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      • Photoswitching and photocatalytic functions of Sn<sub>x</sub>Cu<sub>1−x</sub>S nanostructures

        Ilanchezhiyan, P.,Kumar, G. Mohan,Siva, C.,Venkatasubbu, G. Devanand,Kang, T.W.,Kim, D.Y. Elsevier 2019 APPLIED SURFACE SCIENCE - Vol.489 No.-

        <P><B>Abstract</B></P> <P>Ultra-thin semiconducting nanostructures are garnering strategic importance in energy and environment remediation applications. In this regard, Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were processed through an eco-friendly chemical route and investigated in detail for photoswitching and photocatalytic functions. X-ray diffraction, FT-IR, Raman, UV–vis absorbance and high-resolution microscopic tools were initially used to examine the physico-chemical traits of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures. Ambiguous evidence for the substitution of Sn ions in place of Cu ions was attained through X-ray photoelectron spectroscopy. The photocatalytic performance of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S systems was investigated through effective remediation of organic dye molecules under visible light. Scavenger based photocatalytic experiments were additionally carried out to infer the degradation mechanism. Type II <I>p-n</I> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/In<SUB>2</SUB>S<SUB>3</SUB> heterojunction diodes were also demonstrated for the first time with improved electrical conductivity and photoelectrical performances. The rectification ratio, forward current values and photo switching capabilities of these diodes were noted to improve in the Current vs. Voltage (I-V) and Current vs. Time (I-T) curves as a function of Sn composition and applied bias potential. The excellent photo switching stability augments the photo generated carriers to be effectively separated along the p-n junctions. The enhanced photoelectronic and photocatalytic functionalities in Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S has finally been reasoned to the improved charge transfer kinetics in the respective architectures, resulting from the effective Sn interaction in hexagonal host lattice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were fabricated by hydrothermal route. </LI> <LI> The nanostructures exhibited excellent photocatalytic activity under visible light. </LI> <LI> Sn interaction in hexagonal host lattice promoted their photocatalytic performance. </LI> <LI> p-Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/n-In<SUB>2</SUB>S<SUB>3</SUB> diodes demonstrated improved photoswitching performance. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G<sub>2</sub>/M phase arrest

        Lee, Y.‐,S.,Choi, K.‐,M.,Choi, M.‐,H.,Ji, S.‐,Y.,Lee, S.,Sin, D.‐,M.,Oh, K.‐,W.,Lee, Y.‐,M.,Hong, J.‐,T.,Yun, Y.‐,P.,Yoo, H.‐,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

        <P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

      • Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

        Kim, J C,Ha, Y J,Roh, S A,Choi, E Y,Yoon, Y S,Kim, K P,Hong, Y S,Kim, T W,Cho, D H,Kim, S Y,Kim, Y S Nature Publishing Group 2013 The British journal of cancer Vol.108 No.9

        <P><B>Background:</B></P><P>Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy.</P><P><B>Methods:</B></P><P>A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway.</P><P><B>Results:</B></P><P>For cetuximab regimens, patients homozygous for the wild-type alleles (<I>GG</I>) of <I>LIFR rs3729740</I> exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (<I>GA</I> and <I>AA</I>; <I>P</I>=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (<I>TT</I>) of <I>ANXA11 rs1049550</I> exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (<I>CC</I> and <I>CT</I>; <I>P</I>=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type <I>LIFR rs3729740</I> patients either with wild-type <I>KRAS</I> or skin toxicity (<I>P</I>=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type <I>LIFR rs3729740</I> (<I>P</I>=0.044) and in those expressing minor-type <I>ANXA11 rs1049550</I> (<I>P</I>=0.007), respectively.</P><P><B>Conclusion:</B></P><P><I>LIFR rs3729740</I> and possibly <I>ANXA11 rs1049550</I> may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.</P>

