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      • KCI등재후보

        <i>Col1a1-cre</i> mediated activation of β-catenin leads to aberrant dento-alveolar complex formation

        Kim, Tak-Heun,Bae, Cheol-Hyeon,Jang, Eun-Ha,Yoon, Chi-Young,Bae, Young,Ko, Seung-O,Taketo, Makoto M.,Cho, Eui-Sic Korean Association of Anatomists 2012 Anatomy & Cell Biology Vol.45 No.3

        <P>Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of <I>Catnb<SUP>+/lox(ex3)</SUP></I> mice with <I>Col1a1-cre</I> mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of β-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.</P>

      • KCI등재후보

        Nfic regulates tooth root patterning and growth

        Tak-Heun Kim,Cheol-Hyeon Bae,Siqin Yang,Joo-Cheol Park,Eui-Sic Cho 대한해부학회 2015 Anatomy & Cell Biology Vol.48 No.3

        Molecular interactions between epithelium and mesenchyme are important for root formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of root formation. However, the mechanisms of root formation and their interactions between Hertwig’s epithelial root sheath (HERS) and mesenchyme remain unclear. In this study, we investigated the role of Nfic in root patterning and growth during molar root development. The molars of Nfic knockout mice exhibited an enlarged pulp chamber and apical displacement of the pulpal floor, characteristic features of taurodontism, due to delayed furcation formation. In developing molar roots of mutant mice at P14, BrdU positive cells decreased in the apical mesenchyme of the elongation region whereas those cells increased in the dental papilla of the furcation region. Whereas cytokeratin 14 and laminin were localized in HERS cells of mutant molars, Smoothened (Smo) and Gli1 were downregulated in preodontoblasts. In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars. These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner. From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

      • KCI등재

        Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation

        Tak-Heun Kim,Cheol-Hyeon Bae,Eun-Ha Jang,Chi-Young Yoon,Young Bae,Seung-O Ko,Makoto M,Taketo,Eui-Sic Cho 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.3

        Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb+/lox(ex3) mice with Col1a1-cre mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of β-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.

      • 생쥐 두개안면 형성과정에서 Npr3의 발현양상

        Tak-Heun Kim,Rak-Eun Lee,Young Bae,Eui-Sic Cho 대한구강해부학회 2007 대한구강해부학회지 Vol.31 No.2

        Natriuretic peptides play physiological roles via their specific receptors, natriuretic peptide receptor-A, -B and -c. Unlike NPR-A and NPR-B, NPR-C does not mediate the intracellular signalling processes and called as silence or clearance receptor. A study with knockout mouse, NPR-C mediate the developmental processes of skeletal tissues. However, it is little known that NPR-C mediated signaling mechanisrns in the craniofacial development. Therefore, we purpcsed to analyse expression pattems of 1'1φr3 encoding NPR-C during craniofacial rnorphogenesis of mouse. At EIO.5, 1'1φr3 transcripts were specifically expressed in dorsal root ganglia, trigeminal ganglia, heart and meningeal 따tery. In the lower jaw with tongue of E12.5, Npr3 was restrictedIy expressed in the dorsum of tongue and incisor buds. In the rnaxilla of E13.5 and E14.5, expression of Npr3 was specifically observed in the intermaxillay segment extended to dorsum of the nose. In the developing tooth germs, 1\φr3 was expressed in the epithelial components of tooth germ from E13.5 to E16.5, corresponding to bud to bell stages of tooth development. In addition, expression of Npr3 were restricted in conjunctival and olfactory epithelium, trigeminal ganglion and salivary gland primordia. In conclusion, l\φr3 was specifically expressed in the neuronal structures, intermaxillary segment, intramembranous bone forming regions, tongue and conjunctival epitheliurn. Therefore, it is suggested that NPR-C may mediate the morphogenesis of craniofacial structures via altemative signaling processes.

      • SCOPUSKCI등재

        Original Articles : Clinical outcomes of balloon-occluded retrograde trans-venous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with Liver cirrhosis: a retrospective multicenter study

        ( Se Young Jang ),( Go Heun Kim ),( Soo Young Park ),( Chang Min Cho ),( Won Young Tak ),( Jeong Han Kim ),( Won Hyeok Choe ),( So Young Kwon ),( Jae Myeong Lee ),( Sang Gyune Kim ),( Dae Yong Kim ),( 대한간학회 2012 Clinical and Molecular Hepatology(대한간학회지) Vol.18 No.4

        Background/Aims: This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC). Methods: We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010. Results: Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047). Conclusions: BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO. (Clin Mol Hepatol 2012;18:368-374)

      • KCI등재후보

        The Role of Autonomous Wntless in Odontoblastic Differentiation of Mouse Dental Pulp Cells

        Choi, Hwajung,Kim, Tak-Heun,Ko, Seung-O,Cho, Eui-Sic Korean Academy of Dental Science 2016 Journal of korean dental science Vol.9 No.1

