• 농약과학회지
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• 제13권2호
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• pp.111-116
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• 2009

유약호르몬은 변태를 억제하고 성충의 생식작용을 중개하는 곤충호르몬이다. 이 호르몬은 또한 탈피호르몬과 길항적으로 면역반응에도 관여하여 혈구세포 활동을 억제시킨다. 본 실험은 배추좀나방(Plutella xylostella)의 세포성 면역반응에 대한 피리프록시펜 제형의 효과와 이를 Bacillus thuringiensis(Bt)와 혼합하였을 때의 살충력 제고 효과에 대해 분석하였다. 피리프록시펜 제형은 낮은 농도에서도 혈구세포의 활착능력을 현저히 억제하였다. 피리프록시펜 제형을 배추좀나방 대상으로 실내실험에서 Bt와 혼합하여 섭식처리 한 결과 살충력이 유의성이 있게 증가하였다. 이러한 실내실험 결과 토대로 피리프록시펜 제형과 Bt 혼합제를 배추좀나방이 서식하고 있는 배추포장에 약제처리 했을 때 Bt 단독처리 보다 살충효과를 높이고 살충시간이 효과적으로 줄어드는 것을 보여주었다.

• Toxicological Research
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• 제20권4호
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• pp.329-337
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• 2004

Primiphos-methyl and methidathion as organophosphorus (OP) pesticides were tested for their immunotoxic effects on Balb/c mice. Three dose levels of primiphos-methyl (10, 60, or 120 mg/kg/day) and methidathion (0.5, 2.5 or 5.0 mg/kg/day) were administered orally in the mice for 4 weeks. After, changes in body weight gain, relative weight of spleen and thymus, viable splenic cell numbers, surface marker on immune cell, and proliferation activity were investigated. Results showed that neither Pirimiphos-methyl nor methidathion dosages changed significantly body weight, relative thymus and spleen weight, and thymus and spleen cellularities of the mice, but high dose treatment (120 mg/kg) of pirimiphos-methyl significantly decreased relative spleen weight and spleen cellularity of the mice. No alterations were observed in changes of LPS-proliferation response of splenocytes by exposure to any dose of pirimiphos-methyl and methidathion. However, pirimiphos-methyl dosages reduced ConA-proliferation response of splenocytes and both methidathion and pirimiphos-methyl decreased the ability of antibody production to SRBC. The results indicate that 28 days exposure to the high dose of pirimiphos-methyl suppress the function of splenic T and B cell function, and methidathion reduce the immune responsibility of B cell in mice without the changes in lymphoid organ weight or viability of splenocytes. Pirimiphos-methyl is more immunotoxic than methidathion although this has higher general toxicity than that.

• Journal of Chest Surgery
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• 제39권11호
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• pp.854-857
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• 2006

환자는 8세 여자 환자로 확장성 심근병증을 진단 받은 환자이다. 환자는 심부전으로 인하여 양심실 순환보조를 15일간 시행하였다. 15일 중 후반기 7일은 급성 신부전증이 발생하여 지속적 정맥-정맥간 혈액투석을 시행하였다. 이후 뇌사상태의 A형 혈액형을 가진 심장 공여자에게서 심장을 이식받아 심장이식술을 시행하였다. 면역 억제제는 급성 신부전증을 고려하여 사용하였다. 신부전 상해는 2주간 지속되었고, 심장 이식술 후 약 14일 후 배뇨가 시작되었다. 환자는 수술 후 12일째에 시행한 우심실 조직검사에서 특별한 거부반응의 증거가 없었으며, 면역요법 후 수술 후 52일째에 특별한 문제 없이 퇴원하였다. 환자는 술 후 약 14개월간 조직검사에서 면역 거부반응 없이 외래 경과관찰 중이다.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2002년도 학술대회
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• pp.123-126
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• 2002

Pollutants that are persistent, bioaccurnulative, and toxic have been linked to numerous adverse effects in human and animals, PBTs include heavy metals, polychlorinated biphenyls (PCBs), dioxins, polycyclic aromatic compounds (PACs) in addition to pesticides. This study focuses on toxic effects of the PBTs except pesticides on insects. Eight PBTs were selected from subgroups: three heavy metals (Pb, Hg, and Cd), two PCB mixtures (Aroclor mixtures 1 and 2), 2,3,7,8-tetrachlorodibenzo-p-dioxin, two monophenols (4-octylphenol and 4-nonylphenol), and tetrabutyltin, Beet armyworm, Spodoptera exigua, was used as test target insect species. Three physiological markers (metamorphosis, immune reaction, and follicle patency) were assessed in each exposure to different doses of the PCBs. Heat-shock proteins as molecular markers were also analyzed in response to the PCBs. All tested PBTs were toxic to metamorphosis from larvae to pupae when they were applied with diet. Two PCB mixtures were the most toxic compounds in this assay by giving significant toxicity at 0.005 ppm, while others had from 10 to 1000 ppm. Dioxin (0.1 ppb), tetrabutyltin (0.1 ppb), Pb (10 ppb), and Hg (0,01 ppb) were potent to inhibit immune reactions analyzed by inducing phenoloxidase activity and blocked phospholipase $A_2$ enzyme, Tetrabutyltin and dioxin significantly induced follicle cell patency, but their effects were lower than that of endogenous juvenile hormone, Dioxin, Pb, Hg, and Cd could induce the expression of heat shock proteins that were detected by immunoblotting against human HSP70 monoclonal antibody. HSP78 and HSP80 were upregulated in response to the PBTs. This expression was detected from the fat body and epidermis at as fast as 4h after injection. All these results clearly suggest that PBTs give significant ecotoxicity to insects that are valuable organisms in our environment.

