• Childhood Kidney Diseases
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• v.8 no.2
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• pp.138-148
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• 2004

Purpose: Regardless of the underlying diseases, the proteinuric condition demonstrates ultrastructural changes in podocytes with retraction and effacement of the highly specialized interdigitating foot processes. We examined the molecular basis for this alteration of the podocyte phenotypes, including quantitative and distributional changes of ZO-1 protein as a candidate contributing to the pathogenic changes in the barrier to protein filtration. Methods: To investigate whether high glucose and advanced glycosylation endproduct(AGE) induce podocyte cytoskeletal changes, we cultured rat GEpC under 1) normal glucose(5 mM=control) or 2) high glucose(30 mM) or 3) AGE-added or 4) high glucose plus AGE-added conditions. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. Results: By confocal microscopy, we observed that ZO-1 moves from peripheral cytoplasm to inner actin filaments complexes in both AGE-added and high glucose condition. In Western blotting, high glucose or AGE-added condition decreased the ZO-1 protein expression by 11.1%(P>0.05) and 2.3%(P>0.05), respectively compared to the normal glucose condition. High glucose plus AGE-added condition further decreased ZO-1 protein expression to statistically significant level(12%, P<0.05). No significant change was seen in the osmotic control. In RT-PCR, high glucose plus AGE-added condition significantly decreased the expression of ZO-1 mRNA by 12% compared to normal glucose condition. Conclusion: We suggest that both high glucose and AGE-added condition induce the cytoplasmic translocation and suppresses the production of ZO-1 at transcriptional level and these changes may explain the functional changes of podocytes in diabetic conditions.

• Journal of Chest Surgery
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• v.31 no.6
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• pp.560-566
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• 1998

Background: Bovine pericardial bioprosthesis treated with glutaraldehyde (GA) is one of the most popular prosthetic materials, but late calcific degeneration after implantation is a problem that remains unsolved. For the purpose of mitigating the calcific degeneration, we added MgCl2 into the 0.625% GA solution to compete with calcium for binding to the free aldehyde from GA and pretreated with the surfactants like sodium dodecyl sulfate (SDS) and Triton X-100 before GA fixation for preventing the phospholipid infiltration into the pericardial tissue, the first step of the calcific degeneration. Material and Method: 40 square-shaped pieces of bovine pericardia were fixed in 0.625% GA solution with 4g/L MgCl2 6H2O as a control group (group 1). 40 pieces pretreated with 1% SDS were also fixed in the same GA solution (group 2) and other 40 pieces pretreated with 1% Triton X-100 were prepared with the same method (group 3). After 1 month of fixation these were implanted into the belly of 40 Sprague-Dawley subdermally and extracted 1 month, 2 months, 3 months and 6 months after implantation. With atomic absorption spectrophotometry we measured the deposited calcium amount. Result: 1 month after implantation we could not find any differences between the three groups, but by the 2nd month calcium deposition was 0.921$\pm$0.121 mg/g in group 1, 0.481$\pm$0.037 mg/g in group 2 and 1.369$\pm$0.200 mg/g in group 3. By the 3rd month it was 0.786$\pm$0.080 mg/g in group 1, 0.584$\pm$0.054 mg/g in group 2 and 1.139$\pm$0.188 mg/g in group 3, and on the 6th month 1.623$\pm$0.601 mg/g in group 1,0.501$\pm$0.043 mg/g in group 2 and 1.625$\pm$0.382 mg/g in group 3, with statistical significance in group 2(p<0.05). Conclusion: Pretreatment with SDS showed meaningful calcium mitigation effects on subcutaneously implanted bovine pericardium in the rat models but the neutral type surfactant, Triton X-100, had no positive mitigation effect in this experiment.

• Journal of Chest Surgery
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• v.36 no.3
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• pp.131-135
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• 2003

