研究者データベース

昆 泰寛(コン ヤスヒロ)
獣医学研究院 獣医学部門 基礎獣医科学分野
教授

基本情報

所属

  • 獣医学研究院 獣医学部門 基礎獣医科学分野

職名

  • 教授

学位

  • 獣医学博士(北海道大学)

J-Global ID

研究キーワード

  • 尿生殖器   不妊症   自己免疫疾患   精子形成   

研究分野

  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学

職歴

  • 2017年04月 - 現在 北海道大学 大学院獣医学研究院 教授
  • 2003年04月 - 2017年03月 北海道大学 大学院獣医学研究科 教授
  • 1994年10月 - 2003年03月 北海道大学 大学院獣医学研究科・獣医学部 准教授・助教授
  • 1984年11月 - 1994年09月 北海道大学 獣医学部 助手

学歴

  • 1983年04月 - 1984年11月   北海道大学   大学院獣医学研究科   博士課程
  • 1981年04月 - 1983年03月   北海道大学   大学院獣医学研究科   修士課程
  • 1977年04月 - 1981年03月   北海道大学   獣医学部

所属学協会

  • 日本獣医腎泌尿器学会   日本解剖学会   日本繁殖生物学会   日本獣医学会   

研究活動情報

論文

  • Masaya Hiraishi, Md Abdul Masum, Takashi Namba, Yuki Otani, Yaser Ha Elewa, Osamu Ichii, Yasuhiro Kon
    Experimental biology and medicine (Maywood, N.J.) 245 12 999 - 1008 2020年06月 [査読有り][通常論文]
     
    IMPACT STATEMENT: Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren's syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.
  • Yuki Otani, Osamu Ichii, Md. Abdul Masum, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Cell and Tissue Research 2020年04月04日 [査読有り][通常論文]
  • Altered ciliary morphofunction in the oviductal infundibulum of systemic autoimmune disease-prone MRL/MpJ-Faslpr/lpr mice
    Hosotani M, Ichii O, Nakamura T, Masum MA, Otani Y, Elewa YHA, Kon Y
    Cell and Tissue Research 2020年02月 [査読有り][通常論文]
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Yuki Otani, Marina Hosotani, Md Abdul Masum, Rashedul Md Islam, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Histochemistry and cell biology 153 1 27 - 36 2019年10月 [査読有り][通常論文]
     
    The increased prevalence of aging-related chronic kidney disease (CKD) among humans is a problem worldwide. Aged cotton rats (Sigmodon hispidus) are considered novel model animals for studying CKD, especially as the females develop severe tubulointerstitial lesions with anemia. To investigate the renal pathologic features in aged male cotton rats and their characteristic glomerular injuries, the animals were divided into young, adult, old-aged, and advanced-aged groups (1-4, 5-8, 9-12, and 13-17 months, respectively) and pathologically analyzed. Anemia and renal dysfunction, as indicated by hematologic and serologic parameters, were significantly milder in the advanced-aged males than in the old-aged females. The males had increased urinary albumin-to-creatinine ratios from the old-age period, with the advanced-aged males having significantly higher levels than those in the old-aged females and young males. The old-aged females did not show clear glomerular injuries, whereas the advanced-aged males showed membranous lesions characterized by irregular and thickened glomerular basement membranes (GBMs). Characteristically, several large-sized projections from the GBM toward the podocytes were observed by microscopy, and podocytes covering these projections effaced their foot processes. The advanced-aged males showed aging-related IgG immune-complex depositions in the paramesangial regions and along the GBM. Furthermore, the positive reaction for podocin (a podocyte molecule) was granulated along the GBM. Thus, we clarified the albuminuria associated with altered glomerular structures in advanced-aged cotton rats, and that these phenotypes were closely associated with aging. These data help to clarify the aging-related pathogenesis of glomerular injury.
  • Teppei Nakamura, Michael Schubert, Osamu Ichii, Yuji Sunden, Yaser Hosny Ali Elewa, Tomoji Yoshiyasu, Hideki Hattori, Osamu Tatsumi, Yasuhiro Kon, Ken-ichi Nagasaki
    PLOS ONE 2019年08月29日 [査読有り][通常論文]
  • Takashi Suzuki, Osamu Ichii, Teppei Nakamura, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Cell and Tissue Research 2019年08月 [査読有り][通常論文]
  • Ai Dantsuka, Osamu Ichii, Annika Hanberg, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Teppei Nakamura, Yasuhiro Kon
    BMC Gastroenterology 19 1 2019年06月 [査読有り][通常論文]
  • Takashi Namba, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Experimental Biology and Medicine 153537021983281 - 153537021983281 2019年04月28日 [査読有り][通常論文]
  • Hosotani M, Ichii O, Nakamura T, Masum MA, Otani Y, Otsuka-Kanazawa S, Elewa YHA, Kon Y
    Reproduction, fertility, and development 31 4 760 - 773 2019年04月 [査読有り][通常論文]
  • Hajime Asada, Osamu Ichii, Hirotaka Tomiyasu, Kazuyuki Uchida, James K Chambers, Yuko Goto-Koshino, Koichi Ohno, Yasuhiro Kon, Hajime Tsujimoto
    The Journal of veterinary medical science 81 3 353 - 356 2019年03月14日 [査読有り][通常論文]
     
    The mutations of TP53 gene are frequently observed in canine histiocytic sarcoma (HS). The objective of this study was to examine the distribution of tumor cells with TP53 gene mutations. Tumor tissues were divided into three or four regions and TP53 gene mutations were examined. TP53 gene mutations were detected only in parts of the HS tissues from six of the eight dogs, and the frequency of the mutant allele varied (0-65%) among the tumor regions. This study suggests that canine HS can exhibit intratumor heterogeneity. Further studies are needed to examine the clinical significance of the intratumor heterogeneity of TP53 gene mutations.
  • Yaser H A Elewa, Amany Abdel-Rahman Mohamed, Azza A A Galal, Nesma I El-Naseery, Osamu Ichii, Yasuhiro Kon
    Ecotoxicology and environmental safety 169 696 - 706 2019年03月 [査読有り][通常論文]
     
    Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4 mL/kg), the RJ group (300 mg/kg), the FY4 group (500 mg/kg b.w.), and the co-treated groups (FY4 + CLO or FY4 + RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.
  • M A Masum, O Ichii, Y H A ELewa, Y Kon
    Lupus 28 3 324 - 333 2019年03月 [査読有り][通常論文]
     
    BACKGROUND: Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. METHODS: Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. RESULTS: Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24 wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24 wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24 wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24 wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P < 0.05 and 0.01). CONCLUSION: Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.
  • Teppei NAKAMURA, Miyuki NORIMURA, Kanako SUMI, Osamu ICHII, Yaser Hosny Ali ELEWA, Yasuhiro KON, Osamu TATSUMI, Hideki HATTORI, Tomoji YOSHIYASU, Ken-ichi NAGASAKI
    Experimental Animals 2019年 [査読有り][通常論文]
  • Ichii O, Ohta H, Horino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Sasaki N, Takiguchi M, Sato R, Oyamada K, Elewa YHA, Kon Y
    Frontiers in veterinary science 6 2  2019年 [査読有り][通常論文]
  • Yaser Hosny Ali Elewa, Tatsuya Mizoguchi, Osamu Ichii, Teppei Nakamura, Yasuhiro Kon
    PLOS ONE 13 12 e0201330  2018年12月 [査読有り][通常論文]
  • Masum MA, Ichii O, Hosny Ali Elewa Y, Nakamura T, Otani Y, Hosotani M, Kon Y
    Autoimmunity 51 8 386 - 398 2018年12月 [査読有り][通常論文]
  • Nesma Ibraheim El-Naseery, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 220 9 - 20 2018年11月 [査読有り][通常論文]
     
    The current study was conducted on a menopause rat model induced by ovariectomy to assess the histological and immunohistochemical alterations in the parotid glands and to verify the efficiency of human umbilical cord derived-mesenchymal stromal cell (hUCB-MSCs) in treating this condition. Eighteen adult female rats were equally divided into three groups: sham-operated (SHAM), ovariectomized (OVX) and OVX injected with hUCB-MSCs (OVX+hUCB-MSCs). At 3months post-ovariectomy, the salivary flow rate and size of the parotid glands were measured. The parotid glands were histologically investigated via H&E stained sections. Furthermore, immunohistochemical analysis for human CD105, human CD34, proliferating cell nuclear antigen (PCNA), single strand DNA (ssDNA), caspase 3, aquaporin (AQP)1, α-smooth muscle actin (α-SMA) and mouse CD34 were performed. The OVX group showed interstitial hemorrhage, dispersed acini and intracytoplasmic vacuoles in the acinar cells. Furthermore, immunohistochemical staining revealed a significant decrement in the number of ssDNA positive apoptotic cells, but a significant increment of PCNA positive proliferating cells, AQP1 positive blood capillaries, α-SMA positive myoepithelial cells and endogenous CD34 positive hematopoietic progenitor cells in the OVX+hUCB-MSCs group as compared with the OVX group. These findings suggest a potential regenerative therapy of MSCs to injured parotid gland structures. However, further investigations are required to illustrate the mechanism of hUCB-MSCs mediated parotid gland regeneration.
  • Teppei Nakamura, Yaser Hosny Ali Elewa, Osamu Ichii, Marina Hosotani, Wael A M Ghonimi, Osamu Tatsumi, Ken-Ichi Nagasaki, Yasuhiro Kon
    The Journal of veterinary medical science 80 9 1368 - 1372 2018年09月13日 [査読有り][通常論文]
     
    Parafollicular cells (C-cells) exist within the thyroid glands and display different distributions within the glands among mammalian species. In the one-humped camel (Camelus dromedarius), localization of the C-cells remains under debate. We herein investigated appearance of C-cells and the remnants of the ultimobranchial body, origin of C-cells, in the thyroid glands of one-humped camels. Macroscopically, a white mass was present at one-third the length from the cranial end of the thyroid glands where the cranial thyroid artery entered. In addition, large fossae were frequently found adjacent to the white mass. Histologically, the mass was mainly composed of connective tissues, thyroid follicles, and two types of cell clusters: one was composed of cells with clear cytoplasm and the other was composed of non-keratinized epidermoid cells. The mass and the fossae contained p63-positive cells, indicating that they consisted of ultimobranchial body remnants. Calcitonin was expressed in cells with clear cytoplasm, which were localized just beneath the fossae and in the cell clusters of the white mass. C-cells also resided in both subfollicular and interfollicular spaces adjacent to the white mass, but gradually decreased toward the periphery. C-cells tended to display round shapes in the ultimobranchial body remnants and subfollicular spaces, and spindle shapes in interfollicular spaces. In conclusion, we demonstrated that the ultimobranchial body remnants were limited to the region around the entrance of cranial thyroid artery and vein, and C-cells were mainly concentrated within and around the ultimobranchial body remnants.
  • Osamu Ichii, Teppei Nakamura, Taro Horino, Akira Yabuki, Yaser H A Elewa, Yasuhiro Kon
    The American journal of pathology 188 9 2120 - 2138 2018年09月 [査読有り][通常論文]
     
    The distal tubule (DT) helps regulate blood pressure and electrolytes. We describe a novel, autosomal recessive, morphofunctional DT abnormality in inbred mice evident as columnar alternations and age-related cystic changes. This abnormality developed in both sexes of DBA/2Cr. Similar phenotypes were observed in A/J, C3H/He, DBA/1J, and FVB/N strains, but not in AKR/N, BALB/c, or C57BL/6N strains. In DBA/2Cr, abnormal DT localized to straight and convoluted segments and showed IL-36α DT injury marker expression. However, DT epithelial proliferation, examined by bromodeoxyuridine incorporation, was not remarkably altered with the progression of abnormality. Abnormal DT epithelial cells in DBA/2Cr displayed elongated primary cilia, loose intercellular adhesions, and numerous vesicles with altered localization of CD9, Na+/K+ATPase, and E-cadherin, indicating altered cell function, adhesion, and polarity. DBA/2Cr-type D12Mit182-D12Mit83 was identified as a candidate locus designated DBA/2 renal cyst (drecy). Within drecy, the gene regulated by estrogen in breast cancer protein (Greb1) transcript variant 2 was significantly up-regulated in DBA/2Cr kidney versus C57BL/6N. Greb1 localized to DT cytoplasm in C57BL/6 and to cytoplasm and nucleus in DBA/2Cr. Greb1-overexpressing M-1 kidney cells showed an altered epithelial-mesenchyme phenotype. B6.D2-(D12Mit182-D12Mit83) congenic mice carrying drecy did not show DT abnormalities, whereas DBA/2Cr × B6.D2-(D12Mit182-D12Mit83) mice did. Identification of this novel DT abnormality regulated by a DBA/2Cr mouse chromosome 12-derived locus and additional genetic factors improve the understanding of DT pathogenesis.
  • Cotton rat (Sigmodon hispidus) develops metabolic disorders associated with visceral adipose inflammation and fatty pancreas without obesity.
    Nakamura T, Ichii O, Irie T, Kouguchi H, Sotozaki K, Chihara M, Sunden Y, Nagasaki KI, Tatsumi O, Elewa YHA, Kon Y
    Cell Tissue Res 2018年08月 [査読有り][通常論文]
  • マウス自己免疫性糸球体炎において見出された有足細胞傷害はToll様受容体9の過剰発現と関連する(Overexpression of Toll-like receptor 9 correlates with podocyte injury found in murine autoimmune glomerulonephritis)
    Masum Md. Abdul, 市居 修, Elewa Yaser Hosny Ali, 中村 鉄平, 大谷 祐紀, 細谷 実里奈, 昆 泰寛
    日本獣医学会学術集会講演要旨集 161回 294 - 294 2018年08月 [査読有り][通常論文]
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yuki Otani, Marina Hosotani, Yasuhiro Kon
    Scientific reports 8 1 10276 - 10276 2018年07月06日 [査読有り][通常論文]
     
    This study evaluated endothelial cells and podocytes, both being primary components of the glomerular filtration barrier, in the progression of membranoproliferative glomerulonephritis (MPGN) using modified scanning electron microscopy (mSEM) analysis. BXSB/MpJ-Yaa model mice exhibited autoimmune-mediated MPGN characterised by elevated serum autoantibody levels, albuminuria, renal dysfunctional parameters, and decreased glomerular endothelial fenestrations (EF) and podocyte foot process (PFP) effacement with immune cell infiltration. Similar to transmission electron microscopy, mSEM revealed a series of pathological changes in basement membrane and densities of EF and PFP in BXSB/MpJ-Yaa compared with control BXSB/MpJ at different stages. Further, immunopositive area of endothelial marker (CD34), podocyte functional molecules (Nephrin, Podocin, Synaptopodin, and Wilms' tumour 1 (WT1)), and vascular endothelial growth factor A (VEGF A) significantly decreased in the glomerulus of BXSB/MpJ-Yaa compared with BXSB at final stage. The indices of glomerular endothelial injuries (EF density and immunopositive area of CD34 and VEGF A) and podocyte injuries (PEP density and immunopositive area of podocyte functional molecules) were also significantly correlated with each other and with indices of autoimmune disease and renal dysfunction. Thus, our results elucidated the pathological crosstalk between endothelial cells and podocytes in MPGN progression and the usefulness of mSEM for glomerular pathological analysis.
  • Analysis for genetic loci controlling protoscolex development in the Echinococcus multilocularis infection using congenic mice.
    Islam MA, Torigoe D, Kameda Y, Irie T, Kouguchi H, Nakao R, Masum MA, Ichii O, Kon Y, Tag-El-Din-Hassan HT, Morimatsu M, Yagi K, Agui T
    Infect Genet Evol 65 65 - 71 2018年07月 [査読有り][通常論文]
  • Teppei Nakamura, Osamu Ichii, Takao Irie, Tatsuya Mizoguchi, Akio Shinohara, Hirokazu Kouguchi, Yuji Sunden, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Chihiro Koshimoto, Ken-Ichi Nagasaki, Yasuhiro Kon
    Histology and Histopathology 33 6 555 - 565 2018年06月01日 [査読有り][通常論文]
     
    Pharyngeal pouches in mammals develop into specific derivatives. If the differentiation of the pharyngeal pouches is anomalous, their remnants can result in cysts, sinuses, and fistulae in the differentiated organs or around the neck. In the present study, we found several pharyngeal pouch remnants, such as cystic structures in thymus and parathyroid gland and fossulae extended from the piriform fossa, in the inbred cotton rats maintained at Hokkaido Institute of Public Health (HIS/Hiph) and University of Miyazaki (HIS/Mz). In HIS/Hiph, the fossulae extended from the apex of the piriform fossa into the thyroid glands and were lined with stratified squamous and cuboidal epithelium. Calcitonin-positive C-cells were present within their epithelium in HIS/Hiph. In contrast, the fossulae of HIS/Mz ran outside the thyroid glands toward the parathyroid glands they were lined with columnar ciliated epithelium and a few goblet cells, but had no C-cells, which was consistent with the cystic structures in the thymus and the parathyroid gland. These results indicated that the fossulae were a remnant of the ultimobranchial body in HIS/Hiph and of the thymopharyngeal duct in HIS/Mz. Thus, the fossulae of the piriform fossa resembled the piriform sinus fistula in human. In conclusion, cotton rats frequently possessed pharyngeal pouch remnants, including the piriform sinus fistula, and therefore, might serve as a novel model to elucidate the mechanisms of pharyngeal pouch development.
  • Ahmed E. Noreldin, Yaser Hosny Ali Elewa, Yasuhiro Kon, Katsuhiko Warita, Yoshinao Z. Hosaka
    Acta Histochemica 120 4 323 - 328 2018年05月01日 [査読有り][通常論文]
     
    Osteoblast activating peptide (OBAP) is a newly discovered peptide detected in the rat stomach, which has a major role in osteogenesis. Recently, we revealed its localization in the parietal cells of the rat stomach. There have been no data regarding OBAP expression in the kidney, despite its role in calcium reabsorption in renal tubules. The current study aimed to inspect the expression of OBAP in the kidney of twelve 10-week-old male C3H/HeNJc1 mice using immunohistochemistry, and immunoelectron microscopic localization. The immunohistochemical investigation revealed an OBAP positive reaction mainly in the medulla, which was stronger than the cortex of the kidney and was concentrated in the distal convoluted tubules (DCT), connecting tubules (CT), and the thick limbs of the loop of Henle (HL). Moreover, we clarified that the OBAP was co-distributed with ghrelin and calbindin (markers of the DCT). Interestingly, immunoelectron microscopy demonstrated that OBAP was concentrated in the mitochondrial inner membrane of the DCT and CT. Based on these results, it was concluded that the mitochondria of the DCT, CT, and HL of the mice kidney generate OBAP. Furthermore, our results suggest that OBAP might have a role in the regulation of calcium reabsorption by the renal tubule however, further investigations are required to clarify this potential role.
  • Teppei Nakamura, Masataka Chihara, Osamu Ichii, Saori Otsuka-Kanazawa, Ken-ichi Nagasaki, Yaser Hosny Ali Elewa, Osamu Tatsumi, Yasuhiro Kon
    PLoS ONE 13 4 e0196364  2018年04月01日 [査読有り][通常論文]
     
    MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0) however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection. The neonatal ovarian MCs showed intermediate characteristics of MMC and connective tissue MC (CTMC), and the latter phenotype became evident with aging. However, the expression ratio of the MMC to CTMC marker increased from P0 to P4 in the MRL/MpJ mouse ovary. Similarly, the ratio of MCs facing SE to total MC number increased with aging, although the number of ovarian MCs decreased, indicating the relative increase in MMC phenotypes in the early neonatal ovary. Neither proliferating nor apoptotic MCs were found in the MRL/MpJ mouse ovaries. The parenchymal cells surrounding MCs at ovary-fimbria connection showed similar molecular expression patterns (E-cadherin+/Foxl2-/Gata4+) as that of the ovarian surface epithelial cells. At P2, around the ovary-fimbria connection, c-kit- immature oocytes formed clusters called nests, and some MCs localized adjacent to c-kit- oocytes within the nests. These results indicated that in postnatal MRL/MpJ mice, ovarian MCs changed their distribution by migrating toward the parenchymal cells composing ovary-fimbria connection, which possessed similar characteristics to the ovarian surface epithelium. Thus, we elucidated the spatiotemporal alterations of the ovarian MCs in MRL/MpJ mice, and suggested their importance during the early follicular development by migrating toward the ovary-fimbria connection. MRL/MpJ mice would be useful to elucidate the relationship between neonatal immunity and reproductive systems.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Kozue Sotozaki, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Experimental Biology and Medicine 243 5 418 - 427 2018年03月01日 [査読有り][通常論文]
     
    Cotton rat (Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement: The increasing number of elderly individuals in the overall population has led to a concomitant age-related increase in chronic kidney disease. Moreover, the global prevalence of patients with chronic kidney disease is gradually increasing, which poses a serious public health problem. The limited number of spontaneous chronic kidney disease animal models, which resemble chronic kidney disease pathogenesis in elderly individuals, is a major limitation in the development of experimental and curative medicines for chronic kidney disease. This pathological study clarified that sex-related factors, including hormones, and abnormalities of the female reproductive system, such as pyometra, are closely associated with chronic kidney disease development by using cotton rats (Sigmodon hispidus). Further, ovariectomy inhibited the phenotypes of the female reproductive system, immunological abnormalities, and chronic kidney disease. Thus, this laboratory rodent serves as a novel and useful spontaneous chronic kidney disease model to elucidate the candidate disease factors and the pathogenesis of chronic kidney disease both in human and experimental medicine.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Kensuke Takada, Teppei Nakamura, Md. Abdul Masum, Yasuhiro Kon
    Frontiers in Immunology 9 271  2018年02月15日 [査読有り][通常論文]
     
    Bleomycin (BLM) has been reported to induce lung inflammation and fibrosis in human and mice and showed genetic susceptibility. Interestingly, the C57BL/6 (B6) mice had prominent mediastinal fat-associated lymphoid cluster (MFALCs) under healthy condition, and showed susceptibility to development of lung fibrosis following BLM administration. However, the pathogenesis of lung lesion progression, and their correlation with MFALC morphologies, remain to be clarified. To investigate the correlations between MFALC structures and lung injuries in B6 mice, histopathological examination of mediastinal fat tissues and lungs was examined at 7 and 21 days (d) following a single 50 μL intranasal (i.n.) instillation of either BLM sulfate (5 mg/kg) (BLM group) or phosphate-buffered saline (control group). The lung fibrosis was examined by Masson's trichrome (MT) stain of paraffin sections and mRNA expression levels of Col1a1, Col3a1, and Acta2 in different frozen lung samples. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1, BrdU, LYVE-1, and peripheral node addressin (PNAd) was performed to detect T- and B-cells, macrophages, granulocytes, proliferating cells, lymph vessels (LVs), and high endothelial venules (HEVs). We found that MFALCs were more abundant in the BLM group as compared to the control group. The lung of BLM group developed pneumonitis with severe cellular infiltrations at 7 days and significant collagen deposition (MT) and higher expression of Col1a1, and Col3a1 at 21 days post-administration. Numerous immune cells, proliferating cells, HEVs, and LVs were observed in both MFALCs and lungs of the BLM group. Interestingly, PNAd + HEVs were observed in the lungs of the BLM group, but not the control group. Moreover, numerous Gr1 + polymorphonuclear and mononuclear-like ring cells were found in the MFALCs and lungs of the BLM group. Interestingly, flow cytometric analysis revealed a significant increase of B-cell populations within the MFALCs of BLM group suggesting a potential proliferative induction of B-cells following inflammation. Furthermore, significant positive correlations were observed between quantitative parameters of these immune cells in both the lungs and MFALCs. Thus, we suggest a potentially important role for MFALCs and HEVs in the progression of lung disease, especially in inflammatory lung disease.
  • Ichii O, Ohta H, Horino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Sasaki N, Takiguchi M, Sato R, Oyamada K, Elewa YHA, Kon Y
    Frontiers in veterinary science 5 289  2018年 [査読有り][通常論文]
  • M. Hosotani, O. Ichii, T. Nakamura, S. O. Kanazawa, Y. Hosny Ali Elewa, Y. Kon
    LUPUS 27 1 82 - 94 2018年01月 [査読有り][通常論文]
     
    Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas(lpr/lpr) mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of oocyte cumulus complexes found in the ampulla was macroscopically counted, and that of ovulated oocytes was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas(lpr/lpr) mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas(lpr/lpr) mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas(lpr/lpr) mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.
  • Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Front Immunol 8 1346  2017年10月 [査読有り][通常論文]
     
    IL-36 alpha, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36 alpha was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36 alpha in kidney injury. IL-36 alpha mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36 alpha localized to dilated DTs. IL-36 alpha expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36 alpha(+) DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36 alpha receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36 alpha stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36 alpha-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36 alpha-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36 alpha overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36 alpha may be a novel kidney injury marker useful for evaluating DT damages.
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yasuhiro Kon
    BMC NEPHROLOGY 18 1 280  2017年09月 [査読有り][通常論文]
     
    Background: The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Methods: Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Results: Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34(+) glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34(+) tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34(+) glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. Conclusions: From the analysis of mouse models, we identified inverse pathological correlations between the number of local capillaries in GLs and TILs and the severity of kidney diseases.
  • Teppei Nakamura, Naoya Karakida, Ai Dantsuka, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon, Ken-ichi Nagasaki, Hideki Hattori, Tomoji Yoshiyasu
    JOURNAL OF VETERINARY MEDICAL SCIENCE 79 7 1230 - 1235 2017年07月 [査読有り][通常論文]
     
    Syrian golden hamsters (Mesocricetus auratus) are useful laboratory rodents for studying human infectious diseases, metabolic diseases and cancer. In other rodents, such as mice and rats, a mixture of medetomidine, midazolam and butorphanol functions as a useful anesthetic, although it alters some blood biochemical parameters. In this study, we examined the effects of this mixture on anesthesia and blood biochemical parameters, and the action of atipamezole, a medetomidine antagonist, in hamsters. Intramuscular injection of a mixture of medetomidine, midazolam and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, had a short induction time (within 5 min) and produced an anesthetic duration of approximately 100 min in hamsters. We also demonstrated that 0.15 mg/kg of atipamezole, corresponding to the same dose as medetomidine, made hamsters recover quickly from anesthesia. The anesthetic agent markedly altered metabolic parameters, such as plasma glucose and insulin; however, 0.15 mg/kg of atipamezole returned these levels to normal range within approximately 10 min after the injection. The anesthetic also slightly altered mineral levels, such as plasma inorganic phosphorus, calcium and sodium; the latter two were also improved by atipamezole. Our results indicated that the mixture of medetomidine, midazolam, and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, functioned as an effective anesthetic, and atipamezole was useful for antagonizing both anesthesia and biochemical alteration in hamsters.
  • Tohru Yamamori, Tomoya Sasagawa, Osamu Ichii, Mie Hiyoshi, Tomoki Bo, Hironobu Yasui, Yasuhiro Kon, Osamu Inanami
    JOURNAL OF RADIATION RESEARCH 58 3 292 - 301 2017年05月 [査読有り][通常論文]
     
    Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown. In this study, we examined how IR influences mitochondrial abundance in mouse fibroblasts. When mouse NIH/3T3 cells were exposed to X-rays, a time-dependent increase was observed in mitochondrial DNA (mtDNA) and mitochondrial mass, indicating radiation-induced upregulation of mitochondrial abundance. Meanwhile, not only did we not observe a significant change in autophagic activity after irradiation, but in addition, IR hardly influenced the expression of two mitochondrial proteins, cytochrome c oxidase subunit IV and cytochrome c, or the mRNA expression of Polg, a component of DNA polymerase gamma. We also observed that the expression of transcription factors involved in mitochondrial biogenesis was only marginally affected by IR. These data imply that radiation-induced upregulation of mitochondrial abundance is an event independent of macroautophagy and mitochondrial biogenesis. Furthermore, we found evidence that IR induced long-term cell cycle arrest and cellular senescence, indicating that these events are involved in regulating mitochondrial abundance. Considering the growing significance of mitochondria in cellular radioresponses, we believe the present study provides novel insights into understanding the effects of IR on mitochondria.
  • Osamu Ichii, Masataka Chihara, Shin-Hyo Lee, Teppei Nakamura, Saori Otsuka-Kanazawa, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
    AUTOIMMUNITY 50 2 114 - 124 2017年03月 [査読有り][通常論文]
     
    Inbred MRL/MpJ mice show several unique phenotypes in tissue regeneration processes and the urogenital and immune systems. Clarifying the genetic and molecular bases of these phenotypes requires the analysis of their genetic susceptibility locus. Herein, hydronephrosis development was incidentally observed in MRL/MpJ-derived chromosome 11 (D11Mit21-212)-carrying C57BL/6N-based congenic mice, which developed bilateral or unilateral hydronephrosis in both males and females with 23.5% and 12.5% prevalence, respectively. Histopathologically, papillary malformations of the transitional epithelium in the pelvic-ureteric junction seemed to constrict the ureter luminal entrance. Characteristically, eosinophilic crystals were observed in the lumen of diseased ureters. These ureters were surrounded by infiltrating cells mainly composed of numerous CD3(+)T-cells and B220(+)B-cells. Furthermore, several Iba-1(+)macrophages, Gr-1(+)granulocytes, mast cells and chitinase 3-like 3/Ym1 (an important inflammatory lectin)-positive cells were detected. Eosinophils also accumulated to these lesions in diseased ureters. Some B6.MRL-(D11Mit21-D11Mit212) mice had duplicated ureters. We determined>100 single nucleotide variants between C57BL/6N- and MRL/MpJ-type chromosome 11 congenic regions, which were associated with nonsynonymous substitution, frameshift or stopgain of coding proteins. In conclusion, B6.MRL-(D11Mit21-D11Mit212) mice spontaneously developed hydronephrosis due to obstructive uropathy with inflammation. Thus, this mouse line would be useful for molecular pathological analysis of obstructive uropathy in experimental medicine.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    AUTOIMMUNITY 50 5 306 - 316 2017年 [査読有り][通常論文]
     
    MRL/MpJ-Fas(lpr) (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice. We compared the morphological features of MFALCs and lung mononuclear cell aggregates (LMCAs) in 5-month-old male and female lpr mice. The females showed significantly elevated anti-dsDNA autoantibody titers and larger MFALCs, with a higher ratio of lymphatic vessel (LV) and high endothelial venule (HEV) areas to MFALC area, and greater numbers of T- and B-cells, macrophages, and proliferating and dendritic cells in MFALCs and LMCAs than males. Our data indicated that MFALCs were more developed and lung lesions were more severe in female than in male lpr mice, thereby suggesting a potential role for LVs and HEVs in the establishment of MFALCs and lung lesions. Further investigation in female lpr mice will be needed for treatment of human respiratory diseases and autoimmune disorders.
  • Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Yuki Hoshino, Satoshi Takagi, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yasuhiro Kon
    SCIENTIFIC REPORTS 7 40340  2017年01月 [査読有り][通常論文]
     
    MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/ b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study.
  • Nakamura T, Ichii O, Irie T, Hosotani M, Dantsuka A, Nakamura S, Sato S, Sotozaki K, Kouguchi H, Yoshiyasu T, Nagasaki KI, Kon Y
    The Japanese journal of veterinary research 64 4 273 - 276 2016年11月 [査読有り][通常論文]
  • Teppei Ikeda, Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY 37 4-5 153 - 164 2016年10月 [査読有り][通常論文]
     
    Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd (mdx) (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6-30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice.
  • Dugar Delgermurun, Soichiro Yamaguchi, Osamu Ichii, Yasuhiro Kon, Shigeo Ito, Ken-ichi Otsuguro
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 187 43 - 49 2016年09月 [査読有り][通常論文]
     
    Epithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5-HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3 mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca2+. outflow induced by NaHS (0.3 mM) was also significantly inhibited by voltage-dependent L- and N-type Ca2+ channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10 M) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage-dependent Ca2+ channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta. (C) 2016 Elsevier Inc. All rights reserved.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Daisuke Nakamura, Saori Nakamura, Shinobu Sato, Keisuke Yokoyama, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    HISTOCHEMISTRY AND CELL BIOLOGY 146 3 351 - 362 2016年09月 [査読有り][通常論文]
     
    The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.
  • Truc Quynh Thai, Huy Bang Nguyen, Sei Saitoh, Bao Wu, Yurika Saitoh, Satoshi Shimo, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon, Takashi Takaki, Kensuke Joh, Nobuhiko Ohno
    MEDICAL MOLECULAR MORPHOLOGY 49 3 154 - 162 2016年09月 [査読有り][通常論文]
     
    Serial block-face imaging using scanning electron microscopy enables rapid observations of three-dimensional ultrastructures in a large volume of biological specimens. However, such imaging usually requires days for sample preparation to reduce charging and increase image contrast. In this study, we report a rapid procedure to acquire serial electron microscopic images within 1 day for three-dimensional analyses of subcellular ultrastructures. This procedure is based on serial block-face with two major modifications, including a new sample treatment device and direct polymerization on the rivets, to reduce the time and workload needed. The modified procedure without uranyl acetate can produce tens of embedded samples observable under serial block-face scanning electron microscopy within 1 day. The serial images obtained are similar to the block-face images acquired by common procedures, and are applicable to three-dimensional reconstructions at a subcellular resolution. Using this approach, regional immune deposits and the double contour or heterogeneous thinning of basement membranes were observed in the glomerular capillary loops of an autoimmune nephropathy model. These modifications provide options to improve the throughput of three-dimensional electron microscopic examinations, and will ultimately be beneficial for the wider application of volume imaging in life science and clinical medicine.
  • Sawa Onouchi, Osamu Ichii, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 365 2 367 - 379 2016年08月 [査読有り][通常論文]
     
    Although gut flexures characterize gut morphology, the mechanisms underlying flexure formation remain obscure. Previously, we analyzed the mouse duodenojejunal flexure (DJF) as a model for its formation and reported asymmetric morphologies between the inner and outer bending sides of the fetal mouse DJF, implying their contribution to DJF formation. We now present the extracellular matrix (ECM) as an important factor for gut morphogenesis. We investigate ECM distribution during mouse DJF formation by histological techniques. In the intercellular space of the gut wall, high Alcian-Blue positivity for proteoglycans shifted from the outer to the inner side of the gut wall during DJF formation. Immunopositivity for fibronectin, collagen I, or pan-tenascin was higher at the inner than at the outer side. Collagen IV and laminins localized to the epithelial basement membrane. Beneath the mesothelium at the pre-formation stage, collagen IV and laminin immunopositivity showed inverse results, corresponding to the different cellular characteristics at this site. At the post-formation stage, however, laminin positivity beneath the mesothelium was the reverse of that observed during the pre-formation stage. High immunopositivity for collagen IV and laminins at the inner gut wall mesenchyme of the post-formation DJF implied a different blood vessel distribution. We conclude that ECM distribution changes spatiotemporally during mouse DJF formation, indicating ECM association with the establishment of asymmetric morphologies during this process.
  • Daichi Shiozuru, Osamu Ichii, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 31 2 189 - 204 2016年02月 [査読有り][通常論文]
     