• Fisheries and Aquatic Sciences
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• 제9권1호
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• pp.14-21
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• 2006

The aim of this study was to investigate in vivo toxicity and effects of two phthalate esters (PEs), di-n-butylphthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), on the immune system of the bagrid catfish, Pseudobagrus fulvidraco. Groups of experimental fish were subjected to daily intraperitoneal injections of 300 or 1000 mg $kg^{-1}$ of DBP or DEHP for 3 days, and the cellularity and functional activity of phagocytes were measured in the spleen and pronephros (head kidney). The number of spleen leukocyte cells increased significantly (p<0.05) in response to low and high doses of DEHP and DBP, respectively; however, the cellularity of the pronephros was more susceptible to higher dose of DEHP than DBP. Nonspecific immunity, as determined by the phagocytic index (PI) and phagocytic capacity (PC), was significantly depressed by DEHP at 1000 $1000mg\;kg^{-1}\;day^{-1}$ in the pronephros at 3 days after injection. Furthermore, significantly (p<0.05) increased levels of serum glutamic oxaloacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT) indicated marked hepatic dysfunction in immunosuppressed fish. Treated fish showed a significant reduction in total serum protein but no significant alteration in lysozyme activity. These results demonstrate the sensitivity of the fish immune response for predicting PE-induced immunotoxicity.

• Journal of Gynecologic Oncology
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• 제29권6호
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• pp.93.1-93.11
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• 2018

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

• Molecules and Cells
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• 제45권11호
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• pp.855-867
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• 2022

For proper function of proteins, their subcellular localization needs to be monitored and regulated in response to the changes in cellular demands. In this regard, dysregulation in the nucleocytoplasmic transport (NCT) of proteins is closely associated with the pathogenesis of various neurodegenerative diseases. However, it remains unclear whether there exists an intrinsic regulatory pathway(s) that controls NCT of proteins either in a commonly shared manner or in a target-selectively different manner. To dissect between these possibilities, in the current study, we investigated the molecular mechanism regulating NCT of truncated ataxin-3 (ATXN3) proteins of which genetic mutation leads to a type of polyglutamine (polyQ) diseases, in comparison with that of TDP-43. In Drosophila dendritic arborization (da) neurons, we observed dynamic changes in the subcellular localization of truncated ATXN3 proteins between the nucleus and the cytosol during development. Moreover, ectopic neuronal toxicity was induced by truncated ATXN3 proteins upon their nuclear accumulation. Consistent with a previous study showing intracellular calcium-dependent NCT of TDP-43, NCT of ATXN3 was also regulated by intracellular calcium level and involves Importin α3 (Imp α3). Interestingly, NCT of ATXN3, but not TDP-43, was primarily mediated by CBP. We further showed that acetyltransferase activity of CBP is important for NCT of ATXN3, which may acetylate Imp α3 to regulate NCT of ATXN3. These findings demonstrate that CBP-dependent acetylation of Imp α3 is crucial for intracellular calcium-dependent NCT of ATXN3 proteins, different from that of TDP-43, in Drosophila neurons.

• Toxicological Research
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• 제22권2호
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• pp.95-102
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• 2006

Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose ($40{\mu}M$) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.170-170
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• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• Journal of Preventive Medicine and Public Health
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• 제45권6호
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• pp.353-363
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• 2012

Methylmercury is a hazardous substance that is of interest with regard to environmental health, as inorganic mercury circulating in the general environment is dissolved into freshwater and seawater, condensed through the food chain, ingested by humans, and consequently affects human health. Recently, there has been much interest and discussion regarding the toxicity of methylmercury, the correlation with fish and shellfish intake, and methods of long-term management of the human health effects of methylmercury. What effects chronic exposure to a low concentration of methylmercury has on human health remains controversial. Although the possibility of methylmercury poisoning the heart and blood vessel system, the reproductive system, and the immune system is continuously raised and discussed, and the carcinogenicity of methylmercury is also under discussion, a clear conclusion regarding the human health effects according to exposure level has not yet been drawn. The Joint FAO/WHO Expert Committee on Food Additives proposed to prepare additional fish and shellfish intake recommendations for consumers based on the quantified evaluation of the hazardousness of methylmercury contained in fish and shellfish, methylmercury management in the Korea has not yet caught up with this international trend. Currently, the methylmercury exposure level of Koreans is known to be very high. The starting point of methylmercury exposure management is inorganic mercury in the general environment, but food intake through methylation is the main exposure source. Along with efforts to reduce mercury in the general environment, food intake management should be undertaken to reduce the human exposure to methylmercury in Korea.