• Title/Summary/Keyword: 세포성 면역

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Crystal Structure of an Activity-enhancing Mutant of DUSP19 (효소활성 증가 돌연변이를 함유한 DUSP19의 결정구조)

  • Ju, Da Gyung;Jeon, Tae Jin;Ryu, Seong Eon
    • Journal of Life Science
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    • v.28 no.10
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    • pp.1140-1146
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    • 2018
  • Dual-specificity phosphatases (DUSPs) play a role in cell growth and differentiation by modulating mitogen-activated protein kinases. DUSPs are considered targets for drugs against cancers, diabetes, immune diseases, and neuronal diseases. Part of the DUSP family, DUSP19 modulates c-Jun N-terminal kinase activity and is involved in osteoarthritis pathogenesis. Here, we report screening of cavity-creating mutants and the crystal structure of a cavity-creating L75A mutant of DUSP19 which has significantly enhanced enzyme activity in comparison to the wild-type protein. The crystal structure reveals a well-formed cavity due to the absent Leu75 side chain and a rotation of the active site-bound sulfate ion. Despite the cavity creation, residues surrounding the cavity did not rearrange significantly. Instead, a tightened hydrophobic interaction by a remote tryptophan residue was observed, indicating that the protein folding of the L75A mutant is stabilized by global folding energy minimization, not by local rearrangements in the cavity region. Conformation of the rotated active site sulfate ion resembles that of the phosphor-tyrosine substrate, indicating that cavity creation induces an optimal active site conformation. The activity enhancement by an internal cavity and its structural information provide insight on allosteric modulation of DUSP19 activity and development of therapeutics.

Overexpression of Galectin-3 in Macrophages of C57BL/6 mice with Experimental Autoimmune Encephalomyelitis (자가면역성 뇌척수염을 유도한 C57BL/6 마우스 큰포식세포에서의 Galectin-3의 과발현)

  • Kim, Dae Seung;Hwang, Insun;Park, Suk-jae;Ahn, Ginnae;Park, Sang-Joon;Park, Hyun Jeong;Joo, Hong-Gu;Jee, Youngheun
    • Korean Journal of Veterinary Research
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    • v.51 no.2
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    • pp.139-149
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    • 2011
  • Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and has long been used as an animal model for human multiple sclerosis. Development of EAE requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. Galectin-3 (Gal-3) is a member of the betagalactoside- binding lectin family and plays an important role in inflammatory responses through its functions on cell activation, cell migration or inhibition of apoptosis. We investigated the functional role of Gal-3 in EAE mice following immunization with myelin oligodendrocyte glycoprotein $(MOG)_{35-55}$ peptide. During the peak stage of EAE, the localization of Gal-3 in inflammatory cells markedly increased in subarachnoid membranes and perivascular regions of CNS. In contrast, Gal-3 was weakly detected in cerebrum and spinal of the recovery stage of EAE. Consistent with this finding, western blot analysis revealed that Gal-3 expression was significantly increased at the peak stage while it was slightly decreased at the recovery stage in the CNS. In addition, the population of $CD11b^{+}$ macrophage expressing Gal- 3 in spleen of EAE mice was markedly increased compared with control mice. In fact, most of activated macrophages isolated from spleen of EAE mice expressed Gal-3. Taken together, our results demonstrate that the over-expression of Gal-3 in activated macrophages may play a key role in promoting inflammatory cells in the CNS during EAE.

The Preconceptional Level of Peripheral Natural Killer Cells which was Expected to Bring Successful Treatment Outcome using Low-dose Intravenous Gamma Immunoglobulin (IVIg) Infusion in Patients with Recurrent Spontaneous Abortion (습관성 유산 환자에서 저용량 면역글로불린 치료와 말초혈액 내 Natural Killer (NK) 세포의 임계치에 관한 연구)

