記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hemophagocytic lymphohistiocytosis (HLH) associated with Epstein-Barr virus (EBV) infection can be self-limiting, severe/aggressive, or fatal. We report a case of EBV-HLH with persistent fever, severe pancytopenia, hypertriglyceridemia, and hypofibrinogenemia in a 4-year-old boy. Levels of plasma cytokines and chemokines were measured with a Bio-Plex system at 1, 2, 3, 4, 5, and 8 days after hospital admission. Administration of steroid and high-dose intravenous immunoglobulin (1 g/kg) did not alleviate fever or reduce cytokine production; however, after administration of etoposide (an antineoplastic agent), fever decreased immediately, the patient's general condition improved, and levels of IL-6, IL-10, IL-8, MCP-1, IFN-γ, and TNF-α declined after etoposide administration. In particular, IFN-γ production sharply declined, from 1,104.1 pg/mL to 101.5 pg/mL, and IL-6 level decreased from 229.8 pg/mL to 11.0 pg/mL, on the day after initial etoposide administration. There was no later recurrence of symptoms during treatment with dexamethasone, etoposide, and cyclosporine A. This case suggests that early etoposide administration is critical for treatment success and indicates that etoposide promptly inhibits cytokine production.

DOI： 10.1272/jnms.JNMS.2020_87-307

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. METHODS: Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. RESULTS: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17, RANTES, INF-γ, and TNF-α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. CONCLUSIONS: These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.

DOI： 10.1111/ped.14062

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Therapeutic outcomes for childhood malignancy have dramatically improved. However, secondary malignancies are a major concern, as they greatly affect the quality of life of survivors. This retrospective study evaluated the cumulative incidence, clinical features, and outcomes of secondary malignancies at Nippon Medical School Hospital. METHODS: We examined data from 275 cases of primary childhood malignancy diagnosed between 1980 and 2014. Information regarding treatment of the primary malignancy, including irradiation dose, site, and cumulative dose of anticancer drugs, was assessed. We also collected data on secondary malignancy, including patient sex, age at diagnosis, malignancy site, time from primary to secondary malignancy, and outcomes. RESULTS: Secondary malignancies developed in 11 patients and included acute myeloid leukemia (AML) (4), meningioma (4), Ewing sarcoma (1), germ cell tumor (1), and malignant parotid gland tumor (1). The primary malignancies included acute lymphoblastic leukemia (ALL) (9), non-Hodgkin lymphoma (1) and brain tumor (1). In 7 of the 9 ALL patients, chemoradiotherapy was the primary treatment. The meningiomas and 1 solid tumor developed within the radiation field. All AMLs and meningiomas developed within 5 years and after 20 years, respectively, of the primary diagnosis. The 10- and 20-year cumulative incidence rates for secondary malignancy in our hospital were 1.9% and 5.8%, respectively. CONCLUSIONS: Our results revealed that the type of secondary malignancy depends on the interval after the end of treatment for primary malignancy. Meningioma, notably, develops many years after completion of primary malignancy treatment. Early detection during long-term follow-up is therefore essential.

DOI： 10.1272/jnms.JNMS.2018_86-401

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記述言語：英語  

Anhidrotic ectodermal dysplasia (AED) is a rare hereditary disorder with a triad of sparse hair, dental hypoplasia, and anhidrosis. Here we report a case of AED with food allergy and atopic eczema. The patient was a 11-month-old boy admitted to our hospital with pyrexia for 2 weeks. He presented with a history of dry skin, eczema, and food allergy to egg. On clinical examination, his body temperature was 38.8°C, with dry skin and eczema almost all over the body, sparse eyebrows, and scalp hair. Laboratory investigations and physical examination did not show any evidence of infection. Radioallergosorbent test was positive to egg yolk, egg white, ovomucoid, milk, house dust, and house dust mite. As the child did not sweat despite the high fever, we performed the sweat test which revealed a total lack of sweat glands. Genetic examination revealed a mutation of the EDA gene and he was diagnosed as AED. His pyrexia improved upon cooling with ice and fan. His mother had lost 8 teeth and her sweat test demonstrated low sweating, suggestive of her being a carrier of AED. Atopy and immune deficiencies have been shown to have a higher prevalence in patients with AED. Disruption of the skin barrier in patients with AED make them more prone to allergic diseases such as atopic eczema, bronchial asthma, allergic rhinitis and food allergy. Careful assessment of the familial history is essential to differentiate AED when examining patients with pyrexia of unknown origin and comorbid allergic diseases.

DOI： 10.5415/apallergy.2019.9.e3

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Peters' plus syndrome is a rare autosomal recessive condition characterized by a combination of typical ocular defects and other systemic abnormalities. We present a case of this uncommon syndrome that we diagnosed during a fetal ultrasonographical examination. Because the patient exhibited microcephaly and anterior staphyloma of the right eye and because impending rupture was feared, we performed ophthalmectomy during the neonatal period. Fetal ophthalmological anomalies are often detected during ultrasonographic examination targeting other systemic abnormalities, with positive family histories providing important diagnostic clues. This case is, to our knowledge, the first to be reported of prenatally diagnosed Peters' plus syndrome in a patient with no known family history in whom total blindness was prevented with an early referral to specialists.

DOI： 10.1272/jnms.83.130

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Expression of imprinted genes is regulated by DNA methylation of differentially methylated regions (DMRs). Beckwith-Wiedemann syndrome is an imprinting disorder caused by epimutations of DMRs at 11p15.5. To date, multiple methylation defects have been reported in Beckwith-Wiedemann syndrome patients with epimutations; however, limited numbers of DMRs have been analyzed. The susceptibility of DMRs to aberrant methylation, alteration of gene expression due to aberrant methylation, and causative factors for multiple methylation defects remain undetermined. METHODS: Comprehensive methylation analysis with two quantitative methods, matrix-assisted laser desorption/ionization mass spectrometry and bisulfite pyrosequencing, was conducted across 29 DMRs in 54 Beckwith-Wiedemann syndrome patients with epimutations. Allelic expressions of three genes with aberrant methylation were analyzed. All DMRs with aberrant methylation were sequenced. RESULTS: Thirty-four percent of KvDMR1-loss of methylation patients and 30% of H19DMR-gain of methylation patients showed multiple methylation defects. Maternally methylated DMRs were susceptible to aberrant hypomethylation in KvDMR1-loss of methylation patients. Biallelic expression of the genes was associated with aberrant methylation. Cis-acting pathological variations were not found in any aberrantly methylated DMR. CONCLUSION: Maternally methylated DMRs may be vulnerable to DNA demethylation during the preimplantation stage, when hypomethylation of KvDMR1 occurs, and aberrant methylation of DMRs affects imprinted gene expression. Cis-acting variations of the DMRs are not involved in the multiple methylation defects.