Bovine pericardium fixed in glutaraldehyde solution (GA) has been one of the most popular surgical bioprosthesis, however, late calcific degeneration after implantation remains to be solved. To mitigate calcific degeneration, we posttreated the bovine pericardium with amino acids after GA fixation. Material and Method: 40 small pieces of bovine pericardia were fixed in 0.625% GA solution with 4 g/L $MgCl_26H_2O$as a control group (group 1). 40 pieces fixed in the same GA solution were posttreated with 2% chitosan solution (group 2) and the other 40 pieces posttreated with 8% glutamate (group 3). These were implanted into the belly of forty Fisher 344 rats subdermally and extracted at f month, 2 months, 3 months and 4 months after implantation. Result: With atomic absorption spectrophotometry we measured the deposited calcium amount and the results were as follows; 2.01 $\pm$0.13 mg/g in group 1, 2.34$\pm$0.73 mg/g in group 2, 2.49$\pm$0.15 mg/g in group 3 at 1 month after implantation, and 3.57$\pm$0.15 mg/g in group 1, 3.52$\pm$0.92 mg/g in group 2, 3.46$\pm$0.12 mg/g in group 3 at the second month. But 5.45$\pm$0.42 mg/g in group 1, 3.22 $\pm$1.31 mg/g in group 2 and 4.20$\pm$0.55 mg/g in group 3 at the 3rd month, which have statistical significance in group 2 (p<0.05). Finally at 4th month, 6.01$\pm$1.21 mg/g in group 1, 3.78$\pm$1.82 mg/g in group 2, 3.92$\pm$0.92 mg/g in group 3, which also have statistical significance (p < 0.05). Conclusion: This means posttreatment with 2% chitosan shows meaningful calcium mitigation effects after 3rd month on subcutaneously implanted bovine pericardium in the rat models but 8% glutamate shows mitigation effect after 4months in this experiment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.6
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• pp.465-473
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• 2004

Purpose : The essential triad for nerve regeneration is nerve conduit, supporting cell and neurotrophic factor. In order to improve the peripheral nerve regeneration, we used polyglycolic acid(PGA) tube and brain-derived neurotrophic factor(BDNF) gene transfected Schwann cells in sciatic nerve defects of SD rat. Materials and methods : Nerve conduits were made with PGA sheet and outer surface was coated with poly(lactic-co-glycolic acid) for mechanical strength and control the resorption rate. The diameter of conduit was 1.8mm and the length was 17mm Schwann cells were harvested from dorsal root ganglion(DRG) of SD rat aged 1 day. Schwann cells were cultured on the PGA sheet to test the biocompatibility adhesion of Schwann cell. Human BDNF gene was obtained from cDNA library and amplified using PCR. BDNF gene was inserted into E1 deleted region of adenovirus shuttle vector, pAACCMVpARS. BDNF-adenovirus was multiplied in 293 cells and purified. The BDNF-Adenovirus was then infected to the cultured Schwann cells. Left sciatic nerve of SD rat (250g weighing) was exposed and 14mm defects were made. After bridging the defect with PGA conduit, culture medium(MEM), Schwann cells or BDNF-Adenovirus infected Schwann cells were injected into the lumen of conduit, respectively. 12 weeks after operation, gait analysis for sciatic function index, electrophysiology and histomorphometry was performed. Results : Cultured Schwann cells were well adhered to PGA sheet. Sciatic index of BDNF transfected group was $-53.66{\pm}13.43$ which was the best among three groups. The threshold of compound action potential was between 800 to $1000{\mu}A$ in experimental groups which is about 10 times higher than normal sciatic nerve. Conduction velocity and peak voltage of action potential of BDNF group was the highest among experimental groups. The myelin thickness and axonal density of BDNF group was significantly greater than the other groups. Conclusion : BDNF gene transfected Schwann cells could regenerate the sciatic nerve gap(14mm) of rat successfully.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.189-199
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• 2006

