새로운 Anthracycline계 항암제 DA-125의 일반약리작용

김명석,박종완,김영훈,김순회,신명수,김원배,양중익,Kim, Myung-Suk,Park, Jong-Wan,Kim, Young-Hoon,Kim, Soon-Hoe,Shin, Myeong-Soo,Kim, Won-Bae,Yang, Junn-Ick 대한약리학회 1994 대한약리학잡지 Vol.30 No.2

The general pharmacological effects of a new anthracycline anticancer agent, DA-125 $[7-0-(2,\;6-dideoxy-2-fluoro-{\alpha}-L-talopyranosyl)-adriamycinone-14-{\beta}-alaninate{\cdot}HCI]$ were investigated in mice, rats, guinea pigs, rabbits and dogs. Intravenous administration of DA-125 presented no significant effects on the central and peripheral nervous systems of ICR mice except a decrease in the numbers of acetic acid-induced writhing response at a dose of 10 mg/kg. In anesthetized rats and dogs, DA-125 produced a transient depression of blood pressure and an increase in heart rate, but did not affect the peripheral blood flow in the isolated ear vessels of rabbits and the mechanical functions of the isolated hearts of guinea pigs. No significant effects were observed on the gastrointestinal functions and the contractilities of smooth muscle preparations obtained from guinea pig trachea, rabbit ileum, pregnant and non-pregnant uterus and vas deferens of rats. DA-125 Increased the contractility of the isolated ileum of guinea pigs in a dose range of $10^{-6}{\sim}10^{-9}g/ml$, and also increased, but weaker than adriamycin, the vascular permeability in rat skin. DA-125 had no effect on the kallikrein-induced increase in permeability and the permeability of the visceral organs. DA-125 did not adversely affect the liver function and the blood coagulation system, and did not induce hemolysis in vitro. It is concluded from the results that the general pharmachological effects of DA-125 are similar to or weaker than those of adriamycin, and that little adverse effects are anticipated with a therapeutic dose range.

흰쥐의 위산분비 및 혈장 Gastrin농도에 미치는 대상회전 제거의 영향

김명석,조양혁,김태욱,최현,Kim, Myung-Suk,Jo, Yang-Hyeok,Kim, Tae-Uk,Choi, Hyun 대한생리학회 1984 대한생리학회지 Vol.18 No.2

It has been recently reported that cingulate cortex mar facilitate gastric acid secretion, but its facilitatory mechanism on the gastric acid secretion is still unclear. This study was undertaken to investigate the facilitatory mechanism of the cingulate cortex upon gastric acid secretion in rats. Twenty·three male albino rats were divided into the cingulate(N= 13) and the operated control(N= 10) groups. The cingulate group in which cingulate cortex was removed by suction through a slit-shaped opening on each side of, and parallel to, the sagittal suture. In the operated control group, the surgical procedure was ended with the skull opening and the incision of dura mater. The gastric juice was collected via a chronic gastric cannula after 24 hours of fast, with water ad libitum. The juice was collected continuously for 6 hours, starting 3 hours prior to the injection of gastric secretagogue, pentagastrin$(12\;{\mu}g/kg)$ or histamine dihydrochloride $(320\;{\mu}g/kg)$. Three one·hour samples were obtained before ana after the administration of each secretagogue. The two agents were injected separately and subcutaneously at intervals of 1 week, the blood samples were drawn from the abdominal aorta for the radioimmunoassay of postprandial plasma gastrin concentration in response to the forced feeding of 10% cod liver oil. 1) After pentagastrin administration, the volume of gastric juice tended to decrease, but its acidity tended to increase in the cingulate group compared with those of the operated control group. However, there was no any difference in the acid output between the two groups. 2) Histamine-stimulated acid output and volume of the gastric juice of the cingulate group decreased significantly compared with those of the operated control group, while there was not significantly different in the acidity between the two groups. 3) Before pentagastrin or histamine administration, any change was not observed in the gastric acid secretion following the cingulate cortical ablation. 4) Postprandial plasma gastrin concentration in response to the forced feeding of 10% cod liver oil was insignificantly lower in the cingulate group than in the operated control group. It is inferred from the above results that the cingulate cortex exerts a facilitatory influence upon the histamine-stimulated gastric acid secretion in rats, and its influence may not be mediated by the stimulation of gastrin secretion.

