• Title/Summary/Keyword: K_{cat}/K_m$

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Role of Catecholamines in Ventricular Fibrillation (Catecholamines에 관(關)하여 -제4편(第四編) : 심실전동발생(心室顫動發生)에 있어서의 catecholamines의 의의(意義)-)

  • Lee, Woo-Choo
    • The Korean Journal of Pharmacology
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    • v.19 no.1
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    • pp.15-35
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    • 1983
  • Although it has been well known that ventricular fibrillation is the most important complication during hypothermia, much investigation has failed to show the exact nature of the etiology of ventricular fibrillation. Recently, there has been considerable research on the relationship between sympathetic activity and ventricular fibrillation under hypothermia. Cardiac muscle normally contains a certain amount of norepinephrine and the dramatic effect of this catecholamines on the cardiac muscle is well documented. It is, therefore, conceivable that cardiac catecholamines might exert an influence on the susceptibility of heart muscle to tachycardia, ventricular fibrillation and arrhythmia, under hypothermia. Hypothermia itself is stress enough to increase tonus of sympatheticoadrenal system. The normal heart is supplied by an autonomic innervation and is subjected to action of circulating catecholamines which may be released from the heart. If the reaction of the heart associated with a variable amount of cardiac catecholamines is. permitted to occur in the induction of hypothermia, the action of this agent on the heart has not to be differentiated from the direct effects of cooling. The studies presented in this paper were designed to provide further information about the cardio-physiological effects of reduced body temperature, with special reference to the role of catecholamines in ventricular fibrillation. Healthy cats, weighing about 3 kg, were anesthetized with pentobarbital(30 mg/kg) intraperitoneally. The trachea was intubated and the endotracheal tube was connected to a C.F. Palmer type A.C. respirator. Hypothermia was induced by immersing the cat into a ice water tub and the rate of body temperature lowering was $1^{\circ}C$ per 5 to 8 min. Esophageal temperature and ECG (Lead II) were simultaneously monitored. In some cases the blood pH and serum sodium and potassium were estimated before the experiment. After the experiment the animals were killed and the hearts were excised. The catecholamines content of the cardiac muscle was measured by the method of Shore and Olin (1958). The results obtained are summarized as follows. 1) In control animal the heart rate was slowed as the temperature fell and the average pulse rates of eight animals were read 94/min at $31^{\circ}C$, 70/min at $27^{\circ}C$ and 43/min at $23^{\circ}C$ if esophageal temperature. Ventricular fibrillation was occurred with no exception at a mean temperature of $20.3^{\circ}C(21-l9^{\circ}C)$. The electrocardiogram revealed abnormal P waves in each progressive cooling of the heart. there was, ultimately, a marked delay in the P-R interval, QRS complex and Q-T interval. Inversion of the T waves was characteristic of all animals. The catecholamines content of the heart muscle excised immediately after the occurrence of ventricular fibrillation was about thirty percent lower than that of the pre-hypothermic heart, that is, $1.0\;{\mu}g/g$ wet weight compared to the prehypothermic value of $1.41\;{\mu}g/g$ wet weight. The changes of blood pH, serum sodium and potassium concentration were not remarkable. 2) By the adrenergic receptor blocking agent, DCI(2-3 mg/kg), given intramuscularly thirty minutes before hypothermia, ventricular fibrillation did not occur in one of five animals when their body temperature was reduced even to $16^{\circ}C$. These animals succumbed at that low temperature, and the changes of heart rate and loss of myocardial catecholamines after hypothermia were similar to those of normal animals. The actual effect of DCI preventing the ventricular fibrillation is not predictable. 3) Administration of reserpine(1 mg/kg, i.m.) 24 hours Prior to hypothermia disclosed reduced incidence of ventricular fibrillation, that is, six of the nine animals went into fibrillation at an average temperature of $19.6^{\circ}C$. By reserpine myocardial catecholamines content dropped to $0.045\;{\mu}g/g$ wet weight. 4) Bretylium pretreatment(20 mg/kg, i.m.), which blocks the release of catecholamines, Prevented the ventricular fibrillation under hypothermia in four of the eight cats. The pulse rate, however, was approximately the same as control and in some cases was rather slower. 5) Six cats treated with norepinephrine(2 mg/kg, i.m.) or DOPA(50 mg/kg) and tranylcypromine(10 mg/kg), which tab teen proved to cause significant increase in the catecholamines content of the heart muscle, showed ventricular fibrillation in all animals under hypothermia at average temperature of $21.6^{\circ}C$ and the pulse rate increased remarkably as compared with that of normal. Catecholamines content of cardiac muscle of these animals markedly decreased after hypothermia but higher than control animals. 6) The functional refractory periods of isolated rabbit atria, determined by the paired stimulus technique, was markedly shortened by administration of epinephrine, norepinephrine and isoproterenol. 7) Adrenergic beta-blocking agents, such as pronethalol, propranolol and sotalol(MJ-1999), inhibited completely the shortening of refractory period induced by norepinephrine. 8) Pretreatment with either phenoxftenbamine or phentolamine, an adrenergic alphatlocking agent, did not modify the decrease in refractory period induced by norepinephrine. From the above experiment it is possible to conclude that catecholamines play an important role in producing ventricular fibrillation under hypothermia. The shortening of the refractorf period of cardiac muscle induced by catecholamines mar be considered as a partial factor in producing ventriculr fibrillaton and to be mediated by beta-adrenergic receptor.

