記述言語：英語   掲載種別：研究論文（学術雑誌）  

Non-obese diabetic (NOD) mice develop diabetes mediated by pathogenic T-helper type 1 (Th1) cells. V alpha 14 Natural killer (NKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective Th2 cytokines. We recently developed a Th2-skewing NKT cell ligand, OCH. OCH, a sphingosine truncated derivative of alpha-galactosylceramide (alpha-GC), stimulates NKT cells to selectively produce Th2 cytokines. Here we show that OCH prevented the development of diabetes and insulitis in NOD mice. The suppression of insulitis by OCH was more profound compared to alpha-GC. Infiltration of T cells, B cells and macrophages into islets is inhibited in OCH-treated NOD mice. OCH-mediated suppression of diabetes is associated with Th2 bias of anti-islet antigen response and increased IL-10 producing cells among islet-infiltrating leukocytes. Considering the non-polymorphic and well conserved features of the CD1d molecule in mice and humans, these findings not only support the proposed role of NKT cells in the regulation of self-tolerance but also highlight the potential use of OCH for therapeutic intervention in type I diabetes.

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Bentham Science Publishers Ltd.  

DOI： 10.2174/1566523033347516

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The treatment of Alzheimer's disease (AD) remains a major challenge because of the incomplete understanding of the triggering events that lead to the selective neurodegeneration characteristic of AD brains. Here we describe a new protein, CGI-94, that is down-regulated at the mRNA level in the hippocampus of early stage AD brain. Transfection experiments with CGI-94 as a green fluorescent protein (GFP)-fusion-protein show that this protein is translocated into the nucleus of the cell. The finding that this protein, which has a bipartite nuclear localization signal, is also observed in the cytoplasm and extracellular space points to a multifunctional protein. Immunohistochemical analyses reveal that CGI-94 is mainly expressed in neurons of the hippocampal formation and the cortex but not in the cerebellar nucleus. In conclusion, the expression of the nucleolar phosphoprotein CGI-94 appears to be disturbed in early processes of neuronal degeneration.

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1006/bbrc.2001.5609

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1006/bbrc.2001.4968

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0168-0102(01)00195-x

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CiNii Books

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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  

Increasing evidence suggests the presence of apoptotic cell death in many neuro-degenerative diseases. However, in Binswanger's disease (BD), no information is available concerning the apoptosis-related pathologic changes that may occur in the white matter. To investigate whether apoptotic cell death is included in the pathophysiology of the white matter changes in BD, autopsied brains from patients with BD (n = 5) were compared with those of non-neurologic controls (n = 5). Terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL) was used as a marker for cell damage with DNA fragmentation. A proteolipid protein (PLP) messenger RNA (mRNA) hybridization signal was also used as a sensitive and specific marker of oligodendrocytes as well as glial fibrillary acidic protein (GFAP) immunoreactivity as a marker of astrocytes. There were frequent TUNEL-positive cells in the rarefied white matter of patients with BD. TUNEL-positive cells were found 15-fold more numerously in BD than in controls (P &lt
.01). TUNEL-positive cells were presumably oligodendrocytes because of their coexpression with PLP mRNA. The numbers of GFAP-positive astrocytes were significantly decreased in BD compared with those in control subjects. The reduction in numbers of PLP mRNA-positive oligodendrocytes were also seen in BD, but these changes did not reach the level of significance. The pathologic alterations in BD brains include increased TUNEL-positive oligodendrocytes, associated with degradation of myelin. Although TUNEL-positive glial cells did not show typical apoptotic morphologic features, these findings suggest that increase in in situ nick end labeling of oligodendrocytes in white matter may play an important role in the pathophysiology of BD. © 2001 by National Stroke Association.

DOI： 10.1053/jscd.2001.24660

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/s0169-328x(00)00163-7

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1006/gcen.1999.7438

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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：Mary Ann Liebert Inc.  

The expression of alternatively spliced mRNAs for amyloid precursor protein (APP) isoforms and their translation products were examined in the rat cerebral cortex 1, 3, 6, and 12 h and 1, 3, and 7 days (n = 4-5 in each group) after fluid-percussion brain injury. In situ hybridization studies demonstrated that the expression of APP695 mRNA decreased in and around the damaged area of the cerebral cortex exposed to fluid-percussion injury 1 h after the insult. On the other hand, APP751/770 mRNAs were increased in the regions surrounding the damaged cortical areas 1 day after the injury. An increase of immunoreactive APP was detected in the regions around the damaged cortical areas 3 h after traumatic injury and maintained for the following 3 days. The APP immunoreactivity in the damaged cortices declined to the level of sham-operated animals by post-experimental day 7. Using an anti-amyloid β (Aβ) protein (17-24) antibody, no deposits of immunoreactive Aβ (17-24) were observed in any of the samples examined in these experiments. These results suggest that the induction of Kunitz-type protease inhibitor (KPI) domain-containing APP mRNAs and the increased accumulation of APP are involved in the physiological and neuropathological responses of brains under various neurodegenerative conditions, including head trauma.

DOI： 10.1089/neu.2000.17.123

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The effects of an insect insulin-related peptide, bombyxin, on carbohydrate metabolism were investigated in the silkworm Bombyx mori. Bombyxin lowered the concentration of the major hemolymph sugar, trehalose, in a dose-dependent manner when injected into neck-ligated larvae. Bombyxin also caused elevated trehalase activity in the midgut and muscle, suggesting that bombyxin induces hypotrehalosemia by promoting the hydrolysis of hemolymph trehalose to glucose anti thereby facilitating its transport into tissues. In addition, bombyxin reduced the glycogen content in the fat body and concurrently raised the percentage of active glycogen phosphorylase in this tissue. Because hemolymph trehalose is also a major storage form of carbohydrate in insects, our results indicate that bombyxin reduces the amount of both principal storage carbohydrates in B. mori larvae. It is therefore suggested that although bombyxin is involved in the control of carbohydrate metabolism like insulin, the physiological role of bombyxin in insects is different from that of insulin in mammals.

DOI： 10.1016/S0305-0491(97)00166-1

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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：Elsevier Ireland Ltd  

The expression of the mRNA of four members of the fibroblast growth factor (FGF) receptor family, was examined in rats subjected to temporal middle cerebral artery occlusion using an in situ hybridization technique. Fibroblast growth factor receptor-1 (FGFR-1) mRNA was strongly expressed in neurons of the cerebral cortex, whereas mRNAs of the other 3 subtypes of FGFRs (FGFR-2, -3, and -4) were not expressed. After temporal occlusion of the middle cerebral artery, expression of FGFR-1 mRNA in cerebral cortical neurons markedly increased in association with the progressive neuronal death
this increase was evident for at least 5 days after the focal ischemia. In view of the neuroprotective activity of basic FGF reported so far, the present results suggest that FGFR-1 induction may subserve to self-protect neurons in the ischemic penumbral field of the cerebral cortex.

DOI： 10.1016/0304-3940(96)12841-X

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