• Title/Summary/Keyword: human interference

Search Result 327, Processing Time 0.037 seconds

BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

  • Zhu, Xi-Shan;Lin, Zi-Ying;Du, Jing;Cao, Guang-Xin;Liu, Gang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.12
    • /
    • pp.4773-4780
    • /
    • 2014
  • Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

Some New Problems of International Aviation Security- Considerations Forcused on its Legal Aspects (최근국제항공보안대책(最近國際航空保安対策)의 제간제(諸間題) -특히 법적측면(法的測面)을 중심(中心)으로-)

  • Choi, Wan-Sik
    • The Korean Journal of Air & Space Law and Policy
    • /
    • v.5
    • /
    • pp.53-75
    • /
    • 1993
  • This article is concerned with the comment on "Some New Problems of International Aviation Security-Considerations Forcused on its Legal Aspects". Ever since 1970, in addition to the problem of failure to accept the Tokyo, Hague and Montreal Conventions, there has been also the problem of parties to them, failing to comply with their obligations under the respective treaties, in the form especially of nominal penalties or the lack of any effort to prosecute after blank refusals to extradite. There have also been cases of prolonged detention of aircraft, passengers and hostages. In this regard, all three conventions contain identical clauses which submit disputes between two or more contracting States concerning the interpretation or application of the respective conventions to arbitration or failing agreement on the organization of the arbitration, to the International Court of Justice. To the extent to which contracting States have not contracted out of this undertaking, as I fear they are expressly allowed to do, this promision can be used by contracting States to ensure compliance. But to date, this avenue does not appear to have been used. From this point of view, it may be worth mentioning that there appears to be an alarming trend towards the view that the defeat of terrorism is such an overriding imperative that all means of doing so become, in international law, automatically lawful. In addition, in as far as aviation security is concerned, as in fact it has long been suggested, what is required is the "application of the strictest security measures by all concerned."In this regard, mention should be made of Annex 17 to the Chicago Convention on Security-Safeguarding International Civil Aviation against Acts of Unlawful Intereference. ICAO has, moreover, compiled, for restricted distribution, a Security Manual for Safeguarding Civil Aviation Against Acts of Unlawful Interference, which is highly useful. In this regard, it may well be argued that, unless States members of ICAO notify the ICAO Council of their inability to comply with opecific standards in Annex 17 or any of the related Annexes in accordance with Article 38 of the 1944 Chicago Convention on International Civil Aviation, their failure to do so can involve State responsibility and, if damage were to insure, their liability. The same applies to breaches of any other treaty obligation. I hope to demonstrate that although modes of international violence may change, their underlying characteristics remain broadly similar, necessitating not simply the adoption of an adequate body of domestic legislation, firm in its content and fairly administered, but also an international network of communication, of cooperation and of coordination of policies. Afurther legal instrument is now being developed by the Legal Committee of ICAO with respect to unlawful acts at International airports. These instruments, however, are not very effective, because of the absence of universal acceptance and the deficiency I have already pointed out. Therefore, States, airports and international airlines have to concentrate on prevention. If the development of policies is important at the international level, it is equally important in the domestic setting. For example, the recent experiences of France have prompted many changes in the State's legislation and in its policies towards terrorism, with higher penalties for terrorist offences and incentives which encourage accused terrorists to pass informations to the authorities. And our government has to tighten furthermore security measures. Particularly, in the case an unarmed hijacker who boards having no instrument in his possession with which to promote the hoax, a plaintiff-passenger would be hard-pressed to show that the airline was negligent in screening the hijacker prior to boarding. In light of the airline's duty to exercise a high degree of care to provide for the safety of all the passengers on board, an acquiescence to a hijacker's demands on the part of the air carrier could constitute a breach of duty only when it is clearly shown that the carrier's employees knew or plainly should have known that the hijacker was unarmed. The general opinion is that the legal oystem could be sufficient, provided that the political will is there to use and apply it effectively. All agreed that the main responsibility for security has to be borne by the governments. A state that supports aviation terrorism is responsible for violation of International Aviation Law. Generally speaking, terrorism is a violation of international law. It violates the sovereign rights of states, and the human rights of the individuals. We have to contribute more to the creation of a general consensus amongst all states about the need to combat the threat of aviation terrorism. I think that aviation terrorism as becoming an ever more serious issue, has to be solved by internationally agreed and closely co - ordinated measures.

