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      • Endocervical-like (Müllerian) mucinous borderline tumours of the ovary are frequently associated with the <i>KRAS</i> mutation

        Kim, Kyu-Rae,Choi, Jene,Hwang, Jeong-Eun,Baik, Young-Ae,Shim, Jeong Yeon,Kim, Yong Man,Robboy, Stanley J Blackwell Publishing Ltd 2010 Histopathology Vol.57 No.4

        <P>Kim K-R, Choi J, Hwang J-E, Baik Y-A, Shim J Y, Kim Y M & Robboy S J(2010) <I>Histopathology</I><B>57</B>, 587–596<B>Endocervical-like (Müllerian) mucinous borderline tumours of the ovary are frequently associated with the <I>KRAS</I> mutation</B></P><P>Aims: </P><P>Clinicopathological aspects of the endocervical-like mucinous borderline tumour of the ovary (EMBT), including higher frequencies of bilaterality, endometriosis and hormone receptor reactivity, and often admixtures of various Müllerian-type epithelia, closely resembles endometrioid tumour more than mucinous borderline tumour of the intestinal type (IMBT). Thus, the aims of this study were to determine whether EMBT is really a subtype of mucinous borderline tumours, as shown in the current classification system, and to determine the best classification for EMBT.</P><P>Methods and results: </P><P>The clinicopathological and immunohistochemical features of 17 EMBTs were analysed, including oestrogen receptor (ER), progesterone receptor (PR), <I>PTEN</I>, cytokeratins (CK) 7 and 20, and <I>&bgr;-catenin</I>. Additionally, mutational analyses of the <I>KRAS</I> (exon 1) and <I>PTEN</I> genes (all nine exons) were performed in all cases, and the results were compared with literature findings for IMBT and endometrioid tumours. Twelve patients (71%) were confirmed histologically to have endometriosis in one or both ovaries. In seven cases, gradual transitions from endometriotic foci to the EMBT were identified. Immunohistochemically, all cases were reactive for ER and PR, with no nuclear expression of &bgr;-catenin. CK7 positivity was strong in all patients, whereas there was no reactivity for CK20. <I>PTEN</I> reactivity was diffuse in the nuclei of epithelial and underlying stromal cells. Sixty-nine per cent showed <I>KRAS</I> mutations in exon 1 and codon 12, but no <I>PTEN</I> mutation was identified in any of the nine exons.</P><P>Conclusion: </P><P>Our study suggests that EMBT has features of both mucinous and endometrioid tumours and is an additional tumour type arising in endometriosis. While clinicopathological features of EMBTs are closer to endometrioid tumours, they still have molecular characteristics closer to IMBTs.</P>

      • KCI등재

        연령에 따른 각막난시와 내부난시의 변화

        이현(Lee, Hyun),김정현(Kim J.H.),이성복(Lee, Sung-Bok),엄정희(Eom, Jeong-Hee),이강오(Rhee, Kang-Oh),이태용(Lee, Tae-Yong) 한국산학기술학회 2013 한국산학기술학회논문지 Vol.14 No.8