    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    IMMUNOLOGY 147 1 30 - 40 2016年01月 [査読有り][通常論文]
     
    We previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as novel lymphoid clusters associated with mediastinal fat tissue in healthy mice. However, no data about their morphology in immune-associated disease conditions, and their relationship with lung infiltration, is available to date. In the present study, we compared the morphological features of MFALCs in 4-month-old male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice) with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ, respectively). In addition, we analysed their correlation with lung infiltration. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed to detect T cells and B cells, macrophages, granulocytes and proliferating cells, respectively. The spleen weight to body weight ratios and anti-double-stranded DNA autoantibody titres were found to be significantly higher in the autoimmune models than in the control strains. Furthermore, the autoimmune model presented prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to total mediastinal fat tissue area, and more apparent diffused cellular infiltration into the lung lobes than the other studied strains. Higher numbers of T and B cells, macrophages and proliferating cells, but fewer granulocytes, were observed in the autoimmune models than in the control strains. Interestingly, a significant positive Pearson's correlation between the size of the MFALCs and the density of CD3-, B220- and Iba1-positive cells in the lung was observed. Therefore, our data suggest a potentially important role for MFALCs in the progression of lung disease. However, further investigation is required to clarify the pathological role of MFALCs in lung disease, especially in inflammatory disorders.
  • Ken-ichi Otsuguro, Yuki Tomonari, Saori Otsuka, Soichiro Yamaguchi, Yasuhiro Kon, Shigeo Ito
    NEUROPHARMACOLOGY 97 160 - 170 2015年10月 [査読有り][通常論文]
     
    Adenosine kinase (AK) inhibitor is a potential candidate for controlling pain, but some AK inhibitors have problems of adverse effects such as motor impairment. ABT-702, a non-nucleoside AK inhibitor, shows analgesic effect in animal models of pain. Here, we investigated the effects of ABT-702 on synaptic transmission via nociceptive and motor reflex pathways in the isolated spinal cord of neonatal rats. The release of adenosine from the spinal cord was measured by HPLC. ABT-702 inhibited slow ventral root potentials (sVRPs) in the nociceptive pathway more potently than monosynaptic reflex potentials (MSRs) in the motor reflex pathway. The inhibitory effects of ABT-702 were mimicked by exogenously applied adenosine, blocked by 8CPT (8-cyclopentyl-1,3-dipropylxanthine), an adenosine A(1) receptor antagonist, and augmented by EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), an adenosine deaminase (ADA) inhibitor. Equilibrative nucleoside transporter (ENT) inhibitors reversed the effects of ABT-702, but not those of adenosine. ABT-702 released adenosine from the spinal cord, an effect that was also reversed by ENT inhibitors. The ABT-702-facilitated release of adenosine by way of ENTs inhibits nociceptive pathways more potently than motor reflex pathways in the spinal cord via activation of A1 receptors. This feature is expected to lead to good analgesic effects, but, caution may be required for the use of AK inhibitors in the case of ADA dysfunction or a combination with ENT inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
  • M. Chihara, T. Nakamura, S. Otsuka-Kanazawa, O. Ichii, Y. H. A. Elewa, Y. Kon
    ANDROLOGY 3 5 991 - 999 2015年09月 [査読有り][通常論文]
     
    MRL/MpJ mice possess highly heat-shock-resistant spermatocytes (HRS) in comparison with C57BL/6 mice. This resistance depends on the MRL/MpJ-type loci at the 81 cM region of Chromosome (Chr) 1 and the 40 cM region of Chr 11. To evaluate the functions of these loci in detail, we examined the histopathological changes resulting from experimental cryptorchidism or transient scrotal heat stress (SHS) in the testes of C57BL/6-based congenic strains (B6.MRLc1, B6.MRLc11, and B6.MRLc1c11) carrying the MRL/MpJ-derived loci responsible for HRS. Among cryptorchid testes from congenic strains, those in B6.MRLc1c11 mice showed the highest heat resistance, indicating that the genetic interactions between MRL/MpJ-derived HRS loci on Chrs 1 and 11 may be important for maintaining spermatogenesis under continuous testicular hyperthermia. In contrast, immediately after SHS induction, germ cell loss via apoptosis was inhibited in B6.MRLc11 and B6.MRLc1c11 mice, similar to that in MRL/MpJ mice. However, this HRS phenotype was not observed in C57BL/6 or B6.MRLc1 mice after SHS induction. Furthermore, testicular calcification owing to long-term damage by SHS induction was inhibited in all congenic strains in comparison with that in C57BL/6 mice, indicating that each MRL/MpJ-derived locus on Chrs 1 and 11 acted independently to facilitate the recovery of heat-induced testicular damage by inhibiting calcification. B6.MRLc11 and B6.MRLc1c11 mice showed greater recovery in spermatogenesis than B6.MRLc1 mice 60 days after SHS induction. Therefore, the MRL/MpJ-derived HRS locus on Chr 11 might play an important role in recovery from heat stress damage. On the basis of these results, we concluded that MRL/MpJ-derived loci on Chrs 1 and 11 cooperatively or independently regulate testicular heat sensitivity depending on the various heat stresses.
  • Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon
    MECHANISMS OF DEVELOPMENT 137 23 - 32 2015年08月 [査読有り][通常論文]
     
    In general, mammalian males produce only spermatozoa in their testes and females produce only oocytes in their ovaries. However, newborn MRL/MpJ male mice produce oocytes within their testes. In this study, we examined the initiation and progression of oogenesis in fetal and neonatal MRL/MpJ mouse testes and evaluated the characteristics of testicular oocytes. Germ cells with positive reactions to oogenesis markers such as NOBOX oogenesis homeobox and synaptonemal complex protein 3 were observed in the MRL/MpJ fetal testes on embryonic day 18.5. These fetal testicular oocytes possessed maternal-specific methylation patterns of histone and DNA. The level of DNA methylation was still low in postnatal testicular oocytes at day 14 after birth. Additionally, the postnatal testicular oocytes contained both X and Y chromosomes and had the ability to fuse with sperm. These results suggest that some XY germ cells in fetal testes of MRL/MpJ mice enter meiosis prematurely, undergo oogenesis, and differentiate into oocytes. In addition, MRL/MpJ testicular oocytes have the ability to carry on oogenesis before and shortly after birth until they obtain some of the morphological, epigenetic, and functional characteristics of oocytes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Sawa Onouchi, Osamu Ichii, Saori Otsuka-Kanazawa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 360 2 273 - 285 2015年05月 [査読有り][通常論文]
     
    The asymmetric shape of component cells determines the asymmetric features of developing organs. Here, we focused on the murine duodenojejunal flexure (DJF), which bends without affecting the mesentery, and analyzed the morphological asymmetries of the mucosal epithelium and gut wall cells between the inner and outer bending sides at embryonic days 10.75-11.75. In the mucosal epithelium, the cell shape and the expression of epithelial markers (Cdx2, Ecadherin) showed no differences between the two DJF sides. In contrast, the gut wall cells comprising the inner and outer sides of the DJF were elongated along the inner-outer axis and perpendicular to this axis, respectively. Furthermore, the gut wall cells in the outer side possessed cytoplasmic processes connecting cells via adherens junctions, but those in the inner side were attached via adherens junctions of juxtaposed cell bodies and were relatively more crowded. In immunohistochemistry experiments, there was no remarkable difference in the positive reactions of markers for mesenchyme (vimentin), smooth muscle cells (alpha SMA), endothelial cells (LYVE-1, CD34), and undifferentiated neurons (Sox10) between the DJF sides. Interestingly, Tuj1-positive cells, indicating differentiated neurons, were observed in the middle layer of the gut wall, and these cells were significantly more abundant and tended to be larger in the inner side than in the outer side of the DJF. In conclusion, we clarified the asymmetries of gut wall cell morphology and neural differentiation between the inner and outer sides of the DJF. These characteristics of the developing murine DJF indicate its asymmetric formation.
  • Yuma Yamashita, Teppei Nakamura, Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 63 1 25 - 36 2015年02月 [査読有り][通常論文]
     
    In perinatal mice, the ovary undergoes drastic morphological changes, as clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. We studied perinatal oocyte development in MRL/MpJ mice, and compared it to that observed in C57BL/6 mice between embryonic day 18.5 and postnatal day 4. Throughout the observation period, compared to C57BL/6 mice, MRL/MpJ mice displayed significantly fewer oocytes in their ovaries. Morphologically, there were no clear differences between the strains at embryonic day 18.5. However, the beginning of folliculogenesis, as evidenced by the expression of NOBOX. oogenesis homeobox (Nobox) transcript and protein, was more enhanced in MRL/MpJ mice than in C57BL/6 mice at embryonic day 18.5 and postnatal day 0. In addition, developed follicles were more frequently observed in MRL/MpJ mice than in C57BL/6 mice between postnatal days 0 and 4. In conclusion, the oocyte development during nest breakdown and folliculogenesis was accelerated in MRL/MpJ mice when compared to that observed in C57BL/6 mice.
  • Yuki Otani, Osamu Ichii, Saori Otsuka-Kanazawa, Masataka Chihara, Teppei Nakamura, Yasuhiro Kon
    AUTOIMMUNITY 48 6 402 - 411 2015年 [査読有り][通常論文]
     
    The immune system is known to affect reproductive function, and maternal-fetal immune tolerance is essential for a successful pregnancy. To investigate the relationship between autoimmune disease and female reproductive function, we performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice, autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas(lpr) (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset. Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice of the other two strains, respectively. Histological analysis at 3 months revealed that the number of primordial follicles was smaller in MRL-background mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months, and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months, respectively. In particular, MRL/lpr mice showed numerous infiltrating lymphocytes within the ovarian interstitia, and partially stratified ovarian surface epithelia with more developed microvilli than that observed in C57BL/6 mice at 6 months. No significant differences in serum hormone levels were observed between the strains. In conclusion, MRL/lpr mice display altered ovarian development, morphology and function consistent with the progression of severe autoimmune disease, as these findings are less severe in MRL/+ counterparts.
  • Junpei Kimura, Osamu Ichii, Kosuke Miyazono, Teppei Nakamura, Taro Horino, Saori Otsuka-Kanazawa, Yasuhiro Kon
    SCIENTIFIC REPORTS 4 7290  2014年12月 [査読有り][通常論文]
     
    Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury.
  • Okada Y, Nakamura T, Ichii O, Otsuka S, Kon Y
    Lupus 23 11 1112 - 1123 2014年10月 [査読有り][通常論文]
  • Osamu Ichii, Saori Otsuka-Kanazawa, Taro Horino, Junpei Kimura, Teppei Nakamura, Manabu Matsumoto, Makoto Toi, Yasuhiro Kon
    PLOS ONE 9 10 e110383  2014年10月 [査読有り][通常論文]
     
    MicroRNAs contribute to the pathogenesis of certain diseases and may serve as biomarkers. We analyzed glomerular microRNA expression in B6. MRLc1, which serve as a mouse model of autoimmune glomerulonephritis. We found that miR-26a was the most abundantly expressed microRNA in the glomerulus of normal C57BL/6 and that its glomerular expression in B6. MRLc1 was significantly lower than that in C57BL/6. In mouse kidneys, podocytes mainly expressed miR-26a, and glomerular miR-26a expression in B6. MRLc1 mice correlated negatively with the urinary albumin levels and podocyte-specific gene expression. Puromycin-induced injury of immortalized mouse podocytes decreased miR-26a expression, perturbed the actin cytoskeleton, and increased the release of exosomes containing miR-26a. Although miR-26a expression increased with differentiation of immortalized mouse podocytes, silencing miR-26a decreased the expression of genes associated with the podocyte differentiation and formation of the cytoskeleton. In particular, the levels of vimentin and actin significantly decreased. In patients with lupus nephritis and IgA nephropathy, glomerular miR-26a levels were significantly lower than those of healthy controls. In B6. MRLc1 and patients with lupus nephritis, miR-26a levels in urinary exosomes were significantly higher compared with those for the respective healthy control. These data indicate that miR-26a regulates podocyte differentiation and cytoskeletal integrity, and its altered levels in glomerulus and urine may serve as a marker of injured podocytes in autoimmune glomerulonephritis.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 357 3 731 - 741 2014年09月 [査読有り][通常論文]
     
    The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs "mediastinal fat-associated lymphoid clusters". These clusters can be considered as niches for Th cell production.
  • Masataka Chihara, Teppei Nakamura, Naoki Sakakibara, Saori Otsuka, Osamu Ichii, Yasuhiro Kon
    AMERICAN JOURNAL OF PATHOLOGY 184 9 2480 - 2492 2014年09月 [査読有り][通常論文]
     
    Spermatocytes of MRL/MpJ mice are more heat resistant than those of C57BL/6 mice in experimental cryptorchidism. This phenotype depends in part on the locus at the 81-cM region of MRL/MpJ-type chromosome 1 (Chr 1). To evaluate the function of this locus, we examined pathological changes in mouse testes resulting from transient scrotal heat stress. Immediately after scrotal heat stress, meiosis progression and blood-testis barrier integrity were preserved in MRL/MpJ but not in C57BL/6 mice, nor in a C57BL/6-based congenic strain carrying the MRL/MpJ-derived Chr 1 locus (B6.MRLc1). Testicular damage was severe in the weeks after scrotal heat stress in all three strains; however, testicular calcification was observed only in C57BL/6 and MRL/MpJ mice (initially as nanocrystals in mitochondria of degenerating germ cells). In testes, expression of gremlin 2, a bone morphogenetic protein antagonist encoded on Chr 1, was markedly higher in B6.MRLc1 than in C57BL/6 or MRL/Mp3 mice. Furthermore, gremlin-2 and bone morphogenetic protein 2 mRNA levels in heated testes correlated negatively and positively, respectively, with calcification. Thus, although the MRL/MpJ-derived Locus on Chr 1 may play a pivotal role in recovery from heat-induced testicular damage, especially via inhibition of calcification, MRL/MpJ mice have a precipitating factor for testicular calcification and heat shock-resistant factors that reside outside the 81-cM region of Chr 1.
  • Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Masaaki Ueno, Yasuhiro Kon, Weiping Chen, Avi Z. Rosenberg, Jeffrey B. Kopp
    PLOS ONE 9 9 e108448  2014年09月 [査読有り][通常論文]
     
    Indoxyl sulfate is a uremic toxin and a ligand of the aryl-hydrocarbon receptor (AhR), a transcriptional regulator. Elevated serum indoxyl sulfate levels may contribute to progressive kidney disease and associated vascular disease. We asked whether indoxyl sulfate injures podocytes in vivo and in vitro. Mice exposed to indoxyl sulfate for 8 w exhibited prominent tubulointerstitial lesions with vascular damage. Indoxyl sulfate-exposed mice with microalbuminuria showed ischemic changes, while more severely affected mice showed increased mesangial matrix, segmental solidification, and mesangiolysis. In normal mouse kidneys, AhR was predominantly localized to the podocyte nuclei. In mice exposed to indoxyl sulfate for 2 h, isolated glomeruli manifested increased Cyp1a1 expression, indicating AhR activation. After 8 w of indoxyl sulfate, podocytes showed foot process effacement, cytoplasmic vacuoles, and a focal granular and wrinkled pattern of podocin and synaptopodin expression. Furthermore, vimentin and AhR expression in the glomerulus was increased in the indoxyl sulfate-exposed glomeruli compared to controls. Glomerular expression of characteristic podocyte mRNAs was decreased, including Actn4, Cd2ap, Myh9, Nphs1, Nphs2, Podxl, Synpo, and Wt1. In vitro, immortalized-mouse podocytes exhibited AhR nuclear translocation beginning 30 min after 1 mM indoxyl sulfate exposure, and there was increased phospho-Rac1/Cdc42 at 2 h. After exposure to indoxyl sulfate for 24 h, mouse podocytes exhibited a pro-inflammatory phenotype, perturbed actin cytoskeleton, decreased expression of podocyte-specific genes, and decreased cell viability. In immortalized human podocytes, indoxyl sulfate treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, as well as integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. We propose that basal levels of AhR activity regulate podocyte function under normal conditions, and that increased activation of podocyte AhR by indoxyl sulfate contributes to progressive glomerular injury.
  • Y. H. A. Elewa, O. Ichii, S. Otsuka, Y. Hashimoto, Y. Kon
    ANATOMIA HISTOLOGIA EMBRYOLOGIA 43 4 265 - 272 2014年08月 [査読有り][通常論文]
     
    Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.
  • Teppei Nakamura, Yuko Sakata, Saori Otsuka-Kanazawa, Osamu Ichii, Masataka Chihara, Ken-ichi Nagasaki, Yuka Namiki, Yasuhiro Kon
    PLOS ONE 9 6 e100617  2014年06月 [査読有り][通常論文]
     
    In MRL/MpJ mice, ovarian mast cells (OMCs) are more abundant than in other mouse strains, and tend to distribute beneath the ovarian surface epithelium at birth. This study investigated the factors regulating the appearance of neonatal OMCs in progeny of the cross between MRL/MpJ and C57BL/6N strains. F1 neonates had less than half the number of OMCs than MRL/MpJ. Interestingly, MRLB6F1 had more neonatal OMCs than B6MRLF1, although they were distributed over comparable areas. Furthermore, in MRL/MpJ fetuses for which parturition was delayed until embryonic day 21.5, the number of OMCs was significantly higher than in age-matched controls at postnatal day 2. These results suggest that the number of OMCs was influenced by the environmental factors during pregnancy. Quantitative trait locus analysis using N2 backcross progeny revealed two significant loci on chromosome 8: D8Mit343-D8Mit312 for the number of OMCs and D8Mit86-D8Mit89 for their distribution, designated as mast cell in the ovary of MRL/MpJ 1 (mcom1) and mcom2, respectively. Among MC migration-associated genes, ovarian expression of chemokine (C-C motif) ligand 17 at mcom1 locus was significantly higher in MRL/MpJ than in C57BL/6N, and positively correlated with the expression of OMC marker genes. These results indicate that the appearance of neonatal OMCs in MRL/MpJ is controlled by environmental factors and filial genetic factors, and that the abundance and distribution of OMCs are regulated by independent filial genetic elements.
  • Yasui H, Takeuchi R, Nagane M, Meike S, Nakamura Y, Yamamori T, Ikenaka Y, Kon Y, Murotani H, Oishi M, Nagasaki Y, Inanami O
    Cancer letters 347 151 - 158 1 2014年05月 [査読有り][通常論文]
  • Kimura J, Ichii O, Nakamura T, Horino T, Otsuka S, Kon Y
    Genes and immunity 15 3 182 - 189 2014年04月 [査読有り][通常論文]
  • Ichii O, Otsuka S, Ohta H, Yabuki A, Horino T, Kon Y
    Research in veterinary science 96 2 299 - 303 2014年04月 [査読有り][通常論文]
  • Chihara M, Otsuka S, Ichii O, Kon Y
    The Journal of reproduction and development 59 6 525 - 535 2013年12月 [査読有り][通常論文]
  • Keigo Kosenda, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 41 8 788 - 797 2013年11月 [査読有り][通常論文]
     
    BackgroundDacryoadenitis is characteristic of an autoimmune exocrinopathy, e.g. Sjogren syndrome. We pathologically examined the lacrimal glands of autoimmune-prone BXSB/MpJ-Yaa mice for the appearance of pathological signs of dacryoadenitis progression in autoimmune dacryoadenitis models, particularly focusing on messenger RNAs in the lacrimal fluid. MethodsThe lacrimal glands of the BXSB/MpJ-Yaa and C57BL/6 mice were histopathologically analyzed in parallel with the evaluation of lacrimation and messenger RNA expression of water channels (Aqp3, Aqp4 and Aqp5). In addition, autoimmune model mice (MRL/MpJ-lpr/lpr and NZB/NZWF1) were used for evaluating cell infiltration and detecting inflammatory cell marker messenger RNAs (Cd68, Ptprc and Cd3e) in the lacrimal fluids by polymerase chain reaction-based methods. ResultsB-cell predominant lymphocytic infiltrations and the destruction of acini were observed in the lacrimal glands of BXSB/MpJ-Yaa mice. There was no significant difference in the quantity of lacrimal fluid between the BXSB/MpJ-Yaa and C57BL/6 mice. In the BXSB/MpJ-Yaa mice, Aqp3 expression increased significantly with the cell infiltration score, whereas expression of Aqp4 and Aqp5 tended to decrease. Aqp3 expression increased significantly with the cell infiltration score in BXSB/MpJ-Yaa mice. Among inflammatory cell markers, Cd68 was more frequently detected in the lacrimal fluid of the BXSB/MpJ-Yaa, MRL/MpJ-lpr/lpr and NZB/NZWF1 mice than in that of the C57BL/6 mice. ConclusionBXSB/MpJ-Yaa mice clearly developed autoimmune dacryoadenitis. The altered expression of water channels in lacrimal glands might be associated with the preservation of lacrimal fluid excretion in BXSB/MpJ-Yaa mice. The detection of inflammatory cell markers in lacrimal fluid could be used as a diagnostic marker for autoimmune dacryoadenitis.
  • Onouchi S, Ichii O, Otsuka S, Hashimoto Y, Kon Y
    Journal of anatomy 223 4 385 - 398 2013年10月 [査読有り][通常論文]
  • Junpei Kimura, Osamu Ichii, Saori Otsuka, Hayato Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon
    American Journal of Nephrology 38 1 27 - 38 2013年07月 [査読有り][通常論文]
     
    Background: Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. Methods: The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa+ and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. Results: Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl.Conclusion: MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN. © 2013 S. Karger AG, Basel.
  • Masataka Chihara, Ryoyo Ikebuchi, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Atsushi Suzuki, Yumiko Saga, Yasuhiro Kon
    BIOLOGY OF REPRODUCTION 89 1 1 - 12 2013年07月 [査読有り][通常論文]
     
    Claudin 3 is a protein component of the tight junction strands. Tight junctions between adjacent Sertoli cells form the blood-testis barrier (BTB). During spermatogenesis, seminiferous stage-specific expression of claudin 3 is believed to regulate the migration of preleptotene/leptotene spermatocytes across the BTB. Here, we determined the cell types expressing claudin 3 in adult mouse testis and investigated spermatogenesis after testis-specific in vivo knockdown of claudin 3. The results of in situ hybridization revealed that claudin 3 mRNA was predominantly expressed in germ cells near the basal lamina of seminiferous tubules at stages VI-IX. Furthermore, claudin 3 protein was localized not only to the BTB but also to the cell membrane of STRA8-expressing preleptotene/leptotene spermatocytes in the testis of adult ICR. Cg-Tg(Stra8-EGFP)1Ysa/YsaRbrc mice. Although claudin 3 knockdown did not affect BTB integrity, it did cause a partial delay in spermatocyte migration across the BTB. Moreover, claudin 3 knockdown resulted in a prolonged preleptotene phase during spermatogenesis. These data indicate that the seminiferous stage-specific expression and localization of claudin 3 during spermatogenesis regulate the progression of meiosis by promoting germ cell migration across the BTB.
  • Yuki Naganuma, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 75 3 283 - 290 2013年03月 [査読有り][通常論文]
     
    Caspase activation is associated with skeletal muscle differentiation in mouse embryos. We examined the relationship between cardiac myogenesis and cell death using mice hearts at embryonic days (E) 11.5-15.5 and fetal rat heart H9C2 cells. The number of TdT-mediated dUTP nick erid labeling (TUNEL)-positive cells increased with fetal age and was much higher than that of single-stranded DNA (ssDNA)- and active caspase-3 (aCasp3)-positive cells. TUNEL and aCasp3 double staining resulted in 3 types of positive cells: TUNEL+/aCasp3(+), TUNEL+/aCasp3(-) and TUNEL-/aCasp3(+). TUNEL+/aCasp3(-) cells were the most common but lacked morphological features of apoptosis, such as nuclear condensation or fragmentation. The expression of anti-apoptotic factors increased during E11.5-15.5. Furthermore, TUNEL-positive H9C2 cells without nuclear condensation or fragmentation were observed only in myotubes later in the culture period. In this study, the dynamics of TUNEL-positive cardiomyocyte was inconsistent with the activation of apoptosis cascade, and their morphological feature was clearly different from representative apoptosis. From these findings, we concluded that the increased number of TUNEL-positive cardiomyocyte, having the DNA strand breaks, would be associated with the progression of cardiac myogenesis.
  • Nakamura T, Otsuka S, Ichii O, Sakata Y, Nagasaki K, Hashimoto Y, Kon Y
    PloS one 8 10 e77246  2013年 [査読有り][通常論文]
  • Saori Otsuka, Osamu Ichii, Yuka Namiki, Nobuya Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon
    MAMMALIAN GENOME 23 11-12 741 - 748 2012年12月 [査読有り][通常論文]
     
    Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y-MRL), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and two consomic strains, male B6-Y-MRL and MRL-Y-B6. Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y-B6 mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least one other causative gene on the MRL-type autosomes (MRL testicular oocyte production, mtop) other than that on Y-MRL. Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8-17 cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y-MRL.
  • Tomohiro Nishino, Nobuya Sasaki, Masataka Chihara, Ken-ichi Nagasaki, Daisuke Torigoe, Yasuhiro Kon, Takashi Agui
    EXPERIMENTAL ANIMALS 61 5 525 - 532 2012年10月 [査読有り][通常論文]
     
    Tensin family members are cytoplasmic proteins that are localized to the integrin-mediated cell-basement membrane junctions and implicated in cytoskeletal organization, cell migration, and proliferation. The mammalian genome contains four paralogs, Tns1, Tns2, Tns3, and Tns4. Murine mutations in the Tns1 and Tns2 genes cause polycystic kidney disease and glomerular sclerosis, respectively, and Tns3-null mice exhibit an impaired intestinal epithelial development. However, the knowledge concerning the localization of each tensin is still fragmentary. In this study, the cellular and subcellular distributions of tensin members were defined and compared with each other. RT-PCR analysis indicated that Tns2 and Tns3 were more abundant in isolated glomeruli and that Tns1 was highly expressed in areas other than the glomeruli, but no Tns4 expression was observed in the kidney. All tensin members were detected in the small intestine. Immunohistochemical staining revealed that Tns1 was predominantly localized to the mesangium of glomeruli and renal tubules. In contrast, Tns2 and Tns3 were highly expressed in the podocytes and the partial collecting system. In the small intestine, Tns2 and Tns3 were highly expressed in crypt and villous epithelial cells. Furthermore, we found that Tns3 was colocalized with TJ protein ZO-1 in renal tubules. These results indicate distinct differences in the cellular expression of Tns1, Tns2, and Tns3, and suggest that they may be able to function independently of each other in the kidney and the small intestine.
  • Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    KIDNEY INTERNATIONAL 81 3 280 - 292 2012年02月 [査読有り][通常論文]
     
    MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that act as post-transcriptional regulators of target mRNA. In this study, we sought to identify the microRNA underlying local inflammation in a murine model of chronic kidney disease (CKD). In microarray analysis of kidneys, the expression of miR-146a/b was elevated in B6.MRLc1 CKD mice that spontaneously develop renal inflammation with age. Primary-microRNA analysis found that elevated miR-146a/b expression in the kidneys of B6.MRLc1 mice was mainly derived from miR-146a rather than miR-146b, and this expression increased with the development of CKD. Histopathological scores for glomerular and interstitial lesions, mRNA expression of inflammatory mediators, and macrophage infiltration were significantly higher in B6.MRLc1 than C57BL/6 mice and were positively correlated with miR-146a expression. In situ hybridization and laser microdissection-RT-PCR showed that miR-146a expression in interstitial lesions containing inflammatory cells was higher than in the glomerulus. The increased expression of the inflammatory-associated genes RELA, IRAK1, IL1B, IL10, and CXCLs was noted in miR-146a/b-silenced human monocytes. The amount of miR-146a was higher in urine sediments of B6.MRLc1 than of C57BL/6 mice. Thus, miR-146a expression in the kidneys and its urinary excretion was specifically associated with the development of interstitial lesions and correlated with inflammatory cell infiltration. Kidney International (2012) 81, 280-292; doi: 10.1038/ki.2011.345; published online 5 October 2011
  • Tomohiro Nishino, Nobuya Sasaki, Ken-ichi Nagasaki, Osamu Ichii, Yasuhiro Kon, Takashi Agui
    BIOMEDICAL RESEARCH-TOKYO 33 1 53 - 56 2012年02月 [査読有り][通常論文]
     
    The ICGN mouse strain is a glomerulosclerosis (GS) model that shows significant proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which represent the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we demonstrated that GS in ICGN mice can be attributed to the deletion mutation of the tensin2 (Tns2) gene (Tns2(nep)). Further, the C57BL/6J (B6) mouse is resistant to GS caused by this mutation. 129/Sv is also a popular strain; however, its susceptibility to GS has not been defined. Thus, to determine whether 129/Sv is resistant or susceptible to GS, we produced a congenic strain carrying Tns2(nep)) on the 129(+Ter)/Sv (129T) background. 129T congenic mice (129T-Tns2(nep)) did not exhibit albuminuria, renal anemia, increases in BUN, or any severe pathological changes until at least 16 weeks of age. These results indicate that 1291 is resistant to GS. Although their usage in biomedical studies is already widespread, 129/Sv mice may afford a late-onset and unique strain applicable to kidney disease research.
  • Seto T, Nagata N, Yoshikawa K, Ichii O, Sanada T, Saasa N, Ozaki Y, Kon Y, Yoshii K, Takashima I, Kariwa H
    Virus research 163 1 284 - 290 2012年01月 [査読有り][通常論文]
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Elewa Yaser Hosney, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF ANATOMY 219 6 743 - 755 2011年12月 [査読無し][通常論文]
     
    MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
  • Lee SH, Ichii O, Otsuka S, Yaser Hosney E, Namiki Y, Hashimoto Y, Kon Y
    Journal of anatomy 219 6 743 - 755 6 2011年12月 [査読有り][通常論文]
     
    MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
  • Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 11 e27783  2011年11月 [査読無し][通常論文]
     
    Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents. F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters. We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.
  • Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 11 e27783  2011年11月 [査読有り][通常論文]
     
    Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents. F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters. We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.
  • Osamu Ichii, Akira Yabuki, Nobuya Sasaki, Saori Otsuka, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi, Yuka Namiki, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 26 10 1243 - 1255 2011年10月 [査読無し][通常論文]
     
    Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e. g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats.
  • Ayo Yila Simon, Nobuya Sasaki, Osamu Ichii, Kiichi Kajino, Yasuhiro Kon, Takashi Agui
    MICROBES AND INFECTION 13 8-9 783 - 797 2011年08月 [査読有り][通常論文]
     
    Respiratory viral infections result in severe pulmonary injury, to which host immune response may be a significant contributor. At present, it is not entirely clear the extent to which lung injury is a necessary consequence of host defense. In this report, we use functional genomics approach to characterize the key roles of cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in resistant C57BL/6J and susceptible DBA/2J mice. Infected mice manifested an immune-inflammatory response characterized by the pulmonary influx of neutrophils and mononuclear cells. DBA/2J mice mounted a vigorous immune response, with significant up-regulation of cytokine/chemokine genes in two successive waves through the course of infection. Whereas, C57BL/6J mice displayed an efficient immune response with less severe pathology and clusters of immune-inflammatory responsive genes were exclusively up-regulated on day 4 in this strain. Overall, DBA/2J mice exhibited a dysregulated hyper-inflammatory cytokine/chemokine cascades that does not limit viral spread resulting in a predisposition to severe lung pathology. This response is similar to severe human respiratory paramyxovirus infections, which will serve as a model for the elucidation of hyper-immune inflammatory response that result to severe immunopathology in respiratory viral infections. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 59 2-3 79 - 88 2011年08月 [査読有り][通常論文]
     
    MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal mesonephric tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice.
  • Daisuke Torigoe, Osamu Ichii, Ruihua Dang, Takayuki Ohnaka, Shinya Okano, Nobuya Sasaki, Yasuhiro Kon, Takashi Agui
    JOURNAL OF VETERINARY MEDICAL SCIENCE 73 5 707 - 710 2011年05月 [査読無し][通常論文]
     
    To identify a gene responsible for the hooded phenotype in the rat, high-resolution linkage mapping for the hooded locus was performed using IS (non-hooded) and LEA (hooded) rats. The map revealed that only Kit gene existed in the critical region, suggesting that the Kit is a strong candidate gene. However, mutation was not found in the coding region of the LEA rat Kit gene. Further, the expressions of Kit mRNA were not different in fetal neural tubes and both neonatal and adult skins between IS and LEA rats. Furthermore, Kit-positive cells, possibly melanocytes, were found in the non-pigmented hair follicles of hooded phenotype rats. Several hypotheses are conceivable to account for mechanisms in the appearance of hooded phenotype.
  • Tomonori Kanazawa, Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 73 5 601 - 607 2011年05月 [査読無し][通常論文]
     
    During kidney development, the metanephric mesenchyme (MM) develops into the nephron through mesenchymal-epithelial transition (MET). We have previously reported that knock-down of the expression of hepatocyte nuclear factor 4 alpha (Huf4a) gene induces failure of cellular organization in the condensed mesenchyme (CM) of cultured embryonic kidneys. To elucidate the details of MET during nephrogenesis, embryonic mouse kidneys were analyzed by electron microscopy, immunohistochemistry, and molecular biology. The findings showed that the intercellular junction, but not the basal lamina, was present in the CM. Additionally, immediately after Hnf4a gene expression, the expression of epithelial genes (Krt8, Tjp1, and Cdh1) increased, and those of mesenchymal genes (Acta1 and Vim) decreased, in the CM compared to the MM. To clarify the relationship between MET and Hnf4 alpha, the fibroblast cell line with forced expression of Hnf4 alpha protein were analyzed. In this model, it was noted that Hnf4a induced increasing epithelial and decreasing mesenchymal gene expression. In these, up-regulation of Pvrl1, -2, and Mllt4 genes which mediate the formation of apico-basal polarity, were found. These results, and those of previous findings, indicate that Hnf4 alpha protein is associated with the initiation of MET in early nephrogenesis.
  • Takahiro Seto, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Yoichi Tanikawa, Sergey I. Kolominov, Sergey N. Belov, Ichiro Nakamura, Nobuo Hashimoto, Yasuhiro Kon, Alexander E. Balakiev, Tamara K. Dzagurnova, Olga A. Medvedkina, Mina Nakauchi, Mariko Ishizuka, Kentaro Yoshii, Kumiko Yoshimatsu, Leonid V. Ivanov, Jiro Arikawa, Ikuo Takashima, Hiroaki Kariwa
    JOURNAL OF VIROLOGICAL METHODS 173 1 17 - 23 2011年04月 [査読無し][通常論文]
     
