Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

Youn, Cha Kyung,Park, Seon Joo,Li, Mei Hong,Lee, Min Young,Lee, Kun Yeong,Cha, Man Jin,Kim, Ok Hyeun,You, Ho Jin,Chang, In Youp,Yoon, Sang Pil,Jeon, Young Jin The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

원인 불명의 실신 환자의 진단에 있어서 Head - up tilt Test 의 유용성과 혈관미주신경성 실신 환자의 임상적 특징

윤호중(Ho Joong Youn),정욱성(Wook Sung Chung),백상홍(Sang Hong Baek),김철민(Chul Min Kim),박인수(In Soo Park),김재형(Jae Hyung Kim),최규보(Kyu Bo Choi),홍순조(Soon Jo Hong) 대한내과학회 1994 대한내과학회지 Vol.47 No.2

Background: Syncope, defined as a transient loss of consciousness, is a frequently encountered symptom, but despite thorough clinical and invasive diagnostic investigation, the cause of syncope remains unexplained. In recent years, head-up tilt test has been of increasing interest as a diagnostic aids in patients with unexplained syncope. We studied to define the usefulness of various diagnostic test in the evaluation of patients with recurrent syncope, to assess the usefulness of head-up tilt test in the working of syncope of unknown origin and to evaluate the clinical characteristics of subgroups of patients with syncope induced by head-up tilt test. Methods: Between June, 1991 and November, 1992 at St. Mary`s hospital, 21 patients with history of syncope and 24 control subjects without history of syncope underwent 60° head-up tild test for 60 min. Results: 1) The definite cause for recurrent syncope were diagnosed in 10 of patients (47,6%) after clinical and invasive tests. 2) During head-up tilt test, vasovagal responses were provoked in 5 of 21 patients (23.8%) with recurrent syncope and 1 of 24 patients (4.2%) without syncope (p<0,05). 3) The head-up tilt test induced symptomatic bradycardia or hypotension in 3 of 10 patients (30%.) with negative electrophysiologic results. 4) During tilt induced vasovagal response, a) mean heart rate decreased to 42±24 beat/min from supine control of 70±12 beat/min (p<0. 05), b) mean systolic blood pressure decreased to 95±12 mmHg from supine control of 120±S mmHg (p<0,05), c) mean diastolic blood pressure decreased to 60±21mmHg from supine control of 72±13 mmHg (p<0.05), d) the time interval to onset of vasovagal response was 22±12 min. Conclusions: 1) In a large proportion of patients with recurrent syncope, the diagnosis remains unexplained despite a neurologic and cardiologic investigation including an electrophysiologic study. 2) Vasovagal responses are frequent cause in patients with recurrent unexplained syncope. 3) The head-up tilt test may be a simple, safe and highly yielding provocative test in the investigation of syncope of unknown origin.

Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

Cha Kyung Youn,Seon Joo Park,Mei Hong Li,Min Young Lee,Kun Yeong Lee,Man Jin Cha,Ok Hyeun Kim,Ho Jin You,In Youp Chang,Sang Pil Yoon,Young Jin Jeon 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-Ձ, IFN-Ճ, and IL-1Ղ). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-ՊB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Intracavitary Radiation Therapy for Recurrent Cystic Brain Tumors with Holmium-166-Chico : A Pilot Study

Ha, Eun Jin,Gwak, Ho-Shin,Rhee, Chang Hun,Youn, Sang Min,Choi, Chang-Woon,Cheon, Gi Jeong The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.54 No.3

Objective : Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. Methods : Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. Results : There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. Conclusion : Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

동충하초 투여가 최대하 운동 시 지방연소에 미치는 영향

김철우,이용수,이상현,이상호,하민수,윤영조,이재일 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.14 No.4

The purpose of this study was to evaluate effects of Cordyceps militaris on fat oxidation during submaximal exercise. Fifteen healthy male collegiate students(ingestion group, N=7; control group, N=8) participated as subjects after signing an informed consent following overnight, subjects completed maximal graded execise test on treadmill to determine exercise intensity(50%VO2max). To evaluate the fat oxidation using indirect calorimeter, it was performed submaximal treadmill to determine exercise lasting. 40min at 50%VO2max after 5day and consumed Cordyceps militaris on separate days. This study was used 2×4 two way repeated ANOVA to analyze physiological and metabolic variables between two groups and metabolic variables between two groups and four exercise periods(l0min, 20min, 30min 40min), and used Scheffe to post-hoc test. Significance was set at α=.05. The results of this study were as followed: First, there were significantly highest in ingestion group for V02, percentage of fat oxidetion(%fat), fat per kilocarolies(Fkcal), and total per kilocarolies(Tkcal)(p<.05), but respiratory exchange ration(RER) and heart rete(HR) were significantly lower in ingestion group(p<.05). Second, RER, %fat, Fkcal were significantly difference in 10, 20, 30, 40min of exercise period(p<.05). This results suggest that there is the effect of Cordyceps militaris on fat oxidation submaximal exercise. Additionally, to evaluate effect of Cordyceps militaris as ergogenic aid, it should be required the future study that included extend subjects, various dosage, and chronic consumption.