적출한 고양이 위(胃)의 전기활동에 미치는 prostaglandin $E_2$ 및 indomethacin의 영향

김명석,이윤렬,Kim, Myung-Suk,Lee, Yoon-Lyur 대한생리학회 1983 대한생리학회지 Vol.17 No.1

This study was conducted to investigate the effect of prostaglandin $E_2(PGE_2)$ and indomethacin upon the electrical activity of the isolated cat stomach muscle strips$(1.5{\times}7.0\;cm)$. Fifty-seven muscle strips, obtained from 57 cat stomachs(including corpus and antrum) were studied in a muscle chamber filled with Krebs solution(pH 7.4, temperature $36{\pm}0.5^{\circ}C$) aerated with 5% $CO_2$ in $O_2$. The electrical activity was recorded by five capillary electrodes (Ag-AgCl), of which two were placed on the corpus and three on the antrum. After recording of the electrical activity in normal Krebs solution, $PGE_2$ in concentrations of 0.25(N=7), 0.5(=7), 1(N=7) and $2{\times}10^{-7}\;M(N=6)$ were administered to 27 muscle strips, while indomethacin was applied in concentretions of 0.25(N=9), 0.5(N=10), 1(N=6) and $2{\times}10^{-3}\;M(N=5)$ to the remaining 30 strips. The mean frequency were minutely measured from each electrogastrogram. 1) By adding $PGE_2$ in all doses, gastric slow wave frequency increased significantly compared with that in resting state. 2) Following $PGE_2$ administration, peak slow wave frequency increased dose-dependently. 3) After indomethacin addition in all doses, the slow wave frequency decreased significantly compared with that in resting state. 4) Following indomethacin administration, incidence of complete abolition of slow wave increased dose-dependently, and its latent period decreased also in a dose-dependent manner. It is inferred from the above results that prostaglandin $E_2$ has a facilitatory role in the development of gastric slow wave in cat.

고양이 위(胃)의 수축 및 전기활동에 대한 에탄올과 칼슘의 관계

김명석,심상수,윤신희,한상준,김정진,최현,Kim, Myung-Suk,Sim, Sang-Soo,Yoon, Shin-Hee,Han, Sang-Jun,Kim, Chung-Chin,Choi, Hyun 대한생리학회 1987 대한생리학회지 Vol.21 No.2

This was study carried out to investigate the effect of calcium on spontaneous contraction and electrical activity induced by ethanol in gastric smooth muscle. After peeling off the mucous membrane from the isolated whole stomach of 102 cats, two kinds of small muscle preparations $(2.0{\times}0.2\;cm)$, one longitudinal and the other circular, were excised from the fundus, the corpus and the antrum portion of each whole stomach specimen. The isometric contraction of the small muscle preparation was measured in a cylinder-shaped chamber filled with Krebs-Ringer-dextrose solution (pH 7.4, temperature $36{\pm}0.5^{\circ}C$) bubbling with 5% $CO_2$ in $O_2$. A large muscle preparation $(5.0{\times}1.2\;cm)$ was excised from the anterior wall of the corpus-antrum portion of the same specimen in 72 of 102 cats. The gastric electrical activity (slow wave and spike potential) was monopolarly recorded by four capillary electrodes (Ag-AgCl), of which two were placed on the corpus and two on the antrum, in a muscle chamber filled with the same solution as described above. Changes in the amplitude of the contraction, frequency of the gastric slow wave and the production of the spike potential were observed after adding ethanol and/or under the treatments with verapamil, $CaCl_2$ and Ca-free Krebs-Ringer-dextrose solution. The results were as follows: 1) After adding ethanol, the spontaneous phasic contraction of the corpus was reduced dose-dependently (0.125-2.0%), which was totally abolished by higher concentrations (2.0-8.0%) of ethanol. 2) The corporal phasic contraction was also completely abolished by verapamil $(3{\times}10^{-5}\;M)$ or Ca-free Krebs-Ringer-dextrose solution. The contraction was increased by $CaCl_2\;(1.8{\times}10^{-3}\;M)$, but the inhibitory effect of ethanol on the contraction persisted even under the treatment with $CaCl_2$. 3) At higher concentrations, ethanol caused tonic contraction of both preparations from the fundus, the corpus and the antrum in a dose-dependent manner. The tonic contraction of the fundus produced by ethanol was not influenced by $CaCl_2$ or verapamil, whereas the tonic contraction was not produced by ethanol in tile Ca-free solution. 4) Frequency of gastric slow wave was decreased dose-dependently by the addition of ethanol (0.25-1.0%), and tile slow wave was not produced by higher concentration of ethanol (2.0%). 5) The frequency of slow wave was significantly reduced by verapamil only and the inhibitory influence of ethanol on the slow wave frequency was reinforced by verapamil. 6) The treatment of $CaCl_2$ increased significantly the slow wave frequency, and attenuated the inhibitory effect of ethanol on the frequency. It is therefore suggested that ethanol regulates the phasic contraction and the production of slow wave by interfering with the transport of calcium in the stomach muscle of the cat.