        본 연구의 목적은 연령별 난시빈도를 알아보고 굴절난시와 각막난시, 내부난시의 연령에 따른 변화와 변화 요인을 알아보고자 하였다. 2010년 7월에 만5~59세의 청주지역 거주자 1,017명을 대상으로 굴절력과 각막전면굴절력 을 자동굴절검사기로 측정하였다. 난시빈도는 전체적으로 22.7%이었고, 5~9세에 8.9%에서 20대에 36.8%로 증가하였 다. 40대에는 19.2%로 감소하였다가 50대에 28.6%로 다시 증가하였다. 굴절난시와 각막난시, 내부난시의 J<sub>45</sub>성분은 연 령군에 상관없이 거의 일정하였으나 굴절난시와 각막난시의 J<sub>0</sub>성분은 30대 이후 감소하는 경향성을 보였다. 또한 J<sub>0</sub>성 분 중에서 수직방향 굴절력은 연령에 따라 변화가 없이 일정하였지만 수평방향 굴절력은 연령에 따라 큰 변화가 있 었다. 연령에 따른 난시빈도의 변화는 수평방향 굴절력의 변화에 기인하는 것으로 판단된다. The purpose of present study was to determine the frequency of RA with age and to investigate the age-related trends and changing-factors in RA, CA and IAs. The refractive power of the eye and the power of corneal anterior surface were measured with auto-refractor among 1,017 inhabitants aged 5 to 59 years in Cheongju in July 2010. The overall frequency of RA was 22.7%, and frequency of RA increased from 8.9% in 5~9 years age group to 36.8% in 20~29 years age group. It then dipped to 19.2% in 40~49 years age group but increased again 28.6% in 50~59 years age group. J<sub>45</sub> components for RA, CA, and IAs were fairly stable in different age groups, the changes in J<sub>0</sub> components for both RA and CA appeared to be decreased after age of 30 years. In addition, the refractive power on the vertical direction was changed slightly with age, but the refractive power on the horizontal direction was changed significantly with age. It was expected that the change in the frequency of astigmatism with age was due to the change in the refractive power of horizontal meridian.

      • Glucose deprivation increases O-GlcNAc protein modification in cancer cells through glycogen breakdown

        Jeong Gu Kang,Sang Yoon Park,Suena Ji,Insook Jang,Sujin Park,Hyun Sil Kim,Sung-Min Kim,Jong In Yook,Yong-Il Park,Jürgen Roth,Jin Won Cho 한국당과학회 2011 한국당과학회 학술대회 Vol.2011 No.1

        In general the extent of protein O-GlcNAc modification (O-GlcNAcylation) decreases when cellular glucose concentrations fall below normal levels. However, recent reports demonstrated that O-GlcNAcylation was increased by glucose deprivation in HepG2 and Neuro-2a cells. Here, we report increased O-GlcNAcylation in non-small cell lung carcinoma A549 cells and various cells in response to glucose deprivation. Although the level of O-GlcNAc transferase was not changed, it contained less O-GlcNAc and the activity was increased. Also, the activity of O-GlcNAcase was reduced. The studied glycogen containing cells, and we show that its degradation by glucose deprivation provides a source for UDP-GlcNAc required for increased O-GlcNAcylation under this condition. This required active glycogen phosphorylase and resulted in increased glutamine:fructose-6-phosphate amidotransferase, the first and rate-limiting enzyme in the hexosamine biosynthetic pathway. Interestingly, glucose deprivation reduced the amount of phosphofructokinase 1, a regulatory glycolytic enzyme, and blocked ATP synthesis. These findings suggest that glycogen is the source for increased O-GlcNAcylation but not for generating ATP in response to glucose deprivation and it may be useful for cancer cells to survive.

      • SCOPUSKCI등재

        혈액투석 중인 만성 신부전 환자에서 TT Virus의 감염률과 임상적 의의

        이용욱,허우성,도재혁,백승운,최문석,김소정,이준행,고광철,이풍렬,이종철,최규완,박상종,이준혁,김재준,오하영,임윤정 대한소화기학회 2001 대한소화기학회지 Vol.37 No.1

        Background/Aims: TT virus (TTV) is a unenveloped, single-stranded and circular DNA virus isolated from the serum of a patient with posttransfusion hepatitis of unknown etiology. We evaluated the prevalence, risk factors, and clinical significance of TTV in patients with chronic renal failure(CCRF) undergoing maintenance hemodialysis (HD). Methods: We examined TTV DNA in serum of HD-undergoing patients and healthy controls using the nested polymerase chain reaction. Results: TTV DNA was detected in 15 (20.0%) of 75 HD-undergoing patients and 10 (13.2%) of 76 healthy controls (p$gt;0.05). The prevalence of TTV did not differ according to the duration of HD or transfusion history of the patients. The prevalence of TTV was higher in IgG anti-HBc positive patients than IgG anti-HBc negative patients (27.5% vs. 4.2%, p=0.03). There was no relationship between TTV infection and liver diseases. Conclusions: The prevalence of TTV infection in CRF patients undergoing HD was similar with that of healthy controls. These results suggest that TTV infection may share the route of transmission with HBV infection in adults.