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Genetic Alteration of Tumor Suppressor Gene and Microsatellite in Nonsmall Cell Lung Cancer (비소세포폐암에서 종양억제유전자와 극소위성 변이에 관한 연구)

  • Shin, Tae-Rim;Hong, Young-Sook;Kim, Jhin-Gook;Chang, Jung-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.4
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    • pp.453-465
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    • 2000
  • Background : Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH). Methods : We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53. Results : In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location of microsatellite, D3S1285 as a marker of FH1T was observed in 5 cases out of 26 specimens; D9S171 as a marker of p16 in 5 out of 17; and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally. Conclusion : Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

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Formation of Superoxide Anion in the Autoxidation of L-Ascorbic Acid in the Presence of Heavy Metal Ions (중금속 이온 존재하에서의 아스코르빈산 자동산화 과정에서 $O_2\bar{{\bullet}}$ 생성)

  • Kim, Mi-Ok
    • Korean Journal of Food Science and Technology
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    • v.33 no.3
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    • pp.378-383
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    • 2001
  • Formation of superoxide anion $O_2\bar{{\bullet}}$ in the autoxidation of L-ascorbic acid (AsA) in the presence of heavy metal ions were determined. The generation of $O_2\bar{{\bullet}}$ was studied by using superoxide dismutase (SOD) in aqueous and buffer solution, and using nitro bule tetrazolium (NBT) in methanol solution. The remaining amount of AsA was significantly higher in the presence of SOD than in its absence. It suggested that SOD stabilizes AsA in aqueous and buffer solution because of scavenging $O_2\bar{{\bullet}}$ formed during the autoxidation reaction of AsA in the presence of heavy metal ions. NBT has an absorption maximum at about 560 nm in methanol solution. The absorbance at 560 nm increased during the oxidation of AsA, suggested the formation of $O_2\bar{{\bullet}}$in methanol solution. Thus, the formation of $O_2\bar{{\bullet}}$ was confirmed during the autoxidation of AsA not only in aqueous solution but also in methanol solution in the presence heavy metal ions.

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Certains problemes fondamentaux de la syntaxe $reconsid{\acute{e}}r{\acute{e}}s$ du point de vue de la syntaxe positionnelle (위치통사론을 통해 살펴 본 몇 가지 통사론의 본질적 문제)