DOI： 10.1038/gim.2014.46

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Osteoblastic cells are a key component of the bone marrow (BM) stem cell niche and help regulate hematopoietic stem cells (HSCs). We have previously demonstrated that adipose-derived stromal cells (ADSCs) can differentiate into both osteogenic and chondrogenic cells in vitro. The current study examined whether the anatomical architecture of the BM could be regenerated in vivo by using ADSCs cultured on a hydroxyapatite (HA) scaffold. ADSCs from GFP transgenic mice were cultured in vitro on an HA scaffold. The scaffold with the attached cells was implanted subcutaneously onto the backs of C57/BL6 (Ly5.2) recipient mice. Lineage-negative (Lin-) Ly5.1 BM cells transduced with a lentiviral vector containing the luciferase (Luc) gene were intravenously administered to the recipient mice after lethal irradiation. Eight weeks after BM transplantation, the scaffolds were removed from the first recipient mice and subcutaneously implanted into lethally irradiated second recipient mice. The biodistribution and kinetics of Luc(+) Ly5.1 cells were monitored by bioluminescence imaging and flow cytometry. Luc(+) hematopoietic cells were present in the scaffolds of the secondary implanted mice for at least 8 months. Subcutaneous injection of G-CSF resulted in wide distribution of bioluminescence signals from the original scaffolds to the whole body. Therefore, BM regenerated using ADSCs grown on an HA scaffold can support HSC populations in vivo, suggesting that a functional BM niche is reconstituted. These results may have a significant impact on the development of therapeutic strategies for various hematopoietic diseases.

DOI： 10.1002/cbin.10254

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The aim of this study was to examine the effects of a newly established neonatal intensive care unit (NICU) on clinical work practice and educational activity at Nippon Medical School Musashikosugi Hospital. METHODS: This retrospective study analyzed the clinical records of all neonates admitted to the NICU from December 2010 through November 2013. Anthropometric data, clinical status, problems, and outcomes of patients and the related obstetrical history were extracted and analyzed. RESULTS: Of the 568 neonatal admissions, about half were related to preterm birth (49%) and low birth weight (55%). Forty-eight percent of patients were born via caesarean delivery. Maternal hypertension, diabetes, and thyroid disease were found in 8%, 5%, and 2% of cases, respectively. Mechanical ventilatory support was provided for 20% of patients. Neonates from multiple pregnancy and with significant congenital anomalies accounted for 17% and 10% of all patients, respectively. Five patients died during hospitalization. In addition training was provided in the NICU for an average of 10 residents and 20 medical students per year. CONCLUSION: Since the NICU was established, closer cooperation beyond the framework of a single department has come to be needed. In addition, NICUs in teaching hospitals are expected to provide opportunities for medical students and residents to observe and participate in multidisciplinary medical care.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Gaucher disease is an autosomal recessively inherited lysosomal storage disease in which a deficiency of glucocerebrosidase is associated with the accumulation of glucocerebroside in reticuloendothelial cells. Clinically, 3 types of Gaucher disease have been defined on the basis of the presence or absence of neurological symptoms. The frequency of gallbladder involvement is reportedly greater in patients with type 1 Gaucher disease than in healthy persons. We report a case of recurrent cholelithiasis and liver failure in a patient with type 2 Gaucher disease who showed severe progressive neurological involvement.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of the study was to determine factors that affect adverse long-term pulmonary outcome in premature infants. METHODS: This retrospective analysis was done using 306 clinical records of preterm singleton neonates at <32 weeks of gestation. Two definitions of adverse pulmonary outcome were used: chronic lung disease (CLD), defined as a need for supplemental oxygen for at least 28 days after birth; and bronchopulmonary dysplasia (BPD), defined as oxygen dependency for at least 28 days after birth plus at 36 weeks postmenstrual age and/or a need for positive-pressure ventilatory support. Selected perinatal variables were compared between these definitions, and factors related to disease development were identified on multivariate analysis. RESULTS: The incidence of CLD and of BPD were 42% and 17%, respectively. Regardless of the definitions, the incidence of patent ductus arteriosus and of neonatal infection were significantly higher in the patients who met the disease criteria, but that of chorioamnionitis and of small for gestational age (SGA) were significantly higher in the patients only when the BPD definition was applied. Multivariate analysis identified SGA as an independent risk factor for the development of BPD after controlling for gestational age. CONCLUSIONS: Among selected perinatal variables, prenatal risk factors, particularly SGA, contributed to prolonged dependency on oxygen and/or positive-pressure ventilatory support, in combination with neonatal risk factors.

DOI： 10.1111/ped.12151

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Group B Streptococcus (GBS) is an important pathogen that causes neonatal sepsis and meningitis, which have high mortality and morbidity. Most cases of infection are early onset, with late onset infections being less common. Moreover, many cases of infection are caused by type III GBS, while type Ib GBS infections are rare. We report a case of late-onset infection by type Ib GBS. A female neonate weighing 574 g was delivered at 27 weeks' gestation. An endotracheal tube was inserted shortly after birth because of respiratory distress syndrome, and ampicillin was administered by the age of 3 days. At the age of 54 days after cardiopulmonary adaptation had been achieved, the patient presented with tachycardia following refractory apnea and bradycardia, and her skin became pale. She was suspected of having sepsis, and intensive treatment, including intubation and administration of catecholamines, was started. Despite these measures, the patient died after 5 hours after the onset of sepsis. Type Ib GBS infection may be more frequent in Japanese infants because of the low concentration of IgG antibodies against type Ib in pregnant Japanese women.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A case of herpes simplex virus (HSV) encephalitis in a neonate after delivery from a woman whose genital HSV infection had been treated with acyclovir is reported. The main approach to prevent genital HSV infection in the neonate is interruption of transmission at the time of delivery. Guidelines for prophylactic therapy with acyclovir have been established, but the risk of neonatal infection remains. A fever began to develop in a male neonate delivered vaginally from a 35-year-old woman. Treatment with intravenous acyclovir was started on the basis of a diagnosis of HSV encephalitis, because polymerase chain reaction was positive for HSV in the cerebrospinal fluid. The mother had had a first genital HSV infection during the second trimester, but treatment with injected acyclovir had caused the blisters and erosion to resolve by the time of delivery. Important steps for preventing neonatal HSV infection are the appropriate treatment of mothers with a history of genital HSV infection, the assessment of delivery methods, and the appropriate treatment of neonates.