      • KCI등재

        알쯔하이머병 환자에서 Capgras 증후군 3예

        강수진,정용,진주희,윤수진,나덕렬 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.2

        Capgras′ syndrome, one form of the selusional misidentification syndromes, is the delusional belief in the existence of 'doubles' or 'impostors' of significant people in a patient′s life Capgras′ syndrome has been considered to be associated with psychiatric disorders other than dementia however, many recent studies have reported that this syndrome emerges frequently during the course of organic diseases such as Alzheimer′s disease Despite numerous reports about Capgras′ syndrome. there have been only two case reports in Korea. in which Capgras′ syndrome was caused by non-Alzheimer′s disease. We described detailed history of three patients with capgras′ syndrome associated with Alzheimer′s disease These three patientswere in the early stage of Alzheimer′s disease (CDR 1 or CDR 0 5) When they showed Capgras′ syndrome. Target people for the delusional misbelief in all three patients were the spouses who were believed as 'a thief' or 'a stranger' in case 1, 'a stranger' in case 2, 'a mother or a father' in case 3. Two of the three patients also had negative emotion toward their husbands. Capgras′ syndrome in our cases was accompanied by other behavior disturbances that included delusion of 'one's house not being one's home', paranoid delusion, and aggressiveness in case 1, Capgras' syndrome disappeared spontaneously one year later. In contrast. in case 2 and 3, Capgras' syndrome persisted for three years and two years respectively, despite treatment with olanzapine Our detailed description of the patients' symtoms and their caregivers' response verbatim wound help Korean clinicians to manage the patients with Capgras' syndrome and to educate their caregivers.

      • SCIESCOPUS

        Preparation and Characterization of Aripiprazole Cocrystals with Coformers of Multihydroxybenzene Compounds

        Cho, Min-Yong,Kim, Paul,Kim, Ga-Young,Lee, Ju-Yeon,Song, Keon-Hyoung,Lee, Min-Jeong,Yoon, Woojin,Yun, Hoseop,Choi, Guang J. The American Chemical Society 2017 CRYSTAL GROWTH AND DESIGN Vol.17 No.12

        <P>A novel co-crystal of aripiprazole (ARI), the active substance in the atypical antipsychotic Abilify, with orcinol (ORC) as a coformer, was prepared, characterized, and compared with other ARI co-crystals with dihydroxy- and trihydroxy-benzene coformers [catechol (CAT), resorcinol (RES), and phloroglucinol (PHL)] reported previously (Nanubolu, J. B.; Ravikumar, K. <I>CrystEngComm</I> <B>2016</B>, <I>18</I>, 1024–1038). Three preparation methods were used: neat grinding (NG), liquid-assisted grinding (LAG), and solvent evaporation (SE). Based on single-crystal X-ray diffraction (SC-XRD) measurements, the crystal structure of the ARI–ORC co-crystal was determined to be monoclinic. The melting point of ARI–ORC co-crystal was found to be 184–185 °C, higher than existing ARI co-crystals with multihydroxybenzene coformers. Additionally, the ARI–ORC co-crystal showed the highest dissolution rate among those in the test group in an acetonitrile–water 10/90 cosolvent. We investigated how the co-crystallization pathway and the dissolution behavior might correlate with the coformer moiety, primarily in terms of its chemical structure and melting point. Co-crystallization between ARI and PHL via grinding (NG or LAG) required the highest activation energy, mainly due to the coformer’s higher melting point. The dissolution rate of ARI co-crystals was not obviously correlated with the coformer’s melting point or its molecular weight. However, the high dissolution rate of ARI–ORC co-crystals was possibly associated with the bond angle of D–H···A for O3–H3O···N2 in the co-crystal’s superlattice structure. The stability of ARI co-crystals was examined by aging these powders in a controlled oven at 80 °C/98% relative humidity for 1 week. We observed that all of the co-crystal powders, except for the aripiprazole–catechol (ARI–CAT) pair, underwent no noticeable degradation or physicochemical change upon treatment. In conclusion, we can consider the novel ARI–ORC co-crystal as a potential drug substance with the enhanced dissolution behavior in aqueous media and good stability under stressed conditions.</P><P>A novel co-crystal of aripiprazole (ARI), the active substance in the atypical antipsychotic Abilify, with orcinol (ORC) as a coformer, was prepared, characterized, and compared with other ARI co-crystals with dihydroxy- and trihydroxy-benzene coformers [catechol (CAT), resorcinol (RES), and phloroglucinol (PHL)] reported previously. In conclusion, we can consider the novel ARI−ORC co-crystal as a potential drug substance with the enhanced dissolution behavior in aqueous media and good stability under stressed conditions.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/cgdefu/2017/cgdefu.2017.17.issue-12/acs.cgd.7b01281/production/images/medium/cg-2017-01281j_0014.gif'></P>

