Cord blood index predicts engraftment and early non-relapse mortality in adult patients with single-unit cord blood transplantation.

How to select optimal cord blood (CB) remains an important clinical question. We developed and validated an index of CB engraftment, the cord blood index (CBI), which uses three weighted variables representing cell doses and HLA mismatches. We modeled the neutrophil engraftment time with competing events by random survival forests for competing risks as a function of the predictors: total nucleated cells, CD34, colony-forming units for granulocytes/macrophages, and the number of HLA mismatches at the antigen and allele levels.

Umbilical artery tissue contains p75 neurotrophin receptor-positive pericyte-like cells that possess neurosphere formation capacity and neurogenic differentiation potential.

Introduction: The p75 neurotrophin receptor (p75NTR) is known as an efficient marker for the prospective isolation of mesenchymal stem cells (MSCs) and neural crest-derived stem cells (NCSCs). To date, there is quite limited information concerning p75NTR-expressing cells in umbilical cord (UC), although UC is known as a rich source of MSCs. We show for the first time the localization, phenotype, and functional properties of p75NTR cells in UC.

Isolation and characterization of neural crest-like progenitor cells in human umbilical cord blood.

Introduction: Neural crest (NC)-like stem/progenitor cells provide an attractive cell source for regenerative medicine because of their multipotent property and ease of isolation from adult tissue. Although human umbilical cord blood (HUCB) is known to be a rich source of stem cells, the presence of the NC-like stem/progenitor cells in HUCB remains to be elucidated. In this study, we have isolated NC-like progenitor cells using an antibody to p75 neurotrophin receptor (p75NTR) and examined their phenotype and stem cell function in vitro.

Multimodal treatment including standard chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for the Ewing sarcoma family of tumors in Japan: Results of the Japan Ewing Sarcoma Study 04.

Background: The survival rate in patients with Ewing sarcoma family of tumors (ESFT) in Japan was reported to be < 50% in the 1990s. The Japan Ewing Sarcoma Study Group was established to improve the prognosis of ESFT in Japan. The aim of this phase II trial was to determine the efficacy and safety of multimodal treatment for nonmetastatic ESFT.

Registration-directed phase 1/2 trial of irinotecan for pediatric solid tumors.

Background: Although irinotecan hydrochloride (IRI) is a promising chemotherapeutic agent for pediatric solid tumors, its indications had been off-label in the USA, EU and Japan. Therefore, we conducted a phase 1/2 trial of IRI monotherapy in a registration-directed setting.

Methods: Children aged 2-18 years with solid tumors who were either refractory to or relapsed after standard chemotherapy were enrolled.

Phase I study of perifosine monotherapy in patients with recurrent or refractory neuroblastoma.

Purpose: Perifosine is an alkylphospholipid analog that inhibits or modulates signaling through signal transduction pathways such as Akt, which is enhanced in neuroblastoma (NB) by activation of tyrosine kinase receptors. We conducted a phase I study of perifosine in Japanese patients with recurrent or refractory NB.

Experimental Design: All patients enrolled were over 2 years of age; all had refractory or relapsed NB and a performance status of greater than 50%.

Jagged-1 Signaling in the Bone Marrow Microenvironment Promotes Endothelial Progenitor Cell Expansion and Commitment of CD133+ Human Cord Blood Cells for Postnatal Vasculogenesis.

Notch signaling is involved in cell fate decisions during murine vascular development and hematopoiesis in the microenvironment of bone marrow. To investigate the close relationship between hematopoietic stem cells and human endothelial progenitor cells (EPCs) in the bone marrow niche, we examined the effects of Notch signals [Jagged-1 and Delta-like ligand (Dll)-1] on the proliferation and differentiation of human CD133+ cell-derived EPCs. We established stromal systems using HESS-5 murine bone marrow cells transfected with human Jagged-1 (hJagged-1) or human Dll-1 (hDll-1).

A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors.

Introduction: MC710, a 1:10 protein weight ratio mixture of plasma-derived activated factor VII (FVIIa) and factor X (FX), is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. We evaluated the haemostatic efficacy and safety of one to two administrations of MC710 in 21 joint, muscle, and subcutaneous bleeding episodes in 14 male patients, in a multi-centre, open-label, non-randomized clinical trial.

Methods: Subjects were intravenously administered one or two doses of 60 or 120 μg kg MC710 (as FVIIa) once or twice (to a maximum of 180 μg kg ) over up to five bleeding episodes per subject.

Hematopoietic stem cell transplantation for inborn errors of metabolism: A report from the Research Committee on Transplantation for Inborn Errors of Metabolism of the Japanese Ministry of Health, Labour and Welfare and the Working Group of the Japan Society for Hematopoietic Cell Transplantation.

A total of 216 patients with IEM were treated by allogeneic HSCT in Japan from 1985 until 2010. The results of UCBT have improved, and the OS rate of UCBT (81.9%) was not different from those of RBMT (87.

One-time umbilical cord milking after cord cutting has same effectiveness as multiple-time umbilical cord milking in infants born at <29 weeks of gestation: a retrospective study.

