71 results on '"Takeda, Naoki"'
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2. The diagnostic utility of cytology specimen in a case of EWSR1::NFATC2 sarcoma.
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Takeda, Naoki, Makise, Naohiro, Kageyama, Hajime, Takahashi, Tsukasa, Katoh, Hiroshi, Odaka, Akiko, Oikawa, Mariko, Sugiyama, Takahiro, Kawana, Hidetada, Araki, Akinobu, Kinoshita, Hideyuki, Hagiwara, Yoko, Kamoda, Hiroto, Yonemoto, Tsukasa, and Itami, Makiko
- Abstract
EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma. Following histologic review, we successfully performed immunocytochemistry and fluorescence in situ hybridization (FISH) on archival cytology specimens. The tumor cells were positive for NKX2-2, NKX3-1, and PAX7 and showed amplified 5ʹ single signals of EWSR1 gene. Reverse transcriptase-polymerase chain reaction revealed an in-frame fusion of EWSR1 and NFATC2. This report describes the cytological features of EWSR1::NFATC2 sarcoma and highlights the diagnostic utility of archival cytology specimens. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Loss of Dja2 accompanies pH deviation in lysosomes and lysosome‐related organelles.
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Terada, Kazutoyo, Endo, Motoyoshi, Kiyonari, Hiroshi, Takeda, Naoki, and Oike, Yuichi
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ORGANELLES ,ALVEOLAR macrophages ,PROTEIN C ,LYSOSOMES ,MECONIUM aspiration syndrome ,GLYCOLIPIDS ,AMILORIDE - Abstract
The Dja2 knockout (Dja2−/−) mice had respiratory distress, and >60% died within 2 days after birth. The surviving adult Dja2−/− mice were infertile and the lungs of Dja2−/− mice showed several abnormalities, including the processing defect of prosurfactant protein C in the alveolar epithelial type II cells and the accumulation of glycolipids in enlarged alveolar macrophages. The luminal pH of acidic organelles in Dja2−/− cells was shifted to pH 5.37–5.45. This deviated pH was immediately restored to control levels (pH 4.56–4.65) by the addition of a diuretic, ethyl isopropyl amiloride (EIPA). Although the role of DJA2 in maintaining the pH homeostasis of lysosome‐related organelles is currently obscure, this rapid and remarkable pH resilience is best explained by an EIPA‐sensitive proton efflux machinery that is disorganized and overactivated due to the loss of Dja2. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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4. Independent origins of fetal liver haematopoietic stem and progenitor cells.
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Yokomizo, Tomomasa, Ideue, Takako, Morino-Koga, Saori, Tham, Cheng Yong, Sato, Tomohiko, Takeda, Naoki, Kubota, Yoshiaki, Kurokawa, Mineo, Komatsu, Norio, Ogawa, Minetaro, Araki, Kimi, Osato, Motomi, and Suda, Toshio
- Abstract
Self-renewal and differentiation are tightly controlled to maintain haematopoietic stem cell (HSC) homeostasis in the adult bone marrow1,2. During fetal development, expansion of HSCs (self-renewal) and production of differentiated haematopoietic cells (differentiation) are both required to sustain the haematopoietic system for body growth3,4. However, it remains unclear how these two seemingly opposing tasks are accomplished within the short embryonic period. Here we used in vivo genetic tracing in mice to analyse the formation of HSCs and progenitors from intra-arterial haematopoietic clusters, which contain HSC precursors and express the transcription factor hepatic leukaemia factor (HLF). Through kinetic study, we observed the simultaneous formation of HSCs and defined progenitors—previously regarded as descendants of HSCs5—from the HLF
+ precursor population, followed by prompt formation of the hierarchical haematopoietic population structure in the fetal liver in an HSC-independent manner. The transcription factor EVI1 is heterogeneously expressed within the precursor population, with EVI1hi cells being predominantly localized to intra-embryonic arteries and preferentially giving rise to HSCs. By genetically manipulating EVI1 expression, we were able to alter HSC and progenitor output from precursors in vivo. Using fate tracking, we also demonstrated that fetal HSCs are slowly used to produce short-term HSCs at late gestation. These data suggest that fetal HSCs minimally contribute to the generation of progenitors and functional blood cells before birth. Stem cell-independent pathways during development thus offer a rational strategy for the rapid and simultaneous growth of tissues and stem cell pools.In fetal liver, the structure of the differentiated haemapoietic progenitor cell population is established directly from precursor cells, independently of haemapoietic stem cells. [ABSTRACT FROM AUTHOR]- Published
- 2022
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5. Association between functional foods and cardiometabolic health in a real-life setting: a longitudinal observational study using objective diet records from an electronic purchase system.
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Shirai, Yoshiro, Sakuma, Masae, Nagasaka, Yuji, Takeda, Naoki, Matsui, Kunio, and Nakamura, Mieko
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- 2022
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6. High salt exacerbates acute kidney injury by disturbing the activation of CD5L/apoptosis inhibitor of macrophage (AIM) protein.
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Wang, Ching-Ting, Tezuka, Tetsushi, Takeda, Naoki, Araki, Kimi, Arai, Satoko, and Miyazaki, Toru
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ACUTE kidney failure ,IMMUNOGLOBULIN M ,PROXIMAL kidney tubules ,CHRONIC kidney failure ,MACROPHAGES ,SALT ,DISEASE exacerbation - Abstract
The influence of excess salt intake on acute kidney injury (AKI) has not been examined precisely except for some clinical data, unlike in chronic kidney disease. Here, we addressed the influence of high salt (HS) on AKI and its underlying mechanisms in terms of the activity of circulating apoptosis inhibitor of macrophage (AIM, also called CD5L) protein, a facilitator of AKI repair. HS loading in mice subjected to ischemia/reperfusion (IR) resulted in high mortality with advanced renal tubular obstruction and marked exacerbation in biomarkers of proximal renal tubular damage. This AKI exacerbation appeared to be caused mainly by the reduced AIM dissociation from IgM pentamer in serum, as IgM-free AIM is indispensable for the removal of intratubular debris to facilitate AKI repair. Injection of recombinant AIM (rAIM) ameliorated the AKI induced by IR/HS, dramatically improving the tubular damage and mouse survival. The repair of lethal AKI by AIM was dependent on AIM/ kidney injury molecule-1 (KIM-1) axis, as rAIM injection was not effective in KIM-1 deficient mice. Our results demonstrate that the inhibition of AIM dissociation from IgM is an important reason for the exacerbation of AKI by HS, that AIM is a strong therapeutic tool for severe AKI. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. Novel powder electroluminescent device enabling control of emission color by thermal response.
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Tsuneyasu, Shota, Takeda, Naoki, and Satoh, Toshifumi
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ELECTROLUMINESCENT devices ,EMISSION control ,POWDERS ,TEMPERATURE control ,BLUE light - Abstract
We demonstrated the emission of multicolored light from a powder electroluminescent device using a thermochromic material through temperature control. At 20°C, the emission of a sapphire blue light was observed. Upon increasing the temperature, the color of the thermochromic materials changed, leading to sky‐blue emission. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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8. VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet-Induced Stress.
