Differential Manifestation of Ocular Phenotypes in TALEN-mediated p19arf Knockout FVB/N and C57BL/6J mouse lines

Jin‑Sung Park,Joo‑Il Kim,Hyun‑Jin Lim,Soo‑Kyung Ryu,Euna Kwon,Kang‑Min Han,Ki‑Taek Nam,Han‑Woong Lee,Byeong‑Cheol Kang 한국유전학회 2020 Genes & Genomics Vol.42 No.9

Background p19arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19arf has been associated with ocular defects, but the mixed background of the knockout (KO) mouse strain used raised a concern on the accuracy of the phenotypes observed in association with the targeted gene due to genetic heterogeneity. Object We carried out a study to investigate into the efect of genetic background on the manifestation of p19arf KO associated phenotypes. Methods We characterized the phenotypes of novel p19arf KO mouse lines generated in FVB/N and C57BL/6J using a transcription activator-like efector nuclease (TALEN) system in comparison to the reported phenotypes of three other p19arf-defcient mouse lines generated using homologous recombination. Results Ninety-fve percent of FVB/N-p19arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19arf KO mice from week 4. Besides these, both strains developed normally from birth to week 26 without increased tumorigenesis except for a subcutaneous tumor found in a C57BL/6J-p19arf KO mouse. Conclusion Our fndings demonstrated surprisingly variable manifestation of p19arf-linked phenotypes between FVB/N and C57BL/6J mice, and furthermore between our mouse lines and the established lines, indicating a critical impact of genetic background on functional study of genes using gene targeting strategies in mice.

소화불량(消化不良)과 과심상(過心傷)의 상관성(相關性)에 대(對)한 고찰(考察) -스트레스, 기울(氣鬱), 비병증(脾病證)의 평가(評價)를 통(通)해-

김진성,윤상협,류봉하,류기원,이상욱,Kim, Jin-Sung,Yoon, Sang-Hyub,Ryu, Bong-Ha,Ryu, Ki-Won,Lee, Sang-Wook 대한한방내과학회 2004 大韓韓方內科學會誌 Vol.25 No.4

Background & Object : Dyspepsia for which no organic causes are disclosed is referred to as functional dyspepsia. Functional dyspepsia is here studied in connection with a biopsychosocial model. From the aspect of individual response to external environment, in connection with stress response, functional dyspepsia is studied by both the psychology department and the internal medicine departments. The disease is taken as approachable from the aspect of internal injury due to seven emotions and stress as differentiated by Oriental medicine. Materials and Methods : Targeted at 223 patients underwent medical checks and endoscopy at Kangnam Korean Hospital, Kyunghee University. They agreed to join this clinical experiment. Stress response inventory, GARS (global assessment of recent stress scale), GSRS (gastrointestinal symptom rating scale), diagnostic scores for Ki-depression, and Spleen Disease Differentiation of Syndromes were all measured and evaluated. The test group was comprised of functional dyspepsia patients. The control group was comprised of nonsymptomatic chronic gastritis patients who were found to suffer from chronical gastritis in endoscopy and thus could be diagnosed with functional dyspepsia if symptoms would arise, but did not complain of subjective symptoms. Results showed these corelations: Functional dyspepsia patients were found to have more serious Ki-depression compared to nonsymptomatic chronic gastritis patients. The more serious Ki-depression the more serious the dyspepsia symptoms. The higher the stress response inventory the more serious the dyspepsia. Deficiency of spleen Eum, and Deficiency and Sinking of spleen Gi were found to coincide with serious Ki-depression.