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記述言語：英語   出版者・発行元：W B SAUNDERS CO LTD  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hypophosphatasia (HPP), caused by mutations in the gene ALPL encoding tissue-nonspecific alkaline phosphatase (TNALP), is an inherited systemic skeletal disease characterized by mineralization defects of bones and teeth. The clinical severity of HPP varies widely, from a lethal perinatal form to mild odontohypophosphatasia showing only dental manifestations. HPP model mice (Akp2(-/-)) phenotypically mimic the severe infantile form of human HPP; they appear normal at birth but die by 2 weeks of age because of growth failure, hypomineralization, and epileptic seizures. In the present study, we investigated the feasibility of fetal gene therapy using the lethal HPP model mice. On day 15 of gestation, the fetuses of HPP model mice underwent transuterine intraperitoneal injection of adeno-associated virus serotype 9 (AAV9) expressing bone-targeted TNALP. Treated and delivered mice showed normal weight gain and seizure-free survival for at least 8 weeks. Vector sequence was detected in systemic organs including bone at 14 days of age. ALP activities in plasma and bone were consistently high. Enhanced mineralization was demonstrated on X-ray images of the chest and forepaw. Our data clearly demonstrate that systemic injection of AAV9 in utero is an effective strategy for the treatment of lethal HPP mice. Fetal gene therapy may be an important choice after prenatal diagnosis of life-threatening HPP.

DOI： 10.1089/hum.2011.148

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Intussusception occurring in premature infants is exceedingly rare and shows substantially different characteristics from that in the typical age group or non-premature neonates. We present a case of intussusception in an extremely premature infant following bacterial sepsis, in which necrotizing enterocolitis was initially suspected. The correct diagnosis was made at 35 days old using abdominal ultrasonography, but the general condition of the infant had deteriorated to the point where surgery could not be performed. The patient died of multiple organ failure, and autopsy revealed ileo-ileal intussusception without a recognizable anatomical leading point. Possible mechanisms for this rare clinical entity are discussed.

DOI： 10.1007/s00431-011-1635-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant women at 20 to 23 and 27 to 30 weeks of gestation before PE onset compared with those with normal pregnancies. The sensitivities/specificities for predicting PE at 20 to 23 and 27 to 30 weeks of gestation were 0.75/0.67 (cutoff value=21.9 ng/mL) and 0.88/0.51 (cutoff value=30.5 ng/mL), and the odds ratios were 6.09 (95% CI: 2.35-15.77) and 7.83 (95% CI: 1.70-36.14), respectively. We conclude that HSD17B1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placenta and that reducing plasma level of HSD17B1 precedes the onset of PE and is a potential prognostic factor for PE.

DOI： 10.1161/HYPERTENSIONAHA.111.180232

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Idiopathic intrauterine constriction/closure of the ductus arteriosus, which is distinct from that secondary to maternal exposure to non-steroidal anti-inflammatory drugs, such as indomethacin, or structural cardiac defect, is an uncommon event that often results in severe fetal-neonatal morbidity and mortality. We reported a case of idiopathic fetal ductal constriction, in which the diagnosis was confirmed by documentation of an abnormal four-chamber view of the fetal heart at 38 weeks of gestation on obstetric ultrasound examination. A female infant weighing 2,816 g was born by Cesarean section, and her postnatal course was mild; transient tachypnea requiring only several days of supplemental oxygen with spontaneous regression of the abnormal echocardiographic findings by 3 months of age. The incidence of idiopathic constriction/closure of the fetal ductus arteriosus may be underestimated, particularly with a negative history of maternal drug exposure and mild postnatal clinical presentation.

DOI： 10.1007/s00431-010-1295-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hemoglobin H (HbH) disease is the severe nonfatal form of α-thalassemia syndrome. It is usually caused by molecular defects of 3 of 4 α-globin genes (--/-α) which cause α-globin expression to be decreased. HbH disease is rare in Japan. Here, we report on a 6-year-old girl with HbH disease who had profound hypochromatic and microcytic anemia. Analysis of the α-globin genes of the patient's family showed that the father, who was Japanese, had an abnormal gene with a 3.7-kb deletion (-α(3.7)/αα), and the mother, who was Filipino, had a deletion removing both α-globin genes of the Filipino type (--(FIL)/αα). Neither parent had anemia. The patient was found to have HbH disease with a heterozygous genetic abnormality (--(FIL)/-α(3.7)). Recently, the number of marriages of Japanese to natives of areas where thalassemia is epidemic has increased. Therefore, the incidence of HbH disease can be expected to increase in Japan. Long-term follow-up will be needed to evaluate the long-term complications and to improve the quality of life of patients with HbH disease.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

C1q deficiency is a rare complement deficiency in the early part of the complement cascade. Patients with C1q deficiency have severe recurring life-threatening infections and systemic lupus erythematosus (SLE)-like symptoms. We report on a boy with recurrent life-threatening infections and SLE-like recurrent skin conditions before 2 years of age. Immunological studies revealed an undetectable level of C1q. No abnormality was observed in the urine, but renal biopsy showed segmental granulonephritis. However, the changes observed were atypical for SLE nephritis. This case of C1q deficiency was unusual because the SLE-like symptoms appeared earlier than that normally seen in complement deficiency. Therefore, this case provides insights into the development of autoimmune disease, particularly in the early phase of component deficiency, and in managing renal disease that may develop in the future.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Obstructive sleep apnea syndrome affects 1% to 2% of children. It is caused mainly by upper airway obstruction and manifests as snoring and sleep disturbance. Adenotonsillectomy can improve quality of life because airway obstruction occurs when both tonsils and adenoids are enlarged. We describe an 8-year-old girl with a recurrence of obstructive sleep apnea syndrome caused by hypertrophy of the tubal tonsils 4 years after adenotonsillectomy. The findings from this case highlight the importance of 1) identifying hypertrophy of the residual adenoid and compensatory hypertrophy of the tubal tonsils in patients with obstructive sleep apnea syndrome after adenotonsillectomy and 2) determining the optimal timing of adenotonsillectomy with respect to both the severity of obstructive sleep apnea and compensatory hypertrophy of other lymphoid tissue of Waldeyer's ring, as growth of such tissues is most active during the first several years of life.