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Sakano, Daisuke, Uefune, Fumiya, Tokuma, Hiraku, Sonoda, Yuki, Matsuura, Kumi, Takeda, Naoki, Nakagata, Naomi, Kume, Kazuhiko, Shiraki, Nobuaki, and Kume, Shoen
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REACTIVE oxygen species ,MONOAMINE transporters ,DOPAMINE ,MONOAMINE oxidase ,BLOOD sugar - Abstract
Vesicular monoamine transporter 2 (VMAT2) uptakes cytoplasmic monoamines into vesicles for storage. VMAT2 plays a role in modulating insulin release by regulating dopamine levels in the pancreas, although the exact mechanism remains elusive. We found that VMAT2 expression in β-cells specifically increases under high blood glucose conditions. The islets isolated from β-cell-specific Vmat2 knockout (βVmat2KO) mice show elevated insulin secretion levels in response to glucose stimulation. Under prolonged high-fat diet feedings, the βVmat2KO mice exhibit impaired glucose and insulin tolerance and progressive β-cell dysfunction. Here we demonstrate VMAT2 uptake of dopamine to protect dopamine from degradation by monoamine oxidase, thereby safeguarding β-cells from excess reactive oxygen species (ROS) exposure. In the context of high demand for insulin secretion, the absence of VMAT2 leads to elevated ROS in β-cells, which accelerates β-cell dedifferentiation and β-cell loss. Therefore, VMAT2 controls the amount of dopamine in β-cells, thereby protecting pancreatic β-cells from excessive oxidative stress. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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9. A vegetable oil–based biopesticide with ovicidal activity against the two‐spotted spider mite, Tetranychus urticae Koch.
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Takeda, Naoki, Takata, Ayumi, Arai, Yuka, Sasaya, Kazuhiro, Noyama, Shimpei, Wakisaka, Shigekazu, Ghazy, Noureldin Abuelfadl, Voigt, Dagmar, and Suzuki, Takeshi
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TWO-spotted spider mite ,SPIDER mites ,PREDATORY mite ,COTTONSEED oil ,SAFFLOWER oil ,VEGETABLE oils - Abstract
A recently developed biopesticide made of safflower and cottonseed oils has excellent ovicidal activity against the hard‐to‐control spider mite Tetranychus urticae Koch (Acari: Tetranychidae). It has attracted attention as a sustainable treatment for controlling T. urticae because it has low potential for promoting resistance and little effect on the predatory mite Neoseiulus californicus (McGregor) (Acari: Phytoseiidae), which is an important natural enemy of spider mites. Here, we investigated the mechanism of its ovicidal activity against T. urticae. The oil droplets in the oil‐in‐water emulsion of the biopesticide strongly adhered to T. urticae eggs, seeped through the chorion being cut during hatching, and inhibited the embryonic rotational movement necessary for cutting and hatching. No adverse effect was observed on N. californicus eggs even in undiluted biopesticide. We conclude that this biopesticide and N. californicus can be used simultaneously in the integrated management of T. urticae in oily biopesticide‐tolerant plant species. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. Phosphorylation of the Anaphase Promoting Complex activator FZR1/CDH1 is required for Meiosis II entry in mouse male germ cell.
- Author
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Tanno, Nobuhiro, Kuninaka, Shinji, Fujimura, Sayoko, Takemoto, Kazumasa, Okamura, Kaho, Takeda, Naoki, Araki, Kimi, Araki, Masatake, Saya, Hideyuki, and Ishiguro, Kei-ichiro
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ACTIVATORS (Chemistry) ,ANAPHASE ,UBIQUITIN ligases ,CELL cycle ,PHOSPHORYLATION ,CELL culture ,SEXUAL dimorphism - Abstract
FZR1/CDH1 is an activator of Anaphase promoting complex/Cyclosome (APC/C), best known for its role as E3 ubiquitin ligase that drives the cell cycle. APC/C activity is regulated by CDK-mediated phosphorylation of FZR1 during mitotic cell cycle. Although the critical role of FZR1 phosphorylation has been shown mainly in yeast and in vitro cell culture studies, its biological significance in mammalian tissues in vivo remained elusive. Here, we examined the in vivo role of FZR1 phosphorylation using a mouse model, in which non-phosphorylatable substitutions were introduced in the putative CDK-phosphorylation sites of FZR1. Although ablation of FZR1 phosphorylation did not show substantial consequences in mouse somatic tissues, it led to severe testicular defects resulting in male infertility. In the absence of FZR1 phosphorylation, male juvenile germ cells entered meiosis normally but failed to enter meiosis II or form differentiated spermatids. In aged testis, male mutant germ cells were overall abolished, showing Sertoli cell-only phenotype. In contrast, female mutants showed apparently normal progression of meiosis. The present study demonstrated that phosphorylation of FZR1 is required for temporal regulation of APC/C activity at meiosis II entry, and for maintenance of spermatogonia, which raised an insight into the sexual dimorphism of FZR1-regulation in germ cells. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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11. Flexible powder electroluminescent device on transparent electrode of printed invisible silver-grid laminated with conductive polymer.
- Author
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Ohsawa, Masato, Hashimoto, Natsuki, Takeda, Naoki, Tsuneyasu, Shota, and Satoh, Toshifumi
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- 2020
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12. Palliative Care of Malignant Fibrous Histiocytoma of Spine with Cord Compression and Multiple Bone Metastases Treated by Multidisciplinary Therapy: Case Report.
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Sekiguchi, Ivan, Takeda, Naoki, and Ishida, Naoki
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DERMATOFIBROMA ,BONE metastasis ,SPINAL canal ,SPINE ,THORACIC vertebrae ,SPINAL cord cancer - Abstract
Malignant fibrous histiocytoma (MFH) of the spine is rare, with only a few dozen cases reported in the literature. A 60-year-old male was referred to us with symptoms of thoracic myelopathy. A solid tumor in the Th8 right costovertebral junction invading the spinal canal and compressing the spinal cord, and multiple bony metastases were discovered. Biopsy confirmed MFH. The thoracic spine tumor showed good response to irradiation followed by embolization and partial resection. The patient was followed until his death 22 months later. A good quality of life was sustained for more than 18 months. Despite a poor prognosis and an aggressive course of MFH of the spine, a good quality of life could be sustained for more than a year with palliative interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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13. Sialyl Tn Unit with TFA‐Labile Protection Realizes Efficient Synthesis of Sialyl Glycoprotein.
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Takeda, Naoki, Takei, Toshiki, Asahina, Yuya, and Hojo, Hironobu
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GLYCOPROTEINS ,AMINO acids ,SIALIC acids ,GLYCOPEPTIDES ,THIOESTERS - Abstract
Abstract: Amino acids bearing 4‐methylbenzyl (MBn) and 4‐methoxybenzyl (MPM)‐protected sialic acid were synthesized and used for the 9‐fluorenylmethoxycarbonyl (Fmoc) solid‐phase synthesis of a glycopeptide. The α‐sialyl linkage of the MBn‐protected unit was partially cleaved under the final deprotection by trifluoroacetic acid (TFA). In addition, the removal of several MBn groups were incomplete. On the other hand, the MPM‐protected unit gave the desired glycopeptide without decomposition of the α‐sialyl linkage. Using this unit, peptide thioesters of the tandem repeat unit of MUC1 mucin were synthesized by the
N ‐alkylcysteine (NAC) method and used for the one‐pot ligation by the thioester method. As a result, the three tandem repeats of MUC1 carrying sialyl Tn antigens were successfully synthesized. [ABSTRACT FROM AUTHOR]- Published
- 2018
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14. Changes in expression of C2cd4c in pancreatic endocrine cells during pancreatic development.
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Omori, Hisayoshi, Ogaki, Soichiro, Sakano, Daisuke, Sato, Mutsumi, Umeda, Kahoko, Takeda, Naoki, Nakagata, Naomi, and Kume, Shoen
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GENE expression ,PANCREATIC physiology ,CYTOPLASM ,LABORATORY mice ,ENDOCRINE cells - Abstract
C2cd4c, encoded by a gene belonging to the C2cd4 family, contains a C2 domain conserved across species and is localized to the cytoplasm. To examine the role of C2cd4c in the pancreas, we studied its localization and generated C2cd4c knockout (KO) mice. C2cd4c was expressed in pancreatic endocrine progenitors at early embryonic stages. When endocrine cells arise from their precursors, C2cd4c is gradually confined to the insulin- and pancreatic polypeptide-expressing cells of the endocrine. In the adult pancreas, C2cd4c is restricted to the beta cells. C2cd4c KO mice showed normal embryonic pancreatic development and adult pancreatic function. Thus, our results suggest that C2cd4c is dispensable for pancreatic development. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Three-dimensional conformal fractionated radiotherapy for spinal schwannoma with a paravertebral or an intraosseous component.
