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Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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A Study on Developing a VKOSPI Forecasting Model via GARCH Class Models for Intelligent Volatility Trading Systems (지능형 변동성트레이딩시스템개발을 위한 GARCH 모형을 통한 VKOSPI 예측모형 개발에 관한 연구)

  • Kim, Sun-Woong
    • Journal of Intelligence and Information Systems
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    • v.16 no.2
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    • pp.19-32
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    • 2010
  • Volatility plays a central role in both academic and practical applications, especially in pricing financial derivative products and trading volatility strategies. This study presents a novel mechanism based on generalized autoregressive conditional heteroskedasticity (GARCH) models that is able to enhance the performance of intelligent volatility trading systems by predicting Korean stock market volatility more accurately. In particular, we embedded the concept of the volatility asymmetry documented widely in the literature into our model. The newly developed Korean stock market volatility index of KOSPI 200, VKOSPI, is used as a volatility proxy. It is the price of a linear portfolio of the KOSPI 200 index options and measures the effect of the expectations of dealers and option traders on stock market volatility for 30 calendar days. The KOSPI 200 index options market started in 1997 and has become the most actively traded market in the world. Its trading volume is more than 10 million contracts a day and records the highest of all the stock index option markets. Therefore, analyzing the VKOSPI has great importance in understanding volatility inherent in option prices and can afford some trading ideas for futures and option dealers. Use of the VKOSPI as volatility proxy avoids statistical estimation problems associated with other measures of volatility since the VKOSPI is model-free expected volatility of market participants calculated directly from the transacted option prices. This study estimates the symmetric and asymmetric GARCH models for the KOSPI 200 index from January 2003 to December 2006 by the maximum likelihood procedure. Asymmetric GARCH models include GJR-GARCH model of Glosten, Jagannathan and Runke, exponential GARCH model of Nelson and power autoregressive conditional heteroskedasticity (ARCH) of Ding, Granger and Engle. Symmetric GARCH model indicates basic GARCH (1, 1). Tomorrow's forecasted value and change direction of stock market volatility are obtained by recursive GARCH specifications from January 2007 to December 2009 and are compared with the VKOSPI. Empirical results indicate that negative unanticipated returns increase volatility more than positive return shocks of equal magnitude decrease volatility, indicating the existence of volatility asymmetry in the Korean stock market. The point value and change direction of tomorrow VKOSPI are estimated and forecasted by GARCH models. Volatility trading system is developed using the forecasted change direction of the VKOSPI, that is, if tomorrow VKOSPI is expected to rise, a long straddle or strangle position is established. A short straddle or strangle position is taken if VKOSPI is expected to fall tomorrow. Total profit is calculated as the cumulative sum of the VKOSPI percentage change. If forecasted direction is correct, the absolute value of the VKOSPI percentage changes is added to trading profit. It is subtracted from the trading profit if forecasted direction is not correct. For the in-sample period, the power ARCH model best fits in a statistical metric, Mean Squared Prediction Error (MSPE), and the exponential GARCH model shows the highest Mean Correct Prediction (MCP). The power ARCH model best fits also for the out-of-sample period and provides the highest probability for the VKOSPI change direction tomorrow. Generally, the power ARCH model shows the best fit for the VKOSPI. All the GARCH models provide trading profits for volatility trading system and the exponential GARCH model shows the best performance, annual profit of 197.56%, during the in-sample period. The GARCH models present trading profits during the out-of-sample period except for the exponential GARCH model. During the out-of-sample period, the power ARCH model shows the largest annual trading profit of 38%. The volatility clustering and asymmetry found in this research are the reflection of volatility non-linearity. This further suggests that combining the asymmetric GARCH models and artificial neural networks can significantly enhance the performance of the suggested volatility trading system, since artificial neural networks have been shown to effectively model nonlinear relationships.

