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.

Bupivacaine과 ropivacaine이 Xenopus oocyte에 발현된 HERG 전류에 미치는 영향

김국성,이규승,김효신,손숙진,이상도,김광진,전병화,김윤희,박진봉 충남대학교 의과대학 의학연구소 2003 충남의대잡지 Vol.30 No.1

Bupivacaine is an amide-type local anesthetic widely used for regional anesthesia. Ropivacaine is developed as a less cardiotoxic alternatives to bupivacaine. In the present study, we have analyzed the effects of bupivacaine and ropivacaine on HERG currents expressed in Xenopus oocytes. Bupivacaine and ropivacaine(3∼1,000μM) blocked HERG currents in a concentration dependent manner. EC_(50) was 26.1±3.1μM(n_(R) 0.65±0.04) and 43.5±7.9μM(n_(H) 0.99±0.13) in bupivacaine and ropivacaine, respectively. Bupivacaine and ropivacaine did not affect the activation and deactivation kinetics of HERG channels. However, the drugs decreased the slope conductance measured from fully activated current-voltage relationship curves. These results suggest that bupivacaine and ropivacaine have a similarinhibitory effect on HERG channels, which could be a possible cellular mechanism of LQT or ventricular arrythmia by the drugs.

Characterization of the European type of maternal lineage evident in extant Jeju native pigs

Byeong‐Woo Kim,In‐Cheol Cho,Moon‐Sung Park,Tao Zhong,임현태,Sung‐Soo Lee,Hee‐Bok Park,Moon‐Suck Ko,Jun‐Heon Lee,Jin‐Tae Jeon 한국유전학회 2011 Genes & Genomics Vol.33 No.2

Using a partial D‐loop sequence of mtDNA, an intensive analysis was conducted of the maternal lineages of Jeju native pigs (JNPs) from Korea. In total, 100 mtDNA sequences were obtained from Asian wild boars (AWBs), European wild boars (EWBs), Asian domestic pigs (ADPs), European domestic pigs (EDPs), and JNPs and were used for phylogeny and network analyses. Two distinct JNP groups - one (JNPA) in the Asian cluster and the other (JNPE) in the European cluster - were identified in the estimated phylogenetic tree and network. The maternal lineage of JNPE was the closest to that of EWB and a clear haplogroup was identified that shared an identical haplotype (hap04) among 15 individuals of JNPE and 2 individuals of EWB. A Landrace and an EWB shared hap03with a JNPE. EWB, Landrace, Large White, and Duroc formed two clear haplogroups with JNPE in a parsimonious medianjoining network analysis, suggesting that an obvious maternal contribution of EDP has occurred in JNPE in recent years. A pair‐wise mismatch analysis also indicated that JNPE may have experienced a sudden population expansion, suggesting a more recent establishment compared with the gradual population expansion of JNPA. The JNPE group therefore should be further evaluated in order to decide whether this group should be culled or accepted into further programs for maintenance of the JNP population as a pure breed.

저강도 펄스형 초음파를 이용한 개의 슬개골 탈구 치료 효과

조성진,김남수,김화영,김선균,이성호,김병수 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

The effect of low-intensity ultrasonography on dislocation of the patella and fracture healing is controversial, and current management of that does not generally involve the use of ultrasound therapy. Nine patients with dislocation of the patella were treated with low-intensity ultrasonography(l5 mW/㎠, 1∼3.3 MHz) per 10-15 min/days, with an interval of 3 days during the last 3 weeks, at Family Animal Hospital(in Kunsan city). Ultrasound therapy may be beneficial to dislocation of the patella and healing. This finding is of considerable importance in that treatment with a low-intensity pulsed ultrasound signal may reduce healing time and could yield substantial cost savings and decreases in disability associated with delayed healing of dislocation of the patella.

세포질내 정자주입법(ICSI)에 있어서 정자흡입 및 난자내 주입방법에 관한 연구

이택후,김항진,송건호,김대근,전상식,박윤규,서태광,전병균,류은경,이은숙,문진수,김광철 경북대학교 의학연구소 2000 경북대학교병원의학연구소논문집 Vol.4 No.1