      • 면양(緬羊)에 의한 Formaldehyde 처리 Alfalfa 엽(葉) 분미의 단백질 가치평가에 관한 연구

        강희신,R. H. Weston,J. R. Ashes,P. Davis,R. W. Edols 한국낙농학회 1985 韓國酪農學會誌 Vol.7 No.4

        低質 粗飼科 밀짚으로 飼育되는 交雜種 緬羊 6頭를 供試하며 alfalfa 葉 粉末, 當年葉, 貯藏葉, 2% HCHO處理 當年葉 및 4% HCHO處理貯藏葉을 供試 飼料로 하고 밀짚 基本飼料 700g 및 alfalfa 粉末 補充飼料 300g 計 1.0㎏를 日量 飼料로 連續 給餌器에서 3시간 間隔으로 1日 8回 給與하며 20日間씩의 代謝試驗을 4回 實施하였다. ^(51)Cr-EDTA 및 ^(103)Ru-phe의 二重 標識物質을 使用하여 腸內 內容物의 通過量 및 滯在時間反芻胃 溶量, 有機物 및 窒素의 利用性을 測定한 結果 다음과 같은 結果를 얻었다. 1. 反芻胃 溶液中의 NH₃態 窒素 濃度는 貯藏葉이 當年葉보다 17.5% 높으며(P<.01) 2% HCHO處理 當年葉은 그 無處理보다 7% 程度 減少되고 4% HCHO處理 貯藏葉은 無處理보다 34.0% 程度 減少(P<.01)되었다. 2. 反芻胃로부터 流入되는 NH₃態 窒素 量은 當年葉보다 貯藏葉이 18% 增加(P<.01)되고 2% HCHO處理 當年葉은 無處理보다 6% 減少 (P<.05)되며, 4% HCHO處理 貯藏葉은 無處理보다 32% 減少(P<.01)를 나타내었다. 3. 第4胃內 NAN含量은 當年葉이 貯藏葉보다 6% 增加되며 2% HCHO處理 當年葉은 無處理보다 5.6%의 增加(P<.05) 4% HCHO處理 貯藏葉은 그 無處理보다 17% 程度의 增加(P<.01)를 나타내었다. 4. 第4胃로부터 排出되어 小腸에 流入되는 NAN의 量은 當年葉보다 貯藏葉이 9.0% 더 流入되며(P<.05) 2% HCHO 處理 當年葉은 그 無處理보다 6% 程度 增加(P<.05) 流人되었다. 5. 飼料源 室素 100g 攝取量當 NAN의 小腸內 消化量은 當年葉보다 貯藏葉이 10% 程度 消化가 增進(P<.05)되며 2% HCHO 處理 當年葉은 無處理보다 6% 程度 消化가 增進(P<.05)되었다. 6. 飼料源 室素 100g 攝取量 當 糞中 窒素의 排泄量은 當年葉보다 貯藏葉이 8% 정도(P<.01), 2% HCHO處理 當年葉은 無處理보다 6% 程度(P<.05) 더 排泄되었으며 4% HCHO處理葉은 그 無處理에 比하여 2% 程度 더 排泄되었으나 有意差는 認定되지 않았다. 7. 反芻胃液(Y, ㎎ N%)과 第4胃 濾液(X, ㎎ N%)中의 NH₃態 室素 濃度와의 關係는 다음 回歸 方程式으로 表示되었다. Y = 3.981 + 1.2783(±0.3736)X (r = 0.59, n-2=22) 8. 飼料 窒素 攝取量에 對한 補充飼料 alfalfa 葉 粉末의 小腸內 流入 NAN의 百分比는 當年葉, 2% HCHO處理 當年葉 및 無處理 貯藏葉의 順으로 각각 57.0%, 68.0% 및 65%로 推定되었다. 따라서 小腸內 流入 NAN은 2% HCHO處理 當年葉이 無處理보다 19%, 貯藏葉은 當年葉 無處理보다 14% 程度 增加된 것으로 推定된다. 9. 貯藏葉 補充時 音機物 消化率은 當年葉을 補充할 때 보다 約 1% 減少되고 當年葉 및 貯藏葉에 HCHO處理는 葉中 有機物의 排泄量을 0∼3.4% 程度 增加시키는 傾向이었으나 有意差는 當年葉과 貯藏葉 間에만 認定되었다. 10. 反芻胃液 및 第4胃液의 各 腸器 通過率, 反芻胃 容量 및 그 內容物의 滯在時間은 處理間有意差가 認定되지 않았다. 1. The OM out-put in the faeces was about 3% unit higher with the Old than that with the New, while with the HCHO treated meals there was only a slightly and insignificantly increasing tendency in the OM out-put. 2. No significant differences in the liquor flow rate of the rumen and the abomasum fluid, and in the rumen volume and retention time were found between the treatments. 3. The ruminal NH₃-N concentration in the Old was about 17.5% unit higher (P<0.01) than that in the New, while the New + 2% HCHO was about 7.0% unit (P<0.10) and the Old + 4% HCHO was about 34% lower (P<0.01) than those in the untreated-New and Old. 4. The amount of NH₃-N excreted from the rumen in the Old was 18% unit higher (P<0.01) than that in the New, and that in the New + 2% HCHO about 6% unit was lower, though insignificant, than that in the New, while that in the Old + 4% HCHO was about 32% unit lower (P<0.01) than that in the Old. 5. The NAN content of the intestine in the New was about 6% unit higher (P<0.10) than that in the Old, while in the New + 2% HCHO and the Old + 4% HCHO about 6% unit (P<0.05) and 17% unit (P<0.01) were higher than those in the New and the Old, respectively. 6. The amount of NAN excreted from the abomasum in the Old was about 9% unit higher (P<0.05) than that in the New, while the New + 2% HCHO resulted about 6% unit higher (P<0.01) NAN excretion than the New. 7. The NAN digested in the intestine per 100g of dietary nitrogen intake in the Old was about 10% unit higher (P<0.10) than that in the New, while in the New + 2% HCHO about 6% unit was higher (P<0.05) than that in the New. 8. The fecal nitrogen output per 100g of dietary nitrogen intake in the Old was about 8% unit (P<0.01), in the New + 2% HCHO was about 6% unit and in the Old + 4% HCHO about 2.4% unit was higher (P<0.10) than in the New and the Old. 9. The significant correlation between the concentrations of NH₃-N in the abomasal filtrates and those in the ruminal fluids permitted to draw a predictive equation by regression analysis as follows: y = 3.981 + 1.2783(+0.3736) X, where, Y = Ruminal NH₃-N concentration (㎎ N%) X= NH₃-N concentration in abomasal filtrates (㎎ N%), (n-2=22) and (r=0.59) 10. The percent of NAN entered the intestines over supplemental leaf meal nitrogen intake in the New, the New + 2% HGHO and the Old were 57.0, 68.0 and 65%, respectively. The NAN entered the intestine in the New + 2% HCHO and the Old were 19% and 14% higher than those in the New, respectively.

