혈관평활근세포에서 산화에너지대사 억제에 의한 아밀로이드전구단백질 대사의 변화

한문구,최웅,김헌식,안희열,한설희 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.1

Background: A reduction in the activity of cytochrome c oxidase(COX) has been recently identified in mitochondria from platelets and postmortem brain tissue of AD patients Sodium azide (NaN₃). a COX inhibitor, is an effective chemical agent producing energy shortage and oxidative stress both in vitro and in vivo system Furthermore it has been suggested that vascular compromise could be either directly involved AD pathogenesis or indirectly associated with triggering pathogenetic events leading to AD This study was performed to investigate amyloid precursor protein (APP) metabolism by inhibition of mitochondrial energy metabolism in cultured vascular smooth muslce cells (VSMCs) Materials and Methods: VSMCs isolated from the aorta of seven weeks old Spraque-Dawley rat were treated with NaN₃in a low concentration (100-500μM) or in a high concentration (1-100mM) Cellular proliferation and viability were determined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenly)-2H-tetrazolium) assay Cellular APP was detected with N-terminal specific antibody 22C11. Celldeath was determined by observation of morphology and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end labeling stain (TUNEL) We used ginkgo biloba extract(EGb761) and melatonin as anti-oxidants to investigate the mechanism of latered APP metabolism Results: The viability of VSMCs was increased after treatment with 1 mM and 10mM NaN₃(p<0.05) unitl 3 hr and then dimnished Many TUNEL positive cells were found in 10mM and 100mM treatment group. but were not apoptotic in nature 22C11 immunoreactivity was not changed at 3 hr, 6hr, 12hr Anti-oxidants reduced cellular proliferation (p<0.05). but did not block TUNEL positivities and did not influence the 22C11 immunoreactivity In a low concentration NaN₃ treatment group the viability of VSMCs was increased concentration dependently(p<0.05) Immunoblot with 22C11 showed the concentration dependent decrease at 145 kDa, 125 kDa. and high molecular weight range (>160kDa) TUNEL staining showed DNA fragmentations and condensations of nuclear chromatin suggesting apoptosis After treatment with anti-oxidants, the cellular proliferation was more decreased (p<0.05), and TUNEL positive cell deaths were blocked Immunoreactivities of 125 kDa (immature APP). 145 kDa (mature APP). and higher molecular weight bands were recovered below 400μM of NaN₃ Immunoreactivity of 145 kDa was recovered in 100 μM NaN₃ treated group Conclusions: The presumed mechanism of low concentration COX inhibitor is the overproduction of reactive oxygen species resulting from a depression of the mitochondiral electron transport chain. whereas potential consequence of high concentration COX inhibitor might be related to decreassion of ATP synthesis and bioenergetic impairment Reactive oxygen radicals in response to low concentration COX inhibitor alter the processing of APP in VSMCs This investigation demonstrated analtered APP metabolism as a peripheral marker of AD Therefore VSMCs treated with low concentration COX inhibitor could be concsidered as a novel in vitro model of AD.