A Thermal Time-Driven Dormancy Index as a Complementary Criterion for Grape Vine Freeze Risk Evaluation (포도 동해위험 판정기준으로서 온도시간 기반의 휴면심도 이용)

  • Kwon, Eun-Young;Jung, Jea-Eun;Chung, U-Ran;Lee, Seung-Jong;Song, Gi-Cheol;Choi, Dong-Geun;Yun, Jin-I.
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.8 no.1
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    • pp.1-9
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    • 2006
  • Regardless of the recent observed warmer winters in Korea, more freeze injuries and associated economic losses are reported in fruit industry than ever before. Existing freeze-frost forecasting systems employ only daily minimum temperature for judging the potential damage on dormant flowering buds but cannot accommodate potential biological responses such as short-term acclimation of plants to severe weather episodes as well as annual variation in climate. We introduce 'dormancy depth', in addition to daily minimum temperature, as a complementary criterion for judging the potential damage of freezing temperatures on dormant flowering buds of grape vines. Dormancy depth can be estimated by a phonology model driven by daily maximum and minimum temperature and is expected to make a reasonable proxy for physiological tolerance of buds to low temperature. Dormancy depth at a selected site was estimated for a climatological normal year by this model, and we found a close similarity in time course change pattern between the estimated dormancy depth and the known cold tolerance of fruit trees. Inter-annual and spatial variation in dormancy depth were identified by this method, showing the feasibility of using dormancy depth as a proxy indicator for tolerance to low temperature during the winter season. The model was applied to 10 vineyards which were recently damaged by a cold spell, and a temperature-dormancy depth-freeze injury relationship was formulated into an exponential-saturation model which can be used for judging freeze risk under a given set of temperature and dormancy depth. Based on this model and the expected lowest temperature with a 10-year recurrence interval, a freeze risk probability map was produced for Hwaseong County, Korea. The results seemed to explain why the vineyards in the warmer part of Hwaseong County have been hit by more freeBe damage than those in the cooler part of the county. A dormancy depth-minimum temperature dual engine freeze warning system was designed for vineyards in major production counties in Korea by combining the site-specific dormancy depth and minimum temperature forecasts with the freeze risk model. In this system, daily accumulation of thermal time since last fall leads to the dormancy state (depth) for today. The regional minimum temperature forecast for tomorrow by the Korea Meteorological Administration is converted to the site specific forecast at a 30m resolution. These data are input to the freeze risk model and the percent damage probability is calculated for each grid cell and mapped for the entire county. Similar approaches may be used to develop freeze warning systems for other deciduous fruit trees.

A Study on Recent Research Trend in Management of Technology Using Keywords Network Analysis (키워드 네트워크 분석을 통해 살펴본 기술경영의 최근 연구동향)

  • Kho, Jaechang;Cho, Kuentae;Cho, Yoonho
    • Journal of Intelligence and Information Systems
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    • v.19 no.2
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    • pp.101-123
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    • 2013
  • Recently due to the advancements of science and information technology, the socio-economic business areas are changing from the industrial economy to a knowledge economy. Furthermore, companies need to do creation of new value through continuous innovation, development of core competencies and technologies, and technological convergence. Therefore, the identification of major trends in technology research and the interdisciplinary knowledge-based prediction of integrated technologies and promising techniques are required for firms to gain and sustain competitive advantage and future growth engines. The aim of this paper is to understand the recent research trend in management of technology (MOT) and to foresee promising technologies with deep knowledge for both technology and business. Furthermore, this study intends to give a clear way to find new technical value for constant innovation and to capture core technology and technology convergence. Bibliometrics is a metrical analysis to understand literature's characteristics. Traditional bibliometrics has its limitation not to understand relationship between trend in technology management and technology itself, since it focuses on quantitative indices such as quotation frequency. To overcome this issue, the network focused bibliometrics has been used instead of traditional one. The network focused bibliometrics mainly uses "Co-citation" and "Co-word" analysis. In this study, a keywords network analysis, one of social network analysis, is performed to analyze recent research trend in MOT. For the analysis, we collected keywords from research papers published in international journals related MOT between 2002 and 2011, constructed a keyword network, and then conducted the keywords network analysis. Over the past 40 years, the studies in social network have attempted to understand the social interactions through the network structure represented by connection patterns. In other words, social network analysis has been used to explain the structures and behaviors of various social formations such as teams, organizations, and industries. In general, the social network analysis uses data as a form of matrix. In our context, the matrix depicts the relations between rows as papers and columns as keywords, where the relations are represented as binary. Even though there are no direct relations between papers who have been published, the relations between papers can be derived artificially as in the paper-keyword matrix, in which each cell has 1 for including or 0 for not including. For example, a keywords network can be configured in a way to connect the papers which have included one or more same keywords. After constructing a keywords network, we analyzed frequency of keywords, structural characteristics of keywords network, preferential attachment and growth of new keywords, component, and centrality. The results of this study are as follows. First, a paper has 4.574 keywords on the average. 90% of keywords were used three or less times for past 10 years and about 75% of keywords appeared only one time. Second, the keyword network in MOT is a small world network and a scale free network in which a small number of keywords have a tendency to become a monopoly. Third, the gap between the rich (with more edges) and the poor (with fewer edges) in the network is getting bigger as time goes on. Fourth, most of newly entering keywords become poor nodes within about 2~3 years. Finally, keywords with high degree centrality, betweenness centrality, and closeness centrality are "Innovation," "R&D," "Patent," "Forecast," "Technology transfer," "Technology," and "SME". The results of analysis will help researchers identify major trends in MOT research and then seek a new research topic. We hope that the result of the analysis will help researchers of MOT identify major trends in technology research, and utilize as useful reference information when they seek consilience with other fields of study and select a new research topic.

