• Journal of the Korean Chemical Society
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• v.62 no.3
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• pp.181-186
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• 2018

Nitrosamines are the nitrosocompounds which are produced by nitrosation reactions of the secondary amine and nitrite, and has been found to be produced through the vulcanization process during the production of rubber products Recently, nitrosamines have been detected in rubber products and become a major topic. Condoms are disposable medical devices, so safety is important because they come into direct contact with the skin and mucous membranes. In this study, we developed an analytical method for nitrosamines in condoms by applying ISO 29941 method. The samples were eluted by distilled water, and target compounds were extracted by liquid-liquid extraction with dichloromethane. And then after concentrated, and quantitatively analyzed by LC-MS/MS. The accuracies of the analytical method were ranged from 85.8 to 108.7%, precisions were lower than 11.5%, and the detection limits were from 0.11 (NDPA and NDBA) to 0.48 (NPYR) ng/mL. Among the 31 condom samples, NDBA was detected from 2 cases by extraction of distilled water, and NDMA were detected from 1 case, NDEA from 4 cases and NDBA from 26 cases by extraction of artificial saliva (pH 4.5). The total amount of nitrosamines in all samples were less than $500{\mu}g/kg$.

• Pediatric Infection and Vaccine
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• v.28 no.2
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• pp.66-81
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• 2021

The coronavirus disease 2019 pandemic has been continuously spreading throughout the world. As of July 15, 2021, there have been more than 188 million confirmed cases and more than 4.06 million deaths. Although the incidence of severe infections is relatively low in children and adolescents compared to adults, a complication called multisystem inflammatory syndrome in children (MIS-C) may occur in some cases at approximately 2-6 weeks after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MIS-C can be seen in patients of various ages, from young infants to adolescents, and may present with diverse clinical manifestations. While fever present in a great majority of patients, symptoms suggesting the involvement of the digestive or nervous system and the skin and mucous membranes (Kawasaki disease-like symptoms) also appear in many cases. Cardiac involvement may also be observed, including left ventricular dysfunction, myocarditis, coronary artery dilatation, and coronary aneurysm. In some cases, hypotension or shock can occur, and mechanical ventilation or treatment in the intensive care unit may be necessary. Fortunately, recovery is generally reported after appropriate treatment. MIS-C is a rare but important complication of SARS-CoV-2 infection in children and adolescents. As such, it is important to recognize the clinical symptoms and provide appropriate treatment at an early stage. In this review, the epidemiology, clinical symptoms, suggested pathophysiology, diagnostic approach, and treatment of MIS-C will be discussed.

• Development and Reproduction
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• v.12 no.3
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• pp.243-250
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• 2008

Mast cells containing a variety of mediators in their cytoplasmic granules are widely distributed in connective tissues and mucosal surfaces of skin, airways, and guts. Within these tissues, mast cells are involved in the pathophysiological conditions such as inflammation, self-defense, tissue-remodeling, and autoimmunity. In order to understand the functional roles of master cells in the uterus, we histologically examined the distribution and density of uterine mast cells in the different aged mice. Until 6 weeks mast cells were sparsely detected in the uterus. But at 7 weeks after birth, when estrous cycle begins, the number of mast cells within uterine tissues increased dramatically and the increment of mast cell density continued up to 32 weeks-age. After then, uterine glandular tissue degenerated gradually and density of uterine mast cell decreased. Uterine mast cells were mainly found in the myometrium and they were closely associated with smooth muscle cells, fibroblasts, and collagens, which contents were changed according to the uterine development in the myometrium. These results suggest that uterine mast cells could be involved in myometrial contractions mediated by smooth muscle cells and tissue reconstitution or remodeling during estrous cycle and parturition including the various immunological functions.