    Puumala virus (PUUV) and other Arvicolinae-borne hantaviruses are difficult to cultivate in cell culture. To isolate these hantaviruses efficiently, hantavirus nucleocapsid protein (NP)-positive but seronegative wild rodents were selected by NP-detection ELISA. Three of 68 Myodes glareolus captured in Samara, Russia, were NP-positive and seronegative. Syrian hamsters were inoculated with lung homogenates from NP-positive rodents for virus propagation. Virus isolation in vitro was carried out by inoculation of lung homogenates of NP-positive hamsters to Vero E6 cell monolayers. Two PUUV strains (Samara49/CG/2005 and Samara94/CG/2005) from M. glareolus were isolated in Vero E6 cells. Nucleotide and amino acid sequence identities of the S segment of these isolates to those of PUUV F-s808 from a fatal HFRS patient in Samara region were 96.7-99.3% and 99.3-100.0%, respectively. Morphologic features of Vero E6 cells infected with PUUV strain Samara49/CG/2005 were quite similar to those of Hantaan virus-infected cells. Isolation of Hokkaido virus from Myodes rufocanus captured in Hokkaido, Japan, was also performed. Hokkaido virus NP and RNA were recovered and maintained in hamsters. These results suggest that inoculation of Syrian hamsters with rodent samples is an efficient method for the isolation and maintenance of PUUV and other Arvicolinae-borne hantaviruses. (C) 2011 Elsevier B.V. All rights reserved.
  • Junpei Kimura, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 1 e16472  2011年01月 [査読無し][通常論文]
     
    The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology. Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons. These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.
  • Takayuki Oishi, Shoichi Date, Yoko Shimamoto, Tomoko Saito, Keiko Hirota, Takeshi Sugaya, Yasuhiro Kon, Akiyoshi Fukamizu, Keiji Tanimoto
    JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION 30 6 484 - 492 2010年12月 [査読無し][通常論文]
     
    Angiotensinogen (AGT), mainly produced in the liver, is the precursor of angiotensin II, an important regulator of blood pressure and electrolyte homeostasis. We previously showed, in hepatoma-derived HepG2 cells that a hepatocyte nuclear factor 4 (HNF4) potentiated human AGT (hAGT) promoter activity and identified its binding sites (termed regions C and J) in the hAGT promoter region. We also showed in transgenic mouse (TgM) that the hAGT is abundantly expressed in the kidney where the level of endogenous mouse AGT (mAGT) expression is low. To elucidate molecular mechanisms of the AGT gene activation in the kidney, we first investigated the HNF4 and AGT expression in the mouse kidney. Northern blot, in situ hybridization and immunohistochemical analyses revealed that the hAGT and HNF4 were both expressed in the proximal tubular (PT) cells of the kidney. We then transfected the hAGT reporter constructs into immortalized mouse PT (mProx) cells and found that regions C and J contributed additively to the HNF4-potentiated hAGT promoter activity. Curiously, no obvious HNF4 binding motif was found in the corresponding region of the mAGT promoter and co-transfected HNF4 failed to activate this promoter in neither HepG2 nor mProx cells. These results suggest that the high-level hAGT expression in the TgM kidney is, at least in part, due to a presence of high-affinity HNF4 binding sites in its promoter.
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    Veterinary Research Communications 34 8 727  2010年12月 [査読有り][通常論文]
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abu Al Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    VETERINARY RESEARCH COMMUNICATIONS 34 6 557 - 567 2010年08月 [査読無し][通常論文]
     
    Previously, the distribution of myoepithelial cells (mecs) in the salivary glands was studied by both immunohistochemistry, and transmission electron microscopy; however, little was elucidated concerning their morphological features, especially in goats. This study was performed to investigate the correlation between the cytoarchitecture of the mecs in goat major salivary glands (parotid, mandibular, and sublingual glands) and the nature of the saliva secretion. The cytoarchitectural features of the mecs were examined by scanning and transmission electron microscopy as well as immunohistochemically. The secretory endpieces in the parotid gland are of the pure serous type, but in both the mandibular and sublingual glands they are of the mixed type. In all studied glands, the intercalated ducts were covered by mecs which, unlike the large stellate cells that surrounded the secretory endpieces, were spindle-shaped with few cytoplasmic processes. Interestingly, the mecs were found to bulge on the basal surfaces of the serous acini and intercalated ducts in all glands and to be in close contact to the seromucous tubules surface in the mandibular and sublingual glands forming a continuous network around it. In conclusion, the differences in the degree of development of the mecs as well as the number of their cytoplasmic processes may be correlated with the nature of the secretion and the number of the secretory granules. Thus these observations may have some relevance in the diagnosis of atrophy and pathogenic conditions of these glands.
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shinhyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 58 2 121 - 135 2010年08月 [査読無し][通常論文]
     
    The structural characteristics of the parotid glands in small ruminants (goat, sheep) were observed and compared to those of a major laboratory animal, the mouse. Their parotid glands consist of the purely serous type. Ultrastructurally, the serous acini of goats and sheep were characterized by the presence of well-developed basolateral expansions of folds, which are characteristics of electrolyte- and water-transporting epithelium. Moreover in ruminants, unlike the mouse, the presence of numerous intercellular canaliculi as well as microvilli projecting into both the intercellular canaliculi and the lumina of the serous acini provided a large surface area for osmotic equilibrium and isotonic saliva secretion. Most of the secretory granules in goats and sheep contained peripherally located inclusions that showed dense reaction products for acid phosphatase. This indicates that most of the secretory granules undergo lysosomal degradation rather than secretion. An apocrine mode of secretion of some secretory granules was occasionally observed in some acini of goats and sheep but only exocytotic features were observed in mice. In the goat, the serous acini showed three morphologically different types, which might be an indication of different activity phases. Furthermore, alpha-smooth muscle actin-, and vimentin-positive myoepithelial cells were observed only around the serous acini and the intercalated ducts. From these findings, we consider that the structural characteristics of ruminant parotid glands might reflect their physiological role in the copious isotonic saliva secretion with a low protein concentration.
  • Masataka Chihara, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    MOLECULAR REPRODUCTION AND DEVELOPMENT 77 7 630 - 639 2010年07月 [査読無し][通常論文]
     
    The blood testis barrier (BTB) separates the seminiferous epithelium into the ad-luminal and basal compartments. During murine spermatogenesis, preleptotene/leptotene spermatocytes migrate from the basal to the adluminal compartment through the BTB during stages VIII-IX. In the present study, we focused on the tight junction (TJ) molecules and analyzed their spatiotemporal expression during the murine seminiferous epithelial cycle. Structural analysis revealed that the principal components of the BTB, for example, claudin-3, claudin-11, occludin, and zonula occludens-1 (ZO-1), were localized at the basal and luminal sides of the preleptotene/leptotene spermatocytes during the migration stages (VIII-IX). Although we detected claudin-11, occludin, and ZO-1 throughout spermatogenesis, claudin-3 was only detected during stages VI-IX. Quantitative PCR using dissected seminiferous tubules from three stages (Early: II-VI, Middle: VII-VIII, Late: IX-I) clarified that the mRNA levels of TJ molecules were not correlated with the histoplanimetrical protein levels during spermatogenesis. Additionally, tubulobulbar complexes, considered to be involved in the internalization of TJ, were observed at the BTB site. Furthermore, a significant reduction in the mRNA levels of genes for the degradation of occludin (Itch) and endocytic recycling (Rab13) were observed during the Late and Middle stages, respectively. Therefore, we hypothesized that the lag between mRNA and protein expression of TJ molecules may be due to posttranslational modulation, for example, tubulobulbar complexes and endocytic recycling processes. In conclusion, these findings indicate that the integrity of the BTB is maintained throughout spermatogenesis, and the stage-specific localization of claudin-3 protein plays an important role in regulating BTB permeability. Mol. Reprod. Dev. 77: 630-639, 2010. (C) 2010 Wiley-Liss, Inc.
  • O. Ichii, A. Kamikawa, S. Otsuka, Y. Hashimoto, N. Sasaki, D. Endoh, Y. Kon
    LUPUS 19 8 897 - 905 2010年07月 [査読無し][通常論文]
     
    B6. MRLc1(82-100) congenic mice carrying the telomeric region of lupus-prone MRL chromosome 1 develop autoimmune glomerulonephritis (GN). The GN susceptibility locus of B6. MRLc1(82-100) contains the interferon activated gene 200 (Ifi200) family, which consists of Ifi202, 203, 204, and 205. Recently, Ifi202 was suggested as a candidate gene for murine lupus. In this study, we assessed the association between Ifi200 family and GN in several disease models. We compared the expression of Ifi200 family members in 24 organs between the C57BL/6 and B6. MRLc1(82-100). The expressions of Ifi200 family members differed between strains, and the most dramatic differences appeared in Ifi202 expression. Briefly, in the blood, immune organs, lungs, and testes mRNA expression was higher in B6. MRLc1(82-100) mice. In the kidney and immune organs, only Ifi202 expression increased with the development of GN in B6. MRLc1(82-100), and significant differences from C57BL/6 were observed even before disease onset. Ifi202 expression in the kidneys of BXSB, NZB/WF1, and MRL/lpr was also significantly high in the early- and late-disease stages. Furthermore, laser microdissection-reverse-transcriptase-polymerase chain reaction analysis confirmed the high Ifi202 expression in all areas of B6. MRLc1(82-100) kidneys. In conclusion, in the Ifi200 family, Ifi202 expressions in the kidney and immune organs significantly increased with GN progression. Lupus (2010) 19, 897-905.
  • Tomonori Kanazawa, Akihiro Konno, Yoshiharu Hashimoto, Yasuhiro Kon
    DEVELOPMENTAL DYNAMICS 239 4 1145 - 1154 2010年04月 [査読無し][通常論文]
     
    Hepatocyte nuclear factor 4 alpha (Hnf4 alpha) is a transcription factor required for embryogenesis and organogenesis. In the adult kidney, Hnf4 alpha is expressed at a high level in proximal tubules. Although its expression begins from the embryonic period, its function in the developing kidney has remained almost unknown. In this study, we investigated the role of Hnf4 alpha in the cultured embryonic mouse kidney by gene silencing using the RNA interference method. Additionally, we identified the dynamics of Hnf4 alpha in the microenvironment of the developing kidney. As a result of gene silencing, the cellular organization in the condensed mesenchyme (CM) fell into disorder and many apoptotic cells appeared. In addition, laser microdissection-reverse transcriptase-polymerase chain reaction provided evidence that Hnf4 alpha gene expression began first in the CM. These results suggest the possibility that Hnf4 alpha plays an important role in the regulation of the cell survival at the CM stage in nephrogenesis. Developmental Dynamics 239:1145 1154, 2010. (C) 2010 Wiley-Liss, Inc.
  • Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    MAMMALIAN GENOME 21 3-4 162 - 171 2010年04月 [査読無し][通常論文]
     
    MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of mesonephric tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.
  • Saori Otsuka, Yuka Namiki, Osamu Ichii, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon
    MAMMALIAN GENOME 21 3-4 153 - 161 2010年04月 [査読無し][通常論文]
     
    MRL/MpJ (MRL) mouse testes have several unique characteristics, including the appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the present study we used chromosomal mapping to determine the genomic background associated with small testis size in MRL mice. We prepared and analyzed C57BL/6-based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL) analysis revealed susceptibility loci for small testis size at 100 cM on chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed that low testis weight in MRL mice was caused by germ cell apoptosis. Through histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage-specific apoptosis in their testes, the former at metaphase stage XII and the later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1. Thus, the mutation of the Exo1 gene is also responsible for low testis weight caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2.
  • Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Akira Yabuki, Hiroshi Ohta, Mitsuyoshi Takiguchi, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon
    LABORATORY INVESTIGATION 90 3 459 - 475 2010年03月 [査読無し][通常論文]
     
    Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In PCR array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6. MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the DCTs to CCDs, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin- or alpha-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of TILs in the B6. MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, TGF-beta receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.
  • Teppei Ikeda, Tomonori Kanazawa, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 71 9 1161 - 1168 2009年09月 [査読無し][通常論文]
     
    The caspases (Casps) are a family of cysteine proteases that are known to regulate apoptotic signaling. Apoptosis by activation of Casp is strongly associated with embryonal development and regeneration in many organs, therefore indicating that disorders caused by homozygous mutation in Casp genes can result in embryonic lethality. In the present study, the authors investigated the causative relationship between skeletal myogenesis and the activation of Casps by analyzing their dynamics during Mouse embryogenesis. Individual myogenetic tissues were obtained from C57BL/6 Mouse embryos aged 12.5-17.5 days post-conception (dpc), and the expression of Casps was analyzed by histochemical and molecular biological methods. Immunoreactions for Casp-3, -9 and -12 were detected first in myoblasts, increasing according to embryonal development, as a result Of Which myoblasts differentiated into myotube cells. On the other hand, the immunoreaction for ssDNA, which is well-known as an apoptosis marker, was little detected during the skeletal myogenesis. Quantification analysis for Casp mRNA expression by RT-PCR as well as by in situ hybridization showed a peak at 15.5 dpc but a decrease at 17.5 dpc. Similar dynamics were detected for Myod1 mRNA, one of the Muscle regulatory factors, but not for Fast, Bax and Rock1, apoptosis-associated factors during skeletal myogenesis. These results Suggest that the activation of Casps in skeletal myogenesis is deeply associated with myoblast differentiation, but not directly related to apoptosis.
  • Keisuke Hino, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 57 1 3 - 11 2009年05月 [査読無し][通常論文]
     
    Hydrocephalus is an intractable disease characterized by the excessive accumulation of cerebrospinal. fluid (CSF) in the cerebral ventricles. There are many cases in both human and animals; however, the cause and mechanism of it's development is not clearly understood. In this study, differences of cerebral ventricles in 5 inbred mice strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2 and BALB/c) were investigated. by histological techniques to determine the possibility of a new animal model for hydrocephalus. Our analysis showed that significant differences in the volume and the surface area of lateral ventricles in the 5 inbred strains, with MRL/MpJ mice having the largest lateral, third, aqueduct and fourth ventricles. In addition, when MRL/MpJ mice were compared to BALB/c mice on 0 day after birth, the former already had larger lateral ventricles than the latter. Although there were no significant difference in the ratios of ependymal cell types in MRL/MpJ mice and BALB/c mice, the number and the diameter of lipid droplets in MRL/MpJ mice were, interestingly, smaller than those in BALB/c mice. It is well known that ependymal cells absorb nutritional substances in CSF by endocytosis, suggesting the possibility that their decrease may relate to the larger cerebral ventricles in MRL/MpJ. In conclusion, MRL/MpJ mice have greater volumes in cerebral ventricles than other strains and may be useful for a model showing high susceptibility to hydrocephalus.
  • Akihiro Kamikawa, Osamu Ichii, Daisuke Yamaji, Takeshi Imao, Chihairu Suzuki, Yuko Okamatsu-Ogura, Akira Terao, Yasuhiro Kon, Kazuhiro Kimura
    DEVELOPMENTAL DYNAMICS 238 5 1092 - 1099 2009年05月 [査読無し][通常論文]
     
    Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin. Developmental Dynamics 238:1092-1099, 2009. (C) 2009 Wiley-Liss, Inc.
  • Aki Ogura, Shigeru Oowada, Yasuhiro Kon, Aki Hirayama, Hironobu Yasui, Shunsuke Meike, Saori Kobayashi, Mikinori Kuwabara, Osamu Inanami
    CANCER LETTERS 277 1 64 - 71 2009年05月 [査読無し][通常論文]
     
    Mitochondria in mammalian cells are well-known to play an important role in the intrinsic pathway of genotoxic-agent-induced apoptosis by releasing cytochrome c into cytosol and to be a major source of reactive oxygen species (ROS). The aim of this study was to examine whether mitochondrial ROS are involved in radiation-induced apoptotic signaling in A549 cells. Post-irradiation treatment with N-acetyl-L-cystein (NAC) inhibited cytochrome c release from mitochondria but did not affect expression levels of Bcl-2, Bcl-X-L and Bax, suggesting that late production of ROS triggered cytochrome c release. Experiments using DCFDA (a classical ROS fluorescence probe) and MitoAR (a novel mitochondrial ROS probe) demonstrated that intracellular and mitochondrial ROS were enhanced 6 h after X irradiation. Furthermore, the O-2(-center dot) production ability of mitochondria isolated from A549 cells was evaluated by ESR spectroscopy combined with a spin-trapping reagent (CYPMPO). When isolated mitochondria were incubated with NADH, succinate and CYPMPO, an ESR spectrum due to CYPMPO-OOH was detected. This NADH/succinate-dependent O-2(-center dot) production from mitochondria of irradiated cells was significantly increased in comparison with that of unirradiated cells. These results indicate that ionizing radiation enhances O-2(-center dot), production from mitochondria to trigger cytochrome c release in A549 cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • O. Ichii, A. Konno, N. Sasaki, D. Endoh, Y. Hashimoto, Y. Kon
    LUPUS 18 6 491 - 500 2009年05月 [査読無し][通常論文]
     
    Female B6. MRLc1(82-100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6. MRLc1(82-100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones. Lupus (2009) 18, 491-500.
  • Mina Nakauchi, Hiroaki Kariwa, Yasuhiro Kon, Kentaro Yoshii, Akihiko Maeda, Ikuo Takashima
    MICROBIOLOGY AND IMMUNOLOGY 52 12 625 - 630 2008年12月 [査読無し][通常論文]
     
    SARS-CoV has four major structural proteins: the N, S, M, and E proteins. To investigate the mechanism of SARS-CoV assembly, we cloned the genes encoding these four proteins into the eukaryotic expression vector pCAGGS and transfected them into 293T cells. When all four expression vectors were co-transfected VLP formed, as confirmed using electron microscopy. Using a rabbit polyclonal antibody specific to the N protein, N-protein-containing particles similar in size to the VLP were also observed by immunoelectron microscopy, indicating that the VLP contained the N protein. Co-immunoprecipitation analyses demonstrated an interaction between the N and M proteins, suggesting that N protein binds directly to M protein to be incorporated into VLP.
  • Saori Otsuka, Akihiro Konno, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 56 3 129 - 138 2008年11月 [査読無し][通常論文]
     
    Although mammals produce either sperm or eggs depending on their sex, newborn MRL/MpJ male mice contain oocytes within their testes. In our previous study, the testicular oocyte appears as early as day 0 afterbirth and has morphological characteristics as an oocyte such as zona pellucida and follicular epithelial cells. Based on the observation of F1 between MRL/MpJ and C57BL/6, one of the genes causing the appearance of testicular oocyte exists on the Y chromosome. In the present study, we found testicular oocytes within newborn AKR mice. We have also analyzed the Sry genes from several inbred mouse strains and identified a shortened glutamine repeat near the C-terminal region that is unique to MRL and AKR. These results suggest that polymorphism of glutamine repeat within SRY correlates with the appearance of testicular oocyte and this phenotype is derived from AKR, one of the original strains of MRL mice.
  • Osamu Ichii, Akihiro Konno, Nobuya Sasaki, Daiji Endoh, Yoshiharu Hashimoto, Yasuhiro Kon
    KIDNEY INTERNATIONAL 74 3 339 - 347 2008年08月 [査読無し][通常論文]
     
    Mag is an MRL-derived glomerulonephritis susceptibility locus that includes the Fcgr2b and Fcgr3 genes encoding the inhibitory Fc gamma receptor IIB (Fc gamma RIIB) and active Fc gamma RIII, respectively. We measured changes in gene balance in three B6.MRLc1 congenic mouse strains containing the 82-86, 92-100 and 100 cM regions of the MRL chromosome 1. We found that only the strain that has 92-100 (which includes Fcgr loci) developed glomerulonephritis. These congenic mice had splenomegaly, elevated blood urea nitrogen, anti-dsDNA antibodies and higher urinary albumin excretion compared to the parental strain C57BL/6(B6). Prior to the development of glomerulonephritis, large CD3- (T cell) and B220- (B cell) positive areas were identified in the spleens of B6. MRLc1(92-100) mice. Both Fc receptors were found in mesangial and dendritic cells; important sites of immune-complex clearance and antigen presentation. The Fc gamma RIII-positive areas were more prominent in the congenic strain. Fcgr2b mRNA was lower in the B6. MRLc1(92-100) kidney and spleen than in those organs of the B6 mice while Fcgr3 expression and the Fcgr3 to Fcgr2b mRNA ratio was higher in the congenic strain kidneys, spleen and thymus than in those of the B6 prior to and at an early stage of glomerulonephritis. We conclude that the imbalance of inhibitory and active Fc gamma receptors influences the pathogenesis of glomerulonephritis.
  • Saori Otsuka, Akihiro Konno, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon
    BIOLOGY OF REPRODUCTION 79 1 9 - 16 2008年07月 [査読無し][通常論文]
     
    Although mammals produce either sperm or eggs depending on their sex, we found oocytes in the testes of newborn MRL/MpJ male mice. In the present study, we report the morphological characteristics of testicular oocytes, the postnatal change of oocyte number per testis, and the expression of a few oocyte-specific genes in the testes of MRL/MpJ mice. The testicular oocytes had a diameter of 50-70 mu m and were surrounded by zonae pellucidae, which were observed between oocytes and follicular epithelial cells. Ultrastructurally, the testicular oocytes contained numerous microvilli and cortical granules, receiving cytoplasmic projections from follicular epithelial cells. The testicular oocytes appeared as early as at birth, and the largest number was found on Day 14. The testicular oocytes were detected in only MRL strains and B6MRLF1, but not in C57BL/6, C3H/He, BALB/c, DBA/2, A/J, and MRLB6F1. The expression of the oocyte-specific genes Zp1, Zp2, Zp3, and Omt2a was detected in testes from MRL/MpJ mice. These results suggest that newborn male MRL/Mpj mice with XY chromosomes can produce oocytes in their testes and that one of the genes causing this exists on the Y chromosome.
  • Osamu Ichii, Akihiro Konno, Nobuya Sasaki, Daiji Endoh, Yoshiharu Hashimoto, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 23 4 411 - 422 2008年04月 [査読無し][通常論文]
     
    In lupus erythematosus-prone mice, including the BXSB, NZW and NZB strains, telomeric regions of chromosome 1 (Chr.1) contain major glomerulonephritis susceptibility loci such as Bxs3, Sle1, and Nba2. To assess whether strain MRL, a model for lupus erythematosus, had glomerulonephritis susceptibility loci on Chr.1, we created B6.MRLc1 (82-100) congenic mice carrying MRL/MpJ Chr.1 (82-100cM) based on the C57BL/6 background and investigated renal pathology. From 6 months of age, B6.MRLc1 (82-100) showed the onset of diseases such as splenomegaly due to proliferation of CD3-or B220-positive cells, glomerular damage, and an increased serum anti-dsDNA antibody concentration, and these were earlier and severer in females. The score for glomerular damage was higher in B6.MRLc1 (82-100) mice over 12 months old than in C57BL/6 or even in wild-type MRL/MpJ. Immune-complex depositions were demonstrated on glomerular basement membrane in B6.MRLc1 (82-100) by immunohistochemistry and electron microscopy. For the percentage of IgG1-positive glomeruli, B6.MRLc1 (82-100) had significantly higher values than C57BL/6. In evaluations of clinical parameters, serum levels of blood urea nitrogen and the anti-dsDNA antibody in B6.MRLc1 (82100) were significantly higher than those in C57BL/6. In conclusion, B6.MRLc1 (82-100) clearly developed autoimmune-mediated glomerulonephritis, and we demonstrated that MRL Chr.1 contained a novel glomerulonephritis susceptibility locus. We named this locus Mag (MRL autoimmune glomerulonephritis) and it provided new insights into the genetic basis and pathogenesis of lupus nephritis.
  • Saori Otsuka, Masatsugu Suzuki, Naoki Kamezak, Tatsuya Shima, Motoki Wakatsuki, Yasuhiro Kon, Noriyuki Ohtaishi
    JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL GENETICS AND PHYSIOLOGY 309A 3 166 - 174 2008年03月 [査読無し][通常論文]
     
    Studies on the population dynamics of sea turtles require histological evaluation of the ontogenetic development and the activity of the gonads for reproduction. To investigate the growth-related changes of gonads in the immature male green turtle (Chelonia mydas), the histological changes of testes and epididymides and the localization of the androgen receptor, estrogen receptor alpha, estrogen receptor beta, and progesterone receptor were examined. The testes were categorized histologically into six developmental stages, and a scarce relationship between straight carapace length and gonadal development was confirmed based on the histological analysis. Several kinds of steroid hormone receptors were examined to show distributions in both testes and epididymides, for which their immunoreactivities were enhanced according to the developmental stage of the testes. These results suggest that straight carapace length is not an adequate indicator of maturity determination, whereas histological and immunohistochemical evaluations are useful in identifying the growth stages of green turtles, owing to the higher sensitivity to steroid hormones that appear during growth.
  • M. Z. I. Khan, S. H. Akter, M. N. Islam, M. R. Karim, M. R. Islam, Y. Kon
    ANATOMIA HISTOLOGIA EMBRYOLOGIA 37 1 52 - 59 2008年02月 [査読無し][通常論文]
     
    The present research has been designed to understand the effect of selenium and vitamin E on the lymphocyte and changes in the frequency of Ig-containing plasma cells in the lymphatic organ and ileum (representative organ for mucosa-associated lymphatic tissues) of different postnatal stages of Kasilla broiler chickens. A routine haematoxylin and eosin (H and E) stain were used to study the histology of the lymphocytic changes, and indirect immunoperoxidase staining method was performed for the study of the distributional and dynamical changes of the Ig-containing plasma cells within the lymphatic tissues and in the ileum of control broilers and in the broilers supplemented with different concentration of selenium and vitamin E in the diet. Histologically, the population of lymphocytes decreased in the lobules of the thymus, medulla of bursal follicles, splenic masses, lymphatic nodules of the cecal tonsil, and villi of the ilium in 0.1 mg and 0.5 mg selenium supplemented broilers in comparison with the control. The population of these cells was found to increase in 150 mg and 300 mg vitamin F supplemented chickens in the present study. In the spleen IgG- and the IgM-containing plasma cells were more than IgA-containing plasma cells. In contrast, in the cecal tonsil and ileum IgA-containing plasma cells were more than IgG- and IgM-containing plasma cells. The frequency of these immunopositive cells were decreased in 0.1 mg and 0.5 mg selenium supplementated chickens, and increased their frequency in the chickens supplemented with 150 mg and 300 mg vitamin E. In the spleen the frequency of IgM-containing plasma cells and both in the cecal tonsil and ileum, the IgG-containing plasma cells were more decreased by selenium supplementation which restored in their population by vitamin E supplementation.
  • Expression of hepatic nuclear factor 4α in developing mice.
    Anat. Histol. Embryol. doi: 10.1111/j.1439-0264.2008.00889.x.  2008年 [査読無し][通常論文]
  • Mohammad N. Islam, Mohammad Z. I. Khan, Mir R. Jahan, Mohammad R. Karim, Yasuhiro Kon
    Journal of Poultry Science 45 2 125 - 131 2008年 [査読有り][通常論文]
     
    The aims of this study was to find out the histological differences of the mucosa and comparative analysis of Ig-containing plasma cells among the different segments of the gastrointestinal tract of broiler and native chickens of Bangladesh. The conventional histological study revealed that the lining epithelium of the proximal segments (esophagus, crop, and proventriculus) were thicker in the broiler. The esophageal glands were more in the broiler than the native chickens. The villi of the duodenum, jejunum and ileum were slender and longer in the broiler in comparison to the native chickens. The number of goblet cells in the duodenum, jejunum, and ileum was more in the native chickens than the broiler. The indirect immunohistochemistry revealed that very few immunoglobulin (Ig)-containing plasma cells were present in the epithelium and lamina propria of esophagus, crop, and proventriculus of the broiler and native chickens. The frequency of the population of these cells were abundantly located in the lamina propria, around the intestinal gland and in the core of the villi from duodenum to ileum of broiler and native chickens. The intraepithelial IgA-containing epithelium was observed only in the epithelium of the native chickens. Segmental variation of Ig-containing plasma cells was noticed in these two strains of chickens. The IgA-, IgG-, and IgM-containing plasma cells were significantly more in the most of the segments of the small intestine of the native chickens. This suggested that besides the existence of histological variation in the gastrointestinal tract of broiler and native chickens, the Ig-containing plasma cells were significantly more in the different segments of the digestive tract of native chickens possible due to their scavenging. Copyright © 2008, Japan Poultry Science Association.
  • Akihiro Konno, Mitsuyoshi Takiguchi, Kensuke Takada, Takeshi Usami, Kaoru Azumi, Hisayo Kubota, Mutsumi Inaba, Junzo Saegusa, Yasuhiro Kon
    Immunogenetics 59 11 853 - 859 2007年11月 [査読無し][通常論文]
     
    Sjogren's syndrome (SS) is caused by an autoimmune sialodacryoadenitis, and up to 5% of patients with SS develop malignant B cell growth. The IQI mouse is a spontaneous model of primary SS in which B cells are the dominant cellular subpopulation among mononuclear infiltrates in sialitis lesions. Understanding the genetic control of aberrant B cell growth in IQI mice may help elucidate the genetic mechanisms involved in B-lineage hyperplasia leading to malignant transformation in human SS. B cell-dominant infiltration in the submandibular glands of 6-month-old IQI and C57BL/6 (B6) mice and their F1 and F2 progenies was quantified as B-lymphocytic sialitis score, and a genome-wide scan of 179 (IQI x B6) F2 females was performed to identify a quantitative trait locus (QTL) controlling this phenotype. A QTL significantly associated with variance in B-lymphocytic sialitis score was mapped to the D6Mit138 marker (position of 0.68cM) on proximal chromosome 6, with a logarithm of odds score of 4.3 (p=0.00005). This QTL, named autoimmune sialitis in IQI mice, associated locus 1 (Asq1), colocalized with Islet cell autoantigen 1 (Ica1), which encodes a target protein of the immune processes that define the pathogenesis of primary SS in humans and in the nonobese diabetic mouse model.
  • M. Z. I. Khan, M. R. Jahan, M. N. Islam, Z. Haque, M. R. Islam, Y. Kon
    TISSUE & CELL 39 3 141 - 149 2007年06月 [査読無し][通常論文]
     
    The distribution and frequency of immunoglobulin (Ig)-containing plasma cells, their variations due to sex, and the mode of secretion of Ig cells into the duct system of the Harderian gland was investigated in broiler and native chickens of both sexes in Bangladesh. The Harderian gland is covered by a capsule, and the connective tissue septa divide the gland into numerous unequal-sized numerous lobes and lobules. The Ig-containing plasma cells were located in the interstitial space, interacinar space, apical part of the lobule, and lumina of the lobules of the Harderian gland in both broiler and native chickens. The population of these Ig-containing plasma cells varied in between broiler and native chickens. and also between male and female broiler and native chickens. In the broiler, the number of IgM-containing plasma cells was higher; in contrast. in the native chickens, the population of IgA-containing plasma cells was larger. In the broiler, there were more IgA- and IgG-containing plasma cells in the male; in contrast, there were more IgM-containing plasma cells in female. In native chickens the frequency of IgA-containing plasma cells was greater in the female than male. When the data for broiler and native birds were compared, it was found that there were significantly more IgA- and IgG-containing plasma cells in the native male and female chickens than in the broiler males and females. The secretory Igs were located in the lumina of acini and the duct system of the Harderian gland. In the present study Ig-containing plasma cells were observed to be released in the lumina of the lobules of Harderian gland by the breakdown of acinar tissues in broilers, and by holocrine mode of secretion in the native chicken. These results suggested that the Harderian gland, even though it is not a lymphoid organ as a whole, but acts as an immunopotent organ in chickens, and that the gland in native chicken contains more Ig-containing plasma cells due to their scavening, (c) 2007 Elsevier Ltd. All rights reserved.
  • Y. Kon, A. Konno, Y. Hashimoto, D. Endoh
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C 36 3 172 - 178 2007年06月 [査読無し][通常論文]
     
    In MRL mice aged more than 1 year, but not in C57BL/6 mice, ovaries had grossly visible cysts presenting unilaterally or bilaterally. Postnatally, all MRL mice developed ovarian cysts by 8 months of age. Observations by light microscopy, including lectin histochemistry, indicated that the cysts sometimes included papillomatous tissues located at the hilar region and were similar to the rete ovarii system, but not to follicles. Two types of epithelial cells, ciliated and non-ciliated, were arranged on the cysts, in which both cell types had many microvilli projecting in various directions and random ramifications in the cystic lumen. These characteristics suggest that ovarian cysts developing in MRL mice originate mostly from the rete ovarii. Cysts derived from the rete ovarii at 8 months of age were histologically detected in all C3H mice as well as MRL mice, with variable incidence in ICR, AKR, CBA/N and ddY, and none in C57L/6, DBA/2, BALB and A/J mice. However, measurement of the maximum diameters of the ovarian cysts indicated that MRL mice regularly possessed the largest cysts visible to the naked eye. This is the first report of ovarian cysts in this inbred strain, suggesting that ovarian cysts in MRL mice appear with stable incidence and development.
  • Hironobu Yasui, Osamu Inanami, Taketoshi Asanuma, Daisuke Iizuka, Takayuki Nakajima, Yasuhiro Kon, Akira Matsuda, Mikinori Kumwabara
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 68 1 218 - 228 2007年05月 [査読無し][通常論文]
     
    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth. (c) 2007 Elsevier Inc.
  • Masanobu Hayashi, Hide Nishiya, Toshiaki Chiba, Daiji Endoh, Yasuhiro Kon, Toyo Okui
    JOURNAL OF VETERINARY MEDICAL SCIENCE 69 2 137 - 142 2007年02月 [査読無し][通常論文]
     