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記述言語：英語  

DOI： 10.3109/10428194.2010.488707

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined whether regenerated bone marrow (BM) with BM-derived stromal cells (BMSCs) on hydroxyapatite (HA) scaffolds can reconstitute the functional niche. Ly5.2 BMSCs on HA scaffolds were implanted s.c. onto the backs of Ly5.2 recipient mice. Lineage negative Ly5.1 BM cells expressing luciferase (luc) were i.v. administered into the recipient mice. Eight weeks after primary transplantation, secondary implantation was performed; the scaffolds removed from the first recipient mice were s.c. implanted into secondary recipient mice. Luc+ cells were detected in the scaffolds for 6 mo after secondary implantation. Injection of G-CSF resulted in wide distribution of bioluminescence from the original scaffolds to the whole body. Even after removing the scaffolds from the secondary recipient mice, luc+ cells were emitted by G-CSF stimulation, indicating that regenerated BM is capable of supporting hematopoietic stem cells (HSCs) and delivering HSCs to native BM in vivo. These data suggest that the functional niche is reconstituted at least partly and that regenerated BM on the scaffold may be used as a portable source of HSCs.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Full-term cord blood (TCB) hematopoietic stem/progenitor cells (HSC/HPCs) are used for stem cell transplantation and are well characterized. However, the properties of preterm cord blood (PCB) HSC/HPCs remain unclear. In the present study, we compared HSC/HPCs from TCB and PCB with respect to their expression of surface markers, homing capacity and ability to repopulate HSCs in the NOD/Shi-scid mice bone marrow. The proportion of CD34+CD38- cells was significantly higher in PCB. On the other hand, the engraftment rate of TCB CD34+ cells into NOD/Shi-scid mice was significantly higher than PCB CD34+ cells. The expression of VLA4 was stronger among TCB CD34+ cells than PCB CD34+ cells. Moreover, there was a positive correlation between the proportion of CD34+CXCR4+ cells and gestational age. These data suggest that the homing ability of HSCs increases during gestation, so that TCB may be a better source of HSCs for transplantation than PCB.

DOI： 10.1016/j.bbrc.2009.08.139

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although the homing of hematopoietic stem cells (HSC) to the bone marrow (BM) is a crucial step in hematopoietic development and BM repopulation, the mechanisms underlying these processes have not been fully clarified. Recent studies suggest that interaction between the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1), plays a critical role in these processes. In addition, dextran sulfate increases plasma SDF-1 levels in mice and nonhuman primates. Thus, we examined the effects of preconditioning with SDF-1 and dextran sulfate on the homing efficiency of HSCs following BM transplantation in mice. We found that the preconditioning of donor mice with either SDF-1 or dextran sulfate enhanced the homing efficiency of infused HSCs in vivo. The greatest effects were obtained with dextran sulfate. Moreover, reverse transcriptase polymerase chain reaction analysis demonstrated that SDF-1 and dextran sulfate increased transcription of a variety of homing-related genes, including those for CXCR4, lymphocyte function associated antigen-1, matrix metalloproteinase-9, very late antigen-4/5, and macrophage inflammatory protein-1. We suggest that whereas SDF-1 directly acts to upregulate CXCR4 expression in HSCs, dextran sulfate acts via multiple pathways involved in the induction of various homing-related molecules, in addition to SDF-1. Thus, preconditioning donors with dextran sulfate offers a novel clinical approach for improving the homing and engraftment of HSCs in the BM.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac defect characterized by the atria connecting with anatomically discordant ventricles and the ventricles connecting with discordant and transposed great arteries, which allows hemodynamic compensation. Most patients with ccTGA have associated intracardiac anomalies, which could be a diagnostic clue, whereas isolated forms are infrequently diagnosed during the neonatal period and in utero. We describe a fetus that was diagnosed with ccTGA and without additional cardiac anomalies at 25 weeks of gestation. The parallel course of the great arteries discovered during a routine obstetric scan indicated this rare cardiac anomaly. Further detailed examination of the ventricular morphology helped to confirm the diagnosis. Despite hemodynamic compensation, the long-term prognosis of ccTGA is uncertain because of the possible development of arrhythmias or heart failure later in life. Our findings showed that fetal echocardiography can detect prenatal ccTGA.

DOI： 10.1007/s00404-008-0739-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe an infant with nemaline myopathy accompanied by hypertrophic cardiomyopathy. The patient required long-term, intermittent positive-pressure ventilation after birth owing to muscle weakness, and cardiac failure developed during infancy. We diagnosed hypertrophic cardiomyopathy with outflow tract obstruction, and treated the heart failure with beta-adrenergic and angiotensin II receptor blockers. We discuss the prognosis of nemaline myopathy combined with hypertrophic cardiomyopathy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a case of Diphyllobothrium nihonkaiense infection in a 2-year-old Japanese girl. When infection occurs in early childhood, it is necessary to offer supportive care in addition to standard treatment with oral praziquantel or with of a duodenal tube using a radiopaque contrast medium. We treated D. nihonkaiense infection in a 2-year-old girl successfully treated with oral praziquantel and a laxative.