뇌경색 발병후 병발된 만성 애역(Chronic hiccup)의 뜸치료 1례

전우현,김진석,홍종희,홍상선,박석규,김진성,류봉하,류기원,박재우,Jeon, Woo-Hyeon,Kim, Jin-Seok,Hong, Jong-Hee,Hong, Sang-Sun,Park, Seok-Kyu,Kim, Jin-Seong,Ryu, Bong-Ha,Ryu, Ki-Won,Park, Jae-Woo 대한한방내과학회 2001 大韓韓方內科學會誌 Vol.22 No.1

Hiccups, also known as singultus, are spasmodic involuntary contractions of respiratory muscles that shorten respiration. The characteristic sound is caused by rapid closure of the glottis. In oriental medicine, the mechanism of hiccups is "reversed flow of Ki". Hiccups have been associated with neoplasm, infections, seizures, diabetes. renal failure, alcohol ingestion, various drugs, and ischemic events of the myocardium or central nervous system. We present a case of chronic hiccups after cerebral infarction that was successfully treated using moxibustion therapy.

수족냉증(手足冷症) 환자(患者)에 대(對)한 컴퓨터 적외선(赤外線) 체열촬영(體熱撮影)의 의의(意義)

조유경,오수완,조남희,김동묵,김진성,류봉하,박동원,류기원,Cho, Yu-Kyung,Oh, Su-Wan,Cho, Nam-Hee,Kim, Dong-Mook,Kim, Jin-Seong,Ryu, Bong-Ha,Park, Dong-Won,Ryu, Ki-Won 대한한방내과학회 1998 大韓韓方內科學會誌 Vol.19 No.2

To make a objective diagnosis of the syndrome of cold-limbs, We investigated the 20 patients with cold limbs and GI trouble and 20 normal people as a control group. And we compared the thermal difference between Chon-jung(CV17) and Chung-wan(CV12 中脘), Chon-jung(CV17) and Ki-hae(氣海 CV6) and we compared the thermal differences of No-gung(PE8 勞宮) and Yong-chon(湧泉 KI1), too. The results were as follows. 1. All 20 patients had GI trouble and cold limbs. They had the symptom-Indigestion(16 cases-80%) with heart burn, tympanites, abdominal distention, hiccup, belching. Beside that symptom they also had constipation(6 cases-30%), diarrhea(3 cases-15%), headache & dizziness(6 cases-30%). And some had the menstrual syndrome, chronic fatigue, palpitation, insomnia, edema, arthralgia. 2. The thermal difference of the palms between the patients group and the control group were $25.70^{\circ}C,\;25.82^{\circ}C$, but they were not significant. 3. The thermal difference of the soles between the patients group and the control group were $23.58^{\circ}C,\;24.42^{\circ}C$ and the significancy was P=0.020 so it was significant(P<0.05). 4. The thermal difference of the palms and Chon-jung(CV17) between the patients group and the control group were $1.08^{\circ}C,\;0.76^{\circ}C$, but they were not significant. 5. The thermal difference of the sales and Chon-jung(CV17) between the patients group and the control group were $3.01^{\circ}C,\;1.90^{\circ}C$ and the significancy was P=0.003 so it was significant(P<0.05). 6. The thermal difference of Chon-jung(CV17) and Chung-wan(CV12 中脘) between the patients group and the control group was $0.30^{\circ}C,\;0.62^{\circ}C$ and the significancy was P=0.793 so it was significant(P<0.05). 7. The thermal difference of Chon-jung(CV17) and Ki-hae(CV6 氣海) between the patients group and the control group was $0.53^{\circ}C,\;0.68^{\circ}C$, but they were not significant. From the above, I could find the significance of D.I.T.I to diagnose the cold-feet not the cold-hands and the thermal difference between the trunk and limbs was more significant on cold-feet than on cold-hand, either.

N/O/N 박막 다이아프레임을 이용한 광섬유 압력센서의 제작 및 그 압력특성

유양욱,김명규,박동수,김창원,김진섭,이정희,손병기 경북대학교 센서기술연구소 1995 센서技術學術大會論文集 Vol.6 No.1

The 0.6 μm N/O/N triple layer, Si_(3)N_(4)(150 nm)/SiO_(2)(300 nm)/Si_(3)N_(4)(150 nm), was deposited on silicon substrate and the N/O/N thin film diaphragm was formed using anisotropic etching technique. The stress of the formed diaphragm was very small with temperature variations. Combining this diaphragm and the optical fiber, intensity-type pressure sensor was fabricated and its pressure characteristics were investigated. The relation between the optical output power, inversely proportional to the deflection of the diaphragm, and the applied pressure was almost linear in 0~77 torr range.

