• Tuberculosis and Respiratory Diseases
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• 제44권1호
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• pp.124-135
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• 1997

연구배경 : 미만성 범세기관지염 (Diffuse panbronchiolitis)은 만성 기침, 화농성 객담과 호흡곤란을 주증상으로 하며, 호흡세기관지에 국한된 만성 염증성 질환으로 비교적 근래에 알려진 질환이다. 이 질환은 주로 일본에서 많이 보고되었는데, 우리나라에서 지금까지 발견된 환자의 수는 적으나 최근 수년간 이 질환에 대한 인식이 높아지면서 보고되는 증례가 많아지고 있다. 이 질환은 주로 임삼증상, HRCT 및 조직검사로 진단되는데, 특히 HRCT가 진단에 중요한 비중을 차지하는 것으로 알려져 있다. 하지만 HRCT 소견과 임상소견간에 어떤 상관관계가 있는지에 대해서는 아직 불확실하며, 폐환기주사에서 어떤 특정적인 소견이 나타나는 지에 대해서도 별로 연구된 바가 없다. 방법 : 이에 저자들은 최근 2년동안 미만성 범세기관지염으로 진단된 12명 환자들을 대상으로 임상적 특징을 관찰하고, HRCT 소견과 임상소견과의 상관관계를 관찰하는 한편, 폐환기주사에서 나타나는 특징적인 소견을 분석해 보았다. 결과 : l. 연령은 31-83세(평균 54.4세)에 분포하였고 남녀비는 4:8이었으며, 부비동염이 동반되었던 환자가 9명(75%)였다. 임상적 단계는 임상소견에 따라 3단계로 나누었는데, 각각 l 기(기관지수축과 저산소증)에 속하는 환자는 5명, 2기(기관지수축, 저산소증 및 호흡기 감염증)는 4명, 3기(기관지수축, 저산소증, 고탄산혈증, Pseudomonas에 의한 호흡기 감염증 및 우심부전)는 3명이었다. 2. HRCT 소견에 따라 4기로 나누었는데 l기는 한명도 없었으며, 2기가 4명, 3기가 5명, 4기가 3명으로서, 거의 모든 환자들이 발견 당시에 2기 이상임을 알 수 있었다. 그중 7예에서는 폐환기주사를 실시해 보았는데, 5예 (71.4 %)에서 이행부와 기도 중간부에 비정상적인 연무질침착이 나타나면서 말단 폐실질의 환기 결손소진을 보여서, 만성폐쇄성폐질환과는 대조적인 소견을 나타냈다. 3. 폐기능검사상 l예를 제외한 모든 환자에서 중등도 또는 중중의 폐쇄성 환기장애 소견을 보였고, 산소 투여없이 시행한 동맥혈가스 검사장 10예에서 저산소증, 2예에서 고탄산혈증의 소견을 나타냈다. 객담배양 검사상 P.aeruginosa가 자란 경우가 3예, K.pneumoniae는 2예, H. influenzae는 2예, S. aureus는 2예로 나타났다. 4. HRCT 병기가 높아질수록, 임상적 병기 (r=0.801, P < 0.01) 및 저산소증(r= -0.615, P < 0.05)이 심해지는 양상을 보였으며, ESR(r= 0.818, p < 0.01)도 상승되는 경향을 보였다. 또한 임상적 병기가 높아질수록 저산소증(r = -0.728, p < 0.01) 및 고탄산혈증 (r = 0.620, P < 0.05)이 심해지고, ESR(r= 0.662, p < 0.01)이 증가함을 알 수 있었다. 결론 : 이상의 결과로 보아 미만성 범세기관지염에서 HRCT 소견이 임상소견과도 밀접한 상관관계가 있기 때문에, HRCT는 미만성 범세기관지염의 진단, 중증도의 판정 및 경과 관찰에 유용할 것으로 생각된다. 또한 폐환기주사 역시 미만성 범세기관지염에서 특징적인 소견을 나타내므로, 이를 흉부 HRCT와 함께 병행한다면 미만성 범세기관지염의 진단이 더욱 용이할 것으로 추측되는 바이다.