    Anti-copper treatments have been investigated to determine whether they suppress angiogenesis and tumor development since Cu is widely accepted as being required for angiogenesis. We examined the effects of treatment with trientine, a copper-chelating agent, on tumor development in a murine xenograft model using fibrosarcoma-derived transplantable QRsp-11 cells and C57BL/6 mice and induction of apoptosis in tumor cells and endothelial cells in vivo and in vitro. The tumor volumes increased more slowly in trientine-treated mice than in untreated mice. Tumor volumes in the treated mice were significantly smaller than those in the untreated mice at 24 days postinoculation (d.p.i.) of tumor cells. A cluster of pyknotic tumor cells and morphological abnormalities in capillary endothelial cells were observed in the tumors of trientine-treated mice but not in the tumors of untreated mice. The proportions of apoptotic and necrotic cells in the tumors of treated mice were approximately 3.5-fold higher than those in the tumors of untreated mice at 14 d.p.i. When the cells were treated with trientine in vitro, mouse endothelial cells and bovine primary endothelial cells showed an approximately 10-fold higher sensitivity to trientine than QRsp-11 cells in terms of D-37. However, the proportion of apoptotic cells in endothelial cells was significantly lower than that in QRsp-11 cells after treatment with trientine. These results show that apoptosis was induced in tumor cells by treatment with trientine in vivo and in vitro.
  • Taketoshi Asanuma, Hironobu Yasui, Osamu Inanami, Kenji Waki, Momoko Takahashi, Daisuke Iizuka, Taketo Uemura, Gregory Durand, Ange Polidori, Yasuhiro Kon, Bernard Pucci, Mikinori Kuwabara
    Chem Biodivers. 4 9 2253 - 2267 2007年 [査読無し][通常論文]
     
    A new amphiphilic derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl) nitrone.
  • Masanobu Hayashi, Sayaka Fuse, Daiji Endoh, Noboru Horiguchi, Kenji Nakayama, Yasuhiro Kon, Toyo Okui
    EXPERIMENTAL ANIMALS 55 5 419 - 426 2006年10月 [査読無し][通常論文]
     
    Copper accumulation and induction of DNA strand breaks were investigated in the brain of Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson disease that is a heritable disease of copper accumulation and copper toxicity in the liver, kidney and brain. Copper contents in the brain of LEC rats increased from 20 weeks of age and were approximately 3.5 to 6 folds higher than those in the brain of WKAH rats at 24 weeks of age. Hepatic copper contents in LEC rats increased from 4 to 12 weeks of age in an age-dependent manner, and then decreased from 16 to 20 weeks of age. Thus, we consider that copper accumulated in the liver was released from severely damaged hepatocytes and deposited in the brain, although copper contents in the brain were 1120-fold lower than those in the liver. We also evaluated the amounts of DNA single-strand breaks (SSBs) in the brain by comet analysis. The proportions of nuclei in the cerebrum and cerebellum without DNA damage decreased, and nuclei with severe DNA damage appeared in LEC rats at 24 weeks of age. The comet scores of cerebrum and cerebellum cells significantly increased in LEC rats and were significantly higher than those in WKAH rats at 24 weeks of age. The results show that SSSs in LEC rat brain cells are induced at a lower concentration of copper than are SSBs in hepatic cells.
  • Junko Nio, Hiromi Takahashi-Iwanaga, Masami Morimatsu, Yasuhiro Kon, Toshihiko Iwanaga
    Histochem. Cell. Biol. 126 1 45 - 56 2006年07月 [査読無し][通常論文]
     
    Galectin is an animal lectin that has high affinity to beta-galactoside of glycoconjugates. In the present study, cellular expression of galectin subtypes in the urinary system of adult mice was examined by in situ hybridization and immunohistochemistry. The major subtype expressed in the murine urinary system was galectin-3, which was expressed continuously from the kidney to the distal end of the urethra. The renal cortex expressed galectin-3 more intensely than the medulla. Renal galectin-3 immunoreactivity was strongest in the cortical collecting ducts, where principal cells were the sole cellular source. All cell layers of the transitional epithelium from the renal pelvis to the urethra strongly expressed galectin-3 at the mRNA and protein levels. An electron microscopic study demonstrated diffuse cytoplasmic localization of galectin-3 in principal cells of the collecting ducts and in the bladder epithelial cells. Urethral galectin-3 expression at the pars spongiosa decreased in intensity near the external urethral orifice, where the predominant subtype of galectin was substituted by galectin-7. The muscular layer of the ureter and urinary bladder contained significant signals for galectin-1. Taken together, the observations indicate that the adult urinary system shows intense and selective expression of galectin-3 in epithelia of the uretic bud- and cloaca-derivatives.
  • AR Cho, K Uchio-Yamada, T Torigai, T Miyamoto, Miyoshi, I, J Matsuda, T Kurosawa, Y Kon, A Asano, N Sasaki, T Agui
    MAMMALIAN GENOME 17 5 407 - 416 2006年05月 [査読無し][通常論文]
     
    The ICGN mouse is a model for nephrotic syndrome (NS) which presents with proteinuria, hyperlipidemia, and edema. In this study we attempted to identify the gene(s) responsible for NS. By analyzing albuminuria in 160 (ICGN x MSM)F-1 x ICGN backcross progenies, we found that NS in the ICGN mouse is caused by more than one gene. We then performed a quantitative trait locus (QTL) analysis and detected a QTL with a very high LOD score peak in the telomeric region of Chr 15. By analyzing the nucleotide sequence of 22 genes located close to the QTL, we found that the tensin2 gene of the ICGN mouse possessed an 8-nucleotide deletion mutation in exon 18, leading to a frameshift and giving rise to a terminal codon at a premature position. Analyses of in situ hybridization and immunohistochemistry revealed that tensin2 was expressed in podocytes and tubular epithelial cells in normal mice but not in the ICGN mouse. These data raise the possibility that a mutation of the tensin2 gene is responsible for NS of the ICGN mouse and tensin2 is a prerequisite for the normal kidney function.
  • D Yamaji, K Kimura, A Watanabe, Y Kon, T Iwanaga, MM Soliman, MM Ahmed, M Saito
    DOMESTIC ANIMAL ENDOCRINOLOGY 30 3 239 - 246 2006年03月 [査読無し][通常論文]
     
    Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine that plays a crucial role in the embryonic and postnatal development of various organs including the mammary gland. We cloned bovine HGF and its c-Met receptor cDNAs, and examined their expression during mammary gland development in dairy cows. The 2.5-kbp HGF cDNA clone contained a 2190 bp open reading frame coding a 730 amino acid protein, while the 4.8-kbp c-Met cDNA clone contained a 4152 bp open reading frame coding a 1384 amino acid protein. The bovine HGF and c-Met sequences exhibited more than 87% identity with those of other mammals. RT-PCR analysis revealed ubiquitous expression of both HGF and c-Met mRNAs in various bovine tissues tested. HGF mRNA was detected only in the inactive stage of bovine mammary gland development and not in the developing, lactating, and involuting stages, while c-Met mRNA was detected in the inactive and involuting stages. Immunohistochemical analysis demonstrated that the c-Met protein was found on mammary epithelial cells in the inactive, developing, and involuting stages, and on myoepithelial cells in all stages. These results suggest pivotal roles of HGF and c-Met in the development of bovine mammary gland. (c) 2005 Elsevier Inc. All rights reserved.
  • J Nio, Y Kon, T Iwanaga
    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 53 11 1323 - 1334 2005年11月 [査読無し][通常論文]
     
    Galectin is an animal lectin that recognizes beta-galactosides of glycoconjugates and is abundant in the gut. This study revealed the cellular expression of galectin subtypes throughout the mouse digestive tract by in situ hybridization. Signals for five subtypes (galectin-2, -3, -4/6, and -7) were detected exclusively in the epithelia. In the glandular stomach, galectin-2 and -4/6 were predominantly expressed from gastric pits to neck of gastric glands, where mucous cells were the main cellular sources. The small intestine exhibited intense, maturation-associated expressions of galectin-2, -3, and -4/6 mRNAs. Galectin-2 was intensely expressed from crypts to the base of villi, whereas transcripts of galectin-3 gathered at villous tips. Signals for galectin-4/6 were most intense at the lower half of villi. Galectin-2 was also expressed in goblet cells of the small intestine but not in those of the large intestine. In the large intestine, galectin-4/6 predominated, and the upper half of crypts simultaneously contained transcripts of galectin-3. Stratified epithelium from the lip to forestomach and anus intensely expressed galectin-7 with weak expressions of galectin-3. Because galectins in the digestive tract may be multi-functional, information on their cell/ stage-specific expression contributes to a better understanding of the functions and pathological involvements of galectins.
  • M Hayashi, K Miyane, M Senou, D Endoh, H Higuchi, H Nagahata, K Nakayama, Y Kon, T Okui
    EXPERIMENTAL ANIMALS 54 5 403 - 412 2005年10月 [査読無し][通常論文]
     
    The effects of treatment with trientine, a specific copper-chelating agent, on the accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the kidneys of LEC rats in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, renal copper contents did not increase and were maintained at the same levels as those in 4-week-old LEC rats. Estimation of the amounts of DNA single-strand breaks (SSBs) by comet assay showed that SSBs of DNA were induced in a substantial population of LEC rat renal cortex cells around 12 weeks of age and that the amounts of SSBs increased in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that SSBs of DNA in LEC rat kidney cells are induced prior to occurrence of clinical signs of hepatic injury and that treatment of LEC rats with trientine decreases the number of DNA strand breaks.
  • Yasuhiro Kon
    Anatomical Science International 80 3 141 - 152 2005年09月 [査読無し][通常論文]
     
    An MRL/MpJ strain of mice, including lpr mutants, reveals the complex pathological manifestations of collagen disease, such as systemic vasculitis, glomerulonephritis, arthritis and sialoadenitis, in association with several autoimmune factors. Studies involving this mouse strain have shown that it exhibits a much-enhanced healing response compared with other mouse strains, together with reduced scarring in the periphery. Recently, unique characteristics were found in the testis of the MRL/MpJ mouse: metaphase-specific apoptosis (MSA) of meiotic spermatocytes, heat stress resistance in spermatocytes and the appearance of oocyte-like cells. The present review describes the morphological and genetic analysis of MSA, culminating in the conclusion that inherent mutation of exonuclease 1 induces checkpoint activity during meiotic division in MRL mice.
  • J Tamura, A Konno, Y Hashimoto, Y Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 53 1-2 13 - 26 2005年08月 [査読無し][通常論文]
     
    The aim of this study was to clarify the role of the renal renin-angiotensin system (RAS) in diabetic nephropathy (DN), which was induced by injection of streptozotocin (STZ). Male CBA/N and CBA/J mice were compared in this study. The former possesses a single renin gene, Ren1, whereas the latter carries two renin genes, Ren1 and Ren2. To examine the molecular dynamics of renal RAS, including renin, angiotensinogen (Agt), angiotensin-converting enzyme (Ace), angiotensin type 1 (Agtr1) and type 2 (Agtr2) receptors in experimental DN, we performed laser-microdissection (LMD) followed by reverse transcriptase nested polymerase chain reaction using each specific primer pairs and immunobistochemistry for renin and angiotensin II. CBA/N mice had a higher response after injection of STZ than CBA/J mice, showing a significant increase of the kidney/body weight ratio, although there was no significant difference between the two strains for the blood glucose level or pancreatic beta-cell response. The onset of renal pathological changes associated with DN was earlier and more severe in CBA/N mice than in CBA/J mice. Distinct immunoreactivities for renin and angiotensin H were newly distributed on the flattened epithelial cells in the dilated distal tubules in the cortex as well as the collecting ducts in the cortex and medulla, and were demonstrated more intensely in CBA/N mice than in CBA/J mice. Micro-dissectional analysis in both DN models revealed a higher incidence of RAS-related gene expression in CBA/J, Ren 1 Ren 2 mice than in CBA/N, Ren 1 mice.
  • T Shimizu, T Oishi, A Omori, A Sugiura, K Hirota, H Aoyama, T Saito, T Sugaya, Y Kon, JD Engel, A Fukamizu, K Tanimoto
    MOLECULAR AND CELLULAR BIOLOGY 25 8 2938 - 2945 2005年04月 [査読有り][通常論文]
     
    The function of putative regulatory sequences identified in cell transfection experiments can be elucidated only through in vivo experimentation. However, studies of gene regulation in transgenic mice (TgM) are often compromised by the position effects, in which independent transgene insertions differ in expression depending on their location in the genome. In order to overcome such a dilemma, a method called transgene coplacement has been developed in Drosophila melanogaster. In this method, any two sequences can be positioned at exactly the same genomic site by making use of Cre/loxP recombination. Here we applied this method to mouse genetics to characterize the function of direct repeat (DR) sequences in the promoter of the human angiotensinogen (hAGT) gene, the precursor of the vasoactive octapeptide angiotensin II. We modified a hAGT bacterial artificial chromosome to use Cre/loxP recombination in utero to generate TgM lines bearing a wildtype or a mutant promoter-driven hAGT locus integrated at a single chromosomal position. The expression analyses revealed that DR sequences contribute 50 or > 95% to hAGT transcription in the liver and kidneys, respectively, whereas same sequences are not required in the heart and brain. This is the first in vivo dissection of DNA cis elements that are demonstrably indispensable for regulating both the level and cell type specificity of hAGT gene transcription.
  • T Nakamura, A Asano, S Okano, JH Ko, Y Kon, T Watanabe, T Agui
    JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 25 3 169 - 173 2005年03月 [査読無し][通常論文]
     
    Mx is an interferon (IFN)-induced protein that shows antiviral activities against RNA viruses. We examined an expression of mRNA, an intracellular localization of protein, and an antiviral property of canine Mx1 and Mx2. Both Mx1 and Mx2 mRNAs were induced in a canine kidney cell line Madin-Darby canine kidney (MDCK), stimulated with an IFN-inducer, poly(I) (.) poly(C) for 12 h, suggesting the presence of regulatory mechanisms consistent with Mx genes in other species. By immunostaining BALB/3T3 fibroblasts transiently transfected FLAG epitope-tagged canine Mx1 and Mx2 cDNAs with an anti-FLAG tag, it was revealed that both Mx1 and Mx2 proteins are localized in cytoplasm. BALB/3T3 fibroblasts expressing stably Mx2 but not Mx1 had an antiviral activity against recombinant vesicular stomatitis virus (VSV). This is the first report demonstrating the functional analysis of canine Mx proteins.
  • Y Namiki, Y Kon, K Kazusa, A Asano, N Sasaki, T Agui
    MAMMALIAN GENOME 16 2 96 - 102 2005年02月 [査読無し][通常論文]
     
    The MRL/MpJ mouse has previously been reported to possess an interesting phenotype in which spermatocytes are resistant to the abdominal temperature heat shock. In this study genetic analysis for it was performed. The phenotypes of F-2 progenies produced by mating MRL/MpJ and control strain C57BL/6 mice were not segregated into two types as parental phenotypes, suggesting that the phenotype is controlled by multiple genetic loci. Thus, quantitative trait loci (QTL) analysis was performed using 98 microsatellite markers. The weight ratio of the cryptorchid testis to the intact testis (testis weight ratio) and the Sertoli cell index were used for quantitative traits. QTL analysis revealed two significant QTLs located on Chrs 1 and 11 for testis weight ratio and one significant QTL located in the same region of Chr 1 for the Sertoli cell index. A microsatellite marker locus located in the peak of the QTL on Chr 1 did not recombine with the exonuclease 1 (Exo1) gene locus in 140 F-2 progenies. Mutation of the Exo1 gene was previously reported to be responsible for metaphase-specific apoptosis (MSA) of spermatocytes in the MRL/MpJ mouse. These results raise the possibility that mutation of the Exo1 gene is responsible for both MSA and heat stress resistance of spermatocytes in the MRL/MpJ mouse.
  • S Okano, A Asano, N Sasaki, Y Kon, T Watanabe, T Agui
    JAPANESE JOURNAL OF VETERINARY RESEARCH 52 4 145 - 149 2005年02月 [査読無し][通常論文]
     
    The CKH-Jsr (jumbled spine and ribs) mouse was found as a spontaneous mutant with malformation of vertebrae, that is, a short trunk and kinky tail. We examined Lunatic Fringe (Lfng) and Uncx4.1 expression in the presomitic mesoderm (PSM) and somites of Jsr-mutant (CKH-Jsr/+) embryos to elucidate pathogenesis of the Jsr mutation. Expression pattern of Lfng in the PSM of Jsr-mutant embryos was similar to that of the normal (C57BL/6) embryos. However, expression pattern of Uncx4.1 in the somites of Jsr-mutant embryos was impaired to be irregular and mosaic, suggesting that the anterior-posterior (A-P) polarity is disordered in the Jsr mutant. These results indicate that the Jsr mutation disrupts the A-P polarity of somites during the somitogenesis without altering Lfng expression pattern in the PSM.
  • D Endoh, T Mizutani, R Kirisawa, Y Maki, H Saito, Y Kon, S Morikawa, M Hayashi
    NUCLEIC ACIDS RESEARCH 33 6 e65  2005年 [査読無し][通常論文]
     
    A method for the isolation of genomic fragments of RNA virus based on cDNA representational difference analysis (cDNA RDA) was developed. cDNA RDA has been applied for the subtraction of poly(A)(+) RNAs but not for poly(A)(-) RNAs, such as RNA virus genomes, owing to the vast quantity of ribosomal RNAs. We constructed primers for inefficient reverse transcription of ribosomal sequences based on the distribution analysis of hexanucleotide patterns in ribosomal RNA. The analysis revealed that distributions of hexanucleotide patterns in ribosomal RNA and virus genome were different. We constructed 96 hexanucleotides (non-ribosomal hexanucleotides) and used them as mixed primers for reverse transcription of cDNA RDA. A synchronous analysis of hexanucleotide patterns in known viral sequences showed that all the known genomic-size viral sequences include non-ribosomal hexanucleotides. In a model experiment, when non-ribosomal hexanucleotides were used as primers, in vitro transcribed plasmid RNA was efficiently reverse transcribed when compared with ribosomal RNA of rat cells. Using non-ribosomal primers, the cDNA fragments of severe acute respiratory syndrome coronavirus and bovine parainfluenza virus 3 were efficiently amplified by subtracting the cDNA amplicons derived from uninfected cells from those that were derived from virus-infected cells. The results suggest that cDNA RDA with non-ribosomal primers can be used for species-independent detection of viruses, including new viruses.
  • Transgenic co-placement strategy reveals a cell-type dependent role for direct repeat sequences in human angiotensinogen gene transcription in BAC transgenic mice.
    Mol. Cell. Biol. 25 8 2938 - 2945 2005年 [査読無し][通常論文]
  • 妊娠高血圧モデルマウスを用いたAT1a受容体の機能解析
    斉藤 知子, 石田 純治, 大西 英理子[瀧本], 菅谷 健, 加藤 秀樹, 松岡 俊樹, 南岳 正臣, 昆 泰寛, 八神 健一, 深水 昭吉
    血管 28 1 16 - 16 日本心脈管作動物質学会 2005年01月 [査読有り][通常論文]
  • O Inanami, D Iizuka, A Iwahara, T Yamamori, Y Kon, T Asanuma, A Matsuda, Kashiwakura, I, K Kitazato, M Kuwabara
    RADIATION RESEARCH 162 6 635 - 645 2004年12月 [査読無し][通常論文]
     
    1-(3-C-Ethynyl-beta-(D)-ribo-pentofuranosyl)cytosine (ECyd, TAS106) is a newly developed anti-tumor agent that targets RNA synthesis. We report here that a low dose of ECyd induces radiosensitization of caspase-dependent apoptosis and reproductive cell death in cells of the gastric tumor cell lines MKN45 and MKN28 and murine rectum adenocarcinoma Colon26. Flow cytometry demonstrated that TAS106 induced the abrogation of the X-ray-induced G2/M checkpoint. Western blot analysis showed that X rays increased the expression of cyclin B1, phospho-Cdc2 and Weel, whereas co-treatment with X rays and TAS106 decreased the expression of these cell cycle proteins associated with the G2/M checkpoint. Furthermore, TAS106 was shown to decrease the radiation-induced expression of survivin but not Bcl2 and BcIX(1) regardless of TP53 status and cell type. Overexpression of wild-type survivin in MKN45 cells inhibited the induction of apoptosis induced by co-treatment with X rays and TASI06. These results suggest that TAS106 enhances X-ray-induced cell death through down-regulation of survivin and abrogation of the cell cycle machinery. (C) 2004 by Radiation Research Society.
  • M Hayashi, K Miyane, T Hirooka, D Endoh, H Higuchi, H Nagahata, K Nakayama, Y Kon, T Okui
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1674 3 312 - 318 2004年11月 [査読無し][通常論文]
     
    Effects of treatment with trientine, a specific copper-chelating agent, on accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the livers of LEC rats in an age-dependent manner from 4 to 13 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, hepatic copper contents did not increase and were maintained at the same levels as those in 10-week-old LEC rats. When the amounts of DNA single-strand breaks (SSBs) were estimated by a comet assay, SSBs of DNA were induced in a substantial population of LEC rat hepatic cells around 8 weeks of age and the amounts of SSBs increased in an age-dependent manner from 8 to 15 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased dramatically, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that treatment of LEC rats with trientine decreases the number of DNA strand breaks observed, although copper contents remain high in the liver. (C) 2004 Elsevier B.V All rights reserved.
  • Y Hashimoto, Y Sadamoto, A Konno, Y Kon, T Iwanaga
    JAPANESE JOURNAL OF VETERINARY RESEARCH 52 3 113 - 124 2004年11月 [査読有り][通常論文]
     
    dDistribution of ASCT 1, a neutral amino acid transporter, in non-neuronal peripheral tissues of adult and developing mice was examined by immunohistochemistry and immunoelectron microscopy. Immunoreactivity for ASCT I in the digestive system was localized in basal cells of stratified squamous epithelia from oral parietes to nonglandular region of the stomach, chief cells of the glandular stomach, acinar cells of the salivary gland and exocrine pancreas, and Paneth's cells of the small intestine, in all of which the basolateral membrane was selectively immuno-labeled. In the liver of adult mice, ASCT I immunoreactivity was detected on the plasma membrane of hepatocytes surrounding central veins, and a temporal expansion of immunoreactive hepatocytes was observed in the embryonic and CCl4-treated adult livers. ASCT 1 was also localized on the plasma membranes of proximal uriniferous tubule epithelial cells in the kidney of adult mice, and those of supporting cells in the medulla of adrenal gland. These results suggest that ASCT1 is expressed in various non-neuronal peripheral tissues in mice, and it contributes to the amino acid transport throughout non-neuronal tissues.
  • A Konno, Y Oota, Y Hashimoto, Y Kon, T Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 25 4 195 - 200 2004年08月 [査読無し][通常論文]
     
    The non-essential amino acid L-serine is biosynthesized from 3-phosphoglycerate by astrocytes, and functions as a key mediator of neurotrophic support in the brain. In the present study, the cellular localization of 3-phosphoglycerate dehydrogenase (3PGDH), a key enzyme in L-serine production, in tissue outside the central nervous system of the mouse was examined by immunohistochemistry and in situ hybridization. In the peripheral nervous system of adult mice, 3PGDH immunoreactivity was found in satellite cells of the dorsal root ganglia and intestinal nerve plexuses. Endocrine tissues contained 3PGDH-immunoreactive supporting cells, such as stellate cells of the adenohypophysis and sustentacular cells of the adrenal medulla. In genital tissues, Sertoli cells and spermatogonia of the testis and oocytes in the primary ovarian follicle were immuno-labeled with the 3PGDH antibody. The lens epithelium and retinal pigment epithelium were most intensely immunoreactive among sensory organs. The expression of 3PGDH mRNA in the eye and testis was detected by in situ hybridization in cells corresponding to those in which it was detected by immunohistochemistry. Moreover, 3PGDH immunoreactivity was confirmed in the lens placode and in both the Sertoli and primitive germ cells of embryos, all of which are tissues affected by congenital diseases in human 3PGDH deficiency.
  • J Nio, W Fujimoto, A Konno, Y Kon, M Owhashi, T Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY 121 6 473 - 482 2004年06月 [査読無し][通常論文]
     
    Ym is one of the chitinase family proteins, which are widely distributed in mammalian bodies and can bind glycosaminoglycans such as heparin/heparan sulfate. Ym1 is a macrophage protein produced in parasitic infections, while its isoform, Ym2, is upregulated in lung under allergic conditions. In the present study, we revealed the distinct cellular expression of Ym1 and Ym2 in normal mice by in situ hybridization and immunohistochemistry. Ym1 was principally expressed in the lung, spleen, and bone marrow, while Ym2 was found in the stomach. Ym1-expressing cells in the lung were alveolar macrophages, and the immunoreactivity for Ym1 was localized in rough endoplasmic reticulum. In the spleen, Ym1-expressing cells gathered in the red pulp and were electron microscopically identified as immature neutrophils. In the bone marrow, immature neutrophils were intensely immunoreactive, but lost this immunoreactivity with maturation. Moreover, needle-shaped crystals in the cytoplasm of macrophages, which formed erythroblastic islands, also showed intense Ym1 immunoreactivity. Ym2 expression was restricted to the stratified squamous epithelium in the junctional region between forestomach and glandular stomach. The function of Ym1 and Ym2 is still unclear; however, the distinct cellular localization under normal conditions suggests their important roles in hematopoiesis, tissue remodeling, or immune responses as an endogenous lectin.
  • Tilladit Rung-Ruangkijkrai, Daisuke Fujikura, Yasuhiro Kon, Toshihiko Iwanaga
    Biomedical Research 25 3 155 - 164 2004年06月 [査読無し][通常論文]
     
    Src-suppressed C kinase substrate (SSeCKS) is expressed in a variety of cells and plays an important role in cell differentiation, migration and shaping via remodeling of the actin-based cytoskeleton. In the present study, the cellular distribution of SSeCKS was studied in the peripheral nervous system and sensory organs of mice by in situ hybridization and immunohistochemistry. In the dorsal root ganglia and trigeminal ganglia, small- and medium-sized neurons expressed SSeCKS, whereas large-sized neurons showed negative or faintly positive reactions. Definite positive signals of SSeCKS mRNA and protein in the sensory ganglia were also found in some satellite cells which frequently enveloped ganglion cells without SSeCKS expression. In autonomic ganglia (celiac ganglia, pelvic ganglia, and intestinal myenteric nerve plexus), SSeCKS immunoreactivity was confined to satellite cells, and not detectable in neuronal somata. No significant immunoreactivity for SSeCKS appeared in most sensory organs, including the retina, organ of Corti, taste buds, and olfactory mucosa. In contrast, the vomeronasal organ displayed intense and selective expression of SSeCKS in the sensory epithelium, where only supporting cells were immunolabeled. SSeCKS-immunoreactive Schwann cells were widely distributed in nerve bundles including the vomeronasal nerve, olfactory nerve, and dorsal root. These findings suggest that SSeCKS might be involved in regulation and homeostasis of the peripheral nervous system and of the vomeronasal organ among sensory organs. Copyright © 2005 Biomedical Research Press.
  • T Asanuma, O Inanami, K Tabu, K Waki, Y Kon, M Kuwabara
    NEUROSCIENCE LETTERS 359 1-2 57 - 60 2004年04月 [査読無し][通常論文]
     
    The present experiments were carried out to provide direct in vivo evidence for the involvement of c-Jun N-terminal kinase (JNK) in the induction of ischemic brain injury. Malonate, which produces lesions similar to those of focal ischemia-reperfusion by a reversible inhibition of succinate dehydrogenase in mitochondria, was injected into the left striatum in the rat brain without or with the simultaneous injection of a cell permeable peptidic JNK inhibitor, (L)-HIV-TAT(48-57)-PP-JP-JBD(20). Two regions of malonate-induced brain injury were visualized as a hyperintense region with surrounding hypointense regions by apparent diffusion coefficient mapping magnetic resonance imaging. The INK inhibitor significantly counteracted both hyper- and hypointense regions at the early stage of brain injury. Histological examination clarified that the inhibitor suppressed the induction of coagulation necrosis and spongy degeneration at early and late stages. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
  • Kazusa K, Namiki Y, Asano A, Kon Y, Endoh D, Agui T
    Comparative medicine 54 2 179 - 184 2004年04月 [査読有り][通常論文]
  • JH Ko, A Asano, Y Kon, T Watanabe, T Agui
    JAPANESE JOURNAL OF VETERINARY RESEARCH 51 3-4 123 - 133 2004年02月 [査読無し][通常論文]
     
    The double-stranded RNA-dependent protein kinase (PKR) is induced in mouse and human cells on treatment with interferon. In this study, we have cloned and determined the nucleotide sequences of chicken PKR cDNA in various chicken breeds. Chicken PKR was a 550 - amino-acid protein as deduced from the cDNA open reading frame (ORF), and there were specific domains (two double-stranded RNA binding domains (DRBDs) and numerous kinase subdomains) characterized in RNA binding proteins and kinase families. Furthermore, it was suggested that chicken PKR was polymorphic. Transfected cell clones expressing chicken PKR mRNA were demonstrated to confer antiviral responses to vesicular stomatitis virus, except for Koshamo type - 3 (KS - 3). KS - 3 PKR, which has an amino acid substitution at position 507 (Arg to Gln), showed amphibious antiviral responses. This specific amino acid substitution was considered to determine the antiviral function of chicken PKR in addition to essential domains as DRBDs and kinase subdomains.
  • Tomoko Saito, Junji Ishida, Eriko Takimoto-Ohnishi, Shoko Takamine, Taku Shimizu, Takeshi Sugaya, Hideki Kato, Toshiki Matsuoka, Masaomi Nangaku, Yasuhiro Kon, Fumihiro Sugiyama, Ken-ichi Yagami, Akiyoshi Fukamizu
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 2 388 - 90 2004年02月 [査読有り][通常論文]
     
    Little is known about an in vivo significance of angiotensin II Type-1 receptor (AT1) for pregnancy-associated diseases, including hypertension and intrauterine growth retardation (IUGR). We previously demonstrated that female mice carrying the human angiotensinogen gene (hAG+/+), when mated with human renin transgenic (hRN+/+) male mice, displayed hypertension in late pregnancy due to secretion of human renin from the fetal side into the maternal circulation. In the present study, to investigate a role for AT1 in pregnancy-associated hypertension, we generated a new strain of hAG+/+/mAT1a-/- mice by genetically deleting the AT1a gene from hAG+/+ mice. When mated with hRN+/+ male mice, excessive increases in human renin, angiotensin, and plasma renin activity were detected in the plasma of pregnant hAG+/+/mAT1a-/- mice as found in that of pregnant hAG+/+ mice. Surprisingly, however, blood pressure of hAG+/+/mAT1a-/- mice was not elevated in late pregnancy despite the presence of AT1b, a subtype of AT1. The maternal and fetal defects, such as cardiac and placental abnormalities, and IUGR observed in pregnant hypertensive hAG+/+ mice were not recognized in pregnant hAG+/+/mAT1a-/- mice. The limited term administration of AT1 antagonists to hypertensive hAG+/+ mice in late pregnancy dramatically improved hypertension and IUGR, showing the clinical importance of AT1a.
  • Strain difference of spermatogenesis in cryptorchid testis in mice.
    Comp. Med. 54 2 179 - 184 2004年 [査読無し][通常論文]
  • Hashimoto, Y., Sadamoto, Y., Konno, A., Kon, Y. and Iwanaga, T. : Distribution of neutral amino acid transporter ASCT1 in the non-neuronal tissues of mice. Jpn. J. Vet. Res., 52(3), 113-124.*
    2004年 [査読無し][通常論文]
  • Namiki, Y., Kon, Y., Sasaki, N., Agui, T. and Endoh, D. : Exon skipping of exonuclease 1 in MRL/MpJ mice is caused by a nucleotide substitution of the branchpoint sequence in intron eight. Jpn. J. Vet. Res., 52(3), 125-134.*
    2004年 [査読無し][通常論文]
  • Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. : An essential role for angiotensin II type 1a receptor in pregnancy-associated h・・・
    2004年 [査読無し][通常論文]
     
    Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. : An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J., 18(2), 388-90.*
  • Asano, A., Kon, Y. and Agui, T. : The mRNA regulation of porcine double-stranded RNA-activated protein kinase gene. J. Vet. Med. Sci., 66(12), 1523-1528.*
    2004年 [査読無し][通常論文]
  • Okamura Tadashi, Miyoshi Ichiro, Takahashi Kazuhiro, Mototani Yasumasa, Ishigaki Sadao, Kon Yasuhiro, Kasai Noriyuki
    Genomics 81 4 361 - 368 2003年04月 [査読有り][通常論文]
  • S Taharaguchi, Y Kon, S Yoshino, E Ono
    VIROLOGY 307 2 243 - 254 2003年03月 [査読無し][通常論文]
     
    Pseudorabies virus (PRV) infection in animals other than its natural host almost always gives rise to fatal diseases in the central nervous system as a result of infection of peripheral neurons and subsequently to the brain. PRV immediate-early protein (IE180) activates transcription of the PRV early and late genes, and other viral and cellular genes, and represses its own transcription. To examine specific effects of IE180 in neuropathogenicity, we have generated four transgenic mouse lines expressing 1E1 80 in a tetracycline-regulated system. In the transgenic mouse lines, cerebellar symptoms such as ataxic gait, tremor and motor discoordination were observed. Histopathology of the cerebella in the transgenic mouse lines showing severe symptoms was remarkable for a failure of layer formation and a reduction in cerebellar size. These findings suggest that IE180 affects the cascade of gene expression for development of the murine cerebellum, resulting in the impairment of the cerebellar development and differentiation. (C) 2003 Elsevier Science (USA). All rights reserved.
  • Kariwa, H., Tanabe, H., Mizutani, T., Kon, Y., Lokugamage, K., Lokugamage, N., Iwasa, M. A., Hagiya, T., Araki, K., Yoshimatsu, K., Arikawa, J. and Takashima, I. (2003): Synthesis of Seoul virus RNA and structural proteins in cultured cells. Arch. Viro・・・
    2003年 [査読無し][通常論文]
     
    Kariwa, H., Tanabe, H., Mizutani, T., Kon, Y., Lokugamage, K., Lokugamage, N., Iwasa, M. A., Hagiya, T., Araki, K., Yoshimatsu, K., Arikawa, J. and Takashima, I. (2003): Synthesis of Seoul virus RNA and structural proteins in cultured cells. Arch. Virol., 148, 1671-1685.*
  • Namiki, Y., Endoh, D. and Kon, Y. (2003): Genetic mutation associated with meiotic metaphase-specific apoptosis in MRL/MpJ mice. Mol. Reprod. Dev., 64, 179-188.*
    2003年 [査読無し][通常論文]
  • Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. (2003): An essential role for angiotensin II type 1a receptor in pregnancy-associ・・・
    2003年 [査読無し][通常論文]
     