Platinum sensitive 재발성 난소암에서 Carboplatin/Paclitaxel의 효과

장혜진,유희석,임윤경,문세희,장기홍,이정필 대한부인종양 콜포스코피학회 2003 Journal of Gynecologic Oncology Vol.14 No.4

목적 : 재발성 난소암에서 platinum 감수성을 기준으로 2차 항암요법으로 사용한 Carboplatin과 Paclitaxel의 효과를 알아보기 위하여 본 연구를 진행하였다. 연구방법 : 1998년 1월 1일부터 2003년 8월 31일까지 만 5년 8개월 간 아주대학교병원 산부인과에 재발성 난소암으로 입원한 환자 중에서 최초 수술로 난소암을 확진한 후 Cisplatin 또는 Carboplatin 등 platinum 제재가 포함된 항암치료를 받은 후 6개월 이후에 재발한 환자 29명을 대상으로 Carboplatin은 5 AUC를 그리고 Paclitaxel은 175 mg/m^(2)를 투여하였으며, 최소 3회에서 최고 16회까지 투여하였다. 치료효과의 판정은 CT, MRI, Ultrasonography등 영상진단상 암종괴의 크기가 완전히 소실되었을 경우를 완전반응(complete response)으로, 50%이상 감소되었을 경우를 부분반응(partial response)으로, 50% 미만으로 감소되었거나 20% 미만 증가하였을 경우를 불변(stable disease)으로, 그리고 20% 이상 증가되었을 경우를 진행(progressive disease)로 정의하였다. 결과 : 대상 환자에서 완전반응은 6명(21%), 부분반응은 11명(38%), 그리고 불변은 5명(17%)로 전체 반응율 (overall response rate)은 59% 그리고 임상적 유용성(clinical benefit=CR+PR+SD)은 76%이었다. 결론 : 재발성 난소암환자에서 기왕에 사용한 Platinum 제재에 민감한 환자에서는 Carboplatin과 Paclitaxel의 병행 투여가 효과적이었다. Objective : To ascertain the effect of Carboplatin and Paclitaxel combination as a second line regimen for recurrent ovarian carcinoma based on platinum sensitivity. Methods : From January 1st, 1998 through to August 31st, 2003, 29 patients were retrospectively reviewed who had previously underwent primary cytoreductive surgery and adjuvant chemotherapy with Cisplatin or Carboplatin for ovarian carcinoma, and who had later recurred during follow up. All 29 patients had recurred at least 6 months after therapy, and thereafter received second line chemotherapy consisting of Carboplatin (5 AUC) and Paclitaxel (175 mg/㎡) for a minimum of least 3 cycles and a maximum of 16 cycles. Treatment efficacy was assessed by imaging studies including Computerized tomography, Magnetic Resonance Imaging, or Ultrasonography. Complete response was determined as complete disappearance of tumor, partial response at least than 50% reduction in tumor volume, stable disease as less than 50% reduction or less than 20% increase in tumor volume, and progressive disease as more than 20% increase. Results : There was complete response in 6 (21%) patients, partial response in 11 (38%), stable disease in 5 (17%), showing an overall response rate of 59%. The clinical benefit (CR+PR+SD) was 76%. Conclusion : The combination of Carboplatin and Paclitaxel administration seems to be an effective mode of second line therapy in patients with recurrent ovarian carcinoma who had been sensitive to prior platinum based chemotherapy.

