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Shigeru Chiba

Publications and source records attributed to Shigeru Chiba.

At least 73 records · Page 4Linked to original sources
PubMed2003

Valpha24+ natural killer T-cell responses against T-acute lymphoblastic leukaemia cells: implications for immunotherapy.

Human Valpha24+ natural killer T (NKT) cells correspond to mouse Valpha14+ NKT cells, both cell types use an invariant T-cell receptor-alpha chain and are activated by glycolipids in a CD1d-dependent manner. Mouse Valpha14+ NKT cells have been reported to have an antitumour effect in vivo. Human Valpha24+ NKT cells can kill a proportion of tumour cells in a CD1d-dependent manner in vitro. We report here that many human leukaemic T-cell lines express CD1d and can be directly killed by Valpha24+ NKT cells. This killing activity was enhanced in the presence of alpha-galactosylceramide (alpha-GalCer), a ligand of Valpha24+ NKT cells. Moreover, primary leukaemic T cells from five of eight T-cell acute lymphoblastic leukaemia (T-ALL) patients expressed CD1d and were good targets of Valpha24+ NKT cells. This cytotoxicity was increased in the presence of alpha-GalCer. Our results suggest that T-ALL is a good candidate for Valpha24+ NKT-cell-based immuno-cell therapy.

Antigens, CD1↗
PubMed2003

[Investigation of the cause of polyurethane catheter cracking during constant infusion of etoposide (VP-16) injection (2)--Analysis of ethanol eluting materials from catheter].

We studied the cause of cracking of clinically used polyurethane (PU) catheters during the constant infusion of etoposide (VP-16) injection (Lastet inj.) without dilution. After the vehicles used for VP-16 injection, ethanol or polyethylene glycol 400 (PEG400), were infused into the PU catheters at a constant infusion rate (30 ml/h) for 24 h, obvious degradation of the internal wall of the catheter was observed under an electron microscope. When the PU catheter was immersed in ethanol for 24 h, condensed polymers of 1,4-butanediol (BD), contained in PU catheters as an elasticizer, were detected in the ethanol elute using the ESI/MS method. Moreover, time-dependent elution of BD from PU catheters with the infusion of ethanol into the catheter for 24 h at 30 ml/h was observed using the GC/MS method. The cumulative amount of BD eluted from the PU catheter with ethanol vehicle for 24 h was 130 micrograms. In conclusion, degradation and subsequent cracking of PU catheters during the infusion of VP-16 injection were caused by ethanol and PEG400 contained in the injection solution. Furthermore, to prevent the elution of BD from PU catheters, we suggest that PU catheters should not be used for the administration of VP-16 injection without dilution in consideration of safety and efficacy.

Butylene Glycols↗
PubMed2003

Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

Adult↗
PubMed2002

Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies.

An approach was used to identify the oxidized nucleoside, 8-hydroxyguanosine in brains of dementia with Lewy bodies. Neurons with marked immunoreaction of 8-hydroxyguanosine in the cytoplasm were widely distributed in the hippocampal region and temporal neocortex. Relative intensity measurements of neuronal 8-hydroxyguanosine immunoreactivity showed that there was a significant increase in nucleic acid oxidation in dementia with Lewy bodies compared with controls. Treatment with nuclease (DNase or RNase) before the immunostaining demonstrated that RNA was a major site of nucleic acid oxidation. Together with the previously reported RNA oxidation in vulnerable neurons in Alzheimer and Parkinson diseases, neuronal RNA oxidation in dementia with Lewy bodies might represent one of the fundamental abnormalities in age-associated neurodegenerative diseases.

Aged↗
PubMed2002

HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo.

Mouse long-term hematopoietic reconstituting cells exist in the c-Kit+Sca-1+Lin- (KSL) cell population; among them, CD34(low/-) cells represent the most highly purified population of hematopoietic stem cells in the adult bone marrow. Here, we demonstrate that retrovirus-mediated transduction of CD34(low/-)c-Kit+Sca-1+Lin- (34-KSL) cells with the HES-1 gene, which encodes a basic helix-loop-helix transcription factor functioning downstream of the Notch receptor, and is a key molecule for the growth phase of neural stem cells in the embryo, preserves the long-term reconstituting activity of these cells in vitro. We also show that cells derived from the HES-1-transduced 34-KSL population produce progenies characterized by negative Hoechst dye staining, which defines the side population, and by CD34(low/-) profile in the bone marrow KSL population in each recipient mouse at ratios 3.5- and 7.8-fold those produced by nontransduced 34-KSL-derived competitor cells. We conclude that HES-1 preserves the long-term reconstituting hematopoietic activity of 34-KSL stem cells ex vivo. Up-regulation of HES-1 protein in the 34-KSL population before unnecessary cell division, that is, without retrovirus transduction, may represent a potent approach to absolute expansion of hematopoietic stem cells.