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Onimaru, Rikiya, Hida, Kazutoshi, Takeda, Naoki, Onodera, Shunsuke, Nishikawa, Yukiko, Mori, Takashi, and Shirato, Hiroki
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SPINE radiography ,COMPUTED tomography ,LONGITUDINAL method ,RADIATION doses ,RADIOTHERAPY ,SPINAL tumors ,THREE-dimensional imaging ,NERVE tissue ,TREATMENT effectiveness ,RETROSPECTIVE studies ,TUMORS - Abstract
Introduction: We retrospectively evaluated the efficacy of three-dimensional conformal radiotherapy (3D-CRT) for spinal schwannoma.Methods: Nine patients with spinal schwannoma were treated with 3D-CRT. All patients had a paravertebral or intraosseous component. Tumor sizes ranged from 0.8 to 8.7 cm, with a median of 3.5 cm. The prescribed dose was 50 Gy in 25 fractions at the isocenter, except for 1 patient who received 66 Gy in 33 fractions for a large sacral tumor. The follow-up period ranged from 20 to 137 months, with a median of 72 months.Results: Tumor shrinkage within 3 mm occurred in 4 patients and tumor expansion within 3 mm occurred in 3. One tumor showed neither expansion nor shrinkage at the last follow-up. One patient experienced transient expansion by 8 mm in diameter at 12 months after the completion of radiotherapy (35-43 mm), and then the tumor size remained unchanged for 7 years. No severe late toxicity ≥ grade 3 was observed.Conclusions: Only 1 of 9 tumors showed transit expansion over 3 mm after 3D-CRT, and severe late radiation toxicity was not observed. Use of 3D-CRT should be considered a treatment option for spinal schwannoma. [ABSTRACT FROM AUTHOR]- Published
- 2015
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16. The effect of changing toe direction on knee kinematics during drop vertical jump: a possible risk factor for anterior cruciate ligament injury.
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Ishida, Tomoya, Yamanaka, Masanori, Takeda, Naoki, Homan, Kentaro, Koshino, Yuta, Kobayashi, Takumi, Matsumoto, Hisashi, and Aoki, Yoshimitsu
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ANTERIOR cruciate ligament injuries ,RANGE of motion of joints ,VERTICAL jump ,HUMAN kinematics ,TIBIA ,ANGULAR velocity measurement ,ANATOMY ,INJURY risk factors - Abstract
Purpose: The purpose of this study was to examine the effect of changing toe direction on knee kinetics and kinematics associated with anterior cruciate ligament injury during drop vertical jumps. Methods: Fourteen females performed drop vertical jumps under three toe conditions (natural, toe-in, and toe-out). The knee kinetics and kinematics during landing were evaluated using a motion analysis system. Results under three toe conditions were compared using a one-way repeated measures analysis of variance and a post hoc Bonferroni test. Results: Toe-in landing was associated with a significantly greater knee abduction angle, tibial internal rotation angle, and knee abduction moment than the natural and toe-out conditions. Toe-out landing was associated with significantly greater tibial internal rotational angular velocity. Conclusions: Changing toe direction significantly affects knee kinetics and kinematics during landing. It is important to avoid changing toe direction excessively inward or outward during landing to prevent the increases in knee abduction and tibial internal rotation which might increase the risk of ACL injury. Level of evidence: Prognosis, Level IV. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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17. Determining c- Myb Protein Levels Can Isolate Functional Hematopoietic Stem Cell Subtypes.
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Sakamoto, Hiroshi, Takeda, Naoki, Arai, Fumio, Hosokawa, Kentaro, Garcia, Paloma, Suda, Toshio, Frampton, Jon, and Ogawa, Minetaro
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MYB gene ,HEMATOPOIETIC stem cells ,TRANSCRIPTION factors ,LEUKEMIA treatment ,LABORATORY mice ,BROMODEOXYURIDINE - Abstract
The transcription factor c-Myb was originally identified as a transforming oncoprotein encoded by two avian leukemia viruses. Subsequently, through the generation of mouse models that affect its expression, c-Myb has been shown to be a key regulator of hematopoiesis, including having critical roles in hematopoietic stem cells (HSCs). The precise function of c-Myb in HSCs although remains unclear. We have generated a novel c-myb allele in mice that allows direct observation of c-Myb protein levels in single cells. Using this reporter line we demonstrate that subtypes of HSCs can be isolated based upon their respective c-Myb protein expression levels. HSCs expressing low levels of c-Myb protein (c-Myb
low HSC) appear to represent the most immature, dormant HSCs and they are a predominant component of HSCs that retain bromodeoxyuridine labeling. Hematopoietic stress, induced by 5-fluorouracil ablation, revealed that in this circumstance c-Myb-expressing cells become critical for multilineage repopulation. The discrimination of HSC subpopulations based on c-Myb protein levels is not reflected in the levels of c-myb mRNA, there being no more than a 1.3-fold difference comparing c-Myblow and c-Mybhigh HSCs. This illustrates how essential it is to include protein studies when aiming to understand the regulatory networks that control stem cell behavior. S tem C ells 2015;33:479-490 [ABSTRACT FROM AUTHOR]- Published
- 2015
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18. Meikin is a conserved regulator of meiosis-I-specific kinetochore function.
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Kim, Jihye, Ishiguro, Kei-ichiro, Nambu, Aya, Akiyoshi, Bungo, Yokobayashi, Shihori, Kagami, Ayano, Ishiguro, Tadashi, Pendas, Alberto M., Takeda, Naoki, Sakakibara, Yogo, Kitajima, Tomoya S., Tanno, Yuji, Sakuno, Takeshi, and Watanabe, Yoshinori
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KINETOCHORE ,CHROMOSOME segregation ,MITOSIS ,MEIOSIS ,MICROTUBULES ,COHESINS - Abstract
The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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19. Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background.
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Shen, Jingling, Shi, Dan, Suzuki, Tomohiro, Xia, Zunping, Zhang, Hanli, Araki, Kimi, Wakana, Shigeharu, Takeda, Naoki, Yamamura, Ken-ichi, Jin, Shoude, and Li, Zhenghua
- Published
- 2016
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20. Impaired degradation of WNK1 and WNK4 kinases causes PHAII in mutant KLHL3 knock-in mice.
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Susa, Koichiro, Sohara, Eisei, Rai, Tatemitsu, Zeniya, Moko, Mori, Yutaro, Mori, Takayasu, Chiga, Motoko, Nomura, Naohiro, Nishida, Hidenori, Takahashi, Daiei, Isobe, Kiyoshi, Inoue, Yuichi, Takeishi, Kenta, Takeda, Naoki, Sasaki, Sei, and Uchida, Shinichi
- Published
- 2014
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21. The Relationships between Pre-landing Muscle Activation and Ankle Position at Ground Contact during Single-Leg Drop Landing.
