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Hiroko Nagafuchi

Publications and source records attributed to Hiroko Nagafuchi.

7 recordsLinked to original sources
PubMed2005

The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice.

BACKGROUND: High-mobility group 1 (HMGB-1) is a late mediator of endotoxin lethality in mice. The release of HMGB-1 is delayed compared to other proinflammatory cytokines that mediate shock and tissue injury. The purpose of this study was to investigate the role of HMGB-1 levels in response to hepatic ischemia, hepatic I/R injury, and the relationship between changes in HMGB-1 and other cytokines. MATERIALS AND METHODS: Three murine models were employed: our robust model of segmental hepatic warm ischemia (SHWI), a model of partial hepatic ischemia/reperfusion injury (PHIRI), and a model of total hepatic ischemia/reperfusion injury (THIRI). Over a 48-h period following ischemic insult and reperfusion using these models, serum HMGB-1 concentrations, concentrations of HMGB-1 in ischemic and nonischemic lobes, and serum concentrations of TNF-alpha and IL-6 levels were determined in mice. An anti-HMGB-1 antibody treatment was used in SHWI and THIRI to evaluate what aspects of response to ischemia and reperfusion were potentially mediated by HMGB-1. RESULTS: Hepatic HMGB-1 tissue concentrations exhibited biphasic changes in SHWI mice, which were increased in the ischemic lobes relative to nonischemic lobes at 12 h but decreased relative to nonischemic lobes at 24 h after ischemic insult. These results suggested that HMGB-1 was released into the systemic circulation by necrotic cells over the first 12 h but this process may be complete by 24 h postischemia. By 6 to 12 h after SHWI, serum TNF-alpha began to increase significantly and continued to increase for 18 h, followed by a sudden decline. Similarly, serum IL-6 increased over 1-3 h after SHWI and then decreased over the next 6 h. Treatment with an anti-HMGB-1 antibody significantly prolonged survival time in SHWI and THIRI. CONCLUSIONS: HMGB-1 plays a significant role in the response to hepatic ischemia and hepatic ischemia/reperfusion injury. The present study demonstrated a time-dependent production of HMGB-1 following hepatic warm ischemia in mice. The inherent HMGB-1 in ischemic areas was exhausted and HMGB-1 may be released by necrotic cells. HMGB-1 activation is involved in immediate proinflammatory stress response to I/R and anti-HMGB-1 antibody treatment remarkably improved survival. We demonstrated that systemic HMGB-1 accumulation was measured at an earlier phase of the hepatic ischemia and ischemia/reperfusion injury model than LPS-induced endotoxemia.

Animals↗
PubMed2005

[LE cell test].

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Antibodies, Antinuclear↗
PubMed2004

Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage.

We have treated undifferentiated mouse embryonic stem (ES) cells with all-trans retinoic acid (RA) to induce differentiation in vitro into neuron-like cells with good cell viability for use as a graft. Furthermore, we asked whether the RA-induced neuron-like cells restored neurological dysfunction. To this end, the cells were transplanted into right hemiplegia model of mice, developed by a cryogenic injury of motor cortex. Motor function of the recipients was gradually improved, whereas little improvement was observed in control mice. The lesion showed clustering of mature and almost mature neuron-like cells in mice transplanted with the RA-treated cells. The grafted cells had synaptic vesicles. This finding may suggest their maturation and synaptic connection in the recipient brain. Even though further study is necessary to elucidate molecular and cellular mechanisms responsible for the functional recovery, we consider that the ES cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction.

Animals↗
PubMed2003

Abnormal killer inhibitory receptor expression on natural killer cells in patients with Behçet's disease.

Viral infection has been assigned some role in the pathogenesis of Behçet's disease (BD). Defects in natural killer (NK) cell repertoire may be involved in impaired antiviral immunity, leading to the development of BD. We studied killer inhibitory receptor (KIR) expression in 40 patients with BD. CD94 and CD158b expression of NK cells was normal in a great majority of BD patients. NKB1 expression was reduced in eight and increased in six. Twelve of these 14 patients (86%) had severe eye disease. Some had reduced NKB1 and enhanced CD158a expression simultaneously, or enhanced NKB1 and reduced CD158a simultaneously, suggesting a skewed NK cell repertoire in BD. Collectively, KIR expression was abnormal in the BD patients with severe eye disease. This may result from genetic predisposition, or certain viruses may affect the KIR repertoire formation in BD patients. Abnormal KIR expression of NK cells may be associated with the development of BD.

Adult↗
PubMed2002

Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription.

Precise mechanisms responsible for Th1 cell activation and differentiation are not fully elucidated. We have recently reported that Txk, a member of Tec family nonreceptor tyrosine kinase, is expressed on Th1/Th0 cells, and Txk regulates specifically IFN-gamma gene expression. In this study, we found that Txk bound to IFN-gamma promoter region. Txk transfection increased transcriptional activity of IFN-gamma promoter plus luciferase constructs severalfold, including IFN-gamma promoter -538, -208, and -53. IFN-gamma promoter -39 was refractory to the Txk transfection. The actual site to which Txk bound was the element consisting of -53 and -39 bp from the transcription start site of human IFN-gamma gene, a site distinct from several previously characterized binding sites. We found that the entire -53/-39 region was necessary for the binding to and function of Txk, because mutant promoter oligoDNA that contained contiguous five base substitutions dispersed throughout the -53/-39 inhibited the binding, and the mutant promoters did not respond to the Txk transfection. Similar sequences of this element are found within the 5' flanking regions of several Th1 cell-associated protein genes. Thus, Txk is expressed on Th1/Th0 cells with the IFN-gamma production and acts as a Th1 cell-specific transcription factor.

Base Sequence↗
PubMed2002

Flk1+ cells derived from mouse embryonic stem cells reconstitute hematopoiesis in vivo in SCID mice.

OBJECTIVE: Embryonic stem (ES) cells are pluripotent and can differentiate into any cell type, including the hematopoietic lineage. We examined whether hematopoietic progenitor cells derived from ES cells reconstitute hematopoiesis in irradiated SCID mice. MATERIALS AND METHODS: ES cells (E14.1, H2K(b)) were cultured for 4 days in semisolid medium containing methylcellulose. Irradiated SCID mice were used as recipients of hematopoietic progenitor cells. Cell surface antigen expression was analyzed by flow cytometry. The spleens of the recipient mice were studied by hematoxylin and eosin staining and immunohistochemical staining. RESULTS: After cell culture of ES cells in methylcellulose for 4 days, the cells expressing Flk1 (VEGF receptor 2), a tentative marker of hemangioblasts, were increased, whereas cells expressing CD31 (PECAM-1) and E-cadherin (nonmesodermal adhesion molecule) were dramatically reduced. Flk1+ cells expressed c-kit predominantly. Circulating leukocytes and thrombocytes were increased in irradiated SCID (H2K(d)) mice transplanted with ES cell-derived Flk1+ cells compared with vehicle-injected control mice. H2K(b+) and VE-cadherin(+) vascular endothelial cells were prominent in spleens of the recipient mice. Flow cytometric analysis demonstrated that H2K(b+) cells were increased in the bone marrow of recipient mice. In addition, Flk1+ cells accompanying enhanced c-kit expression preferentially repopulated in the bone marrow, and leukopoiesis and thrombopoiesis of the recipient mice were evident. CONCLUSION: The Flk1+ hematopoietic cells derived from ES cells reconstitute hematopoiesis in vivo and may become an alternative donor source for bone marrow transplantation.

Animals↗