2 38 長井伸也 ondanka/pamph_infection/full.pdf Plasmodium
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1 挨拶 巻頭言 地球温暖化と感染症 長井伸也 ( 2 ) 獣医病理学研修会 第 46 回 No.911 リクガメの肝臓 膵臓と十二指腸 麻布大学獣医病理学研究室 ( 3 ) 第 46 回本 No.919 ブタの嚢胞肝 酪農学園大学獣医病理学研究室 ( 4 ) レビュー 胎盤毒性とアポトーシス 土井邦雄 ( 5 ) 発行人の交代について (11) お知らせ (12)
2 2 38 長井伸也 ondanka/pamph_infection/full.pdf Plasmodium WHO 3 5 5,000 8,000 Vibrio cholerae % % % 66 1 ( 常務理事 )
3 リクガメの肝臓 膵臓と十二指腸 麻布大学獣医病理学研究室第 46 回獣医病理学研修会標本 No. 911 動物 Geochelone sp 臨床事項 剖検所見 組織所見 1, 2 3 4, bar 7 m m 診断 考察 Eimeria, Isospora, Cyclospora 参考文献 : 1. Garner, MM et al., Vet. Pathol. 43: (2006). 2. Jacobson, ER et al., J. Zoo Wildl. Med. 25 : (1994).
4 4 40 ブタの嚢胞肝 酪農学園大学獣医病理学研究室第 46 回獣医病理学研修会標本 No. 919 動物 6 臨床事項 剖検所見 1 1 組織所見 診断 考察 参考文献 1. Nakanuma, Y. et al., Virchows. Arch. A. 404 : (1984). 2. Nakanuma, Y., J. Gastroenterol. Hepatol. 16: (2001). 3. Terada, T. et al., Virchows Arch. 430:37 40 (1997).
5 レビュー 胎盤毒性とアポトーシス 土井邦雄 ( 東京大学名誉教授 ) 要約 DNA molecular pathway 2 3 Environmental chemicals Drugs Radiation Dam Placenta Fetus Endogenous factors Fig. 1 Toxicity in pregnant animals. 序 (Fig. 1) genotoxic stress 胎盤の構造と機能 (Fig. 2) Rossant and Cross, 2001 ; Georgiades et al., 2002 (Rossant and Cross, 2001) Bauer et al., 1998 ; Watson and Cross, 2005 ; Cross, 2006 ; Moffett and Loke, 2006
![6 42 Labyrinth zone, Chorionic villi, syncytiotrophoblast, cytotrophoblast] Rossant and Cross, 2001 ; Simmon and Cross, 2005 Labyrinth zone Maternal blood Trophoblast layer Fetal blood Placenta Fig.](/docs-images/91/106896767/images/6-0.jpg "2 Structure of placenta 胎盤におけるアポトーシス Smith et al., 1997a : Halperin et al., 2000 ; Waddell et al., 2000 ; Jurisicova et al., 2005 p53 Ress et al., 1999 ; Ishihara et al., 2000 ; Levy et al.")
