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      • Serum Adipokine Concentrations in Dogs with Acute Pancreatitis

        Paek, J.,Kang, J.&#x2010,H.,Kim, H.&#x2010,S.,Lee, I.,Seo, K.W.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.6

        <P><B>Background</B></P><P>Limited information is available about the role of adipokines in the development and progression of acute pancreatitis (AP) in dogs.</P><P><B>Objectives</B></P><P>To determine whether the circulating concentrations of adipokines differed between healthy dogs and dogs with AP, and whether the circulating concentrations differed between AP survivors and AP nonsurvivors.</P><P><B>Animals</B></P><P>Twenty‐eight healthy dogs and 25 client‐owned dogs with AP.</P><P><B>Methods</B></P><P>Prospective observational cohort study of 25 client‐owned dogs with newly diagnosed AP and 28 otherwise healthy dogs with similar body condition scores. The serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured.</P><P><B>Results</B></P><P>The serum concentrations of leptin (<I>P </I>=<I> </I>.0021), resistin (<I>P </I>=<I> </I>.0010), visfatin (<I>P </I><<I> </I>.0001), IL‐1β (<I>P </I><<I> </I>.0001), IL‐6 (<I>P </I>=<I> </I>.0002), IL‐10 (<I>P </I><<I> </I>.0001), and IL‐18 (<I>P </I><<I> </I>.0001) were significantly higher in dogs with AP than healthy dogs, whereas the adiponectin concentration (<I>P </I>=<I> </I>.0011) was significantly lower. There were significant differences in the serum concentrations of leptin (<I>P </I>=<I> </I>.028) and adiponectin (<I>P </I>=<I> </I>.046) in survivors and nonsurvivors. After the disappearance of clinical signs, the concentrations of resistin (<I>P </I>=<I> </I>.037) and IL‐1β (<I>P </I>=<I> </I>.027) decreased significantly, whereas the serum concentrations of leptin (<I>P </I>><I> </I>.999), adiponectin (<I>P </I>=<I> </I>.11), visfatin (<I>P </I>=<I> </I>.83), IL‐6 (<I>P </I>=<I> </I>.82), IL‐10 (<I>P </I>=<I> </I>.82), IL‐18 (<I>P </I>=<I> </I>.56), and TNF‐α (<I>P </I>=<I> </I>.94) did not differ significantly.</P><P><B>Conclusion and Clinical Importance</B></P><P>This study showed that dysregulation of adipokines might be involved in the pathogenesis of AP. In addition, leptin and adiponectin are likely to be associated with mortality rate in AP.</P>

      • SCISCIESCOPUS

        Induction of bone formation by <i>Escherichia coli</i>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

        Park, J&#x2010,C.,So, S&#x2010,S.,Jung, I‐,H.,Yun, J&#x2010,H.,Choi, S&#x2010,H.,Cho, K&#x2010,S.,Kim, C&#x2010,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.6

        <P><I>Park J‐C, So S‐S, Jung I‐H, Yun J‐H, Choi S‐H, Cho K‐S, Kim C‐S. Induction of bone formation by</I> Escherichia coli<I>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodont Res 2011; 46: 682–690. © 2011 John Wiley & Sons A/S</I></P><P><B>Background and Objective: </B> The potential of the <I>Escherichia coli</I>‐expressed recombinant human bone morphogenetic protein‐2 (ErhBMP‐2) to support new bone formation/maturation using a block‐type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model.</P><P><B>Material and Methods: </B> Critical‐size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague–Dawley rats received implants of rhBMP‐2 (2.5 μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2‐ and 8‐wk healing intervals (eight animals/group/interval).</P><P><B>Results: </B> ErhBMP‐2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (<I>p</I> < 0.01). Bone formation was only observed for the ErhBMP‐2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (<I>p</I> < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption.</P><P><B>Conclusion: </B> ErhBMP‐2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.</P>

      • Radiosynthesis and <i>in vitro</i> evaluation of 1‐(tetrahydro‐5‐hydroxy‐6‐(hydroxymethyl)‐2H‐pyran‐3‐yl)‐5‐[<sup>125</sup>I]iodouracil: A new potential agent for HSV1‐tk

        Jo, Nam Hyun,Kim, Jung Young,El&#x2010,Gamal, Mohammed I.,Choi, Won&#x2010,Kyoung,Park, Jin&#x2010,Hun,Kim, Eun Jung,Cho, Jung&#x2010,Hyuck,Ha, Hyun&#x2010,Joon,Choi, Tae Hyun,Oh, Chang&#x2010,Hyun John Wiley Sons, Ltd. 2011 Journal of labelled compounds & radiopharmaceutica Vol.54 No.2