Purpose of study: Partial thickness skin graft is the golden standard regimen for full-thickness skin defect caused by burn or trauma. However, in case of extensive burns of more than 50% of total body surface area, the donor site is not sufficient to cover all defects. As a second choice, allograft, xenograft and synthetic materials have been used to treat skin defect. Among them the amniotic membrane(AM) was used as a biological dressing for centuries because of its potential for wound healing. In this study, quantification of EGF in AM and effect of AM-collagen complex on full thickness skin defects was examined. Materials & Methods: The concentration of EGF in fresh, deep frozen and freeze-dried AM was evaluated by ELISA. EGF-R immunostaining was performed in freeze-dried AM. SD rats weighing 250${\sim}$300g was used for wound healing experiment. Three full thickness skin defects(28mm diameter) were made on dorsal surface of SD rat. The control group was covered by Vaselin gauze and AM-collagen complex and $Terudermis^{(R)}$. was grafted in two other defects. Healing area, Cinamon's score were evaluated before biopsy. Grafted sites were retrieved at 3 days, 1 week, 2 weeks and 4 weeks after operation. H & E and Factor VIII immunohistochemical stain was performed to evaluate the microscopic adhesion and structural integrity and microvessel formation. Results: 1. EGF concentration of fresh, deep frozen and freeze-dried AM showed similar level and EGF-R was stained in epithelial layer of freeze-dried AM. 2. At 4 weeks after grafting, the healing area of AM-collagen and Terudermis group was 99.29${\pm}$0.71% and 99.19${\pm}$0.77 of original size. However, that of control group was 24.88${\pm}$2.90. 3. The Cinamon's score of AM-Collagen and $Terudermis^{(R)}$. group at 4 weeks was 15.6${\pm}$1.26 and 14.6${\pm}$3.13 and that of control group was 3.7${\pm}$0.95. Significant difference was observed among control and experimental groups(p<0.05). 4. Histologic examination revealed that AM protected leukocyte infiltration and epithelial migration was nearly completed at 4 weeks. $Terudermis^{(R)}$. group showed mild neutrophil infiltration until 2 weeks and completion of epithelization at 4 weeks. Control group showed massive leukocyte infiltration until 4 weeks. 5. Microvessels were increased sharply at 1 week and control group at 1 and 4 week showed significant differences with $Terudermis^{(R)}$. group of same interval(p<0.05) but no differences were found with AM group(p<0.05). Conclusion: EGF and EGF-R were well preserved in freeze-dried AM. AM attached to collagen acted as excellent biologic dressing which had similar effect with $Terudermis^{(R)}$. AM showed anti-inflammatory action and healing was completed at 4 weeks after full-thickness skin defect.

• Science of Emotion and Sensibility
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• v.10 no.2
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• pp.243-252
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• 2007

Anti-depressant and anti-anxiety effects of Saccharomyces cerevisiae extract and its hydrolyzed fraction. The purpose of the present study was to examine the effect of Saccharomyces cerevisiae extract (SCE) and its hydrolyzed fraction (SCE-40) on depression and anxiety-related behaviors in mice. Actions of SCE and SCE-40 on serotonin, norepinephrine and GABAergic systems in the rat cerebral cortex membranes were also examined. SCE and SCE-40 significantly reduced the immobility time in the forced swimming and tail suspension test in mice. Duration time of the open arms in the elevated plus maze test was significantly increased in the SCE and SCE-40-treated groups, compared with the saline-treated control group. SCE and its fraction SCE-40 significantly inhibited serotonin and norepinephrine transporter and GABA receptor binding, compared to the saline-treated group. In addition, serotonin and norepinephrine reuptake were significantly suppressed by SCE and SCE-40. These results demonstrate that SCE and SCE-40 produce anti-depressant and anti-anxiety effects through enhancing central serotonin, norepinephrine and GABAergic transmissions. These results suggest that SCE and SCE-40 as functional food might prove to be an effective antidepressant and anti-anxiety agent.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.135-140
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• 2009

Background: Chronic rejection after a cardiac allograft usually occurs about six months after the operation. Vasculopathy due to chronic rejection causes atherosclerosis in the coronary artery of the transplanted heart and then this causes myocardial injury. We intended to discover and document those findings that occur in a transplanted ascending aorta. Material and Method: In rats weighting $200{\sim}300gm$ (Spraque-Dawley rat), we carried out heterotopic heart allo-transplantation with the modified Ono-Lindsey method and then the rats were administrated cyclosporine (10mg/kg/day). After three months survival, we acquired biopsy materials from the native ascending aorta and the allo-transplanted ascending aorta and we compared them. We classified each severity of 1) intimal thickening, 2) medial hyperplasia, 3) medial calcification, 4) medial inflammation and 5) chondroid metaplasia, which are specific biopsy findings for chronic rejection after a cardiac allograft. Each severity was classified, according to the opinion of one pathologist, in the native ascending aorta biopsies (n=9) and the allo-transplanted ascending aorta biopsies (n=13). The data of the control group and the study group were statistically analyzed with using the Mann-Whitney test (SPSS version 12.0 window). Result: The important changes of the allo-transplanted aorta were intimal thickening (p<0.0001), medial calcification (p=0.045), medial inflammation (p<0.0001) and chondroid metaplasia (p=0.045), but not medial hyperplasia (p=0.36). Conclusion: Cardiac allograft vasculopathy was seen in the transplanted ascending aorta, the same as was seen in the coronary artery, after allograft cardiac transplantation. We have reached the conclusion that chronic rejection also progresses in the aorta.