6 6 42 Labyrinth zone, Chorionic villi, syncytiotrophoblast, cytotrophoblast] Rossant and Cross, 2001 ; Simmon and Cross, 2005 Labyrinth zone Maternal blood Trophoblast layer Fetal blood Placenta Fig. 2 Structure of placenta 胎盤におけるアポトーシス Smith et al., 1997a : Halperin et al., 2000 ; Waddell et al., 2000 ; Jurisicova et al., 2005 p53 Ress et al., 1999 ; Ishihara et al., 2000 ; Levy et al., 2000 ; Ka et al., 2003 Smith et al., 1997b ; Kokawa et al., 1998 ; Ishihara et al., NG-nitro-Larginine methyl ester Miller et al., 1996 lipopolysaccharides Ejima et al., 2000 glucocorticoides Waddell et al., 2000 Miller et al., 1996 ; Ejima et al., 2000 ; Waddell et al., 2000 (Table 1) DNA DNA Table 1. Apoptosis induction in mouse or rat placenta Distribution of Labyrinth Basal Decidua Agent Adrenomedullin antagonist,, Bestatin, Ethylnitrosourea, 6-Mercaptopurine, T-2 toxin Dexamethasone, LPS L-NAME, LPS Fas Neale and Mor, 2005 p53 Levy et al., 2002 lipopolysaccharides Fas Ejima et al., 2000 Genotoxic stress と胎盤毒性 DNA genotoxic stress genotoxic stress p53 Katayama et al., 2000 ; Wang et al., 2000 ; D Sa-Eipper et al., 2001 ; Katayama et al., 2002a ; Yamauchi et al., 2004 ; Ueno et al ; 2006
![Changes of proliferative activity in placental trophoblast cells following -treatment to pregnant rats(yamauci et al. 2004b [modified]).](/docs-images/91/106896767/images/7-3.jpg "(%) 40 30 20 10 Mitotic index 1 3 6 9 12 24 48 hr Topoisomerase IIαlabeling index 1 3 6 9 12 24 48 hr TUNEL index 0 1 3 6 9 12 24 48 hours")
7 genotoxic stress Genotoxic stress 5-Azacytidine 5AzC cytidine DNA DNA DNA 5AzC G2/M p53 G1 G2 p53 Ueno et al., 2006 Vlahovic et al., 1999 (1)Ethylnitrosourea(ENU) ENU DNA S p53 p53 Katayama et al., Katayama et al., 2002b p53 Katayama et al., 2002b ENU p53 (2) 1-β-D-Arabinofuranosylcytosine(Cytosine arabinoside; ) 5AzC cytidine DNA polymerase DNA S p53 p53 Yamauchi et al., 2004a ENU Katayama et at al., 2002b (Fig. 3) 6 (Fig. 4) (Fig. 5) Yamauchi et al., 2004b 3 p53 Fig. 6 Yamauchi et al., 2004b molecular pathway p53 (%) (%) (%) BrdU-labeling index 60 Fig. 3. Changes of proliferative activity in placental trophoblast cells following -treatment to pregnant rats(yamauci et al. 2004b [modified]). (%) Mitotic index hr Topoisomerase IIαlabeling index hr TUNEL index hours after treatment hr Phospho-histone H3 immunostaining 6 hr 6 hr TUNEL staining Fig. 4. Induction of apoptosis in placental trophoblast cells following -treatment to pregnant rats (Yamauchi et al. 2004b. [modified]).
![2004b [modified]).](/docs-images/91/106896767/images/8-2.jpg "P p53 P target gene Cell cycle arrest p21 Others cyclin G1 Gadd45 P P p53 Fig. 7.")
8 8 44 (mm) Thickness of the labyrinth zone (48 hr) P p53 P DNA damage p53 Mdm2 Degradation Fig. 5. Atrophy of placental labyrinth zone following -treatment to pregnant rats(yamauchi et al. 2004b [modified]). P p53 P target gene Cell cycle arrest p21 Others cyclin G1 Gadd45 P P p53 Fig. 7. p53 and its transcriptional target genes. P Apoptosis target gene Bax Fas p53 immunostaining (%) hr DNA damage Transcriptional activation Phosphorylation p53 Mitochondrial pathway hours after treatment Fig. 6. Changes of p53 protein expression in placental trophoblast cells following treatment to pregnant rats (Yamauchi et al. 2004b [modified]). Cell cycle arrest DNA repair BAX p21 Apoptosis Fig. 8. Hypothesis of mechanisms involved in induced placental toxicity in pregnant rats. DNA p53 (Fig. 7) p53 DNA (Fig. 7) p53 (Fig. 7) mrna Yamauchi et al., 2004b Fas Bax Fas extrinsic pathway Bax intrinsic pathway Fig. 8 p53 Bax intrinsic pathway Yamauchi et al., 2007 (3)T-2 toxin T-2 toxin Fusarium Doi and Shinozuka, 2006 Sehata 2005 T-2 toxin (Fig. 9) DNA 3