    Saito, T., Ishida, J., Takimoto-Ohnishi, E., Takamine, S., Shimizu, K., Sugaya, T., Kato, H., Matsuoka T., Nangaku, M., Kon, Y., Sugiyama, F., Yagami, K. and Fukamizu, A. (2003): An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J., (on line).*
  • Okamura, T., Miyoshi, I., Takahashi, K., Mototani, Y., Ishigaki, S., Kon, Y. and Kasai, N. (2003): Bilateral congenital cataracts results from a gain-of-function mutation in the gene for aquaporin-0 in mice. Genomics, 81(4), 361-368.*
    2003年 [査読無し][通常論文]
  • Yasuhiro Kon, Yuka Namiki, Daiji Endoh
    Japanese Journal of Veterinary Research 50 2-3 115 - 123 2002年11月 [査読有り][通常論文]
     
    Nitric oxide (NO) is a simple and relatively unstable radical under physiological conditions. It is synthesized by three isoforms of NO synthase, that is neuronal, endothelial and inducible (iNOS) isoforms. In the present study, we investigated the distribution of iNOS with immunohistochemical methods in the mouse testis. The iNOS-immunoreactivity was detected on the basal region of the seminiferous tubules, where the cytoplasm of Sertoli cells was selectively immunolabeled. This immunoreactivity was observed by both immunofluorescent and immunoenzyme methods. Weak immunoreactivity was detected on the perinuclear cytoplasm of Sertoli cells throughout the seminiferous stages, whereas in stages I-VIII, it was remarkable on the processes of Sertoli cells surrounding the spermatogonia and early spermatocytes, and elongating into the lumina of seminiferous tubules. By reverse transcriptase-polymerase chain reaction, mRNA for iNOS was found to be expressed in the mouse testis. These results reveal that iNOS is consistently distributed at the front of the testicular environment.
  • Miyoshi, I, K Takahashi, Y Kon, T Okamura, Y Mototani, Y Araki, N Kasai
    MOLECULAR REPRODUCTION AND DEVELOPMENT 63 2 168 - 176 2002年10月 [査読無し][通常論文]
     
    Miyoshi, I., Takahashi, K., Kon, Y., Okamura, T., Mototani, Y., Araki, Y. and Kasai, N. (2002): "Mouse transgenic for murine oviduct-specific glycoprotein promoter-driven Simian Virus 40 large-T antigen: Tumor formation and its hormonal regulation." Mol. Reprod. Dev., 63, 168-176.*
  • S Okano, A Asano, Y Kon, H Miyoshi, T Watanabe
    BIOCHEMICAL GENETICS 40 9-10 311 - 322 2002年10月 [査読有り][通常論文]
     
    The jumbled spine and ribs (Jsr) mouse was derived from a spontaneous mutation. As the phenotype, a shortened trunk and kinky tail are characteristic Jsr traits. In this study, on high resolution mapping it was found that Lunatic fringe (Lfng) mapped at the same position as Jsr. Lfng was identified as the candidate gene for Jsr, but sequence analysis of this gene revealed no substitution in the coding region of cDNA. Therefore, we adopted the strategy of positional cloning for Jsr using a mouse bacterial artificial chromosome (BAC) library. A BAC contig was constructed from three BAC clones showing positive signals of Lfng and 11MMHAP75FRD8.seq near the Jsr locus on chromosome 5. Based on the genetic mapping of both T7 and sp6 ends of a clone of BAC382-O-7 (BAC382), the Jsr gene was considered to exist in BAC382 and to be positioned near the sp6 side.
  • T Asanuma, H Ishibashi, A Konno, Y Kon, O Inanami, M Kuwabara
    NEUROSCIENCE LETTERS 329 3 281 - 284 2002年09月 [査読有り][通常論文]
     
    Ischemic brain injury induced by injection of 3-mumol malonate into the left striatum of male Sprague-Dawley rats was examined by apparent water diffusion coefficient (ADC) mapping of magnetic resonance imaging. The region surrounding the injection core was imaged as a hypointense area in ADC mapping and ADC values in the regions were significantly decreased 3 and 6 h after ischemia. Significant reduction of the hypointense area and the recovery of ADC values were observed in rats to which alpha-phenyl-N-tert-butylnitrone (PBN) was intraperitoneally administered 1 h before ischemia. Since ADC mapping has been reported to be a suitable method for evaluating the extent and the degree of cytotoxic edema in the early period after the onset of ischemia, the present results prove that PBN is able to prevent early ischemic insults such as cytotoxic edema. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • Endoh D, Okui T, Ozawa S, Yamato O, Kon Y, Arikawa J, Hayashi M
    The Journal of veterinary medical science / the Japanese Society of Veterinary Science 64 9 761 - 765 9 2002年09月 [査読有り][通常論文]
  • G Kitamura, T Ohta, T Kai, Y Kon, S Ito
    BRAIN RESEARCH 942 1-2 11 - 22 2002年06月 [査読無し][通常論文]
     
    The inhibitory effects of opioids on voltage-dependent calcium channels (VDCCs) were investigated in cultured porcine adrenal chromaffin cells using whole-cell patch clamp technique. The effects of the opioid on [Ca2+], increase and catecholamine secretion induced by high K+ were also examined in single cells by fura-2 micro fluorimetry and amperometry. A depolarizing pulse to 0 mV (test pulse) from a holding potential of -80 mV evoked an inward barium current (I-Ba), which was reversibly inhibited by methionine-enkephalin. This inhibitory effect of methionine-enkephalin was abolished by naloxone. Selective agonists of opioid receptor subtypes (DAMGO: mu, DPDPE: 8, U50488: kappa) dose-dependently inhibited I-Ba. In inhibitory potency, the order was DAMGO>U50488>DPDPE. These agonists applied sequentially produced a reversible I-Ba inhibition in the same cells. The inhibitory effect of DAMGO on I-Ba almost disappeared in the presence of omega-conotoxin GVIA but not omega-agatoxin IVA plus nifedipine. Application of a conditioning prepulse to + 100 mV prior to the test pulse partly retrieved the I-Ba inhibition by DAMGO, suggesting the involvement of voltage-sensitive components in opioid-induced VDCC inhibition. Intracellular application of GDPbetaS or GTP-gammaS as well as pretreatment with pertussis toxin significantly reduced the extent of I-Ba inhibition induced by DAMGO. DAMGO reversibly inhibited the [Ca2+], increase and catecholamine release induced by high K+. RT-PCR revealed the expression of mu-, delta- and K-Opioid receptor mRNAs in cultured adrenal chromaffin cells. These results suggest that porcine adrenal chromaffin cells possess mu-, delta- and kappa-opioid receptors and activation of Opioid receptors mainly inhibits N-type VDCCs via pertussis toxin-sensitive G-proteins. (C) 2002 Elsevier Science B.V. All rights reserved.
  • T Okui, D Endoh, Y Kon, M Hayashi
    RADIATION RESEARCH 157 5 553 - 561 2002年05月 [査読有り][通常論文]
     
    The DNA-dependent protein kinase (DNA-PK) complex has been implicated in the repair of DNA double-strand breaks (DSBs). DNA-PK is a heterotrimeric protein complex comprised of two components: a large catalytic subunit, Prkdc, with serine/threonine kinase activity and a DNA-targeting component, G22p1 and Xrcc5. In previous report, we showed that approximately 80% of the G22p1 and Xrcc5 proteins were observed in the cytoplasm of rat fibroblasts, and that nuclear translocation of the proteins from the cytoplasm is important for the repair of DNA DSBs. In the present study, we showed that nuclear accumulation of the G22p1 and Xrcc5 proteins was not observed in fibroblasts from a mutant strain of Long-Evans Cinnamon (LEC) rat that has an enhanced radiosensitivity and a reduced level of repair of DSBs after X irradiation. Nuclear translocation of the proteins was observed in both LEC rat cells and control rat cells with normal radiosensitivity at 5 min after X irradiation. Although high levels of G22p1 and Xrcc5 proteins were observed in the nuclei of control rat cells until 60 min postirradiation, the amounts of the proteins decreased rapidly in the nuclei of LEC rat cells in the first 10 min after X irradiation. These findings suggest that there are some defects in maintaining the levels of G22p1 and Xrcc5 proteins in the nuclei of LEC rat cells. An analysis of fibroblasts from backcross rats showed that the deficiency in nuclear accumulation of G22p1 and Xrcc5 proteins is genetically linked to enhanced radiosensitivity. Since the nucleotide sequences of the G22p1 and Xrcc5 genes of the LEC rats coincided with those of the control rats, the deficiency in nuclear accumulation may not be caused by mutations of the G22p1 and Xrcc5 proteins. (C) 2002 by Radiation Research Society.
  • Asanuma, T., Ishibashi, H., Konno, A., Kon, Y., Inanami, O. and Kuwabara, M. (2002): "Assessment of neuroprotective ability of a spin trap, a-phenyl-N-tert-butylnitrone, against malonate-induced ischemic injury of rat brain by apparent water diffusion ・・・
    2002年 [査読無し][通常論文]
     
    Asanuma, T., Ishibashi, H., Konno, A., Kon, Y., Inanami, O. and Kuwabara, M. (2002): "Assessment of neuroprotective ability of a spin trap, a-phenyl-N-tert-butylnitrone, against malonate-induced ischemic injury of rat brain by apparent water diffusion coefficient mapping. Neurosci." Lett., 329, 281-284.*
  • Kon, Y., Namiki, Y. and Endoh, D. (2002): "Expression and distribution of inducible nitric oxide synthase in mouse testis." Jpn. J. Vet. Res., 50(2-3).*
    2002年 [査読無し][通常論文]
  • K Mori, Y Kon, A Konno, T Iwanaga
    ARCHIVES OF HISTOLOGY AND CYTOLOGY 64 3 319 - 327 2001年08月 [査読無し][通常論文]
     
    Mori, K., Kon, Y., Konno, A. and Iwanaga, T.: "Cellular Distribution of Napsin (Kidney-derived Aspartic Protease-like Protein, KAP) mRNA in the Kidney, Lung and Lymphatic Organs of Adult and Developing Mice", Archaevs Histology and Cytology,64:319-327(2001)*
  • J Ohuchi, T Arai, Y Kon, A Asano, H Yamauchi, T Watanabe
    MOLECULAR REPRODUCTION AND DEVELOPMENT 59 4 350 - 358 2001年08月 [査読有り][通常論文]
     
    During mammalian spermatogenesis, many specific molecules show the dynamics of expression and elimination, corresponding with the morphological differentiation of germ cells. We have isolated a novel cDNA designated F77 from mouse testis by cDNA subtractive hybridization between normal and sterile mice, using the C57BL/6 congenic strain for the hybrid sterility-3 (Hst-3) allele from Mus spretus. The full-length F77 mRNA was 3.4 kb and showed significant nonmatching with entries in the databases. F77 was mapped at a proximal position between D8Mit212 and D8Mit138 on mouse chromosome 8, in which no corresponding genes related to its nucleotide sequence were found. F77 mRNA was not detected in any other organs except the testis of adult fertile mice. F77 protein was only seen in normal adult testis and epididymis. in contrast to normal C57BL/6 mice, F77 mRNA and protein were not seen in germ cell-deficient Kit(W)/Kit(Wv) mice. By in situ hybridization, F77 mRNA was detected mainly at round spermatids in the sexually mature testis, and immunohistochemical analysis revealed that F77 protein was located at the tail of elongated spermatids. We are proposing the name, sperm-tail-associated protein (Stap), for the gene encoding F77 cDNA. (C) 2001 Wiley-Liss, Inc.
  • Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning
    Takayoshi Kiba, Satoru Saito, Kazushi Numata, Yasuhiro Kon, Tetsuya Mizutani, Hisahiko Sekihara
    Am J Physiol Gastrointest Liver Physiol. 280 5 G958 - 967 2001年05月 [査読無し][通常論文]
  • D Endoh, T Okui, Y Kon, M Hayashi
    RADIATION RESEARCH 155 2 320 - 327 2001年02月 [査読有り][通常論文]
     
    The effects of X irradiation and hypertonic treatment with 0.5 M NaCl on the subcellular localization of the Ku proteins G22p1 (also known as Kn70) and Xrcc5 (also known as Ku80) in rat fibroblasts with normal radiosensitivity were examined using confocal laser microscopy and immunoblotting, Although these proteins were observed mainly in the nuclei of human fibroblasts, approximately 80% of the intensities of immunofluorescence from both G22p1 and Xrcc5 was observed in the cytoplasm of rat fibroblasts. When the rat cells were X-irradiated with 4 Gy, the intensities of the fluorescence derived from G22p1 and Xrcc5 in the nuclei increased from 20% to 50% of the total cellular fluorescence intensity at 20 min postirradiation, No significant differences were observed between the total intensities of the cellular fluorescence from the proteins in unirradiated and irradiated rat fibroblasts. The results showed that the proteins were translocated from the cytoplasm to the nucleus in the rat cells after X irradiation. The nuclear translocation of the proteins from the cytoplasm was inhibited by hypertonic treatment of the cells with 0.5 M NaCl for 20 min, which inhibits the fast repair process of potentially lethal damage (PLD). When the rat cells were treated with 0.5 M NaCl immediately after X irradiation, the repair of DNA DSBs was inhibited, The surviving fraction was approximately 60% of that of irradiated cells that were not treated with 0.5 M NaCl. The,surviving fraction increased with incubation time in the growth medium before treatment with NaCl, The proportions of the intensities of fluorescence from G22p1 in the nuclei of X-irradiated cells also increased from 20% to 50% with increasing interval between X irradiation and treatment with Nad; These results suggest that nuclear translocation of G22p1 and Xrcc5 is important for the fast repair process of PLD in rat cells. (C) 2001 by Radiation Research Society.
  • Y Kon, D Endoh
    MOLECULAR REPRODUCTION AND DEVELOPMENT 58 2 216 - 222 2001年02月 [査読有り][通常論文]
     
    Cryptorchidism is commonly used for research on spermatogenesis. However, there are few comparative investigations about the strain differences in mice, especially in long-term experiments. In the present study, the authors demonstrate its specific dynamics in the MRL/MpJ mouse strain, and discuss the cause of strain differences. In the mouse strains A/J BALB/c, C3H/He, and C57BL/6, after 2 weeks of experimental cryptorchidism, the ratios of the cryptorchid testis weight against; the intact one were 0.38 +/- 0.05, 0.43 +/- 0.05, 0.38 +/- 0.02, and 0.44 +/- 0.14, respectively. On the other hand, in the MRL/MpJ strain it was shifted to 0.69 +/- 0.08. The details of this strain difference were compared by calculation of germ cells with the Sertoli cell index at 2 weeks after operation. The indices of spermatogonia in all strains were not significantly different; however, in MRL/MpJ mice remarkable numbers of late spermatocytes and round spermatids were detected. The decrease of the testis weight ratio was similar until 10 days in the C57BL/6 and MRL/MpJ strains, but continued in C57BL/6 until 21 days, whereas in MRL/MpJ mice it plateaued after 10 days. Northern blot analysis for heat shock protein 70-2 using total RNA prepared from the cryptorchid and intact testes at 2 weeks after operation revealed that the expression was decreased in the cryptorchid testis of C57BL/6, but not MRL/MpJ mice. The results suggested that heat-resistant germ cells were present in MRL/MpJ, originating possibly from the genetic background. (C) 2001 Wiley-Liss, Inc.
  • I. Miyoshi, K. Maki, Y. Kon, T. Yamashita, S. Aoyama, Y. Hayashizaki, N. Kasai
    Endocrine Research 27 4 387 - 398 2001年 [査読無し][通常論文]
     
    Miyoshi, I., Maki, K., Kon, Y., Yamashita, T., Aoyama, S., Hayashizaki, Y. and Kasai, N.: "Targeting oncogenesis by introduction of a 5.2-Kbp segment of the 5ユ regulatory region of the human thyrotropin b-subunit gene", Endocrine Research,27:387-398(2001)*
  • Asanuma, T., Ohkura, K., Yamamoto, T, Kon, Y., Shimokawa, S. and Kuwabara, M.: "Three-dimensional magnetic resonance imaging of lung and liver tumors in mice by use of transversal multislice magnetic resonance images", Comparative Medicine,51:138-144(2・・・
    2001年 [査読無し][通常論文]
     
    Asanuma, T., Ohkura, K., Yamamoto, T, Kon, Y., Shimokawa, S. and Kuwabara, M.: "Three-dimensional magnetic resonance imaging of lung and liver tumors in mice by use of transversal multislice magnetic resonance images", Comparative Medicine,51:138-144(2001)*
  • Kiba, T., Saito, S., Numata, K., Kon, Y., Mizutani, T. and Sekihara, H.: "Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning", American Journal of Physiology: Gastrointestinal and Liver Physio・・・
    2001年 [査読無し][通常論文]
     
    Kiba, T., Saito, S., Numata, K., Kon, Y., Mizutani, T. and Sekihara, H.: "Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning", American Journal of Physiology: Gastrointestinal and Liver Physiology,280:G958-G967(2001).*
  • D. Endoh, T. Okui, Y. Kon, M. Hayashi
    Radiation Research 155 2 320 - 327 2001年 [査読無し][通常論文]
     
    The effects of X irradiation and hypertonic treatment with 0.5 M NaCl on the subcellular localization of the Ku proteins G22p1 (also known as Ku70) and Xrcc5 (also known as Ku80) in rat fibroblasts with normal radiosensitivity were examined using confocal laser microscopy and immunoblotting. Although these proteins were observed mainly in the nuclei of human fibroblasts, approximately 80% of the intensities of immunofluorescence from both G22p1 and Xrcc5 was observed in the cytoplasm of rat fibroblasts. When the rat cells were X-irradiated with 4 Gy, the intensities of the fluorescence derived from G22p1 and Xrcc5 in the nuclei increased from 20% to 50% of the total cellular fluorescence intensity at 20 min postirradiation. No significant differences were observed between the total intensities of the cellular fluorescence from the proteins in unirradiated and irradiated rat fibroblasts. The results showed that the proteins were translocated from the cytoplasm to the nucleus in the rat cells after X irradiation. The nuclear translocation of the proteins from the cytoplasm was inhibited by hypertonic treatment of the cells with 0.5 M NaCl for 20 min, which inhibits the fast repair process of potentially lethal damage (PLD). When the rat cells were treated with 0.5 M NaCl immediately after X irradiation, the repair of DNA DSBs was inhibited. The surviving fraction was approximately 60% of that of irradiated cells that were not treated with 0.5 M NaCl. The surviving fraction increased with incubation time in the growth medium before treatment with NaCl. The proportions of the intensities of fluorescence from G22p1 in the nuclei of X-irradiated cells also increased from 20% to 50% with increasing interval between X irradiation and treatment with NaCl. These results suggest that nuclear translocation of G22p1 and Xrcc5 is important for the fast repair process of PLD in rat cells. © 2001 by Radiation Research Society.
  • Ohuchi, J., Arai, T., Kon, Y., Asano, A., Yamauchi, H. and Watanabe, T.: "Characterization of a novel gene, sperm-tail-associated protein (Stap), in mouse post-meiotic testicular germ cells", Molelucar Reproduction and Development,59:350-358(2001)*
    2001年 [査読無し][通常論文]
  • Kon, Y. and Endoh, D.: "Heat-shock resistance in experimental cryptorchid testis of mice", Molecular Reproduction and Development, 58:216-222(2001)*
    2001年 [査読無し][通常論文]
  • D Endoh, KO Cho, K Tsukamoto, T Morimura, Y Kon, M Hayashi
    JOURNAL OF CLINICAL MICROBIOLOGY 38 12 4310 - 4314 2000年12月 [査読有り][通常論文]
     
    A rapid and simple method for isolation of DNA fragments of Marek's disease virus (MDV) based on representational difference analysis (RDA) was developed. Multiple viral DNA fragments, the sizes of which were restricted to 0.3 to 3.5 kbp, were simultaneously amplified after subtraction of chicken DNA from BamHI-, BglII-, EcoRI-, HindIII-, or XhoI-digested DNA fragments of MDV-infected cells. Nucleotide sequence of two RDA-derived fragments coincided with the sequence determined from direct sequencing of the MDV genome. We detected an interstrain difference in the size of restriction enzyme-digested fragments on agarose gel. This method was used on a single feather pulp to generate sufficient MDV DNA for cloning.
  • Y Kon, D Endoh
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C 29 5 313 - 319 2000年10月 [査読有り][通常論文]
     
    Apoptosis of male germ cells is a complex phenomenon in many animal species. Understanding its mechanisms could be useful in the diagnosis and therapy of male infertility. To examine the differences of distribution of apoptosis among mouse strains, the terminal transferase-mediated nick end labelling (TUNEL) method was employed. In the testes of MRL mice, many TUNEL-positive cells were identified at the metaphases of meiotic spermatocytes. Morphometrical analysis revealed that metaphase-specific apoptosis occurred at the region between secondary spermatocytes and step I spermatids in stage XII seminiferous tubules. In the investigation of the developing first-wave of seminiferous tubules, there were some metaphases showing apoptotic morphology prior to becoming secondary spermatocytes. Details of the apoptotic structure revealed by electron microscopy showed that cellular arrest occurred after the beginning of the M phase of the cell cycle. These results suggested that metaphase-specific apoptosis in the testis of the MRL mouse strain took place at least at the first meiotic division, perhaps showing the spindle assembly checkpoint of the cell cycle.
  • KW Seo, Y Kon, T Watanabe
    COMPARATIVE MEDICINE 50 1 27 - 31 2000年02月 [査読無し][通常論文]
     
    Background and Purpose: The Td(ho) allele is an X-linked dominant, embryonic male-lethal mouse mutation that occurs between embryonic day (E) 12.5 and E14.5. The lethal cause and responsible gene have not been identified until now. The cause of lethality in Td(ho) male embryos was examined with respect to the defect of hematopoiesis. Methods: Suppression subtractive hybridization and Northern blot analysis were performed on E12.5 male Td(ho) and normal mouse embryos. In addition, histochemical examinations and blood cell counts of normal and mutant E12.5 embryos were carried out. Results: Diminished expression of embryonic globin genes (zeta and epsilon globins) in the blood of E12.5 Td(ho) male embryos were documented by use of Northern blot analysis and subtractive hybridization, Increased apoptosis of yolk sac-derived erythrocytes was found in E12.5 Td(ho) male embryos. Furthermore, diminished numbers of anucleated erythrocytes were observed in E12.5 mutant embryos. Conclusions: A defect of embryonic hematopoiesis in Td(ho) mice was suggested as one of the possible causes of embryo lethality.
  • Yanai, K., Saito, T., Kakinuma, Y., Kon, Y., Hirota, K., Taniguchi-Yanai, K., Nishijo, N., Shigematsu, Y., Horiguchi, H., Kasuya, Y., Sugiyama, F., Yagami, K., Murakami, K. and Fukamizu, A. "Renin-dependent cardiovascular functions and renin-independen・・・
    2000年 [査読無し][通常論文]
     
    Yanai, K., Saito, T., Kakinuma, Y., Kon, Y., Hirota, K., Taniguchi-Yanai, K., Nishijo, N., Shigematsu, Y., Horiguchi, H., Kasuya, Y., Sugiyama, F., Yagami, K., Murakami, K. and Fukamizu, A. "Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice." J. Biol. Chem., 275(1), 5-8, (2000)*
  • Okamura, T., Gotoh, M., Kon, Y., Imai, Y., Yamamoto, M. and Watanabe, T. "Molecular cloning and characterization of mouse testis poly(A) binding protein II encoded by Pabp3 gene which transcomponents a meiotic mutant sme2 of S. pombe." Biochem. Genet.,・・・
    2000年 [査読無し][通常論文]
     
    Okamura, T., Gotoh, M., Kon, Y., Imai, Y., Yamamoto, M. and Watanabe, T. "Molecular cloning and characterization of mouse testis poly(A) binding protein II encoded by Pabp3 gene which transcomponents a meiotic mutant sme2 of S. pombe." Biochem. Genet., 38(1-2), 1-11, (2000)*
  • Kon, Y. and Endoh, D. "Morphological study of metaphase-specific apoptosis in MRL mouse testis." Anat. Histol. Embryol., 29(5), 313-319, (2000)*
    2000年 [査読無し][通常論文]
  • Endoh, D., Cho, K. O., Tsukamoto, K., Morimura, T., Kon, Y. and Hayashi, M. "Application of representational differential analysis to genomic fragments of Marekユs disease virus." J. Clin. Microbiol., 38(12), 4310-4314, (2000)*
    2000年 [査読無し][通常論文]
  • K Yanai, T Saito, Y Kakinuma, Y Kon, K Hirota, K Taniguchi-Yanai, N Nishijo, Y Shigematsu, H Horiguchi, Y Kasuya, F Sugiyama, K Yagami, K Murakami, A Fukamizu
    JOURNAL OF BIOLOGICAL CHEMISTRY 275 1 5 - 8 2000年01月 [査読有り][通常論文]
     
    Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI), Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen-deficient mice. We recently found the decreased density in granular layer cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.
  • Y Kon, D Endoh, T Iwanaga
    MOLECULAR REPRODUCTION AND DEVELOPMENT 54 4 333 - 341 1999年12月 [査読無し][通常論文]
     
    Protein gene product 9.5 (PGP9.5), originally isolated as a neuron-specific protein, belongs to a family of ubiquitin carboxyl-terminal hydrolases that play important roles in the nonlysosomal proteolytic pathway. Antibodies against PGP9.5 have been used for immunohistochemical detection of neural elements, although some non-neuronal cells are also immunoreactive for PGP9.5. In the present study, developing testes of the mouse were immunostained after autoclave pretreatment of sections. In the testes of days 8 and 16, PGP9.5 was only localized on the spermatogonia, whereas on day 30 and in adults it appeared not only on spermatogonia, but also on Sertoli cells. In the testis of the male sterile W/W-v mutant, very little, but strong, immunoreactivity was detected at some Sertoli cells, which were phagocytizing Sertoli cell aggregations that had fallen from the basal membrane. Additionally, it was confirmed that the nucleotide sequence of PGP9.5 in mice was highly conserved, like that in other mammals. These results suggest that PGP9.5 is a useful marker for activated Sertoli cells, playing an important role in degradation of abnormal proteins. (C) 1999 Wiley-Liss, Inc.
  • HK Jin, A Takada, Y Kon, O Haller, T Watanabe
    JOURNAL OF VIROLOGY 73 6 4925 - 4930 1999年06月 [査読無し][通常論文]
     
    Jin, H.-K., Takada, A., Kon, Y., Haller, O. and Watanabe, T. "Identification of the murine Mx2 gene: Interferon-induced expression of the Mx2 protein from the feral mouse gene confers resistance to vesicular stomatitis virus", J. Virol., 73(6): 4925-4930 (1999)
  • Y Kon, D Endoh
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C-ZENTRALBLATT FUR VETERINARMEDIZIN REIHE C 28 2 119 - 124 1999年05月 [査読有り][通常論文]
     
    Coagulating gland (CG) renin is one of the components of the local renin-angiotensin system (RAS), which plays important roles in the maintenance of homeostasis in several tissues. Although the existence of local renin has been reported in many tissues, its function is not yet well understood. In the present study, the relationship between CG renin and uterine angiotensinogen was investigated by immunohistochemical and in situ hybridization techniques. In mating experiments with male and female C57BL/6 mice, renin was demonstrated immunohistochemically on the epithelial cells of the uterus on the first day after coitus; however, it was not detected on the second and third days after coitus. Neither immunoreactive cells nor messenger signals for renin were demonstrated on the epithelial cells of the uterus throughout the experiments. On the first day after mating, it was noted that positive signals for angiotensinogen mRNA were expressed on the epithelial cells of the uterus in in situ hybridization, but not on the second and third days after coitus. These results suggest the possibility that CG renin is transferred to the uterine epithelium at mating and temporarily activates the expression of angiotensinogen in the uterus. Angiotensin II produced by angiotensinogen may act as an important mediator for vascularization of the first step of pregnancy.
  • Taketoshi Asanuma, Yoshiko Hirano, Keizo Yamamoto, Yasuhiro Kon, Shigezou Shimokawa, Mikinori Kuwabara
    Journal of Veterinary Medical Science 61 3 239 - 244 1999年03月 [査読有り][通常論文]
     
    Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T1 and T2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the TI and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.
  • T Asanuma, Y Hirano, K Yamamoto, Y Kon, S Shimokawa, M Kuwabara
    JOURNAL OF VETERINARY MEDICAL SCIENCE 61 3 239 - 244 1999年03月 [査読有り][通常論文]
     
    Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T-2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T-1 and T-2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the T1 and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.
  • Khlood, E. B. M., Miyoshi, H., Iwata, H., Kazusaka, A., Kon, Y., Hadid, A. H. A., Moustafe, E. K., Ghonim, M. H. and Fijita, S. "Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats", Jpn. J. Vet. Res., 47(1・・・
    1999年 [査読無し][通常論文]
     
    Khlood, E. B. M., Miyoshi, H., Iwata, H., Kazusaka, A., Kon, Y., Hadid, A. H. A., Moustafe, E. K., Ghonim, M. H. and Fijita, S. "Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats", Jpn. J. Vet. Res., 47(1-2): 13-23 (1999)
  • Kon, Y. and Endoh, D. "Renin in exocrine glands of variable mouse strains", Anat. Histol. Embryol., 28(4): 239-242 (1999)
    1999年 [査読無し][通常論文]
  • Kon, Y., Horikoshi, H. and Endoh, D. "Metaphase-specific cell death in meiotic spermatocytes in mice", Cell Tissue Res., 296(2): 359-369 (1999)
    1999年 [査読無し][通常論文]
  • Hiroyuki Miyoshi, Yasuhiro Kon, Kwang-Won Seo, Hee-Kyung Jin, Ai Hasegawa, Tomomasa Watanabe
    Mammalian Genome 10 3 213 - 217 1999年 [査読無し][通常論文]
     
    Jumbled spine and ribs (Jsr) is an autosomal dominant mutation that results in malformation of the axial skeleton. The vertebrae of mutant mice (Jsr/+) are all shorter than those of normal mice (+/+) in the inbred line and show various abnormalities. In addition, several ribs are fused at their proximal region because of fusion of thoracic vertebrae. In this study, we localized the Jsr mutation on distal Chromosome (Chr) 5 and constructed a high-resolution map. Chromosomal mapping was performed with an inter- subspecific backcross of (CKH-Jsr/+ x MOG) F1 carrying the Jsr allele and CKH-+/+. The predicted gene order around Jsr was determined to be cen-(Epo, Pdgfa, D5Mit31, D5Mit374)-(Jsr, Nfe2u, D5Mit99, D5Mit247, D5Mit284, D5Mit292, D5Mit327)-D5Mit328-tel. Subsequently, high-resolution mapping concluded the Jsr localization to be cen-Nfe2u-1.0cM-Jsr-0.2cM-D5Mit247,292-tel. Jsr/Jsr homozygotes are alive, as the mutation is not lethal. Based on histological analysis of mutant embryos, Jsr is hypothesized to be caused by abnormal development of primordial cells in the axial skeleton.
  • Kon, Y. and Endoh, D. "Expression of angiotensinogen in the uterus induced by coagulating gland renin in mice", Anat. Histol. Embryol., 28(2): 119-124 (1999)
    1999年 [査読無し][通常論文]
  • Ishida, J. , Asada, S., Daitoku, H., Fujiwara, K., Kon, Y., Sugaya, T., Murakami, K., Nakajima, T., Kasuya, Y. and Fukamizu, A. "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells", ・・・
    1999年 [査読無し][通常論文]
     
    Ishida, J. , Asada, S., Daitoku, H., Fujiwara, K., Kon, Y., Sugaya, T., Murakami, K., Nakajima, T., Kasuya, Y. and Fukamizu, A. "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells", Int. J. Mol. Med., 3(3): 263-270 (1999)
  • Asanuma T, Shimokawa S, Inanami O, Kon Y, Kuwabara M
    The Journal of veterinary medical science 60 12 1311 - 1314 1998年12月 [査読有り][通常論文]
  • M Ui, D Endoh, KO Cho, Y Kon, A Iwata, Y Maki, F Sato, M Kuwabara
    JOURNAL OF VETERINARY MEDICAL SCIENCE 60 7 823 - 829 1998年07月 [査読有り][通常論文]
     
    Spontaneously activated MDV is rarely included in MDV-transformed cells, while it may influence the result of transcriptional analysis. A population consisting of 10(3) MDV-transformed cells probably did not include spontaneously activated MDV, since the estimated frequency of MDV-transformed cells including activated MDV was below 0.01% according to limiting-dilution polymerase chain reaction (PCR) and the presence of the major early antigen pp38 in 6 transformed cell lines. Reverse transcriptase-PCR (RT-PCR) products corresponding to ICP27, pol, TK, US3, A41, gA, gB and UL50 genes were undetectable in 10(3) cells by Southern hybridization of the RT-PCR products. Transcripts of the VP16 and SORF2 genes were detected in the 10(3) cells of MSB-1, and the pp14 gene transcript was found in 10(3) cells of RPL-1 but not in 10(3) cells of HPRS-1, MOGA-1, MOGA-2, MSB-1 or MTB-1. A transcript corresponding to the ICP4 sequence was detected as a 0.7 kbp RT-PCR product in 10(3) cells of these MDV cell lines but not in the retrovirus-transformed 1104B1 cell line. The transcript corresponding to the 0.7 kbp RT-PCR product suggested a splice by its size and sequence. Thus, transcriptional analysis of 10(3) MDV-transformed cells revealed that the transcript corresponding to the ICP4 sequence was a common transcript in latently infected MDV-transformed cells, while most of the genes did not transcribe in these cells.
  • D Endoh, M Ito, KO Cho, Y Kon, T Morimura, M Hayashi, M Kuwabara
    JOURNAL OF VETERINARY MEDICAL SCIENCE 60 2 227 - 235 1998年02月 [査読有り][通常論文]
     