  • PDF

Radiolabeling of NOTA and DOTA with Positron Emitting $^{68}$Ga and Investigation of In Vitro Properties (양전자 방출핵종 $^{68}$Ga을 이용한 NOTA와 DOTA의 표지 및 시험관내 특성 연구)

  • Jeong, Jae-Min;Kim, Young-Ju;Lee, Yun-Sang;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
    • /
    • v.43 no.4
    • /
    • pp.330-336
    • /
    • 2009
  • Purpose: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide $^{68}$Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Materials and Methods: Various concentrations of NOTA 3HCl and DOTA 4HCl were labeled with 1 mL $^{68}$GaCl$_3$ (0.18$\sim$5.75 mCi in 0.1 M HCl in various pH. NOTA 3HCl (0.373 mM) was labeled with $^{68}$GaCl$_3$(0.183$\sim$0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl$_2$, FeCl$_2$, InCl$_3$, FeCl$_3$, GaCl$_3$, MgCl$_2$ or CaCl$_2$ (0$\sim$6.07 mM) at room temperature. The labeling efficiencies of $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. Results: $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37$^{\circ}C$. NOTA was labeled at room temperature while DOTA required heating for labeling. $^{68}$Ga-NOTA labeling efficiency was reduced by CuCl$_2$, FeCl$_2$, InCl$_2$, FeCl$_3$ or CaCl$_3$, however, was not influenced by MgCl$_2$ or CaCl$_2$. The protein binding was low (2.04$\sim$3.32%). Log P value of $^{68}$Ga-NOTA was -3.07 indicating high hydrophilicity. Conclusion: We found that NOTA is a better bifunctional chelating agent than DOTA for $^{68}$Ga labeling. Although, $^{68}$Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

Studies on the Selective Separation and Preconcentration of Cr(VI) Ion by XAD-16-Chromotropic Acid Chelating Resin (XAD-16-Chromotropic Acid 킬레이트 수지에 의한 몇 가지 금속이온의 선택적 분리 및 농축에 관한 연구)

  • Lee, Won;Lee, Chang-Youl;Kim, Mi-Kyoung;Kim, In-Whan
    • Analytical Science and Technology
    • /
    • v.17 no.3
    • /
    • pp.199-210
    • /
    • 2004
  • A new polystyrene-divinylbenzene chelating resin containing 4,5-dihydroxy-naphthalene-2,7-disulfonic acid (chromotropic acid : CTA) as functional group has been synthesized and characterized. The sorption and desorption properties of this chelating resin for Cr(III) ion and Cr(VI) ion including nine metal bloodstain. As a results, FOB test kit could be effectively applied to identification of human blood at chelating resin was stable in acidic and alkaline solution. The Cr(VI) ion is selectively separated from Cr (III) ion at pH 2 and the maximum sorption capacity of Cr(VI) ion is 1.2 mmol/g. In the presence of anions such as $F^-$, $SO{_4}^{2-}$, $CN^-$, $CH_3COO^-$, $NO{_3}^-$, the sorption of Cr(VI) ion was reduced but anions such as $PO{_4}^{3-}$ and $Cl^-$ revealed no interference effect. The elution order of metal ions obtained from breakthrough capacity and overall capacity at pH 2 was Cr(VI)>Sn(II)>Fe(III)>Cu(II)>Cd(II)${\simeq}Pb(II){\simeq}Cr(III){\simeq}Mn(II){\simeq}Ni(II){\simeq}Al(III)$. Desorption characteristics for Cr(VI) ion was investigated with desorption agents such as $HNO_3$, HCl, and $H_2SO_4$. It was found that the ion showed high desorption efficiency with 3 M HCl. As the result, the chelating resin, XAD-16-CTA was successfully applied to separation and preconcentration of Cr (VI) ion from several metal ions in metal finishing works.

Comparison of Movement Distance and Home Range Size of Gold-spotted Pond Frog (Pelophylax chosenicus) between Rice Paddy and Ecological park - Focus on the Planning Alternative Habitat - (논과 생태공원에서 금개구리 이동 거리 및 서식영역 크기 비교 - 대체서식지 조성 중심으로 -)

  • Park, Su-Gon;Ra, Nam-Yong;Jang, Young-Soo;Woo, Seung Hyun;Koo, Kyo Soung;Chang, Min-Ho
    • Ecology and Resilient Infrastructure
    • /
    • v.6 no.4
    • /
    • pp.200-207
    • /
    • 2019
  • The movement distance and home range size of Pelophylax chosenicus were identified in the rice paddy and ecological park as alternative habitats from July to November 2017. A total of 39 frogs were tracked by radio tracking method. As a result, the average move distance in the population of rice paddy was 11.7 ± 1.9 m (n = 64) and the population of ecological park was 24.7 ± 4.3 m (n = 39). The move distance between the two populations was significantly different. The mean MCP of the population of rice paddy was 181.2 ± 110.8 m2 (n = 11) and the population of ecological park was 416.1 ± 276.2 m2 (n = 10), but there was no significant difference. The population area of rice paddy was 4,160 m2 (Kernel density 95%) and the core area was 1,080 m2 (Kernel density 50%). The population area (Kernel density 95%) of ecological park was 5,391 m2 and the core area (Kernel density 50%) was 736 m2. This study shows that it is appropriate to construct the area of alternative habitat for P. chosenicus at least 1.33 ha, and it is more advantageous for the ecological park to be constructed than the paddy field with high development pressure and human interference. If the rice paddies were to be abandoned for several years, or to be used traditional farming methods, such as refraining from using agricultural machinery and chemicals, they could be used as alternative habitat for P. chosenicus.