• Journal of Animal Science and Technology
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• 제59권9호
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• pp.20.1-20.9
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• 2017

Background: Ribonuclease (RNase) is one of the few toxic proteins that are present constantly in snake venoms of all types. However, to date this RNase is still poorly studied in comparison not only with other toxic proteins of snake venom, but also with the enzymes of RNase group. The objective of this paper was to investigate some properties of RNase from venom of Vietnam cobra Naja atra. Methods: Kinetic methods and gel filtration chromatography were used to investigate RNase from venom of Vietnam cobra. Results: RNase from venom of Vietnam cobra Naja atra has some characteristic properties. This RNase is a thermostable enzyme and has high conformational stability. This is the only acidic enzyme of the RNase A superfamily exhibiting a high catalytic activity in the pH range of 1-4, with $pH_{opt}=2.58{\pm}0.35$. Its activity is considerably reduced with increasing ionic strength of reaction mixture. Venom proteins are separated by gel filtration into four peaks with ribonucleolytic activity, which is abnormally distributed among the isoforms: only a small part of the RNase activity is present in fractions of proteins with molecular weights of 12-15 kDa and more than 30 kDa, but most of the enzyme activity is detected in fractions of polypeptides, having molecular weights of less than 9 kDa, that is unexpected. Conclusions: RNase from the venom of Vietnam cobra is a unique member of RNase A superfamily according to its acidic optimum pH ($pH_{opt}=2.58{\pm}0.35$) and extremely low molecular weights of its major isoforms (approximately 8.95 kDa for RNase III and 5.93 kDa for RNase IV).

• IMMUNE NETWORK
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• 제5권4호
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• pp.237-246
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• 2005

Background: Little information is available on the identification and characterization of the upstream regulators of the signal transduction cascades for Mycobacterium tuberculosis (M. tbc)-induced ERK 1/2 activation and chemokine expression. We investigated the signaling mechanisms involved in expression of CCL3 /MIP-1 and CCL4/MIP-1 in human primary monocytes infected with M. tbc. Methods: MAP kinase phosphorylation was determined using western blot analysis with specific primary antibodies (ERK 1/2, and phospho-ERK1/2), and the upstream signaling pathways were further investigated using specific inhibitors. Results: An avirulent strain, M. tbc H37Ra, induced greater and more sustained ERK 1/2 phosphorylation, and higher CCL3 and CCL4 production, than did M. tbc H37Rv. Specific inhibitors for mitogen-activated protein kinase (MAPK) kinase (MEK; U0126 and PD98059) significantly inhibited the expression of CCL3 and CCL4 in human monocytes. Mycobactetia-mediated expression of CCL3 and CCL4 was not inhibited by the Ras inhibitor manumycin A or the Raf-1 inhibitor GW 5074. On the other hand, phospholipase C (PLC) inhibitor (U73122) and protein kinase C (PKC)specific inhibitors ($G\ddot{o}6976$ and Ro31-8220) significantly reduced M. tbc-induced activation of ERK 1/2 and chemokine synthesis. Conclusion: These results are the first to demonstrate that the PLC-PKC-MEK-ERK, not the Ras-Raf-MEK-ERK, pathway is the major signaling pathway inducing M. tbc-mediated CCL3 and CCL4 expression in human primary monocytes.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2743-2746
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• 2013

Background: Dilantin sodium (phenytoin) is an antiepileptic drug, which is routinely used to control generalized tonic clonic seizure and partial seizure episodes. A few case reports of oral squamous cell carcinomas arising from regions of phenytoin induced gingival overgrowth (GO), and overexpression of mitogenic factors and p53 have presented this condition as a pathology with potential to transform into malignancy. We recently investigated the genetic status of p53 and H-ras, which are known to be frequently mutated in Indian oral carcinomas in GO tissues and found them to only contain wild type sequences, which suggested a non-neoplastic nature of phenytoin induced GO. However, besides p53 and H-ras, other oncogenes and tumor suppressors such as PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$, are frequently altered in oral squamous cell carcinoma, and hence are required to be analyzed in phenytoin induced GO tissues to be affirmative of its non-neoplastic nature. Methods: 100ng of chromosomal DNA isolated from twenty gingival overgrowth tissues were amplified with primers for exons 9 and 20 of PIK3CA, exons $1{\alpha}$, $1{\beta}$ and 2 of p16INK4a and p14ARF, and exon 2 of $p21^{Waf1/Cip1}$, in independent reactions. PCR amplicons were subsequently gel purified and eluted products were sequenced. Results: Sequencing analysis of the twenty samples of phenytoin induced gingival growth showed no mutations in the analyzed exons of PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$. Conclusion: The present data indicate that the mutational alterations of genes, PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$ that are frequently mutated in oral squamous cell carcinomas are rare in phenytoin induced gingival growth. Thus the findings provide further evidence that phenytoin induced gingival overgrowth as a non-neoplastic lesion, which may be considered as clinically significant given the fact that the epileptic patients are routinely administered with phenytoin for the rest of their lives to control seizure episodes.