      • <i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms

        Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. ‐,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. ‐,K.,Yoon, Y. ‐,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4

        <P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>

      • Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

        Westhovens, R,Robles, M,Ximenes, A C,Nayiager, S,Wollenhaupt, J,Durez, P,Gomez-Reino, J,Grassi, W,Haraoui, B,Shergy, W,Park, S-H,Genant, H,Peterfy, C,Becker, J-C,Covucci, A,Helfrick, R,Bathon, J BMJ Group 2009 Annals of the Rheumatic Diseases Vol.68 No.12

        <P><B>Objectives:</B></P><P>To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.</P><P><B>Methods:</B></P><P>In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout.</P><P><B>Results:</B></P><P>At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone.</P><P><B>Conclusions:</B></P><P>In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.</P>

      • Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study

        Keystone, E C,Genovese, M C,Klareskog, L,Hsia, E C,Hall, S T,Miranda, P C,Pazdur, J,Bae, S-C,Palmer, W,Zrubek, J,Wiekowski, M,Visvanathan, S,Wu, Z,Rahman, M U BMJ Publishing Group 2009 Annals of the Rheumatic Diseases Vol.68 No.6

        <P><B>Objective:</B></P><P>The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.</P><P><B>Methods:</B></P><P>Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n  =  133), golimumab 100 mg injections plus placebo capsules (group 2, n  =  133), golimumab 50 mg injections plus methotrexate capsules (group 3, n  =  89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n  =  89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.</P><P><B>Results:</B></P><P>The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.</P><P><B>Conclusion:</B></P><P>The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.</P>

      • Effect of <i>CYP3A5*3</i> genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

        Park, P.-W.,Seo, Y. H.,Ahn, J. Y.,Kim, K.-A.,Park, J.-Y. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.5

        <P>Abstract</P><P>Background and Objective: </P><P>Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the <I>CYP3A5*3</I> genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the <I>CYP3A5*3</I> genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients.</P><P>Method: </P><P>The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their <I>CYP3A5</I> genotype was determined. Fourteen patients were <I>CYP3A5</I> expressors (two for <I>CYP3A5*1/*1</I> and 12 for <I>CYP3A5*1/*3</I>) and 21 patients were <I>CYP3A5</I> non-expressors (<I>CYP3A5*3/*3</I>). Dose-normalized concentrations (mean ± SD) of CBZ were 9·9 ± 3·4 ng/mL/mg for <I>CYP3A5</I> expressors and 13·1 ± 4·5 ng/mL/mg for <I>CYP3A5</I> non-expressors (<I>P</I> = 0·032). The oral clearance of CBZ was significantly higher in <I>CYP3A5</I> non-expressors than that of <I>CYP3A5</I> expressors (0·056 ±0·017 L/h/kg vs. 0·040 ± 0·014 L/h/kg, <I>P</I> = 0·004). The <I>CYP3A5</I> genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.</P>

      • SCIESCOPUS

        Identification of a novel <i>FAM83H</i> mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta

        Hyun, H.-K.,Lee, S.-K.,Lee, K.-E.,Kang, H.-Y.,Kim, E.-J.,Choung, P.-H.,Kim, J.-W. Blackwell Publishing Ltd 2009 International endodontic journal Vol.42 No.11

        <P>Abstract</P><P>Aim </P><P>To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known <I>FAM83H</I> mutation.</P><P>Methodology </P><P>Mutational screening of the <I>FAM83H</I> on the basis of candidate gene approach was performed. All exons and exon–intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value.</P><P>Results </P><P>A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of <I>FAM83H</I>, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control.</P><P>Conclusions </P><P>Mutational analysis revealed a novel mutation in <I>FAM83H</I> gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.</P>

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