• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.19-29
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• 1996

The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.267-273
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• 2003

We have investigated the effect on inducing substate(s) of positively charged residues replaced in position 172 of the second transmembrane domain in murine inward rectifier potassium channels, formed by stable or transient transfection of Kir2.1 gene in MEL or CHO cells. Single channel recordings were obtained from either cell-attached patches or inside-out patches excised into solution containing 10 mM EDTA to rule out the effect of $Mg^{2+}$ on the channel gating. The substate(s) could be recorded with all mutants D172H, D172K and D172R. The unitary current-voltage (I-V) relation was not linear with D172H at $pH_i$ 6.3, whereas the unitary I-V relation was linear at $pH_i$ 8.0. The relative occupancy at $S_{LC}$ was increased from 0.018 at $pH_i$ 8.0 to 0.45 at $pH_i$ 5.5. In H-N dimer, that was increased from 0.016 at $pH_i$ 8.0 to 0.23 at $pH_i$ 5.5. The larger the size of the side chain or $pK_a$ with mutants (D172H, D172K and D172R), the more frequent the transitions between the fully open state and substate within an opening. The conductance of the substate also depended upon the pKa or the size of the side chain. The relative occupancy at substate $S_{LC}$ with monomer D172K (0.50) was less than that in K-H dimer (0.83). However, the relative occupancy at substate with D172R (0.79) was similar to that with R-N dimer (0.82). In the contrary to ROMK1, positive charge as well as negative charge in position 172 can induce the substate rather than block the pore in murine Kir2.1. The single channel properties of the mutant, that is, unitary I-V relation, the voltage dependence of the mean open time and relative occupancy of the substates and the increased latency to the first opening, explain the intrinsic gating observed in whole cell recordings.

• 대한한의학원전학회지
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• 제10권
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• pp.450-493
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• 1997

Three-yum and three-yang(三陰三陽) is the change state of yum-yang(陰陽) which is caused by six gi(六氣). They mean the flow of six gi(六氣) which exist throughout the viscera, the channel(經絡), and the skin. But it is not easy to understand the meaning because the contents of the attribute of three-yum and three-yang(三陰三陽), the bolt-leaf-hanges(關闔樞) theory and large or small of gi-blood(氣血多少) which is the main clue that explain it in ${\ll}$Somun(素問)${\gg}$ and ${\ll}$Yeongchu(靈樞)${\gg}$ don't coincide with each other. I, the writer, tried to understand the uncertain meaning and the contents which are written about three points above differently in each of the books that are ${\ll}$Somun(素問)${\gg}$ and ${\ll}$Yeongchu(靈樞)${\gg}$. So, from that the course that the book, ${\ll}$Huangjenegeong(黃帝內經)${\gg}$ is handed down is so relatively simple in a wood block-printed book, that the ${\ll}$Huangjenegeongtaeso(黃帝內經太素)${\gg}$ has less wong-words than the Somun(素問) and the Yeongchu(靈樞), and from that Yangshangsun(楊上善) wrote the note in the ${\ll}$Huangjenegeongtaeso(黃帝內經太素)${\gg}$ by royal order about 100 years former than Wangbing(王氷), as making projects of Yangshangsun(楊上善)'s note and the original of the ${\ll}$Huangjenegeongtaeso(黃帝內經太素)${\gg}$ which has relation to the yum-yang(陰陽) attribute of three-yum and three-yang(三陰三陽), the bolt-leaf-hanges(關闔樞) theory, and the large or small of gi-blood(氣血多少) and researching the Yangshangsun(楊上善)'s theory. The result is summarized like this. First, wherease the order of the change of three-yum and three-yang(三陰三陽) which is explained by Yangshangsun(楊上善) consider the change of yangi(陽氣) in body most important, the order of the change gaeggi(客氣)'s three-yum and three-yang(三陰三陽) considers chungi(天氣) most important, and the order of jugi(主氣)'s three-yum and three-yang(三陰三陽) considers jigi(地氣)'s change of ohaeng(五行) most important. If the order of change three-yum and three-yang(三陰三陽) in the ${\ll}$Huangjenegeongtaeso(黃帝內經太素)${\gg}$ is considered, each of taeyang(太陽) and soyum(少陰) are expressed as the base of yum-yang(陰陽) and yangmeong(陽明) and taeyum(太陰) are expressed as the palmy days of yum-yang(陰陽), soyang(少陽) and gyolyum(厥陰) are expressed as pacemaker(樞杻) which controls the change of yum-yang(陰陽). Thus, each has something in common that is fettered by the inside and outside. In the flow of channel(經絡), taeyang(太陽) and soyum(少陰) take charge of the behind of body, yangmeong(陽明) and taeyum(太陰) take charge of the front of body and soyang(少陽) and gyolyum(厥陰) take of the side of body. Second, in Yangshangsun(楊上善)'s bolt-leaf-hanges(關闔樞) theory, three-yum(三陰) is regarded as inside, three-yang(三陽) as outside, so when bolt, leaf and hanges fulfil their duties in inside and outside, the life(life force) is thought to be revealed normally. It is impossible to understand the bolt-leaf-hanges with the conception of the inside and outside which divide three-yum and three-yang(三陰三陽) into taeyang-soyum(太陽-少陰), yangmeong-taeyum(陽明-太陰), soyang-gyolyum(少陽-厥陰) according to yum-yang(陰陽) attribute, hence it need the special conception that is taeyang(太陽)-taeyum(太陰), yangmeong(陽明)-gyolyum(厥陰), soyang(少陽)-soyum(少陰) which center on their duties in inside and outside. In the denunciation of the word open(開) and bolt(關), because Yangshangsun(楊上善) said that the duities of taeyang(太陽) and taeyum(太陰) are shutter(閉禁), bolt(關) is coincided with that significance. Third, with explaining the large or small of gi-blood(氣血多少) of three-yum and three-yang(三陰三陽), Yangshangsun(楊上善) expressed the inside and outside either in the same way or differently. Because the inside and outside is interior of body and exterior of body, it is the explanation that is noticed by the fact that the property of large or small of gi-blood(氣血多少) is either able to be same or different. In this viewpoint, if we unite the contents about large or small of gi-blood(氣血多少) of ${\ll}$Somun(素問)${\gg}$, ${\ll}$Yeongchu(靈樞)${\gg}$, we will find that the descriptions of large or small of gi-blood(氣血多少) of three-yang(三陽) in ${\ll}$Somun(素問)${\gg}$ ${\ll}$Yeongchu(靈樞)${\gg}$ correspond with the ${\ll}$Huangjenegeongtaeso(黃帝內經太素)${\gg}$, but in three-yum(三陰), the contrary presentations exit. The reason is that large or small of gi-blood(氣血多少) of three-yum(三陰) isn't only expressed as che(體) in the point of che-yong(體用), but as a point of yong(用) that is a phenomenon. As researching the original of ${\ll}$Huangjenegeongtaeso(黃帝內經太素)${\gg}$ and Yangshangsun(楊上善)'s notes as a center about three problems that are yum-yang(陰陽) attribute, the bolt-leaf-hanges(關闔樞) and large or small of gi-blood(氣血多少) of three-yum and three-yang(三陰三陽), I, the writer, tried to explain the part which is written differently or has uncertain conception in the book ${\ll}$Somun(素問)${\gg}$ and the book ${\ll}$Yeongchu(靈樞)${\gg}$, but the concrete result of the work like this will be judged according to the question how many theories are correspondent with real presence at a sickbed. Hence, the work to veryfy the theories in the future will be left as assignment.