    A 246-base pair (bp) retroviral sequence, which was homologous to a long terminal repeat of avian erythroblastosis virus (AEV), was detected and cloned from Md5 strain (Md5) of Marek's disease virus type 1 (MDV1) by representational difference analysis (RDA). The retroviral sequence was thought to be located in the border region of short unique region (U-s) and short terminal repeat (TRs), but did not exist in the border region of Us and the inverted short repeat (IRs) of the Md5 genome. A cloned fragment of the US/TRs border region of the Md5 genome showed a construction of U-E'-R-U'-E-TRs with the regions designated as follows: E, expanded TRs reported by Jones et al. [Proc. Natl. Acad. Sci. U.S.A. 90, 3855, 1993]; E', a partial copy of the expanded TRs; R, the retroviral sequence detected in Md5 genome; U, TRs-end sequence of U-s; U', a partial copy of TRs-end sequence of U-s. The sequence unit indicated as E'-R-U' was thought to be heterogeneously repeated in the Md5 genome. Since this retroviral sequence reportedly did not exist in the original stock of Md5, the retroviral sequence is thought to be inserted in the Md5 genome without experimental co-infection of avian cells with retrovirus and MDV1. These results suggest that RDA could be useful for the detection of retroviral sequences in the herpesvirus genome.
  • Asanuma, T., Shimokawa, S., Inanami, O, Kon, Y. and Kuwabara, M.: "Visualization of the topographical structure of the anesthetized mouse brain by MR microimaging." Journal of Veterinary Medical Science, 60:1311-1314(1998)
    1998年 [査読無し][通常論文]
  • Masahiro Ui, Daiji Endoh, Kyoung-Oh Cho, Yasuhiro Kon, Akira Iwata, Yoshiyuki Maki, Fumiaki Sato, Mikinori Kuwabara
    Journal of Veterinary Medical Science 60 7 823 - 829 1998年 [査読無し][通常論文]
     
    Ui, M., Endoh, D., Cho, K.-O., Kom, Y., Iwata, A., Maki, Y., Sato, F. and Kuwabara, M.: "Transcriptional analysis of Merek's disease virus (MDV) genes in MDV-transformed lymphoblastoid cell lines without MDV-activated cells." Journal of Veterinary Medical Science, 60:823-829(1998)*
  • 1998年 [査読無し][通常論文]
     
    Endoh, D., Ito, M., Cho, K.-O., Kon, Y., Morimura, T., Hayashi, M. and Kuwabara, M.: "Retroviral sequence located in border region of short unique region and short terminal repeat of Md5 strain of Marek's disease virus type1.", Journal of Veterinary Medical Science, 60:227-235(1998)*
  • Kon, Y., Endoh, D., Yamashita, T., and Watanabe, T.:
    Anatomia Histologia Embryologia, 27:111-118(1998)* 27 2 111 - 118 1998年 [査読有り][通常論文]
     
    Renin is well-known to be a trigger enzyme in the renin-angiotensin system (RAS). In contrast to the classical RAS, the local RAS has recently been noted in several tissues. The local RAS has a function independent from that of the classical RAS, although its physiological principles are not well known. In the present study, we immunohistochemically demonstrated that hepatocytes in the rat express renin. No renin-immunoreactive cells were detected in rat liver at 0 min after death. At 15 min after death, a small number of renin-positive cells was demonstrated in the lamina hepatica. and they increased with time to the end of observation. Immunoreactivity for renin was scarce throughout the cytoplasm, sometimes condensed to below the cell membrane and around the intracellular granules. Histoplanimetrically, the values from 15 min to 120 min after death were significantly different from that at 0 min after death. Hybridohistochemistry revealed no hybrid signals throughout the liver at either 0 min or 30 min, although renin-immunoreactivity was clearly demonstrated in adjacent sections of liver at 30 min after death. In RT-PCR, the radioactivities in kidney and liver at 0 min after death were nor different from those at 30 min after death, respectively. These results suggest the existence of hepatic renin in the rat.
  • Kon, Y., Miyoshi, M. and Hashimoto, Y.:
    Anatomia Histologia Embryologia, 27:161-166(1998)* 27 3 161 - 166 1998年 [査読有り][通常論文]
     
    Aggregations of granulated epithelioid cells exist in the chicken aorta. In the present study, the locational characteristics of the epithelioid cells were investigated via an electron microscopic approach. Epithelioid cells were found mainly in two regions; the tunica interna just below the endothelial cell layers, and the intermediate region of the tunica media. In the former, the epithelioid cells were in contact with endothelial cells and sometimes directly exposed to the aortic lumen. No contact between the epithelioid cells and the nerve endings was observed in this region. On the other hand, in the intermediate region of the tunica media, five or more epithelioid cells were aggregated, and the cynaptic structures were occasionally observed. Additionally, the epithelioid cells in this region were observed to closely contact smooth muscle cells. In an experiment using horseradish peroxidase injection, reactions were detected in the intercellular spaces between the epithelioid cells and endothelial cells. These results suggest that the epithelioid cells localized in the subendothelial region receive information from the aortic lumen, whereas their aggregations in the tunica media are controlled by the nervous system.
  • K. W. Seo, H. Miyoshi, Y. Kon, T. Watanabe
    Mammalian Genome 8 8 578 - 580 1997年08月 [査読有り][通常論文]
     
    We found a new X-linked dominant mouse mutation. This mouse has the same phenotype as Td, which exhibits hyperkeratotic skin, reduced viability in affected females, a tendency to be smaller, lighter weight than the normal sibs during weaning age, and prenatal lethality in affected males. To map the locus, we tested 267 progeny from an intraspecific backcross between affected females and wild-origin strain males. Polymerase chain reaction (PCR) was performed with microsatellite markers of the proximal region of the mouse X Chromosome (Chr). This mutant showed no recombination with DXMit 123, DXMit 55, or DXMit 26. The gene position and phenotype of this mutant were very similar to those of Td. Therefore, it is speculated that the new mutant gene is a multiple allele of Td, and we designated it Tattered-Hokkaido (Td(ho)). Linkage analysis of these animals suggested a possible gene order of cen-(Td(ho), DXMit123, DXMit55, DXMit26)-DXMit161-DXMit54-DXMit103-DXMit52-DXMit190-DXMit138) in the X Chr. Prenatal lethality of male mutants was also investigated, with 12.5 to 16.5 embryonic day (E) backcrossed embryos from affected F1 females. It was found that the male mutants died between E12.5 and E14.5. The cause of death of male mutants is discussed in relation with the other proximal genes of the X Chr.
  • Akihiko Maeda, Yasuhiro Kon, Tomomasa Watanabe, Masanobu Hayashi
    Journal of Veterinary Medical Science 59 7 545 - 549 1997年 [査読有り][通常論文]
     
    Maeda, A., Kon, Y., Watanabe, T. and Hayashi, M. : "Resistance to infection with mouse hepatitis virus (MHV) in the cell clones derived from persistently infected DBT cells with the JHM strain of MHV", Journal of Veterinary Medical Science, 59 : 545-549 (1997)*
  • Yamashita T, Yamazaki H, Kon Y, Watanabe T, Arikawa J, Miyoshi I, Kasai N, Kuwabara M
    Free Radic Biol Med 23 7 1073 - 1077 1997年 [査読有り][通常論文]
     
    Yamashita, T., Yamazaki, H., Kon, Y., Watanabe, T., Arikawa, J., Miyoshi, I., Kasai, N. and Kuwabara, M. : "Progressive effect of α-phenyl-N-tert-butyl nitrone (PBN) on rat embryo development in vitro", Free Radical Biology and Medicine, 23 : 1073-1077 (1997)*
  • "Morphological study of pituitary tumorigenesis in transgenic mice induced by tryrotropin β-subunit and Simian virus 40 large T-antigen hybrid onco・・・
    Kon Y, Miyoshi I, Maki K, Yamashita T, Aoyama S, Watanabe T, Hayashizaki Y, Kasai N
    Histol Histopathol 12 4 981 - 990 1997年 [査読有り][通常論文]
     
    Kon, Y., Miyoshi, I., Maki, K., Yamashita, T., Aoyama, S., Watanabe, T., Hayashizaki, Y. and Kasai, N. : "Morphological study of pituitary tumorigenesis in transgenic mice induced by tryrotropin β-subunit and Simian virus 40 large T-antigen hybrid oncogene", Histology and Histopathology, 12 : 981-990 (1997)*
  • Asanuma, T., Hirano, Y., Ohkura, K., Kon, Y., Shimokawa, S., Kasai, N. and Muwabara, M. :
    Japanese Journal of Veterinary Research, 45・・・ 45 3 147 - 151 1997年 [査読有り][通常論文]
     
    Asanuma, T., Hirano, Y., Ohkura, K., Kon, Y., Shimokawa, S., Kasai, N. and Muwabara, M. : "Magnetic resonance imaging of hepatocellular carcinona in Long-Evans Cinnamon rats under a magnetic field of 7.05 T", Japanese Journal of Veterinary Research, 45 : 147-151 (1997)*
  • Apoptosis in peripheral CD4+ T cells and thymocytes by Marek\\'s disease virus-infection
    T. Morimura, K. Ohashi, Y. Kon, M. Hattori, C. Sugimoto, H. Onuma
    Leukemia 11 SUPPL. 3 206 - 208 1997年 [査読有り][通常論文]
  • M Hayashi, F Okada, K Ishida, A Maeda, Y Kon, T Mizutani, T Itoh, S Arai, T Watanabe
    JOURNAL OF VETERINARY MEDICAL SCIENCE 58 8 731 - 735 1996年08月 [査読有り][通常論文]
     
    M. Hayashi, F. Okada, K. Ishida, A. Maeda, Y. Kon, T. Mizutani, T. Itoh, S. Arai and T. Watanabe :"Cytolytic activity induced by intramuscular injection of plasmid DNA expressing the nucleocapsid protein of the JHM strain of mouse hepatitis virus into C57BL/6 mice", Journal of Veteterinary Medical Science, 58 : 731-735 (1996)*
  • Y. Kon, D. Endoh, A. Fukamizu, K. Murakami, T. Yamashita and T. Watanabe :
    Anatomia Histologia Embryologia, 25 : 289-294 (1996)* 25 4 289 - 294 1996年 [査読有り][通常論文]
     
    To obtain evidence of renin-synthesizing cells in the murine coagulating gland (CG), CG renin mRNA was detected by hybridohistochemistry, as well as in vitro reverse transcriptase-polymerase chain reaction (RT-PCR) in intact, castrated and testosterone-treated C57BL/6 mice. Hybridohistochemistry using paraffin sections of the kidneys and the CGs for the detection of renin mRNA was performed with digoxigenin-labelled probes. Some paraffin sections were immunohistochemically stained for renin by the peroxidase-anti-peroxidase method. Total RNA was extracted, incubated by reverse transcriptase, and amplified by PCR. In the kidneys, the immunoreactivity and the positive signals of hybridohistochemistry using an antisense probe were restricted to the same juxtaglomerular cells. In the control and at 7 days after testosterone administration to castrated mice, both renin-immunoreactivity and -hybridoreactivity were expressed by the epithelial cells in the CGs, while, in the CGs of the castrated mice and 3 days after testosterone injection of castrated animals, neither renin-immunoreactivity nor -hybridoreactivity was detected in the epithelial cells. Using RT-PCR, renin mRNA from the mice in the control and 7 days after testosterone injection of castrated was amplified, whereas, in the castrated and the 3 days after testosterone injection of castrated groups, it was not detected. The data presented here provide additional evidence that CG renin is regulated by testosterone.
  • "Immunoelectron microscopic study on the endocrine pancreas of the native Korean goat",
    J. -H. Lee, Y. Hashimoto, Y. Kon, M. Sugimura and H. -S. Lee :
    Korean Journal of Electron Microscopy, 26 : 67-77 (1996)* 1996年 [査読有り][通常論文]
  • "Lymphocyte subpopulations in the mammary gland of the goat",
    H. I. Ismail, Y. Hashimoto, Y. Kon, K. Okada, W. C. Davis and T. Iwanaga :
    Veteterinary Immunology and Immunopathology, 52 : 201-212 (1996)* 1996年 [査読有り][通常論文]
  • M. Z. I. Kahn, Y. Hashimoto, A. Konno, Y. Kon and T. Iwanaga :
    Cell and Tissue Research, 284 : 317-325 (1996)* 284 2 317 - 325 1996年 [査読有り][通常論文]
     
    Postnatal development of T-cell subpopulations in the oviduct was investigated in the Dekalb strain of the White Leghorn chicken by using an immunohistochemical method. T-lymphocytes first infiltrated the oviduct at 5 weeks. The number of T cells peaked at 15 weeks in the magnum, isthmus and uterus, and at 19 weeks in the infundibulum and vagina. The epithelium of the oviduct contained both granular and agranular lymphocytes. TcR1(+) cells were predominant in the epithelium, whereas TcR2(+) cells were more numerous than TcR1(+) cells in the lamina propria. TcR3(+) cells were absent from the epithelium and were not numerous in the lamina propria. CT8(+) cells, equivalent to CD8(+) cells in mammals, were located both in the epithelium and in the lamina propria. The relative frequency of T-cell subpopulations was found to be higher in the vaginal part than in other parts of the oviduct. These results suggest that the postnatal developmental changes of T-cell subpopulations depend on different anatomical regions of the oviduct and on the age of the chicken.
  • MORIMURA T, OHASHI K, KON Y, HATTORI M, SUGIMOTO C, ONUMA M
    Archives of Virology 141 11 2243 - 2249 1996年 [査読有り][通常論文]
  • H. I. Ismail, Y. Hashimoto, Y. Kon, A. Konno, H. Yamazoe and T. Iwanaga :
    Biomedical Research, 17 : 105-113 (1996)* 17 2 105 - 113 1996年 [査読有り][通常論文]
     
    The distribution of immunoglobulin (Ig)-containing plasma cells and T lymphocyte subpopulations in the mouse mammary gland was studied in different stages of the reproductive cycle using immunohistochemical techniques. Generally, Ig-containing plasma cells (IgA, IgG and IgM) in the mammary gland were few during pregnancy. They gradually increased in number during lactation, further increased in the first 2 days of the post-weaning period, and then quickly decreased. The rich existence of plasma cells after the suckling period suggests that their main role is the protection of the mammary gland rather than the transference of passive immunity to neonates. IgA-containing plasma cells were the most frequent isotype, while IgG- and IgM-containing cells were much less throughout the reproductive cycle. In contrast to the plasma cells, T lymphocytes were observed to increase markedly in late pregnancy, while they gradually decreased during lactation, a further decrease being recognizable in the post-weaning period. CD8(+) cells, the predominant cell type among T cells, preferentially existed within the epithelia of the alveoli and ducts, whereas CD4(+) cells were mainly located in the connective tissue areas. The difference in the dynamics of plasma cells and T lymphocytes suggests that the mammary gland T lymphocytes may lack an isotype-switching role for plasma cells.
  • Daiji Endoh, Yasuhiro Kon, Masanobu Hayashi, Toshifumi Morimura, Kyoung-Oh Cho, Toshio Iwasaki, Fumiaki Sato
    Journal of Veterinary Medical Science 58 10 969 - 975 1996年 [査読有り][通常論文]
     
    Homologues of herpes simplex virus ICP4 are important genes for the activation of many herpesviruses. We detected transcripts of the Marek's disease virus serotype 1 homologue of ICP4 (MDV1 ICP4) by in situ hybridization (ISH). Using a digoxigenin-labeled-RNA (DIG-RNA) probe, MDV1 ICP4 transcripts were detected in c.a. 90% of MDV1-infected chicken embryo fibroblasts (CEF) cells when cytopathic effect was reached to 90% of the CEF cells and in 0.35% of MDCC-MSB-1 (MSB-1) cells, at a frequency similar to that for MD antigen-positive MSB-1 cells. Using the same in situ procedure, we detected abundant MDV1 ICP4 transcripts in the feather follicle epithelium (FFE) and some lymphoid cells in the liver, kidney and peripheral nerve of infected chickens. The subcellular localization of the transcripts appeared to vary: MSB-1 cells had them in the nucleus, infected CEF cells and FFE had them in the nucleus and cytoplasm, and lymphoid cells contained them in the cytoplasm. The MDV1 ICP4 transcripts were also detected in the FFE and lymphoid cells in the liver by reverse-transcriptase polymerase chain reaction (RT-PCR). Detection of MDV1 ICP4 transcripts by RT-PCR indicated the existance of MDV1 ICP4 transcripts-positive cells in these tissues. And these data suggested that DIG-RNA-ISH can detect MDV transcripts on paraffin sections and provide information about their subcellular localization.
  • M. Nagata, K. Tanimoto, A. Fukamizu, Y. Kon, F. Sugiyama, K. Yagami, K. Murakami and T. Watanabe :
    Laboratory Investigation, 75 : 745-753 (1996)* 75 5 745 - 753 1996年 [査読有り][通常論文]
     
    Angiotensinogen-deficient mice provide a model to examine the roles of angiotensin II as a renal growth factor in vivo. We monitored nephrogenesis and renovascular development in angiotensinogen-deficient mice from Embryonic Day 13 (E13) to 4 weeks after birth. Northern analysis of homozygote (Atg-/-) mice confirmed the absence of angiotensinogen mRNA in the liver and the kidneys. Embryonic kidneys in Atg-/- mice from E13 to E18 exhibited active nephrogenesis, as also observed in Atg+/- mice and Atg+/+ mice. Furthermore, metanephroi harvested at E12 from Atg-/- embryos showed branching morphogenesis of ureteric bud and tubulogenesis similar to metanephroi from Atg-/- embryos grown with exogenous angiotensin II in serum-free culture. In newborn Atg-/- mice, we observed uniform dilation of the pelvis accompanied by a coarse medulla, which was not noted in Atg+/- or Atg+/+ mice. Hydronephrosis in Atg-/- mice continued, and renal papillae underwent atrophy for the 4 weeks after birth. Another characteristic aspect of the morphology of Atg-/- mice was the thickening of vascular walls as little as 2 weeks after birth. Immunohistochemistry revealed recruitment of renin in hyperplastic vascular smooth muscle cells (VSMC) in Atg-/- mice after 2 weeks. Electron microscopy confirmed that the majority of hyperplastic VSMC contained various sized renin granules with abundant endoplasmic reticulum. In situ hybridization demonstrated that expression of renin mRNA became prominent in parallel with hyperplasia of VSMC, as well as recruitment of renin protein. Furthermore, at 4 weeks, Atg-/- mice expressed a-smooth muscle actin in the mesangium, whereas none was ever found in that of Atg+/- mice and Atg+/+ mice. In conclusion, the renin-angiotensin system seems not be essential for nephrogenesis in vivo. Furthermore, hyperplasia of VSMC and expression of the smooth-muscle phenotype in the mesangium are inducible even in the absence of angiotensin II, with hypotension, in vivo.
  • Yamashita T, Ohshima H, Asanuma T, Inukai N, Miyoshi I, Kasai N, Kon Y, Watanabe T, Sato F, Kuwabara M
    Free Radic Biol Med 21 6 755 - 761 1996年 [査読有り][通常論文]
     
    T. Yamashita, H. Ohshima, T. Asanuma, N. Inukai, I. Miyoshi, N. Kasai, Y. Kon, T. Watanabe, F. Sato and M. Kuwabara : "The effects of α-phenyl-tert-butylnitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice", Free Radical Biology and Medicine, 21 : 755-761 (1996)*
  • Y KON, D ENDOH, K MURAKAMI, T YAMASHITA, T WATANABE, Y HASHIMOTO
    ANATOMICAL RECORD 243 2 200 - 207 1995年10月 [査読有り][通常論文]
     
    Background: Renin is classically secreted from juxtaglomerular cells of the kidney by endocrine or paracrine mechanisms. In a previous report, intense renin immunoreactivity was observed in the coagulating gland (CG), a new source for renin in mice. In the present study, immunoelectron microscopical analysis for renin was carried out to clarify the secretory site of CGs, Methods: Five adult male C57BL/6 mice were used in this study, The CGs were fixed with an ice-cold 2% glutaraldehyde and 2% paraformaldehyde mixture and embedded in Lowicryl K4M. Ultrathin sections were treated with antimouse renin antiserum and colloidal gold (15 nm)-labeled protein A complex. Results: In immunoelectron microscopical observation, renin was first detected at the Golgi vacuoles just budding from the lamellae, although it was not demonstrated in all Golgi vacuoles. In the production series of exocrine granules, renin immunoreactivity was observed in some granules that were distributed in the supranuclear region. Both renin-positive and -negative exocrine granules were secreted from the apical cell membrane by exocytosis. The lysosomal granules also showed stronger renin immunoreactivity and contained homogeneous or heterogeneous materials. In the supranuclear region, it was observed that exocrine granules were fused with irregular lysosomal granules. At the apical region, such lysosomal granules were closely associated with cell membrane. At the basolateral region, immunoreactivity for renin was localized in electron dense granules. Conclusions: These results suggest that part of the renin in the CGs is released by exocrine secretion into the genital tract. (C) 1995 Wiley-Liss, Inc.
  • Y KAKU, Y KON, N TAKAGI, T YAMASHITA, M HAYASHI, T WATANABE
    JOURNAL OF VETERINARY MEDICAL SCIENCE 57 5 973 - 975 1995年10月 [査読有り][通常論文]
     
    Hybrid sterility is thought to play an important role in the differentiation and maintenance of respective biological species. In the present study, as a first step to clarify the mechanism of hybrid sterility caused by the Hst-1 gene in mice, the male sterile hybrid between C57BL/6 and M. m. musculus was investigated by histological techniques. Many spermatogonia and primary spermatocytes were observed in the testes of the hybrid sterile mice. Neither secondary spermatocytes nor spermatids were detected throughout the sections. It was noted that some spermatocytes showed degenerations in part of the lumina of the seminiferous tubules. In the chromosomal preparations of primary sterile hybrids, the percentage statistical values for the spermatogonia/leptotene stage were increased and those for the zygotene/pachytene stage were markedly decreased. Neither round nor elongated spermatids were detected throughout the preparations. It was observed that many primary spermatocytes were degenerated. These results suggest that spermatogenesis stops at the leptotene stage and that a small number of cells progress to the next meiosis, but degenerate to die during the pachytene stage.
  • A KONNO, Y HASHIMOTO, Y KON, K OKADA, WC DAVIS, M SUGIMURA
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 48 1-2 105 - 112 1995年09月 [査読有り][通常論文]
     
    Histochemical characteristics and immunological surface phenotypes of globule leukocytes (GLs) of normal goats were investigated in the intestine. In the small intestine, GLs were concentrated in the base of the villus and around the crypt, whereas in the cecum and colon they were randomly distributed. Their cytoplasmic granules exclusively stained with phosphotungstic acid hematoxylin, and were negative for peroxidase and histamine in contrast to those of subepithelial mast cells, The existence of chondroitin sulfate in some granules of GLs and heparin in most granules of mast cells were revealed by alcian blue staining and digestion with chondroitinase ABC, Isolated intestinal GLs were positive for T cell receptor (TcR) 1-N24 (gamma delta) and CD8 alpha, and negative for WC1-N3 and WC1-N4. Cryostat sections of ileum revealed preferential intraepithelial distribution of both TcR1-N24(+) cells and CD8(+) cells, WC1-N3(+) and WC1-N4(+) cells were rarely seen in the epithelium and lamina propria. These results indicate that caprine GLs are a gamma delta T cell subset, which is a different cell population from WC1 positive gamma delta T cells.
  • M MIYOSHI, Y HASHIMOTO, Y KON, M SUGIMURA
    ANATOMICAL RECORD 242 3 302 - 309 1995年07月 [査読有り][通常論文]
     
    Background: The ultrastructural characteristics of epithelioid cells in the wall of the chicken aorta have been studied by several investigators. Their characteristics were homologous to those of carotid body type I cells and are considered to be one of the peripheral chemoreceptors. However, there are few descriptions about their location, distribution, and how they react to chemical signals, nor have there been many reports about the localization of bioactive substances in the epithelioid cells. Therefore we designed this investigation to address these problems. Methods: Wholemount immunohistochemistry using antiserotonin antiserum, scanning (SEM), and transmission (TEM) electron microscopy were used to observe the epithelioid cells and the lumen of the chicken aorta. The localizations of bioactive substances in the epithelioid cells were immunohistochemically investigated using 11 antisera. Results: Epithelioid cells were dispersed in the wall of the aorta, forming a band similar to 1 mm in width, located 10 mm proximal to the confluence of the right and left Ligamenta arteriosa. Serotonin, chromogranin, and neuron specific enolase immunoreactivities were detected in the epithelioid cells. SEM observations clearly demonstrated intraendothelial fenestrations, 1-3 mu m in diameter, on the endothelial surface of the region of the band of epithelioid cells. TEM observations revealed that these fenestrations corresponded to endothelial gaps, directly beneath which epithelioid cells were sometimes located. Conclusions: The epithelioid cells are in direct access to the aortic lumen through endothelial fenestrations. Thus they may be able to perceive chemical signals from arterial blood directly. (C) 1995 Wiley-Liss, Inc.
  • Y KON, D ENDOH, K MURAKAMI, T YAMASHITA, T WATANABE, Y HASHIMOTO, M SUGIMURA
    ANATOMICAL RECORD 241 4 451 - 460 1995年04月 [査読有り][通常論文]
     
    Background: The presence of extrarenal or local renin-angiotensin system (RAS) has been noted in several tissues, although its functions have not yet been clarified. Renin from the coagulating gland (CG) is the most recently discovered local RAS and is a significant subject for investigation because large amounts of both mRNA and proteins are detected in this organ. Recently, it has been reported that testosterone influences renin synthesis in several extrarenal tissues, although it has no effect on intrarenal renin. Therefore, it is possible that CG renin is also regulated by testosterone. Methods: Forty-four male C57BL/6 mice, aged 3 wk to 6 mo, were used in studies on the ontogeny and androgen regulation of the RAS in the CG. The tissues were fixed with Bouin's solution and paraffin sections were stained with immunohistochemical methods using antirenin antiserum, In each inmunostained section, the relative number of renin-containing cells in terminal portions of the CG were counted. Results: Immunoreactivity for renin was first detected at 6 wk after birth. After that time, the number of renin-containing cells gradually increased throughout the experiment, In adults, several patterns of renin immunoreactivity were demonstrated in almost all epithelial cells of CGs, specifically; (1) basolateral granular reaction, (2) diffuse immunoreactivity throughout the cytoplasm, and (3) restricted nuclear reaction. Excretory products of some terminal lumina were also found to be positive for renin, At 10 days after castration, renin-containing cells in ductal termini were decreased and remained at low levels until at 4 wk after castration. After testosterone injection, numerical values of renin-containing cells were high at 1 wk and then decreased at 2-3 wk. Conclusion: It is suggested that CG renin of the mouse is expressed together with sexual maturation during development and that it depends on the testis, possibly the male sex hormone. (C)1995 Wiley-Liss, Inc.
  • Expression of the endogeneous Marek's disease virus ICP4 homolog (MDV ICP4) gene is enhanced in latently infected cells by transient transfection with the recombinant MDV ICP4 gene.
    Jpn. J. Vet. Res., 43 3-4 109 - 124 1995年 [査読有り][通常論文]
  • A KONNO, Y HASHIMOTO, Y KON, M SUGIMURA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 56 6 1101 - 1105 1994年12月 [査読有り][通常論文]
     
    Distributional and immunohistochemical characteristics of the feline globule leukocyte (GL) were investigated by light microscopy. The GL, which contained eosinophilic large granules in the cytoplasm, was frequently found in the epithelia of the intestine and gall bladder, and less frequently found in those of the gastric pit, intrahepatic bile duct, and interlobular secretory duct of the pancreas. No GL was seen in the respiratory and urogenital organs. The GLs composed a homogeneous cell population including no mast cells according to the following histochemical stainings; phosphotungstic acid hematoxylin, alcian blue and peroxidase. The feline GL showed perforin-like immunoreactivity to anti-human perforin monoclonal antibody, but did not show histamine-immunoreactivity to anti-histamine polyclonal antibody. The results suggest that the feline GL is a lineage of large granular lymphocytes. The epitheliotropism and the characteristics as granular lymphocytes of the feline GLs were similar to those of the intestinal gamma delta T cells of the mouse.
  • A FUKAMIZU, M WATANABE, Y INOUE, Y KON, S SHIMADA, N SHIOTA, F SUGIYAMA, K MURAKAMI
    KIDNEY INTERNATIONAL 46 6 1533 - 1535 1994年12月 [査読有り][通常論文]
     
    Cortical expression of the human angiotensinogen gene in the kidney of transgenic mice. We have previously generated ''Tsukuba hypertensive mice'' with elevated blood pressure by cross-mating separate lines of transgenic animals carrying either 15 kb of the human renin gene including its native 3-kb promoter or 14 kb of the human angiotensinogen gene along with its 1.3-kb promoter, the former of which is expressed predominantly in the kidney and the latter of which is also expressed in the kidney to levels comparable to those found in the liver. To investigate whether the integrated human angiotensinogen gene is prominently expressed in the kidney of transgenic mice, we have analyzed a production region of the transgene mRNA by in situ hybridization technique. This analysis clearly demonstrated that human angiotensinogen mRNA is localized specifically to the cortex region of transgenic mouse kidney. The present finding indicates a possible involvement of the renal renin-angiotensin system in the pathogenesis of high blood pressure in transgenic mice.
  • K MAKI, MIYOSHI, I, Y KON, T YAMASHITA, N SASAKI, S AOYAMA, E TAKAHASHI, S NAMIOKA, Y HAYASHIZAKI, N KASAI
    MOLECULAR AND CELLULAR ENDOCRINOLOGY 105 2 147 - 154 1994年11月 [査読有り][通常論文]
     
    We have generated transgenic mice that express the simian virus 40 (SV40) large T antigen under the control of a 1109 bp 5'-flanking sequence of the human thyrotropin beta-subunit (TSH beta) gene. The hybrid gene, termed TTP-1, was microinjected into fertilized mouse eggs and 11 transgenic mice were obtained. One of the transgenic mice, a female, a phenotypical dwarf, developed a pituitary tumor and wasted away from 7 to 9 weeks after birth. To establish the transgenic mouse line, her ovaries were transferred to a normal female, whose ovaries were removed beforehand. To examine the tissue specificity of transgene expression, mRNA of SV40 large T antigen was monitored in various tissues from the transgenic mice by the reverse transcriptase-polymerase chain reaction analysis, and was detected only in the pituitary. Histological and immunohistochemical analyses showed that the pituitary tumors of the transgenic mice were composed of poorly differentiated pituitary cells expressing SV40 large T antigen. These results indicated that the 1109 bp sequence of the human TSH beta 5'-flanking region is essential for pituitary-specific expression of SV40 large T antigen in transgenic mice, which exhibited a dwarf phenotype and developed pituitary tumors. The tumors were composed of undifferentiated cells and did not produce thyrotropin. These transgenic mice should provide a valuable animal model for studying the pathogenesis of anterior pituitary tumors.
  • Y KON, D ALCORN, K MURAKAMI, M SUGIMURA, GB RYAN
    ANATOMICAL RECORD 239 2 191 - 197 1994年06月 [査読有り][通常論文]
     
    Background: Renin-containing (RC) cells in small ruminant kidneys have been known to be widely distributed along the blood vessels. In the present study, RC cells in developing sheep kidneys were studied to investigate not only the appearance but distribution with the potential physiological significance using immunohistochemical and histoplanimetrical techniques. Methods: Seven fetal, 12 newborn, and 3 adult metanephric kidneys were used and immunostained by anti-renin antiserum. In the histoplanimetrical analysis, the numerical values of RC cells existing at the walls of 3 major arterial types in the kidneys were calculated. Results: At day 44 of gestation, RC cells were already demonstrated in the walls of renal, interlobar, and afferent vessels, located in the deep cortex and the medulla. In intermediate gestational periods, RC cells were detected throughout the intrarenal arterial trees. In late gestational periods, RC cells expressed in the walls of interlobar/arcuate and interlobular arteries tended to decrease or disappear gradually, while they were distributed predominantly in the afferent glomerular vessels. In newborn lambs, especially days 1 to 3 after birth, increased numbers of RC cells were demonstrated throughout the arterial trees in the kidneys. In older lambs, RC cells located in the interlobar/arcuate arteries and the proximal region of the interlobular arteries decreased in number and gradually disappeared. Some RC cells were still distributed in the distal portion of the interlobular artery even in the adult sheep. Conclusions: These results suggest that the wide distribution of RC cells in sheep kidney is formed in perinatal life, and that the neuronal regulation is associated with the maintenance of this distribution. (C) 1994 Wiley-Liss, Inc.
  • T IMAGAWA, Y KON, H KITAGAWA, Y HASHIMOTO, M UEHARA, M SUGIMURA
    ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER 176 2 175 - 179 1994年04月 [査読有り][通常論文]
     
    Appendices colli (App. colli) were investigated by anatomical and histological methods in the goat. App. colli were composed of elastic cartilage located at central and the skin covering the cartilage, which included arterioles along the cartilage and nerve bundles. Three types of muscles connected to App. colli; superficial muscle bundles, a branch of the omohyoideus muscle, and a muscle arising from the pharyngeal raphe (appendico-pharyngeal muscle). The latter two muscles were connected to the root of the App. colli where the muscle fibers transformed into the perichondrium of the elastic cartilage. The appendico-pharyngeal muscle was innervated by branches from the glossopharyngeal nerve which were composed of myelinated nerve fibers. The subcutaneous area of the App. colli was supplied by cutaneous rami of the vagus and the second cervical nerves. The innervation and the musculature confirmed that the cartilage of the App. colli were derived from third and fourth branchial arches.
  • Y KON, Y HASHIMOTO, M SUGIMURA, K MURAKAMI
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C-ZENTRALBLATT FUR VETERINARMEDIZIN REIHE C 22 4 324 - 327 1993年12月 [査読有り][通常論文]
     
    Both renin an cathepsin B were co-localized in identical granules of adreno-cortical cells. At day 16 of gestation, many renin-containing granules were observed and gold particles showed homogeneous intragranular distribution; whereas, those for cathepsin B was distributed heterogeneously. At day 18 of gestation, renin immunoreactivity was decreased or undetectable, whereas cathepsin B was still demonstrated at the same level as on day 16 of gestation.
  • Y KON, D ENDOH, A FUKAMIZU, K MURAKAMI, Y HASHIMOTO, M SUGIMURA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 55 3 461 - 463 1993年06月 [査読有り][通常論文]
     