내측연수경색에서 관찰된 안구의 반대편 측방돌진

김지수,문소영,정선미,한문구,박성호 대한평형의학회 2003 Research in Vestibular Science Vol.2 No.2

이중혈류유발 심폐소생술이 심정지를 유발한 개의 단기 생존율에 미치는 영향

황성오,조준휘,강구현,김성환,문중범,이강현,이승환,윤정한,최경훈,홍은석 대한응급의학회 2000 대한응급의학회지 Vol.11 No.3

Background and Objectives: We previously reported that, compared with standard cardiopulmonary resuscitation(S-CPR), better hemodynamic effects could be achieved by simultaneous sterno-thoracic cardiopulmonary resuscitation(SST-CPR) in which we compressed the sternum and constricted the thorax circumferentially during the systolic period by using a device. This study was designed to assess whether SST-CPR, compared with S-CPR, improve the survival rate of dogs with cardiac arrest. Subjects and methods: Twenty-five mongrel dogs(19∼31㎏) were enrolled in this study. After four minutes of ventricular fibrillation induced by an AC current, animals were randomized to resuscitate with either S-CPR(n=13) or SST-CPR(n=12). Epinephrine(1 ㎎) was injected into the right atrium every three minutes after the beginning of CPR. Defibrillation was attempted after 6 minutes of CPR. Standard advanced cardiac life support was started if defibrillation was not successful. Results: SST-CPR resulted in significantly(p<0.001) higher systolic arterial pressure(91±47 vs 47±24 ㎜ Hg), diastolic pressure(43±24 vs 17±10 ㎜ Hg), coronary perfusion pressure(35±25 vs 13±9㎜ Hg), and end tidal CO2 tension(9±4 vs 3±2 ㎜ Hg). Two of 13 animals(15 %) resuscitated with S-CPR and six of 12 animals(50%) resuscitated with SST-CPR survived until 12 hours after cardiac arrest(p<0.05). Donclusion: SST-CPR, compared with S-CPR, improves the short-term survival rate in canine cardiac arrest.

Combined intravenous and intraarterial revascularization therapy using MRI perfusion/diffusion mismatch selection for acute ischemic stroke at 3-6 h after symptom onset.

Han, Moon-Ku,Kim, Sung Hyun,Ko, Sang-Bae,Paik, Nam-Jong,Kwon, O-Ki,Lee, Yong-Seok,Oh, Chang-Wan,Kim, Jae Hyoung,Park, Seong-Ho,Bae, Hee-Joon Humana Press 2008 Neurocritical care Vol.8 No.3

<P>BACKGROUND AND PURPOSE: Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) has demonstrated favorable clinical outcomes in a 3-6 h window in patients selected with perfusion/diffusion mismatch. However, the advantages of combined IV and intraarterial (IA) thrombolysis after 3 h of stroke onset are unexplored. METHODS: Acute ischemic stroke patients with persistent occlusion of intracranial large arteries were screened prospectively for thrombolysis by evaluating perfusion/diffusion mismatch on MRI. The IV rt-PA was initiated within 3-6 h, and additional urokinase (UK) was then administered via the IA route after angiography. RESULTS: Four patients had middle cerebral artery occlusion and one patient had an internal carotid artery occlusion. The median time from the symptom onset to the initiation of IV therapy and to the initiation of IA treatment was 215 +/- 30 min and 292 +/- 41 min, respectively. The median National Institutes of Health Stroke Scale (NIHSS) scores were as follows: initial, 13; immediately after IA treatment, 8; at 24 h, 5; and at 7 days, 3. The Thrombolysis in Myocardial Infarction (TIMI) score after the completion of thrombolysis was 2-3. Four patients without intracerebral hemorrhage recovered completely or exhibited mild disability and one patient with hemorrhage also demonstrated a favorable outcome. CONCLUSION: This preliminary result suggests that if a significant perfusion/diffusion mismatch on MRI is identified, a sequential combination thrombolysis of IV rt-PA and IA UK is potentially beneficial in moderate to severe acute ischemic stroke patients who are treated within 3-6 h after symptom onset.</P>

Efeect of Necropsy Days on Number of Clonorchis sinensis and Plaque Forming Cells after Challenge in Hamsters

Moon, Han Ku,Moon, Chu Hwan,Kong, Hyun Hee,Choi, Dong Wik 慶北大學校 醫科大學 1994 慶北醫大誌 Vol.35 No.2