Objective: To compare two strategies to potentiate the effects of placental transfusion in infants born at <29 weeks of gestation.

Study Design: Twenty infants who received one-time umbilical cord milking after umbilical cord cutting were compared with 20 infants from a previous study group who received multiple-time umbilical cord milking. The primary outcome measurements were the probability of not needing a red blood cell (RBC) transfusion during the hospital stay and the total number of RBC transfusions within 21 days after birth.

Successful Pregnancy and Delivery After Radiation With Ovarian Shielding for Acute Lymphocytic Leukemia Before Menarche.

Total body irradiation is performed as a preconditioning regimen to inhibit graft-versus-host disease after bone marrow transplantation and to eradicate remaining tumor cells. However, these regimens result in delayed secondary sex characteristics and failure of ovarian function recovery, leading to amenorrhea and infertility. Herein, we report a case of an 11-year-old girl diagnosed with acute lymphocytic leukemia who received induction chemotherapy and prophylactic cranial irradiation.

Residual blood volume in the umbilical cord of extremely premature infants.

Background: The aim of this study was to investigate residual blood volume in the umbilical cord of extremely premature infants.

Methods: Twenty extremely premature infants were held at or below the placenta while the umbilical cord was clamped and cut at approximately 2-3 cm from the umbilicus within 30 s after birth. The umbilical cord was then clamped near the placenta to obtain a length of approximately 30 cm and cut.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants.

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants.

Relationship between estimated fatty acid desaturase activities and abdominal adiposity in Japanese children.

Background: Abdominal obesity alters the composition of plasma and tissue long chain fatty acids and thus affects a number of important physiological functions relating to the development of cardiometabolic diseases. The fatty acid composition is modulated by desaturases; stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D). Therefore, we examined the relationship between the desaturase activities and abdominal adiposity.

Changes in cerebral blood oxygenation induced by active standing test in children with POTS and NMS.

Orthostatic dysregulation (OD) has been classified into subtypes by heart rate and blood pressure; however, the hemodynamics of brains have not yet been revealed. Therefore, we investigated changes in cerebral blood flow and oxygenation during an active standing test to clarify the pathophysiology of two subtypes: postural tachycardia syndrome (POTS) and neurally mediated syncope (NMS). We studied 31 children (15 boys, 16 girls; mean age, 14.

[Clinical efficacy and pharmacokinetics of lamotrigine for childhood-onset intractable epilepsy].

Objective: We investigated the clinical efficacy and pharmacokinetics of lamotrigine (LTG) as an add-on therapy in childhood-onset intractable epilepsy.

Methods: We reviewed the charts of 28 outpatients who had received LTG as an add-on therapy. The data collected included epilepsy type, seizure frequency, concomitant anti-epileptic drugs, dosage of LTG and LTG serum levels.

Prospective pharmacokinetic study of intravenous busulfan in hematopoietic stem cell transplantation in 25 children.

The aim of this study was to prospectively evaluate the PK and safety of ivBU in 25 Japanese children (median age six yr; range, five months-17 yr) as one of a combination of drugs in a pretransplant regimen. The patients had acute leukemia (n = 14), CML (2), JMML (5), solid tumors (2), chronic granulomatous disease (1), or metachromatic leukodystrophy (1). Five different dose schedules were used according to the patient's ABW: <9 kg (1.

Apolipoprotein A-V level may contribute to the development of obesity-associated dyslipidemia.

Aim: In a mice study, insulin suppressed apolipoprotein A-V (apoA-V) gene expression in a dose dependent manner. Thus, we investigated the association between apoA-V levels and dyslipidemias in obese children with hyperinsulinemia.

Methods: The subjects were 17 obese children (15 male, 2 female) aged 11.

Pharmacologic treatment strategies in children with type 2 diabetes mellitus.

We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.

Abdominal adiposity is associated with high-density lipoprotein subclasses in Japanese schoolchildren.

Background: The large HDL subclass is considered to possess cardioprotective properties. The purpose of this study is to determine the relationship among abdominal adiposity, insulin resistance and HDL subclass profiles of Japanese schoolchildren.

Methods: The study subjects included 164 children (79 boys and 85 girls).

A Phase II clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: haemostatic efficacy, safety and pharmacokinetics/pharmacodynamics.

MC710, a mixture of plasma-derived activated factor VII and factor X at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In a Phase II trial, we evaluated the haemostatic efficacy and safety of single doses of MC710, and investigated pharmacokinetic and pharmacodynamic parameters in nine joint bleeding episodes in six male haemophilia patients with inhibitors. This trial was a multi-centre, open-label, non-randomized study of two doses (60 and 120 μg kg(-1) as FVIIa dose), allowing the re-administration of different MC710 dosages to the same subjects.

Abdominal adiposity is associated with fatty acid desaturase activity in boys: implications for C-reactive protein and insulin resistance.

Fatty acid composition, which is altered in patients with abdominal obesity, is influenced not only by dietary intake but also by the desaturating enzymes stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D). We investigated desaturase activities and their associations with metabolic risk factors, C-reactive protein levels (CRP) and insulin resistance in Japanese children. There were 237 school children in this study; 115 were boys.