$Na^+$ 및 $K^+$에 의한 심장근 Mitochondria에서의 $Ca^{++}$ 유리작용

김명석,Kim, Myung-Suk 대한약리학회 1978 대한약리학잡지 Vol.14 No.1

가토 심실근에서 추출한 mitochondria에서 $Na^+$ 및 $K^+$이온에 의한 $Ca^{++}$ 유리작용을 관찰하였다. 반응액에 첨가한 1-3mM의 소량 $Na^+$은 mitochondria막에 미리 결합되어있던 $Ca^{++}$을 현저히 유리시켰으며, $K^+$은 단독으로는 $Ca^{++}$ 유리를 유도하지 않았으나 $Na^+$에 의한 $Ca^{++}$ 유리에 대하여는 $Na^+/K^+$비에 따라 그것이 클수록 $Ca^{++}$ 유리를 증가시켰다. 간 및 신장 mitochondria에서도 $Na^+$에 의하 $Ca^{++}$ 유리현상을 보였으나 심근mitochondria에 비하여 $Na^+$에 대한 감수성이 훨씬 미약하여 약 $1/10{\sim}1/5$에 지나지 않았다. 이와같은 mitochondria의 $Ca^{++}$ 유리현상은 비교적 $Na^+$에 특이한 작용이었으며 다른 일가양이온중에서는 $Li^+$에 의해서만 어느 정도 보였다. 부전심근 mitochondria에서의 $Na^+$에 의한 $Ca^{++}$유리는 정상심근 mitochondria에서와 같았으며 이때 digitalis 강심배당체가 직접적으로는 별 영향을 미치지 않았다. 이상에서 심근의 경우 mitochondria는 세포내 $Ca^{++}$을 조절할 수 있는 기구로서 심근수축의 E-C coupling과정에서 세포막의 전기적 흥분현상과 결부하여 $Ca^{++}$을 유리할 수 있을 것으로 추정하였으며, 한편 digitalis배당체의 강심작용기전에 있어서는 digitalis 배당체에 의한 세포막의 $Na^+$, $K^+$-ATPase 억제결과 초래될 수 있는 세포내의 $Na^+$ 증가 및(또는) $K^+$감소가 간접적으로 mitochondria에서부터 $Ca^{++}$ 유리를 증가하여 E-C coupling 과정을 촉진할 수 있을 것을 사료하였다. The $Na^+$-and $K^+$-induced $Ca^{++}$ release was measured isotopically by Milipore filter technique in mitochondria isolated from rabbit ventricles. The release of $Ca^{++}$ from mitochondria could be induced by 1-3 mM of $Na^+$ added in incubating medium under the presence of 0.5mM EGTA to prevent the released $Ca^{++}$ from rebinding with mitochondrial membrane. The amount of $Ca^{++}$ released was increased by increasing the concentration of $Na^+$ added. 100mM $K^+$, in itself, did not induce the $Ca^{++}$ release from cardiac mitochondria, the $Na^+$-induced $Ca^{++}$ release, however, was potentiated by the presence of $K^+$. The potentiation of $Na^+$-induced $Ca^{++}$ release by $K^+$ was proportional to the $Na^+/K^+$ ratio presented in the incubating medium. Among the monovalent cations other than $Na^+$, the release of $Ca^{++}$ from cardiac mitochondria was shared only by $Li^+$. The $Na^+$-induced $Ca^{++}$ release could be also observed in the mitochondria isolated from liver and kidney. However, the $Na^+$ sensitivity was somewhat lower in liver and kidney mitochondria than in heart mitochondria. The release of $Ca^{++}$ induced by $Na^+$ in the mitochondria isolated from the experimentally produced failured heart was not different from that in the normal heart mitochondria, and was not directly modified by $10^{-6}{\sim}10^{-5}$ M of Ouabain. From the experiments, it was suggested that the $Ca^{++}$ released from mitochondria by $Na^+$ could be used in excitation-contraction coupling process to initiate the contraction of the cardiac myofibrils. Futhermore, it appeared that the phenomenon of $Ca^{++}$ release from cardiac mitochondria by $Na^+$ and $K^+$ might be related to the inotropic effect of digitalis glycoside which could bring about the increase of $Na^+$ or the reduction of $K^+$ intracellulary through the inhibition of $Na^+$, $K^+$-ATPase.