        Purpose: Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. Deletion of the Wntless (Wls) gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation. However, it remains unclear if autonomous Wnt ligands are necessary for differentiation of dental pulp cells into odontoblast-like cells to induce reparative dentinogenesis, one of well-known feature of pulp repair to form tertiary dentin. Materials and Methods: To analyze the autonomous role of Wls for differentiation of dental pulp cells into odontoblast-like cells, we used primary dental pulp cells from unerupted molars of Wls-floxed allele mouse after infection with adenovirus for Cre recombinase expression to knockout the floxed Wls gene or control GFP expression. The differentiation of dental pulp cells into odontoblast-like cells was analyzed by quantitative real-time polymerase chain reaction. Result: Proliferation rate was significantly decreased in dental pulp cells with Cre expression for Wls knockout. The expression levels of Osterix (Osx), runt-related transcription factor 2 (Runx2), and nuclear factor I-C (Nfic) were all significantly decreased by 0.3-fold, 0.2-fold, and 0.3-fold respectively in dental pulp cells with Wls knockout. In addition, the expression levels of Bsp, Col1a1, Opn, and Alpl were significantly decreased by 0.7-fold, 0.3-fold, 0.8-fold, and 0.6-fold respectively in dental pulp cells with Wls knockout. Conclusion: Wnt ligands produced autonomously are necessary for proper proliferation and odontoblastic differentiation of mouse dental pulp cells toward further tertiary dentinogenesis.

      • KCI등재후보
      • Clinical Remission of Renal Amyloidosis after Autologous Peripheral Blood Stem Cell Transplantation

        An, Seong Yeong,Kim, Yon Hee,Kwon, Young Eun,Kim, Yung Ly,Nam, Ki Heon,Choi, Heun,Kim, Young Ju,Park, Kyoung Sook,Jeong, Hyeon Joo,Oh, Hyung Jung,Park, Jung Tak,Han, Seung Hyeok,Kang, Shin-Wook,Yoo, T Ewha Womans University School of Medicine 2013 EMJ (Ewha medical journal) Vol.36 No.S

        Primary amyloidosis has unfavorable prognosis, particularly with organ involvement. Here, we report a case of clinical remission of renal amyloidosis after autologous hematopoietic cell transplantation. A 51-year-old female patient visited our hospital due to generalized edema. Initial evaluation showed hyperlipidemia, hypoalbuminemia, and heavy proteinuria, which were consistent with nephrotic syndrome. However, IgM lamda type monoclonal gammopathy was detected in serum and urine electrophoresis studies. Renal biopsy showed Congo red-positive amyloid deposition in mesangial area, glomerular capillary walls, and arterioles and amyloid fibers were confirmed by electron microscopy. Immunohistochemial study of the biopsy tissue demonstrated systemic light-chain amyloidosis (AL amyloidosis). Multiple myeloma was not evident on bone marrow examination. She received autologous hematopoietic cell transplantation after high dose melphalan treatment. Complete remissions were achieved after the treatment, respectively. Our findings suggest the potential role of autologous peripheral blood stem cell transplantation in treatment of AL amyloidosis.

      • KCI등재후보

        Transactivators for the Odontoblast-specific Gene Targeting

        Chung, Kyung-Chul,Kim, Tak-Heun,Yang, Yeon-Mee,Baek, Jin-A,Ko, Seung-O,Cho, Eui-Sic KOREAN ACADAMY OF ORAL BIOLOGY 2009 International Journal of Oral Biology Vol.34 No.2

        Dentin, a major component of teeth, is formed by odontoblasts which produce the dentin matrix beneath the dental epithelium and induce the mineralization of dentin. To date, the biochemical properties of dentin matrix proteins have been well characterized, but upstream regulators of these proteins are not yet well known. Recently in this regard, several transcription factors have been identified as potential regulators of matrix proteins. Most transcription factors are generally involved in diverse biological processes and it is essential to identify those that are odontoblast-specific transactivators to further understand the process of dentin formation. We thus analyzed the expression pattern of dentin matrix protein sand the activities of established transactivators containing a Cre-locus. Expression analyses using in situ hybridization showed that dentin matrtx proteins are sequentially expressed in differentiating odontoblasts, including type-I collagen, Dmp-l and Dspp. The activities of the transactivators were evaluated using β-galactosidase following the generation of double transgenic mice with each transactivator and the ROSA26R reporter line. The β-galactosidase activity of each transactivator paralled the expression of the matrix proteins. These results thus showed that these transactivators could be utilized for odontoblast-specific conditional gene targeting. In addition, time- and tissue-specific conditional gene targeting might also be achieved using a combination of these transactivators. Odontoblast-specific conditional gene targeting with these transactivators will likely also provide new insights into the molecular mechanisms underlying dentin formation.

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