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KOSHINO, YUTA, YAMANAKA, MASANORI, and TAKEDA, NAOKI
- Abstract
[Purpose] To investigate the relationships between pre-landing ankle muscle activities and ankle position at ground contact during single-leg drop landing. [Subjects] Nine healthy subjects (4 men and 5 women, a total of 18 legs) participated in this study. [Methods] The ankle dorsiflexion and inversion angles, EMG activities of the peroneus longus (PL), tibialis anterior (TA), and gastrocnemius medialis (GM) were recorded during a single-leg drop landing from a 30-cm high box. The integrated EMG (IEMG) activity during the pre-landing (100 ms before ground contact), muscle activity ratio for the ankle plantarflexor and dorsiflexor, and the invertor and evertor muscles were calculated using each IEMG activity. [Results] There was a significant positive correlation between TA pre-landing IEMG activity and ankle inversion angle at ground contact, as well as GM pre-landing IEMG activity and ankle dorsiflexion angle at ground contact. Moreover, TA IEMG activity relative to PL and GM IEMG activities were significantly associated with ankle inversion angle at ground contact. [Conclusion] These results suggest that the pre-landing ankle muscle activities and their ratios are associated with ankle position at ground contact. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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22. Enhanced inhibitory neurotransmission in the cerebellar cortex of Atp1a3-deficient heterozygous mice.
- Author
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Ikeda, Keiko, Satake, Shin’Ichiro, Onaka, Tatsushi, Sugimoto, Hiroki, Takeda, Naoki, Imoto, Keiji, and Kawakami, Kiyoshi
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HEMIPLEGIA ,DYSTONIA ,CEREBELLUM ,PURKINJE cells - Abstract
Key points Mutations of ATP1A3 cause rapid-onset dystonia with parkinsonism (RDP) and alternating hemiplegia of childhood (AHC)., The mRNA of Atp1a3 was highly expressed in molecular-layer interneurons and Purkinje cells in the developing mouse cerebellar cortex, and the gene product was observed as dots in the molecular layer, on the surface of Purkinje cell soma and the pinceaux., Here we report that Atp1a3
+/− mice showed increased symptoms of dystonia when being administrated kainate into cerebellum. We also found enhanced inhibitory neurotransmission between molecular-layer interneurons and Purkinje cells in the developing cerebellum of Atp1a3+/− mice., These findings suggest that ATP1A3 haploinsufficiency in the cerebellum has some effect on the inhibitory, but not the excitatory, circuitry and the interaction among different cell types during development. Disturbances of the cerebellar inhibitory network seem to be the underlying pathophysiological mechanism of dystonia among the increasing spectrum of complex neurological symptoms in RDP and AHC., Abstract Dystonia is characterized by excessive involuntary and prolonged simultaneous contractions of both agonist and antagonist muscles. Although the basal ganglia have long been proposed as the primary region, recent studies indicated that the cerebellum also plays a key role in the expression of dystonia. One hereditary form of dystonia, rapid-onset dystonia with parkinsonism (RDP), is caused by loss of function mutations of the gene for the Na pump α3 subunit ( ATP1A3). Little information is available on the affected brain regions and mechanism for dystonia by the mutations in RDP. The Na pump is composed of α and β subunits and maintains ionic gradients of Na+ and K+ across the cell membrane. The gradients are utilized for neurotransmitter reuptake and their alteration modulates neural excitability. To provide insight into the molecular aetiology of RDP, we generated and analysed knockout heterozygous mice ( Atp1a3+/− ). Atp1a3+/− showed increased symptoms of dystonia that is induced by kainate injection into the cerebellar vermis. Atp1a3 mRNA was highly expressed in Purkinje cells and molecular-layer interneurons, and its product was concentrated at Purkinje cell soma, the site of abundant vesicular γ-aminobutyric acid transporter (VGAT) signal, suggesting the presynaptic localization of the α3 subunit in the inhibitory synapse. Electrophysiological studies showed that the inhibitory neurotransmission at molecular-layer interneuron-Purkinje cell synapses was enhanced in Atp1a3+/− cerebellar cortex, and that the enhancement originated via a presynaptic mechanism. Our results shed light on the role of Atp1a3 in the inhibitory synapse, and potential involvement of inhibitory synaptic dysfunction for the pathophysiology of dystonia. [ABSTRACT FROM AUTHOR]- Published
- 2013
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23. The Effect of Plantar Sensation on the Postural Sway of Individuals with Knee Osteoarthritis.
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Chiba, Takeshi, Yamanaka, Masanori, and Takeda, Naoki
- Abstract
[Purpose] The purpose of this study was to compare the plantar sensation of individuals with knee osteoarthritis (KOA) with controls, and to examine the effect of plantar sensation on the postural sway in individuals with KOA. [Subjects] Sixteen KOA patients and seventeen control participants volunteered. [Methods] Plantar sensations were assessed using Semmes-Weinstein Monofilaments. The path length of center of pressure (LNG), root mean square area and LNG/envelope area (LNG/E.AREA) were measured in the standing position under two different surface conditions (firm and foam). [Result] In the KOA group, the portion of patients whose plantar sensation at the area of 1st metatarsal head was more sensitive than that of 5th metatarsal head was larger than in the control group. Although there was no significant correlation between plantar sensation and LNG/E.AREA in the control group, there was a significant negative correlation in the KOA group. [Conclusion] This result suggests that plantar sensation plays an important role in the postural control of individuals with KOA. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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24. Protective role of the leukotriene B4 receptor BLT2 in murine inflammatory colitis.
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Iizuka, Yoshiko, Okuno, Toshiaki, Saeki, Kazuko, Uozaki, Hiroshi, Okada, Shinji, Misaka, Takumi, Sato, Tetsuya, Toh, Hiroyuki, Fukayama, Masashi, Takeda, Naoki, Kita, Yoshihiro, Shimizu, Takao, Nakamura, Motonao, and Yokomizo, Takehiko
- Subjects
BIOLOGICAL research ,ARACHIDONIC acid ,EICOSANOIDS ,G protein coupled receptors ,INFLAMMATORY bowel diseases - Abstract
BLT2 is a low-affinity leukotriene B
4 (LTB4) receptor that is activated by 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4 . Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. To clarify the role of BLT receptors in intestinal inflam mation, we assessed susceptibility to dextran sodium sulfate (DSS)-induced colitis in mice lacking either BLT1 or BLT2. BLT2-/- mice exhibited increased sensitivity to DSS as compared to wild-type and BLT1-/- mice, with more severe body weight loss and inflammation. Expression of inflammatory cytokines such as interferon (IFN)-γ interleukin (IL)-1β, and IL-6, chemokines such as CXC chemokine ligand 9 (CXCL9) and C-C motif chemokine 19 (CCL19), and metalloproteinases was highly up-regulated in the colons of DSS-treated BLT2-/- mice, and there was an enhanced accumulation of activated macrophages. Phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was also markedly accelerated in the crypts of DSS-treated BLT2-/- mice. Madin-Darby canine kidney II (MDCKII) cells transfected with BLT2 exhibited enhanced barrier function as measured by transepithelial electrical resistance (TER) and FITC-dextran leakage through MDCK monolayers. Thus, BLT2 is expressed in colon cryptic cells and appears to protect against DSS-induced colitis, possibly by enhancing barrier function in epithelial cells of the colon. These novel results suggest a direct anti-inflammatory role of BLT2 that is distinct from the proinflammatory roles of BLT1. [ABSTRACT FROM AUTHOR]- Published
- 2010
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25. Sall4 Is Essential for Stabilization, But Not for pluripotency,of Embryonic Stem Cells by Repressing Aberrant Trophectoderm Gene Expression.