Validity and Pertinence of Administrative Capital City Proposal (행정수도 건설안의 타당성과 시의성)

  • 김형국
    • Journal of the Korean Geographical Society
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    • v.38 no.2
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    • pp.312-323
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    • 2003
  • This writer absolutely agrees with the government that regional disequilibrium is severe enough to consider moving the administrative capital. Pursuing this course solely to establish a balanced development, however, is not a convincing enough reason. The capital city is directly related to not only the social and economic situation but, much more importantly, to the domestic political situation as well. In the mid-1970s, the proposal by the Third Republic to move the capital city temporarily was based completely on security reasons. At e time, the then opposition leader Kim, Dae-jung said that establishing a safe distance from the demilitarized zone(DMZ) reflected a typically military decision. His view was that retaining the capital city close to the DMZ would show more consideration for the will of the people to defend their own country. In fact, independent Pakistan moved its capital city from Karachi to Islamabad, situated dose to Kashmir the subject of hot territorial dispute with India. It is regrettable that no consideration has been given to the urgent political situation in the Korean peninsula, which is presently enveloped in a dense nuclear fog. As a person requires health to pursue his/her dream, a country must have security to implement a balanced territorial development. According to current urban theories, the fate of a country depends on its major cities. A negligently guarded capital city runs the risk of becoming hostage and bringing ruin to the whole country. In this vein, North Koreas undoubted main target of attack in the armed communist reunification of Korea is Seoul. For the preservation of our state, therefore, it is only right that Seoul must be shielded to prevent becoming hostage to North Korea. The location of the US Armed Forces to the north of the capital city is based on the judgment that defense of Seoul is of absolute importance. At the same time, regardless of their different standpoints, South and North Korea agree that division of the Korean people into two separate countries is abnormal. Reunification, which so far has defied all predictions, may be realized earlier than anyone expects. The day of reunification seems to be the best day for the relocation of the capital city. Building a proper capital city would take at least twenty years, and a capital city cannot be dragged from one place to another. On the day of a free and democratic reunification, a national agreement will be reached naturally to find a nationally symbolic city as in Brazil or Australia. Even if security does not pose a problem, the governments way of thinking would not greatly contribute to the balanced development of the country. The Chungcheon region, which is earmarked as the new location of the capital city, has been the greatest beneficiary of its proximity to the capital region. Not being a disadvantaged region, locating the capital city there would not help alleviate regional disparity. If it is absolutely necessary to find a candidate region at present, considering security, balanced regional development and post-reunification scenario of the future, Cheolwon area located in the middle of the Korean peninsula may be a plausible choice. Even if the transfer of capital is delayed in consideration of the present political conflict between the South and the North Koreas, there is a definite shortcut to realizing a balanced regional development. It can be found not in the geographical dispersal of the central government, but in the decentralization of power to the provinces. If the government has surplus money to build a new symbolic capital city, it is only right that it should improve, for instance, the quality of drinking water which now everyone eschews, and to help the regional subway authority whose chronic deficit state resoled in a recent disastrous accident. And it is proper to time the transfer of capital city to coincide with that of the reunification of Korea whenever Providence intends.

