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The Influence of Biomarker Mutations and Systemic Treatment on Cerebral Metastases from NSCLC Treated with Radiosurgery

  • Lee, Min Ho;Kong, Doo-Sik;Seol, Ho Jun;Nam, Do-Hyun;Lee, Jung-Il
    • Journal of Korean Neurosurgical Society
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    • v.60 no.1
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    • pp.21-29
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    • 2017
  • Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

Protodioscin protects porcine oocytes against H2O2-induced oxidative stress during in vitro maturation

  • So-Hee Kim;Seung-Eun Lee;Jae-Wook Yoon;Hyo-Jin Park;Seung-Hwan Oh;Do-Geon Lee;Da-Bin Pyeon;Eun-Young Kim;Se-Pill Park
    • Animal Bioscience
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    • v.36 no.5
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    • pp.710-719
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    • 2023
  • Objective: The present study investigated whether protodioscin (PD), a steroidal saponin mainly found in rhizome of Dioscorea species, alleviates oxidative stress-induced damage of porcine oocytes during in vitro maturation. Methods: Oocytes were treated with different concentrations of PD (0, 1, 10, 100, and 200 µM) in the presence of 200 µM H2O2 during in vitro maturation. Following maturation, spindle morphology and mitogen-activated protein kinase activity was assessed along with reactive oxygen species level, GSH activity, and mRNA expression of endogenous antioxidant genes at the MII stage. On the day 7 after parthenogenetic activation, blastocyst formation rate was calculated and the quality of embryo and mRNA expression of development-related genes was evaluated. Results: Developmental competence was significantly poorer in the 0 µM PD-treated (control) group than in the non-treated (normal) and 10 µM PD-treated (10PD) groups. Although the reactive oxygen species level did not significantly differ between these three groups, the glutathione level and mRNA expression of antioxidant genes (superoxide dismutase 1 [SOD1], SOD2, nuclear factor erythroid 2-related factor 2 [Nrf2], and hemo oxygenase-1 [HO-1]) were significantly higher in the normal and 10PD groups than in the control group. In addition, the percentage of oocytes with defective spindle and abnormal chromosomal alignment was significantly lower and the ratio of phosphorylated p44/42 to total p44/42 was significantly higher in the normal and 10PD groups than in the control group. The total cell number per blastocyst was significantly higher in the 10PD group than in the control group. The percentage of apoptotic cells in blastocysts was highest in the control group; however, the difference was not significant. mRNA expression of development-related genes (POU domain, class 5, transcription factor 1 [POU5F1], caudal type homeobox 2 [CDX2], Nanog homeobox [NANOG]) was consistently increased by addition of PD. Conclusion: The PD effectively improves the developmental competence and quality of blastocysts by protecting porcine oocytes against oxidative stress.

Effect of Hollow Glass Powder on the Self-Compacting Concrete (유공 유리분말이 자기충전 콘크리트의 특성에 미치는 영향)

  • Yoon, Seob;Han, Min-Cheol
    • Journal of the Korea Institute of Building Construction
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    • v.18 no.2
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    • pp.141-149
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    • 2018
  • In this study, compacting, passing performance, segregation resistance and rheological properties were tested to improve the stability of fresh concrete in the production and construction of self-compacting concrete (SCC) using hollow glass powder(GB). As a result, T50 reaching time was shortened up to amount of GB $2.0kg/m^3$. The compacting according to the amount of GB was improved by ball bearing effect of GB. However, T50 reaching time was slightly increased at $4.0kg/m^3$. In the case of passing performance, the result showed that plain was Class 1, GB $0.5{\sim}2.0kg/m^3$ was Class 0, GB $4.0kg/m^3$ was Class 1. Therefore, the passing performance was improved with 'No blocking' up to amount of GB $2.0kg/m^3$. Passing performance Block step (PJ) number by J-ring method was also best at GB $1.0kg/m^3$. In the case of segregation resistance according to the amount of GB, dynamic segregation resistance was increased compared to plain regardless of the amount of GB. And static segregation resistance showed 2.5% of segregation rate at GB $1.0kg/m^3$. Therefore, it was greatly improved compared to plain (12.5%). In the case of rheology property according to the amount of GB, plastic consistency by increasing of GB content didn't show big difference. However, yield stress by increasing of GB content was decreased with GB $1.0kg/m^3$. In conclusion, GB $1.0kg/m^3$ was effective for improvement of compacting, passing performance and yield stress. Also, it will be useful for stability of SCC by improving segregation.