- Author
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Yuri, Shunsuke, Fujimura, Sayoko, Nimura, Keisuke, Takeda, Naoki, Toyooka, Yayoi, Fujimura, Yu-Ichi, Aburatani, Hiroyuki, Ura, Kiyoe, Koseki, Haruhiko, Niwa, Hitoshi, and Nishinakamura, Ryuichi
- Subjects
EMBRYONIC stem cells ,GENE expression ,CELL proliferation ,CELL cycle ,HOMOLOGY (Biology) - Abstract
Sall4 is a mouse homolog of a causative gene of the autosomal dominant disorder Okihiro syndrome. We previously showed that the absence of Sall4 leads to lethality during peri-implantation and that Sall4-null embryonic stem (ES) cells proliferate poorly with intact pluripotency when cultured on feeder cells. Here, we report that, in the absence of feeder cells, Sall4-null ES cells express the trophectoderm marker Cdx2, but are maintained for a long period in an undifferentiated state with minimally affected Oct3/4 expression. Feeder-free Sall4-null ES cells contribute solely to the inner cell mass and epiblast in vivo, indicating that these cells still retain pluripotency and do not fully commit to the trophectoderm. These phenotypes could arise from derepression of the Cdx2 promoter, which is normally suppressed by Sall4 and the Mi2/NuRD HDAC complex. However, proliferation was impaired and G1 phase prolonged in the absence of Sall4, suggesting another role for Sall4 in cell cycle control. Although Sall1, also a Sall family gene, is known to genetically interact with Sall4 in vivo, Sall1-null ES cells have no apparent defects and no exacerbation is observed in ES cells lacking both Sall1 and Sall4, compared with Sall4-null cells. This suggests a unique role for Sall4 in ES cells. Thus, though Sall4 does not contribute to the central machinery of the pluripotency, it stabilizes ES cells by repressing aberrant trophectoderm gene expression. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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26. Establishment of germline-competent embryonic stem cell lines from the MSM/Ms strain.
- Author
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Araki, Kimi, Takeda, Naoki, Yoshiki, Atsushi, Obata, Yuichi, Nakagata, Naomi, Shiroishi, Toshihiko, Moriwaki, Kazuo, and Yamamura, Ken-ichi
- Subjects
EMBRYONIC stem cell research ,TUMOR growth ,GERM cells ,BLASTOCYST ,LABORATORY mice - Abstract
MSM/Ms is an inbred mouse strain established from the Japanese wild mouse, Mus musculus molossinus, which has been phylogenetically distinct from common laboratory mouse strains for about 1 million years. The nucleotide substitution rate between MSM/Ms and C57BL/6 is estimated to be 0.96%. MSM/Ms mice display unique characteristics not observed in the commonly used laboratory strains, including an extremely low incidence of tumor development, high locomotor activity, and resistance to high-fat-diet-induced diabetes. Thus, functional genomic analyses using MSM/Ms should provide a powerful tool for the identification of novel phenotypes and gene functions. We report here the derivation of germline-competent embryonic stem (ES) cell lines from MSM/Ms blastocysts, allowing genetic manipulation of the M. m. molossinus genome. Fifteen blastocysts were cultured in ES cell medium and three ES lines, Mol/MSM-1, -2, and -3, were established. They were tested for germline competency by aggregation with ICR morulae and germline chimeras were obtained from all three lines. We also injected Mol/MSM-1 ES cells into blastocysts of ICR or C57BL/6 × BDF1 mice and found that blastocyst injection resulted in a higher production rate of chimeric mice than did aggregation. Furthermore, Mol/MSM-1 subclones electroporated with a gene trap vector were also highly efficient at producing germline chimeras using C57BL/6 × BDF1 blastocyst injection. This Mol/MSM-1 ES line should provide an excellent new tool allowing the genetic manipulation of the MSM/Ms genome. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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27. Administration of factor XIII B subunit increased plasma factor XIII A subunit levels in factor XIII B subunit knock-out mice.
- Author
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Souri, Masayoshi, Koseki-Kuno, Shiori, Takeda, Naoki, Degen, Jay, Ichinose, Akitada, and Degen, Jay L
- Subjects
RECOMBINANT proteins ,ANIMAL experimentation ,BIOLOGICAL models ,BLOOD coagulation factors ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,RESEARCH ,EVALUATION research ,THERAPEUTICS - Abstract
Factor XIII (FXIII) is a proenzyme of plasma transglutaminase consisting of enzymatic A (FXIII-A) and noncatalytic B subunits (FXIII-B), and acts in hemostasis and wound healing. We freshly generated mice lacking either FXIII-A or FXIII-B to investigate the physiological functions of FXIII in vivo. Mice carrying the disrupted allele were born at the expected Mendelian ratios, and the homozygous mice were viable and fertile under specific pathogen-free conditions. Although all homozygous and heterozygous mice showed no marked difference from the wild-type animals in general appearance, homozygous mice of either FXIII-A- or FXIII-B-deficiency did have prolonged bleeding times. It was confirmed that thrombin-dependent amine incorporation and fibrin-crosslinking in plasma were undetectable in the FXIII-A-deficient mice and markedly reduced in the FXIII-B-deficient mice; however, the gene expression of each subunit was regulated independently. Recombinant human FXIII-B (rFXIII-B) was expressed in a baculovirus expression system. When rFXIII-B was injected into FXIII-B-deficient mice, FXIII-A levels, fibrin crosslinking, and amine-incorporation activities increased in their plasma, indicating that FXIII-B assisted the maintenance of FXIII-A levels in the circulation. These mouse strains will be useful in exploring the possible pathophysiological roles of each subunit in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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28. Functional dynamics of H3K9 methylation during meiotic prophase progression.
- Author
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Tachibana, Makoto, Nozaki, Masami, Takeda, Naoki, and Shinkai, Yoichi
- Subjects
HISTONES ,METHYLATION ,EMBRYOLOGY ,CELLS ,SPERMATOGENESIS ,AMINO acids ,GENETIC regulation - Abstract
Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. G9a is a major mammalian H3K9 methyltransferase at euchromatin and is essential for mouse embryogenesis. Here we describe the roles of G9a in germ cell development. Mutant mice in which G9a is specifically inactivated in the germ-lineage displayed sterility due to a drastic loss of mature gametes. G9a-deficient germ cells exhibited perturbation of synchronous synapsis in meiotic prophase. Importantly, mono- and di-methylation of H3K9 (H3K9me1 and 2) in G9a-deficient germ cells were significantly reduced and G9a-regulated genes were overexpressed during meiosis, suggesting that G9a-mediated epigenetic gene silencing is crucial for proper meiotic prophase progression. Finally, we show that H3K9me1 and 2 are dynamically and sex-differentially regulated during the meiotic prophase. This genetic and biochemical evidence strongly suggests that a specific set of H3K9 methyltransferase(s) and demethylase(s) coordinately regulate gametogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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29. The Rab8 GTPase regulates apical protein localization in intestinal cells.
- Author
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Sato, Takashi, Mushiake, Sotaro, Kato, Yukio, Sato, Ken, Sato, Miyuki, Takeda, Naoki, Ozono, Keiichi, Miki, Kazunori, Kubo, Yoshiyuki, Tsuji, Akira, Harada, Reiko, and Harada, Akihiro
- Subjects
INTESTINES ,CYTOGENETICS ,PROTEINS ,EPITHELIAL cells ,PEPTIDASE ,PROTEOLYTIC enzymes ,LYSOSOMES ,LABORATORY mice - Abstract
A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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30. Heat Shock Protein 40/DjB1 Is Required for Thermotolerance in Early Phase.
- Author
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Uchiyama, Yukako, Takeda, Naoki, Mori, Masataka, and Terada, Kazutoyo
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HEAT shock proteins ,MOLECULAR chaperones ,ADENOSINE triphosphatase ,LABORATORY mice ,APOPTOSIS - Abstract
DjB1 (Hsp40/DnajB1/Hdj1) is a member of the Hsp40/DnaJ family that functions as a co-chaperone of mammalian Hsp70s. DjB1 recognizes substrate proteins and facilitates the ATPase activity of Hsp70. We generated DjB1 deficient mice. The DjB1–/– mice were viable and fertile with no obvious abnormalities, thus indicating that DjB1 is dispensable for development and viability. No difference was found between the DjB1–/– and wild-type peritoneal macrophages regarding resistance against various types of apoptosis-inducing reagents. However, DjB1–/– cells showed decreased thermotolerance in the early phase after mild heat treatment, but not in the late phase. After the heat treatment, Hsp70 was induced similarly in wild-type and DjB1–/– cells. Immunofluorescence staining of wild-type cells revealed the accumulation of DjB1 and Hsc70 in the nucleus after heat treatment. DjB1 also accumulated in the centrosome. The accumulation of Hsc70 in the nucleus was also observed in DjB1–/– cells. These results suggest that the impaired thermotolerance of DjB1–/– cells is not due to a mislocation of the Hsp70 family. [ABSTRACT FROM PUBLISHER]
- Published
- 2006
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31. Abnormalities Caused by Carbohydrate Alterations in Iβ6 -N-Acetylglucosaminyltransferase-Deficient Mice.