      • SCISCIESCOPUSKCI등재
      • SCIE

        PEGylated lipid bilayer-supported mesoporous silica nanoparticle composite for synergistic co-delivery of axitinib and celastrol in multi-targeted cancer therapy

        Choi, J.Y.,Ramasamy, T.,Kim, S.Y.,Kim, J.,Ku, S.K.,Youn, Y.S.,Kim, J.R.,Jeong, J.H.,Choi, H.G.,Yong, C.S.,Kim, J.O. Elsevier Science B.V. Amsterdam 2016 ACTA BIOMATERIALIA Vol. No.

        Small-molecule drug combination therapies are an attractive approach to enhancing cancer chemotherapeutic responses. Therefore, this study aimed to investigate the potential of axitinib (AXT) and celastrol (CST) in targeting angiogenesis and mitochondrial-based apoptosis in cancer. Therefore, we prepared AXT/CST-loaded combination nanoparticles (ACML) with CST loaded in the mesoporous silica nanoparticles (MSN) and AXT in PEGylated lipidic bilayers. We showed that ACML effectively inhibited angiogenesis and mitochondrial function and was efficiently internalized in SCC-7, BT-474, and SH-SY5Y cells. Furthermore, hypoxia-inducible factor (HIF)-1α expression, which increased under hypoxic conditions in all cell lines exposed to ACML, markedly decreased, which may be critical for tumor inhibition. Western blotting showed the superior anticancer effect of combination nanoparticles in different cancer cells. Compared to the cocktail (AXT/CST), ACML induced synergistic cancer cell apoptosis. The AXT/CST-based combination nanoparticle synergism might be mediated by AXT, which controls vascular endothelial growth factor receptors while CST acts on target cell mitochondria. Importantly, ACML-treated mice showed remarkably higher tumor inhibition (64%) than other groups did in tumor xenograft models. Tumor xenograft immunohistochemistry revealed elevated caspase-3 and poly (ADP-ribose) polymerase and reduced CD31 and Ki-67 expression, clearly suggesting tumor apoptosis through mitochondrial and antiangiogenic effects. Overall, our results indicate that ACML potentially inhibited cell proliferation and induced apoptosis by blocking mitochondrial function, leading to enhanced antitumor efficacy. Statement of Significance: In this research, we formulated an anticancer drug combination nanoparticle loaded with axitinib (AXT) in the lipidic bilayer of PEGylated liposomes and celastrol (CST) in mesoporous silica nanoparticles. The anticancer effects of the AXT/CST-loaded combination nanoparticle (ACML) were synergistic and superior to the other formulations and involved more efficient drug delivery to the tumor site with enhanced effects on angiogenesis and mitochondrial function. Therefore, our study demonstrated that the inhibition of cell proliferation and induction of apoptosis by ACML, which was mediated by blockade of mitochondrial function and anti-angiogenesis, led to enhanced antitumor efficacy, which may be potentially useful in the clinical treatment of cancer.

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