Challenge 感染된 햄스터에서 屠殺日이 肝吸蟲과 PFC의 數에 미치는 影響을 決定하기 위해 肝吸蟲 成蟲의 代謝産物과 Freund's incomplete adjuvant로 感作된 golden 햄스터의 腹腔渗出細胞와 血淸을 recipient 햄스터의 腹腔內에 注入하였다. 第1次 感作한지 7日 後에 肝吸蟲 被囊幼蟲 20個씩 經口感染시킨 다음, 50日, 70日, 90日 그리고 110日에 各各 屠殺하였다. Challenge感染 後, EpG는 對照群에서 感作群보다 하루 일찍 나타났고, 對照群과 感作群 모두 漸次로 增加되다가 40日에서 65日사이에 最高値를 나타낸 후 漸次 減少하였다. 그러나, 感作群 사이에 EpG의 有意的 差는 認定할 수가 없었다. 蟲體回收率은 感作群과 對照群 사이에 有意的 差를 認定할 수 있었다. 蟲體回收率은 Challenge感染후, 약 70日 前後에 減少되었다. Plaque 形成細胞는 感作後 50日과 70日의 感作群에서 檢出되었으나, 그 以後의 感作群 및 對照群에서는 檢出되지 않았다. 以上의 成績으로 미루어 보아 golden 햄스터의 適切한 屠殺日은 Challenge感染 後 50日에서 70日이 適當함을 알 수 있었다. OBJECTIVE, MATERIALS AND METHODS: To determine the appropriate necropsy day in the passive transfer of immunity against Clonorchis sinensis in golden hamsters, the donor hamsters were sensitized with two injections of the admixture of the metabolic products of C. sinensis and Freund's incomplete adjuvant into footpads at 2 weeks' intervals. The peritoneal cells and sera of sensitized and control donor hamsters were injected intraperitoneally to the recipient hamsters, seven days after primary sensitiza-tion. Four groups of the recipient and control hamsters were challenged with 20 metacercariae of C. sinensis, and killed on the 50th, 70th, 90th and 110th day after challenge infection. RESULTS: The eggs of control hamsters appeared one day earlier than those of the recipient groups, and the eggs per gram of feces in both recipient and control groups increased stepwise and continued at high levels from the 40th to 65th day and then decreased irregularily after challenge infection. There was no significant difference in EpG of feces between the sensitized recipient and control groups, but there was significant difference in the worm burden of C. sinensis between the recipient and control groups. The recovery number of the fluke in the recipient and control hamsters decreased about the 70th day after challenge infection. CONCLUSIONS: These results indicate in part that the appropriate necropsy day of golden hamsters would be estimated around the 50th day after challenge infection of C. sinensis.

출생 직후 증상이 관찰된 hemifacial spasm 1례

문한구(Han Ku Moon),신손문(Son Moon Shin) 대한소아신경학회 1993 대한소아신경학회지 Vol.1 No.2

Hemifacial spasm characterized by involuntary, irregular twitching of muscles innervated by the facial nerve, occurs almost exclusively in adults. In infancy and childhood, it is extremely rare. At least 10 cases of hemifacial spasm in children were reported in the English literature by 1992. We describe one young female child with symptom of hemifacial spasm starting shortly after birth. Diagnostic tests such as EEG, video EEG monitoring, brain CT and brain MRI were normal. Our patient did not respond to treatment of three months with carbamiazepine, phenobarbital, dilantin and valproic acid during infancy. The hemifacial spasm remained unchanged when she was 3 years and 2 month of age.

소아 연령에서 간질성 경련과 감별을 요하는 질환

문한구(Han Ku Moon),이영환(Young Hwan Lee),박용훈(Yong Hoon Park) 대한소아신경학회 1995 대한소아신경학회지 Vol.2 No.2