- Author
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Guo-Yun Chen, Muramatsu, Hisako, Kondo, Mineo, Kurosawa, Nobuyuki, Miyake, Yozo, Takeda, Naoki, and Muramatsu, Takashi
- Subjects
CARBOHYDRATES ,IMMUNE system ,LEUCOCYTES ,EPITHELIAL cells ,MICE ,KIDNEYS - Abstract
Iβ6-N-acetylglucosaminyltransferase (IGnT) catalyzes the branching of poly-N-acetyllactosamine carbohydrate chains. In both humans and mice, three spliced forms of IGnT have been identified, and a common exon is present in all of them. We generated mice deficient in the common exon to understand the physiological function of poly-N-acetyllactosamine branching. IGnT activity was abolished in the stomach, kidney, bone marrow, and cerebellum of the deficient mice, while a low level of the activity persisted in the small intestine. Immunohistochemical analysis confirmed the loss of I antigen from the lung, stomach, and kidney. The deficient mice had reduced spontaneous locomotive activity. The number of peripheral blood lymphocytes was also reduced and renal function decreased in the deficient mice. Furthermore, in aged mice, vacuolization occurred in the kidney, and epidermoid cysts were frequently formed. However, cataracts did not develop earlier in the deficient mice. Decreased levels of lysosomal proteins, LAMP-2 and synaptotagmin VII, were found in the kidney of the deficient mice and correlated with renal abnormalities. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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32. Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAT-1) Is Required for Branching Morphogenesis in the Chorioallantoic Placenta.
- Author
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Tanaka, Hiroyuki, Nagaike, Koki, Takeda, Naoki, Itoh, Hiroshi, Kohama, Kazuyo, Fukushima, Tsuyoshi, Miyata, Shiro, Uchiyama, Shuichiro, Uchinokura, Shunro, Shimomura, Takeshi, Miyazawa, Keiji, Kitamura, Naomi, Yamada, Gen, and Kataoka, Hiroaki
- Subjects
GROWTH factors ,CYTOKINES ,PEPTIDES ,MICE ,MOLECULAR biology ,CYTOLOGY - Abstract
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-associated Kunitz-type serine proteinase inhibitor that was initially identified as a potent inhibitor of hepatocyte growth factor activator. HAI-1 is also a cognate inhibitor of matriptase, a membrane-associated serine proteinase. HAI-1 is expressed predominantly in epithelial cells in the human body. Its mRNA is also abundant in human placenta, with HAI-1 specifically expressed by villous cytotrophoblasts. In order to address the precise roles of HAI-1 in vivo, we generated HAI-1 mutant mice by homozygous recombination. Heterozygous HAI-1
+/- mice underwent normal organ development. However, homozygous HAI-1-/- mice experienced embryonic lethality which became evident at embryonic day 10.5 postcoitum (E10.5). As early as E9.5, HAI-1-/- embryos showed growth retardation that did not reflect impaired cell proliferation but resulted instead from failed placental development and function. Histological analysis revealed severely impaired formation of the labyrinth layer, in contrast all other placental layers, such as the spongiotrophoblast layer and giant cell layer, which were formed. Our results indicate that mouse HAI-1 is essential for branching morphogenesis in the chorioallantoic placenta and lack of HAI-1 function may result in placental failure. [ABSTRACT FROM AUTHOR]- Published
- 2005
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33. Quadriparesis complicating atlantoaxial subluxation and ossification of the posterior longitudinal ligament in a patient with rheumatoid arthritis. A case report.
- Author
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Shirado O, Azuma H, Takeda N, Minami A, Shirado, Osamu, Azuma, Hirotaka, Takeda, Naoki, and Minami, Akio
- Published
- 2005
34. QUADRIPARESIS COMPLICATING ATLANTOAXIAL SUBLUXATION AND OSSIFICATION OF THE POSTERIOR LONGITUDINAL LIGAMENT IN A PATIENT WITH RHEUMATOID ARTHRITIS.
- Author
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Shirado, Osamu, Azuma, Hirotaka, Takeda, Naoki, and Minami, Akio
- Subjects
RHEUMATOID arthritis ,RHEUMATISM ,ARTHRITIS ,SPINE ,OSSIFICATION ,BONES - Abstract
Presents the case report on quadriparesis complicating atlantoaxial subluxation and ossification of the posterior longitudinal ligament in a patient with rheumatoid arthritis. Cause of the rheumatoid arthritis in the cervical spine; Ossification of the posterior longitudinal ligament; Therapeutic criteria in rheumatoid arthritis.
- Published
- 2005
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- View/download PDF
35. A type I DnaJ homolog, DjA1, regulates androgen receptor signaling and spermatogenesis.
- Author
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Terada, Kazutoyo, Yomogida, Kentaro, Imai, Tomoaki, Kiyonari, Hiroshi, Takeda, Naoki, Kadomatsu, Tsuyoshi, Yano, Masato, Aizawa, Shinichi, and Mori, Masataka
- Subjects
ANDROGENS ,ANDROSTANE ,SEX hormones ,SPERMATOGENESIS ,TESTIS ,GAMETOGENESIS - Abstract
Two type I DnaJ homologs DjA1 (DNAJA1; dj2, HSDJ/hdj-2, rdj1) and DjA2 (DNAJA2; dj3, rdj2) work similarly as a cochaperone of Hsp70s in protein folding and mitochondrial protein import in vitro. To study the in vivo role of DjA1, we generated DjA1-mutant mice. Surprisingly, loss of DjA1 in mice led to severe defects in spermatogenesis that involve aberrant androgen signaling. Transplantation experiments with green fluorescent protein-labeled spermatogonia into DjA1
-/- mice revealed a primary defect of Sertoli cells in maintaining spermiogenesis at steps 8 and 9. In Sertoli cells of DjA1-/- mice, the androgen receptor markedly accumulated with enhanced transcription of several androgen-responsive genes, including Pem and testin. Disruption of Sertoli-germ cell adherens junctions was also evident in DjA1-/- mice. Experiments with DjA1-/- fibroblasts and primary Sertoli cells indicated aberrant androgen receptor signaling. These results revealed a critical role of DjA1 in spermiogenesis and suggest that DjA1 and DjA2 are not functionally equivalent in vivo. [ABSTRACT FROM AUTHOR]- Published
- 2005
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36. Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking.
