function of human skeletal muscle as a reservoir of HC.

Adolescent↗
PubMed2005

Fatal adenovirus infection indistinguishable from thrombotic microangiopathy after allogeneic CD34+ peripheral progenitor cell transplantation.

A 10-year-old boy with acute lymphoblastic leukemia in second relapse received CD34+ purified allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical father. The patient developed grade II acute GVHD and received high-dose methyl-prednisolone starting on day + 13 posttransplant. Renal dysfunction followed by massive gastrointestinal bleeding was observed from day + 14. The laboratory findings including elevated serum LDH, increased RBC fragmentation, higher level of thrombomodulin and undetectable haptoglobin corresponded with the diagnosis of thrombotic microangiopathy (TMA). In spite of various treatments, the patient died of multiple organ failure on day + 93. Post-mortem examination revealed systemic adenovirus infection without histological findings of TMA. Severe adenovirus infection may be confused with TMA, and should be distinguished by rapid virological assay.

Adenoviridae Infections↗
PubMed2005

Secondary G-CSF mobilized blood stem cell transplantation without preconditioning in a patient with Gaucher disease: Report of a new approach which resulted in complete reversal of severe skeletal involvement.

Gaucher disease has been treated by allogeneic bone marrow transplantation (BMT), however, severe bone involvement that is probably the most disabling aspect of this disease is difficult to reverse. Other problem of BMT is the use of intensive preconditioning that adversely affects growth and development of the patients. In this study, a patient with type I Gaucher disease was treated by allogeneic BMT from HLA-matched sibling donor. However, the treatment resulted in late graft failure and the patient developed severe bone involvement. Fifty months after the first BMT, the patient was treated by allogeneic peripheral blood stem cell (PBSC) transplantation without preconditioning. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) was used to mobilize PBSC. Cyclosporine A (CyA) was administered for the prophylaxis of graft-versushost disease (GVHD). Full donor-derived hematopoiesis was obtained, and clinical symptoms including severe bone involvement improved completely with increased glucocerebrosidase activity. It was shown that an engraftment could be obtained without intensive preconditioning when a recipient receives an rhG-CSF-mobilized PBSCs infusion as a secondary transplant. Another important finding of this study is the complete reversal of severe bone involvement by the supply of abundant glucocerebrosidase from high proliferating PBSC graft.

Bone Marrow Transplantation↗
PubMed2005

[Ethical guidelines of the Japan Society for Transplantation].

The Ethics Committee of the Japan Society for Transplantation (JST) renewed its Ethical Guidelines for Organ Transplantation in 2003, and the major points are as follows; 1. The role of the Japan Network of Organ Transplantation was described. 2. The following ethical principles and informed consent standards should be implemented for living donors and should be confirmed by third-party personnels who have no relation or interests with the donor and/or with the recipient and who can act as an advocate of the donor. * voluntary willingness to donate; * free from coercion; * medically and socialy suitable (20 years old or older); * fully informed of the risks and benefits as a donor and; * fully informed of the risk, benefits, and alternative treatment to the recipient. 3. Living donors should be limited to the relatives within the 6th degree and the third by marriage. 4. Living donation other than those relatives should be individually approved by the institutional ethics committee (IEC) and should be reviewed by the JST. 5. Donors between 16 and 19 years can be chosen as an exception if they are interviewed and judged to be psychosocially suitable as the donor by psychiatricians, and such a transplantation should be individually approved by IEC.

Ethics, Medical↗
PubMed2004

Platelets, after exposure to a high shear stress, induce IL-10-producing, mature dendritic cells in vitro.

There is evidence for immune system involvement in atherogenesis. In the present study the effect of platelets on dendritic cells (DC), an important immunologic regulator, was examined in vitro. Platelet-rich plasma, after exposure to shear stress, was added to human monocyte-derived immature DC, which were then examined for surface Ag expression, allogeneic T lymphocyte stimulatory activity, and cytokine production. After exposure, the number of anti-CD40 ligand (anti-CD40L) and anti-P-selectin IgG molecules bound per platelet was increased. These activated platelets induced DC maturation, as revealed by significant up-regulation of CD83, CD80, and CD86 Ags. The addition of platelets in the presence of IFN-gamma plus LPS significantly enhanced IL-10 production from immature DC. After platelet addition, mature DC provoked a significant proliferation of allogeneic naive T lymphocytes. These activated T cells showed lower IFN-gamma production than those stimulated by LPS- and IFN-gamma-treated DC. CD40L on the platelet surface was not involved in maturation of DC, as mAb to CD40L failed to block maturation. The effect of platelets was observed even if platelets and DC were separated using large pore-sized membranes or when platelets were depleted from plasma by centrifugation. Furthermore, it was abrogated after the depletion of protein fraction. Thus, soluble protein factors excreted from activated platelets contribute to IL-10-producing DC maturation.

Adult↗