깨죽이 정상 성인의 혈장 Gastrin 농도에 미치는 영향

김명석,이윤렬,권경옥,조양혁,박형진,Kim, Myung-Suk,Lee, Yoon-Lyeur,Kwon, Kyoung-Ok,Jo, Yang-Hyeok,Park, Hyoung-Jin 대한생리학회 1982 대한생리학회지 Vol.16 No.2

This study was conducted to investigate the effect of ingestion of sesame (Sesamum indicum) gruel as a nourishing meal upon the plasma gastrin concentration in normal Korean. Sixteen normal persons with no history of gastrointestinal diseases, including male and female were studied. After an overnight(about 15 hrs) fast, eight persons(mean age: 26.6, range: $20{\sim}40$ years) of them ingested a 350 ml sesame gruel corresponding to 12 g protein, 13 g fat and 99 g carbohydrate, and the remaining 8 subjects(mean age: 21.3, range: $20{\sim}24$ years) ingested a 350 ml glutinous rice gruel(control meal) corresponding to 8 g protein, 1 g fat and 115 g carbohydrate. The venous blood samples were drawn before and after the ingestion of the test meal for the measurement of gastrin by means of radioimmunoassay. 1) Plasma gastrin concentration in response to the ingestion of sesame gruel or glutinous rice gruel increased significantly compared with the concentration in fasting state. 2) Mean increment or percent increment in postprandial plasma gastrin concentration after the ingestion of sesame gruel was not significantly different from that after the control meal, i.e. the glutinous rice gruel. It is inferred from the above results that the ingestion of sesame contained in sesame gruel may have no significant influence on gastrin release in normal human subjects.

자율신경계에 작용하는 약물이 위장 전기도에 미치는 영향

김명석,박형진,배선호,최현,김철,Kim, Myung-Suk,Park, Hyoung-Jin,Bai, Sun-Ho,Choi, Hyun,Kim, Chul 대한생리학회 1980 대한생리학회지 Vol.14 No.2

