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Effect of Exercise on Antioxidant Enzyme Activities of Skeletal Muscle and Liver in STZ-diabetic Rats (STZ-당뇨쥐에서 운동부하가 골격근 및 간의 항산화효소 활성도에 미치는 영향)

  • Seok, Kwang-Ho;Lee, Suck-Kang
    • Journal of Yeungnam Medical Science
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    • v.17 no.1
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    • pp.21-30
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    • 2000
  • Background: The purpose of the present study was to investigate the effect of exercise on the activities of antioxidant enzymes, super oxide dismutase(SOD), glutathione peroxidase(GPX) and catalase(CAT) of skeletal muscle(gastrocnemius) and liver in streptozotocin(STZ) induced diabetic rats. The malondialdehyde(MDA) concentration was also measured as an index of lipid poroxidation of tho tissues by exercise-induced oxidative stresses in diabetic rats. Material and Methods: Male Sprague-Dawley rats were randomly divided into control and STZ-induced diabetic rats. The STZ in citrate buffer solution was injected twice at S days intervals intraperitoneally(50, 70 mg/kg respectively). On the 28th day after the first STZ injection, the diabetic animals were randomly divided into pre- and post-exercise groups, The exercise was introduced to the rats of post-exercise group by treadmill running until exhaution with moderate intensity ($V_{O2max}$: 50-70%) of exercise. The duration of average running time was 2 hours and 19 minutes. Results: The blood glucose concentration was increased(p<0.001) and plasma insulin concentration was decreased(p<0.001) in the diabetic rats. The glycogen concentration in the muscle and liver was decreased by exhaustive exercise in the diabetic rats(p<0.001), In the skeletal muscle, the activities of GPX was increased(p<0.05) and the activities of SOD and CAT were not changed in the diabetic rats compare to those of the control rats. The activities of GPX was not changed by exercise but the activities of SOD(p<0.01) and CAT(p<0.01) were decreased by exercise in the diabetic rats, The concentration of MDA was not changed by exercise in diabetic rats, and the values of pre-exercise and post-exercise diabetic rats were not different from the value those of control rats, In the liver, the activities of SOD was decreased(p<0.01), and the activities of GPX and CAT were not changed in diabetic rats compared to the values of control rats, The activities of SOD, GPX and CAT were not changed by exercise in diabetic rats but the activity of SOD seemed to decrease slightly, The MDA concentration was increased in the diabetic rats compared to the values of control rats(p<0.001), but there was no change of MDA concentration by exercise in diabetic rats, Conclusions: In summary, exhaustive physical exercise did not seem to impose oxidative stress on the skeletal muscle because of due to oxygen free radicals, regardless of the decrease in SOD and CAT in the diabetic rats, In liver tissue, the tissue damage by oxidative stress was observed in diabetic rats but the additional tissue damage by exhaustive physical exercise was not observed.

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Efficacy of Self-manipulation Technique in the Treatment of Patients with Anterior Disc Displacement without Reduction (비정복성 관절원판 전방변위 환자의 치료에 있어서 자가 수조작술의 효과에 대한 연구)

