• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.121-132
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• 2005

연구목적: 본 연구에서는 비폐쇄성 무정자증 환자에서 나타나는 정자형성과정의 이상과 고환세포의 세포자연사와의 연관관계 여부를 확인하였다. 또한 SELDI-TOF MS 분석을 통하여 고환 내 단백질 발현 양상을 확인하고, 질환에 따른 효과적인 biomarker 개발 가능성 여부를 확인하였다. 재료 및 방법: RT-PCR 및 면역조직화학법을 사용하여 고환에서의 Fas, FasL, Bcl-2, Bax와 Caspase-3의 발현 양상을 확인하고, in situ DNA 3'-end-labelling 방법으로 고환세포의 세포자연사 양상을 확인하였다. SELDI-TOF MS 분석법에 의한 고환의 병리학적 소견에 따른 단백질 발현 변화는 소수성 칩 ($H_4$)을 사용하여 분자량 10~100 kDa 범위 내에서 분석하였다. 결 과: 정상적인 정자형성과정을 보이는 폐쇄성 무정자증 환자의 고환에 비해 지주세포 증후군 (Sertoli cell only syndrome)과 성숙정지 (maturation arrest)를 보이는 고환 내 생식세포와 지주세포에서 세포자연사가 현저하게 증가한 것을 확인할 수 있었다. 세포자연사 관련인자들의 발현 양상을 확인한 결과, 지주세포 증후군과 성숙정지 환자군에서 Fas와 FasL mRNA의 발현이 증가하였으나, bcl-2, bax와 caspase-3 mRNA 발현의 경우에는 두 질환 모두에서 유의한 차이를 확인할 수 없었다. FasL 단백질 발현의 경우, 세포자연사의 증가가 관찰되었던 지주세포 증후군과 성숙정지를 보이는 환자의 간질세포와 지주세포에서 증가하는 양상을 나타내었다. SELDI-TOF MS 분석 결과에서 폐쇄성 무정자증 환자군에 비해 전체적인 단백질 발현양이 지주세포 증후군과 성숙정지 환자의 고환에서 감소하는 양상을 보였으며, 특히, 16.730 kDa 단백질의 현저한 감소를 확인할 수 있었다. 결 론: 본 연구결과를 통해 비폐쇄성 무정자증 환자에서 나타나는 정자형성과정의 장애는 생식세포의 비정상적인 세포자연사와 연관되어 있으며, 고환 내 Fas와 FasL의 비정상적인 발현이 주된 원인인 것을 확인할 수 있었다. 또한, SELDI-TOF MS 분석법을 통한 단백질 발현 양상의 연구는 무정자증 환자에서의 다양한 병리학적 소견을 쉽게 파악할 수 있는 biomarker 발굴뿐만 아니라 질환의 원인규명을 위한 연구에도 유용하게 이용될 수 있을 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.239-253
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• 2022

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

• Journal of Dairy Science and Biotechnology
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• v.33 no.1
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• pp.35-46
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• 2015

Recently, much attention has been paid to the development of a value-added food category containing probiotics so as to improve human health and prevent diseases. Among various foods, the health benefits of milk and dairy products are known to humanity, and could be attributed to the bioactive components present in milk. In fermented milk products, the health benefits could be due to suitable modulation activities produced by the action of probiotic bacteria. Besides the modification of various milk components, probiotics might also act directly as preventive and therapeutic agents against some severe diseases. Probiotics promote health via their positive effects on the immune response, stimulation of natural immunity, and modulation of the production of antimicrobial peptides, cytokines, and so on. Whey proteins, a byproduct of cheese production could also have anticarcinogenic, immunostimulatory, antimicrobial, and health-promoting activities such as improving insulin sensitivity and reducing fat deposition. Therefore, milk and dairy products containing probiotics could provide various opportunities in the field of functional foods. Additionally, these functional foods may be important in the human diet and may help improve human health and prevent diseases.