In order to investigate the effect of cholinergic substance on the electrical and the mechanical activities of the stomach muscle, 10 isolated cat stomachs were studied. At various sites of a stomach muscle preparation, the electrical activity was monopolarly recorded by using capillary electrodes containing chlorided silver wires, and the isometric contractile activity was recorded simultaneously at the terminal portion of the antrum in Krebs solution$(36^{\circ}C)$ which was aerated with a gas mixture consisting of 95% $O_2$ and 5% $CO_2$. The recording of these activities were performed before (control period) and after acetylcholine$(10^{-5}M)$ and atropine $(10^{-6}M)$ administrations serially. Following results were obtained: 1) The mean frequency of the slow wave was $4.36{\pm}0.22\;cycles/min$ at all the various sites of the cat stomach. The slow wave was propagated caudad in sequence and its velosity of propagation increased as the slow wave approached the pylorus in normal Krebs solution. 2) After acetylcholine administration, the frequency of the slow wave increased transiently and the increase of slow wave frequency was followed by the isometric contraction of antral muscle in association with the second potential which succeeded the slow wave. 3) By atropine administration, the stimulatory effect of acetylcholine on the antral muscle contraction was abolished completely, and the frequency of the slow wave decreased significantly compared with that of the control period, which tendency was more prominent in the antrum. The above results suggest that the transient increase in the frequency of gastric slow wave by acetylcholine may have some influence upon the contraction mechanism of the cat antral muscle.

Effect of Damage to Medial Amygdaloid Nucleus on Pancreatic Exocrine Secretion Stimulated by Hydrochloric Acid in the Rat

김명석,윤신희,한상준,김미혜,Kim, Myung-Suk,Yoon, Shin-Hee,Hahn, Sang-June,Kim, Mie-Hye The Korean Physiological Society 1988 대한생리학회지 Vol.22 No.2

본 연구는 십이지장내 생리 식염수와 0.01 N HCl을 주입했을때 내측 편도핵의 손상이 췌액 분비와 혈장 secretin 농도에 미치는 영향을 구명하기 위하여 44마리의 수컷 흰쥐를 사용하였다. 그 중 21마리의 흰쥐는 뇌정위 고정장치에 의해 내측 편도핵에 삽입된 전극을 통해 양측성으로 내측 편도핵을 파괴한 내측 편도핵 손상군이고, 나머지 23마리는 편도핵의 손상없이 동일한 수술 조작만을 가한 수술 대조군이다. urethan 마취후에 십이지장 근위부에 위치한 관을 통해 십이지장 내강에 0.01 N HCl 또는 생리 식염수(0.9% NaCl)를 0.18ml/min 속도로 주입하면서 20분간 췌액을 채취하였다. 췌액 체취후 복대동맥에서 채혈하여 혈장 secretin농도를 측정하였다. 내측 편도핵 손상군에서 십이지장내 생리 식염수는 물론 0.01 N HCl 주입에 의한 췌액량은 수술 대조군의 것보다 유의하게 감소하였다. 내측 편도핵 손상군의 췌액내 단백질량은 생리 식염수 주입시 수술대조군의 것보다 유의하게 감소하였고, 0.01 N HCI 주입시에는 유의하지는 않지만 감소한 경향을 보였다. 그러나 기초상태 및 염산 자극에 의한 혈장 secretin 농도는 내측 편도핵의 손상에 의하여 아무런 영향을 받지 않았다. 따라서 내측 편도핵은 기초 상태 및 염산 자극에 의한 췌액의 분비에 촉진적 영향을 미치는 것으로 생각되나, secretin 분비기전이 이 촉진 영향에 관련되는 것으로는 보이지 않는다. This study was undertaken to investigate the effect of the medial amygdaloid nucleus on the pancreatic exocrine secretion and plasma secretin concentration in 44 male albino rats. Twenty-three rats in which the medial amygdaloid nucleus was damaged bilaterally by radio frequency a.c. through stereotaxically inserted electrodes (medical amygdaloid group, MA) and twenty-one rats which received the same operation without damage (operated control, OC), were prepared. Under urethan anesthesia, 0.01 N hydrochloric acid (HCl) or physiological saline (0.9% NaCl) was infused at a rate of 0.18 ml/min into the duodenum for 20 minutes. Pancreatic jucie was collected for the 20 min infusion period. After collection of pancreatic juice, blood was sampled from the abdominal aorta for the radioimmunoassay of plasma secretin concentration. In the MA group, the exocrine pancreatic secretory response to 0.01 N HCI as well as saline infusion was significantly inhibited compared with that in the OC group. The pancreatic protein output of the MA group significantly decreased after the saline infusion and tended to decrease after the 0.01 N HCI infusion, compared with that of the OC group. However, there was no significant difference in plasma secretin concentration between the two groups. Therefore it is strongly suggested that the rat medial amygdaloid nucleus has a facilitatory influence on both basal and acid-stimulated pancreatic exocrine secretion, but the releasing mechanism of secretin appears not to be involved in the influence.