연구 배경: 간질성 경련과 다양한 비간질성 유사경련 증상과의 감별에서 비간질성 유사경련 증상마다의 임상적 특징을 이해하고 각 연령마다 호발하는 질환의 분포를 이해함이 필요할 것으로 생각된다. 방법: 소아 신경 크리닉에서 진료받았던 환아 중 간질성 경련이 의심되거나 감별 진단이 필요했던 환자로서 비간질성 유사경련 증상으로 확인 된 56명의 소아를 대상으로 병력지를 검토 분석하는 후향적 연구를 시행하였다. 결과: 대상 환아의 남녀비는 1:1.33으로 여아에서 많았고 연령은 생후 2개월에서 2세 사이가 8례(14.3%), 2-6세 연령이 19례(33.9%), 6-10세 연령군이 10례(17.9%), 10-15세군이 19례로 33.9%였다. 질환별로는 수면 장애가 20례(35.7%)로 가장 많았고 심인성 경련이 8례(14.3%) 그리고 호흡 정지 발작과 약물에 의한 근긴장 이상이 각각 4례(7.1%)씩의 순으로 많았다. 각 연령별로 생후 2개월에서 2세까지에서는 호흡 정지 발작과 약물에 의한 근긴장의 이상이 각각 2례씩 있었고, 2-6세 연령에서는 수면 장애, 행동 장애의 순으로, 6-10세에서 수면 장애, 심인성 경련의 순으로, 10-15세 연령에서는 심인성 경련, 수면 장애, 실신 발작의 순으로 많았다. 결론: 간질성 경련이 아니면서 간헐적으로 발작의 소견을 보이는 질환은 소아에서 다양하며 그 빈도 또한 적지 않다. 세밀한 병력 청취 및 video EEG를 포함한 적절한 검사가 진단에 필수적이며 정확한 진단으로 간질의 오진 및 부적절한 치료를 예방할 수 있을 것으로 생각된다. Background : A number of conditions cause intermittent and recurring symptoms that suggest epilepsy especially in children. They must not be confused with seizures because treatment with anticonvulsants is unnecessary and even harmful to immature developing brain. This study was conducted to investigate the clinical characteristics of non-epileptic seizure-like events in children. Method : The medical records of 56 children(24 male, 21 female, younger than 15 years of age) refered to pediatric neurology outpatient clinic for evaluation of epileptic seizures but later shown to have non-epileptic non-seizure events by detailed history with appropriate laboratory tests including video EEG studies were reviewed. Results : The final diagnoses included sleep disorder(35.7%), psychogenic seizure(14.3%), breath holding spell(7.1%), drug induced dystonia(7.1%), syncope(5.4%) and behavioral disorder(5.4%). Sleep disorders were common between 2-10 years of age and psychogenic seizures were common in female adolescent girls. Conclusion : Our study illustrates that non-epileptic seizure-like events are common and different types are observed depending on age and sex. Detailed history with appropriate laboratoty tests including video-EEG studies is important for preventing erroneous diagnosis of epilepsy and for management of these patients.

Hemiconvulsion-Hemiplegia-Epilepsy 증후군 1 예

문한구 ( Han Ku Moon ) 영남대학교 기초/임상의학연구소 2007 Yeungnam University Journal of Medicine Vol.24 No.2S

Hemiconvulsion-Hemiplegia-Epilepsy syndrome is characterized by a prolonged unilateral convulsion in the form of status producing a persisting hemiplegia during a febrile illness, followed by epilepsy. It occurs in a child, between 5 months and 4 years old, with a peak incidence during the first 2 years of life. Although the etiologies of this syndrome are diverse, preexisting asymptomatic lesion of perinatal or prenatal origin is found in a number of cases. I experienced a case of HHE syndrome in a 11 month old girl with abnormal perinatal history and developmental delay, who showed predominant right sided focal motor seizures followed by right hemiparesis.

PEHO 증후군 1례

문한구(Han Ku Moon) 대한소아신경학회 2007 대한소아신경학회지 Vol.15 No.2

PEHO 증후군은 초기 영아기에 관찰되는 근 긴장 저하, 정신운동발달의 지연 혹은 퇴행, 시신경위축으로 인한 시력소실, 특히 소뇌에서 저명한 진행성 뇌 위축, 고부정뇌파와 영아 연축과 같은 간질 발작이 나타나는 아주 드문 퇴행성 신경질환으로 상염색체 열성으로 유전된다고 알려져 있다. 1991년, 핀란드 소아들 증례를 시작으로 주로 핀란드에서 보고되었으며 드물게 핀란드 아닌 국가에서도 보고되어 왔다. 저자는 24개월된 여아로서 시신경위축, 소뇌 위축, 간질 발작, 발달의 퇴행 등 PEHO 증후군에 부합되는 1례를 경험하였기에 보고하는 바이다. Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy(PEHO) syndrome was first described in 1991 by Salonen. It is a rare, autosomal recessive, and severe neurodegenerative disease with onset in early infancy and guarded prognosis. The distinct clinical criteria for the PEHO syndrome are infantile hypotonia, convulsion, early arrest of mental development, poor or absent visual fixation with optic atrophy by 2 years of age and progressive brain atrophy, particularly of the cerebellum and the brainstem. Most of reported patients with PEHO syndrome are Finnish, and only very few patients in other countries including Japan, Canada and Netherlands have been described. I report a Korean girl with the distinct clinical features of PEHO syndrome and this child is the first Korean patient reported.