• Journal of the Korean Society of Radiology
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• v.81 no.5
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• pp.1260-1265
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• 2020

Kaposi's sarcoma (KS) is a multicentric human immunodeficiency virus-associated neoplasm characterized by multiple vascular nodules in the skin, mucous membranes, and viscera. Gastrointestinal acquired immunodeficiency syndrome (AIDS)-related KS is the most common visceral involvement reported in disseminated disease. Here, we present the findings of a rare case of KS involving multiple organs with abdominal pain and active bleeding in the colon. Multiple intraluminal lesions were found in the terminal ileum, sigmoid colon, and rectum by ileocolonoscopy, and in the jejunum and ileum by fluoroscopy. Abdominopelvic CT revealed multiple enhanced flat lesions in the ileum and enlarged lymph nodes. The diagnosis was confirmed by histopathology, and antiretroviral therapy was initiated as the treatment of choice for KS. Owing to the increasing number of AIDS patients, it is essential for radiologists and clinicians to be aware of the imaging characteristics of KS to protect physicians from indiscriminate exposure to AIDS.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.337-344
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• 2005

A tactile sensor employs a piezoelectric element to detect contact frequency shifts and thereby measure the stiffness or softness of material such as tissue, which allows the sensor to be used in many fields of research for urology, cardiology, gynecology, sports medicine and caner detection and especially for cosmetics and skin care. In this study, reliability of the tactile sensor system was investigated with its manual application to the muscles susceptible to temporomandibular disorders. Stiffness and elasticity of anterior temporalis, masseter and trapezius muscles were calibrated bilaterally from 5 healthy men with an average of 24.5$\pm$0.94 years. The tactile sensor used in this study had a computer-controlled and motor-driven sensor unit which automatically pressed down on the skin surface over the muscles being measured and retracted, thereby providing the hysteresis curve. The slope of the tangent of the hysteresis curve (${\Delta}f/{\Delta}x$) is defined as stiffness of the muscle being measured and the distance between the two parts of the curve as its elasticity. To determine inter-examiner reliability, all the measurements were performed by the two examiners A and B, respectively and the same examination were repeated with an interval of 2 days for intra-examiner reliability. The results from this study demonstrated high reliability in measuring stiffness and elasticity of anterior temporalis, masseter and upper trapezius muscles using a tactile sensor system. It is suggested that the tactile sensor system can be a highly reproducible and effective instrument for quantitative evaluation of the muscle in head and neck region.

• The Korean Journal of Pesticide Science
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• v.14 no.4
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• pp.478-489
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• 2010

Penthiopyrad is a fungicide agent in types of pyrazole which is showing the effect of prevention in fungal disease and powdery mildew. In order to register this new pesticide, reports of acute toxicity and chronic toxicity by animal study were examined to set acceptable daily intake to evaluate hazards of consumers. Acute toxicity was low in toxic, and it did not have the effect of acute dermal toxicity, acute eye irritation, or skin sensitization. As the result of the study in chronic toxicity, the common effect of chemical appeared in the liver and thyroid which was proven as a toxic effect. Two-generation reproduction toxicity, genotoxicity, and prenatal development toxicity were not proven. As the result of carcinogenic study, increase of thyiroid follicular adenoma in the rat and the frequency of liver hepatocellar adenoma in mice were also increased. However, it was decided that the threshold value on the effect in chemicals could be controlled through study liver enzyme induction. Therefore, the ADI for penthiopyrad is 0.081 mg/kg/ bw/day, based on the NOAEL of 8.10 mg/kg bw/day of twelve-months dogs study and applying an uncertainty factor of 100.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.372-385
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• 1999

Background: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. Method: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. Results: The experimental group was divided into two subgroups-those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 $cells/mm^3$ while control group's mean was 0.4 $cells/mm^2$(p=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 $cells/mm^2$ with 28.4 $cells/mm^2$ of control group(P=0.026). In addition, the mean thickness of the basement membrane of experimental group was $14.20{\pm}5.20{\mu}m$ in contrast of control group whose mean was $3.50{\pm}1.37{\mu}m$(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough variant asthma ; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive (21.4%) with the skin prick test In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). Conclusion: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.2
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• pp.183-192
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• 2006