• Korean Journal of Biological Psychiatry
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• v.12 no.1
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• pp.42-61
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• 2005

Objectives:The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. Methods:SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1($80{\mu}M$, $40{\mu}M$, $20{\mu}M$). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. Results:Treatment of SH-SY5Y cells with $80{\mu}M$ ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(${\geq}$3 fold) in Rg1 treated cells and 40 genes were up-regulated(${\geq}$2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1-group. Conclusion:Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

• Journal of Dairy Science and Biotechnology
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• v.32 no.1
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• pp.17-29
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• 2014

GRAS probiotics can be used to modulate intestinal microbiota and to alleviate various gastrointestinal disorders. In several recent studies, researchers have explored the potential expansion and usability of probiotics to reduce the risk factors associated with diseases, including obesity, hypercholesterolemia, arterial hypertension, hyperhomocysteinemia, and oxidative stress. In this review, our aim was to clarify the mechanism underlying interactions between hosts (animal or human) and probiotics and the beneficial effects of probiotics on human health.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.37-60
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• 1983

The uterus receives adrenergic terminals from the mesenteric ganglia and considerably large amount of catecholamines have been shown to be contained in this organ. On the other hand, the activities of epinephrine, norepinephrine or adrenergic nerve on uterine motility is so complicated that many controversial results have been reporter. Recently, a large number of reports concerning the changes of uterine catecholamines content have appeared, but little is known about the role of uterine catecholamines in their activities on uterine motility. The present experiments were undertaken to determine the significance of the intrinsic uterine catecholamines in the physiology of uterus. Female albino rabbits weighing approximately 2 kg were employed in this experiment. uterine strip3 were prepared and suspended in a constant temperature $bath(38^{\circ}C)$ containing 100 ml of Locke's solution aerated with 95% oxygen and 5% carbon dioxide. Spontaneous motility was recorded on a smoked drum with an isotonic lever. The catecholamines concentration of the uterus was determined according to the Procedure described of Shore and Olin (1958). Human uterus obtained from patients was also used to determine the catecholam ines content of myometrium. Followings are summarized results. 1) On the non-pregnant rabbit uterine strips, epinephrine and norepinephrine significantly elevated the tonus and stimulated the spontaneous motility. Pretreatment with dichloroisoproterenol(DCI), an adrenergic beta-receptor blocker, enhanced the stimulatory activity of epinephrine or norepinephrine. On the other hand, pretreatment with dibenamine, an adrenergic alpha-receptor blocker, rendered the uterine muscle to exhibit inhibition after the administration of epinephrine or norepinephrine. Following the treatment with both DCI and dibenamine, epinephrine or norepinephrine produced no appreciable effects on the spontaneous motility of the uterus. These results suggest there exist both alpha and beta-adrenergic receptors in the uterine muscle and the response to epinephrine of the former is predominant over that of latter in the non-pregnant uterus of rabbits. The total catecholamines concentration of the non-pregnant uterus was $351\;m{\mu}g/g$ and the fractional concentrations of epinephrine and norepinephrine were $125\;m{\mu}g/g(35.7%)$ and $226\;m{\mu}g/g$ respectively. It is interesting to note that the catecholamines content of uterus was characterized by a high fractional corcentration of epinephrine relative to norepinephrine. 