  • Kim, Ju-Sik;Lee, Chae-Hoon;Kim, Young-Ku
    • Journal of Oral Medicine and Pain
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    • v.32 no.4
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    • pp.441-447
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    • 2007
  • Internal derangement of the temporomandibular joint(TMJ) is defined as an abnormal relationship of the articular disc to the condyle. Mandibular manipulation is one of the conservative treatments to be considered first to manage the patients with anterior disc displacement without reduction. Mandibular manipulation is used to increase articular mobility and to restore the displaced disc into an anatomically normal position. While Farrar's technique has been popularly used, Minagi et al., Mongini and Suarez introduced the manipulation technique conducted by the patients themselves. But there is no study on the efficacy of self-manipulation technique, comparing with conventional one. The aim of this study was to investigate the efficacy of the conventional and self-manipulation technique, which was modified to complement the previously described technique by Minagi et al., in the treatment of patients with anterior disc displacement without reduction. TMD patients, who visited Department of Oral Medicine of Seoul National University Dental Hospital from December, 2002 to November, 2004 and were diagnosed as anterior disc displacement without reduction by TMJ magnetic resonance imaging (MRI) were enrolled. Conservative treatments including physical therapy, exercise, behavioral therapy, stabilization splint therapy, and manipulation therapy were done to every single patient until the symptomsimproved enough to discharge the patient. The charts were reviewed retrospectively according to the type of manipulation. In the results, patients whose maximum mouth opening was more than 40 mm was higher in the self-manipulation group(69.9%) than in the conventional manipulation group(42.9%). But difference between two groups was not significant. According to the fact that we decided to discharge the patients whentheir mouth opening increased to more than 40 mm and subjective symptoms such as pain and discomfort were improved as well, treatment period of discharged patients was significantly shorter in the self-manipulation group($29.2{\pm}12.3$ weeks) than in the conventional manipulation group ($61.0{\pm}38.0$ weeks) (p<0.01). In conclusion, in the treatment of TMD patients with anterior disc displacement without reduction, the self-manipulation technique which is performed by patients themselves is an effective treatment modality for increasing the range of mouth opening and shortening the total treatment period.

Weed Occurrence in Upland Crop Fields of Korea (최근(最近) 한국(韓國)의 전작지(田作地) 잡초발생(雜草發生) 분포(分布)에 관(關하)여)

  • Chang, Y.H.;Kim, C.S.;Youn, K.B.
    • Korean Journal of Weed Science
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    • v.10 no.4
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    • pp.294-304
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    • 1990
  • For the survey of weed distribution in the cultivated upland of Korea, weed species were investigated at 2 field by crop of 2 myon per kun in 81 kun selected among the 139 kun of the whole country. 232 species in 46 families were observed, totally. From among the result, 165 species in 39 families the in winter crop field, 189 species in 41 families in the summer crop field were classified. 122 species in 34 families were emerged the from the upland crop field of the whole season. Further more, in the 10 dominant weed species which emerged from upland crop field, Alopecurus aequalis, Chenopodium album, slellaria media, Galium spurieum, Capsella bursa-pastoris and Rorippa islandica were dominated in the winter upland and paddy field, and that Erigeron canadensis, Cyperus amuricus, Equisetum arvense and Arenaria serpyllifolia were dominated in the winter upland field, additionally. Stellaria alsine, Bothriospermum tenellum, Trigonotis peduncularis and Polygonum arviculare were dominated in the winter cropping on drained paddy field, additionally. In the summer crop field, Digitaria sanguinalis, Portulaca oleracea, Acalypha australis, Echinochloa crus-galli, Setaria viridis, Persicaria hydropiper, Amaranthus lividus, commelina communis, Chenopodium album and Cyperecs amuricus were dominated.

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Hyperfractionated Radiotherapy Following Induction Chemotherapy for Stage III Non-Small Cell Lung Cancer -Randomized for Adjuvant Chemotherapy vs. Observation- (절제 불가능한 제 3 기 비소세포 폐암의 MVP 복합 항암요법과 다분할 방사선 치료 -추가 항암요법에 대한 임의 선택 -)

  • Choi, Eun-Kyung;Chang, Hye-Sook;Ahn, Seung-Do;Yang, Kwang-Mo;Suh, Cheol-Won;Lee, Kyoo-Hyung;Lee, Jung, Shin;Kim, Sang-Hee;Ko, Youn-Suk;Kim, Woo-Sung;Kim, Won-Dong;Song, Koun-Sik;Sohn, Kwang-Hyun
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.295-301
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    • 1993
  • Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

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Analysis of Critical Control Points through Field Assessment of Sanitation Management Practices in Foodservice Establishments (현장실사를 통한 급식유헝별 위생관리실태 분석)

