혼수의 진단 : 혼수를 유발하는 대사성 질환

명호진 ( Ho Jin Myung ) 대한내과학회 1975 대한내과학회지 Vol.18 No.1

Arachidonate-induced Oxygen Radical Production and Cellular Damage in Ischemic-Reperfused Heart of Rat

이윤송,김용식,박성호,명호진,김명석,Lee, Yun-Song,Kim, Yong-Sik,Park, Seong-Ho,Myung, Ho-Jin,Kim, Myung-Suk The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.2

허혈심근의 재관류시 arachidonic acid가 반응성 산소대사물의 발생원으로서 심근 손상에 미치는 영향을 검토하였다. Langendorff 관류장치를 이용하여 흰쥐 적출심장을 0.5ml/min의 저용량으로 관류 (45분)한 후 정상관류 (7 ml/min)로 복귀 시키므로써 실험적인 허혈-재관류 심장을 만들었다. 재관류시 Na arachidonate $(10^{-7}{\sim}10^{-2}{\mu}g/ml)$를 투여한 후 superoxide anion 생성을 관찰하고, 심근 손상의 지표로 lactic dehydrogenase(LDH)유리를 측정 하였으며 이들에 대한 각종 arachidonic acid 대사 억제 약물의 영향을 비교 검토하였다. Superoxide anion 생성은 SOD-억제성 ferricytochrorme C 환원 반응을 이용하였다. 연구성적은 다음과 같다. 1) 저용량 관류후 재관류시 ferricytochrorme C환원은 superoxide dismutase (SOD, 300 U/ml) 및 indomethacin (60 nmole/ml), ibuprofen $(30\;{\mu}g/ml)$에 의하여 억제되었다. 2) Na arachidonate는 용량의존적으로 ferricytochrorme C 환원을 증가 시켰으며 반응성 산소대사물 제거효소인 superoxide dismutase (SOD, 300 U/ml)에 의하여 현저히 억제되었다. 3) Na arachidonate $(10^{-3}\;{\mu}g/ml)$에 의한 superoxide anion 생성은 cyclooxygenase 억제약물인 indomethacin (60 nmol/ml), lipooxygenase 억제약물인 nordihydroguaiaretic acid$(NDGA,\;0.1\;{\mu}mole/ml)$, arachidonic acid의 substrate inhibitor인 eicosatetraynoic acid $(ETYA,\;1\;{\mu}g/ml)$에 의하여 현저히 억제되었다. 4) Na arachidonate는 LDH 유리를 증가시켰으며 SOD에 의하여 유의하게 억제 되었다. 5) Na archidonate에 의한 LDH 유리증가는 indomethacin, NDGA, ETYA에 의하여 유의하게 억제 되었다. 이상의 결과로 흰쥐의 허혈-재관류심근에서 arachidonic acid는 그 대사 과정에서 반응성 산소대사물을 발생하고 이는 심근세포손상에 부분적으로 기여할 수 있을 것으로 여겨졌다. The present study was conducted to assess the possible contribution of arachidonic acid to generation of reactive oxygen metabolites and myocardial damage in ischemic-reperfused heart. Langendorff preparations of isolated rat heart were made ischemic by hypoperfusion (0.5 ml/min) for 45 min, and then followed by normal oxygenated reperfusion (7 ml/min). The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The myocardial cellular damage was observed by measuring LDH released into the coronary effluent. Oxygenated reperfusion following a period of ischemia produced superoxide anion, which was inhibited by both indomethacin (60 nmole/ml) and ibuprofen $(30\;{\mu}g/ml)$. Sodium arachidonate $(10^{-7}-10^{-2}{\mu}g/ml)$ administered during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide generation was markedly inhibited by indomethacin, a cyclooxygenase inhibitor; nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and by eicosatetraynoic acid (ETYA), a substrate inhibitor of arachidonic acid metabolism. The release of LDH was increased by Na arachidonate and was inhibited by superoxide dismutase. The release of LDH induced by arachidonic acid was also inhibited by indomethacin, NDGA and ETYA. In conclusion, the present result suggests that arachidonic acid metabolism is involved in the production of reactive oxygen metabolite and plays a contributory role in the genesis of reperfusion injuy of myocardium.