Animals↗
PubMed2002

Hypocretin-1 (orexin-A) levels in human lumbar CSF in different age groups: infants to elderly persons.

STUDY OBJECTIVES: Recent CSF and postmortem brain hypocretin measurements in human narcolepsy suggest that hypocretin deficiency is involved in the pathophysiology of the disease. In this study, we measured CSF hypocretin-1 levels in various age ranges from infants to elder people to investigate the age-dependent change of hypocretin concentrations. DESIGN: CSF hypocretin levels were compared by age groups and gender. ANOVA was used to examine the influences of these two parameters on CSF hypocretin levels. SETTING: University-based sleep and biology laboratory. PATIENTS OR PARTICIPANTS: Two hundred seventy two patients were included in this study, with 157 males and 115 females (0-79 years old). INTERVENTIONS: CSF samples were obtained by lumber punctures with informed consents. MEASUREMENTS AND RESULTS: Hypocretin-1 levels are not different in respect to gender or age, although our samples constitute a heterogeneous group with various disease conditions. CSF hypocretin-1 levels in infants under 4 months are similar to those in adults. CONCLUSIONS: Early maturation of hypocretin transmission is suggested. No age- or gender-dependent changes in CSF hypocretin is observed.

Adult↗
PubMed2002

Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in mice.

Notch1 is indispensable for T cell development. It is anticipated that Notch1 and other Notch receptors expressed on the surface of thymic T cell precursors are activated by ligands present on environmental cells, including antigen presenting cells (APCs), and involved in positive and negative selections. Notch receptors on peripheral T cells may also be activated by ligands on APCs. Here, we examined the expression pattern of three Notch ligands, Jagged1, 2 and Delta1 in APCs by an immunofluorescence cell staining method and a reverse transcriptase-polymerase chain reaction (RT-PCR) method. Peritoneal macrophages were strongly positive for Jagged1 staining. In contrast, macrophages separated from spleen and dendritic cells (DCs) separated from spleen and thymus showed positive staining for all the three ligands at a similar intensity. An analysis by RT-PCR revealed that peritoneal and splenic macrophages and splenic and thymic DCs, show a distinct pattern in Notch ligand expression. These findings may represent that expression of various Notch ligands in APCs has a physiological relevance in each organ.

Animals↗
PubMed2002

Cutting edge: analysis of human V alpha 24+CD8+ NK T cells activated by alpha-galactosylceramide-pulsed monocyte-derived dendritic cells.

Human Valpha24(+) NKT cells constitute a counterpart of mouse Valpha14(+) NKT cells, both of which use an invariant TCR-alpha chain. The human Valpha24(+) NKT cells as well as mouse Valpha14(+) NKT cells are activated by glycolipids in a CD1d-restricted manner and produce many immunomodulatory cytokines, possibly affecting the immune balance. In mice, it has been considered from extensive investigations that Valpha14(+)CD8(+) NKT cells that express invariant TCR do not exist. Here we introduce human Valpha24(+)CD8(+) NKT cells. These cells share important features of Valpha24(+) NKT cells in common, but in contrast to CD4(-)CD8(-) (double-negative) or CD4(+) Valpha24(+) NKT cells, they do not produce IL-4. Our discovery may extend and deepen the research field of Valpha24(+) NKT cells as well as help to understand the mechanism of the immune balance-related diseases.

Antigens, CD1↗
PubMed2002

Functional diversity among Notch1, Notch2, and Notch3 receptors.

To clarify functional diversities among the Notch receptors, we generated truncated forms of Notch1, Notch2, and Notch3 comprising the intracellular domain (aN1, aN2, and aN3) and investigated their transcriptional activities for HES1 and HES5 promoters driving the luciferase reporter gene (HES1-Luc and HES5-Luc). The reporter assays demonstrated that the transcriptional activities of aNs were markedly different from each other and dependent on the promoters examined. Furthermore, relative activities between some aN and another for each promoter were altered by the expression level of RBP-J kappa. We also found that the activities of aN1 and aN3 were reduced by coexpression of aN2. These observations suggest that each Notch receptor has a diverse role in the downstream gene expression and that the levels of HES1 and HES5 gene expression are complexly determined by various factors, such as the type and combination of the Notch receptors which confer the downstream signals and the expression level of RBP-J kappa.