Purification and Characterization of Helicobacter pylori ${\gamma}$-Glutamyltranspeptidase

Song, Jae-Young,Choi, Yeo-Jeong,Kim, Jeong-Min,Kim, Yoo-Ree,Jo, Jin-Seong,Park, Jin-Sik,Park, Hee-Jin,Song, Yun-Gyu,Lee, Kon-Ho,Kang, Hyung-Lyun,Baik, Seung-Chul,Youn, Hee-Shang,Cho, Myung-Je,Rhee, Kw The Korean Society for Microbiology 2011 Journal of Bacteriology and Virology Vol.41 No.4

Gamma-glutamyltranspeptidase (GGT) was purified to electrophoretic homogeneity from the cell extract of H. pylori. The purified enzyme consisted of heavy and light subunits with molecular weights of 38 kDa and 21 kDa, respectively. N-terminal amino acid sequence of heavy and light subunits revealed that H. pylori GGT was processed into 3 parts for a signal peptide of 27 amino acid residues, a heavy subunit of 352 residues, and a light subunit of 188 residues during translation. The reaction rate for hydrolysis of ${\gamma}$-GpNA was 84.4 ${\mu}mol/min$ per milligram of protein, and that for the ${\gamma}$-glutamyl transfer from ${\gamma}$-GpNA to gly-gly was 23.8 ${\mu}mol/min$ per milligram of protein. The apparent Km values of H. pylori GGT for ${\gamma}$-glutamyl compounds were on the order of $10^{-3}$ to $10^{-4}$ M and those for acceptor peptides and amino acids were on the order of $10^{-1}$ to $10^{-2}$ M. The GGT protein kept approximately 80% of the initial enzymatic activity on incubation at $60^{\circ}C$ for 15 min. The optimum temperature and pH for reactions of both hydrolysis and transpeptidation were $40^{\circ}C$ and 9.0, respectively. The transpeptidation and hydrolysis reactions catalyzed by H. pylori GGT were strongly inhibited by L-Gln and moderately inhibited by L-Ala, L-Ser, ${\beta}$-chloro-L-Ala, and L-Glu. These results demonstrated that the biochemical properties of H. pylori GGT are different from those of other bacterial GGTs. Further, H. pylori GGT might degrade glutathione in the gastric mucous layer of humans if the enzyme could be secreted in the bacterial niches.

불응성 자가면역질환에서의 자가조혈모세포이식

민도준,양동원,민창기,김완욱,이상헌,박성환,김동욱,이종욱,조철수,민우성,김범생,김호연,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 기존의 치료에 불응하고 예후가 불량한 자가면역질환 환자들에게 최근 고용량 면역억제 및 조혈모 세포이식이 새로운 치료방법으로 대두되고 있다. 저자들은 다발성 경화증(multiple sclerosis, MS) 및 류마티스 관절염(rheumatoid arthritis, RA) 등 2명의 자가면역질환 환자들에서 자가조혈모세포 이식을 시행하였다. 방법: 말초혈액 조혈모세포 가동화를 위하여 cyclophosphamide (4 g/㎡) 및 granulocyte colony stimulating factor (10 g/kg/day)를 투여하였고, CD34+ 세포를 분리·채집 하였다, 이식 전처치로 MS 환자에서 BEAM 및 antihymocyte globulin (ATG) (3.75 mg/kg), RA 환자에서 fludarabine (180 mg/㎡), ATG (10 mg/kg)와 busulfan (8 mg/kg)을 투여하였다. 결과: 호중구 수가 500/㎕ 이상으로 회복되는 기간은 MS 환자에서 9일, RA 환자에서 15일이었다. 혈소판이 20.000/㎕ 이상으로 회복되는 가간은 RA 환자에서 9일 이었고, MS 환자에서는 혈소판 감소증이 발생하지 않았다. 비혈액학적 독성으로 MS 환자에서 WHO 1도의 오심 및 점막염이 관찰되었다. MS 환자는 이식 6개월 후까지 시력감소가 남아있었으나, 이식전에 관찰되던 감각이상 및 운동장애 등의 신경학적 이상 소견은 더 이상 관찰되지 않았다. RA 환자는 이식 1개월 후 관절 증상 및 검사소견의 호전을 보였다. 결론: 불응성 자가면역질환 환자에서 고용량 면역억제 및 조혈모세포이식은 적은 독성으로 높은 치료효과를 기대할수 있으며, 향후 이 시술의 임상적 의의를 규명하기 위하여 전향적이고 장기적인 연구가 필요할 것으로 사료된다. Background: High-dose immunosuppressive therapy followed by autologous hemathpoietic stem cell transplantation (HSCT) has been proposed as a new approach to treat severe, refractory autoimmune diseases. We describe two patients with refractory autoimmune diseases (one multiple sclerosis 〔MS〕and one rheumatoid arthritis〔RA〕) who underwent T-cell-depleted autologous peripheral bleed stem cell transplantation for the first time in Korea. Methods: We mobilized autologous stem cells with cyclophisphamide (4 g/㎡) and granulocyte colony-stimulating factor (10 ㎍/kg/day). Stem cells were enriched ex vivo using CD34-positive immunoselection and reinfused after high-dose chemotherapy with BEAM and antithymocyte globulin (ATG) (3.75 mg/kg) in MS, or fludarabine (180 mg/㎡), ATG (10 mg/kg) and busulfan (8 mg/kg) in RA. Results: The engraftment with an absolute nerutrophil count greater than 500㎕ occurred on day 9 in MS and 15 in RA, respectively. The time to nontransfused platelet count greater than 2.000/㎕ was 9 day in RA. MS patient did not show ant episode of thrombocytopenia. Regimen-related non-hematopoietic toxicity was minimal. For 6 months since HSCT, them patient with MS had been free from previously existed sensory and motor abnormalities except decreased visual acuity. Then patient with RA and only one tender joint and two mildly swollen joints with improvement in laboratory parameters at one month after HSCT. Conclusion: These results underscore the feasibility and potential efficacy of intensive immunosuppression followed by autologous HSCT for treatment of intractable autoimmune diseases. The durability of remission, however, remains to be clarified.