EFFECT OF CAVITY DISINFECTANT ON THE BOND STRENGTH AND MICROLEAKAGE OF DENTIN BONDING AGENTS (와동 세척제가 상아질 결합제의 결합에 미치는 영향)

  • Song, Seung-Ho;Lee, Ju-Hyun;Park, Ho-Won
    • Journal of the korean academy of Pediatric Dentistry
    • /
    • v.32 no.4
    • /
    • pp.595-603
    • /
    • 2005
  • Incomplete removal of bacteria contaminated dentin or enamel associated with caries is a potential problem in restorative dentistry Secondary or residual caries, pulpal inflammation and hypersensitivity may result from bacteria left after the initial preparation, especially if an adequate seal against microleakage is not obtained. A possible solution to eliminate residual bacteria left in a cavity preparation would be to treat the cavity with cavity disinfectant wash. But a potential problem with using a cavity disinfectant with dentin bonding agents could be their interference with the ability of the resin to bond to the tooth micromechanically. The purpose of this study was to evaluate the effect of 2% chlorhexidine containing cavity disinfectant ($Consepsis^{(R)}$) on shear bond strength and microleakage of dentin bonding agents, $Adper ^{TM}$ $Scotchbond^{TM}$ Multi-Purpose, $Adper^{TM}$ Single Bond and $Adper^{TM}\;Prompt^{TM}\; L-Pop^{TM}$ Sixty and sixty sound human third molar teeth, respectively, were used for shear bond strength and microleakage test. For experimental group, cavity disinfectant was applied before dentin bonding agents, and was not applied for the control group. The result from the this study can be summarized as follows ; 1. Use of 2% chlorhexidine containing cavity disinfectant($Consepsis^{(R)}$) does not significantly affect the shear bond strength of dentin bonding agents. 2. Use of 2% chlorhexidine containing cavity disinfectant($Consepsis^{(R)}$) does not significantly affect the microleakage of dentin bonding agents.

  • PDF

Effect of Noise in Human Body (소음이 인체에 미치는 영향)

  • 이영노
    • Proceedings of the KOR-BRONCHOESO Conference
    • /
    • 1972.03a
    • /
    • pp.7-8
    • /
    • 1972
  • The effects of noise exposure are of two types: Nonauditory effects and auditory effects. Nonauditory effects of noise exposure are interference with communication by speech, sleeping and emotional behavior. The noise will cause the high blood pressure and rapid pulse, also that decrease the salivation and gastric juice. in experimentaly showed that the Corticoid hormon: Gonatotropic hormone were decrease and Thyrotropic hormoone is increase. Auditory effect of noise exposure. when the normal ear is exposed to noise at noise at hamful intensities (above 90㏈) for sufficiently long periods of time, a temoral depression of hearing results, disappearing after minutes or hours of rest. When the exposure longer or intesity greater is reached the Permanent threshold shift called noise-induced hearing loss. Hearing loss resulting from noise exposure presents legal as well as medical problems. The otologist who examines and evaluates the industrial hearing loss cases must be properly informed, not only concerning the otologic but also about the physical and legal aspects of the problems. The measurement of hearing ability is the most important part of a hearing conservation, both preplacement and periodic follow-up tests of hearing. The ideal hearing conservation program would be able to reduce or eliminate the hazardous noise at its source or by acoustic isolation of noisy working area and two ear protections (plugs and muff type) were developed for personal protection.

  • PDF

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation (매실 추출물의 산화질소 생성과 NF-κB 활성 조절을 통한 LPS유도성 THP-1 세포 동형성 응집의 억제 효과)

  • Lee, Hye-Rim;Park, Youngsook;Kim, Hyun Jeong;Lee, Aram;Choi, Jihea;Pyee, Jaeho;Park, Heonyong;Kim, Jongmin
    • Journal of Life Science
    • /
    • v.25 no.7
    • /
    • pp.801-809
    • /
    • 2015
  • Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

Combined Treatment of Nonsteroidal Anti-inflammatory Drugs and Genistein Synergistically Induces Apoptosis via Induction of NAG-1 in Human Lung Adenocarcinoma A549 Cells (인간 A549 폐암세포에서 비스테로이드성 항염증제와 genistein의 복합처리에 의한 NAG-1 의존적 세포사멸 증진 효과)

  • Kim, Cho-Hee;Kim, Min-Young;Lee, Su-Yeon;Moon, Ji-Young;Han, Song-Iy;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
    • /
    • v.19 no.8
    • /
    • pp.1073-1080
    • /
    • 2009
  • A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

Enhancement of Sensitivity of Human Lung Cancer Cell Line to TRAIL and Gefitinib by IGF-1R Blockade (폐암세포주에서 IGF-1R 억제를 이용한 TRAIL 및 gefitinib에 대한 감수성 증가를 위한 연구)

  • Lee, Yoon-Jin;Park, Mi-Young;Kang, Young-Ae;Kwon, Sung-Youn;Yoon, Ho-Il;Lee, Jae-Ho;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
    • /
    • v.63 no.1
    • /
    • pp.42-51
    • /
    • 2007
  • Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). Results: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. Conclusion: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.