Generation of Superoxide Radical from Rat Brain Mitochondria and Mechanism of Its Toxic Action to Mitochondrial and Extra-mitochondrial Components

노재규,표장근,정명희,임정규,명호진,Roh, Jae-Kyu,Pyo, Jang-Geun,Chung, Myung-Hee,Lim, Jung-Kyoo,Myung, Ho-Jin The Korean Society of Pharmacology 1985 대한약리학잡지 Vol.21 No.1

흰쥐 뇌 미토콘드리아에 의한 $O^{-}_{2}{\cdot}$ 의 생성과 이 radical의 유해작용 및 그 작용기전을 알아보기 위하여 본실험을 수행하였다. Succinate와 antimycin존재하에서 미토콘드리아는 $O^{-}_{2}{\cdot}$을 생성하였으며 이는 SOD-inhibitable NBT환원으로 확인되었다. 동일 조건에서 $H_2O_2$는 일차생성물인 $O^{-}_{2}{\cdot}$의 dismutation으로 생성됨을 알수 있었다. 상기조건에서 미토콘드리아의 막지질이 파괴되었고 반응액에 첨가된 isocitrate dehydrogenase와 적혈구에 각각 불활성화와 용혈이 초래되었다. 이같은 작용은 $Fe^{++}$이 있을때만 관찰 되었다. 그리고 독작용은 superoxide dismutase 혹은 castalase에 의해서 억제되었다. 또한 methional을 첨가하였을 때 ethylene이 생성되었으며 그 생성은 $Fe^{++}$에 의하여 현저히 증가하였다. Ethylene 생성 역시 상기 효소에 의하여 억제되었다. 따라서 미토콘드리아에서 발생된 $O^{-}_{2}{\cdot}$은 거대분자 및 세포에 독성을 나타낼수 있으며 이같은 작용은 $Fe^{++}$의 촉매작용에 의한 $O^{-}_{2}{\cdot}$와 $H_2O_2$의 상호작용으로 발생되는 $OH{\cdot}$ 에 의한것으로 추측되었다. 이상의 결과는 미토콘드리아가 유독성 산소 radical을 발생하므로 조직손상을 시킬 수 있다는 가능성을 시사하는 증거라고 생각되었다. The generation of $O^{-}_{2}{\cdot}$ and its toxic effects were studied with rat brain mitochondria. The production of $O^{-}_{2}{\cdot}$ from mitochondria in the presence of succinate and antimycin was demonstrated by SOD-inhibitable reduction of NBT. Although succinate can support the $O^{-}_{2}{\cdot}$ formation, the highest rate needs antimycin indicating that blockade of electron flow in the respiratory chain augments the univalent reduction of molecular oxygen. Under this condition, $H_2O_2$ was also observed to be produced. But its formation appears to be derived from the dismutation of the primary product, $O^{-}_{2}{\cdot}$ since the rate of $H_2O_2$ production was markedly decreased by NBT and ferricytochrome c. The $O^{-}_{2}{\cdot}$ and $H_2O_2$ produced were able to cause toxic actions to mitochondrial and extra-mitochondrial components as shown by lipid peroxidation of mitochondrial membrane, and inactivation and lysis of isocitrate dehydrogenase and erythrocytes added to the medium, respectively. In all the toxic actions observed, $Fe^{++}$ was required. It appears that in the toxic actions $OH{\cdot}$ generated from the iron-catalyzed Haber-Weiss reaction acts as a mediator. This was supported by the finding that mitochondria in the presence of succinate and antimycin produced ethylene from methional, and $Fe^{++}$ added increased the ethylene production. The observed toxic actions of mitochondrial $O^{-}_{2}{\cdot}$ may provide evidence supporting a potential role of mitochondria as a source of oxygen radicals to cause tissue damage.

파킨슨병에서 99mTc - HMPAO SPECT를 이용한 국소뇌혈류의 정량적 분석

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이명혜(Myung Hae Lee),노재규(Jae Kyu Roh),명호진(Ho Jin Myung),배상균(Sang Kyun Bae) 대한핵의학회 1992 핵의학 분자영상 Vol.26 No.2

N/A Regional cerebral blood flow were measured in 10 patients with Parkinson's disease and 12 normal persons using Tc-99m-HMPAO SPECT. Reconstructed images were interpreted qualitatively and were compared with those findings of CT. For the quantitative analysis, six pairs of region of interest matched with the perfusion territories of large cerebral arteries and cerebellar hemisphere were determined. From the count values, indices showing the degree of asymmetry between right and left cerebral or cerebellar hemisphere, cerebral asymmetry index (ASI) and percent index of cerebellar asymmetry (PIA), and an index showing change of each region, region to cerebellum ratio (RCR) were obtained. ASI of normal persons and patients were 0.082±0.033 and 0.108±0.062, respectively and PIA were -0.4±0.7% and -0.7±1.0%, respectively, which showed no statistically significant difference between normal persons and patients. Among 10 RCR's, those of both regions of basal ganglia and both regions of anterior cerebral artery were significantly reduced. We concluded that the most significant reduction of regional cerebral blood flow in patients with Parkinson's disease was observed in the regions of basal ganglia and in the regions of anterior cerebral artery, and the degree of change in hemispheric blood flow was similar in both hemisphere.