        <P><B>Abstract</B></P><P>Synthesis, radiolabelling, and <I>in vitro</I> evaluation of a new <SUP>125</SUP>I‐labelled iodouracil hexitol nucleoside analogue are reported. The target compound was successfully synthesized by an iodination–destannylation method and then purified by reverse phase HPLC. The radiochemical purity of the product was >99% with decay‐corrected yields of 48±3%. <I>In vitro</I> cellular uptake testing was carried out using MCA and MCA‐tk cell lines for comparison of compound 1 with [<SUP>18</SUP>F]FHBG. The newly synthesized compound 1 showed higher accumulation in herpex simplex virus type 1 thymidine kinase (HSV1‐tk) gene expression cell line (MCA‐tk cell line) than in the wild type MCA cell line compared with [<SUP>18</SUP>F]FHBG. The MCA‐tk to MCA cellular uptake ratio for compound 1 was higher than that of [<SUP>18</SUP>F]FHBG from 2 h after incubation. The radioiodine‐labelled compound 1 (I‐125, <I>t</I><SUB>1/2</SUB>=59.37 days) has a longer physical half‐life than F‐18‐(<I>t</I><SUB>1/2</SUB>=110 min) labelled FHBG. Radioiodine‐labelled compound 1 could be used for monitoring gene expression for a long time. The selectivity for MCA‐tk cell line makes compound 1 a promising imaging agent for HSV1‐tk expression. Copyright © 2010 John Wiley & Sons, Ltd.</P>

      • Resistance to <i>Rhizoctonia solani</i> AG‐2‐2 (IIIB) in creeping bentgrass plants transformed with pepper esterase gene <i>PepEST</i>

        Cho, K.&#x2010,C.,Han, Y.&#x2010,J.,Kim, S.&#x2010,J.,Lee, S.&#x2010,S.,Hwang, O.&#x2010,J.,Song, P.&#x2010,S.,Kim, Y.&#x2010,S.,Kim, J.&#x2010,I. Blackwell Publishing Ltd 2011 Plant pathology Vol.60 No.4

        <P>A pepper esterase (<I>PepEST</I>) gene was introduced into creeping bentgrass (<I>Agrostis stolonifera</I>) by <I>Agrobacterium</I>‐mediated transformation. Purified recombinant PepEST proteins were sufficient to inhibit the growth of the fungal pathogens <I>Rhizoctonia solani</I> AG2‐2 (IIIB) (causing brown patch) and <I>Sclerotinia homoeocarpa</I> (dollar spot), but not the oomycete responsible for pythium blight, <I>Pythium aphanidermatum</I>. PepEST proteins were most effective against <I>R.?solani</I>. After genetic transformation of creeping bentgrass with <I>PepEST</I>, the genomic integration of transgenes <I>bar</I> and <I>PepEST</I> was confirmed by Southern blot analysis, and their expression was also validated by northern blot and western blot analyses. Disease severity on <I>R.?solani</I>‐inoculated leaves of transgenic plants was <10% compared to <I>ca</I>. 50% in non‐transgenic plants. Microscopic observation of infected leaves indicated that PepEST inhibited the growth of hyphae upon fungal infection.</P>

      • Epidermal regeneration by <i>ent</i>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid isolated from <i>Siegesbeckia pubescens</i>

        Sung, S.&#x2010,H.,Park, S.&#x2010,H.,Song, S.&#x2010,Y.,Lee, S.&#x2010,J.,Lee, H.&#x2010,W.,Kim, S.&#x2010,H.,A Lee, M.,Yoon, I.&#x2010,S.,Kim, D.&#x2010,D.,Kang, S.,Sung, J.&#x2010,H. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.6

        <P><B>Abstract</B></P><P><B>Objectives: </B> Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity.</P><P><B>Materials and methods: </B> Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin‐rejuvenating agent.</P><P><B>Results: </B> <I>Ent</I>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid (DHK) isolated from <I>Siegesbeckia pubescens</I> exhibited a KSC‐stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK‐induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63‐positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63‐positive cells, in animal models.</P><P><B>Conclusion: </B> Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long‐term stability and skin permeability), DHK might be applied to wound‐healing agents and to a basic materials used in cosmetics.</P>

      • SCISCIESCOPUS

        Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration

        Song, D&#x2010,S.,Park, J&#x2010,C.,Jung, I‐,H.,Choi, S&#x2010,H.,Cho, K&#x2010,S.,Kim, C&#x2010,K.,Kim, C&#x2010,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.2