- Author
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Katagiri, Koko, Ohnishi, Noriko, Kabashima, Kenji, Iyoda, Tomonori, Takeda, Naoki, Yoichi Shinkai, Kayo Inaba, and Tatsuo Kinashi
- Subjects
CHEMOKINES ,LYMPHOCYTES ,DENDRITIC cells ,ANTIGEN presenting cells ,B cells ,LYMPH nodes - Abstract
Immunosurveillance requires the coordinated regulation of chemokines and adhesion molecules to guide immune cell migration. However, the critical molecule for governing the high trafficking capability of immune cells is not clear. Here we show that the effector molecule RAPL is indispensable in the integrin-mediated adhesion and migration of lymphocytes and dendritic cells. RAPL deficiency caused defective chemokine-triggered lymphocyte adhesion and migration to secondary lymphoid organs, resulting in atrophic lymphoid follicles and deficient marginal zone B cells, concomitant with increased immature B cells in the blood. Furthermore, splenic dendritic cells were diminished and defective in adhesion. After being activated with inflammatory stimuli, skin and splenic dendritic cells failed to migrate into either the draining lymph nodes or the white pulp of the spleen. Thus, RAPL is a crucial immune cell trafficking regulator essential for immunosurveillance. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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- View/download PDF
37. Bcl11b is required for differentiation and survival of ab T lymphocytes.
- Author
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Wakabayashi, Yuichi, Watanabe, Hisami, Inoue, Jun, Takeda, Naoki, Sakata, Jun, Mishima, Yukio, Hitomi, Jiro, Yamamoto, Takashi, Utsuyama, Masanori, Niwa, Ohtsura, Aizawa, Shinichi, and Kominami, Ryo
- Subjects
GENES ,LYMPHOCYTES - Abstract
The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4[sup -]CD8[sup -] double-negative stage of thymocyte development without any impairment in cells of B- or γδ T cell lineages. The Bcl11b[sup -/-] thymocytes showed unsuccessful recombination of V[sub β] to D[sub β] and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b[sup -/-] mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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- View/download PDF
38. Expression of Tom34 Splicing Isoforms in Mouse Testis and Knockout of Tom34 in Mice.
- Author
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Terada, Kazutoyo, Ueno, Shota, Yomogida, Kentaro, Imai, Tomoaki, Kiyonari, Hiroshi, Takeda, Naoki, Yano, Masato, Abe, Shinichi, Aizawa, Shinichi, and Mori, Masataka
- Subjects
LABORATORY mice ,PROTEINS ,POLYMERASE chain reaction ,GENOMICS ,MESSENGER RNA - Abstract
The 34-kDa translocase of the outer mitochondrial membrane (Tom34) is a putative mammalian-specific factor involved in protein import into mitochondria. We analyzed the genomic sequence of the mouse Tom34 gene and found it has two alternative initial exons. Using reverse transcription and the polymerase chain reaction (RT-PCR), we found that these two mRNAs differs only in the 5′-proximal sequences corresponding to the two initial exons (exon 1a and 1b). Tom34 mRNA with exon 1a (Tom34a) is expressed ubiquitously, while that with exon 1b (Tom34b) is expressed only in mature testicular germ cells. To explore the in vivo function of Tom34 proteins, we generated Tom34-deficient mice by targeted disruption. The Tom34–/– mice were viable and grew normally and had a normal Mendelian inheritance pattern. Male as well as female Tom34–/– mice were fertile. In vitro-preprotein import into isolated mitochondria showed no apparent difference between Tom34–/– and wild-type mice. These results indicate that Tom34 is dispensable for mouse growth and development under optimal conditions. [ABSTRACT FROM PUBLISHER]
- Published
- 2003
- Full Text
- View/download PDF
39. Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy.
- Author
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Takeda, Naoki, Sakuragi, Noriaki, Takeda, Mahito, Okamoto, Kazuhira, Kuwabara, Michiya, Negishi, Hiroaki, Oikawa, Mamoru, Yamamoto, Ritsu, Yamada, Hideto, and Fujimoto, Seiichiro
- Subjects
CERVICAL cancer ,HISTOPATHOLOGY ,HYSTERECTOMY ,RETROPERITONEUM ,ADENOCARCINOMA ,CANCER invasiveness ,REGRESSION analysis ,METASTASIS ,PROGNOSIS ,RETROSPECTIVE studies ,SURVIVAL analysis (Biometry) ,CERVIX uteri tumors ,SURGICAL excision ,LYMPH node surgery - Abstract
Background: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy.Methods: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors.Results: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively.Conclusions: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2002
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- View/download PDF
40. Limited effect of chromatin remodeling on Dβ-to-Jβ recombination in CD4+CD8+ thymocyte: implications for a new aspect in the regulation of TCR β gene recombination.
- Author
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Senoo, Makoto, Mochida, Naoko, Wang, Lili, Matsumura, Yasuko, Suzuki, Daisuke, Takeda, Naoki, Shinkai, Yoichi, and Habu, Sonoko
- Abstract
We have generated mutant mice in which TCR β chain enhancer (Eβ) was replaced with the TCR α chain enhancer (Eα). Using this mouse model, we analyzed (i) recombination status of the TCR β chain genes after functional V(D)J rearrangements occurred in the first allele during double-negative (DN)-to-double-positive (DP) transition and (ii) involvement of Eβ for the expression of rearranged TCR β chain genes. Our data show that Eα substituted for Eβ function to express a similar extent of TCR β chains exactly at the same time as did Eβ (CD25+CD44– DN stage), although the proportion of TCR β+ cells at this stage was low in mutant mice. At the DP stage, germline transcription and histone acetylation of Dβ–Jβ loci were detectable at a high degree in both mutant and wild-type mice. However, DP cells in mutant mice retained the germline Dβ–Jβ configuration at a higher frequency than that of wild-type mice, whereas both DP cells expressed TCR β chains to a similar extent. These data suggest that chromatin opening has a limited impact on Dβ-to-Jβ recombination at the DP stage and that Eα is functionally equivalent to Eβ in promoting expression of functionally rearranged TCR β chain genes through DN-to-DP transition. [ABSTRACT FROM PUBLISHER]
- Published
- 2001
- Full Text
- View/download PDF
41. A multivariate analysis of blood vessel and lymph vessel invasion as predictors of ovarian and lymph node metastases in patients with cervical carcinoma.
- Author
-
Sakuragi, Noriaki, Takeda, Naoki, Hareyama, Hitoshi, Fujimoto, Toshio, Todo, Yukiharu, Okamoto, Kazuhira, Takeda, Mahito, Wada, Shin-ichiro, Yamamoto, Ritsu, and Fujimoto, Seiichiro
- Published
- 2000
- Full Text
- View/download PDF
42. Incidence and distribution pattern of pelvic and paraaortic lymph node metastasis in patients with Stages IB, IIA, and IIB cervical carcinoma treated with radical hysterectomy.
- Author
-
Sakuragi, Noriaki, Satoh, Chikara, Takeda, Naoki, Hareyama, Hitoshi, Takeda, Mahito, Yamamoto, Ritsu, Fujimoto, Toshio, Oikawa, Mamoru, Fujino, Takafumi, Fujimoto, Seiichiro, Sakuragi, N, Satoh, C, Takeda, N, Hareyama, H, Takeda, M, Yamamoto, R, Fujimoto, T, Oikawa, M, Fujino, T, and Fujimoto, S
- Published
- 1999
- Full Text
- View/download PDF
43. Abnormalities of developmental cell death in Dad1-deficient mice.
- Author
-
Nishii, Kiyomasa, Tsuzuki, Teruhisa, Kumai, Madoka, Takeda, Naoki, Koga, Hideya, Aizawa, Shinichi, Nishimoto, Takeharu, and Shibata, Yosaburo
- Subjects
CELL death ,APOPTOSIS ,GENETICS - Abstract
Background: Dad1, the defender against apoptotic cell death, comprises the oligosaccharyltransferase complex and is well conserved among eukaryotes. In hamster BHK21-derived tsBN7 cells, loss of Dad1 causes apoptosis which cannot be prevented by Bcl-2. Results: To determine the role of Dad1 function in vivo, we prepared by gene targeting, mice harbouring a disrupted Dad1 gene. Homozygous mutants died shortly after they were implanted with the characteristic features of apoptosis. In an in vitro blastocyst culture system, Dad1-null cells displayed abnormalities which were comparable to those obtained in vivo. However, oligosaccharyltransferase activity was apparently retained even after the Dad1-null cells were destined to die. Some live-born heterozygous mutants displayed soft-tissue syndactyly. Mild thymic hypoplasia was also indicated in heterozygotes. Conclusion: These results suggest the involvement of the Dad1 gene in the acquisition of a common syndactyly phenotype, as well as in the control of programmed cell death during development. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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- View/download PDF
44. A Preliminary Report of Neoadjuvant Chemotherapy NSH-7 Study in Osteosarcoma: Preoperative Salvage Chemotherapy Based on Clinical Tumor Response and the Use of Granulocyte Colony-Stimulating Factor.