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記述言語：英語   出版者・発行元：AMER SOC HEMATOLOGY  

DOI： 10.1182/blood.V110.11.1419.1419

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by a deficiency of arylsulfatase A (ASA) and is characterized by deposition of sulfatide in all organs, particularly the nervous system. Recently, formylglycine-generating enzyme (FGE) was found to be essential for activation of sulfatases. This study examined the utility of FGE co-expression in AAV type 1 vector (AAV1)-mediated gene therapy of ASA knockout (MLD) mice. AAV1-ASA alone or AAV1-ASA and AAV1-FGE were co-injected into a single site of the hippocampus. Enzyme assay and immunohistochemical analysis showed that ASA was detected not only in the injected hemisphere but also in the non-injected hemisphere by 7 months after injection. Level of ASA activity and extent of ASA distribution were significantly enhanced by co-introduction of AAV1-FGE. Marked reductions in sulfatide levels were observed throughout the entire brain. The unexpectedly widespread distribution of ASA may be due to a combination of diffusion in extracellular spaces, transport through axons, and circulation in cerebrospinal fluid. The rotarod test revealed improvement of neurological functions. These results demonstrate that direct injection of AAV1 vectors expressing ASA and FGE represents a highly promising approach with significant implications for the development of clinical protocols for MLD gene therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report on an infant with Beals syndrome (congenital contractural arachnodactyly [CCA], MIM 121050) with transient cardiomyopathy showing ballon-like dilatation of the left ventricle that was similar to noncompaction. The patients father and two of his brothers were also found to have CCA without cardiovascular complications. CCA, which is caused by a mutation of the gene for fibrillin 2 protein is similar to Marfan syndrome (MIM 154700), which is caused by a mutation of fibrillin 1 but produces a life-threatening cardiovascular complications. This is the first report of CCA with transient cardiomyopathy. We discuss the mechanism of the spontaneous improvement of cardiomyopathy in this case on the basis of expression of the responsible gene.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by mutations in the gene encoding the lysosomal enzyme arylsulfatase A (ASA). In MLD, accumulation of the substrate, sulfated glycoprotein, in the central and peripheral nervous systems results in progressive motor and mental deterioration. Neural progenitor cells are thought to be useful for cell replacement therapy and for cell-mediated gene therapy in neurodegenerative diseases. In the present study, we examined the feasibility of ex vivo gene therapy for MLD using neural progenitor cells. Neural progenitor cells (neurospheres) were prepared from the striatum of E14 embryo MLD knockout mice or GFP transgenic mice and were transduced with the VSV pseudotyped HIV vector carrying the ASA gene (HIV-ASA). For in vivo study, neurospheres from GFP mice were transduced with HIV-ASA and inoculated into the brain parenchyma of adult MLD mice. HIV vector-transduced progenitor cells retained the potential for differentiation into neurons, astrocytes and oligodendrocytes in vitro. Expression of ASA in neurospheres transduced with HIV-ASA was confirmed by spectrophotometric enzyme assay and Western blotting. In vivo, GFP-positive cells were detectable 1 month after injection. These cells included GFAP- and MAP2-positive cells. Immunohistochemistry using anti-ASA antibody demonstrated localization of ASA in both GFP-positive and -negative cells. Partial clearance of accumulated sulfatide was confirmed in vivo in MLD knockout mice. The present findings suggest that ASA enzyme is released from migrated neurospheres and is able to digest sulfatide in surrounding cells. Our results suggest the potential of genetically engineered neural progenitor cells (neurospheres) for ex vivo therapy in MLD.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report an asymptomatic female with Fabry disease immunohistochemically diagnosed by renal biopsy. She was initially diagnosed as having nephrotic syndrome, and renal biopsy was performed for pathological diagnosis. The renal specimen revealed non-specific findings (minor glomerular abnormalities) for nephrotic syndrome. Numerous laminated bodies in glomerular epithelial cells in electron microscopic findings and accumulations of ceramidetrihexoside immunohistochemically were observed and she was diagnosed with Fabry disease. However, no other laboratory data or clinical findings supported the diagnosis of Fabry disease. Since the efficacy of recombinant human alpha-galactosidase replacement therapy in this disease has been reported, whether enzyme replacement therapy for subclinical Fabry female patients is indicated or not is an important issue.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prognosis and clinical and biological characteristics of infant leukemia differ from those of leukemia in children 1 year or older. We reviewed the charts of patients younger than 1 year in whom leukemia was diagnosed from January 1981 through December 2003 at our institution. Fourteen infants had leukemia, 6 had acute lymphoblastic leukemia (ALL), and 8 had acute myeloid leukemia (AML). The age of patients at diagnosis ranged from 2 to 11 months. Five of 8 AML patients presented with cutaneous manifestations, such as erythema and nodules, at diagnosis. Central nervous system (CNS) involvement was seen in 1 AML patient at diagnosis. Hyperleukocytosis of more than 50 x 10(9)/L was seen in 4 of 6 ALL patients and in 4 of 8 AML patients at diagnosis. All ALL patients showed a morphological diagnosis of L1 using the French-America-British classification