척수 천자시 EMLA도포에 의한 통증 완화 효과

문한구(Han Ku Moon),안준형(Jun Hyung Ahn),박용훈(Yong Hoon Park) 대한소아신경학회 1995 대한소아신경학회지 Vol.2 No.2

배 경 : 신경계 질환의 진단이나 치료시 흔히 사용되는 척수 천자술은 치명적인 합병증이나 후유증이 문제가 될 수도 있으나 드물고, 척수 천자 시술 자체에 수반되는 통증이 더 흔하게 겪는 문제점이다. 저자들은 척수 천자 시술시 연고형 국소 마취제인 EMLA의 통증 완화 효과를 알아 보기 위하여 본 연구를 시행하였다. 방 법 : 1993년 5월부터 7월까지 영남대학병원 소아과에 입원하여 척수 천자술을 시행받은 44명의 환아를 대상으로 EMLA를 사용하거나(EMLA사용군), 가약을 사용(대조군)하여 그들이 느꼈던 통증의 정도를 여러 척도로 비교 관찰하였다. 결 과 : 1) 통증에 대한 환아의 반응(verbal rat-ing)은 “조금 아프다”가 EMLA사용군에서는 34례(100%), 대조군에서는 1례(10%)였고, “꽤 아프다”와 “많이 아프다”는 EMLA군에서는 한 예도 없었으나, 대조군에서는 각각 4례(40%), 2례(20%)였다(p<0.01). 2) McGrath's Face Scale은 EMLA군에서는 D와 E가 각각 10례(29.4%)와 22례(64.7%)였으나, 대조군에서는 F,G와 H가 각각 2례(20%), 4례(40%), 2례(20%)로 대조군에 비해 EMLA사용군에서 통증이 적었다(p<0.01). 3) Oucher Pain Scale 은 EMLA사용군에서는 40점이 28례(82.4%), 60점이 6례(17.6%)였으나, 대조군에서는 50,60,100점이 각각 2례(20%), 1례(10%), 2례(20%)로 EMLA사용군에서는 통증 완화 효과가 더 좋았다(p<0.05). 4) Visual analogue scale은 대조군에서 2,4,6 그리고 7점이 각각 2례(20%)였으며, EMLA군에서는 3,4점이 각각 28례(82.4%), 4례(11.8%)로 EMLA사용군에서 통증 완화효과가 있을 것으로 생각되었으나 p값은 0.14로 통계적으로 유의하지 못했다. 5) EMLA를 부착한 부위의 부작용으로는 가려움이 2례에서, 발적이 1례에서 관찰되었으나 전신적인 부작용은 없었다. 결 론 : 소아에서 신경계 질환의 진단이나 치료를 위해 자주 시행되는 척수 천자 시술 전 국소 마취 연고(EMLA)의 도포는 심각한 부작용의 위험없이 불가피하게 발생되는 척수 천자로 인한 통증을 의미있게 완화시켜 줄 수 있는 한 가지 좋은 방법으로 생각된다. Background : A new topical anesthetic ointment(EMLA:eutectic mixture of local anesthetic) composed of eutectic mixture of prilocaine and lidocaine was studied to evaluate its efficiency in allevaiating pain associated with lumbar punctures in children. Method : Pain intensity was scored by verbal rating. McGrath's pain scale. Oucher face scale and visual analogue scale. Lumbar punctures were performed on 44 cases (34 EMLA treated patients. 10 placebo treated patients) from 5 to 15 years of age. Result : EMLA cream was associated with less pain scores than those with placebo ( verbal rating. McGrath's pain scale: p<0.01 Oucher face scale: p<0.05) except in visual analogue scale(P=0.144). Minor local reactions were reported : itching was observed in 2 children and erythema was in a child following EMLA application. Conclusion : It was concluded that the use of EMLA cream substantially reduces pain caused by lumbar punctures in children and may therefore be offered to such procedures.