• Journal of Chest Surgery
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• v.42 no.1
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• pp.1-8
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• 2009

Background: The pathophysiology of acute respiratory distress syndrome with sepsis is acute lung injury (ALI) that's' caused by endotoxin (LPS). We evaluate effects of moxifloxacin on LPS-induced ALI in a rat model. Material and Method: The rats were divided into 3 groups as the control group (C), the LPS insult group (L), and the LPS+moxifloxacin treated group (L-M). ALI was induced by endotracheal instillation of E.coli LPS, then moxifloxacin was given in 30 minutes. Five hours later, we checked the lung weight/body weight ratio(the L/BW ratio), the protein & neutrophils in the bronchoalveolar lavage fluid (BALF), the myeloperoxidase (MPO) activity & the malondialdehyde (MDA) content, the expressions of cytosolic and secretory phospholipase $A_2$ (c, $sPLA_2$), and the morphology of the lung with using a light microscope. Result: The L/BW ratio, the protein content and the neutrophil count in the BALF, and the MPO activity and the MDA content in lung were significantly increased in group L compared to group C, and these factors were markedly decreased in group L-M compare to group L. The $cPLA_2$ expression and the $sPLA_2$ expression were increased in group L and the $cPLA_2$ expression was decreased in group L-M. Yet the $sPLA_2$ expression was not changed in group L-M. Morphologically, many inflammatory findings were observed in group L, but not in group L-M. Conclusion: Many of the inflammatory changes of ALI that were caused by LPS insult were ameliorated by moxifloxacin treatment.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.23-30
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• 1981

1) Effects of McN-A-343, clonidine and cocaine on the contractile response of the rat and rabbit vas deferens to field stimulation were investigated. The action mechanisms of these drugs have shown to be associated with endogenous norepinephrine(NE). 2) The contractile response to the stimulation of 5-10 Hz was markedly inhibited by the cumulative doses of McN-A-343 (0.003, 0.03, $0.3{\mu}g/ml$), clonidine (0.003, $0.3{\mu}g/ml$) and cocaine $(0.03\;{\mu}g/ml)$. The inhibition was antagonized by yohimbine and pjperoxan. 3) The inhibitory effect of McN-A-343 $(0.03{\mu}g/ml)$ and cocaine $(0.03{\mu}g/ml)$ was markedly enhanced by the same dose of cocaine and McN-A-343, respectively. This enhanced inhibition was also antagonized by yohimbine. 4) The contractile response to the stimulation of 0.01 Hz and 5-10 Hz was markedly potentiated by comparatively large doses of McN-A-343 $(30\;{\mu}g/ml)$ and $(3\;{\mu}g/ml)$. This potentiation was not observed in the presence of thymoxamine. The potentiation by McN-A-343 also did not appear in the presence of atropine. 5) The contractile response to the above stimulation was potentiated by muscarine and the potentiation was markedly attenuated in the presence of thymoxamine and atropine.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.47-62
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• 1981

