Biomedical subjects

Takahiro Ueda

Publications and source records attributed to Takahiro Ueda.

25 records · Page 2Linked to original sources

PubMed2002

Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38- cells expressing Flk2/Flt3.

In the present study, we examined the expression of Flk2/Flt3, a tyrosine kinase receptor, on human cord blood CD34+ haematopoietic progenitor/stem cells. In flow cytometric analysis, Flk2/Flt3 was expressed on 80% of CD34+ cells and their immature subpopulations, CD34+CD33- and CD34+CD38- cells. Methycellulose clonal culture of sorted CD34+Flk2/Flt3+ and CD34+Flk2/Flt3- cells showed that most of myelocytic progenitors expressed Flk2/Flt3, but erythroid and haematopoietic multipotential progenitors were shared by both fractions. When 1 x 10(4) lineage marker-negative (Lin-)CD34+Flk2/Flt3- cells were transplanted into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, none of the recipients possessed human CD45+ cells in bone marrow 11-12 weeks after the transplantation. In contrast, all recipients transplanted with 1 x 10(4) Lin-CD34+Flk2/Flt3+ cells showed successful engraftment. Furthermore, clonal cells expanded from single Lin-CD34+CD38-Flk2/Flt3+ cells in the culture with Flk2/Flt3 ligand, stem cell factor, thrombopoietin, and a complex of interleukin 6/soluble interleukin 6 receptor were individually transplanted into NOD/SCID mice. At 20 to 21 weeks after the transplantation, three out of 10 clones harvested at d 7 of culture, and three out of six clones at d 14 could reconstitute human haematopoiesis in recipient marrow. These results demonstrated that Flk2/Flt3 was expressed on a wide variety of human haematopoietic cells including long-term-repopulating haematopoietic stem cells.

Animals↗

PubMed2002

Relationship of neurologic degeneration to genotype in three xeroderma pigmentosum group G patients.

We studied three newly diagnosed xeroderma pigmentosum complementation group G patients with markedly different clinical features. An Israeli-Palestinian girl (XP96TA) had severe abnormalities suggestive of the xeroderma pigmentosum/Cockayne syndrome complex including sun sensitivity, neurologic and developmental impairment, and death by age 6 y. A Caucasian girl (XP82DC) also had severe sun sensitivity with neurologic and developmental impairment and died at 5.8 y. In contrast, a mildly affected 14-y-old Caucasian female (XP65BE) had sun sensitivity but no neurologic abnormalities. XP96TA, XP82DC, and XP65BE fibroblasts showed marked reductions in post-ultraviolet cell survival and DNA repair but these were higher in XP65BE than in XP82DC. XP96TA fibroblasts had very low XPG mRNA expression levels whereas XP65BE fibroblasts had nearly normal levels. Host cell reactivation of an ultraviolet-treated reporter assigned all three fibroblast strains to the rare xeroderma pigmentosum complementation group G (only 10 other patients previously reported). XP96TA and XP82DC cells had mutations in both XPG alleles that are predicted to result in severely truncated proteins including stop codons and two base frameshifts. The mild XP65BE patient had an early stop codon mutation in the paternal allele. The XP65BE maternal allele had a single base missense mutation (G2817A, Ala874Thr) that showed residual ability to complement xeroderma pigmentosum complementation group G cells. These observations agree with earlier studies demonstrating that XPG mutations, which are predicted to lead to severely truncated proteins in both alleles, were associated with severe xeroderma pigmentosum/Cockayne syndrome neurologic symptoms. Retaining residual functional activity in one allele was associated with mild clinical features without neurologic abnormalities.

Adolescent↗

PubMed2002

Zanamivir is an effective treatment for influenza in children undergoing therapy for acute lymphoblastic leukemia.

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.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Formation of cyclobutane pyrimidine dimers and 8-oxo-7,8-dihydro-2'-deoxyguanosine in mouse and organ-cultured human skin by irradiation with broadband or with narrowband UVB.

Narrowband UVB (NB-UVB) is a newly developed UVB source that, in addition to the previously used broadband UVB (BB-UVB), has been effectively used in phototherapy of various skin diseases. Besides its therapeutic effectiveness, NB-UVB also has some adverse effects that should be evaluated. As with all phototherapies, the photocarcinogenic potential of NB-UVB is the major concern. To assess the carcinogenic potential we measured the DNA damage induced by the two UVB sources because exposure of cells to UVB directly or indirectly induces DNA damage such as cyclobutane pyrimidine dimers (CPD) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), respectively. These types of DNA damage cause mutations of oncogenes and tumor suppressor genes, which can lead to photocarcinogenesis. In the present study we measured the yield of CPD and the oxidative DNA damage marker, 8-oxodGuo, in organ-cultured human skin and in mouse skin after exposure to NB-UVB or BB-UVB at therapeutically equivalent doses. We show that a 10-fold higher dose of NB-UVB yields a similar amount of CPD compared with BB-UVB in two types of samples examined. In contrast to CPD, the formation of 8-oxodGuo after irradiation with NB-UVB at a 10-fold higher dose is 1.5-3 times higher than that caused by BB-UVB. These results suggest that although NB-UVB at equivalent erythema-edema doses is not more potent in inducing CPD formation than is BB-UVB, NB-UVB may generate a higher yield of oxidized DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2002

Pulmonary hyalinizing granuloma with hydronephrosis.