Study on Method of Sperm Aspiration and Injection into an Oocyte in Intracytoplasmic Sperm Injection(ICSI) Immobilization of spermatozoa prior to intracytoplasmic sperm iniection(ICSI) sometimes results in crooked tail and this makes it difficult to aspirate sperm into an injection pipette tail first. Head-first sperm aspiration into an injection pipette avoid this problem due to the bigger size of the sperm head. The effect of head or tail-first sperm injection into an oocyte on fertilization cleavage, percentage of grade I embryos and development to blastocyst stage in ICSI program has been studied. A single living immobilized spermatozoa from oligoasthenozoospermic patient was injected into an oocyte head-first or tail-first according to the treatment. Eighteen hours after microinjection, oocytes ware inspected for survival and fertilization Fertilized oocytes with two pronuclei were cultured in 30μl drop of mHTF supplemented with 10% heat-inactivated follicular fluid(FF) at 37℃. On day 2. embryo transfer was performed with cleaved embryos. The remaining 2-8 cell stage embryos were co-cultured with BRL cells in mHTF + 10% FF for 72 hours and the developmental stage was observed. The data were analyzed by Analysis of Variance. A total of 164 oocytes from 36 cycles were assigned to earth treatment and ICSI was performed(88 head-first, tail-first). The rates of normal fertilization were 81.8% and 76.3% for head-first and tail-first, respectively. Of the fertilized oocytes, the percentage of cleaved embryos and the percentage of grade 1 embryo among cleaved embryos were 88.9% and 68.8%, 93.1% and 74.1% for head-first and tail-first, respectively. Of the 2-8 cell embryos cultured, 44.4%(16/36) and 50.0%(10/20) for head first and tail first, respectively developed to blastocyst stage. There were no differences in fertilization, cleavage, rates of grade 1 embryos, and development to blastocyst stage. In conclusion, head-first or tail-first sperm injection into an oocyte in ICSI program does not affect fertilization and subsequent embryo development to blastocyst stage in vitro.

만성 간질환에 대한 DDB(Biphenyl Dimethyl Dicaboxylate)의 임상적 효과

이헌영,임의혁,김성걸,김진희,육은주,성자원,김병호,정형용,강대영,김영건 충남대학교 의과대학 지역사회의학연구소 1994 충남의대잡지 Vol.21 No.2

To investigate the effects of short-term administration of DDB(Biphenyl Dimethyl Dicarboxylate) for decreasing elevated serum aminotransferase levels in chronic liver diseases, authors applied 3 capsules of DDB per day at each meal time for 35 patients and compared with 35 patients treated with other conservative management. The following results were obtained. 1. Serum alanine aminotransferase (ALT) levels significantly decreased from 247.1± 180.0 IU/L of pretreatment level to 96.6±126.0 IU/L, 61.1±62.7 IU/L and 38.0±26.8 IU/L after 1, 3 and 6 months of treatment(p<0.05) and effective rates were observed in 60.0%, 71.4% and 88.6% of patients after 1, 3 and 6 months of treatment. 2. Serum aspartate aminotransferase (AST) levels decreased also significantly from 167.8±96.9 IU/L of pretreatment levels to 124.4±155.0 IU/L, 77.9±49.6 IU/L, 60.6± 46.9 IU/L after 1, 3 and 6 months of treatment(p<0.05), but decreasing pattern of serum AST was less significant than that of serum ALT. 3. No significant difference were observed in the serum ALT and AST changes according to the cause and duration of hepatitis. 4. No significant adverse effects were observed in whole patients treated with DDB. It is suggested that small dose administration of DDB is effective for decreasing serum aminotrans ferase levels in chronic liver disease in which other conservative management was not effective.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

SECKEL 증후군 환자의 증례보고

김추성,김재곤,백병주,양연미,정진우 大韓小兒齒科學會 2010 大韓小兒齒科學會誌 Vol.37 No.1

Seckel 증후군은 상염색체 열성 유전질환으로 태내에서의 성장지연에 따른 출생 후의 소인증, 심한 소두증을 나타내며, 큰눈과 돌출된 코, 후퇴된 하악을 동반한 새 모양의 안모가 특징적이다. 다른 임상증상으로는 관절의 결함, 내반족, 드문드문 난 모발, 비뇨생식기의 이형성, 정신지체, 혈액학적 이상 등이 나타날 수 있다. Seckel 증후군의 구강 내 소견으로는 부정교합, 법랑질 저형성증, 일부 치아의 선천적 결손, 우상치 등이 나타날 수 있다. 본 증례는 Seckel 증후군을 보이는 두 증례에서 발육부전, 새 모양의 안모, 비뇨기과적 기형, 치아의 저형성과 부정교합 등 다양한 전신증상과 구강 내 증상들을 보였기에 이를 보고하는 바이다. Seckel syndrome is an autosomal recessive disorder characterized by intrauterine growth retardation and post-natally by dwarfism, severe microcephaly, bird-headed profile with receding chin, prominent nose, joint defects, clubfoot, sparse hair, malformation of genitourinary tract and rectum, mental retardation and hematological disorders. There is also a reduction in the number of blood cells. Dental anomalies of Seckel syndrome are crowded teeth with malocclusion, enamel hypoplasia, absence of some teeth and taurodontism. This report described the oral and maxillofacial manifestations of children associated with Seckel syndrome. Children with Seckel syndrome have several dental and skeletal irregularities. The purpose of this study was to report the dental and medical characteristics of the patient and review the literatures of Seckel syndrome.