    Hybridohistochemistry was applied for the detection of renin mRNA in the mouse kidney with a digoxigenin-labeled probe, synthesized as the sense and antisense RNAs from Ren-1 cDNA in the presence of digoxigenin-dUTP. Renin mRNA was detected in the juxtaglomerular cells located in the vicinity of the glomerular vascular poles of the kidney using the digoxigenin-labeled antisense RNA as a probe. Using the sense RNA as a probe, no signal was detected anywhere. In neighboring serial sections, the same cells reacted immunohistochemically to rabbit anti-mouse submandibular gland renin serum as in hybridohistochemistry. As we used the probe labeled with digoxigenin as a non-radioisotopic marker, there was no need for special handling other than that in immunohistochemistry. It was concluded that the simple procedure given in the present study is useful for the detection of mRNA.
  • T KONOGURA, Y KON, M ONUMA, T KONDO, Y HASHIMOTO, M SUGIMURA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 55 1 59 - 66 1993年02月 [査読有り][通常論文]
     
    The distributions of T cell subsets in chicken lymphoid tissues were investigated immunohistochemically using monoclonal antibodies (Lc-6, Lc-4) with specificity for chicken CD4 and CD8, respectively. In thymic tissues, CD8+ cells were found only in the cortex, while CD4+ cells were detected not only in the cortex but also in the medulla. The cortex just below the capsule demonstrated no immunoreactivity to either antibody. In the cecal tonsile, CD8+ cells were found restrictly in the subepithelial lamina propria. It was noted that the germinal centers were clearly surrounded with many CD4+ cells in the mid and deep portions of the lamina propria. In the spleen, clusters of CD8+ cells were observed only in the red pulp. Most lymphocytes in the periarteriolar lymphatic tissue and perivenous lymphatic tissue showed a CD4-positive reaction. No lymphocyte in the germinal centers reacted with these two monoclonal antibodies. No immunoreactivity for either CD8 or CD4 was detected anywhere else in the bone marrow or bursa of Fabricius. In the case of exposure to the protein antigen (alum-precipitated bovine serum albumin), CD4+ cells were demonstrated in some germinal centers, which were increased in size, while the areas expressing CD8 in the red pulp were decreased in size. These results suggest that the preferential distributions of T cell subsets are inherent in chicken lymphoid tissues.
  • M HAYASHI, D ENDOH, Y KON, T YAMASHITA, F SATO, N KASAI, S NAMIOKA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 55 1 13 - 18 1993年02月 [査読有り][通常論文]
     
    LEC strain rats, which have been known to develop hereditarily spontaneous fulminant hepatitis 4 to 5 months after birth, were highly sensitive to whole-body X ray-irradiation as compared to WKAH strain rats. Radiation-induced acute bone-marrow death occurred at doses higher than 2.0 Gy in LEC rats, and at doses higher than 7.4 Gy in WKAH rats, respectively. By probit analysis of survival data, it was shown that the LD50/30 value for LEC rats was 3.0 Gy which was significantly lower than that (7.8 Gy) of WKAH rats. Histopathological examinations of the bone marrows from both strains after irradiation at a dose of 4.0 Gy revealed that a number of hemopoietic cells were recovered in WKAH rats on day 8 after irradiation, but not in LEC rats. These results suggested the hypersensitivity of LEC rats to ionizing radiation in connection with acute bone-marrow death.
  • Morphological study on the vasculature of intestine in carp (Cyprinus carpio).
    J. Rakuno Gakuen Univ., 18 21 - 30 1993年 [査読無し][通常論文]
  • A KATO, Y HASHIMOTO, Y KON, M SUGIMURA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 54 5 999 - 1006 1992年10月 [査読有り][通常論文]
     
    A unique morphological cell type, "microfold or membranous (M) cell-like cell", was detected electron-microscopically in the cecal tonsil epithelium of the chicken. M cell-like cells possessed a few short microvilli of irregular arrangement and a large number of lymphocytes and macrophages wedged into their basal surfaces. Triticum vulgaris was found to bind to M cell-like cells. With horseradish peroxidase (HRP) treatment, M cell-like cells showed an active HRP uptake just as did the neighbouring usual absorptive epithelial cells. No uptake of colloidal carbon particles from the intestinal lumen was recognized in any part of the intestinal epithelium. These results suggest that M cell-like cells of the chicken possess some M cell-characteristic morphological and histochemical features, but that their active uptake of foreign materials is not so developed as in mammalian M cells.
  • Y KON, D ENDOH, A FUKAMIZU, K MURAKAMI, Y HASHIMOTO, M SUGIMURA
    JOURNAL OF ANATOMY 181 335 - 343 1992年10月 [査読有り][通常論文]
     
    The comparative localisation of renin in the genital organs, especially in the coagulating glands of male mice of the strains C57BL/6 and Balb/c, was investigated using immunocytochemical, immunoelectron microscopical and Northern blot techniques. Dot-like reactions for renin, of varying diameters, were detected immunocytochemically in the epithelial cells of coagulating glands of C57BL/6 mice, but not in those of Balb/c mice. In both strains, many electron dense granules differing in content and morphology were observed in the epithelial cells of the coagulating glands. Crystalline materials were sometimes contained in these granules. Colloidal gold particles indicating the presence of renin were detected in the electron dense granules of C57BL/6 mice, in which they showed a heterogeneous distribution and were especially located on the crystalline structure. No positive reaction was detected in these crystalline structures in Balb/c mice. Renin mRNA was detected in the coagulating glands of both C57BL/6 and Balb/c mice by Northern blot analysis. However, the expression in C57BL/6 coagulating glands was stronger than that in Balb/c. These findings suggest that renin is synthesised and released in the coagulating glands.
  • Y KON, Y HASHIMOTO, K MURAKAMI, M SUGIMURA
    ACTA ANATOMICA 144 4 354 - 362 1992年08月 [査読有り][通常論文]
     
    Changes in juxtaglomerular (JG; renin-containing) cells in experimental hydronephrosis 1 month after ureteral ligation were investigated with immunoelectron-microscopical techniques. Two types of granules. electron dense (D) and lucent (L), were observed. D type granules were labeled more intensely with gold particles than those of L type. Granules intermediate between D and L types and exocytosis of D types were observed. In the cells containing D types exclusively, gold particles were restricted to the granules, whereas in the cells containing both D and L type granules, the particles were scattered throughout the cytoplasmic cytosol. The authors discuss the mechanisms of renin release in JG cells.
  • Y KON, Y HASHIMOTO, K MURAKAMI, M SUGIMURA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 54 3 589 - 590 1992年06月 [査読有り][通常論文]
  • M HAYASHI, D ENDOH, Y KON, T YAMASHITA, N HASHIMOTO, F SATO, N KASAI, S NAMIOKA
    JOURNAL OF VETERINARY MEDICAL SCIENCE 54 2 269 - 273 1992年04月 [査読有り][通常論文]
     
    LEC strain rats (LEC rats), which have been known to develop hereditarily spontaneous fulminant hepatitis 4-5 months after birth, were highly sensitive to whole-body X-irradiation as compared to WKAH strain rats (WKAH rats). Radiation-induced acute intestinal death occurred at doses higher than 6.5 Gy in LEC rats. and at doses higher than 12.8 Gy in WKAH rats, respectively. By the probit analysis of survival data, it was shown that the LD50/7 value of LEC rats was estimated to be 7.03 Gy which was significantly lower than that (12.99 Gy) of WKAH rats. Histopathological examinations of small intestines from LEC rats 2 days after irradiation at the dose of 8.5 Gy showed severe epithelial death together with edema, whereas little or no significant changes were noted in intestinal epithelium of 8.5 Gy-irradiated WKAH rats. These results suggest that the radiosensitivity of LEC rats to ionizing radiation appears to be higher than that of other strains of rats.
  • Y KON, S TAKAHASHI, A FUKAMIZU, K MURAKAMI, Y HASHIMOTO, M SUGIMURA
    ANATOMICAL RECORD 232 3 393 - 400 1992年03月 [査読有り][通常論文]
     
    The purpose of this study is to demonstrate the developmental changes of the experimental hydronephrotic kidney using immunohistochemical, histoplanimetrical, and Northern blot techniques. At 1 month after ligation of the ureter, a large number of renin-positive cells were detected immunohistochemically even at a dilution of 1:10,000 in this hydronephrotic kidney; however, there were few renin-positive cells in the non-ligated side. At 6 months after ligation, no difference in reactivity for renin between ligated and non-ligated kidneys was demonstrated. In the morphometrical analysis of the renin-positive region, the numerical value of the ligated side was already increased at 2 weeks, reached the highest value at 1 month, and then decreased gradually to almost the same value as the control kidney by the end of the experiment. On the other hand, the value of the non-ligated side decreased immediately after the unilateral ligation, increased later, and finally reached almost the same value as the control kidney. In the Northern blot analysis, the activity of renin mRNA in the ligated side at 1 month after ligation was markedly higher than that in the non-ligated side. However, the difference between the ligated and the non-ligated sides was not demonstrated at 6 months and the value came to be almost the same as in the non-operated kidney.
  • Angioarchitecture of systemic and visceral circulation in carp (Cyprinus carpio).
    Zool. Jb. Anat., 122 43 - 53 1992年 [査読有り][通常論文]
  • Y. Kon, Y. Hashimoto, K. Murakami, M. Sugimura
    Cells Tissues Organs 144 4 354 - 362 1992年 [査読有り][通常論文]
     
    Changes in juxtaglomerular (JG renin-containing) cells in experimental hydro-nephrosis 1 month after ureteral ligation were investigated with immunoelec- tron-microscopical techniques. Two types of granules, electron dense (D) and lucent (L), were observed. D type granules were labeled more intensely with gold particles than those of L type. Granules intermediate between D and L types and exocytosis of D types were observed. In the cells containing D types exclusively, gold particles were restricted to the granules, whereas in the cells containing both D and L type granules, the particles were scattered throughout the cytoplasmic cytosol. The authors discuss the mechanisms of renin release in JG cells. © 1992 S. Karger AG, Basel.
  • HS LEE, Y HASHIMOTO, Y KON, M SUGIMURA
    JAPANESE JOURNAL OF VETERINARY RESEARCH 39 2-4 117 - + 1991年12月 [査読有り][通常論文]
     
    The regional distribution and relative frequencies of gastrointestinal endocrine cells were studied immunohistochemically in the gastrointestinal mucosa of Korean tree squirrels. Seven kinds of endocrine cells were identified in this study. Although a large number of 5-hydroxytryptamine-immunoreactive cells were seen throughout the gastrointestinal tract, they were most predominant in the duodenum. A moderate number of glucagon-immunoreactive cells which were restricted to the cardia and fundus of the stomach was also observed. Bovine chromogranin-immunoreactive cells were numerous in the cardia and pylorus of the stomach, found in moderate numbers in the fundus, duodenum and large intestine, but rare in the jejunum. Porcine chromogranin-immunoreactive cells were found in moderate numbers in the stomach but were rare in the duodenum. Gastrin/cholecystokinin-immunoreactive cells were abundant in the pyloric gland region but scarce in the duodenum. Bovine pancreatic polypeptide-immunoreactive cells were observed to be rare and found only in the pyloric gland region. Somatostatin-immunoreactive cells were distributed moderately in the stomach but were few in number in the intestines. No insulin-immunoreactive cells were found in the gastrointestinal tract of Korean tree squirrels. These results suggest that although the Korean tree squirrel is a herbivorous rodent, the distribution pattern of its gastro-entero-endocrine cells is rather similar to that reported for omnivorous animals.
  • A FUKAMIZU, T HATAE, Y KON, M SUGIMURA, T HASEGAWA, M YOKOYAMA, T NOMURA, M KATSUKI, K MURAKAMI
    BIOCHEMICAL JOURNAL 278 601 - 603 1991年09月 [査読有り][通常論文]
     
    To examine whether expression of human renin in the transgenic mouse kidney is regulated in a cell-specific manner, we have characterized monoclonal antibodies against human renin and determined the renin-production site by immunohistochemistry. By using a monoclonal antibody specific for human renin, A6-11-6, we demonstrated that human renin in the transgenic mouse kidney is localized to the juxtaglomerular cells of afferent arterioles.
  • A FUKAMIZU, S UEHARA, K SUGIMURA, Y KON, M SUGIMURA, T HASEGAWA, M YOKOYAMA, T NOMURA, M KATSUKI, K MURAKAMI
    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS 5 3 112 - 116 1991年07月 [査読有り][通常論文]
     
    We have previously produced transgenic mice carrying the human renin gene, whose expression is regulated in a tissue-specific manner. In the present study, we further characterized expression of the transgene. Northern blot analysis showed that the human renin gene is expressed in the kidney but not in the liver of two lines of transgenic mice with 10 and 50 copies of the transgene, suggesting that the integrated copy number of the human renin gene does not influence the dominant-renal expression pattern. Immunohistochemical study using a monoclonal antibody specific for human renin demonstrated that expression of human renin in the transgenic mouse kidney is confined to the epitheloid juxtaglomerular cells. Transfection experiments indicated that the chloramphenicol acetyltransferase fusion gene containing the 3-kb upstream sequences of the renin gene is activated only in human epitheloid embryonic 293 cells derived from kidney but not in human HepG2 cells from liver. These findings suggest that transfer of the cloned renin gene into mice and in vitro cultured cell lines can give rise to cell type-specific expression.
  • Y KON, Y HASHIMOTO, H KITAGAWA, M SUGIMURA, K MURAKAMI
    JOURNAL OF ANATOMY 176 23 - 33 1991年06月 [査読有り][通常論文]
  • Localization of dopamine in the human ovary.
    Obstet. Gynecol. Therapy, 62 990  1991年 [査読無し][通常論文]
  • T. Imagawa, Y. Hashimoto, Y. Kon, M. Sugimura
    Fish and Shellfish Immunology 1 3 173 - 185 1991年 [査読有り][通常論文]
     
    Immunoglobulin (Ig) containing cells were examined in the carp head kidney after injection of alum-precipitated bovine serum albumin (AP-BSA) using light and electron microscopical immunohistochemistry. The anti-carp Ig immuno-reactive cells were blast cells, large lymphoid type (LC type) and plasmacytoid type (P type) cells. Under the electron microscope the blast cells contained a large nucleus with prominent nucleolus, numerous free ribosomes, variously developed rough endoplasmic reticulum (rER) and Golgi apparatus in the cytoplasm. LC type cells corresponded to plasma cells, and possessed a centrally located round nucleus and well-developed rER with relatively narrow lumina in their cytoplasm. This type of cell was occasionally observed to be migrating through endothelium or to be free in the lumina of sinusoids. P type cells contained a round or oval nucleus, extended rER and perinuclear space, and well-developed Golgi apparatus. Cells intermediate between the two types of plasma cells with both narrow and expanded rER, were occasionally observed. Using immunoelectron microscopy, the existence of Ig was demonstrated in the lumina of rER of blast cells, LC type cells and P type cells. The immunoreactivity in the extended rER was more intense than that in narrow rER. LC type cells were predominantly observed in carp of the control group and in treated carp until day 7. P type cells were found from day 14 after the AP-BSA treatment. At this time AP-BSA was also detected in pigment containing cell (PC) clusters, and prominent pryoninophilic cell (PP) clusters occurred in association with the PC clusters. In light microscopical immunohistochemistry, immunoreactivity for Ig was also detected in the PP clusters. Using electron microscopy, the PP clusters were found to consist of lymphoid cells, LC type plasma cells and a number of the blast cells. It is suggested that the PP clusters are the areas for lymphoid cell proliferation and plasma cell differentiation, and that the plasma cells could morphologically change from blast cells and LC type cells to P type cells with active Ig production. © 1991, Academic Press Limited. All rights reserved.
  • T IMAGAWA, Y HASHIMOTO, B SYUTO, Y KON, M SUGIMURA
    JAPANESE JOURNAL OF VETERINARY SCIENCE 52 6 1329 - 1332 1990年12月 [査読有り][通常論文]
  • T IMAGAWA, Y HASHIMOTO, Y KON, M SUGIMURA
    JOURNAL OF FISH DISEASES 13 6 537 - 540 1990年11月 [査読無し][通常論文]
  • M SUGIMURA, D SHIROGANE, Y ATOJI, Y SUZUKI, K OHSHIMA, Y KON, Y HASHIMOTO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 52 5 1015 - 1021 1990年10月 [査読有り][通常論文]
  • T IMAGAWA, Y HASHIMOTO, Y KON, M SUGIMURA
    JOURNAL OF FISH BIOLOGY 37 3 357 - 366 1990年09月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, M SUGIMURA, K MURAKAMI
    ANATOMICAL RECORD 227 1 124 - 131 1990年05月 [査読有り][通常論文]
  • T KIMIJIMA, Y HASHIMOTO, H KITAGAWA, Y KON, M SUGIMURA
    JAPANESE JOURNAL OF VETERINARY SCIENCE 52 2 299 - 305 1990年04月 [査読有り][通常論文]
  • T IMAGAWA, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO, M SUGIMURA
    JAPANESE JOURNAL OF VETERINARY SCIENCE 51 6 1163 - 1172 1989年12月 [査読有り][通常論文]
  • M NAKAI, Y HASHIMOTO, H KITAGAWA, Y KON, M SUGIMURA
    JAPANESE JOURNAL OF VETERINARY SCIENCE 51 3 521 - 529 1989年06月 [査読有り][通常論文]
  • M NAKAI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    POULTRY SCIENCE 68 4 582 - 589 1989年04月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO
    ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C-ZENTRALBLATT FUR VETERINARMEDIZIN REIHE C 18 1 14 - 26 1989年03月 [査読有り][通常論文]
  • K YANO, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY RESEARCH 36 3-4 205 - 221 1988年10月 [査読有り][通常論文]
  • H KITAGAWA, Y HASHIMOTO, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 3 638 - 647 1988年06月 [査読有り][通常論文]
  • H KITAGAWA, Y HASHIMOTO, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY RESEARCH 36 2 83 - 117 1988年04月 [査読有り][通常論文]
  • H ITO, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 2 395 - 404 1988年04月 [査読有り][通常論文]
  • M NAKAI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 2 371 - 381 1988年04月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 2 325 - 332 1988年04月 [査読有り][通常論文]
  • N ARAI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 1 183 - 192 1988年02月 [査読有り][通常論文]
  • H ITO, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 1 99 - 110 1988年02月 [査読有り][通常論文]
  • N HOSHI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 50 1 83 - 92 1988年02月 [査読有り][通常論文]
  • Jpn. J. Vet. Res., 36 1 15 - 30 1988年 [査読有り][通常論文]
  • N HOSHI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY RESEARCH 36 1 1 - + 1988年01月 [査読有り][通常論文]
  • N HOSHI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY RESEARCH 36 1 15 - 29 1988年01月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 49 2 323 - 331 1987年04月 [査読有り][通常論文]
  • N HOSHI, Y HASHIMOTO, H KITAGAWA, Y KON, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 48 6 1097 - 1107 1986年12月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 48 5 925 - 931 1986年10月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO, K MURAKAMI
    JAPANESE JOURNAL OF VETERINARY RESEARCH 34 2 111 - 123 1986年04月 [査読有り][通常論文]
  • Y KON, Y HASHIMOTO, H KITAGAWA, N KUDO
    JAPANESE JOURNAL OF VETERINARY SCIENCE 46 2 189 - 196 1984年 [査読有り][通常論文]

書籍

  • 獣医組織学 第八版
    (担当:共著範囲:第1章:細胞の一般構造、細胞膜 第12章:尿管、膀胱、尿道)
    学窓社 2020年03月
  • 日本獣医解剖学会, 九郎丸, 正道, 小川, 和重, 尼崎, 肇 (担当:共著範囲:発生学 第1章)
    学窓社 2019年03月 (ISBN: 9784873627656) vii, ,554p
  • McGeady, T. A. (Thomas A.), 木曾, 康郎 (担当:共訳範囲:第25章)
    学窓社 2019年02月 (ISBN: 9784873627632) xiii, 434p
  • 獣医組織学 第七版
    日本獣医解剖学会 (担当:共編者(共編著者)範囲:第1章 細胞学)
    学窓社 2017年03月
  • 猫の解剖 カラーリングアトラス
    九郎丸正道, 監訳 (担当:共編者(共編著者)範囲:図版62、63)
    学窓社 2014年09月
  • カラーアトラス動物発生学
    山本, 谷口, 監訳 (担当:その他範囲:第4章 生殖子発生)
    緑書房 2014年04月
  • 獣医組織学 第六版
    日本獣医解剖学会 (担当:共編者(共編著者)範囲:第1章 細胞学)
    学窓社 2014年03月
  • 獣医組織学 第五版
    日本獣医解剖学会 (担当:共編者(共編著者)範囲:第1章 細胞学)
    学窓社 2010年03月
  • カラーアトラス獣医解剖学 増補改訂版
    カラーアトラス獣医解剖学編集委員会, 監訳 (担当:共編者(共編著者)範囲:第7章 消化器系)
    緑書房 2010年03月
  • Veterinary Histology 5th eition
    2010年
  • 獣医発生学
    谷口, 木曽, 佐藤, 監修 (担当:その他範囲:第22章 外皮系)
    学窓社 2008年09月
  • カラーアトラス獣医解剖学
    カラーアトラス獣医解剖学編集委員会, 監訳 (担当:その他範囲:第7章 消化器系)
    チクサン出版社 2008年03月
  • 獣医組織学 第四版
    日本獣医解剖学会 (担当:共編者(共編著者)範囲:第1章 細胞学)
    学窓社 2008年03月
  • 獣医組織学第三版
    日本獣医解剖学会 (担当:共編者(共編著者)範囲:第1章 細胞学)
    学窓社 2005年03月
  • 一般解剖学 VI-IX. In: 牧田登之、橋本善春 監訳. 犬の解剖アトラス、
    学窓社、東京、 1995年