Purpose: This study was undertaken to evaluate the factors correlated with the clinical course and outcome in patients of Henoch-Sch${\ddot{o}}$nlein Purpura. Methods: The medical records of 104 children diagnosed with Henoch-Sch${\ddot{o}}$nlein Purpura (HSP) from January 1996 to April 2006 were reviewed retrospectively. The patients were divided into two groups: patients with Gastrointestinal (GI) symptoms and those without GI symptoms. When there were joint, scrotum, and renal symptoms except for skin lesion in whole HSP, those patients were excluded. The history of acute infection, duration of admission, treatment requirement, recurrence of HSP, CBC, stool occult blood test, abdominal ultrasonographic findings and GI endoscopic findings were reviewed. Results: Among 104 patients, patients with GI symptoms included 66 cases (63.5%), those without GI symptoms accounted for 38 cases (36.5%). GI symptoms included: abdominal pain in 57 cases (54.8%), vomiting 21 cases (20.2%), GI bleeding 5 cases (4.8%), nausea 3 cases (2.9%) and diarrhea 3 case (2.9%). Positive GI symptoms and GI mucosal lesions on GI endoscopy had a statistically significant correlation with increased admission duration, treatment requirement, recurrence of HSP, and positive stool occult blood. Six cases with small intestinal wall thickening were noted on abdominal ultrasonography. Six cases of hemorrhagic gastritis and hemorrhagic duodenitis, 3 cases of duodenal ulcer, 3 cases of hemorrhagic gastritis and duodenal ulcer, 2 cases of hemorrhagic duodenitis and colitis, and 1 case of colitis were noted on GI endoscopy. Conclusion: These results suggest that GI endoscopic examination may be helpful for the diagnosis and treatment of children with HSP.

• Food preservation and processing industry
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• v.8 no.2
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• pp.6-12
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• 2009