system. For patients with AML, the morphological diagnoses were M0 for 1 patient, M2 for 1 patient, M4 for 2 patients (1 with eosinophilia), M5b for 2 patients, and M7 for 2 patients. One patient showing M7 morphology had Down syndrome. Surface markers were examined in 5 of 6 ALL patients and all AML patients. Five ALL patients showed a B-cell precursor immunophenotype. Two of 5 patients with ALL had CD10-positive leukemic cells and 3 of 5 patients with ALL had CD10-negative leukemic cells. All AML patients were positive for CD13 or CD33 or both. Three of 5 patients with ALL showed abnormal chromosomes related to 11q. Six of 7 patients with AML showed abnormal karyotypes. MLL gene rearrangements were seen in 3 (2 ALL, 1 AML) of 5 (2 ALL, 3 AML) patients. Serum immunoglobulin M levels were increased in 9 of 14 patients. Complete remission (CR) was achieved in all infants with ALL. Three patients relapsed and then died of the original disease. One of these 3 patients died after cord blood transplantation. Three ALL patients are alive without leukemia. CR was achieved in 6 of 8 AML patients. Four of 6 patients are alive without leukemia. Infant leukemia patients in our institution had some special features. CNS involvement at diagnosis was seen in only 1 patient and serum IgM levels were higher than those in children whose leukemia was diagnosed at 1 to 10 years of age.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A case of Henoch-Schönlein purpura (HSP) with necrosis of the small intestine, neurological symptoms, and pericardial tamponade after frequent recurrence is described. Neurological symptoms were controlled well with steroid pulse therapy, and pericardial tamponade was treated successfully with pericardiocentesis and steroid pulse therapy. To treat necrosis of the small intestine, the necrotic tissue was excised and artificial anuses were constructed. Five months later, the small intestine was anastomosed in a curative operation. Periodic administration of coagulation factor XIII was required from the onset of symptoms until curative surgery, but the activity of this factor returned to normal levels after surgery operation. We report a case of Henoch-Schönlein purpura with extremely rare complications: necrosis of the small intestine, neurological symptoms, and pericardial tamponade.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 13-year old boy with acute lymphoblastic leukemia had bilateral paresis of the upper extremities and aphasia 1 week after high dose methotrexate and triple intrathecal therapy (methotrexate, cytarabin, hydrocortisone). The stroke-like neurological symptoms disappeared on the third day. T2-weighted magnetic resonance imaging showed hyperintensities of white matter on the second day. Despite resolution of the neurological symptoms, magnetic resonance images were still abnormal 3 years after the attack. Methotrexate has been considered to be responsible for ischemic damage to oligodendroglial cells, resulting in demyelination. The changes are occasionally prolonged without persistent neurologic symptoms.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies have shown bone marrow (BM) cells to differentiate into a variety of cell types and to thereby participate in the reconstitution of damaged organs. In the present study, we examined the extent to which BM-derived cells are incorporated into glomeruli during recovery from experimentally induced nephritis. To investigate the localization of BM cells in glomeruli, chimeric mice were prepared by transplanting BM cells from green fluorescent protein (GFP) transgenic mice into wild-type mice. Five weeks later, glomerulonephritis was induced by intravenous injection of Habu snake venom. Groups of mice were then killed every few days for 42 d, and harvested kidney samples were subjected to immunohistochemical and immunoelectron microscopic analyses with the aim of detecting the presence of GFP(+) cells within glomeruli. Chimeric animals injected with Habu venom developed proliferative glomerulonephritis within 1-3 d. The lesion gradually subsided and the glomerular structure returned to normal within 42 d. Consistent with the disease course, large numbers of GFP(+) cells were present within glomeruli on d 1-3, but most had disappeared by d 7. Nevertheless, some GFP(+) cells did remain within glomeruli showing mesangial proliferative changes, and were found to express thrombomodulin (TM), a specific endothelial cell marker. These GFP-TM-double-positive cells accounted for a mean of 1.31-2.24% of the total glomerular nuclei from d 7 through d 42, levels that remained stable for at least 12 mo. It thus appears that BM cells can give rise to endothelial cells that participate in the remodeling of glomeruli.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the role of bone marrow cells in bone fracture repair using green fluorescent protein (GFP) chimeric model mice. First, the chimeric model mice were created: bone marrow cells from GFP-transgenic C57BL/6 mice were injected into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated with a lethal dose of 10Gy from a cesium source. Next, bone fracture models were created from these mice: closed transverse fractures of the left femur were produced using a specially designed device. One, three, and five weeks later, fracture lesions were extirpated for histological and immunohistochemical analyses. In the specimens collected 3 and 5 weeks after operation, we confirmed calluses showing intramembranous ossification peripheral to the fracture site. The calluses consisted of GFP- and osteocalcin-positive cells at the same site, although the femur consisted of only osteocalcin-positive cells. We suggest that bone marrow cells migrated outside of the bone marrow and differentiated into osteoblasts to make up the calluses.