Geochemical Equilibria and Kinetics of the Formation of Brown-Colored Suspended/Precipitated Matter in Groundwater: Suggestion to Proper Pumping and Turbidity Treatment Methods (지하수내 갈색 부유/침전 물질의 생성 반응에 관한 평형 및 반응속도론적 연구: 적정 양수 기법 및 탁도 제거 방안에 대한 제안)

  • 채기탁;윤성택;염승준;김남진;민중혁
    • Journal of the Korean Society of Groundwater Environment
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    • v.7 no.3
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    • pp.103-115
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    • 2000
  • The formation of brown-colored precipitates is one of the serious problems frequently encountered in the development and supply of groundwater in Korea, because by it the water exceeds the drinking water standard in terms of color. taste. turbidity and dissolved iron concentration and of often results in scaling problem within the water supplying system. In groundwaters from the Pajoo area, brown precipitates are typically formed in a few hours after pumping-out. In this paper we examine the process of the brown precipitates' formation using the equilibrium thermodynamic and kinetic approaches, in order to understand the origin and geochemical pathway of the generation of turbidity in groundwater. The results of this study are used to suggest not only the proper pumping technique to minimize the formation of precipitates but also the optimal design of water treatment methods to improve the water quality. The bed-rock groundwater in the Pajoo area belongs to the Ca-$HCO_3$type that was evolved through water/rock (gneiss) interaction. Based on SEM-EDS and XRD analyses, the precipitates are identified as an amorphous, Fe-bearing oxides or hydroxides. By the use of multi-step filtration with pore sizes of 6, 4, 1, 0.45 and 0.2 $\mu\textrm{m}$, the precipitates mostly fall in the colloidal size (1 to 0.45 $\mu\textrm{m}$) but are concentrated (about 81%) in the range of 1 to 6 $\mu\textrm{m}$in teams of mass (weight) distribution. Large amounts of dissolved iron were possibly originated from dissolution of clinochlore in cataclasite which contains high amounts of Fe (up to 3 wt.%). The calculation of saturation index (using a computer code PHREEQC), as well as the examination of pH-Eh stability relations, also indicate that the final precipitates are Fe-oxy-hydroxide that is formed by the change of water chemistry (mainly, oxidation) due to the exposure to oxygen during the pumping-out of Fe(II)-bearing, reduced groundwater. After pumping-out, the groundwater shows the progressive decreases of pH, DO and alkalinity with elapsed time. However, turbidity increases and then decreases with time. The decrease of dissolved Fe concentration as a function of elapsed time after pumping-out is expressed as a regression equation Fe(II)=10.l exp(-0.0009t). The oxidation reaction due to the influx of free oxygen during the pumping and storage of groundwater results in the formation of brown precipitates, which is dependent on time, $Po_2$and pH. In order to obtain drinkable water quality, therefore, the precipitates should be removed by filtering after the stepwise storage and aeration in tanks with sufficient volume for sufficient time. Particle size distribution data also suggest that step-wise filtration would be cost-effective. To minimize the scaling within wells, the continued (if possible) pumping within the optimum pumping rate is recommended because this technique will be most effective for minimizing the mixing between deep Fe(II)-rich water and shallow $O_2$-rich water. The simultaneous pumping of shallow $O_2$-rich water in different wells is also recommended.

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Surgical Treatment for Isolated Aortic Endocarditis: a Comparison with Isolated Mitral Endocarditis (대동맥 판막만을 침범한 감염성 심내막염의 수술적 치료: 승모판막만을 침범한 경우와 비교 연구)

