• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

• Journal of Chest Surgery
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• v.36 no.5
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• pp.348-355
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• 2003

Background: The prognostic significance of lymph node micrometastasis in non-small cell lung cancer remains controversial. We therefore investigated the clinicopathologic factors related to lymph node micrometastsis and evaluated the clinical relevance of micrometastasis with regard to recurrence. Material and Method: Five hundred six lymph nodes were obtained from 41 patients with stage 1 non-small ceil lung cancer who underwent curative resection between 1994 and 1998. Immunohistochemical staining using anti-cytokeratin Ab was used to detect micrometastasis in these lymph nodes. Result: Micrometastatic tumor cells were identified in pN0 lymph nodes in 14 (34.1%) of 41 patients. The presence of lymph node micrometastasis was not related to any clinicopathoiogic factor (p) 0.05). The recurrence rate was higher in patients with micrometastasis (57.1%) than in those without (37.0%), but the difference was not significant (p=0.22). Patients with micrometastasis had a lower 5-year recurrence-free survival rate (48.2%) than those without micrometastasis (64.1%), with a borderline significance (p=0.11), The S-year recurrence-free survival rate (25.0%) in the patients with 2 or more micrometastatic lymph nodes was significantly lower than that in the patients with no or single micrometastasis (p=0.02). In multivariate analysis, multiple lymph node micromestasis us was a significant independent predictor of recurrence (p=0.028, Risk ratio=3.568). Conclusion: Immunehistochemical anti-cytokeratin staining was a rapid, sensitive, and easy way of detecting lymph node micrometastasis. The presence of lymph node micrometastasis was not significantly associated with the recurrence, but had a tendency toward a poor prognosis in stage 1 non-small cell lung cancer. Especially, the presence of multiple micrometastatic lymph nodes was a significant and independent predictor of recurrence.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• The korean journal of orthodontics
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• v.26 no.4
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• pp.455-467
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• 1996

This study was designed to evaluate the expression of type I collagen in periodontal tissue during the experimental movement of rat incisors. Twenty-one Sprague-Dawley rats were divided into a control group(3 rats), and experimental groups(18 rats) where a force(75g) from helical springs across the maxillary incisors was applied. Experimental groups were sacrificed at 12 hours, 1, 4, 7, 14 and 28 days after force application, respectively. And tissue slides of control and experimental groups were studied histologically and immunohistochemically by LSAB(Labelled streptavidine Biotin) immunohistochemical staining for type I collagen. The results were as follows: 1. Until 28-day after force application, periodontal fibers were strectched on the tension side, and compressed in pressure side, and the arrangement of periodontal fibers was not recovered by that time. 2. The degree of type I collagen expression in control group was rare in the oral epithelium, predentin, pulp and periodontal ligament, but was mildly positive in osteoblasts, acellular cementum, cementoblasts, intermaxillary suture. 3. At acellular cementum of experimental group, the expression of type I collagen was moderate in 1-day and severe in 7-day, which was maintained until 28-day. 4. Type I collagen was observed in the newly formed fibrous connective tissue and osteoblasts at intermaxillary suture, moderately in 1-day, and severely in 14-day. 5. The tension side of periodontal ligament showed a more positive expression of type I collagen than the pressure side in 4-day. The degree was highest in 7-day and was not differentiated between sides in 14-day. 6. In the side wall of bone matrix on which osteoblasts were attached, type I collagen was expressed severely, especially in 7-day. From the above findings, we could suggest that bone remodeling in tooth movement be intimately related to the cell differentiation and the resulting formation of type I collagen.

