혈관평활근 수축-연관 신호전달 체계에 대한 Endothelin-1의 역할과 Endothelin-1-유도통증-연관 유해감각 -통증전문물리치료 연구를 위한 기초물리치료학적 접근을 중심으로-

김중환,이숙희,이상빈,최유림,김보경,박주현,구자풍,최완석,안호정,최정현,김무기,김순희,Kim, Jung-Hwan,Lee, Sook-Hee,Lee, Sang-Bin,Choi, Yoo-Rim,Kim, Bo-Kyung,Park, Ju-Hyun,Koo, Ja-Pung,Choi, Wan-Suk,An, Ho-Jung,Choi, Jeong-Hyun,Kim, Moo-Gi 대한물리치료과학회 2006 대한물리치료과학회지 Vol.13 No.2

Endothelin (ET) is a 21 amino acid peptide with multifunctional effects on the vasculature as well as a variety of other cell types such as respiratory, gastrointestinal, urogenital, endocrine, central nervous systems, and others. Endothelin has emerged as a modulator by autocrine and paracrine actions for many cellular activities, including vasoconstriction, cell proliferation, hormone production, neurotransmitter and/or neuromodulator. The endothelin family consists of three closely related peptides, ET-1, ET-2, and ET-3 derived from separate genes, such as chromosome 6, 1, and 20, respectively. ET-1 is the predominant isoform produced in the cardiovascular system and about which most is known. Endothelin receptors are seven-transmembrane GTP-binding protein-coupled receptors, which are classified into endothelin-A (ETA) and endothelin-B (ETB) receptors. Interestingly, recent evidence is accumulating to suggest that ET -1 may contribute to a variety of pain states such as allodynia and hyperalgesia in animals and humans. Therefore, in this review the biological characteristics and contraction-related mechanism of endothelin-1 in mammalian cells will be summarized. Especially, we focus on multifunctional roles for ET-1 in noxious stimulation-induced pain for the study of pain specialized physical therapy.

남성단순임질에 대한 Enoxacin의 치료효과

김중환,양홍윤,소순남,백혜승,황유정,김지현,김영태,김재홍 ( Joong Hwan Kim,Hong Yoon Yang,Soon Nam Soh,Hae Seung Paik,Yoo Jung Hwang,Ji Hyun Kim,Young Tae Kim,Jae Hong Kim ) 대한피부과학회 1991 大韓皮膚科學會誌 Vol.29 No.6

N/A In view of high prevalence of penicillinase producing Neisseria gonorrhoeae(PPNG) and chromosomally mediated resistant Neisseria gonorrhoaea(CMRNG) among circulating N. gonorrhoeae and emergence of spectinomycin resistant strains in Korea, more effort is needed to seek new effective treatment regimens for gonorrhea. The objective of this trial was to establish the efficacy of enoxacin, one of new fluoroquinolones, in the treatment of uncomplicated male gonorrhea. A total of 112 male uncomplicated gonorrheal patients were treated with one of the two dose regimens at the VD Clinic, Choong-Ku Public Health Center, in Seoul, between January and August, 1990. The patients were divided randomly into two groups and assigned to one of the two different dose regimens of enoxacin: 300㎎, PO(group A) and 600㎎, PO(group B). One of 47 patients treated with enoxacin, 300㎎, PO, failed(2.1%) and two of 46 patients treated with enoxacin, 600㎎, PO, failed (4.3%) to recover. A single dose regimen of enoxacin, 300㎎, PO is exellent, sa?e and relatively inexpensive in the treatment of male uncomplicated gonococcal urethritis in Korea.

고혈압 혈관조직의 장력-연관 신호전달과 물리치료의 상관성

김중환,김일현,황병용,Kim, Jung-Hwan,Kim, Il-Hyun,Hwang, Byong-Yong 대한물리치료학회 2008 대한물리치료학회지 Vol.20 No.4

Purpose: Alterations in the structure and function of vascular smooth muscle cells (VSMCs) are important in cardiovascular disease and maintaining chronic hypertension. Chronic hypertension is associated with changes in vascular smooth muscle tone. The spontaneous or myogenic tone of a blood vessel reflects the ability to adapt smooth muscle tone to changes in transmural pressure. However, the intracellular signaling mechanisms involved in myogenic tone are not fully understood. Methods: Here, we investigated the relationship between mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3 kinase (PI3K) in isometric contraction and enzymatic activity using muscle strips from rats made hypertensive with aldosterone-analogue deoxycorticosterone acetate (DOCA) salts. Results: Changes in myogenic tone and intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) were different after physiological salt solution (PSS) in normotensive and hypertensive rats. The myogenic tone and quiescent phosphorylation induced by the PSS treatment were inhibited by 10 ${\mu}$M PD098059, an extracellular-regulated protein kinase 1/2 (ERK1/2) inhibitor, and 10 ${\mu}$M wortmannin, an inhibitor of PI3K, in hypertensive rats. Conclusion: The development of DOCA-induced hypertension is associated with altered isometric contractions and $[Ca^{2+}]_i$ via changes in activation of ERK1/2 and PI3K after DOCA-salt treatment. Therefore, ERK1/2 and PI3K activity affect hypertension and may be suitable targets for physical therapy in cardiovascular disease.