9 (Fig. 10) RT-PCR HSP70 T-2 toxin MAPK MEKK1 c-jun T-2 toxin MAPK c-jun (Fig. 11) Bax- (Fig.11) Liver Lipid metabolism Pregnancy specific genes Fig. 10. Summary of microarray analysis on dam s liver, placenta and fetal liver following T-2 toxin-treatment to pregnant rats. T2Toxin Gap junction Placenta Oxidativestress MEKK1 JNK Phase I, II enzymes Oxidative stress Apoptosis Phase II enzymes Caspase-2 Coagulation-related genes Heme biosynthesis- related gene Fetal liver Metabolic Caspase-9 TUNEL-labelong index *p<0.05, P<0.01 (Student s t-test) #p<0.01, ##p<0.01 (Welch s t-test) :GeneChip analysis Placenta Labeling index % Liver 2.50 rol 2.00 T-2 Toxin toxin ## * HET Fetal Liver c-jun Bax-α Genes Caspase-3 Apoptosis Fig. 11. Hypothesis of mechanisms involved in T-2 toxin-induced toxicity in pregnant rats (Sehata et al [modified]) Labeling index % # # # rol T-2 Toxin HET * rol T-2 toxin HET Fig. 9. Induction of apoptosis in dam s liver, placenta and fetal liver following T-2 toxin-treatment to pregnant rats (Sehata et al [modified]). Labeling index % ## # ## ## ## 今後の課題 DNA
10 10 46 DNA de Rijk et al., 2002 ; He et al., 2005 ; He et al., 2006 謝辞 引用文献 1. Bauer et al Fetal growth and placental function. Mol. Cell. Endocrinol., 140: Cross J.C Placental function in development and disease. Reprod. Fertil. Dev., 18: Doi K. and Shinozuka J T 2 toxin and apoptosis. J. Toxicol. Pathol., 19: Ejima K. et al Induction of apoptosis in p l a c e n t a s o f p r e g n a n t m i c e e x p o s e d t o lipopolysaccharides : possible involvement of Fas/ Fas ligand system. Biol. Reprod., 62: de Rijk E.P. et al Pregnancy dating in the rat :placental morphology and maternal blood parameters. Toxicol. Pathol., 30: D Sa-Eipper C. et al DNA damage-induced neural precursor cell apoptosis requirers p53 and caspase 9 but neither BAX nor caspase 3. Development, 128: G e o r g i a d e s P. e t a l C o m p a r a t i v e developmental anatomy of the murine and human definitive placenta. Placenta, 23: Halperin R. et al Placental apoptosis in normal and abnormal pregnancies. Gynecol. Obstet. Invest., 50: He X. J. et al Effects of pregnancy on CYPs protein expression in rat liver. Exp. Mol. Pathol., 78: He X. J. et al. Gene expression profiles of drugmetabolizing enzymes (DEMs) in rat liver during pregnancy and lactation. Exp. Mol. Pathol., in press. 11. Ishihara N. et al Changes in proliferative potential, apoptosis and bcl-2 protein expression in cytotrophoblasts and syncytiotrophoblast in human placenta over the course of pregnancy. Eddocr. J., 47: Ishihara N. et al Increased apoptosis in the syncytiotrophoblast in human term placenta c o m p l i c a t e d b y e i t h e r p r e e c l a m p s i a o r intrauterine growth retardation. Am. J. Obstet. Gynecol., 186: Jurisicova A. et al Molecular mechanisms of trophoblast survival:from implantation to birth. Birth Defects Res. C. Embryo Today, 75: Ka H. and Hunt J. S Temporal and special patterns of expression of apoptosis in human placenta. Am. J. Pathol., 163: Katayama K. et al Teratologic studies on rat perinates and offsprings from dams administered with ethylnitrosourea ENU. Exp. Anim., 49: Katayama K. et al. 2002a. Expression of p53 and its transcriptional target genes mrnas in the ethylnitrosourea-induced apoptosis and cell cycle arrest in the fetal central nervous system. Histol. Histopathol., 17: Katayama K. et al. 2002b. Ethylnitrosourea induces apoptosis and growth arrest in the trophoblastic cells of rat placenta. Biol. Reprod., 67: Katayama K. et al Ethylnitrosourea induces neuronal progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner. Neurobiol. Dis., 18: Kokawa K. et al Apoptosis in human