면역반응은 외부 감염원으로부터 신체를 보호하고 외부감염원을 제거하고자 하는 주요항상성 유지기전의 하나이다. 이들 반응은 골수에서 생성되고 비장, 흉선 및 임파절 등에서 성숙되는 면역세포들에 의해 매개된다. 보통 태어나면서부터 얻어진 선천성 면역반응을 매개하는 대식세포, 수지상 세포 등과, 오랜기간 동안 감염된 다양한 면역원에 대한 경험을 토대로 얻어진 획득성 면역을 담당하는 T 임파구 등이 대표적인 면역세포로 알려져 있다. 다양한 면역질환이 최근 주요 사망률의 원인이 되고 있다. 최근, 암, 당뇨 및 뇌혈관질환 등이 생체에서 발생되는 급 만성염증에 의해 발생된다고 보고됨에 따라 면역세포 매개성 염증질환에 대한 치료제 개발을 서두르고 있다. 또한 암환자의 급격한 증가는 암발생의 주요 방어기전인 면역력 증강에 대한 요구들을 가중시키고 있다. 예로부터 사용되어 오던 고려인삼과 홍삼은 기를 보호하고 원기를 회복하는 명약으로 알려진 대표적인 우리나라 천연생약이다. 특별히, 홍삼은 단백질과 핵산의 합성을 촉진시키고, 조혈작용, 간기능 회복, 혈당강하, 운동수행 능력증대, 기억력 개선, 항피로작용 및 면역력 증대에 매우 효과가 좋은 것으로 보고되고 있다. 홍삼에 관한 많은 연구에 비해, 현재까지 홍삼이 면역력 증강에 미치는 효과에 대한 분자적 수준에서의 연구는 매우 미미한 것으로 확인되어져 있다. 홍삼의 투여는 NK 세포나 대식세포의 활성이 증가하고 항암제의 암세포 사멸을 증가시키는 것으로 확인되어졌다. 현재까지 알려진 주요 면역증강 성분은 산성다당류로 보고되었다. 또 한편으로 일부 진세노사이드류에서 항염증 효능이 확인되어졌으며, 이를 통해 피부염증 반응과 관절염에 대한 치료 효과가 있는 것으로 추측되고 있다 [본 연구는 KT&G 연구출연금 (2009-2010) 지원을 받아 이루어졌기에 이에 감사드린다]. 면역반응은 외부 감염물질의 침입으로 유도된 질병환경을 제거하고 수복하는 중요한 생체적 방어작용의 하나이다. 이들 과정은 체내로 유입된 미생물이나 미세화학물질들과 같은 독성물질을 소거하거나 파괴하는 것을 주요 역할로 한다. 외부로 부터 인체에 들어온 이물질에 대한 방어기전은 현재 두 가지 종류의 면역반응으로 구분해서 설명한다. 즉, 선천성 면역 반응 (innate immunity)과 후천성 면역 반응 (adaptive immunity)이 그것이다. 선천성 면역반응은 1) 피부나 점막의 표면과 같은 해부학적인 보호벽 구조와 2) 체온과 낮은 pH 및 chemical mediator (리소자임, collectin류) 등과 같은 생리적 방어구조, 3) phagocyte류 (대식세포, 수지상세포 및 호중구 등)에 의한 phagocytic/endocytic 방어, 그리고 4) 마지막으로 염증반응을 통한 감염에 저항하는 면역반응 등으로 구분된다. 후천성 면역반응은 획득성면역이라고도 불리고 특이성, 다양성, 기억 및 자기/비자기의 인식이라는 네 가지의 특징을 가지고 있으며, 외부 유입물질을 제거하는 반응에 따라 체액성 면역 반응 (humoral immune response)과 세포성 면역반응 (cell-mediated immune response)으로 구분된다. 체액성 면역은 침입한 항원의 구조 특이적으로 생성된 B cell 유래 항체와의 반응과 간이나 대식세포 등에서 합성되어 분비된 혈청내 보체 등에 의해 매개되는 반응으로 구성되어 있다. 세포성 면역반응은 T helper cell (CD4+), cytotoxic T cell (CD8+), B cell 및antigen presenting cell 중개를 통한 세포간 상호 작용에 의해 발생되는 면역반응이다. 선천성 면역반응의 하나인 염증은 우리 몸에서 가장 빈번히 발생되고 있는 방어작용의 하나이다. 예를 들면 감기에 걸렸을 경우, 환자의 편도선내 대식세포나 수지상세포류는 감염된 바이러스 단독 혹은 동시에 감염된 박테리아를 상대로 다양한 염증성 반응을 유도하게 된다. 또한, 상처가 생겼을 경우에도 감염원을 통해 유입된 병원성 세균과 주위조직내 선천성 면역담당 세포들 간의 면역학적 전투가 발생되게 된다. 이들 과정을 통해, 주위 세포나 조직이 손상되면, 즉각적으로 이들 면역세포들 (주로 phagocytes류)은 신속하게 손상을 극소화하고 더 나가서 손상된 부위를 원상으로 회복시키려는 일련의 염증반응을 유도하게 된다. 이들 반응은 우리가 흔히 알고 있는 발적 (redness), 부종 (swelling), 발열 (heat), 통증 (pain) 등의 증상으로 나타나게 된다. 즉, 손상된 부위 주변에 존재하는 모세혈관에 흐르는 혈류의 양이 증가하면서 혈관의 직경이 늘어나게 되고, 이로 인한 조직의 홍반과, 부어 오른 혈관에 의해 발열과 부종이 초래되는 것이다. 확장된 모세혈관의 투과성 증가는 체액과 세포들이 혈관에서 조직으로 이동하게 하는 원동력이 되고, 이를 통해 축적된 삼출물들은 단백질의 농도를 높여, 최종적으로 혈관에 존재하는 체액들이 조직으로 더 많이 이동되도록 유도하여 부종을 형성시킨다. 