• Bulletin of the Korean Chemical Society
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• 제29권7호
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• pp.1303-1310
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• 2008

Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.386-395
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• 2010

Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and $CoCl_2$. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of $CoCl_2$. Y27632 with high specificity for ROCK at 1-30 ${\mu}M$ was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 ${\mu}M$, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including ${\beta}$-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.

• 수산해양교육연구
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• 제27권1호
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• pp.41-48
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• 2015

Juvenile banded catfish(Pseudobagurus fulvidraco, mean length $10.4{\pm}0.37cm$ and mean weight $14.5{\pm}0.46g$) were exposed to several nitrite(${NO_2}^-$) concentrations for 96h at pH levels of $6.18{\pm}0.54$, $6.5{\pm}0.30$ and $7.07{\pm}0.22$. The result showed that cumulative mortalities of fish to ${NO_2}^-$ levels of 12.4, 19.8, 33.9 and 53.6 mg/L at pH levels of $6.18{\pm}0.54$ were 20, 25, 40 and 85%, respectively. At pH $6.5{\pm}0.54$, mortalities to ${NO_2}^-$ 22.4, 36.4, 45.3 and 63.2 mg/L were 25, 35, 50 and 100%, respectively. At pH $7.07{\pm}0.22$, mortalities to ${NO_2}^-$ 25.5, 45.7, 56.3 and 66.4 mg/L were 0, 55, 70 and 100%, respectively. The 96h-$LC_{50}$(median lethal concentration, $LC_{50}$) of fish to several ${NO_2}^-$ concentrations at pH levels of $6.18{\pm}0.54$, $6.5{\pm}0.30$ and $7.07{\pm}0.22$ were assessed in these experiments. 96h-$LC_{50}$ at pH levels of $6.18{\pm}0.54$, $6.5{\pm}0.30$ and $7.07{\pm}0.22$ were 32.68, 40.49 and 45.85 mg/L, respectively. It indicated that acute toxicity of ${NO_2}^-$ to juvenile banded catfish increased with low levels of pH and lengthening of exposure time to ${NO_2}^-$. In particular, smaller fish(mean weight $14.5{\pm}0.46g$) were more sensitive to ${NO_2}^-$ than larger fish(mean weight $81.7{\pm}1.42g$; not published). The 96h-$LC_{50}$ of juvenile banded catfish to ${NO_2}^-$ would be primary guideline for water quality management in the intensive culture system such as RAS and BFT.

• Journal of Microbiology and Biotechnology
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• 제14권6호
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• pp.1286-1294
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• 2004

In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

• 한국수산과학회지
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• 제46권6호
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• pp.675-681
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• 2013

There have been many studies on biofilter process regarding satisfactory water quality and the operational conditions of Recirculating Aquaculture Systems (RAS). For effective nitrification processes, it is necessary to dynamically identify and apply nitrifying microorganisms. Physical, chemical and biological processes concerning biofilms can be applied and influential factors including substrate, dissolved oxygen concentrations, organic matter, temperature, pH, alkalinity, salinity and mixing velocity intensity need to be considered. Also, designing and managing the process based on the dynamic interpretation of these factors are prerequisites for engineering applications of the biofilter process. This paper draws on current literature on the kinetics of nitrification of biofilms in the biofilter process. Influential factors for nitrification are crucial during the biofilter process and are expected to be critical in informing the design and operation of recirculating aquaculture systems.

• Toxicological Research
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• 제20권1호
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• pp.21-29
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• 2004

We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.