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Salmena L Lemmers B Hakem A Matysiak-Zablocki E Murakami K Au PY Berry DM Tamblyn L Shehabeldin A Migon E Wakeham A Bouchard D Yeh WC McGlade JC Ohashi PS Hakem R 《Genes & development》2003,17(7):883-895
Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency. 相似文献
23.
Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse 总被引:12,自引:0,他引:12
Aizawa H Wakatsuki S Ishii A Moriyama K Sasaki Y Ohashi K Sekine-Aizawa Y Sehara-Fujisawa A Mizuno K Goshima Y Yahara I 《Nature neuroscience》2001,4(4):367-373
Semaphorin 3A is a chemorepulsive axonal guidance molecule that depolymerizes the actin cytoskeleton and collapses growth cones of dorsal root ganglia neurons. Here we investigate the role of LIM-kinase 1, which phosphorylates an actin-depolymerizing protein, cofilin, in semaphorin 3A-induced growth cone collapse. Semaphorin 3A induced phosphorylation and dephosphorylation of cofilin at growth cones sequentially. A synthetic cell-permeable peptide containing a cofilin phosphorylation site inhibited LIM-kinase in vitro and in vivo, and essentially suppressed semaphorin 3A-induced growth cone collapse. A dominant-negative LIM kinase, which could not be activated by PAK or ROCK, suppressed the collapsing activity of semaphorin 3A. Phosphorylation of cofilin by LIM-kinase may be a critical signaling event in growth cone collapse by semaphorin 3A. 相似文献
24.
Kenichi Ohashi Yo Kato Jun Kanno Tsutomu Kasuga 《Virchows Archiv : an international journal of pathology》1990,417(2):137-143
Summary Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined
histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction
in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive
specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase
of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence
between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were
mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly
showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed
most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates.
These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis
may play an important role as a precursor lesion for malignant melanoma in the oesophagus. 相似文献
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Nidhi Sharma Atsushi Ohyabu Yoshiki Murakumo Masahide Takahashl Mitsuhiro Saito Hiroyuki Amo Shin-ichiro Murayama Kyoko Ohno Sen-ichi Oda Mutsushi Matsuyama 《Pathology international》1997,47(7):436-441
The thymoma prone BUF/Mna (B) rat is a useful model for Studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at al stages of life. A locus, Ten-1 , which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the bus, (B×(B×MITE)F1) BC rats were generated by crossing the B strain with the Inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargements were found In genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11 , and D1Mit6 , by X2- test and Student's t -test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1 , in this region. Paradoxically, a suppressive locus, Tsu-1 , to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT D3Mit16 , and D3Mit13 . By analyses of mapmaker/exp and mapmaker/qtl, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively. 相似文献
27.
Shin-ichiro Shoda Akio Komenoi Tomochika Fujioka Yasunori Okumura Shiro Kobayashi 《Macromolecular chemistry and physics.》1996,197(2):633-640
Isopropoxyethyne (1a) and tert-butoxyethyne (1b) were polymerized using group 5 and 6 transition metal catalysts to give poly(isopropoxyethyne) (2a) and poly(tert-butoxyethyne) (2b) , respectively. The weight-average molecular weight (M?w) of the resulting poly(alkoxyethyne)s was up to 1.0 × 104. Among the transition metal catalysts, a tungsten alkoxide or a molybdenum alkoxide having low Lewis acidity were found to effectively promote the polymerization without causing side reactions. Poly(tert-butoxyethyne) was successfully converted to poly(β-ketone) 3 by acid hydrolysis of the tert-butyl vinyl moiety. 相似文献
28.
Kennichi Kakudo Akira Miyauchi Shin-ichiro Takai Shoichi Katayama Kanji Kuma Hajime Kitamura 《Pathology international》1979,29(4):653-659
Two cases of papillary type of C cell carcinoma of the thyroid were reported. They showed papillary arrangement with Abrovascular stalk in properly Axed tissues. Histochemically argyrophil reaction was positive in the cytoplasm and amyloid deposited in the stroma. Ultrastructurally secretory granules were found in their cytoplasm. The papillary type is not an artifact but one of the histologic variations of this carcinoma. ACTA PATH. SAP. 29: 653–659, 1979. 相似文献
29.