Seiji Kojima

..The incidence of AA is approximately 3 fold more common in East Asia than in Europe and United States where yearly incidence rates are approximately two patients per one million...

..Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor...

..40). We recommend BMT as first-line therapy in paediatric severe AA patients with an HLA-matched family donor. Alternative donor BMT is recommended as salvage therapy in patients who relapse or do not respond to initial IST...

..Considering our encouraging results, unrelated donor transplantation for SAA is recommended as a salvage therapy in non-responders to IST...

..Matching of HLA class I alleles and improvement of preparative regimens should result in improved outcomes in patients with severe aplastic anemia who receive transplants from unrelated donors...

..The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST...

..All patients are alive at 9 to 56 months after transplantation (median, 33 months). Considering our encouraging results, HLA-mismatched unrelated-donor BMT for SAA is feasible as a salvage therapy for nonresponders to IST...

..4%-96.9%). This result suggests that UCBT using the optimal conditioning regimen can be a salvage treatment for patients without a suitable bone marrow donor and warrants evaluation in further prospective studies...

..53.1%) or anti-PMS1 antibody (40.0% vs. 59.1%). The current study did not confirm a correlation between these markers and the response to IST, suggesting that there is a difference in the pathophysiologies of adult and paediatric AA...

..012). The study shows the superiority of FK/MTX over CsA/MTX in overall survival because of the lower incidence of transplantation-related deaths. A prospective randomized study comparing FK/MTX and CsA/MTX is warranted...

..2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival...

..The finding that response rate worsens with increasing interval between diagnosis and treatment highlights the importance of prompt immunosuppressive therapy for patients with aplastic anemia...

..Event-free survival did not significantly differ between patients with and without ES regardless of the presence of malignant or non-malignant diseases...

..Decreased expression of GATA-2 might be responsible for the pathogenesis and development of the clinical features of the disease...

..28.6%, p = 0.006). In summary, the survival outcomes of pediatric patients with CML were dramatically improved by treatment with IM compared to HSCT...

..Several reports have shown the efficacy of immunosuppressive therapy (IST) in adult patients with refractory anemia (RA), but its safety and efficacy remains to be fully elucidated in childhood RA...

..However, if such a donor is not available, any single-allele or multiple-allele (HLA-C, -DRB1, -DQB1) mismatched donor is acceptable as an unrelated donor for patients with severe aplastic anemia...

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..These findings provide important information for assessing the indications for and improving outcome in unrelated BMT for the treatment of pediatric CML...

..However, detailed analyses of relapses in aplastic anemia children are limited...

..Similar to other types of lymphoma, the absence of CD20 antigen is likely to be characteristic of rituximab-refractory EBV-PTLD...

..They were alive 10, 66, and 72 months after transplantation, respectively. Long-term follow-up is crucial to determine the late effects of our conditioning regimen...

..8 x 10(2) copies/ml of whole blood, respectively, suggesting that the viruses were associated with the clinical condition. Recognizing that coinfection with these viruses may modulate the clinical course of disease is important...

..Recently, hematopoietic stem cell transplantation (HSCT) has been introduced and has the potential to become a standard treatment, although guidelines for HSCT to treat chronic active EBV infection have not yet been proposed...

..001). All patients who died after relapse had PTPN11 mutation. These results suggest that JMML with PTPN11 mutation might be a distinct subgroup with specific clinical characteristics and poor outcome...

..The CD4, CD56, CD3, CD13, CD19, CD33 profile is highly suggestive of this disease, and the CD123 and blood dendritic cell antigen-2 markers are useful in helping to diagnose pDC leukemia...

..Idiopathic pneumonia syndrome (IPS) is a severe complication that can occur after hematopoietic stem cell transplantation (HSCT) and is often associated with a fatal outcome despite intensive supportive care...

..1 and 39.5%, respectively. These results suggest that GVHD prophylaxis with MTX alone is safe and effective in young children under 10 years old at transplantation and in a setting other than female donor to male recipient...

..The response rate to immunosuppressive therapy did not differ among the 3 groups. To demonstrate whether the two diseases are truly different entities, it is necessary to compare molecular backgrounds between the AA and RCC groups...

..81) with a median follow-up of 78 months (range, 20-243 months). Our study shows the diverse heterogeneity of childhood AMKL and the need for subclassification according to cytogenetic and morphological features...