- Author
-
Wada, Takuro, Isu, Kazuo, Takeda, Naoki, Usui, Masamichi, Ishii, Seiichi, and Yamawaki, Shinya
- Published
- 1996
- Full Text
- View/download PDF
45. Analysis of IFN-γ-Induced Cell Cycle Arrest and Cell Death in Hepatocytes1.
- Author
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Kano, Arihiro, Watanabe, Yoshifumi, Takeda, Naoki, and Aizawa, Toshihiro Shin-ichi
- Subjects
CELL cycle ,CELL death ,LIVER cells ,CYCLOHEXIMIDE ,PROTEIN synthesis - Abstract
The mechanism by which IFN-γ induces cell cycle arrest and cell death in primary cultured hepatocytes was examined. The cell death exhibits apoptotic characters such as the appearance of apoptotic bodies and DNA fragmentation. IFN-γ induced cell cycle arrest at the initial stage, followed by cell death. A protein synthesis inhibitor, cycloheximide, significantly inhibited cell death, implying that IFN-γ induces de novo proteins involved in the death of hepatocytes. One of the most important apoptosis-related proteins, p53, was induced by IFN-γ in hepatocytes in a dose- and time-dependent manner. Northern blot analysis demonstrated that IFN-γ enhanced p53 mRNA expression as well as p21WAF1/C1p1/Sdf1 mRNA expression, which is mediated by the increased expression of the p53 protein. Interestingly, IFN-γ also induced cell death in p53-deficient hepatocytes. The cell death occurred rather earlier in p53-deficient cells than in normal hepatocytes. However, the cell death was not accompanied by apoptotic bodies. Therefore, IFN-γ-induced hepatocyte cell death is p53-independent, and p53 may contribute to the apoptotic characters. In conclusion, IFN-γ is supposed to cause cell cycle arrest by inducing p53 and p21WAF1/clp1/Sdl1 and it was demonstrated that IFN-γ induces p53-independent cell death in primary cultured hepatocytes. [ABSTRACT FROM AUTHOR]
- Published
- 1997
- Full Text
- View/download PDF
46. Extracorporeal Spread and Its Prognostic Impact in Stages I and II (FIGO) Endometrial Carcinoma.
- Author
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Sakuragi, Noriaki, Tanaka, Toshinobu, Satoh, Chikara, Nishiya, Masashi, Ohkouchi, Toshihiro, Tsumura, Norihiko, Takeda, Naoki, Hirahatake, Koji, Sagawa, Tadashi, Ohkubo, Hitoshi, and Fujimoto, Seiichiro
- Published
- 1991
- Full Text
- View/download PDF
47. A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCR α and β chain genes.
- Author
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Kubo, Shuichi, Takayama, Toshinori, Furutani-Seiki, Makoto, Kishimoto, Hidehiro, Hashimoto, Kahoko, Bae, Man-Jong, Yokochi, Taeko, Takeda, Naoki, Aizawa, Shinichi, Asano, Yoshihiro, and Tada, Tomio
- Abstract
Transgenic (TG) mice with TCR α and β chain genes from a CD4-dependent auto-l-A reactive T cell clone were generated. H-2 TG mice had a large number of thymic and splenic CD4 T cells expressing the autoreactive TCR without manifestation of autolmmunlty. The cells were not anergic, as they could respond to autologous antigen presenting cells and antl-TCR antibodies to proliferate and to produce interleuklns. Various degrees of down-regulation of CD2 and CD44 was observed in TG mice, Indicating the presence of a defective co-stlmulatory process in TG T cells. These features indicate that the self tolerance in autoreactive TCR TG mice is due not to clonal deletion and anergy but to a novel mechanism where T cells cannot sufficiently respond to normally existing self ligand . That such an in vivo unresponsiveness of autoreactive T cells is dictated in the thymus during CD4 T cell differentiation as an atypical form of positive selection of autoreactive T cells was suggested by the abnormal surface expression of CD69 and HSA. [ABSTRACT FROM PUBLISHER]
- Published
- 1994
48. Vascularized fibular graft for bone reconstruction of the extremities after tumor resection in limb-saving procedures.
- Author
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Minami, Akio, Kutsumi, Keiji, Takeda, Naoki, and Kaneda, Kiyoshi
- Published
- 1995
- Full Text
- View/download PDF
49. A new strategy of gene trapping in ES cells using 3'RACE.
- Author
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Yoshida, Michio, Yagi, Takeshi, Furuta, Yasuhide, Takayanagi, Kenji, Kominami, Ryo, Takeda, Naoki, Tokunaga, Tomoyuki, Chiba, Joe, Ikawa, Yoji, and Aizawa, Shinichi
- Abstract
'Gene trapping' in embryonic stem (ES) cells is a novel approach to identify a series of genes in mammals concomitant with the production of the corresponding mutant mice. However, this approach is currently unable to identify genes that are not expressed in ES cells. Here we describe a strategy to identify gene trapping clones which is not based on expression of a reporter gene. It uses the neo gene which lacks a polyadenylation signal and has a splice donor signal. Expression of the neo gene as fusion transcripts with the 3′ end containing the polyadenylation signal of tagged genes allows the identification of these clones by 3′ rapid amplification of the cDNA end in undifferentiated ES cells, even if the genes are not expressed in ES cells. Amplification was observed in about 25% of G418-resistant clones. Sequence analyses suggested the amplifications represent gene trapping events. The feasibility of this approach was further assessed by analysing one clone, PAT-12, in detail. [ABSTRACT FROM AUTHOR]
- Published
- 1995
- Full Text
- View/download PDF
50. Depressive disorders as psychiatric complications after obesity surgery.
- Author
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KODAMA, KAZUHIRO, NODA, SHINGO, MURAKAMI, ATSUHIRO, AZUMA, YUKARI, TAKEDA, NAOKI, YAMANOUCHI, NAOTO, OKADA, SHINICHI, KOMATSU, NAOYA, SATO, TOSHIO, MIYAZAWA, YUKIMASA, KAWAMURA, ISAO, and Kodama, Kazuhiro
- Subjects
OVERWEIGHT persons ,MENTAL depression ,BARIATRIC surgery ,PSYCHOLOGY - Abstract
Three case reports of morbidly obese patients (two women and a man) who underwent vertical banded gastroplasty and who subsequently fell into depression, are presented here. The psychiatric diagnosis according to DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised), the eating pattern before obesity surgery, the past history of mental disorder, social adaptation before surgery, psychological gain from their obese state, and the presence of unrealistic expectations of obesity surgery were investigated. Case 1 was diagnosed postoperatively as having a major depressive episode without a personality disorder. Case 2 was diagnosed postoperatively as having a major depressive episode. Case 3 had a depressive disorder not otherwise specified. Cases 2 and 3 had a social phobia with comorbidity of personality disorders. Binge eating disorder was confirmed in all patients before obesity surgery. There were differences between case 1 and cases 2 and 3 based on the presence of personality disorder and the time of onset of depression. When some psychiatric characteristics are confirmed in obese patients, obesity surgery should be undertaken more prudently because the patients may manifest depression postoperatively. The pre-operative psychiatric assessment is essential for a decision on indication of obesity surgery. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
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