  • Hong, Seong-Beom;Park, Jeong-Min;Lee, Kyo-Seon;Ryu, Sang-Woo;Yun, Ju-Sik;CheKar, Jay-Key;Yun, Chi-Hyeong;Kim, Sang-Hyung;Ahn, Byoung-Hee
    • Journal of Chest Surgery
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    • v.40 no.9
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    • pp.600-606
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    • 2007
  • Background: Infective endocarditis shows high surgical mortality and morbidity rates, especially for aortic endocarditis. This study attempts to investigate the clinical characteristics and operative results of isolated aortic endocarditis. Material and Method: From July 1990 to May 2005, 25 patients with isolated aortic endocarditis (Group I, male female=18 : 7, mean age $43.2{\pm}18.6$ years) and 23 patients with isolated mitral endocarditis (Group II, male female=10 : 13, mean age $43.2{\pm}17.1$ years) underwent surgical treatment in our hospital. All the patients had native endocarditis and 7 patients showed a bicuspid aortic valve in Group I. Two patients had prosthetic valve endocarditis and one patients developed mitral endocarditis after a mitral valvuloplasty in Group II. Positive blood cultures were obtained from 11 (44.0%) patients in Group I, and 10 (43.3%) patients in Group II, The pre-operative left ventricular ejection fraction for each group was $60.8{\pm}8.7%$ and $62.1{\pm}8.1%$ (p=0.945), respectively. There was moderate to severe aortic regurgitation in 18 patients and vegetations were detected in 17 patients in Group I. There was moderate to severe mitral regurgitation in 19 patients and vegetations were found in 18 patients in Group II. One patient had a ventricular septal defect and another patient underwent a Maze operation with microwaves due to atrial fibrillation. We performed echocardiography before discharge and each year during follow-up. The mean follow-up period was $37.2{\pm}23.5$ (range $9{\sim}123$) months. Result: Postoperative complications included three cases of low cardiac output in Group I and one case each of re-surgery because of bleeding and low cardiac output in Group II. One patient died from an intra-cranial hemorrhage on the first day after surgery in Group I, but there were no early deaths in Group II. The 1, 3-, and 5-year valve related event free rates were 92.0%, 88.0%, and 88.0% for Group I patients, and 91.3%, 76.0%, and 76.0% for Group II patients, respectively. The 1, 3-, and 5-year survival rates were 96.0%, 96.0%, and 96.0% for Group I patients, and foo%, 84.9%, and 84.9% for Group II patients, respectively. Conclusion: Acceptable surgical results and mid-term clinical results for aortic endocarditis were seen.

Combined Modality Therapy with Selective Bladder Preservation for Muscle Invading Bladder Cancer (침윤성 방광암 환자에서 방광 보존 치료)

  • Youn Seon Min;Yang Kwang Mo;Lee Hyung Sik;Hur Won Joo;Oh Sin Geun;Lee Jong Cheol;Yoon Jin Han;Kwon Heon Young;Jung Kyung Woo;Jung Se Il
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.237-244
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    • 2001
  • Purpose : To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. Method and Materials : From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by $39.6\~45\;Gy$ pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. Results : The Patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients $(81\%)$ successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients $(58\%)$ were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were $80\%\;and\;14\%$, respectively (u=0.001). Conclusion : In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.

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Treatment Results of Radical Radiotherapy in Uterine Cervix Cancer (자궁경부암 환자의 근치적 방사선치료성적)