A 49-year-old man was admitted for the evaluation of a bilateral mass shadow in his chest X-ray film. No definitive diagnosis was established either by brushing cytology or biopsy through bronchoscopy. No malignancies were suggested by general work-up. Both masses were surgically removed, and were diagnosed as pulmonary hyalinizing granuloma (PHG). Fifteen months later, low grade fever continued and the renal function decreased. Laboratory examinations revealed bilateral hydronephrosis with polyclonal hypergammaglobulinemia. The findings of abdominal CT and urography were compatible with retroperitoneal fibrosis. Steroid treatment completely reversed the initial abnormality in laboratory data and the symptoms disappeared.

Glucocorticoids↗

PubMed2001

Hematopoietic capability of CD34+ cord blood cells: a comparison with CD34+ adult bone marrow cells.

The characteristics of hematopoietic progenitor and stem cell (HPC/HSC) populations in mammals vary according to their ontogenic stage. In humans, HPC/HSCs from umbilical cord blood (CB) are increasingly used as an alternative to HPC/HSCs from adult bone marrow (BM) for the treatment of various hematologic disorders. How the hematopoietic activity of progenitor and stem cells in CB differs from that in adult BM remains unclear, however. We compared CD34+ cells, a hematopoietic cell population, in CB with those in adult BM using phenotypic subpopulations analyzed by flow cytometry, the colony-forming activity in methylcellulose clonal cultures, and the repopulating ability of these cells in NOD/Shi-scid (NOD/SCID) mice. Although the proportion of CD34+ cells was higher in adult BM than in CB mononuclear cells, the more immature subpopulations, CD34+ CD33- and CD34+ CD38- cells, were present in higher proportions in CD34+ CB cells. Clonal culture assay showed that more multipotential progenitors were present in CD34+ CB cells. When transplanted into NOD/SCID mice. CD34+ adult BM cells could not reconstitute human hematopoiesis in recipient BM, but CD34+ CB cells achieved a high level of engraftment, indicating that CD34+ CB cells possess a greater repopulating ability. These results demonstrated that human hematopoiesis changes with development from fetus to adult. Furthermore, CD34+ CB cells contained a greater number of primitive hematopoietic cells, including HSCs, than did adult BM, suggesting the usefulness of CD34+ CB cells not only as a graft for therapeutic HSC transplantation but also as a target cell population for ex vivo expansion of transplantable HSCs and for gene transfer in gene therapy.

Adult↗

PubMedDate not supplied

Cobalt-59 NMR and X-ray diffraction studies of hydrated and dehydrated (+/-)-tris(ethylenediamine) cobalt(III) chloride.

Cobalt-59 NMR experiments have been carried out on single-crystal and polycrystalline (powder) samples of (+/-)-tris(ethylenediamine)cobalt(III) chloride trihydrate, (+/-)-[Co(en)(3)]Cl(3) x 3H(2)O, and of its dehydrate. In addition, the X-ray crystal structure of the dehydrated sample has been determined. X-ray diffraction measurements confirm a long-held assumption that dehydration has only minor effects on the structure of the [Co(en)(3)](3+) cation. Nevertheless, these small differences have a detectable effect on the 59Co nuclear magnetic resonance properties of these compounds; in particular, the nuclear quadrupole coupling constant, C(Q). Straightforward identification of the c-axis for large single crystals of (+/-)-[Co(en)(3)]Cl(3).3H(2)O and of its dehydrate allowed us to obtain single-crystal 59 Co NMR data by orienting the crystals in an MAS rotor. Data collected on single crystals and polycrystalline samples indicate that C(Q)=-3.05+/-0.05 and -2.80+/-0.05 MHz for the hydrated and dehydrated samples, respectively; the signs have been assigned on the basis of a point charge model. The chemical shift tensor principal components were also determined: for the hydrated sample, delta(perpendicular)=7281+/-2 ppm, delta(parallel)=7004+/-4 ppm and delta(iso)=7189 ppm; for the dehydrated sample, delta(perpendicular)=7288+/-2 ppm, delta(parallel)=7008+/-4 ppm and delta(iso)=7195 ppm. The electric field gradient and chemical shift tensors are axially symmetric, as required by crystal symmetry.

Journal Article↗