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記述言語：日本語   出版者・発行元：千代田開発(株)  

12歳3ヵ月男児.患者はB前駆型急性リンパ性白血病と診断され,東京小児癌研究グループのL99-15HRプロトコール治療を開始した.第2コース治療終了後に好中球減少を認め,lenograstim投与を開始した.第2回目の投与から数時間後,左側肘関節,膝関節,臀部に有痛性紅斑の主訴を認めた.Lenograstimの過敏症を疑い,投与を中止したが症状に変化はなく,投与を再開した.この有痛性紅斑はlenograstim終了翌日になっても消失せず,以前に使用されていたcytarabinの影響も疑った.化学療法3コース目終了後,再び好中球減少し,lenograstimを投与すると,右大腿部近位部に有痛性結節を認めた.Cytarabinは使用していなかったので,顆粒球コロニー刺激因子製剤の副作用を疑い,filgrastimに変更した.Filgrastimでも大きな変化は認めず,nartograstimに変更した結果,皮膚過敏症はなく,数日後に好中球数が回復した.以後,好中球数減少時にはnartograstimを投与しているが,有害事象は認めていない

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies suggest that human adipose tissue contain pluripotent cells similar to bone marrow-derived stromal cells (BSCs). Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have previously demonstrated that BSCs differentiate into a variety of cell lineages both in vitro and in vivo). In the present study, we extend this approach to characterize adipose-derived stromal cells (ASCs)). These cells derived from human are sometimes called processed lipoaspirate (PLA) cells. ASCs were prepared from inguinal fat pads of GFP transgenic mice after extensive washing with PBS and treatment with collagenase. After the primary culture in control medium (DMEM + 10% FBS), the cells were incubated in either chondrogenic medium (DMEM + 1% FBS + insulin + ascorbate 2-phosphate + TGF-beta 1) or osteogenic medium (DMEM + 10%FBS + dexamethasone + ascorbate-2-phosphate + beta-glycerophosphate) for two to four weeks. Chondrogenic differentiation was assessed by Alcian blue staining, while osteogenic differentiation was by von Kossa and Alkaline phosphatase staining. ASCs incubated in chondrogenic medium induced Alcian blue positive cells. Incubation with osteogenic medium became positive for von Kossa and Alkaline phosphatase staining. No osteochondrogenic differentiation was observed in cells incubated with control medium. This cell population can be easily identified through fluorescence microscope, it should be an ideal source of ASCs for further experiments of stem cell biology and tissue engineering.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have previously demonstrated that adipose-derived stromal cells (ASCs) as well as bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. Both types are considered to include mesenchymal stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have also previously reported the plasticity of BSCs and ASCs. In this study, we focused on adipogenic differentiation in vitro by ASCs harvested from GFP transgenic mice. Moreover, preadipocytes and mature adipocytes were harvested at the same time, and the cells were cultured to compare them with ASCs. Inguinal fat pads from GFP transgenic mice were used for the isolation of ASCs, preadipocytes, and mature adipocytes. After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks. Adipogenic differentiation of ASCs was assessed by Oil Red O staining and the expression of the adipocyte specific peroxisome proliferative activated receptor gamma2 (PPAR-gamma2) gene. These ASCs stained positively, and expression of PPAR-gamma2 was detected. Moreover, we also tried to characterize the influence of sex differences on the adipogenic differentiation of ASCs harvested from both male and female mice. This was assessed by the expression levels of the PPAR-gamma2 gene using real-time PCR. The results showed that the expression levels of ASCs harvested from female mice were a maximum of 2.89 times greater than those harvested from male mice. This suggests that the adipogenic differentiation of ASCs is closely related to sex differences.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Gene therapy targeting hematopoietic stem cells has been proposed as a potential therapy for numerous genetic disorders affecting hematopoiesis. Moloney murine leukemia retroviral vectors are now widely used for clinical gene transfer into hematopoietic progenitors and progeny. However, maintaining expression of therapeutic genes inserted via moloney murine leukemia virus (MoMLV)-based vectors has proven to be more difficult than previously expected. In this study, an MND-IL-2R vector containing IL-2Rc gamma cDNA to treat X-linked severe combined immunodeficiency (X-SCID) was constructed from an MND vector that was modified by substituting the myeloproliferative sarcoma virus (MPSV) enhancer for that of MoMLV, deleting the negative control region located in the long terminal repeat (LTR) as an enhancer, and replacing the primer binding site (PBS) of MoMLV with the PBS of the endogenous murine retrovirus dl587rev. This vector was transduced into human CD34 + progenitor cells with comparable efficiency to that of the MoMLV-based vector. The use of this newly created vector may be advantageous for gene therapy of X-SCID.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies suggest that human adipose tissue contains pluripotent stem cells similar to bone marrow-derived stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have previously demonstrated that bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. In the present study, we extend this approach to characterize adipose tissue-derived stromal cells, sometimes called processed lipoaspirate (PLA) cells. Adipose-derived stromal cells (ASCs) were isolated from inguinal fat pads of GFP transgenic mice after extensive washing with phosphate-buffered saline and treatment with collagenase. After primary culture in a control medium (Dulbecco's modified Eagle's medium+10% fetal bovine serum) and expansion to two passages, the cells were incubated in either an osteogenic medium (Dulbecco's modified Eagle's medium+10% fetal bovine serum+dexamethasone+ascorbate-2-phosphate+beta-glycerophosphate) or a chondrogenic medium (Dulbecco's modified Eagle's medium+1% fetal bovine serum+insulin+ascorbate-2-phosphate+transforming growth factor-beta1) for 2-4 weeks to induce osteogenesis and chondrogenesis, respectively. Osteogenic differentiation was assessed by von Kossa and alkaline phosphatase staining, while chondrogenic differentiation was assessed by Alcian blue staining. Expression of osteocyte specific osteopontin, osteocalcin, and alkaline phosphatase, and chondrocyte specific aggrecan and type II/X collagen was confirmed by RT-PCR. ASCs incubated in the osteogenic medium were stained positively for von Kossa and alkaline phosphatase staining. Expression of osteocyte specific genes, except osteocalcin, was also detected. Incubation with chondrogenic medium induced Alcian blue positive cells and expression of aggrecan and type II/X collagen genes. No osteochondrogenic differentiation was observed in cells incubated in the control medium. ASCs from GFP transgenic mice have both osteogenic and chondrogenic potential in vitro. Since this cell population can be easily identified through fluorescence microscopy, it may be an ideal source of ASCs for further experiments on stem cell biology and tissue engineering.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined whether non-hematopoietic BM cells can migrate into the intestinal graft after fetal small intestinal transplantation (FSITx). Fetal small intestine from donor C57BL/6 mice was transplanted into the rectus abdominis of recipient C57BL/6 mice with only green fluorescent protein (GFP) BM cells (syngeneic FSITx). Intestinal grafts were harvested on days 5, 10, and 30 after FSITx and stained immunohistochemically using anti-CD45 antibody (a marker for hematopoietic BM cells). Although there were no GFP-positive cells identified in the epithelium of the graft intestinal villi, there were a few cells positive for both GFP and CD45 in the lamina propria on day 5 after FSITx, and many present on days 10 and 30. In some grafts there were only cells that were GFP positive/CD45 negative (i.e., non-hematopoietic BM cells) found in the lamina propria on days 10 and 30. These data indicate that non-hematopoietic BM cells as well as hematopoietic BM cells can migrate from the recipient's bone marrow, suggesting that recipient mesenchymal stem cells may be strongly implicated in graft regeneration and development after FSITx.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 +/- 5.9%) and at 3 mo (45.3 +/- 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 +/- 45 cells/50 sections; 3 mo: 458 +/- 100 cells/50 sections; p < 0.05 versus noninfarct, infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