  • Huh Seung Jae;Kim Bo Kyong;Lim Do Hoon;Shin Seong Soo;Lee Jeong Eun;Kang Min Kyu;Ahn Yong Chan
    • Radiation Oncology Journal
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    • v.20 no.3
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    • pp.237-245
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    • 2002
  • Purpose : This study was conducted to evaluate the treatment results, prognostic factors, and complication rates after high dose rate (HDR) brachytherapy in patients with uterine cervix cancer who were treated with curative aim. Materials and Methods : Of 269 cervix cancer patients treated at the department of radiation oncology, Samsung Medical Center from September 1994 to July 1998, the 106 who were treated with radical radio-therapy were analyzed. The median age was 61 years (range 22 to 89). All patients except 4 with carcinoma in situ (CIS) were given external beam radiotherapy (range $30.6\~50.4\;Gy$ to whole pelvis) and HDR brachytherapy. The common regimens of HDR brachytherapy were a total dose of $24\~28\;Gy$ with $6\~7$ fractions to point A at two fractions per week. The median overall treatment time was 55 days (range 44 to 104) in patients given both external beam radiotherapy and HDR brachytherapy. Results : Early responses of radiotherapy were evaluated by gynecologic examination and follow-up MRI 1 month after radiotherapy. Treatment responses were complete remission in 72 patients, partial response in 33 and no response in 1. The overall survival (OS) rate of all patients was $82\%,\;and\;73\%$, and the disease free survival (DFS) rate was $72\%,\;and\;69\%$, at 3, and 5 years, respectively. The pelvic control rate (PCR) was $79\%$ at both 3 and 5 years. According to the FIGO stage,3 and 5 year OS were $100\%\;and\;50\%$ in CIS/IA, $100\%\;and\;100%$ in IB, $83\%\;and\;69\%$ in IIA, $87\%\;and\;80\%$ in IIB, and $62\%\;and\;62\%$ in III, respectively. The 3 year OS in 4 patients with stage IVA was $100\%$. Three-year DFS were $80\%$ in CIS/IA, $88\%$ in IB, $100\%$ in IIA, $64\%$ in IIB, $58\%$ in III, and $75\%$ in IVA. Three-year PCR were $100\%$ in CIS/IA, $94\%$ in IB, $100\%$ in IIA, $84\%$ in IIB, $69\%$ in III, and $50\%$ in IVA. By univariate analysis, FIGO stage and treatment response were significant factors for OS. The significant factors for DFS were age, FIGO stage, treatment response and overall treatment time (OTT). For pelvic control rate, treatment response and OTT were significant factors. By multivariate analysis, FIGO stage had a borderline significance for OS (p=0.0825) and treatment response had a borderline significance for DFS (0=0.0872). A total of 14 patients $(13\%)$ experienced rectal bleeding, which occurred from 3 to 44 months (median, 13 months) after the completion of radiotherapy. Conclusion : HDR brachytherapy protocol of Samsung Medical Center combined with properly optimal external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer. The authors found that OTT of less than 55 days had a positive impact on pelvic control and survival rate.

A Study of Guidelines for Genetic Counseling in Preimplantation Genetic Diagnosis (PGD) (착상전 유전진단을 위한 유전상담 현황과 지침개발을 위한 기초 연구)

  • Kim, Min-Jee;Lee, Hyoung-Song;Kang, Inn-Soo;Jeong, Seon-Yong;Kim, Hyon-J.
    • Journal of Genetic Medicine
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    • v.7 no.2
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    • pp.125-132
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    • 2010
  • Purpose: Preimplantation genetic diagnosis (PGD), also known as embryo screening, is a pre-pregnancy technique used to identify genetic defects in embryos created through in vitro fertilization. PGD is considered a means of prenatal diagnosis of genetic abnormalities. PGD is used when one or both genetic parents has a known genetic abnormality; testing is performed on an embryo to determine if it also carries the genetic abnormality. The main advantage of PGD is the avoidance of selective pregnancy termination as it imparts a high likelihood that the baby will be free of the disease under consideration. The application of PGD to genetic practices, reproductive medicine, and genetic counseling is becoming the key component of fertility practice because of the need to develop a custom PGD design for each couple. Materials and Methods: In this study, a survey on the contents of genetic counseling in PGD was carried out via direct contact or e-mail with the patients and specialists who had experienced PGD during the three months from February to April 2010. Results: A total of 91 persons including 60 patients, 49 of whom had a chromosomal disorder and 11 of whom had a single gene disorder, and 31 PGD specialists responded to the survey. Analysis of the survey results revealed that all respondents were well aware of the importance of genetic counseling in all steps of PGD including planning, operation, and follow-up. The patient group responded that the possibility of unexpected results (51.7%), genetic risk assessment and recurrence risk (46.7%), the reproduction options (46.7%), the procedure and limitation of PGD (43.3%) and the information of PGD technology (35.0%) should be included as a genetic counseling information. In detail, 51.7% of patients wanted to be counseled for the possibility of unexpected results and the recurrence risk, while 46.7% wanted to know their reproduction options (46.7%). Approximately 96.7% of specialists replied that a non-M.D. genetic counselor is necessary for effective and systematic genetic counseling in PGD because it is difficult for physicians to offer satisfying information to patients due to lack of counseling time and specific knowledge of the disorders. Conclusions: The information from the survey provides important insight into the overall present situation of genetic counseling for PGD in Korea. The survey results demonstrated that there is a general awareness that genetic counseling is essential for PGD, suggesting that appropriate genetic counseling may play a important role in the success of PGD. The establishment of genetic counseling guidelines for PGD may contribute to better planning and management strategies for PGD.