2) On the pregnant rabbit uterine strips, the effects of epinephrine and norepinephrine varied according to the period of pregnancy. The response to epinephrine of adrenergic beta receptor of uterus increased during pregnancy, and the effect of catecholamine was inhibitory in the early pregnancy but became stimulatory as the pregnancy progressed. This stimulating action on the uterine motility was found to occur through the action of norepinephrine. The uterine catecholamines concentration was markedly reduced during pregnancy. The catecholamines concentration was started to decrease in the early pregnancy, reached the lowest level in the mid-pregnancy and then started to increaae again in the late pregnancy when the total catecholamines content became the highest level of all. This increase of catefholamines in late pregnancy was chiefly due to the increase of norepinephrine. These results suggest that the uterine motility may be related to the catecholamines content, especially norepinephrine content in the uterus. 3) Bilateral oophorectomy of rabbits results in a marked shrink of the uterus in size. The spontaneous motility of the uterine segment of these animals was very weak and irregular. Norepinephrine produced inhibitory effect, whereas epinephrine was stimulatory or inhibitory effect on the uterine segment. The total catecholamines tontent in whole uterus was markedly reduced. The injection of estrogen into the oophorectornized rabbit increased the weight of uterus to approximately three times of that of oophorectornized animal. The apontaneous motility and the response to epinephrine and norepinephrine of the uterine segment were greatly enhanced. Both epinephrine and norepinephrine produced a marked stimulatory effects of the uterine motility. The uterine content of catecholamines, particularly epinephrine, was markedly increased. The injection of progesterone into the oophorectornized rabbit increaeed the weight of uterus to approximately 2.5 times of that of eophorectornized animal. The spontaneous motility of the uterine segment was weak and irregular. Epinephrine produced stimulatory effect at high concentrations but norepinephrine always prcdnced inhibitory effect on the uterine segment. The uterine content of catecholamines, particularly of norepinephrine, was markedly reduced. These results suggested that ovarian hormones play an important role not only on the growth and spontaneous norepinephrine of uterus but also on the catecholamines content and responee to epinephrine and norepinephrine of the uterus. 4) The intraperitoneal injection of reserpine(3 mg/kg) into the non-pregnant, pregnant and oophorectornieed rabbits markedly decreased the uterine content of catecholamines, particularly of the norepinephrine. The stimulatory response to epinephrine and. norepinephrine of the uterine segment of these reserpinized ratbits was markedly reduced whereas the inhibitory response to these catecholamines was enhanced. This finding further support the close relationship between the uterine catecholamines content and uterine response to epineptrire and norepinephrine. 5) In the human uterus, the concentration of epinephrine was actrally greater than that of norepinephrine and it was significantly greater during the proliferative phase of the menstrtal cycle. In the human pregnant uterus, the concentrations of toth epinephrine and ncrefinephrine were markedly reduced and showed about 45 percent rednction after 6-8 weeks of ectopic Pregnancy. At full term ana during labor, the concentrations of epinephrine and norepinephrine at placental sites were less than those found in the non-pregnant group. Of interest was the finding that the norepinephrine concentration of uterus from toxemic patients was two and half times higher than that of lower uterine segment of the nontoxemic pregnant individuals. Also the epinephrine concentraticn was slightly increaeed.