• Applied Microscopy
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• v.38 no.3
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• pp.221-233
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• 2008

Endogenous nitric oxide (NO) has been known to regulate many physiological and pathological processes, especially the glandular secretion and blood flow. However, nitric oxide synthase (NOS) responsible for NO synthesis has not been well studied ultrastructurally in rat salivary gland. The present study was performed to investigate the distribution of nitric Oxide synthase isoforms (endothelial. neuronal, and inducible NOS). Immunoelectron microscopic study, using monoclonal mouse anti-endothelial NOS, anti-neuronal NOS, and anti-inducible NOS, was performed in the salivary gland of rat. Endothelial NOS (eNOS)-positive immunoreactivities were most prominent in the secretory granules of serous cells of the salivary gland of the rat. Immunoreactivities were well concentrated on serous secretory granules in the serous cells. However, weak eNOS-positive immunoreactivity was observed in the mucous secretory granules of the mucous cells. Positive endothelial NOS (eNOS) immunoreactivities were most prominent in the secretory granules of intralobular ducts. Ductal secretory granules and acinar serous secretory granules have a similar pattern of labeling as eNOS suggestings. Neural NOS (nNOS)-positive immunoreactivity was not detected in duct systems or in acinar cells. Inducible NOS (iNOS)-positive immunoreactivity was not seen in acinar and ductal cells. These results reveal the presence of eNOS in the salivary gland of the rat, which may be related with regulation of the glandular secretion and blood flow through the gland.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.190-198
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• 2001

Purpose : It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We peformed this study to investigate the radioprotective effect and mechanism of Captopril. Methods and Materials : The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains $(TNF\alpha\;and\;TGF\beta1)$ at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. Result : In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the $TNF\alpha$ expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the $TGF\beta1$ expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p<0.02). At 8 weeks, the expression of $TNF\alpha\;and\;TGF\beta1$ of most sites, except $TGF\beta1$ of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. Conclusion : This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of $TNF\alpha\;and\;TGF\beta1$ at 2 weeks and $TGF\beta1$ at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine $(TNF\alpha)$ and fibrogenic cytokine $(TGF\beta1)$ probably play the role of the radioprotective mechanism in Captopril.

• Journal of Veterinary Clinics
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• v.31 no.3
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• pp.258-261
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• 2014

A 4-week-old male piglet being maintained in a research facility was found dead without any previous clinical signs. The piglet had been born from a surrogate mother after somatic nuclear transfer as part of a xenotransplantation study. Ovaries for nuclear transfer were obtained from a private farm outside the research facility. Histopathologically, multifocal to coalescing granulomatous myocarditis was observed in the heart, characterized by infiltration of lymphocytes, macrophages and multinucleated giant cells, and by myocardial necrosis and fibrosis. Lymphoid tissues showed marked lymphoid depletion with infiltration by histiocytes or giant cells. Immunohistochemistry showed PCV-2 antigens in necrotic myocytes, macrophages and multinucleated giant cells in the heart, as well as in macrophages and giant cells in lymphoid depleted areas of lymphoid tissues. Reproductive failure associated with PCV-2 in aborted or stillborn piglets is frequently characterized by myocarditis, and similar lesions were observed in this 4-week-old piglet with PCV-2 infection. The PCV-2 infection in this piglet may have been due to contamination or infection of an ovary from the pig farm.

• Journal of Oral Medicine and Pain
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• v.26 no.3
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• pp.205-214
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• 2001