가정요법 특집-습진 욕창의 간호법

김중환,Kim, Jung-Hwan 한국건강관리협회 1976 건강소식 Vol.4 No.10

탈분극과 근장그물 내 $Ca^{2+}$ 고갈-유도 평활근의 수축 및 세포 내 $Ca^{2+}$ 변동에 관여하는 L-형 $Ca^{2+}$ 통로의 상관성

김중환,Kim, Jung-Hwan 대한물리치료학회 2007 대한물리치료학회지 Vol.19 No.5

Purpose: It is generally accepted that smooth muscle contraction is triggered by intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) released from intracellular $Ca^{2+}$ stores such as sarcoplasmic teticulum (SR) and from the extracellular space. The increased $[Ca^{2+}]^i$ can phosphorylate the 20,000 dalton myosin light chain $(MLC_{20})$ by activating MLC kinase (MLCK), and this initiates smooth muscle contraction. In addition to the $[Ca^{2+}]_i$MACK-tension pathway, a number of intracellular signal molecules, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and others, play important roles in the regulation of smooth muscle contraction. However, the mechanisms regulating contraction of depletion of SR $Ca^{2+}$ in mouse gastric smooth muscle strips is not still clear. Methods: To investigate the rotes of $Ca^{2+}$ influx and SR $Ca^{2+}$ release channel on gastric motility, isometric contraction and $[Ca^{2+}]_i$ were examined in mouse gastric smooth muscle strips. Results: High KCl, ryanodine, an activator of $Ca^{2+-}$induced $Ca^{2+}$ release channel, and cyclopiazonic acid (CPA), an inhibitor of SR $Ca^{2+-}$ATPase evoked a sustained increase in muscle contraction and $[Ca^{2+}]_i$. These increases induced by high KCl, ryanodine, and CPA were partially blocked by application of verapamil ($10{\mu}M$), a L-type $Ca^{2+}$ channel inhibitor. Additionally, in $Ca^{2+-}$free solution (1 mM EGTA), ryanodine and CPA had no effect contraction and $[Ca^{2+}]_i$ in fundic muscle strips. Conclusion: These results that extracellular $Ca^{2+}$ influx and depletion of SR trigger $Ca^{2+}$ influx through verapamil-sensitive $Ca^{2+}$ channel, and extracellular and SR $Ca^{2+}$ store may functionally involve in the subcellular $Ca^{2+}$ mobilization in mouse gastric muscle.

세포 내 $Ca^{2+}$-의존성/-비의존성 평활근 수축기전에 대한 액틴결합단백질-Caldesmon-의 역할 - 노인성 심혈관질환 관련 노인물리치료 연구를 위한 기초의학적 접근 -

김중환,민경옥,최영덕,이준희,천기영,Kim, Jung-Hwan,Min, Kyung-Ok,Choi, Young-Duk,Lee, Joon-Hee,Chon, Ki-Young 대한물리치료과학회 2004 대한물리치료과학회지 Vol.11 No.1

It is widely accepted that smooth muscle contraction is triggered by intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR) and from the extracellular space, The increased $[Ca^{2+}]_i$ can phosphorylate the 20-kDa myosin light chain ($MLC_{20}$) by activating MLC kinase (MLCK), and this initiates smooth muscle contraction. In addition to the $[Ca^{2+}]_i$-MLCK-tension pathway, a number of intracellular signal molecules, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and Rho-associated coiled coil-forming protein kinase (ROCK), play important roles in the regulation of smooth muscle contraction. However, the mechanisms regulating contraction of caldesmon (CaD), actin-binding protein, are not entirely elucidated in the presence of $Ca^{2+}$. It is known that CaD tightly interacts with actin and inhibits actomyosin ATPase activity. Therefore, the purpose of the present study was to investigate the roles of $Ca^{2+}$-dependent CaD in smooth muscle contraction. Endothelin-1 (ET-1), G-protein coupled receptor agonist and vasoconstrictor, increased both vascular smooth contraction and phosphorylation of CaD in the presence of $Ca^{2+}$. These results suggest that ET-1 induces contraction and phosphorylation of CaD in rat aortic smooth muscle, which may he mediated by the increase of $[Ca^{2+}]_i$.

