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81.
Hidetoshi Taniguchi Ikuko Mohri Hitomi Okabe-Arahori Takahisa Kanekiyo Kuriko Kagitani-Shimono Kazuko Wada Yoshihiro Urade Masahiro Nakayama Keiichi Ozono Masako Taniike 《Neuroscience letters》2007
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM1 and GM2 gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24 h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1 h after reoxygenation and that it decreased to the normal level by 24 h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain. 相似文献
82.
Inoue K Yamaguchi A Wada M Yoshimura Y Makino T Nakazaw H 《Journal of chromatography. B, Biomedical sciences and applications》2001,765(2):121-126
Due to the ubiquity of epoxy resin compounds and their potential role in increasing the risk for reproductive dysfunction and cancer, the need for an assessment of human exposure is urgent. Therefore, we developed a method for measuring bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE) metabolites in human blood samples using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS). Human blood samples were processed using enzymatic deconjugation of the glucuronides followed by a novel sample preparation procedure using a solid-phase-cartridge column. This selective analytical method permits rapid detection of the metabolites, free BPA and a hydrolysis product of BADGE (BADGE-40H) with detection limits in the low nanogram per milliliter range (0.1 ng ml(-1) of BPA and 0.5 ng ml(-1) of BADGE-40H). The sample extraction was achieved by Oasis HLB column on gradient elution. The recoveries of BPA and BADGE-40H added to human plasma samples were above 70.0% with a standard deviation of less than 5.0%. This selective, sensitive and accurate method will assist in elucidating potential associations between human exposure to epoxy-based compounds and adverse health effects. 相似文献
83.
Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced by ischemic retinal injury in vivo 总被引:7,自引:0,他引:7
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Harada T Harada C Wang YL Osaka H Amanai K Tanaka K Takizawa S Setsuie R Sakurai M Sato Y Noda M Wada K 《The American journal of pathology》2004,164(1):59-64
Ubiquitin is thought to be a stress protein that plays an important role in protecting cells under stress conditions; however, its precise role is unclear. Ubiquitin expression level is controlled by the balance of ubiquitinating and deubiquitinating enzymes. To investigate the function of deubiquitinating enzymes on ischemia-induced neural cell apoptosis in vivo, we analyzed gracile axonal dystrophy (gad) mice with an exon deletion for ubiquitin carboxy terminal hydrolase-L1 (UCH-L1), a neuron-specific deubiquitinating enzyme. In wild-type mouse retina, light stimuli and ischemic retinal injury induced strong ubiquitin expression in the inner retina, and its expression pattern was similar to that of UCH-L1. On the other hand, gad mice showed reduced ubiquitin induction after light stimuli and ischemia, whereas expression levels of antiapoptotic (Bcl-2 and XIAP) and prosurvival (brain-derived neurotrophic factor) proteins that are normally degraded by an ubiquitin-proteasome pathway were significantly higher. Consistently, ischemia-induced caspase activity and neural cell apoptosis were suppressed approximately 70% in gad mice. These results demonstrate that UCH-L1 is involved in ubiquitin expression after stress stimuli, but excessive ubiquitin induction following ischemic injury may rather lead to neural cell apoptosis in vivo. 相似文献
84.
Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury 总被引:5,自引:0,他引:5
Yamamoto K Tomita N Yoshimura S Nakagami H Taniyama Y Yamasaki K Ogihara T Morishita R 《International journal of molecular medicine》2004,14(4):633-640
Although injury of epithelial cells has been reported to be responsible for renal disease such as acute renal failure, its molecular mechanisms are largely unknown. As hypoxia has been postulated as the initial trigger of epithelial injury, we studied the molecular mechanisms of apoptosis induced by hypoxia in human renal epithelial cells. Severe hypoxia caused epithelial cell death, accompanied by a significant increase in LDH release (p<0.01). In addition, hypoxic treatment of epithelial cells resulted in a significant increase in apoptotic cells as assessed by cell morphology (p<0.01). The apoptotic change in epithelial cells under hypoxic condition was also confirmed by a significant increase in caspase-3-like activity and release of cytochrome c (p<0.01). The decrease in epithelial cell number was completely abolished by addition of a wide-spectrum caspase inhibitor, Z-VAD, rather than Z-DEVD, a specific caspase-3 inhibitor (p<0.01). Thus, we further studied the molecular mechanisms of apoptosis induced by hypoxia. Anti-apoptotic factors, Bcl-2 and Bcl-xL, were significantly decreased in epithelial cells under a hypoxic condition as assessed by Western blotting (p<0.01). In contrast, hypoxia did not alter their location. Of particular importance, translocation of a proapoptotic factor, Bax, from the cytoplasm to the mitochondrial membrane was observed in response to hypoxia, whereas total Bax protein was not changed by hypoxia. Overall, this study demonstrated that hypoxia caused epithelial cell death induced by caspase-3-like activity-dependent apoptosis. The pro-apoptotic mechanisms of hypoxia in epithelial cells largely depend on a significant decrease in Bcl-2 and Bcl-xL. In addition, the present results demonstrate that translocation of Bax from the cytosol to the mitochondrial membrane occurred under hypoxia, thereby leading to pathological tissue destruction. 相似文献
85.
86.
Yajima N Wada R Yamagishi S Mizukami H Itabashi C Yagihashi S 《Human pathology》2005,36(11):1217-1225
Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein. Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors. This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix. 相似文献
87.
Yoshiteru Sakamoto Dr Takehiko Watanabe Hideyuki Hayashi Yoshitaka Taguchi Hiroshi Wada 《Inflammation research》1985,17(1):32-37
The effect of about one hundred compounds on the activity of histidine decarboxylase partially purified from whole bodies of fetal rats was determined. Most of them at their 10 mM concentration had little effect on the enzyme activity; but 12 compounds inhibited the enzyme to a greater extent than 30%. Among these, except for -methylhistidine that has been known to be a strong and specific inhibitor, DOPA, homocysteine, cysteine, methionine and urocanic acid were the best inhibitors; -phenyllactic acid, phenylpyruvic acid and carnosine were less strong inhibitors; valine, oxaloacetic acid andN
-methylimidazole acetic acid were weak inhibitors. Histamine had no inhibitory action. Thus, the substrate binding site of histidine decarboxylase is very rigid and specific forl-histidine. 相似文献
88.
Fuminori Tachibana Hando Hakozaki Kiyoshi Takahashi Mizu Kojima Satoru Enomoto Junji Wada 《Pathology international》1979,29(1):73-97
A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cyto-chemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an imporant role in intralysosomal ceroidogenesis in these histiocytes. 相似文献
89.
We report a case of follicular lymphoma with crystal inclusions. Swollen lymph nodes taken from the left neck of a 53- year-old Japanese woman were replaced by follicular proliferation of atypical centroblastic and centrocytic cells with intracytoplasmic crystal inclusions. The crystals were confined to lymphoma cells and were not found in histiocytes. Lymphoma cells were positively immunostained with lambda light chain and mu heavy chain, but the crystals were only weakly so. In situ hybridization of light chains disclosed a monoclonal expression of lambda light chain mRNA in lymphoma cells. The crystals had a periodic linear substructure with about 5-nm intervals. The worldwide literature reports 8 cases, including the current case of non-Hodgkin's lymphoma with crystals confined to the neoplastic cells. The cases did not accompany paraproteinemia and crystal-storing histiocytosis and appear to follow a favorable clinical outcome. 相似文献
90.