오늘날 스트레스라는 단어는 모든 현대인과 방송, 언론매체에서도 매일 거론되어질 정도로그 중요성이 대두되고 있다. 의학계에서도 스트레스를 단순한 심리적 문제로 국한시키지 않고 과도한 스트레스가 지속될 경우 신경계와 내분비계, 면역계의 변화를 초래해 인체의 항상성에 영향을 미쳐 질병을 일으킨다는 것을 인식하고 있으며 이에 대한 연구가 진행되고 있다. 이러한 질병의 발생과정에서 생체의 일부조직이 파괴됨으로써 기능과 형태변화가 초래될 때 apoptosis가 관여하고 있으며 이에 본 저자는 스트레스와 구강악안면영역에서 발생할 수 있는 질병과의 상관관계를 규명하기 위해 이종의 한냉 스트레스와 다소의 굴신을 허용한 중등도의 구속 스트레스를 부여한 후 측두하악관절 활막의 변화를 전자현미경관찰을 통해 밝혀내고자 한다. Sprague-Dawley계 웅성 백서(200-230 g/bw) 33마리를 구속스트레스부여군 (12마리), 한냉스트레스부여군 (12마리) 및 정상군 (3마리)으로 나누고 이들을 각각 구속장치에 구속한 후 1, 3, 5, 7일에 각각 희생시켰으며 측두하악관절 활막의 변화를 전자현미경으로 관찰하였다. 그 결과는 다음과 같다. 1. 중등도의 구속스트레스군에서 사립체는 부분적으로 농축된 소견을 보였으며 수와 크기에 있어 시간이 지남에 따라 점차 감소하는 소견을 보였다. 2. 중등도의 구속스트레스군에서 과립내형질망은 점점 확장되었으며 불규칙한 형태를 나타내었다. 3. 중등도의 구속스트레스군에서 물결모양의 핵막의 이중구조가 7일군에서 관찰되었다. 4. 한냉 스트레스군에서 사립체는 1일, 3일군에서 약간 부푼 형태를 가지고 그 수가 다소 감소되었으나 시간이 지남에 따라 5일, 7일군에서 건강한 모양으로 점차 증가되었다. 5. 한냉 스트레스군에서 과립내형질망은 1일, 3일군에서 불규칙하게 확장된 소견을 보였으나 5일, 7일군에서는 잘 발달된 형태로 핵 주위에서 다수 관찰되었다. 6. 한냉 스트레스군에서 핵은 전 기간에 걸쳐 큰 변화를 보이지 않았다. 이와 같은 결과를 토대로 측두하악관절 활막조직은 한냉 스트레스 및 중등도의 구속 스트레스에 대하여 중등도의 저항성을 가지고 있는 것으로 생각되며 생리적 적응한계를 넘는 과도하고 지속적인 스트레스에 의하여 활막조직이 apoptosis되어 측두하악관절에 병리적 변화를 초래할 가능성이 있다고 사료되어 이후 지속적인 연구가 요구된다.

• Journal of the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1188-1197
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• 2019

Exposure to stress can lead to sympathetic hyperactivity, which include a systemic disease with lesions in a broad spectrum of organs and a psychiatric condition. The purpose aimed to evaluate the effect of the korea ginger essential oil on stress hormone and brain tissue response in chronic mild stress-induced rats model of sympathetic hyperactivity. Evaluation method carried out cytotoxicity assessment and component analysis, what observe the effects based on serum biomarker and histopathological analysis of brain tissue. As this time, the korea ginger essential oil was treatment at doses of 100 nl/㎖ for 2 weeks after make a chronic mild stress-induced rats model of sympathetic hyperactivity. As a result, the korea ginger essential oil was not toxic at less than 100 nl/㎖, contents of 6-gingerol was 345 ppm. Compared to the control rats, the korea ginger essential oil treatments significantly reduced the serum concentrations of stress hormone (i.e., ACTH, corticosterone, melatonin). Furthermore, The korea ginger essential oil treatments effectively preserved the TH-immune response was occasionally interrupted in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNpc). The results indicate that the korea ginger essential oil improved sympathetic hyperactivity. Thus, the korea ginger may be a novel material of aroma oils for the management of sympathetic hyperactivity.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.9-14
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• 2022

Ulcerative colitis is a disease that causes inflammation in the mucosal or submucosal layer of the colon. Previous studies have reported that obesity increases the prevalence of ulcerative colitis and aggravates the progression. This study was therefore undertaken to investigate whether curcumin inhibits the progression of ulcerative colitis caused by obesity. Mice were bred on a high-fat diet to induce obesity, and curcumin was administered with the high-fat diet to confirm the anti-inflammatory effect. To induce ulcerative colitis, dextran sulfate sodium (DSS) was administered orally, and clinical symptoms of colitis were subsequently observed. For histological evaluation of curcumin, the colon, liver and abdominal fat tissue samples were prepared and analyzed by hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (PAS) staining. Our results confirm that consumption of curcumin resulted in decreasing the score of the disease activity index, and inhibited shortening of the colon length. In addition, inflammatory cell infiltration and mucosal damage were inhibited in the colon tissue of ulcerative colitis exacerbated by obesity. We further confirmed that exposure to curcumin significantly reduced the steatosis area of the liver and adipocytes of abdominal fat. In conclusion, we believe that curcumin can be applied as a therapeutic agent to treat ulcerative colitis, by inhibiting the progression of colitis caused by obesity.