회전원판법에 의한 페놀성 폐수처리시 중금속의 영향에 관한 실험적 연구

정연규,민달기,배범한,신창호 연세대학교 산업기술연구소 1988 논문집 Vol.20 No.2

본 연구는 회전원판법(RBC) 에 의한 페놀성 폐수의 처리시 Cd(II), Zn(II) 가 페놀 및 페놀성 유기물 제거에 미치는 영향을 비교 분석한 것으로 pH , 온도, 체류시간, 회전속도를 일정하게 한 뒤, 일정한 페놀농도 system 에 Cd(II), Zn(II) 농도의 단계적 변화 후 정상상태(Steady State)에서 페놀과 페놀성 유기물 제거율 및 Cd(II), Zn(II) 농도를 측정하였다. 본 연구에서 실험결과를 분석하여 얻은 결론은 다음과 같다. 미생물이 Cd(II), Zn(II)의 독성에 영향을 받아, 페놀 및 페놀성 유기물제거율이 감소되었다. 특히, 페놀농도 400mg/L system 에서 Cd(II), Zn(II) 50mg/L 을 유입시킬 때 페놀 및 페놀성 유기물제거율이 50% 미만으로 감소되었다. 또한 Cd(II), Zn(II) 유입으로 system 내의 미생물 종류변화가 거의 일어나지 않는다는 사실을 알 수 있었다. This study is an experimental research about the effects of heavy metal on treatment of phenol and phenolic organics using Rotating Biological Contactors. The concentrations of phenol, phenolic organics, and heavy metal are measured at study after the concentration of heavy metal is made to be changed by steps in constant phenolic concentration system. The temperature, pH, retention time, and the time of rotation are set to be constant. This results of this study obtained by analysing the experimental data are as follows: (1) Phenol removal efficiency and phenolic organics removal efficiency decreased because micro-organism was affected by the toxicity heavy metal. (2) When heavy metal concentration 50 mg/L was inflowed in phenol concentration 400mg/L system, phenol and phenolic organics removal efficiency decreased less than 50 percents. (3) It can be known that change of microorganism species with system was not occured by heavy metal inflow.

연속 혼합 흐름 반응기에서 평균 체류 시간에 관한 연구

함영민,이창일,차윤호 단국대학교 1999 산업기술연구 Vol.1 No.-

Mean residence time has been measured in a continuous stirred tank reactor by the analysis of age distribution function in order to determine the effect of agitator speed and liquid flow rate. The data were obtained in the ranges of agitator speed from 50 rpm to 100 rpm and liquid flow rate from 50 ml/min to 150 ml/min. Age-distribution curve was studied by measuring the conductivity of KCl as a tracer. The effect of agitator speed and liquid flow rte on the mean residence time are determined. The parameter f(t￣_exp / t￣_p) represents the degree of deviation from perfect mixing. The parameter f was found to be strongly affected by agitator speed but little affect by liquid flow rate.

Ca^(2+)-감수성 증가기전과 평활근 수축

이연리,김보경,최원호,김태경,이창권,배영민,조성일 건국대학교 의과학연구소 2004 건국의과학학술지 Vol.14 No.-

Smooth muscle contraction is regulated by intracellular Ca^(2+) ([Ca^(2+)]_(i)) and the phosphorylation of myosin light chain (MLC). However, various kinds of vasoconstrictors induce a further contraction at a given [Ca^(2+)]_(i), and elicit a sustained contraction under Ca^(2+) -depleted conditions, referred to as "Ca^(2+) -sensitization", in intact and membrane-pen-neabilized smooth muscle. Previously, several molecules, including protein kinase C (PKC), RhoA, and mitogen-activated protein kinases (MAPK), have been suggested as candidate regulators of Ca^(2+) -sensitization. In the present review, we describe the role of PKC, RhoA, and MAPK in the regulation of Ca^(2+) -sensitization, and suggest a new model in research for the regulation of smooth muscle contraction.