마지막으로 혈관 내 존재하는 면역세포들은 혈판 내벽에 점착되고 (margination), 혈관벽의 간극을 넓히는 역할을 하는 히스타민 (histamine)이나 일산화질소(nitric oxide : NO), 프로스타그린딘 (prostagladins : PGE2) 및 류코트리엔 (leukotriens) 등과 같은 chemical mediator의 도움으로 인해 혈관벽 사이로 삼출하게 되어 (extravasation), 손상된 부위로 이동하여 직접적인 외부 침입 물질의 파괴나 다른 면역세포들을 모으기 위한 cytokine (tumor necrosis factor [TNF]-$\alpha$, interleukin [IL]-1, IL-6 등) 혹은 chemokine (MIP-l, IL-8, MCP-l등)의 분비 등을 수행함으로써 염증반응을 매개하게 된다. 염증과정시 발생되는 여러 mediator 중 PGE2나 NO 및 TNF-$\alpha$ 등은 실험적 평가가 용이하여 이들 mediator 자체나 생성관련효소 (cyclooxygenase [COX] 및 nitric oxide synthase [NOS] 등)들은 현재항염증 치료제의 개발 연구시 주요 표적으로 연구되고 있다. 염증 반응은 지속기간에 따라 크게 급성염증과 만성염증으로 나뉘며, 삼출물의 종류에 따라서는 장액성, 섬유소성, 화농성 및 출혈성 염증 등으로 구분된다. 급성 염증 (acute inflammation)반응은 수일 내지 수주간 지속되는 일반적인 염증반응이라고 볼 수 있다. 국소반응은 기본징후인 발열과 발적, 부종, 통증 및 기능 상실이 특징적이며, 현미경적 소견으로는 혈관성 변화와 삼출물 형성이 주 작용이므로 일명 삼출성 염증이라고 한다. 만성 염증 (chronic inflammation)은, 급성 염증으로부터 이행되거나 만성으로 시작된다. 염증지속 기간은 보통 4주 이상 장기화 된다. 보통 염증의 경우에는 염증 생성 cytokine인 Th1 cytokine (IL-2, interferone [IFN]-$\gamma$ 및 TNF-$\alpha$ 등)의 생성 후, 거의 즉각적으로 항 염증성 cytokine인 Th2 cytokine(IL-4, IL-6, IL-10 및 transforming growth factor [TGF]-$\beta$ 등)이 생성되어 정상반응으로 회복된다. 그러나, 어떤 원인에서든 면역세포에 의한 염증원 제거 반응이 문제가 되면, 만성염증으로 진행된다. 이 반응에 주로 작용을 하는 염증세포로는 단핵구와 대식세포, 림프구, 형질세포 등이 있다. 암은 전세계적으로 사망률 1위의 원인이 되는 면역질환의 하나이다. 산화적 스트레스나 자외선 조사 혹은 암유발 물질들에 의해 염색체내 protooncogene, tumor-suppressor gene 혹은 DNA repairing gene의 일부 DNA의 돌연변이 혹은 결손 등이 발행되면 정상세포는 암화과정을 시작하게 된다. 양성세포 수준에서 약 5에서 10여년 후 악성수준의 암세포가 생성되게 되면 이들 세포는 새로운 환경을 찾아 전이하게 되는데 이를 통해 암환자들은 다양한 장기에 동인 오리진의 암세포들이 생성한 종양들을 가지게 된다. 이들 종양세포는 정상 장기의 기능을 손상시켜며 결국 생명을 잃게 만든다. 이들 염색체 수준에서의 돌연변이 유래 암세포는 거의 대부분이 체내 면역시스템에 의해 사멸되는 것으로 알려져 있다. 그러나 계속되는 스트레스나 암유발 물질의 노출은 체내 면역체계를 파괴하면서 최후의 방어선을 무너뜨리면서 암발생에 무방비 상태를 만들게 된다. 이런 이유로 체내 면역시스템의 정상적 가동 및 증강을 유도하게 하는 전략이 암예방시 매우 중요한 표적으로 인식되면서 다양한 형태의 면역증강 물질 개발을 시도하고 있다. 인삼은 두릅나무과의 여러해살이 풀로써, 오랜동안 한방 및 민간에서 원기를 회복시키고, 각종 질병을 치료할 수단으로 사용되고 있는 대표적인 전통생약이다. 예로부터 불로(不老), 장생(長生), 익기(益氣), 경신(經身)의 명약으로 구전되어졌는데, 이는 약 2천년 전 중국의 신농본초경(神農本草經)에서 "인삼은 오장(五腸)을 보하고, 정신을 안정시키고, 혼백을 고정하며 경계를 멈추게 하고, 외부로부터 침입하는 병사를 제거하여주며, 눈을 밝게 하고 마음을 열어 더욱 지혜롭게 하고 오랫동안 복용하면 몸이 가벼워지고 장수한다" 라고 기술되어있는 데에서 유래한 것이다. 다양한 연구를 통해 우리나라에서 생산되는 고려인삼 (Panax ginseng)이 효능 면에서 가장 탁월한 것으로 알려져 있으며 특별이 고려인삼으로부터 제조된 고려홍삼은 전세계적으로도 그 효능이 우수한 것으로 보고되어 있다. 대부분의 홍삼 약효는 dammarane계열의 triterpenoid인 ginsenosides라고 불리는 인삼 saponin에 의해 기인된 것으로 알려져 있다. 이들 화합물군의 기본 골격에 따라, protopanaxadiol (PD)계 (22종) 및 protopanaxatriol (PT)계 (10종)으로 구분되고 있다 (표 1). 실험적 접근을 통해 인삼의 약리작용 이해를 위한 다양한 노력들이 경주되고 있으나, 여전히 많은 부분에서 충분히 이해되고 있지 않다. 그러나, 현재까지 연구된 인삼의 약리작용 관련 연구들은 심혈관, 당뇨, 항암 및 항스트레스 등과 같은 분야에서 인삼효능이 우수한 것으로 보고하고 있다. 그러나 면역조절 및 염증현상과 관련된 최근 연구결과들은 많지 않으나, 향후 다양하게 연구될 효능부분으로 인식되고 있다.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.9-15
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• 1996