$17\beta$-estradiol의 고혈압 유도반응 억제와 인체적용 전기자극의 $17\beta$-estradiol 활성 증가

김중환,Kim, Jung-Hwan 대한물리치료학회 2009 대한물리치료학회지 Vol.21 No.2

Purpose: $17\beta$-estradiol is the most active endogenous estrogen, which is related to favorable changes in the plasma lipid profile, to relaxation of the coronary vessels, and to a decrease in platelet aggregation and vascular smooth muscle cell migration. However, although the beneficial effect of estrogens on plasma lipoproteins (ie, lowering low-density lipoprotein and increasing high-density lipoprotein cholesterol) contributes to cardiovascular protection, it does not fully account for the protective effect, particularly in the application of physical therapy, including low frequency electrical stimulation. Methods: The aim of this study was to demonstrate the inhibition of stressors, such as endothelin-1 (ET-1), serotonin (5-hydroxytryptamine, 5-HT), prostaglandin $F2\alpha$ ($PGF2\alpha$), and a protein kinase C (PKC) activator 12-deoxyphorbol 13-isobutyrate (DPB), induced isometric tension by $17\beta$-estradiol in vascular smooth muscle strips, respectively. In addition, the effects of low frequency electrical stimulation at the meridian points (CV-3, -4, Ki-12, SP-6, LR-3, BL-25, -28, -32, -52) on the indirect antihypertensive effect were examined by monitoring the changes in the serum $17\beta$-estradiol concentration in healthy volunteers. Results: Isometric tension analysis showed that the responses of inhibited tension by $17\beta$-estradiol were similar to the same stressors in rat aortic smooth muscle strips. Furthermore, although the continued amplitude modulation (AM) type of electrical stimulation was not increased significantly by electrical stimulation, the current of the frequency modulation (FM) type of low frequency electrical stimulation increased the serum $17\beta$-estradiol concentration in normal volunteers. Conclusion: These results, in part, suggest that $17\beta$-estradiol has the capacity to supress stressor-induced muscle tension, and electrical stimulation, particularly current of the FM type, has a modulatory effect on the sex steroid hormones, particularly $17\beta$-estradiol, in healthy volunteers.

고혈압-연관 단백질 부활효소 C의 활성과 물리치료의 상관성

김중환,Kim, Jung-Hwan 대한물리치료학회 2008 대한물리치료학회지 Vol.20 No.3

Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.

컴퓨터${\cdot}$소프트웨어 개발시의 완성시간에 관한 연구

김중환,김성식,Kim Jung-Hwan,Kim Seong-Sik 한국국방경영분석학회 1983 한국국방경영분석학회지 Vol.9 No.1

The ideal way of eliminating errors in a large scale software system is to test the software with all possible inputs, providing sufficiently large amount of execution time. However, in practice, the test must be performed within given budget and time limits. Therefore, to perform the test under given constraints, we have to properly select inputs and determine the execution time for each selected inputs. This paper studies the distribution of number of errors at a given time as well as the distribution of time required to reduce the number of errors to a certain level. We assumed that error occurrence times are distributed exponentially (not necessarily identical) and the number of errors at the initial stage is known or estimable.

골격근의 수축과 가소성에 대한 신호전달-매개 단백질 및 관련 효소의 상관성

김중환,Kim, Jung-Hwan 대한물리치료학회 2007 대한물리치료학회지 Vol.19 No.4

Background: It is generally accepted that skeletal muscle contraction is triggered by nerve impulse and intracellular $Ca^{2+}\;([Ca^{2+}]_i)$ released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR). Specifically, this process, called excitation-contraction (E-C) coupling, takes place at intracellular junctions between the plasma membrane, the transverse (T) tubule L-type $Ca^{2+}$ channel (dihydropyridine-sensitive L-rype $Ca^{2+}$ channel, DHPR, also called tetrads), and the SR $Ca^{2+}$ release channel (ryanodine-sensitive $Ca^{2+}$ release channel, RyR, also called feet) of internal $Ca^{2+}$ stores in skeletal muscle cells. Furthermore, it has been reported that the $Ca^{2+-}$ dependent and -independent contraction determine the expression of skeletal muscle genes, thus providing a mechanism for tightly coupling the extent of muscle contraction to regulation of muscle plasticity-related excitation-transcription (E-T) coupling. Purpose: Expression and activity of plasticity-associated enzymes in gastrocnemius muscle strips have not been well studied, however. Methods: Therefore, in this study the expression and phosphorylation of E-C and E-T coupling-related mediators such as protein kinases, ROS(reactive oxygen species)- and apoptosis-related substances, and others in gastrocnemius muscles from rats was examined. Results: I found that expression and activity of MAPKs (mitogen-activated protein kinases, ERK1/2, p38MAPK, and SAPK/JNK), apoptotic proteins (cleaved caspase-3, cytochrome c, Ref-1, Bad), small GTP-binding proteins (RhoA and Cdc42), actin-binding protein (cofilin), PKC (protein kinase C) and $Ca^{2+}$ channel (transient receptor potential channel 6, TRPC6) was observed in rat gastrocnemius muscle strips. Conclusion: These results suggest that MAPKs, ROS- and apoptosis-related enzymes, cytoskeleton-regulated proteins, and $Ca^{2+}$ channel may in part functionally import in E-C and E-T coupling from rat skeletal muscles.