• Journal of Korean Academy of Nursing
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• v.18 no.2
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• pp.162-188
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• 1988

The purpose of this study is to guide the direction of the Korean nursing education to analysize ⑴ the philosophy and objectives ⑵ curriculum, and ⑶ educational environment. This analysis is based on the data from 50 nursing schools (14 4-year colleges and 35 3-year colleges) The survey was conducted from Dec. 1986 through Jan. 1987 by mail. 1) Educational philosophy and objectives 10 4-year colleges and 8 3-year college program have curricular philosoph. Most popular curricular philosophies are human beings, health, nursing, nursology, nursing education, nurses role in the present and in the future. 10 nursing schools mentioned that human being is the subject to interact with : environment physically, mentally and socially. 2 schools mentioned that health is the state of functioning well physically, mentally and socially. 13 schools mentioned that the nursing is the dynamic act to maintain and to promote the highest possible level of health. 4 schools mentioned that the nursology is an applied science. 4 schools mentioned that nursing education is the process to induce the behavioural changes based on the individual ability. There is different opinion about the nurses' role between 4-year college and 3-year college. In the responses from 4-year colleges they focus on the leadership in effective changes, self-regulating and self-determining responsibilities, applying the new technology, continuing education, and participation in research to further nursing knowledge. In the responses from 3-year colleges, they focus on the education in college, primary health care nursing, direct care provider and public health education. Among 50 respondents 40 schools have educational goals which can be divided into two categories. One is to establish the moral and the other is to develop the professionalism. 2) Curriculm The analsis of curriculum is only based on the data from the 4-year colleges because the most of 3-year colleges follow the curriculum guideline set by the Ministry of Education. a) Comparison of the credits in cultural subject and in nursing major. The average required credit for graduation is 154.6 and the median credit is the range of 140-149. The average credit of cultural subjects is 43.4. In detail, the average number of credit of required course and elective courses are 24.1 and 19.3 respectively. The average credit for major subject is 111.2. In detail, the average credit for required courses and electives course are 100.9 and 10.4 respectively. In 5 colleges, students are offered even on elective course b) Comparison of the credit by class. The average earned credits are as follows : 41.1 in freshman, 400 in sophormore 38.3 in junior and 32.4 in senior. Cultural subjects are studied in early phases. c) Comparison of the compulsory and elective cultural subject by institute. The range of credit is 7-43 in compulsory cultural subjects and there are lot of differences among institutions. While all respondents require liberal arts as compulsary subjects, few respondents lists social science, natural science and behavioral science as required subjects. Social science-related subjects are frequently chosen as cultural subjects d) Distribution of creditsin cultural subjects by institute. The liberal art subjects are taught in 20 institute. English and physical education courses are taught in all instituions. The social science subjects are taught in 15 colleges and the basic Psycology and the Basic sociology are the most popular subjects. The natural science subjects are taught in 7 colleges and Biology and Chemistry are the most popular subjects among them. e) Distribution of credits in major basic courses by institute. Most of the institutes select Anatomy, Microbiology, Physiology, biochemistry and Pathology as basic major courses. f) Comparison of the required and elective courses for nursing major by institutions. Subjects and credit ranges in major are varing by institute. More than half of the respondents select the following subjects as required major subjects. (1) Adults Health Nursing and Practice (19.5 credits) (2) Mother and Child Care and Practice (8.9 credits) (3) Community Health Care and Practice (8.5 credits) (4) Psychiatric Nursing Care and Practice (8.1 credits) (5) Nursing Management and Practice (3.9 credits) (6) Fundamental of Nursing, Nursing Research and Health Assessment and Practice. Three institutions select Introduction to nursing, Rehabilitation Nursing, School Nursing, Public Health Nursing, Nursing English, Communication, Human Development as electives in nursing major. 3) Educational environment a) Nursing institution There are forty-three 3-year colleges and seventeen 4-year colleges and 81.4% of which are private b) Number of students and faculty 19.2% of the students are in 4-year colleges and 80.8% of the students are in 3-year colleges. In 4-year colleges, the number of nursing faculty members is in the other of assistant professor, instructor and professor. In 3-year colleges, the orderiis lecturer, associate professor, full time instructor and assistant professor. In 4-year colleges, 18.8 students are allocated per nursing faculty and in 3-year colleges, 33.1 students are allocated per nursing faculty. c) Clinical practices 66.7% of the 4-year colleges practice over 1201 hours in clinic and 28.5% of 3-year colleges practice over 1201 hours in clinic. In 4-year colleges, 11.5 students are allocated per nursing faculty and in 3-year colleges,17 students are allocated per nursing faculty The survey shows no difference in the procedure between 4-year colleges and 3-year colleges but 3-year colleges choose the more variety practicing site such as special hospital and community health clinic. d) Audiovisual facilities The survey shows a lot of difference in audiovisual facilities among institution and 3-year colleges are less equipped than 4-year colleges.

• Progress in Medical Physics
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• v.16 no.4
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• pp.207-213
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• 2005

The severity of carotid Intima-media thickness (IMT) is an Independent predictor of atherosclerosis which causes transient cerebral ischemia, stroke, and coronary events such as myocardial Infarction. The IMT consists of Intima thickness (IT) and media thickness (MT). However, the Individual clinical significance of IT and MT has not been well studied. We devised a method of measuring IT, MT, and IMT using B-mode ultrasound Image processing technique for the diagnosis of atherosclerosis. To inspect the clinical significance of IT, MT, and IMT, one hundred forty-four consecutive patients (mean age; 57 years old, 72 males) were underwent common carotid artery scanning using high-resolution ultrasound. Results showed that, the IT (p<0.05), MT (p<0.05) as well as IMT (p<0.01) of patients with atherosclerotic disease were significantly thicker than that of the patients without atherosclerotic disease. Patients with hyperiension showed significantly thicker IT (p<0.01), MT (p<0.001), and IMT (p<0.001). However, only IT was thicker in patients with smoking (p<0.01). The IT (r=0.374, p=0.001), MT (r=0.433, p=0.000), and IMT (r=0.479, p=0.000) showed positive correlation with age. The coefficients of determination ($r^2$) were estimated to be $92.4\%$ for IMT and MT, $49.1\%$ for IMT and IT, and $27.4\%$ for IT and MT. This result suggests that the Intima layer of the carotid artery has a different physiology with the media layer.

• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.56-66
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• 2003

Purpose : Human umbilical vein endothelial cells(HUVECs) play an important role in regulating blood flow by releasing vasoactive substances. It has been reported that endothelial impairment and dysfunction might be a primary cause of placental vascular disease, which is manifested clinically as preeclampsia in mother and intrauterine growth restriction in fetus. Furthermore, the frequency of apoptotic changes is increased in umbilical and placental tissues from growth-restricted pregnancies. However, the various mechanisms of umbilical endothelial cell apoptosis have not been broadly proposed. We investigate the effects of amiloride derivatives on apoptotic death of HUVECs and identify their ionic mechanism. Methods : HUVECs were purchased from Clonetics, and cultured on endothelial cell growth medium. MTT assay and flow cytometry were used for assessing cytotoxic effect and confirming the apoptosis. Changes in intracellular ion concentrations were measured with specific fluorescent dyes and fluorescence imaging analysis system. Results : Amiloride derivatives elicited cytotoxic effects on HUVECs with dose-dependent manners and the rank order of potency is HMA($IC_{50}\;11.2{\mu}M$), MIA>EIPA>>amiloride. HMA-induced cytotoxicity is dependent on extra- and intracellular pH, that is, increase extra- and intracellular pH augmented the cytotoxic effects of HMA. HMA dose-dependently reduced intracellular major ions, such as $K^+$ and $Cl^-$. Interestingly, the depletion of intracellular ions induced by HMA was also significantly enhanced at alkaline extracellular pH. Conclusion : Amiloride derivatives induce apoptosis of HUVECs with dose and pH dependent manners. They reduce intracellular $K^+$ and $Cl^-$ concentration, which is also extracellular pH dependent.

• Journal of Acupuncture Research
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• v.17 no.1
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• pp.27-41
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• 2000

The meridian system is the most essential and basic connecting structure that maintains the vital activities of viscera and bowels by connecting them with each part of body's surface. Doctors can understand the healthy condition, and the region and deficiency-excessiveness of disease by observing the condition of Qi flowing. Deficiency and excessiveness could be differentiated by various symptoms expressed in meridian system. Especially there could be several clues like pain, heat-cold, protuberance-depression, change of color and shine in the line of channel leads to the judgment of deficiency-excessiveness The diagnosis of deficiency and excessiveness can be generalized by quantification of elastic status in skin surface along the meridian system. By comparing data from measurement of elastic condition with those from traditional deficiency and excessiveness, it could be utilized for the development of oriental medicine. All biological activities in the human body are based on meridian system according to the oriental medicine. Also the meridian system is viewed as basic and essential structure connecting internal viscera and each part of body. The areas of expressed channel phenomena are muscle to bone, muscle to muscle and bone to bone. These areas are called depression where meridian system is present and any changing state on those points can be measured. It could be difficult in diagnosing the reaction of meridian system because doctor can depend on his own judgment. Therefore, it is necessary to quantify and indexate channel reactions. To quantify the channel reactions, specially manufactured instrument was used to quantify the protuberance and depression to differentiate the deficiency and excessiveness. The results follow as below; 1. The elastic index measurement by the equipment proved a pattern of agreement showing the values that ranged within standard deviation 0.05kgf/cm throughout the experiment except few cases' measurement in CV-17. 2. To evaluate the state of deficiency & excessiveness of elastic index measurements in frontal point, elastic index measurements in the front paint were compared to the elastic index measured surrounding the point within 2.5 cm. Such result of indexing procedure was closely matched to the concept of palpitation. 3. If the elastic index values in the surrounding front point closely located to the elastic index values in the front point, the judgement on the state of deficiency and excessiveness was delayed. Otherwise, it was judged as deficiency or excessiveness. 4. Out of total 12 cases of comparing the elastic index values to the elastic index values in the surrounding front point, Three to nine front points were judged as either in the state of deficiency or excessiveness. 5. Among the nine front points judged as either in the state of deficiency or excessiveness, Four cases were matched to the electric index measured by EAV that evaluating the internal organs by five different phases. If more clinical cases are accumulated, it is expected to systematically theorize and improve the concept of deficiency and excessiveness in the internal organs using the front point.