Purpose: The traditional approach with surgery and/or radiotherapy(RT) for advanced head and neck cancer Provides anticipated cure rates of $10-65\%$ depending on stages and sites. Recently, combined modality with chemotherapy have been extensively investigated in attempts to improve survival and local control. We retrospectively analysed our experience of 31 patients with advanced head and neck cancer. Materials and Methods : November 1983 to October 1994. 31 Patients with Stage III and IV squamous cell head and neck cancer were treated with RT. Sixteen patients were treated with RT alone, and IS patients were treated with combined RT plus chemotherapy. All patients were treated with 4-MV LINAC and radiation dose ranged from 5000 cGy to 7760 cGy (median 7010 cGy). In combined group, 7 patients were treated with cisplatin plus 5-FU 2 patients were treated with methotrexate plus leucovorin plus 5-FU plus cisplatin or carboplatin, and 6 patients were treated with cisplatin as a radiosensitizer. Results : Median follow up period was 16 months (range 4-134 months). The major responses (CR+PR) were noted in 10 patient ($66.6\%$) of the RT alone group and 14 patient ($93.3\%$) of the chemoradiation group. There was no statistical difference in CR rate between the two groups The overall survival rates at 5 years were $23.4\%$ in the radiation alone group, $23.5\%$ in the chemoradiation group Disease-free survival rates at 3 years were $44.5\%$ in the radiation alone group, $40\%$ in the chemoradiation group. There was no statistical differences in overall survival rates and disease-free survival rates between the two groups. Local recurrences occurred in $71.5\%$ of the radiation alone group, $72.7\%$ of the chemoradiation group and distant metastasis occurred in $14.4\%$ of radiation alone group, $9.1\%$ of the chemoradiation group. The frequencies of complications were comparable in both groups except hematologic toxicity Conclusion : Total response rates in the combined chemotherapy and radiotherapy was relatively higher than radiotherapy alone. But our result failed to show any survival benefit of the combined chemotherapy and radiotherapy. The accrual of large number of patients and long term follow-un may be necessary to confirm the present result of combined chemotherapy and radiotherapy.