99mTc - HMPAO SPECT를 이용한 정상인 국소뇌혈류의 정량적 분석

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),문대혁(Dae Hyuk Moon),궁성수(Sung Soo Koong),노재규(Jae Kyu Roh),명호진(Ho Jin Myung),이범우(Bum Woo Lee),이경한(Kyung Han Lee),최윤호(Yoon Ho Choi),윤병우(Byung Wo 대한핵의학회 1989 핵의학 분자영상 Vol.23 No.2

N/A Regional cerebral perfusion was evaluated in 15 normal controls by single photon emission comput- ed tomography using Tc HM-PAO. For quantitative analysis, 13 pairs of hornologous region of interest (ROI) were drawn on three transverse slices matching the vascular territories and cerebral cortices, and normal values of '3 semiqunatitative indices including Right to left ratio (R/L ratio), 'Regional index' (RI), and 'Region to cerebellum ratio (R/cbll ratio) were calculated. Mean values of R/L ratios of homologous regions were ranged frorn 0.985 to 1.023, and mean +- 2 s.d. of ali regions did not exceed 11% of mean. Significant difference of Rls (mean count per voxel of a ROJ/mean count per voxel of total ROls) between regions were found (p<0.001) with highest values in occipital cortex and cerebellum. After attenuation correction, Rls in deep gray, cranial portion of anterior cerebral artery and vascular territories in the 2nd siice increased significantly (p< 0.05 0.001). hut vise versa in other ROIs. Reginn to cerebellum ratios also showed regional difference siinifar to Rls.

99mTc - HMPAO SPECT를 이용한 어린이 국소뇌혈류의 정량적 분석 : 정량적 지표들의 참고값 및 연령에 따른 변화

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),김상은(Sang Eun Kim),노재규(Jae Kyu Roh),명호진(Ho Jin Myung),윤병우(Byung Woo Yoon),조수철(Soo Churl Cho),홍승봉(Seung Bong Hong) 대한핵의학회 1991 핵의학 분자영상 Vol.25 No.1

N/A Regional cerebral blood flow (rCBF) was evaluated in 12 children ranging in age from 2.7 to 10.0 yr using 99mTc-HMPAO SPECT. For quantitative analysis, 13 pairs of homologous regions of interest (ROIs) were created on three attenuation-corrected 18,8 mm thick transverse slices matching the cerebral cortical regions, deep gray matter, cerebellar hemisphere, and vascular territories, and the semiquantitative indices including right to left ratio [(mean countjvoxel of homologous right ROI) /(mean count/voxel of homologous left ROI) ] and regional index (RI) [ (mean count/voxel of a ROI) /(rnean count/voxel of all ROIs of each hemisphere)] were calculated. Mean values of right to left ratios of homologous tegions ranged frorn 0.984 to 1.028 in children under 5 yr (group 1) and from 0.982 to 1.012 in children between 5 and 10 yr (group 2), and the mean value +-2 S.D. for each region did not exceed 11%. and 12% in group 1 and group 2, respective]y. There were no statis- tically significant differences between the RIs of the homologous right and left regions. Significant differences of RIs were found both between vascular regions (p<0,0005 for goup 1, and p=0,0001 for goup 2) and between regions of cerebral cortices (p<0,0005 for group 1, and p<0,005 for group 2) with a relatively high value in the occipital cortex and the Iower values in the r.erebellum and deep gray matter among the regions of cerebral cortices in both groups. There were no significant differences between the Rls of corresponding regions of group 1 and group 2, except a significantly higher value of right deep gray matter in group 2 than in group 1(p=0.0301). The RIs of the superior frontal cortex and deep gray matter showed to be positively correlated with age (superior frontal cortex; right: rs=0.5254, p =0.0814, left: rs=0.5919, p=0.0496/deep gray matter; right: rs=0.8246, p=0.0062, left: rs=0.6266, p=0,0377). The results suggest that the rCBF pattern of children approaches that of adults in an occipito-rostraJ direction. This time course of rCBF changes is in agreement with behavioral, neurophysiological, and anatomical alterations known to occur in the developing brain.