유럽聯合의 市場支配的 地位 濫用禁止

李基秀,柳珍熙 한국경영법률학회 2003 經營法律 Vol.13 No.2

Korean antitrust law regulates the abuse of market-dominating position. It does not prohibit the market-dominating position itself, but its abuse. In this regard EU competition law is common with korean antitrust law. However there are some differences between them. The concept of market-dominating position can be recognized only after defining a relevant market. According to korean antitrust law a relevant market means an area in which any competitive relation exists or may exist, by the subject, stage or geographical area of such trade, and criterions for defining a relevant market are described in a notice of Fair Trade Commission. In European Union European Court of Justice or European Commission defines a relevant market in a similar way. A notice of European Commission was recently enacted and it seems that the concept of price elasticity of demand plays more important role than that of functional interchangeability in defining a relevant product and geographic market. According to korean antitrust law market share, barriers to enter into the market and relative size of competitors etc. are taken into account in determining a market-dominating position and an enterpriser whose market share is above a specified level is presumed to have a market-dominating position. On the other hand European Union competition law does not have any provision on criterions which are to be taken into account in determining a marketdominating position. European Court of Justice or European Commission takes into account market structure as well as behaviors of market participant, and, if necessary, it uses the method of enterprise structure analysis. While korean antitrust law enumerates abusive practices, EU competition law refers to some examples. Abuse of trading conditions, refusals to deal, discrimination and tying are not included in the list of abusive practices in Korea, although they affect free competition in many cases. Such practices should be enumerated or a general clause should be included in the list.

궤양성대장염의 관장치료

김진성,류봉하,박동원,류기원 한국전통의학연구소 1998 한국전통의학지 Vol.8 No.1

늘어나는 추세에 있는 궤양성 대장염의 국소요법으로서 관장치료의 효용성에 대하여 알아보고자 본 고찰를 시행하였다. 1995-96년 사이에 간행된 최근의 중국저널에 실려있는 "保留灌腸" 이란 궤양성 대장엽의 국소요법에 대한 내용과 서양의학의 관장요법에 대한 내용을 함께 분석하였다. 관장치료는 기존의 내과적 치료에 반응을 보이지 않는 원위부의 궤양성 대장염에 대하여 지속적인 임상적 효능을 나타내며 안전하며,특히 직장내 출혈의 경우에 즉시형의 효과를 나타낸다. 保留灌腸은 주로 淸熱, 利濕, 解毒, 澁腸, 止血 등의 효과가 있는 한약 전탕액을 항문내로 주입하여 직장내에 국한된 병소에 직접적으로 약물을 투여하는 방법으로서 직장내 주입량은 100-150㎖ 정도이며 15-20일을 기본 치료기간으로 한다. 관장액의 구성 약물로는 주로 淸熱利濕, 澁腸止血의 효능이 있는 白頭翁, 地楡, 白급, 苦蔘, 敗ㅁ草, 五倍子 등이 사용되었다. Ulcerative colitis is an inflammatory disorder of the mucosa of the rectum and colon. The rectum is virtually always involved, and if any portion of the remaining colon is involved, it is in a continuous manner extending proximally from the rectum. Patients with ulcerative colitis typically complain of bloody stool, diarrhea and lower abdominal pain. 5-ASA enemas are safe and effective in maintaining remission in patients with distal ulcerative colitis. Specially, the efficacy is shown by a reduction in rectal bleeding. Retention enema(保留灌腸) is local therapy that the manufactured herbs are administered into the rectum of patients with distal ulcerative colitis, Thp. administered volume is 100-150㎖, and treatment period is 15-20days. The enema-fluid consist of Pulsatillae Radix(白頭翁), Sanguisorbae Radix(地楡), Bletillae Tuber(白급), Sophorae Radix(苦蔘), Patriniae Radix(敗醬草), Chinensis Galla(五倍子) that have effects of clearing away pathogenic heat and dampness(淸熱利濕), astringing intestine to correct diarrhea(澁腸), arresting bleeding(止血). This retention enema is effective, but it needs to be compared with efficacy of 5-ASA enemas. Also, we should investigate about the safety and toxicity of the herbal medicines.