d-amphetamine이 사람에서 paranoid schizophrenia와 아주 유사한 model psychosis를 일으키며 또한 사람과 실험동물에서 실제 정신분열증에서 뚜렷이 관찰되는 behavioral perservation을 일으킬 수 있음이 관찰되었다. 이에 많은 학자들은 이러한 양상의 행동변화가 정신분열증의 원인 추구에 중요한 의미를 주는 뇌변화를 반영할지도 모른다는 생각에 많은 연구를 거듭하여 왔다. 지금까지는 주로 catecholamine기전에 대하여 집중적 연구가 수행되어져 왔으나 최근에는 d-amphetamine의 약리기전의 일부는 5-HT기전이 차지하고 있으며, 여러 행동변화에는 catecholaimin 보다 5-HT 가 더 중요하게 관계하고 있다는 주장이 나오고 있다. 또한 d-amphetamine은 시험관내에서 MAO 특히 신경전달물질 분해요소인 A type를 가역적으로 억제할 수 있음이 보고되어 많은 흥미를 끌어왔으나 생체내에서의 억제여부는 직접적으로 확인이 되고 있지 않다. 그러나 최근에 Braestrup(1977)과 El Hait(1978)등은 간접적인 방법으로 생체내에서도 억제시킬 수 있음을 보고하고 있다. 이에 저자는 d-amphetamine에 의해 야기되는 행동변화와 그 밑바탕을 이루는 생화학적 기전에 5-HT가 차지하는 역할을 알아보기 위해서 다음의 실험을 시행하였다. 첫째, d-amphetamine의 급성, 만성 투여가 5-HT의 5-HIAA 로의 turnover와 MAO활성도에 어떤 영향을 미치며, 더 나아가서 이 양자사이에 어느 정도 상관관계가 있는지를 알아보기 위해서 d-amphetamine을 투여한 후 시간 경과에 따라서 뇌내 5-HT, 5-HIAA, 5-HT turnover rate와 MAO 활성도를 측정하였다. 둘째, d-amphetamine, 5-HT 합성을 증가시키는 약물과 합성을 억제시키는 약물을 투여하고, 위의 생화학적 실험과 행동관찰을 병합 실시하여 비교분석하였다. 그 결과는 다음과 같다. 1) d-amphetamine (6 mg/kg)을 급성투여시, 뇌내 5-HT함량이 투여 1시간 후에 최고로(대조치의 123%, p<0.001) 증가되다가 이후 감소하며, 5-HIAA 함량은 처음 15분부터 감소하기 시작하다가 30분에 최저로 떨어지며(대조치의 78%, p<0.005) 이후 증가하여 24시간째는 약간 대조치 이상으로 회복되었다. 미토콘드리아 MAO활성도는 1시간째에 최저로 떨어지다가(대조치의 89%, p<0.05)이후 회복하기 시작하여 24시간째에 약간 대조치 이상으로 회복되었다. 5-HT의 turnover rate는 MAO활성도 변화와 거의 같은 변화를 보였다. 2) 만성투여시 (하루 2번, 14일간 투여)는 5-HT 함량, 5-HIAA 함량, MAO 활성도 및 5-HT turnover rate 모두가 중등도로 감소되었다. (각각 대조치의 87%, 69%, 80%, 79%). 3) MAO 활성도와 5-HT turnover rate 사이에는 높은 상관관계가 있었다. (r=0.866, p<0.001, N=94). 4) MAO 활성도의 역동학 실험에서는 대조치에 비해 투여군에서 Km 값은 의미가 있는 증가가 있었으나 $V_{max}$값은 큰 변동이 없었다. 5) d-amphetamine을 급성 투여할때는 sleeping과 lying components는 상당한 감소를 보인 반면, locomotor activity 는 1시간까지는 상당한 증가를 보였으며 용량이 적을수록 더 큰 증가가 있었다. 반면 stereotypy는 1시간까지 용량이 증가할수록 더 큰 증가가 나타나서 locomotor activity에서 stereotypy 의 증가로 이행을 나타내었다. 만성 투여시는 locomotor activity는 점차적인 감소를 보였으나 stereotypy는 점차적인 증가가 나타나서 14일쯤에는 평형에 도달하였다. 6) PCPA 단독 투여군(400 mg/kg, 3번)에 있어서는 5-HT와 5-HIAA 함량의 상당한 감소가 나타났으나 MAO 활성도와 행동에는 큰 변화를 나타내지 않았다. PCPA전 처치군에 있어서도 5-HT와 5-HIAA 함량은 마찬가지로 상당한 감소를 나타내었으나 gnawing, sniffing과 locomotor activity는 더 증가를, stereotyped head weaving, forepaw treading과 hindlimb abduction은 상당한 감소를 나타내었다. 7) L-tryptophan(100 mg/kg)단독 투여시는 5-HT 함량은 약간 증가를 나타내었으나 5-HIAA 함량은 상당한 증가를 보였다. MAO활성도나 행동은 큰 변화없었다. L-tryptophan 전처치군에 있어서는 5-HT 함량은 더 큰 증가를 보였으나, 5-HIaa 함량은 MAO 활성도는 별 변화없었으며 stereotypedlateral head waving, forepaw treading 과 hindlimb abduction은 증가를, locomotor activity, gnawing과 sniffing components는 감소를 나타내었다. 8) d-amphetamine 단독투여, 혹은 L-tryptophan 전처치, PCPA 전처치후 측정한 5-HT 함량과 stereotyped head weaving, forepaw treading, hinilimb abduction components 사이에는 높은 상관관계가 있었다(r=0.789, p<0.001). 반면 5-HT 함량과 locomotor activity, stereotyped gnawing과 sniffing components 사이에는 약한 음성의 상관관계가 있었다. (r=0.554, p <0.005). 이상의 결과로 미루어 볼때 5-HT의 5-HIAA 로의 turnover rate 는 주로 MAO 활성도에 의해서 조절되며 5-HT 기전이 d-amphetamine에 의해서 야기된 여러 행동변화 중 상당한 부분에서 중요한 역할을 하리라고 생각된다.