  • Kwak Tong-Kyung;Lee Kyung-Mi;Chang Hye-Ja;Kang Yong-Jae;Hong Wan-Soo;Moon Hye-Kyung
    • Korean journal of food and cookery science
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    • v.21 no.3 s.87
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    • pp.290-300
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    • 2005
  • Increased sanitation management of foodservice establishments is required because most of the reported foodborne-disease outbreaks were in the foodservice industry. The purpose of this study was to determine the important control points for good sanitation. In this study, we inspected twenty foodservice establishments in Seoul, Kyunggi, Kyungnam with a self-developed monitoring tool. These foodservice establishments included secondary schools, universities, and industries. Six of them had appointed as the HACCP-certified establishments from the Korea Food and Drug Administration. The inspection was conducted from June to August in 2002. The inspection tool consisted of nine dimensions and sixty-five items. The dimensions were 'personal sanitation', 'supply of raw food', 'food storage', 'handling of raw food and ready-to-eat', 'cleaning and sterilization', 'waste control', 'pest control', and 'control of establishment and equipment' The highest possible score of this inspection tool is 105 points. Statistical data analysis was completed using the SPSS Package(11.0) for descriptive analysis Kruskal-Wallis. The score for the secondary schools (83.6 points) was higher than for the others and number of in compliance item was 50.9 on average. Therefore, we concluded that the secondary schools' sanitation condition was good. The foodservice establishments acquired HACCP certification was 89.7 points, which was significantly higher than that of establishments not applying foodservices in total score. Instituting the HACCP system in a foodservice is very effective for sanitation management. Many out of the compliance observations were found in the dimensions of 'waste control', 'control of establishment and equipment', and 'supply of raw food' 'Clean condition of refrigerator' item was $65\%$ out of the compliance that was the highest percent in this study. 'Notify and observance of heating/reheating temperature' was $45\%$ out of compliance. Items which were over $30\%$ out of compliance were 'sterilization of knifes and chopping boards in cooking', 'education of workers', 'maintain refrigerator temperature blow $5^{\circ}C$', and 'countermeasure of infection workers' In the results, most of the foodservice establishments were poorly managed in temperature control and cross-contamination. The important control points revealed in this study were preventing contamination, cooking temperature compliance, management of raw food and refrigerator. Therefore foodservice establishments should pay attention to education and training about important control points. The systematic sanitation management monitoring tool developed in this study can be effectively applied for conducting self-inspection and improving the sanitary conditions of their own foodservice operations.

Effect of Nasal Continuous Positive Airway Pressure after Early Surfactant Therapy in Moderate Respiratory Distress Syndrome (중등도 신생아 호흡 곤란 증후군에서 폐 표면 활성제 조기 투여 후 Nasal CPAP의 치료 효과)

  • Kim, Eun Ji;Kim, Hae Sook;Hur, Man Hoe;Lee, Sang Geel
    • Clinical and Experimental Pediatrics
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    • v.45 no.10
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    • pp.1204-1212
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    • 2002
  • Purpose : Early surfactant therapy with either gentle ventilation, high-frequency ventilation or aggressive weaning of mechanical ventilation are principles for the treatment of respiratory distress syndrome(RDS). We studied to determine the accessibility of noninvasive nasal continuous positive airway pressure(CPAP) rather than mechanical ventilation by invasive intubation after early surfactant therapy. Methods : The study group consisted of 14 infants who were born and diagnosed with moderate respiratory distress syndrome and received early surfactant therapy with nasal CPAP of PEEP 5-6 cm $H_2O$ within two hours after birth in the Fatima neonatal intensive care unit for two years from January 1999 to August 2001. The control group consisted of 15 infants who were diagnosed with the disease and could be weaned from mechanical ventilator within five days after birth during the same period. Results : The characteristics, the severity of clinical symptoms and laboratory findings in the two groups at birth showed no significant difference. Neither did the interim analysis of laboratory data in two groups. Of 14 infants in the study group who received nasal CPAP after early surfactant therapy, only two infants showed weaning failure with this therapy. In the response cases, duration of CPAP was five days and mean airway pressure was $5.4{\pm}0.5cm$ $H_2O$. Two had the complication of CPAP with abdominal distension. Final complications and outcomes in the two groups showed no signifcant difference(P>0.05). Conclusion : The clinical courses in the two groups showed no significant difference. Therefore, we suggest that early surfactant therapy with noninvasive nasal CPAP is a simple and safe method rather than aggressive weaning after invasive mechanical ventilation in moderate respiratory distress syndrome.