その他活動・業績

  • ISLAM Md Rashedul, 市居修, 中村鉄平, 中村鉄平, 入江隆夫, MD ABDUL Masum, YASER HOSNY, Ali Elewa, 昆泰寛 日本獣医学会学術集会講演要旨集 162nd 341 2019年08月20日 [査読無し][通常論文]
  • 自己免疫疾患モデルマウスにみられる涙液産生組織の形態学的変化
    平石 真也, 市居 修, 中村 鉄平, 難波 貴志, Hosny Ali Elewa Yaser, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 336 -336 2019年08月 [査読無し][通常論文]
  • コットンラットの下咽頭梨状窩瘻を構成する細胞の組織化学的特徴
    中村 鉄平, 市居 修, 入江 隆夫, 寸田 祐嗣, 細谷 実里奈, 長崎 健一, Ali Elewa Yaser Hosny, 三嶋 隆, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 337 -337 2019年08月 [査読有り][通常論文]
  • 自己免疫疾患モデルマウスで変化する腎臓内Interleukin 1 familyの発現バランス
    難波 貴志, 市居 修, 中村 鉄平, Ali Elewa Yaser Hosny, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 338 -338 2019年08月 [査読有り][通常論文]
  • 動物の尿路関連リンパ組織(UTALT)に発現する分子群
    市居 修, 中村 鉄平, 堀野 太郎, 細谷 実里奈, Ali Elewa Yaser Hosny, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 338 -338 2019年08月 [査読有り][通常論文]
  • マウス生体内異物反応の経時観察 組織局所の炎症と線維化の関連性
    大江 紗央, 市居 修, 難波 貴志, 大谷 祐紀, Masum Md. Abdul, 中村 鉄平, Ali Elewa Yaser Hosny, 西邑 隆徳, 中山 泰秀, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 340 -340 2019年08月 [査読有り][通常論文]
  • マウスの卵巣嚢-腹腔連絡路(卵巣嚢孔)
    細谷 実里奈, 市居 修, 中村 鉄平, 難波 貴志, Ali Elewa Yaser Hosny, 渡邉 敬文, 植田 弘美, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 340 -340 2019年08月 [査読有り][通常論文]
  • 精巣摘出が自己免疫疾患モデルマウスの病態形成へ与える影響
    大谷 祐紀, 市居 修, Ali Elewa Yaser Hosny, 中村 鉄平, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 341 -341 2019年08月 [査読有り][通常論文]
  • 動物の尿路関連リンパ組織(UTALT)に発現する分子群
    市居 修, 中村 鉄平, 堀野 太郎, 細谷 実里奈, Ali Elewa Yaser Hosny, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 338 -338 2019年08月 [査読有り][通常論文]
  • マウスの卵巣嚢-腹腔連絡路(卵巣嚢孔)
    細谷 実里奈, 市居 修, 中村 鉄平, 難波 貴志, Ali Elewa Yaser Hosny, 渡邉 敬文, 植田 弘美, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 340 -340 2019年08月 [査読有り][通常論文]
  • 中村 鉄平, 市居 修, 入江 隆夫, 寸田 祐嗣, 細谷 実里奈, 長崎 健一, Ali Elewa Yaser Hosny, 三嶋 隆, 昆 泰寛 日本獣医学会学術集会講演要旨集 162回 337 -337 2019年08月 [査読無し][通常論文]
  • 中村 鉄平, 市居 修, Elewa Yaser Hosny Ali, 昆 泰寛 臨床免疫・アレルギー科 71 (6) 603 -607 2019年06月 [査読有り][通常論文]
  • “Lymphoid tissues appearing in the urinary tract of animals (Urinary tract-associated lymphoid tissue, UTALT)”.
    O. Ichii, T. Nakamura, R. Ono, T. Horino, Y. H. A. Elewa, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • “Morphological characteristics of the dromedary thyroid gland - and distribution of C cells”.
    T. Nakamura, O. Ichii, Y. H. A. Elewa, W. A. M. Ghonimi, K. Nagasaki, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • “New findings of kidney disease - Kidney lesions found in Casp3 deficient mice”.
    T. Suzuki, O. Ichii, T. Nakamura, Y. H. A. Elewa, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • “Morphological and functional changes observed in bone of autoimmune disease model”.
    T. Namba, O. Ichii, Y. H. A. Elewa, T. Nakamura, J. Kimura, Y. Otani, Md. A. Masum, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • Investigation for meiotic apoptosis of spermatocyte in autoimmune disease model mouse.
    エレワ ヤセル The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan. 161th 2018年09月 [査読無し][通常論文]
  • Effect of systemic autoimmune abnormality in MRL/MpJ-Faslpr/lpr mice on the ciliary function.
    M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan 161th 2018年09月 [査読無し][通常論文]
  • “Mediastinal fat-associated lymphoid cluster and lung asthma development in papain induced lung asthma mice model
    Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon The 64th annual meeting of the Japanese the Anatomical Society (Oral Presentation). Aomori, Japan. 64th 2018年09月 [査読無し][通常論文]
  • 細谷実里奈, 市居修, ALI ELEWA, Yaser Hosny, 中村鉄平, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 296 2018年08月21日 [査読無し][通常論文]
  • 市居修, 中村鉄平, 中村鉄平, 細谷実里奈, 堀野太郎, ALI ELEWA Yaser Hosny, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 294 2018年08月21日 [査読無し][通常論文]
  • 難波貴志, 市居修, 中村鉄平, 木村純平, 木村純平, 大谷祐紀, ABDUL Masum Md, HOSNY Ali Elewa Yaser, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 285 2018年08月21日 [査読無し][通常論文]
  • 鈴木崇史, 市居修, 中村鉄平, 中村鉄平, ALI ELEWA Yaser Hosny, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 294 2018年08月21日 [査読無し][通常論文]
  • 大谷祐紀, 市居修, ALI ELEWA, Yaser Hosny, 木村純平, MASUM Md. Abdul, 中村鉄平, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 295 2018年08月21日 [査読無し][通常論文]
  • 小千田圭吾, 市居修, 中村鉄平, 中村鉄平, 池田哲平, 山下祐輔, 長澤裕哉, ALI ELEWA Yaser Hosny, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 288 2018年08月21日 [査読無し][通常論文]
  • 中村鉄平, 中村鉄平, 市居修, ALI ELEWA, Yaser Hosny, ALI ELEWA Yaser Hosny, 細谷実里奈, GHONIMI Wael A. M, 辰巳治, 長崎健一, 昆泰寛 日本獣医学会学術集会講演要旨集 161st 292 2018年08月21日 [査読無し][通常論文]
  • “Glomerular lesions seen in male cotton rats (Sigmodon hispidus)”
    T. Nakamura, O. Ichii, T. Irie, H. Kouguchi, Sunden, Masum, M. A., Y, Y. H. A. Elewa, Y. Kon The 11th Annual Meeting of the Japanese Society of Veterinary Renal Urology. 11th 2018年08月 [査読無し][通常論文]
  • Local CD34-positive capillary decreased with the progression of lesion in respective area of kidney in mice.
    Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 17th International Conference on Nephrology and Urology. London, UK. 13th March 2018. 17th 2018年03月 [査読無し][通常論文]
  • BXSB/MpJ-Yaa MICE SHOW THE INCREASE OF APOPTOTIC SPERMATOCYTES IN STAGE Ⅻ SEMINIFEROUS TUBULES.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Kuching, Sarawak, Malaysia. October 12-13, 2017. 6th 2017年10月 [査読無し][通常論文]
  • ABNOLMALITY OF OVULATION AND OOCYTE-PICK-UP IN MRL/MpJ-Faslpr/lpr MICE.
    Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, S. Otsuka-Kanazawa, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia 6th 2017年10月 [査読無し][通常論文]
  • IL-1F6/IL-36α SIGNALING REGULATES RENAL INFLAMMATION.
    O. Ichii, J. Kimura, T. Okamura, T. Horino, T. Nakamura, H. Sasaki, H. A. Elewa, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia 6th 2017年10月 [査読無し][通常論文]
  • FAT ACCUMULATION CORRELATES WITH DIABETES MELLITUS IN MALE COTTON RATS (SIGMODON HISPIDUS).
    T. Nakamura, O. Ichii, T. Irie, H. Kouguchi, Y. Sunden, K.-I. Nagasaki, Y. H. A. Elewa, Y. Kon The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia 2017年10月 [査読無し][通常論文]
  • “Mechanism and abnormality of ovulation and picking up of mammalian oocytes-Immune factors affecting the molecular morphology of the oviduct.”
    M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 5th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2017. Sapporo, Japan. 5th 2017年09月 [査読無し][通常論文]
  • “Loss of endothelial fenestration correlates with podocyte injury in the mouse model of membranoproliferative glomerulonephritis.”
    Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 5th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2017. Sapporo, Japan. 5th 2017年09月 [査読無し][通常論文]
  • “The unique phenotype in ovulation and corpus luteum formation in MRL/MpJ mouse.”
    M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 160th Meeting of the Japanese Society of Veterinary Sciences, September 13-16, 2017. Kagoshima, Japan. 160th 2017年09月 [査読無し][通常論文]
  • Histopathological features observed in the testis of autoimmune-prone BXSB/MpJ-Yaa mice.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 5th Sapporo Summer Seminar for One Health. 5th 2017年09月 [査読無し][通常論文]
  • Apoptosis of spermatocytes seen in BXSB / MpJ-Yaa mice - association with autoimmune abnormality.
    Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon The 160th Meeting of the Japanese Society of Veterinary Sciences. 160th 2017年09月 [査読無し][通常論文]
  • “Dual effects of bleomycin on the intra-thoracic immune hemostasis and lung injury in autoimmune disease model mice”.
    Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon The 63th annual meeting of the Japanese the Anatomical Society. 63th 2017年09月 [査読無し][通常論文]
  • 市居修, 堀野太郎, 大田寛, 鈴木崇史, 中村鉄平, 中村鉄平, ELEWA Yaser, Hosny Ali, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 310 -310 2017年08月30日 [査読無し][通常論文]
  • 大谷祐紀, 市居修, ELEWA Yaser, Hosny Ali, 木村純平, MASUM Md. Abdul, 中村鉄平, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 312 -312 2017年08月30日 [査読無し][通常論文]
  • 中村鉄平, 中村鉄平, 市居修, 入江隆夫, 篠原明雄, 孝口裕一, 越本知大, 長崎健一, 寸田祐嗣, ELEWA Yaser Hosny, 辰巳治, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 309 -309 2017年08月30日 [査読無し][通常論文]
  • 細谷実里奈, 市居修, ELEWA Yaser, Hosny Ali, 中村鉄平, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 160th 313 -313 2017年08月30日 [査読無し][通常論文]
  • マウス糸球体の自己免疫関連傷害における内皮細胞と有足細胞との病理学的相関性(Pathological correlations between endothelial cells and podocytes in autoimmune-related injury of the mouse glomerulus)
    Masum Md. Abdul, 市居 修, Elewa Yaser, Hosny Ali, 中村 鉄平, 昆 泰寛 日本獣医学会学術集会講演要旨集 160回 310 -310 2017年08月 [査読無し][通常論文]
  • 獣医組織学 第七版
    昆 泰寛 学窓社 2017年03月 [査読無し][通常論文]
  • 山盛徹, 笹川朋哉, 市居修, 房知輝, 昆泰寛, 稲波修 日本放射線影響学会大会抄録(Web) 59th ROMBUNNO.O7‐3 (WEB ONLY) -13 2016年10月 [査読無し][通常論文]
  • 長澤裕哉, 菊佳男, 菅原和恵, 田邉扶由子, 石川義春, 野地智法, 市居修, 昆泰寛, 麻生久, 門田耕一, 林智人 日本獣医学会学術集会講演要旨集 159th 362 2016年08月30日 [査読無し][通常論文]
  • 團塚愛, HANBERG Annika, 中村鉄平, 中村鉄平, 市居修, 昆泰寛 日本獣医学会学術集会講演要旨集 159th 314 -314 2016年08月30日 [査読無し][通常論文]
  • 中村鉄平, 中村鉄平, 市居修, 入江隆夫, 寸田祐嗣, 孝口裕一, 長崎健一, 吉安友二, 昆泰寛 日本獣医学会学術集会講演要旨集 159th 304 -304 2016年08月30日 [査読無し][通常論文]
  • 市居修, 中村鉄平, 中村鉄平, 矢吹映, 堀野太郎, 昆泰寛 日本獣医学会学術集会講演要旨集 159th 308 -308 2016年08月30日 [査読無し][通常論文]
  • 尾之内佐和, 市居修, 昆泰寛 日本獣医学会学術集会講演要旨集 159th 302 -302 2016年08月30日 [査読無し][通常論文]
  • 細谷実里奈, 中村鉄平, 中村鉄平, HOSNY Ali Elewa Yaser, HOSNY Ali Elewa Yaser, 市居修, 昆泰寛 日本獣医学会学術集会講演要旨集 159th 314 2016年08月30日 [査読無し][通常論文]
  • “Histopathological evaluation of the possible protective role of royal jelly and cod liver oil against reproductive toxicity of tartrazine in adult male albino rats.”
    Y. H. A. Elewa, A. Moustafa, A.A. Mohamed, A. A.A. Galal, O. Ichii, Y. Kon The 8th international Toxicology symposium in Africa. Cairo, Egypt. 8th 2016年08月 [査読無し][通常論文]
  • マウスにおける縦隔脂肪関連リンパクラスターとブレオマイシン誘発性肺炎との病理組織学的関連(Histopathological correlations between the mediastinal fat associated lymphoid clusters and bleomycin-induced pneumonitis in mice)
    Ali Elewa, Yaser Hosny, Masum Md.Abdul, 中村 鉄平, 市居 修, 昆 泰寛 日本獣医学会学術集会講演要旨集 159回 302 -302 2016年08月 [査読無し][通常論文]
  • マウス腎臓病モデルにおける疾患進行に伴うCD34陽性毛細血管の減少(CD34-positive capillary decreased with the progression of kidney disease in mouse models)
    Masum Md.Abdul, Yaser Hosny Ali Elewa, 中村 鉄平, 市居 修, 昆 泰寛 日本獣医学会学術集会講演要旨集 159回 308 -308 2016年08月 [査読無し][通常論文]
  • 鶏胸大動脈におけるグロムス細胞からの5-HT放出に対するH2Sの作用(Effect of H2S on 5-HT release from glomus cells in the chicken thoracic aorta)
    Delgermurun Dugar, 山口 聡一郎, 市居 修, 昆 泰寛, 伊藤 茂男, 乙黒 兼一 日本獣医学会学術集会講演要旨集 159回 495 -495 2016年08月 [査読無し][通常論文]
  • 3D-SEM法を利用した腎生検の迅速電子顕微鏡診断への応用
    高木 孝士, 城 謙輔, 大野 伸彦, 齊藤 成, Thai Quynh T, 昆 泰寛, 市居 修, Yeser Alewa H, 笹野 公伸 日本病理学会会誌 105 (1) 369 -369 2016年04月 [査読無し][通常論文]
  • “Sex-related difference of the mediastinal fat associated lymphoid clusters in MRL/MpJ-Faslpr autoimmune disease model mice.”
    Y. H. A. Elewa, O. Ichii, Y. Kon The 11th Scientific Vet. Med. (second international) conference. El-Ain-El Sokhna, Egypt. 11th 2016年03月 [査読無し][通常論文]
  • THAI Truc Quynh, NGUYEN Huy Bang, SAITOH Sei, SAITOH Yurika, SHIMO Satoshi, ELEWA Yaser, Hosny Ali, ICHII Osamu, KON Yasuhiro, TAKAKI Takashi, JOH Kensuke, OHNO Nobuhiko 日本顕微鏡学会関東支部講演会予稿集 40th 26 2016年 [査読無し][通常論文]
  • 尾之内佐和, 市居修, 昆泰寛 日本獣医学会学術集会講演要旨集 158th 277 -277 2015年08月30日 [査読無し][通常論文]
  • 市居修, 中村鉄平, 中村鉄平, 堀野太郎, 木村純平, 岡村匡史, 昆泰寛 日本獣医学会学術集会講演要旨集 158th 276 -276 2015年08月30日 [査読無し][通常論文]
  • 中村鉄平, 中村鉄平, 入江隆夫, 市居修, 篠原明夫, 浦口宏二, 越本知大, 長崎健一, 昆泰寛 日本獣医学会学術集会講演要旨集 158th 274 -274 2015年08月30日 [査読無し][通常論文]
  • A Novel Mouse Mediastinal Fat-associated Lymphoid Tissue and Its Relationship with Autoimmune Disease
    Y. H. A. Elewa, O. Ichii, S. Otsuka-Kanazaw, Y. Kon The 5th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Bali, Indonesia 5th 2015年02月 [査読無し][通常論文]
  • 安井博宣, 武内亮, 永根大幹, 山盛徹, 池中良徳, 昆泰寛, 室谷憲紀, 大石基, 長崎幸夫, 稲波修 日本放射線影響学会大会講演要旨集 57th 109 2014年09月17日 [査読無し][通常論文]
  • 市居修, 大塚沙織, 矢吹映, 堀野太郎, 中村鉄平, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 328 -328 2014年08月11日 [査読無し][通常論文]
  • 木村純平, 市居修, 大田寛, 中村鉄平, 堀野太郎, 大塚沙織, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 323 -323 2014年08月11日 [査読無し][通常論文]
  • 大谷祐紀, 市居修, 大塚沙織, 中村鉄平, 千原正尚, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 326 -326 2014年08月11日 [査読無し][通常論文]
  • 尾之内佐和, 市居修, 大塚沙織, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 325 -325 2014年08月11日 [査読無し][通常論文]
  • 大塚沙織, 市居修, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 319 -319 2014年08月11日 [査読無し][通常論文]
  • 塩水流大地, 市居修, 中村鉄平, 大塚沙織, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 324 -324 2014年08月11日 [査読無し][通常論文]
  • 中村鉄平, 千原正尚, 市居修, 大塚沙織, 長崎健一, 昆泰寛 日本獣医学会学術集会講演要旨集 157th 320 2014年08月11日 [査読無し][通常論文]
  • マウス縦隔の脂肪関連リンパ球集積の性状解析(Characterization of mouse mediastinal fat-associated lymphoid clusters)
    Elewa Yaser, Hosny Ali, 市居 修, 大塚 沙織, 昆 泰寛 日本獣医学会学術集会講演要旨集 157回 330 -330 2014年08月 [査読無し][通常論文]
  • カラーアトラス動物発生学<山本雅子、谷口和美監訳>
    昆 泰寛 緑書房 2014年04月 [査読無し][通常論文]
  • 獣医組織学 第六版
    昆 泰寛 学窓社 2014年03月 [査読無し][通常論文]
  • 千原正尚, 市居修, 大塚沙織, 昆泰寛 日本獣医学会学術集会講演要旨集 156th 200 -200 2013年08月30日 [査読無し][通常論文]
  • 岡田祐樹, 市居修, 大塚沙織, 昆泰寛 日本獣医学会学術集会講演要旨集 156th 195 -195 2013年08月30日 [査読無し][通常論文]
  • 山下由真, 市居修, 大塚沙織, 昆泰寛 日本獣医学会学術集会講演要旨集 156th 198 -198 2013年08月30日 [査読無し][通常論文]
  • 市居修, 大塚沙織, 矢吹映, 大田寛, 堀野太郎, 昆泰寛 日本獣医学会学術集会講演要旨集 156th 193 -193 2013年08月30日 [査読無し][通常論文]
  • 市居修, 大塚沙織, 中村鉄平, 野元由佳, 橋本善春, 堀野太郎, 昆泰寛 日本獣医学会学術集会講演要旨集 155th 188 -188 2013年03月04日 [査読無し][通常論文]
  • 千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 155th 188 -188 2013年03月04日 [査読無し][通常論文]
  • 中村鉄平, 市居修, 大塚沙織, 坂田侑子, 長崎健一, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 155th 188 -188 2013年03月04日 [査読無し][通常論文]
  • 木村純平, 市居修, 大塚沙織, 佐々木隼人, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 155th 187 -187 2013年03月04日 [査読無し][通常論文]
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yaser Hosny Ali Elewa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon JOURNAL OF ANATOMY 222 (3) 396 -396 2013年03月 [査読無し][通常論文]
  • 尾之内佐和, 市居修, 大塚沙織, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 154th 173 -173 2012年08月31日 [査読無し][通常論文]
  • 千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 154th 176 -176 2012年08月31日 [査読無し][通常論文]
  • 市居修, 若新英史, 村上太一, 堀野太郎, LU Huiyan, TAKAHASHI Hideko, PATRICIA Zerfas, 大塚沙織, 橋本善春, 昆泰寛, KOPP Jeffrey 日本獣医学会学術集会講演要旨集 154th 176 -176 2012年08月31日 [査読無し][通常論文]
  • 節足動物DNAのリボゾームRNA遺伝子ITS領域のサイズ分析による生物種同定の試み
    佐藤 福太郎, 遠藤 大二, 吉村 貴行, 伊東 拓也, 長 雄一, 浅川 満彦, 昆 泰寛, 市居 修, 大塚 沙織, 林 正信 獣医寄生虫学会誌 10 (1-2) 50 -50 2012年03月 [査読無し][通常論文]
  • 中村鉄平, 坂田侑子, 大塚沙織, 市居修, 並木由佳, 長崎健一, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 153rd 194 -194 2012年03月01日 [査読無し][通常論文]
  • 木村純平, 市居修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆泰寛 解剖学雑誌 87 (1) 5 -5 2012年03月01日 [査読無し][通常論文]
  • 千原正尚, 市居修, 大塚沙織, 並木由佳, 池淵良洋, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 153rd 194 -194 2012年03月01日 [査読無し][通常論文]
  • D. Torigoe, O. Ichii, D. Ruihua, T. Ohnaka, S. Okano, Y. Kon, N. Sasaki, T. Agui JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE 50 (5) 793 -793 2011年09月 [査読無し][通常論文]
  • 小千田圭吾, 市居修, 大塚沙織, 並木由佳, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 152nd 175 -175 2011年08月31日 [査読無し][通常論文]
  • 大塚沙織, 市居修, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆泰寛 日本獣医学会学術集会講演要旨集 152nd 168 -168 2011年08月31日 [査読無し][通常論文]
  • 中村鉄平, 市居修, 大塚沙織, 並木由佳, 坂田侑子, 長崎健一, 服部秀樹, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 152nd 172 -172 2011年08月31日 [査読無し][通常論文]
  • 長沼佑季, 市居修, 大塚沙織, 並木由佳, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 152nd 175 -175 2011年08月31日 [査読無し][通常論文]
  • 佐藤福太郎, 遠藤大二, 吉村貴行, 伊東拓也, 長雄一, 浅川満彦, 昆泰寛, 市居修, 大塚沙織, 林正信 日本獣医学会学術集会講演要旨集 152nd 207 2011年08月31日 [査読無し][通常論文]
  • 鳥越大輔, 市居修, 党瑞華, 佐々木宣哉, 昆泰寛, 安居院高志 日本実験動物学会総会講演要旨集 58th 173 2011年05月12日 [査読無し][通常論文]
  • 千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛 解剖学雑誌 86 (1) 12 -12 2011年03月 [査読無し][通常論文]
  • 中村鉄平, 市居修, 大塚沙織, 並木由佳, 長崎健一, 服部秀樹, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 151st 190 -190 2011年03月01日 [査読無し][通常論文]
  • 瀬戸隆弘, 吉川佳佑, 真田崇弘, SAASA Ngonda, 尾崎由佳, 市居修, 好井健太朗, 昆泰寛, 苅和宏明 日本獣医学会学術集会講演要旨集 151st 245 -245 2011年03月01日 [査読無し][通常論文]
  • 市居修, 大塚沙織, 並木由佳, 佐々木宣哉, 橋本善春, 遠藤大二, 昆泰寛 日本獣医学会学術集会講演要旨集 151st 189 -189 2011年03月01日 [査読無し][通常論文]
  • 李愼曉, 大塚沙織, 市居修, 並木由佳, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 151st 190 -190 2011年03月01日 [査読無し][通常論文]
  • 遠藤大二, 吉村貴行, 佐藤福太郎, 伊東拓也, 長雄一, 浅川満彦, 昆泰寛, 市居修, 大塚沙織, 林正信 日本獣医学会学術集会講演要旨集 151st 220 2011年03月01日 [査読無し][通常論文]
  • 西野智博, 佐々木宣哉, 長崎健一, 市居修, 昆泰寛, 安居院高志 日本獣医学会学術集会講演要旨集 151st 276 2011年03月01日 [査読無し][通常論文]
  • 獣医組織学 第五版
    昆 泰寛 学窓社 2011年03月 [査読無し][通常論文]
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon VETERINARY RESEARCH COMMUNICATIONS 34 (8) 727 -727 2010年12月 [査読無し][通常論文]
  • ヤギの大唾液腺における離乳前・後期のアクアポリンファミリー発現の比較解析(Comparative analysis of the expression of aquaporin family between pre- and post-weaning periods in goat major salivary glands)
    Yaser Elewa, 市居 修, 大塚 沙織, 金澤 智則, 李 愼曉, 並木 由佳, 昆 泰寛, 橋本 善春 日本獣医学会学術集会講演要旨集 150回 160 -160 2010年09月 [査読無し][通常論文]
  • 大塚沙織, 市居修, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆泰寛 日本獣医学会学術集会講演要旨集 150th 154 -154 2010年09月01日 [査読無し][通常論文]
  • 市居修, 大塚沙織, 矢吹映, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆泰寛 日本獣医学会学術集会講演要旨集 150th 160 -160 2010年09月01日 [査読無し][通常論文]
  • 木村純平, 市居修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 150th 160 -160 2010年09月01日 [査読無し][通常論文]
  • 多様性の高い複数の塩基配列についてdegenerateプライマーを設計するCoCoMoウェブサーバ
    遠藤 大二, 水谷 哲也, 森川 茂, 浜口 功, 滝澤 和也, 酒井 宏治, 長 雄一, 浅川 満彦, 昆 泰寛, 林 正信 日本獣医学会学術集会講演要旨集 149回 253 -253 2010年03月 [査読無し][通常論文]
  • ヤギ耳下腺の年齢関連の構造変化(Age-related structural changes of parotid salivary glands in goat)
    Elewa Yaser, 橋本 善春, 市居 修, 大塚 沙織, 金澤 智則, 昆 泰寛 日本獣医学会学術集会講演要旨集 149回 211 -211 2010年03月 [査読無し][通常論文]
  • 金澤智則, 大塚沙織, 市居修, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 149th 216 -216 2010年03月 [査読無し][通常論文]
  • 市居修, 矢吹映, 佐々木宣哉, 大田寛, 滝口満喜, 大塚沙織, 橋本善春, 遠藤大二, 昆泰寛 日本獣医学会学術集会講演要旨集 149th 213 -213 2010年03月 [査読無し][通常論文]
  • 大塚沙織, 市居修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆泰寛 日本獣医学会学術集会講演要旨集 149th 213 -213 2010年03月 [査読無し][通常論文]
  • 千原正尚, 大塚沙織, 市居修, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 148th 155 -155 2009年09月 [査読無し][通常論文]
  • 市居修, 昆泰寛, 佐々木宣哉, 橋本善春, 大田寛, 滝口満喜, 矢吹映, 遠藤大二 日本獣医学会学術集会講演要旨集 147th 79 -79 2009年03月01日 [査読無し][通常論文]
  • 市居修, 昆泰寛, 佐々木宣哉, 矢吹映, 大塚沙織, 橋本善春, 遠藤大二 日本獣医学会学術集会講演要旨集 148th 153 2009年 [査読無し][通常論文]
  • 大塚沙織, 市居修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆泰寛 日本顕微鏡学会北海道支部学術講演会講演要旨集 2009 11 2009年 [査読無し][通常論文]
  • 千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛 日本顕微鏡学会北海道支部学術講演会講演要旨集 2009 12 2009年 [査読無し][通常論文]
  • 佐々木宣哉, 市居修, 昆泰寛, 安居院高志 日本獣医学会学術集会講演要旨集 146th 300 -300 2008年09月05日 [査読無し][通常論文]
  • 市居修, 上川昭博, 佐々木宣哉, 今野明弘, 遠藤大二, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 146th 147 -147 2008年09月05日 [査読無し][通常論文]
  • 獣医発生学<谷口和之、木曽康郎、佐藤英明監訳>
    昆 泰寛 学窓社 2008年09月 [査読無し][通常論文]
  • 市居修, 今野明弘, 佐々木宣哉, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 145th 161 -161 2008年03月07日 [査読無し][通常論文]
  • カラーアトラス獣医解剖学(上下巻)<カラーアトラス獣医解剖学編集委員会監訳>>
    昆 泰寛 チクサン出版社 2008年03月 [査読無し][通常論文]
  • 市居修, 今野明弘, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 144th 33 -33 2007年08月27日 [査読無し][通常論文]
  • 動物を犠牲にしない獣医学教育の実践 東南アジア/オセアニア諸国の獣医学教育
    橋本 善春, 昆 泰寛, 奥村 正裕, 伊藤 茂男 日本獣医学会学術集会講演要旨集 144回 23 -23 2007年08月 [査読無し][通常論文]
  • 獣医組織学 第四版
    昆 泰寛 学窓社 2007年03月 [査読無し][通常論文]
  • 市居修, 今野明弘, 橋本善春, 昆泰寛 日本獣医学会学術集会講演要旨集 142nd 40 -40 2006年08月31日 [査読無し][通常論文]
  • 動物を犠牲にしない獣医学教育の実践 EUの獣医学教育
    橋本 善春, 昆 泰寛, 奥村 正裕, 伊藤 茂男 日本獣医学会学術集会講演要旨集 142回 27 -27 2006年08月 [査読無し][通常論文]
  • ヘキサマー頻度分布比較によるウイルスゲノムのヒトゲノムおよびリボゾームRNAとの類似性比較
    遠藤 大二, 水谷 哲也, 斎藤 秀俊, 森川 茂, 浜口 功, 昆 泰寛, 林 正信 日本獣医学会学術集会講演要旨集 142回 92 -92 2006年08月 [査読無し][通常論文]
  • Hironobu Yasui, Taketoshi Asanuma, Osamu Inanami, Gregory Durand, Ange Polidori, Yasuhiro Kon, Bernard Pucci, Mikinori Kuwabara FREE RADICAL BIOLOGY AND MEDICINE 41 S77 -S77 2006年 [査読無し][通常論文]
  • 動物を犠牲にしない獣医学教育の試みーEU圏の獣医解剖学と獣医外科学教育の現状についてー
    獣医臨床 24 (12) 1 -8 2006年 [査読無し][通常論文]
  • 遺伝子配列上のオリゴマー配列パターン解析を利用した新興ウイルス検出技術
    遠藤 大二, 水谷 哲也, 桐沢 力雄, 斎藤 秀俊, 牧 与志幸, 森川 茂, 昆 泰寛, 林 正信 日本獣医学会学術集会講演要旨集 140回 105 -105 2005年08月 [査読無し][通常論文]
  • 牛の解剖アトラス<日本獣医解剖学会監訳>
    昆 泰寛 緑書房 2005年03月 [査読無し][通常論文]
  • 獣医組織学 第三版
    2005年 [査読無し][通常論文]
  • Atsushi ASANO, Yasuhiro KON, Takashi AGUI J. Vet. Med. Sci. 66 (12) 1523 -1528 2004年 [査読無し][通常論文]
  • 犬の解剖カラーリングアトラス<日本獣医解剖学会監訳>
    昆 泰寛 学窓社 2003年10月 [査読無し][通常論文]
  • Y Namiki, D Endoh, Y Kon MOLECULAR REPRODUCTION AND DEVELOPMENT 64 (2) 179 -188 2003年02月 [査読無し][通常論文]
     
    It has been reported that the MRL/MpJ mouse strain shows several unique phenotypes, including rapid wound healing, inherent collagen disease, heat shock-resistant spermatocytes, and metaphase-specific apoptosis (Msa) in the testis. In the present study, we found the genetic mutation associated with Msa by chromosomal mapping with 555 backcross progeny. The Sertoli cell index of abnormal metaphasic spermatocytes was clearly divided into two groups in the first 200 male backcross progeny, which were created by mating female F1 (female C57BL/6 x male MRL/MpJ) with male MRL/MpJ mice, indicating that Msa was caused by only one gene. The result of chromosomal mapping throughout the 555 backcross progeny by using microsatellite markers and single nucleotide polymorphism (SNP) revealed that Msa was mapped on the telomeric region of chromosome 1 and was significantly linked with exonuclease 1 (Exo1) and choroideremia-like (rab escort protein 2) (Chml/Rep2) genes. It was found that the Chml/Rep2 gene was not a candidate for Msa by means of the nucleotide sequences of several inbred strains. On the Exo1 gene in strain MRL/MpJ, but not in other strains, it was surprisingly noted that the truncated forms (tr1-Exo1 and tr2-Exo1) were expressed in all tissues examined as well as normal Exo1 by reverse transcriptase-polymerase chain reaction (RT-PCR). Additionally, the truncated forms of the Exo1 gene were suggested to be transcribed by alternative splicing of the 9th exon, possibly resulting from nucleotide substitution of the branch site existing in the 8th intron. These results suggested that the testicular meiotic Msa in MRL/MpJ mice was a unique phenotype caused by incomplete alternative splicing of the Exo1 gene.
  • 『犬の解剖アトラス(第2版)』
    学窓社 2002年 [査読無し][通常論文]
  • Khlood El.Bohi M, Miyoshi Hiroyuki, Iwata Hisato, Kazusaka Akio, Kon Yasuhiro, Abou Hadid Ali H, Moustafe El. Kelish, Ghonim Mervat H, Fujita Shoichi Japanese Journal of Veterinary Research 47 (1-2) 13 -23 1999年08月 [査読無し][通常論文]
     
    To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Darns were killed on the 20th. day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects : the fetal resorption amounted to similar to 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were: absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.
  • Y Kon, D Endoh ANATOMIA HISTOLOGIA EMBRYOLOGIA-JOURNAL OF VETERINARY MEDICINE SERIES C-ZENTRALBLATT FUR VETERINARMEDIZIN REIHE C 28 (4) 239 -242 1999年08月 [査読無し][通常論文]
     
    The renin-angiotensin system (RAS) controls the regulation of blood pressure and water-mineral balance. Recently, renin has been reported to be synthesized and secreted outside the kidney. The present study investigated immunohistochemically the distribution of renin in exocrine glands, i.e. salivary glands and coagulating glands, in male mice of 13 strains. In some strains, renin was detected in the sublingual and submandibular salivary glands, but not in the parotid glands. It was restricted to the striated or granular portions of excretory ducts. In coagulating glands, variable staining patterns were found. These results demonstrate the existence of variations in renin content in mouse strains and offered a selection of mouse strains for investigation of exocrine gland renin.
  • Y Kon, H Horikoshi, D Endoh CELL AND TISSUE RESEARCH 296 (2) 359 -369 1999年05月 [査読無し][通常論文]
     
    Apoptosis of male germ cells is a widespread but little-understood phenomenon in many animal species. The elucidation of its mechanisms could be useful in the understanding of male infertility. We have examined the distribution of dying cells with the terminal transferase-mediated nick-end labeling (TUNEL) method and by an electron-microscopic procedure in the testes of 10 mouse strains, viz., C57BL/10 (B10), SL/NiA (SL), C57BL/6 (B6), C3H/He (C3H), BALB/c (BALB), DBA2 (DBA), CBA/J (CBA), MRL/MpJ-+/+ (M+), MRL/MpJ-lpr/lpr (lpr), and wild-type NJL mice (Mus musculus musculus). In the testes of the B10, NJL, SL, B6, C3H, BALE, DBA, and CBA mice, very few TUNEL-positive cells are distributed in the seminiferous tubules, whereas in the testes of the M+ and lpr mice, many TUNEL-positive cells, which are restricted to stage XII seminiferous tubules, have been identified. The most important finding is that many metaphases of meiotic spermatocytes show a marked TUNEL-positive reaction. Some metaphases show apoptotic morphology electron-microscopically. These results suggest that the testes of MRL strains will provide a useful model for the study of the mechanism of metaphase-specific apoptosis in meiotic spermatocytes.
  • Y Kon, D Endoh HISTOLOGY AND HISTOPATHOLOGY 11 (1) 257 -266 1996年01月 [査読無し][通常論文]
     
    The presence of an extrarenal or local renin-angiotensin system has been noted in several tissues, although their functions have not yet been clarified. Renin from the coagulating gland (CG), is the most recently discovered local renin, and is a significant subject for investigation with histological and molecular biological techniques. Dot-like reactions for renin are detected immunohistochemically in the epithelial cells of CGs of the strains C57BL/6 mice. Excretory products of some terminal lumina are also found to be positive for renin. Colloidal gold particles, indicating the presence of renin, are detected in the lysosomal granules, in which they are especially located on the crystalline structure. They are also observed in the production of series of exocrine granules. At the apical re ion, both renin- positive exocrine and lysosomal granules are secreted by exocytosis. In the development, immunoreactivity for renin is first detected at 6 weeks after birth. After that time, the number of renin-containing cells gradually increase throughout the development. In adults, several patterns of renin immunoreactivity are demonstrated in almost all epithelial cells of CGs. At 4 weeks after castration, renin-containing cells in terminal ducts are decreased and remain at very low levels. After testosterone injection, the numerical value of renin-containing cells is high at 1 week. Finally, renin mRNA is detected in the CGs by Northern blot analysis and hybridohistochemistry. These findings suggest that renin is synthesized depending on testosterone, and released by exocrine secretion.
  • M NAGATA, K TANIMOTO, A FUKAMIZU, Y KON, F SUGIYAMA, K MURAKAMI, T WATANABE JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 6 (3) 878 -878 1995年09月 [査読無し][通常論文]
  • Y KON, Y HASHIMOTO, M SUGIMURA JOURNAL OF ELECTRON MICROSCOPY 39 (3) 212 -212 1990年06月 [査読無し][通常論文]
  • Y HASHIMOTO, T IMAGAWA, H KITAGAWA, Y KON, M SUGIMURA JOURNAL OF ELECTRON MICROSCOPY 39 (2) 129 -130 1990年04月 [査読無し][通常論文]
  • Y HASHIMOTO, N HOSHI, H KITAGAWA, Y KON, N KUDO JOURNAL OF ELECTRON MICROSCOPY 38 (1) 77 -78 1989年 [査読無し][通常論文]
  • Y HASHIMOTO, M NAKAI, H KITAGAWA, Y KON, N KUDO JOURNAL OF ELECTRON MICROSCOPY 37 (2) 108 -108 1988年 [査読無し][通常論文]

受賞

  • 2013年11月 日本学術振興会 科学研究費優秀審査員賞
  • 1999年04月 日本獣医学会 日本獣医学会賞
     レニン産生細胞の発生機序と新機能に関する研究 
    受賞者: 昆 泰寛

共同研究・競争的資金等の研究課題

  • ウシのリンパ陰部輪の発見 ―粘膜ワクチン投与部位としての有効性―
    日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 2019年04月 -2024年03月 
    代表者 : 昆 泰寛, エレワ ヤセル, 市居 修, 中村 鉄平
     
    我々は、ウシを主として、様々な動物種における尿生殖器の粘膜関連リンパ組織を探索している。特に、生殖器は外界と直接交通しており、抗原に暴露されやすい部位である。一方、動物におけるその存在には不明な点が多い。特に産業動物獣医療では、感染症対策のために局所粘膜免疫の誘導が重要であり、その局在解析は粘膜ワクチン等への臨床応用に繋がると考えている。 まず今年度は、実験動物種(マウス、コットンラット)の尿生殖器を精査し、その有無を組織学的に調べた。これらの動物種の泌尿器には、リンパ球や細網線維・膠原線維で構成されるリンパ組織様構造が観察される一方、生殖器にその存在を見出せなかった。次いで、ウシに加えて、ヤギ、ミニブタおよびイヌの生殖器を形態学的に解析し、粘膜リンパ組織の有無を検証した。ホールマウントヘマトキシリン標本の観察において、いずれの動物においても腟前庭部位に小円形ならびにクレーター状の構造が観察された。これらは特に陰核窩周囲に多い傾向にあった。この構造を組織学的観察したところ、腟前庭の粘膜上皮細胞が一部欠損し、その直下にリンパ球の散在性あるいは濾胞性集簇が認められた。 我々はこのような構造を「生殖器関連リンパ組織」と定義しており、これらは特に外界に接する陰部で発達し、ワルダイエル咽頭輪のように「リンパ陰部輪」を形成して免疫学的関門を担っていると考えている。本年度は形態学的解析を中心に進めたが、来年度は機能的な推察など、更なる解析を進める。
  • アダムからイブを作る ー雄ゲノムのみによる個体作出の挑戦ー
    日本学術振興会:科学研究費助成事業 挑戦的研究(萌芽)
    研究期間 : 2019年06月 -2022年03月 
    代表者 : 昆 泰寛, エレワ ヤセル, 市居 修, 中村 鉄平
     
    一般的な生命科学の知見に基づくと、哺乳類の雄は精子を、雌は卵子を生成し、それらの受精を経て、胚が形成される。一方で、遺伝的な性とは異なる形態的な性を獲得する場合もある。我々はこれまでの研究において、MRL/MpJマウスとAKRマウスの雄の曲精細管内に卵細胞が存在することを報告してきた。つまり、正常な哺乳類においても雄が卵子を作るメカニズムが潜在し、受精卵となる可能性を秘める。本研究の目的は、精子形成細胞が卵細胞に形質転換する(アダムからイブを作り出す)機構を発見・発展させ、オスゲノムのみによる個体の作出に挑戦する。 本年度は、有用な培養法と培養に用いる精巣内卵細胞の適切な回収時期を検討するため、雄のMRL/MpJマウスを用いて、精巣内卵細胞の出現時期の再検討を実施してきた。過去のデータを基に、新生子期から生後1ヶ月のMRL/MpJマウスの精巣内卵細胞を解析したところ、生後12日から14日齢でその出現率が高い傾向にあった。これらの時期は、精巣内卵細胞を効率よく回収できる時期であると考えている。また、MRL/MpJマウスの精巣形態の経時的解析において、精巣内卵細胞は、卵巣内の成熟卵胞に包含されるような卵細胞のようには発達していなかった。つまり、このような精巣内卵細胞の培養には、発生工学や不妊治療等で用いられている卵巣内の未熟卵胞の体外発育培養法やホルモン・成長因子の添加が有用であると考えられた。
  • コットンラット:複数疾患を具有する実験用齧歯目のヒト併存症モデルへの応用
    学術振興会:科学研究費
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 中村鉄平
  • 体液顕微解剖の実践:原尿中エクソソーム由来マイクロRNAに腎障害マーカーを求めて
    学術振興会:科学研究費
    研究期間 : 2018年04月 -2020年03月 
    代表者 : 市居 修
  • 記憶する腸ー屈曲のストーリーー
    学術振興会:科学研究費
    研究期間 : 2013年04月 -2015年03月 
    代表者 : 昆 泰寛
  • 自己免疫疾患と不妊症に関する分子解剖学ー発症と精子発生発生チェックポイントとの関連ー
    学術振興会:科学研究費
    研究期間 : 2012年04月 -2015年03月 
    代表者 : 昆 泰寛
  • 精巣内卵細胞の解析
    科学研究費補助金
    研究期間 : 2007年
  • Analysis for intratesticular oocytes
    Grant-in-Aid for Scientific Research
    研究期間 : 2007年
  • ネフロン形成の分子基盤
    研究期間 : 2000年
  • 精巣内アポトーシスの解析
    研究期間 : 2000年
  • Analysis of apoptosis in testis
    研究期間 : 2000年

教育活動情報

主要な担当授業

  • 研究機器演習
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 大学院共通授業科目(教育プログラム):博物館学
    開講年度 : 2020年
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 学術標本・資料、博物館、学芸員、アドバンストコース
  • 獣医科学特別研究
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 専門獣医科学特論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 専門獣医科学特論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 先端生命科学特論Ⅰ:発生生物学
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医科学特論演習
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 生命科学特論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医科学基礎科目B 研究機器演習
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 研究機器演習(総合成績)
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • 先端獣医科学特論B 生命科学特論Ⅳ:発生生物工学
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 研究機器演習(総合成績)
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医科学特別研究
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 組織学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 顕微鏡、細胞、上皮組織、結合組織、支持組織、筋組織、神経組織、消化器系、呼吸器系、尿生殖器系、内分泌系、免疫系、神経系、感覚器、外皮、鳥類組織学、免疫組織学、超微形態学
  • 獣医科学特論演習
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 魚病学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 魚病、魚類、水産、感染症
  • 研究機器演習
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 獣医倫理・動物福祉
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 生命倫理、獣医倫理、動物福祉、伴侶動物、産業動物、実験動物、展示動物、野生動物
  • 獣医学総合演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 農畜産演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 作物栽培、家畜飼育(ブタ)、搾乳、畜産物加工
  • 獣医学総合実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 一般教育演習(フレッシュマンセミナー)
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 動物、器官、臓器、組織、構造、細胞、発生
  • 卒業論文
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 発生学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 発生生物学、モデル動物、前発生、始原生殖細胞、卵割、着床、胎膜(卵黄嚢、栄養膜、羊膜、尿膜、絨毛膜、胎盤)、外胚葉、中胚葉、内胚葉、神経管、神経堤、心内膜筒、心ループ、心内膜隆起、大動脈弓、主静脈、卵黄?静脈、臍静脈、咽頭弓、前腸、中腸、後腸、中腎管、中腎傍管、尿管芽、生殖索、膜性骨化、軟骨性骨化
  • 解剖学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 組織学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 細胞、上皮組織、結合組織、支持組織、筋組織、神経組織、消化器系、呼吸器系、尿生殖器系、内分泌系、免疫系、神経系、感覚器、外皮、鳥類組織学
  • 解剖学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 獣医学専門セミナーⅡ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 課題研究、研究情報の入手、研究の進め方、獣医学英語
  • 組織学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 解剖学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 骨学、筋学、脈管学、神経学、内臓学、肉眼解剖学、解剖学用語
  • 組織学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 解剖学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 骨学、筋学、脈管学、神経学、内臓学、肉眼解剖学、解剖学用語
  • 発生学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 魚病学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 札幌基礎獣医学演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 獣医学概論
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 獣医法規
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 獣医倫理
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 生物科学基礎演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 水産学概論
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 短期現地実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 長期現地実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 研究・臨床セミナー
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • アドバンスト演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部

大学運営

学内役職歴

  • 2017年4月1日 - 2019年3月31日 大学院獣医学院長
  • 2019年4月1日 - 2021年3月31日 大学院獣医学院長
  • 2013年4月1日 - 2014年3月31日 教育研究評議会評議員
  • 2014年4月1日 - 2016年3月31日 教育研究評議会評議員
  • 2016年4月1日 - 2017年3月31日 教育研究評議会評議員
  • 2017年4月1日 - 2019年3月31日 教育研究評議会評議員
  • 2019年4月1日 - 2021年3月31日 教育研究評議会評議員

委員歴

  • 2017年09月 - 現在   日本獣医学会解剖学分科会   会長
  • 2021年09月 - 2023年08月   公益法人日本獣医学会   理事
  • 2016年09月 - 2017年08月   公益法人日本獣医学会   理事
  • 2014年04月 - 2016年03月   日本獣医学会   監事
  • 日本獣医学会   評議員   日本獣医学会

社会貢献活動

  • 佐藤新渡戸記念寮
    役割 : 運営参加・支援


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