..Collectively, these findings are critical to clarify further the pathogenesis of chronic active EBV infection and aid in the development of effective treatment strategies...

..Accordingly, the status of mismatched HLA on relapsed leukemic cells should be checked before donor lymphocyte infusion...

..These genes may be associated with the inflammatory reaction or with cell proliferation...

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..She was transplanted with cord blood from an unrelated human leukocyte antigen-matched donor and has since remained in complete remission for 20 months...

..These results demonstrate that whole blood is more suitable for the quantification of EBV DNA in transplant patients. However, a cutoff value with clinical relevance still needs to be determined...

..We conclude that patients with CMV infection cannot be discriminated from patients with JMML by this new diagnostic method...

..BMT using FLU/low-dose CY/ATG -based regimens regardless to the donor is a beneficial therapeutic approach for FA patients...

..These data depict clinical characteristics of systemic EBV(+) T/NK-LPD and provide insight into the diagnostic and therapeutic approaches for distinct disease...

..This study sought to clarify chronologic changes in neonatal electroencephalographic (EEG) findings in periventricular leukomalacia (PVL)...

..1%, SD) in the SCT group compared with 9.5% (+/- 9.0%) in the IST group (P = .001). These results suggest that SCT from an alternative donor offers a better chance of FFS than a second IST in patients not responding to an initial IST...

..Acquired somatic mutations of JAK2 have been reported to play a pivotal role in the pathogenesis of BCR-ABL1-negative myeloproliferative neoplasm (MPN). However, the molecular characteristics of childhood MPN remain to be elucidated...

..ASXL1, IDH1/2, DNMT3A, RUNX1 and CBL mutations were not found in any of the patient group studied, while NRAS mutation was identified in two patients with paediatric non-DS-AMKL...

..This method will be useful not only in the diagnosis of JMML, but also to evaluate the difference of GM-CSF sensitivity among patients...

..These results imply that proinflammatory cytokines, in particular IL-6 and TNF-alpha, play a role in the pathogenesis of HHV-6 reactivation after HSCT...

..5% (6/11) died early]. This stratification system may be useful for identifying high-risk patients who need early therapeutic interventions...

..88, P < 0.0001). The FISH assay enabled us to characterize EBV-infected cells and perform a quantitative analysis in patients with EBV infection after stem cell/liver transplantation...

..These findings should help to clarify the pathogenesis of CAEBV infection and facilitate the development of more-effective treatments...

..033). In patients with HHV-6 viremia, mean HHV-6 DNA copy number was higher in the samples collected at 2 weeks after BMT than the samples collected at any other time period...

..Moreover, two patients had constitutional alterations of genes frequently found in AML. Further investigations are required to define the roles of these genetic alterations in the pathogenesis of childhood MDS/MPN-U...

..Since this new assay is rapid, sensitive, and specific, it can be used for quantitative analyses of viruses in urine and serum samples after transplantation...

..An elucidation of the role of mast cells may provide information about the differences between aplastic anemia and MDS or about the transition of aplastic anemia to MDS...

..We speculate that this α-helix plays a key role in assembly-coupled stator activation...

..He received chemotherapy and survived for more than 70 months without transplantation. We speculated that pediatric AML with t(16;21)(q24;q22) showed favorable prognosis, as with t(8;21)(q22;q22)...

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..Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS...

..These findings suggest the efficacy of antithymocyte globulin in treating certain hypoplastic leukemias...

..For patients with AML, decreasing mortality, especially in the early phase of transplantation, is required to improve the outcome for CB recipients...

..To evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival...

..This genetic difference does not explain the higher incidence of AA in Asian populations...

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..These results suggest that apoptosis, which is dependent on the EBV load and could be mediated by TNF-alpha, plays a major role in the pathophysiology of EBV-associated HLH...

..There have been no studies to determine the incidence of these mutations in Asian patients with Diamond-Blackfan anemia...

..Mutations in the neutrophil elastase gene, ELA2, have been reported in patients with CyN and in those with SCN. We examined granulopoietic defects in CyN patients with those in SCN patients...

..These results should help to clarify the pathogenesis of influenza and its neurological complications...

..KS patients are often more susceptible to infection, so splenectomy should be avoided. Therefore, rituximab therapy is an alternative option for KS patients with ITP who fail to respond to first-line therapy...