        <P> <I>Song D‐S, Park J‐C, Jung I‐H, Choi S‐H, Cho K‐S, Kim C‐K, Kim C‐S. Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration. J Periodont Res 2011; 46: 193–203. © 2010 John Wiley & Sons A/S</I> </P><P><B>Background and Objective: </B> Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) is a potent inducer for the regeneration of mineralized tissue, but has a limited effect on the regeneration of cementum and periodontal ligament (PDL). The aim of the present study was to determine the effects of rhBMP‐2 on the <I>in vitro</I> and <I>in vivo</I> biologic activity of well‐characterized human PDL stem cells (hPDLSCs) and to elucidate the underlying mechanism of minimal periodontal regeneration by rhBMP‐2.</P><P><B>Material and Methods: </B> hPDLSCs were isolated and cultured, and then transplanted into an ectopic subcutaneous mouse model using a carrier treated either with or without rhBMP‐2. Comprehensive histologic, histometric and immunohistochemical analyses were performed after an 8‐wk healing period. The effects of rhBMP‐2 on the adipogenic and osteogenic/cementogenic differentiation of hPDLSCs were also evaluated. The effect of rhBMP‐2 on both soluble and insoluble collagen synthesis was analyzed, and the expression of mRNA and protein for collagen types I, II, III and V was assessed.</P><P><B>Results: </B> In the present study, rhBMP‐2 promoted both adipogenic and osteogenic/cementogenic differentiation of hPDLSCs <I>in vitro</I>, and the <I>in vivo</I> potential of hPDLSCs to form mineralized cementum and organized PDL tissue was down‐regulated following treatment with rhBMP‐2. Collagen synthesis, which plays a crucial role in the regeneration of cementum and the periodontal attachment, was significantly reduced, with associated modification of the relevant mRNA and protein expression profiles.</P><P><B>Conclusion: </B> In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear to be partly responsible for the minimal effect of rhBMP‐2 on cementum and PDL tissue regeneration by hPDLSCs.</P>

      • Molecular genetic diversity and population structure of a selected core set in garlic and its relatives using novel SSR markers

        Zhao, W.&#x2010,G.,Chung, J.&#x2010,W.,Lee, G.&#x2010,A.,Ma, K.&#x2010,H.,Kim, H.&#x2010,H.,Kim, K.&#x2010,T.,Chung, I.&#x2010,M.,Lee, J.&#x2010,K.,Kim, N.&#x2010,S.,Kim, S.&#x2010,M.,Park, Y.&#x2010 Blackwell Publishing Ltd 2011 Plant breeding Vol.130 No.1

        <P> <I>With 7 figures and 6 tables</I> </P><P><B>Abstract</B></P><P>Garlic is widely consumed for its culinary and medical benefits. Six hundred and thirteen accessions of garlic and its relatives with diverse origin were evaluated for genetic diversity at eight recently novel simple sequence repeat loci in this study. A total of 113 alleles were detected, the average allelic richness was 14.1 alleles per locus. Using a heuristic approach, a core set of 95 accessions was successfully developed, which showed 100% coverage of alleles with minimum redundancy. The model‐based structure analysis here revealed the presence of four subpopulations in the selected core set, which was basically consistent with clustering based on the genetic distance. The analysis of molecular variance based on this core set showed that between‐population component of genetic variance is <15.6% in contrast to 84.4% for the within population component. Overall <I>F</I><SUB>ST</SUB> value was 0.1560, indicating a moderate differentiation among the four groups. These results will provide an effective aid for future allele mining, association genetics, mapping and cloning gene(s), germplasm conservation, and improvement programs.</P>

      • Epidermal growth factor receptor and <i>K‐Ras</i> mutations and resistance of lung cancer to insulin‐like growth factor 1 receptor tyrosine kinase inhibitors

        Kim, Woo&#x2010,Young,Prudkin, Ludmila,Feng, Lei,Kim, Edward S.,Hennessy, Bryan,Lee, Ju&#x2010,Seog,Lee, J. Jack,Glisson, Bonnie,Lippman, Scott M.,Wistuba, Ignacio I.,Hong, Waun Ki,Lee, Ho&#x2010,Youn Wiley Subscription Services, Inc., A Wiley Company 2012 Cancer Vol.118 No.16