Animals↗
PubMed2002

Integrity of intracellular domain of Notch ligand is indispensable for cleavage required for release of the Notch2 intracellular domain.

The biological activity of the soluble form of the Notch ligand (sNL) and requirement of the intracellular domain (ICD) of the Notch ligand have been debated. Here we show that soluble Delta1 (sD1) activates Notch2 (N2), but much more weakly than full-length Delta1 (fD1). Furthermore, tracing the N2 molecule after sD1 stimulation revealed that sD1 has a defect in the cleavage releasing ICD of N2 (intracellular cleavage), although it triggers cleavage in the extracellular domain of N2. This represents the molecular basis of the lower activity of sD1 and suggests the presence of an unknown mechanism regulating activation of the intracellular cleavage. The fact that Delta1 lacking its ICD (D1Delta(ICD)) exhibits the phenotype similar to that exhibited by sD1 indicates that the ICD of D1 (D1(ICD)) is involved in such an as yet unknown mechanism. Furthermore, the findings that D1Delta(ICD) acts in a dominant-negative fashion against fD1 and that the signal-transducing activity of sD1 is enhanced by antibody-mediated cross-linking suggest that the multi merization of Delta1 mediated by D1(ICD) may be required for activation of the N2 intracellular cleavage.

Animals↗
PubMed2002

Generation of Fas-independent CD4+ cytotoxic T-cell clone specific for p190 minor bcr-abl fusion peptide.

In the majority of Ph+ALL patients, p190 bcr-abl fusion protein is generated in the Philadelphia chromosome. The fusion protein may serve as a leukemia antigen because it is not expressed in normal cells and hardly in any other malignancy. From a healthy donor, we have established a p190 bcr-abl fusion peptide-specific CD4+ cytotoxic T-cell clone, activation of which depends on HLA-DRB1*1501. This T-cell clone has a strong cytotoxic activity against autologus MoDCs pulsed with e1a2 peptide and its cytotoxicity is not mediated by Fas/Fas ligand or perforin pathway. Success in establishment of the p190 bcr-abl fusion peptide-specific T-cell clone encourages us to develop a new approach to an effective immunotherapy for Ph+ALL.

Amino Acid Sequence↗
PubMed2002

CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia.

We measured cerebrospinal fluid (CSF) hypocretin-1 levels in 11 patients with narcolepsy-cataplexy, five with narcolepsy without cataplexy and 12 with idiopathic hypersomnia (IHS). All patients were Japanese. As reported in Caucasian patients, undetectable or very low hypocretin-1 levels were observed in most (9 out of 11) Japanese narcolepsy--cataplexy patients. Our hypocretin-deficient narcoleptics included three prepubertal cases within few months after the disease onset. All nine hypocretin-deficient patients were human leuckocyte antigen (HLA) DR2 positive, while two who had normal CSF hypocretin-1 levels were HLA DR2 negative. In contrast, none of the narcolepsy without cataplexy and IHS subjects had undetectable low levels. Low CSF hypocretin-1 is therefore very specific for HLA DR2 positive narcolepsy-cataplexy, and the deficiency is likely to be established at the early stage of the disease.

Adult↗
PubMed2002

Mutational analyses of the AML1 gene in patients with myelodysplastic syndrome.

The AML1 gene is the most frequent target of translocations associated with human leukemias. We recently found somatic point mutations of the AML1 gene, V105ter and R139G, in two cases of myelodysplastic syndrome (MDS). Both mutations are present in the region encoding the Runt domain of AML1, and cause loss of the DNA-binding ability of the resultant products. Of these mutants, V105ter has also lost the ability to heterodimerize with PEBP2beta/CBFbeta. On the other hand, the R139G mutant acts as a dominant negative inhibitor through competing with wild-type AML1 for interaction with PEBP2beta/CBFbeta. In this review, we summarize mutational changes of the AML1 gene in hematological malignancies, especially in MDS and discuss the mechanism whereby the mutant acts as a dominant negative inhibitor of wild-type AML1.

Core Binding Factor Alpha 2 Subunit↗
PubMed2002

[Syncope].

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Autonomic Nervous System↗