The recent essay of Bijeung - Study of III- (비증(痺證)에 대(對)한 최근(最近)의 제가학설(諸家學說) 연구(硏究) - 《비증전집(痺證專輯)》 에 대(對)한 연구(硏究) III -)

  • Yang, Tae-Hoon;Oh, Min-Suk
    • Journal of Haehwa Medicine
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    • v.9 no.1
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    • pp.513-545
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    • 2000
  • I. Introduction Bi(痺) means blocking. It can reach at the joints or muscles or whole body and make pains. Numbness and movement disorders. BiJeung can be devided into SilBi and HeoBi. In SilBi there are PungHanSeupBi, YeolBi and WanBi. In HeoBi, there are GiHyeolHeoBi, EumHeoBi and YangHeoBi. The common principle for the treatment of BiJeung is devision of the chronic stage and the acute stage. In the acute stage, BiJeung is usually cured easily but in the chronic stage, it is difficult. In the terminal stage, BiJeung can reach at the internal organs. BiJeung is one kind of symptoms making muscles, bones and jonts feel pain, numbness or edema. For example it can be gout or SLE etc. Many famous doctors studied medical science by their fathers or teachers. So the history of medical science is long. So I studied ${\ll}Bijeungjujip{\gg}$. II. Final Decision 1. BanSuMun(斑秀文) thought that BiJeung can be cured by blocking of blood stream. So he insisted that the important thing to cure BiJeung is to improve the blood stream. He usually used DangGuiSaYeokTang(當歸四逆湯), DangGuiJakYakSanHapORyeongSan, DoHong-SaMulTang(桃紅四物湯), SaMyoSanHapHeuiDongTang and HwangGiGyeJiOMulTang. 2. JangGeonBu(張健夫) focused on soothing muscles and improving blood seam. So he used many herbs like WiRyeongSeon(威靈仙), GangHwal(羌活), DokHwal(獨活), WooSeul(牛膝), etc. Especially he pasted wastes of the boiled herbs. 3. OSeongNong(吳聖農) introduced four rules to treat arthritis. So he usually used SeoGak-SanGaGam(犀角散加減), BoYanHwanOTang(補陽還五湯), ODuTang(烏頭湯), HwangGiGyeJiOMulTang. 4. GongJiSin thought disk hernia as one kind of BiJeung. And he said that Pung can hurt upper limbs and Seup can hurt lower limbs. He used to use GyeJiJakYakJiMoTang(桂枝芍藥知母湯). 5. LoJiJeong(路志正) introduced four principles to treat BiJeung. He used BangPungTang(防風湯), DaeJinGuTang) for PungBi(風痺), OPaeTang(烏貝湯) for HanBi(寒痺), YukGunJaTang(六君子湯) for SeupBi(濕痺) and SaMyoTang(四妙湯), SeonBiTang(宣痺湯), BaekHoGaGyeTang(白虎加桂湯) for YeolBi(熱痺). 6. GangChunHwa(姜春華) discussed herbs. He said SaengJiHwang(生地黃) is effective for PungSeupBi and WiRyungSun(威靈仙) is effective for the joints pain. He usually used SipJeonDaeBoTang(十全大補湯), DangGuiDaeBoTang(當歸大補湯), YoukGunJaTang(六君子湯) and YukMiJiHwanTang(六味地黃湯). 