..Our results indicate that amphotericin B oral solution and early intravenous fluconazole may be effective in reducing the incidence and mortality of IFI in pediatric patients with hematologic malignancies...

..Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA...

..Gluconeogenesis compensated for chronic fetal hypoxia and decreased glycogen storage. Energy metabolism in the FGR brain is likely to be disrupted as a consequence of lower reserves of energy substrates...

..Delineation of the precise role of each gene product in ribosomal biogenesis and hematopoiesis may have both therapeutic and prognostic significance...

..After complete resection of the nephroblastoma, she received standard chemoradiotherapy for nephroblastoma. She is alive without relapse 14 months after initial presentation...

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..Results from each of the tests show good agreement, from which strong conclusion can be drawn...

..Based on recent advances in the understanding of the pathogenesis of JMML, the development of novel targeted therapies, which might improve the outcome of patients, is keenly awaited...

..It is shown that the rotational speed might be controllable by changing the spouting velocity of Na (+)-containing solution with multiplying the applied dc voltage...

..In isolated left-sided CDH, the %RFLV is a good predictor not only of postnatal mortality but also of the requirement for ECMO...

..031) for HHV-6 viremia. Rash occurring within 1 month after transplantation was observed in 17 (54.8%) of 31 recipients with HHV-6 viremia but in only 8 (19.5%) of 41 recipients without HHV-6 viremia (P=.001)...

..We propose that the MotB(C) dimer domain plays an important role in targeting and stable anchoring of the MotA/MotB complex to putative stator-binding sites of the motor...

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..Finally, the penetration forces at different cell growth phases also show the increment pattern from log (early, mid, and late) to saturation phases, i.e., 161 +/- 25, 216 +/- 15, 255 +/- 21, and 408 +/- 41 nN, respectively...

..This may represent a functional difference between the two flagellar systems in Vibrio cells, and between the chemotaxis systems affecting the two types of flagella...

..842; P < 0.0001). These results indicate that the real-time PCR assay is useful for diagnosing symptomatic EBV infection and for monitoring the virus load...

..We propose that an EBV load > 10(2.5) copies/microg DNA is the reactivation of EBV, and that an EBV load > 10(4.0) copies/microg DNA is indicative of developing LPD...

..The delay in re-constitution in CMV-specific cellular immunity was associated with reactivation of CMV. These results indicated that the recombinant protein pp65 can be used to study specific immunity in CMV infections...

..Neither anti-Fas MoAb (ZB4) nor a broad caspase inhibitor (z-VAD FMK) prevented this increase in Annexin-V binding. These results suggest that ATG induces leukemic cell death in a Fas/Fas-ligand- and caspase-independent manner...

..We analyzed the features and outcome of neonatal leukemia in Japan to establish an appropriate treatment strategy for this rare disorder...

..Multivariate analysis showed that tacrolimus concentration was significantly associated with clinical outcomes. Mean whole-blood level of tacrolimus as continuous infusion should be maintained at > or =7 ng/ml for pediatric patients...

..Low frequencies of EBV-specific CD8+ T cells may be one of the immunological features of chronic active EBV infection...

..Our results suggest that flagellar basal bodies diffuse in the cytoplasmic membrane until the axial structure and/or other structures assemble...

..0 vs 87.2%, P=0.000). Considering that we are lacking optimal therapies for LONIPCs, strategies aimed at the prevention of LONIPCs should be attempted...

..3%) cases in group A, compared with none of 10 (0%) cases in group B (P = 0.001). Thus, this study suggests that HHV-6 may be involved in the development of skin rash in the first month after allogeneic BMT...

..The high incidence associated with malignant disease may be affected by changes in GVHD prophylaxis in order to ensure graft-versus-tumor effects...

..In addition, presumed SDS patients without SBDS mutations may be included in other disorders...

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..These studies have revealed several differences in clinical outcome between Western and Eastern patients, differences that may reflect the effects of genetic background on response to treatment or development of adverse effects...

..We are now trying to adapt our laboratory scale study to a clinical scale study under good manufacturing practices (GMP) conditions...

..The findings obtained in this study provide important clues to the mechanism of ion binding in the stator complex...

..coli, and marine species Vibrio alginolyticus, supplemented with distinct aspects of other bacterial species revealed by recent studies...

..This novel murine xenotransplant model should be useful for investigating the nature of stem cells and testing new therapies for patients with JMML...