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記述言語：英語  

DOI： 10.1007/s00431-001-0859-7

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Studies have indicated that bone marrow contains both hematopoietic stem cells and mesenchymal stem cells that can differentiate into a variety of mesenchymal tissues, such as bone, cartilage, muscle, and adipose tissue. Therefore, bone marrow cells are thought to be very useful for cell and gene therapy for various diseases. However, the multipotentiality of these cells remains unclear. To address this issue, we established a chimeric model mouse stably reconstituted with green fluorescent protein (GFP)-marked bone marrow cells. We injected bone marrow cells from GFP-transgenic C57BL/6 mice into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated with a lethal dose of 10 Gy from a cesium source. Microscopic examination and fluorescence-assisted cell sorter (FACS) analysis showed that bone marrow cells, including mesenchymal cells, were almost completely reconstituted with GFP+ cells 5 weeks after transplantation. FACS analysis with lineage-specific antibodies confirmed that the GFP+ cells could differentiate into all types of blood cells. To confirm the usefulness of this mouse model, we studied the role of circulating bone marrow-derived cells in healing of damaged intestine. We performed amputation and anastomosis of the jejunum 10 cm from the pyloric region of the stomach. On the third day after operation, a large number of GFP+ cells were infiltrated in the area of anastomosis, and these cells were positive for CD45 and F4/80 antigens. In 7 days, several cells became negative for CD45 and F4/80 and positive for alpha smooth muscle actin antigen, which is specific for smooth muscle. This finding suggested that bone marrow-derived cells had differentiated into smooth muscle. Because reconstituted bone marrow cells as opposed to injected bone marrow cells, behave naturally, this model is ideal for studying the multipotentiality of bone marrow cells in vivo.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chimeric mice stably reconstituted with bone marrow cells represent a good model for analysis of the mechanism of bone marrow cell infiltration in the brain. However, in preparing chimeric mice, irradiation of the recipient mice is necessary to kill their own bone marrow before transplantation, which induces gliosis and inflammatory response by activation of astrocytes and microglia in the brain. Here, we determined the most suitable dose of irradiation associated with the least brain damage before transplantation for reconstitution of chimeric mice, using FACS analysis. Our mouse model of 10 Gy body/5 Gy head irradiation should be useful for investigating the mechanism(s) of microglial activation in various neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a floppy infant with Werdnig-Hoffmann disease (spinal muscular atrophy: SMA type 1) and Klinefelter syndrome. After genetic counseling with parents, a genetic diagnosis using DNA from the infant's peripheral blood mononuclear cells was performed. The parents' deletion of exons 7 and 8 of the survival motor neuron (smn) gene and exons 4 and 5 of the neuronal apoptosis inhibitory protein (naip) gene were noted in the infant, so he was confirmed to have SMA type 1. The parents wanted to receive a prenatal diagnosis on the next pregnancy. However this genetic test is achieved by confirming that a specific band can not be detected by PCR. Therefore, this method should be applied with great care to prenatal diagnosis using chorionic villi, which may be contaminated with maternal tissue.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fabry disease is a systemic disease caused by genetic deficiency of a lysosomal enzyme, alpha-galactosidase A (alpha-gal A), and is thought to be an important target for enzyme replacement therapy. We studied the feasibility of gene-mediated enzyme replacement for Fabry disease. The adeno-associated virus (AAV) vector containing the alpha-gal A gene was injected into the right quadriceps muscles of Fabry knockout mice. A time course study showed that alpha-gal A activity in plasma was increased to approximately 25% of normal mice and that this elevated activity persisted for up to at least 30 weeks without development of anti-alpha-gal A antibodies. The alpha-gal A activity in various organs of treated Fabry mice remained 5-20% of those observed in normal mice. Accumulated globotriaosylceramide in these organs was completely cleared by 25 weeks after vector injection. Reduction of globotriaosylceramide levels was also confirmed by immunohistochemical and electronmicroscopic analyses. Echocardiographic examination of treated mice demonstrated structural improvement of cardiac hypertrophy 25 weeks after the treatment. AAV vector-mediated muscle-directed gene transfer provides an efficient and practical therapeutic approach for Fabry disease.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We diagnosed influenza infection in 2 children receiving maintenance treatment for acute lymphoblastic leukemia. Both patients received zanamivir within 1 d of the onset of fever and their symptoms of influenza were rapidly alleviated. We conclude that inhaled zanamivir seems to be an effective treatment for influenza infection in immunocompromised patients.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

Background. Bone marrow transplantation is reportedly effective in preventing the progression of neurological deterioration in lysosomal storage disorders, although the mechanism underlying the therapeutic effects remains to be elucidated. Recent research on stem cell biology suggests that bone marrow cells contain nonhematopoietic stem cells, including brain precursor cells. To evaluate the contribution of bone marrow cells as carriers for cell and gene therapy of neurological disorders, we studied the fate of transplanted bone marrow cells in the adult mouse brain. Methods. Bone marrow cells were genetically marked with a retroviral vector containing the green fluorescence protein gene and then transplanted into irradiated mice by either systemic infusion or direct injection. To identify cell types, brain sections were stained with specific antibodies against neuronal cell markers - neuron specific enolase for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1 (Iba1) for microglia - and then examined under a confocal microscope. Results. Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but none of the other brain cell markers. Conversely, 12 weeks after direct injection, transplanted cells were stained with antibodies against GFAP, CAII, and Iba1. Conclusions. Bone marrow contains cells capable of differentiating into oligodendrocytes, astrocytes, and microglia when exposed to the brain microenvironment. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for lysosomal disorders with neurological symptoms.

DOI： 10.1097/00007890-200106270-00006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders Ltd  

Complications of influenza include respiratory disorders (pneumonia, bronchitis and croup) and occasionally myocarditis, myositis, encephalitis, encephalopathy and Reye's syndrome, which may be life-threatening and cause various sequelae. We report two patients who developed unusual complications of influenza infection: one had ptosis and impaired ocular movement, and the other suffered from Guillain-Barré syndrome with paralysis of the extraocular muscles.

DOI： 10.1053/ejpn.2001.0470

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In recent years, enzyme replacement therapy has been shown to be useful for the treatment of Gaucher disease. A 10 year old Japanese boy with Gaucher disease underwent splenectomy at the age of 5 years and received enzyme replacement therapy from the age of 6 years. He had avascular necrosis of the bilateral femoral heads, which was not seen at the beginning of the therapy, without deterioration of hematological variables during maintenance therapy. The enzyme dosage was increased from 20 to 120 IU/kg per month resulting in an improvement of the clinical symptoms and bone lesion. In enzyme replacement therapy, dose increase is considered to be essential for improvement in bone disease
however, it is important to watch for the development of bone lesion. © 1996 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1996.tb03482.x

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

We report on 10 premature infants with acute hemolytic anemia and Heinz bodies treated from 1999 to 2007 and discuss their clinical characteristics. All patients were very low birth weight infants (mean gestational age, 27 weeks; range, 24～30 weeks; mean birth weight, 889g; range, 598～1,412g), and hemolytic anemia developed after cardiopulmonary adaptation had been achieved. Heinz body appeared an average of 20 days after birth (range, 11～25 days), and hemolysis persisted for an average of 9 days (range, 4～16 days) and spontaneously resolved. Hemolytic anemia and jaundice developed suddenly, during which time Heinz bodies were observed on hematologic examination. The affected infants showed refractory apnea just before the onset of hemolytic anemia.&lt;br&gt; The exact cause of these hemolytic episodes remains unclear. However, the immature antioxidant function of the red blood cell membrane against oxygen radicals was a suspected cause, because most of the infants required ventiratory managements with high concentration of supplemental oxygen.&lt;br&gt;

DOI： 10.1272/manms.7.16

CiNii Books

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC HEMATOLOGY  

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DOI： 10.1182/blood.V110.11.4108.4108

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本小児がん学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：NATURE PUBLISHING GROUP  

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記述言語：日本語   出版者・発行元：日本小児血液学会  

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記述言語：日本語   出版者・発行元：日本小児血液学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本先天代謝異常学会  

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記述言語：日本語   出版者・発行元：日本小児血液学会  

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記述言語：日本語   出版者・発行元：(一社)日本血液学会  

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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