점액낭종의 외과적 처치

김재곤,김영진,김미라,백병주 대한소아치과학회 2000 大韓小兒齒科學會誌 Vol.27 No.2

점액낭종은 타액선의 분비도관이 외상, 타석, 반흔조직등에 의해 폐쇄되거나 파열되어 점액이 조직내로 유출 및 저류되어 발생하는 가성의 낭종으로, 이 중 하마종은 구강저에서 발생하는 점액낭종에 사용하는 용어이다. 염증에 이환되지 않았다면 대부분이 무통의 양상을 나타내며 심부에 위치할수록 정상색조를 띄게된다. 점액낭종의 치료는 주로 재발을 방지하기 위하여 인접소타액선을 포함한 완전절제를 시행하며, 병소의 크기가 큰 경우 부분절제를 시행하기도 한다. 하마종의 치료는 조대술과 완전절제술이 있으며, 조대술은 잦은 재발을 일으키는 단점이 있으나 치료가 성공적으로 시행되었을 경우, 환자에게 타액선이 제거되는 불편감을 덜 할 수 있다. 본 증례에서는 하순과 구강저에 발생한 점액낭종과 하마종을 완전절제술과 조대술로 치료하고 그 경과를 관찰한 바 술 후 재발이 관찰되지 않았고, 정상기능을 회복하였다. 향후 치료부위의 재발여부에 대한 계속적인 관찰이 필요하리라 생각되며, 하마종의 치료시 조대술이 적절히 이용되었을 때 환아의 불필요한 타액선 절제를 피할 수 있다고 사료된다. 또한 점액낭종의 치료시, 병력과 임상적 특징을 바탕으로 한 정확한 감별진단과 적절한 치료법의 선택이 중요하다는 결론을 얻었다 주요어 : 점액낭종, 하마종, 조대술, 완전절제술

교합면 우식병소의 다양한 진단법에 관한 비교연구

김재곤,김영진,김영신,백병주 大韓小兒齒科學會 2001 大韓小兒齒科學會誌 Vol.28 No.4

교합면의 열구는 우식이 발생하기 쉬운 위치이며, 특히 초기우식병소는 건전해 보이는 법랑질 하방에서 진행되는 경우가 많고, 주위 건전 법랑질과 잘 구별되지 않아서 주기적인 검사에도 불구하고 우식의 치료 시기를 놓치는 경우가 종종 있다. 초기 우식을 조기에 진단할 경우 불소도포, 식이조절, 치태조절 능력개선 그리고 타액분비 촉진 등의 방법으로 그 병리적 과정을 차단하고, 조기에 치료할 수 있다는 관점에서 조기 진단은 중요시 되고 있다. 본 연구는 발거된 치아에서 교합면 우식을 검출하기 위해 두가지 전통적인 진단법인 시진, 방사선 검사법에 대하여 레이저 형광측정법을 이용한 새로운 우식진단기구인 Diagnodent (Biberach , Germany)의 민감도, 특이도 그리고 정확도를 비교함으로서 교합면 초기 우식 병소에 대한 가장 신뢰성 있는 진단 방법에 대하여 평가하고자 하였으며 다음과 같은 결론을 얻었다. 1. Diagnodent는 건전치에서 7.8, 초기우식에서 25.4, 법랑질 우식에서는 30.5 그리고 상아질 우식에서는 53.8의 평균값을 나타냈다. 2. 염료를 이용한 치아조직표본검사와 스피어만과 피어슨 상관계수에서 Diagnodent(0.736, 0.619)와 시진(0.664, 0.666)에서 높은 상관성을 나타냈고 방사선 촬영검사(0.333, 0.335)에서 가장 낮은 상관성을 나타냈다(P<0.01, 전체). 3. 교합면 우식진단의 정확도는 Diagnodent의 민감도와 특이도가 가장 높았고 방사선 검사가 34%로 가장 낮았다. 4. 초기 우식의 경우, Diagnodent의 민감도와 특이도가 가장 높았고 법랑질 우식의 경우, 시신의 민감도가 가장 높았으며 Diagnodent의 특이도가 가장 높았다. 상아질 우식의 경우, Diagnodent의 민감도와 특이도가 가장 높았으며 시진의 민감도가 가장 낮았다. The aims of this study were to compare the accuracy, sensitivity and specificity of cnventional visual examination, radiography and a new laser fluorescence method, KaVo Diagnodent, for the detection of occlusal caries lesions. One hundred sound human premolars and molars which had no restorations or interproximal cavities were tested by three methods. Tooth lesions depth was assessed at histologic examination using Caries detector dye The following results were obtained. 1. Diagnodent show 7.8 in sound tooth, 25.4 in initial caries, 30.5 in enamel caries, and 53.8 in dentin caries with average score 2. Spearman and Pearson relation coefficient was high between tooth-specimen test with dye and Diagnodent(0.736, 0.619), visual examination(0.664, 0.666), and was low between tooth-specimen test with dye and radiographic examination(P<0.01, total) 3. Accuracy of occlusal caries was highest on Diagnodent(65%) and lowest on radiographic examination(35%) 4. In initial caries, the sensitivity and specificity of Diagnodent method was the highest. In enamel caries, the sensitivity of visual examination was the highest and specificity of Diagnodent method was the highest. In dentinal caries, the sensitivity and specificity of Diagnodent method was the highest and sensitivity of visual examination was the lowest.