허혈-재관류 적출심장에서 Arachidonic Acid에 의한 산소라디칼 생성 및 심근손상

이윤송(Yun Song Lee),김용식(Yong Sik Kim),박성호(Seong Ho Park),명호진(Ho Jin Myung),김명석(Myung-suk Kim) 대한약리학회 1991 대한약리학잡지 Vol.27 No.2

허혈심근의 재관류시 arachidonic acid가 반응성 산소대사물의 발생원으로서 심근 손상에 미치는 영향을 검토하였다. Langendorff 관류장치를 이용하여 흰쥐 적출심장을 0.5ml/min의 저용량으로 관류 (45분)한 후 정상관류 (7 ml/min)로 복귀 시키므로써 실험적인 허혈-재관류 심장을 만들었다. 재관류시 Na arachidonate (10^-7 ~ 10^-2μg/ml)를 투여한 후 superoxide anion 생성을 관찰하고, 심근 손상의 지표로 lactic dehydrogenase(LDH)유리를 측정 하였으며 이들에 대한 각종 arachidonic acid 대사 억제 약물의 영향을 비교 검토하였다. Superoxide anion 생성은 SOD-억제성 ferricytochrorme C 환원 반응을 이용하였다. 연구성적은 다음과 같다. 1) 저용량 관류후 재관류시 ferricytochrorme C환원은 superoxide dismutase (SOD, 300 U/ml) 및 indomethacin (60 nmole/ml), ibuprofen (30μg/ml)에 의하여 억제되었다. 2) Na arachidonate는 용량의존적으로 ferricytochrorme C 환원을 증가 시켰으며 반응성 산소대사물 제거효소인 superoxide dismutase (SOD, 300 U/ml)에 의하여 현저히 억제되었다. 3) Na arachidonate (10^-3μg/ml)에 의한 superoxide anion 생성은 cyclooxygenase 억제약물인 indomethacin (60 nmol/ml), lipooxygenase 억제약물인 nordihydroguaiaretic acid(NDGA, 0.1μmole/ml), arachidonic acid의 substrate inhibitor인 eicosatetraynoic acid (ETYA, 1μg/ml)에 의하여 현저히 억제되었다. 4) Na arachidonate는 LDH 유리를 증가시켰으며 SOD에 의하여 유의하게 억제 되었다. 5) Na archidonate에 의한 LDH 유리증가는 indomethacin, NDGA, ETYA에 의하여 유의하게 억제 되었다. 이상의 결과로 흰쥐의 허혈-재관류심근에서 arachidonic acid는 그 대사 과정에서 반응성 산소대사물을 발생하고 이는 심근세포손상에 부분적으로 기여할 수 있을 것으로 여겨졌다. The present study was conducted to assess the possible contribution of arachidonic acid to generation of reactive oxygen metabolites and myocardial damage in ischemic-reperfused heart. Langendorff preparations of isolated rat heart were made ischemic by hypoperfusion (0.5 ml/min) for 45 min, and then followed by normal oxygenated reperfusion (7 ml/min). The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The myocardial cellular damage was observed by measuring LDH released into the coronary effluent. Oxygenated reperfusion following a period of ischemia produced superoxide anion, which was inhibited by both indomethacin (60 nmole/ml) and ibuprofen (30μg/ml). Sodium arachidonate (10^-7-10^-2μg/ml) administered during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide generation was markedly inhibited by indomethacin, a cyclooxygenase inhibitor; nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and by eicosatetraynoic acid (ETYA), a substrate inhibitor of arachidonic acid metabolism. The release of LDH was increased by Na arachidonate and was inhibited by superoxide dismutase. The release of LDH induced by arachidonic acid was also inhibited by indomethacin, NDGA and ETYA. In conclusion, the present result suggests that arachidonic acid metabolism is involved in the production of reactive oxygen metabolite and plays a contributory role in the genesis of reperfusion injuy of myocardium.