11 chorionic villi and deciduas during normal embr yonic development and spontaneous abortion in the first trimester. Placenta, 19: Levy R. and Nelson D.M To be, or not to be, that is the question. Apoptosis in human trophoblast. Placenta, 21: Levy R. et al Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression. Am. J. Obstet. Gynecol., 186 : Miller M. J. et al Fetal growth retardation in rats may result from apoptosis : role of peroxynitrite. Free Radic. Biol. Med., 21 : Moffett A. and Loke C Immunology of placentation in eutherian mammals. Nat. Rev. Immunol., 6: Neale D. M. and Mor G The role of Fas mediated apoptosis in preeclampsia. J. Perinat. Med., 33: Ress W. D Expression of the growth arrest genes (GAS and GADD) changes during organogenesis in the rat fetus. J. Nutr., 129: Rossant J. and Cross J.C Placental development : Lessons from mouse mutants. Nature Rev. Genetics, 2: Sehata et al Microarray analysis of T-2 toxin-induced liver, placenta and fetal liver lesions in pregnant rats. Exp. Toxicol. Pathol., 57: S i m m o n s D. G. a n d C r o s s J. C Determination of trophoblast lineage and cell subtype specification in the mouse placenta. Dev. Biol., 284: Smith S. C. et al. 1997a. Placental apoptosis in normal human pregnancy. Am. J. Obstet. Gynecol., 177: Smith S.C. et al. 1997b. Increased placental apoptosis in intrauterine growth restriction. Am. J. Obstet. Gynecol., 177: Ueno M. et al Cell cycle and cell death regulation of neural progenitor cells in the 5-azacytidine (5AzC)-treated developing fetal brain. Exp. Neurol., 198: Vlahovic M. et al Changes in the placental a n d i n t h e r a t e m b r y o c a u s e d b y t h e demethylating agent 5-azacytidine. Int. J. Dev. Biol., 43: Waddell B. J. et al Apoptosis in rat placenta i s z o n e - d e p e n d e n t a n d s t i m u l a t e d b y glucocorticoids. Biol. Reprod., 63: Wang B. et al Prenatal radiation-induced limb defects mediated by Trp53-dependent apoptosis in mice. Radiat. Res., 154: Watson E. D. and Cross J. C Development of structures and transpor t functions in the mouse placenta. Physiology (Bethesda), 20 : Yamauchi H. et al. 2004a. Involvement of p53 in 1- -D-arabinofuranosylcytosine-induced rat fetal brain lesions. Neurotox. Teratol., 26: Yamauchi H. et al. 2004b. Involvement of p53 in 1- -D-arabinofuranosylcytosine-induced trophoblastic cells and impaired proliferation in rat placenta. Biol. Reprod., 70: Yamauch H. et al The essential role of p53 in trophoblastic apoptosis of the developing rodent placenta induced by treatment with a DNA-damaging agent. Apoptosis, in press. 発行人の交代について ( 前発行人井圡俊郎 )
12 12 48 お知らせ (1) 評議員 2. 理事 監事 氏 名 役職 担当 氏 名 役 職 お知らせ (2) 創立 60 周年記念シンポジウムの開催について 60 記 O : : 50 UTL: http//nibs.lin.go.jp Tel: Fax: info@nibs.lin.go.jp 生命の 共生 調和 を理念とし, 生命体の豊かな明日と, 研究の永続性を願う気持ちを心よいリズムに整え, 視覚化したものです カラーは生命の源, 水を表す 青 としています 稕 日生研たより昭和 30 年 9 月 1 日創刊 ( 隔月 1 回発行 ) ( 通巻 545 号 ) 平成 19 年 6 月 25 日印刷平成 19 年 7 月 1 日発行 ( 第 53 巻第 4 号 ) 発行所財団法人日本生物科学研究所 東京都青梅市新町 9 丁目 2221 番地の 1 TEL0428(33)1056( 企画学術部 ) FAX0428(31)6166 発行人長井伸也編集室委員 / 小山智洋 ( 委員長 ), 中村圭吾, 川原史也事務 / 企画学術部印刷所株式会社精案社 ( 無断転載を禁ず )
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