Spatial Genetic Structure at a Korean Pine (Pinus koraiensis) Stand on Mt. Jumbong in Korea Based on Isozyme Studies (점봉산(點鳳山) 잣나무임분(林分)의 개체목(個體木) 공간분포(空間分布)에 따른 유전구조(遺傳構造))

  • Hong, Kyung-Nak;Kwon, Young-Jin;Chung, Jae-Min;Shin, Chang-Ho;Hong, Yong-Pyo;Kang, Bum-Yong
    • Journal of Korean Society of Forest Science
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    • v.90 no.1
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    • pp.43-54
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    • 2001
  • Genetic differentiation of populations is resulted from the environmental and the genetic effects, and the interactions between them. Whereas, the major factors influencing to the genetic differentiation within populations are the gene flow induced by seed or pollen dispersial, the microsite heterogeneity, and the density-dependent distribution of individuals. For the purpose of studying spatial genetic structure and the distribution pattern of Korean pines(Pinus koraiensis), we set up one $100{\times}100m$ plot at a Korean pine stand in Quercus mongolica community on Mt. Jumbong in Korea. To estimate the coefficient of spatial autocorrelation as Moran's index and an analogue, simple block distance, isozyme markers were analyzed in 325 Korean pines. For 11 polymorphic loci observed in 9 enzyme systems, the average percentage of polymorphic loci, the observed and expected heterozygocity were 72.2% 0.200, and 0.251, respectively. It was revealed the excess of homozygotes was observed in the plot, which suggests that here may be more number of consanguineous trees than expected. On the basis of isozyme genotypes observed in this study, 325 trees were classified into 147 groups in which the maximum number of trees for one group was 34. From the distance class of 24-32m, the genetic heterogeneity began to increase. The variation of simple block distance against the growth performance by tree height and diameter also showed the same trend at 24~32m class. According to high fixation index(F=0.204), the spatial genetic structure within a stand, the analysis of the growth performance, and the distribution patterns of identical genotypes, we inferred that the genetic structure of a Korean pine stand in Mt. Jumbong has been maintained rather density-dependent mechanism than the gene flow, such as the pollen dispersial or the heavy input of seeds following the forest gaps. The genetic patchy size was determined between 24~32m, which suggests that the selection of individuals for the ex situ conservation of Korean pine in Mt. Jumbong may be desirable to be made with the spatial distance over 37 meters between trees.

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Changes of Microbial Community Associated with Construction Method and Maintenance Practise on Soil Profile in Golf Courses (지반 조성과 관리방법에 따른 골프장 토양내 미생물 군집의 변화)

  • Moon, Kyung-Hee;Kim, Ki-Dong;Joo, Young-Kyoo
    • Asian Journal of Turfgrass Science
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    • v.23 no.2
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    • pp.219-228
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    • 2009
  • The construction procedures and artificial turf maintenance program on golf course definitely influence on the distortion of its environment. Soil microbial communities in soil profile were affected directly by those practises on turf areas. In Jeju island, the environmental impact assessment has been required to apply the first quality class granular activated carbon(GAC), which has a high absorbent character to agricultural chemicals, on the soil profiles of golf green system to reduce the pesticide leaching to ground water. This research was carried out to analyze the changes of microbial communities and chemical properties on soil profiles where GAC had been applied at the construction stage at two golf courses in Jeju. The changes of soil microbial population and chemical properties associated with construction methods of soil profile and agrochemical management program were analyzed by monthly at the surface and sub-soil profiles during April through October, 2007. The total numbers of bacteria and fungi, soil moisture content, soil physio-chemical properties were measured on greens and fairways of the both golf courses with different GAC treatment on the green and fairway soil profiles. The results showed that GAC had positive effects on the water holding capacity, pH and EC, however, it did not improved the holding capacity of available nutrients ${NO_3}^-,{NH_4}^+$, and phosphorus by its sorption phenomenon. In microbial count test, the total numbers of bacteria and fungi showed a great variation during sampling dates. That may directly relate to the agrochemical application, however, the ratio of total bacterial number versus total fungus number showed a constant value on a sub-soil of 15~30cm depth. Thus, the construction method of GAC in soil profile, and application of fertilizer and pesticide, both impacted on the changes of microbial population. It's means that the construction method of soil profile and turf management using agro-materials might greatly affect on the turfgrass culture and the environment of golf course.