  • Leem, Jai-Ho
    • Lingua Humanitatis
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    • v.7
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    • pp.271-289
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    • 2005
  • Dans cet article, nous discutons de certains $probl{\grave{e}}mes$ syntaxiques en ayant recours $\grave{a}$ la $th{\acute{e}}orie$ linguistique de Milner. Nous remettons en question $l'ind{\acute{e}}pendance$ et $l'identit{\acute{e}}$ de la structure syntaxique, la relation entre le plan syntaxique et le plan lexical, le $caract{\grave{e}}re$ de la $g{\acute{e}}om{\acute{e}}trie$ de la syntaxe, etc.. La discussion est non seulement linguistique mais aussi interdisciplinaire et ${\acute{e}}pist{\acute{e}}mologique$, dans la mesure $o{\grave{u}}$ nous examinons la nature de $l'entit{\acute{e}}$ syntaxique et la $m{\acute{e}}thode$ "scientifique" de la syntaxe qui donne $acc{\grave{e}}s$ $\grave{a}$ $l'entit{\acute{e}}$ syntaxique. Selon Milner, il faut distinguer la place du terme lexical avec la position syntaxique qui est $l'entit{\acute{e}}$ syntaxique. La $premi{\grave{e}}re$ n'est pas syntaxique $\grave{a}$ strictement parler, mais elle, observable contrairement $\grave{a}$ la seconde, sert $\grave{a}$ conjecturer la dimension syntaxique, $c'est-\grave{a}-dire$ le $syst{\grave{e}}me$ positionnel. Le dispositif $th{\acute{e}}orique$ dans la $th{\acute{e}}orie$ linguistique de Milner n'est rien d'autre que l'ensemble des propositions qui permet, en absence d'observatoire, de conjecturer le $syst{\grave{e}}me$ positionnel sur la base du $syst{\grave{e}}me$ des places. Dire $l'ind{\acute{e}}pendance$ de la structure syntaxique revient $\grave{a}$ dire qu'il y a une coupure entre le $syst{\grave{e}}me$ positionnel et le $syst{\grave{e}}me$ des places. Autrement dit, sans cette coupure, on ne peut parler de $l'ind{\acute{e}}pendance$ de la structure syntaxique. Ainsi $distingu{\acute{e}}s$, les deux $syst{\grave{e}}mes$ en cause se mettent en relation soit naturels soit non naturels ou par distorsion $d'apr{\grave{e}}s$ Milner. La relation naturelle est une relation lexico-syntaxique $n{\acute{e}}e$ au moment $o{\grave{u}}$ un terme lexical occupe une position syntaxique dont la $cat{\acute{e}}gorie$ est identique $\grave{a}$ celle de son occupant. A la $diff{\acute{e}}rence$ de cette relation d'occupation naturelle $suppos{\acute{e}}e$ chez Milner comme une tendance du langage naturel, la relation d'occupation non naturelle est "paradoxale" dans le sens $o{\grave{u}}$ elle est produite dans la rencontre plus ou moins "anomale" entre l'occupant lexical et $l'occup{\acute{e}}$ syntaxique. Le $degr{\acute{e}}$ de l'anomalie qu'une langue autorise peut ${\hat{e}}tre$ $mesur{\acute{e}}$ empiriquement et doit ${\hat{e}}tre$ $vari{\acute{e}}$ en fonction de la langue $concern{\acute{e}}e$. Le $caract{\grave{e}re$ $g{\acute{e}}om{\acute{e}}trique$ de la syntaxe $am{\grave{e}}ne$ ${\grave{a}}$ remettre en cause, entre autres, $l'empiricit{\acute{e}}$ et la $mat{\acute{e}}rialit{\acute{e}}$ de la $g{\acute{e}}om{\acute{e}}trie$ syntaxique. En ce qui concerne ces sujets, nos $th{\grave{e}}ses$ sont les suivantes : la nature de la $g{\acute{e}}om{\acute{e}}trie$ syntaxique n'est pas a priori mais empirique ; la $g{\acute{e}}om{\acute{e}}trie$ de la syntaxe peut et doit ${\hat{e}}tre$ construite $\grave{a}$ l'aide de la logique "empirique".

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Ultrastructural Changes on the Cuticular Surface, Excretory and Digestive Organs of Anisakis simplex Larvae Chronologically Recovered from Experimental Cats (실험감염 고양이로부터 경시적으로 회수한 고래회충 유충의 표피, 배설기 및 소화기의 미세구조 변화)

  • Sohn, Woon-Mok
    • Applied Microscopy
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    • v.29 no.2
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    • pp.211-221
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    • 1999
  • The ultrastructural changes of cuticular surface, excretory and digestive organs of Anisakis simplex larvae chronologically recovered from experimental cats were observed with a SEM and TEM. The larva recovered from an experimental cat at 3 days post-infection (PI) retained the cuticular surface with regular transverse striations and a longitudinal groove on the lateral side of body. This finding suggests that the molting of the 3rd stage larva of A. simplex to 4th one occurred from the 3rd day after infection in cats. The excretory organ (renette cell) consisted of a large cell with numerous ductules ramified from the main duct, mitochondria and secretory granules in cytoplasm. Secretory granules in the renette cell of larvae recovered at 24 hours PI were round whereas those of control and larvae recovered at 6 hours PI were amorphous. Muscular esophagus and ventriculus also retained many secretory granules in the cytoplasm. The secretory granules in these organs of larvae recovered at $6\sim24$ hours PI were electron-dense and widely distributed whereas those of control worm were packed in a pocket and retained various electron densities. In the cytoplasm of intestinal epithelial cells, numerous fine glycogen particles and mitochondria were distributed. The chronological changes of secretory granules in renette cell, muscular esophagus and ventriculus seem to be related with the worm penetration into host tissue.

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