자연재해로 인한 총 피해액의 위험 측정과 지역별 분배 - Copula 기법 적용

김명석 ( Myung Suk Kim ) 한국보험학회 2018 保險學會誌 Vol.116 No.-

자연재해로 인한 피해는, 근접한 여러 지역에 동시다발적으로 발생하여 지역 간 피해액의 종속적 패턴을 보이는 경향이 있다. 특히, 재앙적인 피해를 초래하는 자연재해가 발생할 경우에는 지역별 피해액의 극단치 간의 종속성이 발견될 수 있다. 기존 문헌에는 이러한 지역별 종속성의 영향력을 고려하여 피해액을 추정한 연구는 없었다. 한편, 자연재해로 야기되어지는 피해는 그 규모의 막대함으로 인하여 이에 대한 복구는 대체로 중앙정부와 지방정부의 예산이나 기금으로부터 직접 지원을 받거나, 부분적으로는 풍수해보험과 같은 정책보험을 통하여 이루어져 왔다. 재난 및 재해 관련 지방비의 비중이 점차 증가하고 있는 데도 불구하고, 지방정부가 확보해야 할 정확한 예산규모에 대한 연구도 전무하였다. 본 연구에서는 코퓰라기법과 Tail Value at Risk 기법을 활용하여 재난으로 인한 정확한 피해액을 산정하는 방법을 제시함으로서 향후 중앙정부나 지방정부가 재난 관련 예산 또는 정책보험금 산정에 대비할 수 있는 근거를 제시하였다. 1979년부터 2016년까지의 전국 시도별 자연재해로 인한 연간 총 피해액 자료를 이용하여 지역 간 피해 액의 종속성을 가정하였을 경우의 위험 측정치와 독립성을 가정하였을 경우를 비교하여 종속성이 반영된 경우의 위험 측정치가 반영되지 않았을 경우에 비해서 얼마나 차이가 나는지도 보였다. The losses caused from natural disasters tend to show dependence patterns among the neighboring areas. In particular, the catastrophic losses have resulted in tail dependence between provinces. There has been no studies on the catastrophe risk measurement reflecting the impact of dependence. Meanwhile, the restoration of damage have been mostly funded from the central and local governments budgets. Partly, the damage has been restored by the help of the insurance supported by government like the storm and flood insurance. Regardless of increasing importance of local government support for the recovery, there has been no rigorous research on estimating the precise amount of budget which the local government should secure. This study proposes a novel method of the catastrophe risk measurement and allocation for local areas using the copula and Tail Value at Risk mechanisms. The aggregate annual loss data over several major provinces in Korea during the period from 1979 to 2016 are utilized for the analysis. The risk measure and allocation results using copula-based aggregate loss are compared with those using independence-based aggregate losses.

뉴 오피스 환경과 경영혁신에 관한 연구 ( 2 ) - 기업문화와 오피스 환경 -

김명석(Kim Myung-Suk) 한국가구학회 1991 한국가구학회지 Vol.2 No.2

The greatest social change at present is conversion industrial society to informationized society.<br/> In such organization of society, the number of white collar is larger than that of blue collar, so that importance of office is gathering strength.<br/> <br/> This research was carried out to study relation between corportate culture and office environment through case study of foreign conutries as the second parter of New Office Environment and Innovation of the Management. As the subject of cased study, 5 companies are Asahi Beer, Nihon Kougyo and Bandai of Japan. Hongkong Shanghai Bank and Nederlandse Middenstands Bank.