7. DongGeonHwa(董建華) said that the most important thing to treat BiJeung is how to use herbs. He usually used CheonO(川烏), MaHwang(麻黃) for HanBi, SeoGak(犀角) for YeolBi, BiHae) or JamSa(蠶沙) for SeupBi, SukJiHwang(熟地黃) or Vertebrae of Pigs for improving the function of kidney and liver, deer horn or DuChung(杜沖) for improving strength of body and HwangGi(黃?) or OGaPi(五加皮) for improving the function of heart. 8. YiSuSan(李壽山) devided BiJeung into two types(PungHanSeupBi, PungYeolSeupBi). And he used GyeJiJakYakJiMoTang(桂枝芍藥知母湯) for the treatment of gout. And he liked to use HwanGiGyeJiOMulTangHapSinGiHwan 枝五物湯合腎氣丸) for the treat ment of WanBi(頑痺). 9. AnDukHyeong(顔德馨) made YongMaJeongTongDan(龍馬定痛丹)-(MaJeonJa(馬錢子) 30g, JiJaChung 3g, JiRyong(地龍) 3g, JeonGal(全蝎) 3g, JuSa(朱砂) 0.3g) 10. JangBaekYou(張伯臾) devided BiJeung into YeolBi and HanBi. And he focused on improving blood stream. 11. JinMuO(陳茂梧) introduced anti-wind and dampness prescription(HoJangGeun(虎杖根) 15g, CheonChoGeun 15g, SangGiSaeng(桑寄生) 15g, JamSa(蠶絲) 15g, JeMaJeonJa(制馬錢子) 3g). 12. YiChongBo(李總甫) explained basic prescriptions to treat BiJeung. He used SinJeongChuBiEum(新定推痺陰) for HaengBi(行痺), SinJeongHwaBiSan(新定化痺散) for TongBi(痛痺), SinJeongGaeBiTang(新定開痺湯) for ChakBi(着痺), SinJeongCheongBiEum(新定淸痺飮) for SeupYeolBi(濕熱痺), SinRyeokTang(腎瀝湯) for PoBi(胞痺), ORyeongSan for BuBi(腑痺), OBiTang(五痺湯) for JangBi(臟痺), SinChakTang(腎着湯) for SingChakByeong(腎着病). 13. HwangJeonGeuk(黃傳克) used SaMu1SaDeungHapJe(四物四藤合制) for the treatment of a acute arthritis, PalJinHpPalDeungTang(八珍合八藤湯) or BuGyeJiHwangTangHapTaDeungTang(附桂地黃湯合四藤湯) for the chronic stage and ByeolGapJeungAekTongRakEum(鱉甲增液通絡飮) for EumHeo(陰虛) 14. GaYeo(柯與參) used HwalRakJiTongTang(活絡止痛湯) for shoulder ache, SoJongJinTongHwalRakTank(消腫鎭痛活絡湯) for YeolBi(熱痺), LiGwanJeolTang(利關節湯) for ChakBi(着痺), SinBiTang(腎痺湯) for SinBi(腎痺) and SamGyoBoSinHwan(三膠補腎丸) for back ache. 15. JangGilJin(蔣길塵) liked to use hot-character herbs and insects. And he used SeoGeunLipAnTang(舒筋立安湯) as basic prescription. 16. RyuJangGeol(留章杰) used GuMiGangHwalTang(九味羌活湯) and BangPungTang(防風湯) at the acute stage, ODuTang(烏頭湯) or GyeJiJakYakJiMoTang(桂枝芍藥知母湯) for HanBi of internal organs, YangHwaHaeEungTang(陽和解凝湯) for HanBi, DokHwalGiSaengTang(獨活寄生湯), EuiYiInTang(薏苡仁湯) for SeupBi, YukGunJaTang(六君子湯) for GiHeoBi(氣虛痺) and SeongYouTang(聖兪湯) for HyeolHeoBi(血虛痺). 17. YangYuHak(楊有鶴) liked to use SoGyeongHwalHyelTang(疏經活血湯) and he would rather use DoIn(桃仁), HongHwa(紅花), DangGui(當歸), CheonGung(川芎) than insects. 18. SaHongDo(史鴻濤) made RyuPungSeupTang(類風濕湯)-((HwangGi 200g, JinGu 20g, BangGi(防己) 15g, HongHwa(紅花) 15g, DoIn(桃仁) 15g, CheongPungDeung(靑風藤) 20g, JiRyong(地龍) 15g, GyeJi(桂枝) 15g, WoSeul(牛膝) 15g, CheonSanGap(穿山甲) 15g, BaekJi(白芷) 15g, BaekSeonPi(白鮮皮) 15g, GamCho(甘草) 15g).