  • Cha, Sun Hwa;Kim, Hae Suk;Kim, Hye Ok;Song, In Ok;Yoo, Keun Jai;Koong, Mi Kyung;Kang, Inn Soo;Yang, Kwang Moon
    • Clinical and Experimental Reproductive Medicine
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    • v.32 no.3
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    • pp.217-222
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    • 2005
  • Objectives: We aimed to investigate the clinical effect of low-dose intravenous immunoglobulin treatment in unexplained recurrent spontaneous aborters (RSA) with elevated peripheral CD56+ natural killer (NK) cell levels and to determine the pre-conceptional NK cell percentage predictive of subsequent successful pregnancy outcome. Materials and Methods: Sixty four cases of unexplained recurrent miscarriage with elevated peripheral NK cells (>15%) were received low dose IVIg infusion at the dosage of 400 mg/Kg/month after confirmation of gestational sac and continued until 20 weeks. The patients were divided into two groups according to the pregnancy outcome: Group I was success of treatment defined as live birth at or after 25 gestational weeks and Group II was failure of treatment. The preconceptional levels of the peripheral blood NK cells were compared between two groups. Results: Fifty-three pregnancies resulted in live births after 25 weeks and 11 resulted in abortion (Overall success rate of IVIG treatment was 82.8%). Preconceptional CD56+ NK cell percentage in group II ($27.4{\pm}1.9%$) was higher than those in group I ($22.3{\pm}0.8%$). By using ROC curve, optimal discrimination between success and failure of treatment was achieved with ${\leq}27%$ of preconceptional NK cell percentage. Conclusion: In RSA patients with elevated NK cells, we suggest that preconceptional peripheral blood CD56+ NK cell level could be a useful marker for predicting successful treatment outcome of low-dose IVIg infusion.

Traditional Korean Medicine for Non-Small Cell Lung Cancer Patient Undergoing Pembrolizumab Immunotherapy: A Case Report (Pembrolizumab 면역치료를 시행 중인 비소세포성 폐암환자의 한방치료 증례보고)

  • Shim, So-hyun;Seo, Hee-jeong;Seo, Hyung-bum;Cho, Im-hak;Lee, Chan;Kim, So-yeon;Han, Chang-woo;Park, Seong-ha;Yun, Young-ju;Lee, In;Kwon, Jung-nam;Hong, Jin-woo;Choi, Jun-yong
    • The Journal of Internal Korean Medicine
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    • v.40 no.4
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    • pp.709-722
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    • 2019
  • Objective: The purpose of this study was to report the effect of traditional Korean medicine (TKM) in alleviating the side effects of lung cancer patient undergoing immunotherapy. Method: A 43-year-old man, who was diagnosed with non-small cell lung cancer, received pembrolizumab treatments. The patient was treated with acupuncture and herbal medicine (Geoeoyangpye-tang) to control various uncomfortable symptoms. The degree of pain was measured by the numeric rating scale (NRS). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and the EORTC 13-item lung cancer-specific module (EORTC LC-13 questionnaire) were used to assess the change in the quality of life. Results: After the TKM treatment, the flank pain and arthralgia based on the NRS were significantly improved. Various uncomfortable symptoms such as fatigue, dyspnea, insomnia, and loss of appetite were also significantly improved, based on the EORTC QLQ-C30 and EORTC QLQ-LC13. The size of the primary tumor was decreased during treatment. The disease status was stable radiologically after two months from discharge.

Eicosapentaenoic Acid (EPA) Antioxidant Activity Study (에이코사펜타엔산(EPA) 항산화활성 연구)

  • Kim, Yong Shin
    • Journal of the Korean Applied Science and Technology
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    • v.39 no.1
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    • pp.108-114
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    • 2022
  • In this study, the antioxidant effect of black sea ginseng containing a large amount of eicosapentaenoic acid, a natural physiologically active substance, was investigated, and its superiority as a functional cosmetic raw material was presented. The ability of the sea cucumber extract to remove active oxygen was evaluated for the inhibitory effect on intracellular nitric oxide (NO) production. The physiologically active substances of sea cucumber have an antioxidant effect that removes free radicals, and as a result of evaluation, it was confirmed that excellent NO production was suppressed. Studies have shown that bioactive substances are involved in antioxidant effects, immune and inflammatory response regulation by showing high antioxidant efficacy even at low concentrations. It is thought that the antioxidant removal ability of sea cucumber greatly contributes to the antioxidant efficacy of phenolic components containing EPA (eicosapentaenoic acid) of the sea cucumber extract. It was found to be similar to the report that the antioxidant component of sea cucumber works. In addition, it is excellent for wound healing with the eicosapentaenoic acid (EPA) component contained in a large amount of sea cucumber extract, which has been proven to be involved in the inhibitory effect of inflammatory activity. As a result of this study, it was confirmed that the effect of the phenol component contained in the sea cucumber extract had a close causal relationship with the antioxidant activity.