Stressful Life Events, Health Symptoms, Social Support and Coping/in Early Adolescents (스트레스생활사건, 건강문제, 대응, 사회적 지지의 관계 -청소년을 대상으로-)

  • 오가실;한정석
    • Journal of Korean Academy of Nursing
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    • v.20 no.3
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    • pp.414-429
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    • 1990
  • Numerous research reports have substantiated the role of stressful life events in relation to the onset of health changes. The relationship tends to hold across different age groups. Theoretically, adolescence has been considered a developmental crisis period of great stress, impoverished coping skills and high vulnerability to biological, social and psychological demands. The research problem addressed by this study was to examine the relationships between stressful life events and health symptom patterns, and the effect of two variables, coping and social, support, theoretically considered to mediate the relationship between stress and health symptoms in adolescents. The following five hypotheses were tested in this research : 1. Health symptoms are positively related to stressful life events in adolescents, 2. Health symptoms are negatively related to coping in adolescents, 3. Health symptoms are negatively related to social support in adolescents, 4. When coping is controlled, the relationship between health symptoms and stressful life events will decrease, and 5. When social support is controlled, the relationship between health symptoms and stressful life events will increase. The study subjects consisted of 1090 high school students of the metropolitan city of Seoul. The following sampling procedure was used : 1. Of the 169 high schools in nine school administrative districts in the city, a proportional sample of ten schools was selected. 2. One class from each of the freshman and sophomore was randomly selected and all the students who were in the sampled class were used as the study sample. The study was limited to freshman and sophomore adolescents, aged 15 to 18(mean=16.6). Of the 1090 subjects 688(63%) were boys and 402(37%) were girls. An Adolescent Inventory of Stressful Life Events, a Health Symptom Questionnaire and an Adolescent Coping Inventory were adapted for this study. The Norbeck Social Support questionnaire was utilized to collect the data on perceived social support. Five high school teachers in the areas of school health and counselling reviewed the items of each questionnaire for content validity. A pilot study was undertaken to ascertain reliability. Fifty three high school students responded to the questionnaires and gave their opinions on the items. For stressful life events, health symptoms, coping, and social support, the Cronbach's alpha's on the study were .70, .94, .77, and .76, respectively. Research assistants attended all the sampled classes with the school proctor to explain the purpose and procedures of the study to the students. The questionnaires along with a ballpoint pen were distributed to the students who were asked to complete each item. The research assistants left the ballpoint pen with the students as a gift for their cooperation. An average of 50 minutes was required to complete the questionnaires. Using an SPSS, the first, three hypotheses were tested using Gamma, a measure of association for ordinal variables. Partial gamma was used to test the fourth and fifth hypotheses. Patterns of elaboration described by Babbie were selected to interpret the relationship of the three variable analyses. The significance of gamma was determined by Chisquare at a .05 level of significance. There was a positive relationship between health symptoms and stressful life events(Gamma=.35, p=.000). Thus the first hypothesis was supported. Unexpectedly, coping was positively related with health symptoms(Gamma=.13, p=.000). That is, the higher the coping levels, the greater number of health problems. The third hypothesis, the higher the level of social support, the fewer the health symptoms, was not accepted in this adolescent study group. When coping was controlled, under the condition of low coping the association between health symptoms and stressful life events increased significantly to a partial gamma of .39, and under the condition of high coping it was .30. According to the elaboration model, when one partial relationship is the same or greater than the original and the other is smaller, the control variable should be considered to be specifying the conditions. When social support was controlled the relationship between stressful life events and health symptoms increased under the condition of low social support, but with high social support, the relationship decreased. Both partial gamma were statistically significant at .05 level(.43 and .26 relatively). It can be interpreted that stressful life events are strongly and positively related to health symptoms under the condition of low social support, however this relationship can not be expected with high social support. Thus, the last two hypotheses were conditionally sustained. In this study, the relationships between stressful life events and health symptoms, and the specified me diating roles of coping and social support were found to have statistical interaction. This finding supports the theoretical position of this study. It suggests that stressful life events would create high susceptability to biological social and psychological health symptoms and coping and social support buffering the relationship between stressful life events and health symptom. The findings of this study have implications for nursing practice. When adolescents are confronted with non-developmental life events that are perceived as stressful, nurses should recognize the evidence of the stress-buffering effect of coping and social support on health symptoms and utilize the diverse sources of social support that are readily available to adolescents.

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The Development and Application of Informal Gifted and Talented Education program utilizing Local Resources in Yeongheung Island (영흥도 지역자원을 활용한 학교 밖 영재 프로그램 개발 및 적용 효과)

  • Ock, Seong-Hyun;Choi, SunYoung
    • Journal of Science Education
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    • v.38 no.2
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    • pp.356-375
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    • 2014
  • The purpose of this study was to develop the informal education based elementary gifted education program utilizing local resources in Yeongheung island for enhancing the creative problem solving, science process skills, scientific attitudes. This program was totally consisted 36 lessons and 3 part. For this purpose, 7 weeks' informal gifted education program utilizing local resources was treated to a class students who were 5th graders of elementary school in Yeongheung island. The results of this study were as follows : First, the change of science creative problem solving ability in the gifted class was found statistically meaningful difference. Second, science process skills were showed statistically meaningful difference. Third, scientific attitudes were not showed statistically meaningful difference. Fourth, the student responses about effectiveness of this programs were generally positive. Therefore, the gifted education programs showed meaningful results. Based on the results of this study, a number of studies to overcome the limitations will be needed.