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The Effect of Pleural Thickening on the Impairment of Pulmonary Function in Asbestos Exposed Workers (석면취급 근로자에서 늑막비후가 폐기능에 미치는 영향)

  • Kim, Jee-Won;Ahn, Hyeong-Sook;Kim, Kyung-Ah;Lim, Young;Yun, Im-Goung
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.923-933
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    • 1995
  • Background: Pleural abnormality is the the most common respiratory change caused by asbestos dust inhalation and also develop other asbestos related disease after cessation of asbestos exposure. So we conducted epidemiologic study to investigate if the pleural abnormality is associated with pulmonary function change and what factors are influenced on pulmonary function impairment. Methods: Two hundred and twenty two asbestos workers from 9 industries using asbestos in Korea were selected to measure the concentration of sectional asbestos fiber. Ouestionnaire, chest X-ray, PFT were also performed. All the data were analyzed by student t-test and chi-square test using SAS. Regressional analysis was performed to evaluate important factors, for example smoking, exposure concentration, period and the existence of pleural thickening, affecting to the change of pulmonary function. Results: 1) All nine industries except two, airborn asbestos fiber concentration was less than an average permissible concentration. PFT was performed on 222 workers and the percentage of male was 88.3%, their mean age was $41{\pm}9$ years old, and the duration of asbestos exposure was $10.6{\pm}7.8$ yrs. 2) The chest X-ray showed normal(89.19%), pulmonary Tb(inactive)(2.7%), pleral thickening (7.66%), suspected reticulonodular shadow(0.9%). 3) The mean values of height, smoking status, concentration of asbestos fiberwere not different between the subjects with pleural thickening and others, but age, cumulative pack-years, the duration of asbestos exposure were higher in subjects with pleural thickening. 4) All the PFT indices were lower in the subjects with pleural thickening than in the subjects without pleural thickening. 5) Simple regression analysis showed there was a significant correlation between $FEF_{75}$ which is sensitive in small airway obstruction and cumulative smoking pack-years, the duration of asbestos exposure and the concentration of asbestos fiber. 6) Multiple regression analysis showed all the pulmonary function indices were decreased as the increase of cumulative smoking pack-years and especially in the indices those are sensitive in small airway obstruction. Pleural thickening was associated with reduction in FVC, $FEV_1$, PEFR and $FEF_{25}$. Conclusion: The more concentration of asbestos fiber and the more duration of asbestos exposure, the greater reduction in $FEF_{50}$, $FEF_{75}$. Therefore PFT was important in the evaluation of early detection for small airway obstruction. Furthermore pleural thickening without asbesto-related parenchymal lung disease is associated with reduction in pulmonary function.

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Prognostic Value of the Expression of p53 and bcl-2 in Non-Small Cell Lung Cancer (비소세포폐암에서 p53과 bcl-2의 발현이 예후에 미치는 영향)

  • Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee;Keum, Joo-Seob;Kong, Gu;Lee, Jung-Dal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.962-974
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    • 1998
  • Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

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Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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