        <P><B>Abstract</B></P><P><B>BACKGROUND:</B></P><P>Most patients with nonsmall cell lung cancer (NSCLC) have responded poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The authors investigated the involvement of insulinlike growth factor 1 receptor (IGF‐1R) signaling in primary resistance to EGFR TKIs and the molecular determinants of resistance to IGF‐1R TKIs.</P><P><B>METHODS:</B></P><P>Phosphorylated IGF‐1R/insulin receptor (pIGF‐1R/IR) was immunohistochemically evaluated in an NSCLC tissue microarray. The authors analyzed the antitumor effects of an IGF‐1R TKI (PQIP or OSI‐906), either alone or in combination with a small‐molecular inhibitor (PD98059 or U0126) or with siRNA targeting <I>K‐Ras</I> or mitogen‐activated protein kinase/extracellular signal‐regulated kinase kinase (MEK), in vitro and in vivo in NSCLC cells with variable histologic features and <I>EGFR</I> or <I>K‐Ras</I> mutations.</P><P><B>RESULTS:</B></P><P>pIGF‐1R/IR expression in NSCLC specimens was associated with a history of tobacco smoking, squamous cell carcinoma histology, mutant <I>K‐Ras</I>, and wild‐type (WT) <I>EGFR</I>, all of which have been strongly associated with poor response to EGFR TKIs. IGF‐1R TKIs exhibited significant antitumor activity in NSCLC cells with WT EGFR and WT <I>K‐Ras</I> but not in those with mutations in these genes. Introduction of mutant <I>K‐Ras</I> attenuated the effects of IGF‐1R TKIs on NSCLC cells expressing WT <I>K‐Ras</I>. Conversely, inactivation of MEK restored sensitivity to IGF‐TKIs in cells carrying mutant <I>K‐Ras</I>.</P><P><B>CONCLUSIONS:</B></P><P>The mutation status of both <I>EGFR</I> and <I>K‐Ras</I> could be a predictive marker of response to IGF‐1R TKIs. Also, MEK antagonism can abrogate primary resistance of NSCLC cells to IGF‐1R TKIs. Cancer 2012. © 2012 American Cancer Society.</P>

      • Acute necrotic stomatitis (noma) associated with methicillin‐resistant <i>Staphylococcus aureus</i> infection in a newly acquired rhesus macaque (<i>Macaca mulatta</i>)

        Lee, J.&#x2010,I.,Kim, K.&#x2010,S.,Oh, B.&#x2010,C.,Kim, N.&#x2010,A.,Kim, I.&#x2010,H.,Park, C.&#x2010,G.,Kim, S.&#x2010,J. Blackwell Publishing Ltd 2011 Journal of medical primatology Vol.40 No.3

        <P><B>Abstract</B></P><P><B>Backgroud </B> A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis.</P><P><B>Methods </B> To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied.</P><P><B>Results </B> <I>Staphylococcus aureus</I> and <I>Enterococcus faecalis</I> were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin‐resistant <I>Staphylococcus aureus</I> infection. Vancomycin and ampicillin‐sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion.</P><P><B>Conclusions </B> Simian noma associated with methicillin‐resistant <I>Staphylococcus aureus</I> (MRSA) had not previously been reported in non‐human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.</P>

      • Application of <i>groEL</i> gene for the species‐specific detection of <i>Vibrio parahaemolyticus</i> by PCR

        Hossain, M.T.,Kim, E.&#x2010,Y.,Kim, Y.&#x2010,R.,Kim, D.&#x2010,G.,Kong, I.&#x2010,S. Blackwell Publishing Ltd 2012 Letters in applied microbiology Vol.54 No.1

        <P><B>Abstract</B></P><P><B>Aims: </B> <I>Vibrio parahaemolyticus</I> is a significant cause of human gastrointestinal disorders and is transmitted through ingestion of raw or undercooked contaminated seafood. We used the <I>groEL</I> gene for the species‐specific detection of <I>V.?parahaemolyticus</I> from artificially inoculated shellfish, fish and seawater.</P><P><B>Methods and Results: </B> The nucleotide sequences of 24 <I>Vibrio</I> and seven non‐<I>Vibrio</I> spp. were compared, and less conserved regions were selected for the designing of primer sets. To detect <I>V.?parahaemolyticus</I> specifically, PCR conditions were standardized and tested to evaluate the specificity of primers. A 510‐bp band was appeared only from <I>V.?parahaemolyticus</I> by PCR. Notably, the detection was shown to be functional at high annealing temperature above 68°C. The <I>groEL</I> primers detected 100 pg and 1 ng of DNA purified from <I>V.?parahaemolyticus</I> culture and artificially infected oyster tissue, respectively.</P><P><B>Conclusions: </B> The <I>groEL</I> gene is a potential marker for the species‐specific detection of <I>V.?parahaemolyticus</I> and could be used to detect this bacterium in contaminated food by PCR.</P><P><B>Significance and Impact of the Study: </B> PCR using primers designed from <I>groEL</I> gene provide an efficient method for the accurate identification of <I>V.?parahaemolyticus</I> from contaminated samples.</P>

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