기능성 소화불량증 환자에 대한 반하사심탕 엑기스제의 임상효과

윤상협,류봉하,류기원,김진성 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Objective : We evaluated the therapeutic effect of Banwhasasimtang dry extract powder on gastrointestinal symptoms and its side effects in patients with functional dyspepsia. Methods : Patients with functional dyspepsia, defined as discomfort in the epigastrium. A total 45 patients participated participated in this study. Dyspeptic symptoms ratio was obtained by patients, total point of symptom score / total 21 points x 100(%). On each of symptom after 4 weeks administration of Banwhasashim-tang was made by variation of symptom score: If symptoms score of posttreatment is lower than that of pretreatment, It is improved ; Otherwise aggravated, and if there is no change between them, unchangeable. When a full health condition of normal control is assumed 100%, relative health condition of dyspeptic patient could be calculated from 'full health condition- dyspeptic symptoms ratio. Therefore a whole satisfaction rate on symptom improvement was presented with variation of a relative health condition to dyspepsia between pretreatment and post. Results : Banwhasashimtang significantly unproved symptoms in patients. The significance was shown in both all seven items(p< 0.01, respectively) and 19.2% (p<0.01) of increase of a whole symptom improvement. There is no remarkable side-effect in all laboratory test, excepting 1 case abdominal pain another one case of recurred pain of chronic prostatitis. Conclusion : Banwhasashimtang extract provides symptomatic relief in functional dyspepsia and is no remarkable side-effect drug.

消癌去痰益氣湯의 cyclophosphamide 부작용 형성 억제효과

홍종희,류기원,류봉하,윤상협,김진성 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2002 東西醫學硏究所 論文集 Vol.2002 No.-

Object : It is well known that modern chemotherapy against cancer has side effcts to a living body, especially hemopoietic and immunologial disfunctions. However, there are no effctive ways to reduce them.Recently, traditonal Korean herb medicine has been repoted to have some biological modifying responses. Therefore, we hypothesized that additional application of herb medicine during chemotherapy is more effective to reduce its side effects. While we were studying the effects, we have observed the inhibitory effect of Soamgudamikgitang on formation of side effects derived from Cyclophosphamide, it has been used in clinical practice at Kyung Hee Medicd Center.Methods : We injected 200㎎/㎏ of Cyclophosphamide, one time, to an experimental group, consisting of ten mice. We divided them into eight groups: normal, CPX, SAKT 2㎎, SAKT 10㎎, SAKT 50㎎, SAKI 2㎎+CPX, SAKT 10㎎+CPX, SAKT 50㎎+CPX. We injeted Soamgudamikgitang seven days, five days, three days, and one day before we injected CPX. One day, three days, and five days after CPX injection, we injected Soamgudamikgitang again and then killed all the mice.The parameters determined in this experiment were daily body weight liver and spleen weight, RBC, WBC, and platelet for hemopoietic dysfunction and AST, ALT for hepatotoxicity, BUN, creatine for renal toxcity, Iymphocyte proliferation activity and lymphocyte subsets for immunological toxvity.Results : We have found that Soamgdamikgitang has inhibitory effects on the formation of Cyclophosphamide 's side effects. Significant differences between the group, which contained Cyclophosphamide, and the other group, which contains Cyclophosphamide and 2, 10, 50㎎ of Soamgudamikgitang respectively were observed. Platelets(2㎎ of Soamgudamikgitang, p<O.05 ;10㎎, p<0.Ol ;50㎎, p<0.001), liver weight(SOw p.001), spieen weight(10mg, p<0.05), AST(all groups, p<0.01), ALT(2㎎, p<001 ;10㎎, p<O.05 ;50㎎, p<0.01), BUN(2㎎, p<0.01 ;50㎎, p<0.05). Althought immunological in both lymphocyte proliferation and its subsets were not observed, which shows that Soamgudamikgilang has a strong effect on T cell activities Conclusions : From the above results, we can expect that the combined therapy of Soamgudamikgitang and Cyclophosphamide is more effective for treating cancer Patients.