Effect of Potassium Iodide on Erythrosine-Mediated Photodynamic Therapy on Streptococcus Mutans Biofilms (Streptococcus mutans 바이오필름에 대한 에리스로신 매개 광역동 치료 시 potassium iodide의 효과)

  • Yongsoon, Kim;Howon, Park;Juhyun, Lee;Haeni, Kim;Siyoung, Lee
    • Journal of the korean academy of Pediatric Dentistry
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    • v.49 no.3
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    • pp.321-328
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    • 2022
  • The aim of this in-vitro study is to evaluate the effect of potassium iodide (KI) on erythrosine-mediated photodynamic therapy (PDT) against Streptococcus mutans biofilms. S. mutans ATCC 25175 was cultured to form a biofilm on a hydroxyapatite disk. After diluting erythrosine to 20 μM and KI to 10, 50, and 100 mM, respectively, PDT was performed. The number of surviving bacteria was calculated as colony forming units (CFU)/mL and the statistical significance of the difference between groups was confirmed by Bonferroni post-hoc analysis. Cell viability was visually evaluated using confocal laser scanning microscopy (CLSM). As a result of the experiment, a significant decrease (p < 0.05) in CFU was observed in the experimental groups in which PDT was performed after applying KI regardless of the concentration of KI. In addition, a significant reduction (p < 0.05) in CFU was observed in the experimental group to which 100 mM KI was applied compared to 10 mM KI. The same results were confirmed when observing CLSM. KI significantly improved the efficacy of erythrosine-mediated PDT on S. mutans biofilms at all concentrations. This may compensate for the low sensitivity of PDT to biofilm-state bacteria strains, but it is necessary to establish an optimal clinical protocol through further research.

Pictorial Review of Rare Pancreatic Tumors and Tumor-Like Lesions (췌장에서 생기는 희귀 종양 및 종양 유사 병변들의 영상 소견)

  • Seung Jae Lee;Sang Soo Shin;Suk Hee Heo;Yong Yeon Jeong
    • Journal of the Korean Society of Radiology
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    • v.81 no.5
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    • pp.1134-1150
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    • 2020
  • Various types of tumors and tumor-like lesions may affect the pancreas. Among them, pancreatic ductal adenocarcinoma is the most common and is generally referred to as "pancreatic cancer." Recently, the detection rates of rare pancreatic tumors and tumor-like lesions have increased owing to technological advancements and increased frequency of imaging tests. Considering that rare pancreatic tumors and tumor-like lesions differ from pancreatic ductal adenocarcinoma in terms of the treatment plan and prognosis, the differential diagnosis of these diseases is clinically relevant. Various imaging tests play an important role in the differential diagnoses of rare tumors, such as acinar cell carcinoma and schwannoma, tumor-like lesions, such as autoimmune pancreatitis and inflammatory pseudotumor, and pancreatic ductal adenocarcinoma, but accurately distinguishing these diseases solely based on imaging findings is difficult. The aim of this pictorial review was to present the imaging findings of rare pancreatic tumors and tumor-like lesions and discuss important points for the differential diagnosis.

Clinical and Cytogenetic Analysis of Children with Maternal Chromosomal Balanced Translocation (모체의 염색체 균형전좌를 가진 환아들의 임상적 세포 유전학적 관찰)

  • Lim, Han Hyuk;Jeong, Hee Jeong;Park, Kyung Duk;Kim, Sook Ja
    • Clinical and Experimental Pediatrics
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    • v.48 no.7
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    • pp.701-705
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    • 2005
  • Purpose : Parents' genetic information plays an important role in their children's genetic expression. Human chromosome has 23-paternal chromosomes and 23-maternal chromosomes. Parental chromosomal translocation can induce clinical problems in their children because of imbalance in genetic information. We intent to analyze the cytogenentic and clinical features about children with maternal balanced translocation between chromosome 15 and 18. Methods : We detected by one family's FISH study of chromosome 15. We have evaluated children born to clinically normal parents about peripheral bood analysis, endocrine, metabolic, radiologic study, electroencephalogram and social & intelligence scale. and We analysis their clinical manifestation by hospital records. Results : Patient's father and elder sister are normal clinically and genetically. Her mother's chromosome show balanced translocation, 46, XX, t(15;18)(p11.2;p11.3). One child has 46, XX, der(18) t(15;18)(p11.2;p11.3), mental retardation, growth retardation, speech & social developmental delay, recurrent infection and mild mitochondria dysfunction. Her young brother has 46, XY, der(15) t(15;18) (p11.2;p11.3), mental retardation, aggressive behavior, obesity and speech developmental delay. Conclusion : In this study we observed the children with developmental delay, dysmorphic facial features, mental retardation, growth retardation associated with growth hormone deficiency and aggressive behavior due to unbalanced translocation between chromosome 15 and 18.