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The Effect of Science Class based on Havruta Learning on the Logical Thinking and the Science Related Attitude of Elementary Students (질문중심 하브루타 과학수업이 학생들의 논리적 사고력 및 과학 관련 태도에 미치는 영향)

  • Kang, Ji-na;Lee, Hyeong-cheol
    • Journal of the Korean Society of Earth Science Education
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    • v.9 no.3
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    • pp.309-322
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    • 2016
  • This study was conducted to investigate the effect of science based on question-centered Havruta learning on the logical thinking and the science related attitude of elementary students. The number of participants were 93, 4 classes of 4th graders in G elementary school in C city. The experimental group, 2 classes including 46 participants, took science lessons based on question centered Havruta learning while the comparative group, 2 classes including 47 participants, took teacher-driven lessons using teacher's guidebook. Pre and post tests were done before and after executing lessons to assess the changing in each group's logical thinking and the science related attitude. And targeting experimental group, a perception survey toward Havruta learning was carried out and the results were arranged. The results of this study can be summarized as follows: First, the pre and post test results of logical thinking revealed that the experimental group showed higher improvement compared to the comparative group and the difference was meaningful. This implies that question centered Havruta classe has the effect of improving students' logical thinking. Second, from the pre and post test results of the science related attitude, we saw that the experimental group showed higher improvement compared to the comparative group and the difference was meaningful. This confirms that question centered Havruta class has the effect of improving students' science related attitude. Third, the survey regarding perspectives of experimental group students toward Havruta learning showed that students had a high satisfaction level.

Protective Effects on A2Kb Transgenic Mice That Were Immunized with Hepatitis B Virus X Antigen Peptides by the Activation of CD8+ T Cells; XEP-3 Specific CTL Responses in the in vitro Culture (B형 간염 바이러스 X 항원을 면역한 A2Kb Transgenic Mice에서 CD8+ T Cell의 활성화에 의한 X 항원 표현 재조합 Vaccinia Virus에 대한 방어 효과; in vitro 배양을 통한 XEP-3 특이적인 CTL의 반응)

  • Hwang, Yu Kyeong;Kim, Hyung-Il;Kim, Nam Kyung;Park, Jung Min;Cheong, Hong Seok
    • IMMUNE NETWORK
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    • v.2 no.1
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    • pp.41-48
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    • 2002
  • Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.

A Study on the Design of Standard Code for Hazardous and Noxious Substance Accidents at Sea (해상 HNS 사고 표준코드 설계에 관한 연구)

  • Ha, Min-Jae;Jang, Ha-Lyong;Yun, Jong-Hwui;Lee, Moonjin;Lee, Eun-Bang
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.22 no.2
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    • pp.228-232
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    • 2016
  • As the quantity of HNS sea trasport and the number of HNS accidents at sea are increasing recently, the importance of HNS management is emphasized so that we try to develop marine accident case standard code for making HNS accidents at sea databased systemically in this study. First and foremost, we draw the related requisites of essential accident reports along with internal and external decrees and established statistics of classified items for conducting study, and we referred to analogous standard codes obtained from developed countries in order to research code design. Code design is set like 'Accident occurrence ${\rightarrow}$ The initial accident information ${\rightarrow}$ Accident response ${\rightarrow}$ Accident investigation' in accordance with the general flow of marine HNS accidents of in which the accident information is input and queried. We classified initial accident information into the items of five categories and constructed "Preliminary Information Code(P.I.C.)". In addition we constructed accident response in two categories and accident investigation in three categories that get possible after the accident occurrence as called "Full Information(F.I.C.)", including the P.I.C. It is represented in 3 kinds of steps on each topic by departmentalizing the classified majority as classified middle class and classified minority. As a result of coding marine HNS accident and of the code to a typical example of marine HNS accident, HNS accident was ascertained to be represented sufficiently well. We expect that it is feasible to predict possible trouble or accident henceforward by applying code, and also consider that it is valuable to the preparedness, response and restoration in relation to HNS accidents at sea by managing systemically the data of marine HNS accidents which will occur in the future.