흰쥐 뇌 미토콘드리아에 의한 superoxide radical의 생성과 이 radical이 미토콘드리아 및 미토콘드리아 외 물질에 대한 독작용과 그 기전에 관한 연구

노재규(Jae-Kyu Roh),표장근(Jang-Geun Pyo),정명희(Myung-Hee Chung),임정규(Jung-Kyoo Lim),명호진(Ho-Jin Myung) 대한약리학회 1985 대한약리학잡지 Vol.21 No.1

흰쥐 뇌 미토콘드리아에 의한 O₂^-⋅ 의 생성과 이 radical의 유해작용 및 그 작용기전을 알아보기 위하여 본실험을 수행하였다. Succinate와 antimycin존재하에서 미토콘드리아는 O₂^-⋅을 생성하였으며 이는 SOD-inhibitable NBT환원으로 확인되었다. 동일 조건에서 H₂O₂는 일차생성물인 O₂^-⋅의 dismutation으로 생성됨을 알수 있었다. 상기조건에서 미토콘드리아의 막지질이 파괴되었고 반응액에 첨가된 isocitrate dehydrogenase와 적혈구에 각각 불활성화와 용혈이 초래되었다. 이같은 작용은 Fe⁺⁺이 있을때만 관찰 되었다. 그리고 독작용은 superoxide dismutase 혹은 castalase에 의해서 억제되었다. 또한 methional을 첨가하였을 때 ethylene이 생성되었으며 그 생성은 Fe⁺⁺에 의하여 현저히 증가하였다. Ethylene 생성 역시 상기 효소에 의하여 억제되었다. 따라서 미토콘드리아에서 발생된 O₂^-⋅은 거대분자 및 세포에 독성을 나타낼수 있으며 이같은 작용은 Fe⁺⁺의 촉매작용에 의한 O₂^-⋅와 H₂O₂의 상호작용으로 발생되는 OH⋅ 에 의한것으로 추측되었다. 이상의 결과는 미토콘드리아가 유독성 산소 radical을 발생하므로 조직손상을 시킬 수 있다는 가능성을 시사하는 증거라고 생각되었다. The generation of O₂^-⋅ and its toxic effects were studied with rat brain mitochondria. The production of O₂^-⋅ from mitochondria in the presence of succinate and antimycin was demonstrated by SOD-inhibitable reduction of NBT. Although succinate can support the O₂^-⋅ formation, the highest rate needs antimycin indicating that blockade of electron flow in the respiratory chain augments the univalent reduction of molecular oxygen. Under this condition, H₂O₂ was also observed to be produced. But its formation appears to be derived from the dismutation of the primary product, O₂^-⋅ since the rate of H₂O₂ production was markedly decreased by NBT and ferricytochrome c. The O₂^-⋅ and H₂O₂ produced were able to cause toxic actions to mitochondrial and extra-mitochondrial components as shown by lipid peroxidation of mitochondrial membrane, and inactivation and lysis of isocitrate dehydrogenase and erythrocytes added to the medium, respectively. In all the toxic actions observed, Fe⁺⁺ was required. It appears that in the toxic actions OH⋅ generated from the iron-catalyzed Haber-Weiss reaction acts as a mediator. This was supported by the finding that mitochondria in the presence of succinate and antimycin produced ethylene from methional, and Fe⁺⁺ added increased the ethylene production. The observed toxic actions of mitochondrial O₂^-⋅ may provide evidence supporting a potential role of mitochondria as a source of oxygen radicals to cause tissue damage.

측두엽성간질의 간질병소 편측화에서 99mTc - HMPAO SPECT의 유용성 : 뇌파 , 자기 공명 영상 및 전산화 단층 영상과의 비교

김종호,김종순,김상은,최창운,이동수,정준기,이명철,고창순,이남수,명호진 ( Jong Ho Kim,Jong Soon Kim,Sang Eun Kim,Chang Woon Choi,Dong Soo Lee,June Key Chung,Myung Chul Lee,Chang Soon Koh,Nam Soo Lee,Ho Jin Myung,) 대한핵의학회 1991 핵의학 분자영상 Vol.25 No.1

腦肉芽腫의 腦波所見 : 전산화 단층촬영술과의 상관관계를 중심으로 in correlation with brain C.T. findings

李景哲,明好鎭 大韓神經精神醫學會 1982 신경정신의학 Vol.21 No.4

The authors analyzed the electroencephalgraphic findings of 36 patients diagnosed as brain granuloma which are confirmed by C.T. scan. More often EEG records were read as "within normal limit" in cases which had less frequent attacks of clinical seizure. Electroencephalographic records showed polymorphic delta activity in 33.3% of patients involving cerebral white matter and depressed background amplitude in only 13.9% involving cerebral cortex. This incidence of abnormal electroencephalographic findings in brain granuloma is relatively low compared to that of rapid growing brain tumor. The focal abnormalities of electroencephalography were found in 61.6% of patients. Therefore we concluded the serial recordings of electroencephalography are relatively useful methods in evaluating the prognosis of brain granuloma.