Cell Surface Antigenic Relationship of Pathogenic Mycobacteria (병원성 Mycobacteria의 세포표면항원간의 항원적 상관 관계)

  • Kwon, Hyuk-Han;Saito, Hajime;Kim, Sang-Jae
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.5
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    • pp.483-494
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    • 1993
  • Cell surface antigenic relationships between pathogenic mycobacteria have been investigated by the enzyme-linked immunosorbent assay using phenolkilled cells and their rabbits antisera. Homologous and heterologous reactions of Mycobacterium avium-intracellulare antisera before and after homologous and heterologous absorption revealed a close antigenic relationship between strains of the same species and between species if they were members of M. avium(MA)-intracellulare(MI)-scrofulaceum(MG) complex. MAI sera showed a considerable reaction with M. kansasii(MK) and tuberculosis(MTB), but not with the other species. MA(K40004) antiserum reacted with other mycobacteria except few strains of MI and 50~89% of homologous reaction was reduced by heterologous absorption with cells of MI or MS. Intraspecific reaction of MI antisera was natural1y stronger than interspecific reaction and different in extent due to a magnitude of antigenic sharing. Antigenic relationships between N-260D, N-260R, N-260T, and K41014 was somewhat closer than that with N-242D, N-257T, N-28ID, and N-275T. M. nonchromogenicum(MNC) antisera showed a strong interspecific reaction with exception of M. chelonei(MC) and triviale(MTV) to which they reacted weakly or none. Antigenic sharing with M. terrae(MTR) and MG(K30003) was next to intraspecific sharing. NC-3 shared antigens considerably with MA, MC, and M. fortuitum(MF) while NC-11 did not. MTR antisera showed a strong cross-reaction with MI but their homologous reaction was not reduced by MI absorption indicating a paucity of shared antigen of MTR surface. Intraspecific antigenic sharing of course was large with on exception between T-8 and T-13. A considerable amount of antigenic sharing was also found with MNC, MC and MF. Unlike T-8 serum, T-13 antiserum strongly cross-reacted with MA, MG, MK, and MTB. In general, antigenic relationships of mycobacteria, that have been elucidated in this study, well conformed to taxons delineated by the various biological and biochemical means.

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The Effects of Unpredictable Stress on the LHR Expression and Reproductive Functions in Mouse Models (실험적 마우스 모델에서 예측 불가능한 스트레스가 황체형성호르몬 수용체의 발현과 생식기능에 미치는 영향에 관한 연구)

  • Choi, Sung-Young;Park, Jin-Heum;Zhu, Yuxia;Kim, Young-Jong;Park, Jae-Ok;Moon, Changjong;Shin, Taekyun;Ahn, Meejung;Kim, Suk-Soo;Park, Young-Sik;Chae, Hyung-Bok;Kim, Tae-Kyun;Kim, Seung-Joon
    • Journal of Veterinary Clinics
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    • v.31 no.5
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    • pp.394-402
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    • 2014
  • The objective of this study was to investigate the effect of chronic unpredictable stress on the reproductive function and ovarian luteinizing hormone receptor (LHR) expression. 9-week-old C57BL/6 female mice were randomly divided into two groups: control group and stressed group. Mice have been stressed twice a day for 35 days with 12 different stressors which were randomly selected. The results demonstrate that there is significant increase in the anxiety-related behaviors (P < 0.05), decrease body weight gain rate (P < 0.01) and decrease in the average of litter size in stressed mice compared with control group (P < 0.01). Furthermore, the rate of primary, secondary and early antral follicles in stressed mice significantly decreased (P < 0.05), whereas that of atretic follicles significantly increased compared with control mice (P < 0.01). The immunohistochemical analysis revealed that reduced LHR expression in granulosa cells of follicle and luteal cells of corpus luteum in response to chronic unpredictable stress. The western blot analysis revealed significantly decrease in LHR expression in the stressed mice ovaries compared with the control (P < 0.05). These results suggest that ovarian LHR expression affected by chronic unpredictable stress and the modulated ovarian LHR is responsible for ovarian follicular maldevelopment and reproductive dysfunction.