• 한국산림과학회지
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• 제32권1호
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• pp.36-63
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• 1976

1974년(年) 천연(天然)소나무집단(集團)에 대한 유전적변이(遺傳的變異)를 분석(分析)하고져 먼저 경북(慶北) 청송군(靑松郡) 소재(所在) 주왕산(周王山)소나무림(林), 충남(忠南) 서산군(瑞山郡) 소재(所在) 안면도(安眠島) 소나무림(林), 그리고 강원도(江原道) 평창군(平昌郡) 소재(所在) 소나무림(林)을 대상(對象)으로하여 각(各) 집단(集團)에서 되도록 소면적(小面積)의 범위내(範圍內)에 서있는 소나무 개체(個體)를 각(各) 20주(株)씩 총 60주(株)를 택(擇)하여 그 모수(母樹)에 대한 형태학적(形態學的) 특성(特性)등을 조사측정(調査測定)하고 집단간(集團間)에 보이는 차이(差異) 그리고 한 집단내(集團內)에 있는 각개체수목(各個體樹木)의 형질(形質)을 조사보고(調査報告)한바 있다(제일보고문(第一報論文). 1974년(年) 가을에 가계별(家系別)로 종자(種字)을 채취(採取)하여서 가계별(家系別) 및 산지별(産地別)의 차이(差異)를 분석(分析)하고 동시(同時)에 그 종자(種字)를 파종하여서 1-0묘(苗) 및 1-1묘(苗)를 대상(對象)으로 생장인자(生長因子)에 대한 측정(測定)을 하고 그 유전력(遺傳力)을 계산(計算)해 보았다. 그밖에 엽록소함량(葉綠素含量) 또는 monoterpene등의 함량(含量)의 차이(差異)를 분석(分析)해 보았다. 종자(種字)의 형태학적(形態學的) 특성(特性)에 있어서는 집단간(集團間) 또 가계간(家系間)에 유의차(有意差)를 보이지 않는 것도 있었으나 대체(大體)로 유의차(有意差)가 인정(認定)되었다. 그리고 각형질간(各形質間)의 상관(相關)을 보았는데 구과폭(毬果幅)과 종자익(種字翼)의 폭(幅), 구과장(毬果長)과 종자익(種字翼)의 길이간(間), 그리고 구과(毬果) 생중량(生重量)과 종자중량간(種字重量間)에는 정(正)의 상관(相關)이 보였다. 묘고(苗高)와 근원경(根元徑)의 성장(成長)에 있어서는 가계간(家系間) 그리고 집단간(集團間)에 차이(差異)가 인정되었다. 묘고(苗高)의 유전력(遺傳力)은 집단(集團)의 평균치(平均値)를 가지고 분석(分析)하였다. 즉 집단(集團)에 관계(關係)되는 분산(分散)을 유전분산(遺傳分散)으로 보고서 유전력(遺傳力)을 계산(計算)해 보았는데 1-0묘(苗)의 묘고(苗高)에서는 0.29, 1-1묘(苗)에서는 0.14가 그리고 근원경(根元徑)에 있어서는 1-0묘(苗)는 0.15, 1-1묘(苗)에서는 0.06이였다. 기공열수(氣孔列數)에 있어서는 집단간차이(集團間差異)가 있었으나 거치밀도(鋸齒密度)에는 차이(差異)가 없었다. 침엽(針葉)의 특성(特性)에 관(關)해서는 모수(母樹)와 차대간(次代間)에 상관(相關)이 없었다. 엽록소함량(葉綠素含量)은 집단간차이(集團間差異)는 보였으나 가계간차이(家系間差異)는 없었다. monoterpene의 성분(成分)에 있어서는 myrcene과 ${\beta}$-phellandrene의 함량(含量)으로 집단차(集團差)를 볼 수 있었다.