• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.122-134
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• 2001

Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

• The Korean Journal of Nuclear Medicine
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• v.38 no.5
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• pp.338-343
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• 2004

Purpose: The purpose of this study was to develop a small animal PET using dual layer phoswich detector to minimize parallax error that degrades spatial resolution at the outer part of field-of-view (FOV). Materials and Methods: A simulation tool GATE (Geant4 Application for Tomographic Emission) was used to derive optimal parameters of small PET, and PET was developed employing the parameters. Lutetium Oxyorthosilicate (LSO) and Lutetium-Yttrium Aluminate-Perovskite(LuYAP) was used to construct dual layer phoswitch crystal. $8{\times}8$ arrays of LSO and LuYAP pixels, $2mm{\times}2mm{\times}8mm$ in size, were coupled to a 64-channel position sensitive photomultiplier tube. The system consisted of 16 detector modules arranged to one ring configuration (ring inner diameter 10 cm, FOV of 8 cm). The data from phoswich detector modules were fed into an ADC board in the data acquisition and preprocessing PC via sockets, decoder block, FPGA board, and bus board. These were linked to the master PC that stored the events data on hard disk. Results: In a preliminary test of the system, reconstructed images were obtained by using a pair of detectors and sensitivity and spatial resolution were measured. Spatial resolution was 2.3 mm FWHM and sensitivity was 10.9 $cps/{\mu}Ci$ at the center of FOV. Conclusion: The radioactivity distribution patterns were accurately represented in sinograms and images obtained by PET with a pair of detectors. These preliminary results indicate that it is promising to develop a high performance small animal PET.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.39-49
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• 1996

In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.104-111
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• 1996

We did Tc-99m sestamibi myocardial perfusion SPECT in 36 patients with acute myocardial infarction when they arrived at the emergency room. And we compared myocardial perfusion images with ECG findings. Then we obtained the follows. The myocardial infarction by the obstruction of left coronary descending artery and right coronary artery showed a good concordance in the diagnosis and infarction site between myocardial perfusion images and ECG findings. The 7 patients with myocardial infarction by a left circumflex coronary artery showed a perfusion defect in the lateral wall in myocardial perfusion SPECT images. But 4 patients of them showed ST segment elevation, 2 patients showed ST depression and 1 patient showed normal ECG findings. The diagnostic sensitivity of Tc-99m sestamibi myocardial perfusion SPECT was 100% by a qualified analysis. The perfusion defect site in the myocardial perfusion SPECT were corresponded with the infarct related coronary artery in 31 patients which was diagnosed by coronary angiograpy. The size of perfusion defect in the po1ar map was $31{\pm}18%(M{\pm}SD)$, in the myocardial infarction with left anterior descending coronary arery obstruction, $31{\pm}13% (M{\pm}SD)$ in the myocardial infarction with right coronary artery obstruction and $25{\pm}5.9%(M{\pm}SD)$ in the myocardial infarction with left circumflex coronary artery obstruction. We concluded that emergency myocardial perfusion SPECT images are useful in the diagnose of myocardial infarction and it's very useful when we are difficult to diagnose with ECG like as lateral wall infarction or left bundle branch block.

• Bulletin of the Society of Naval Architects of Korea
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• v.27 no.3
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• pp.131-136
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• 1990

여러해 전부터 선박의 생산실적이나 생산성 관련 자료를 기록하고 보완하는 작업을 꾸준히 개선토록 노력해온 결과중 중요한 것 하나는, 선박의 여러 가지 설계 검토과정에서 충분히 활용할 수 있는 함축성 있고 믿을만한 형태의 생산정보를 제공해줄 수 있게 되었다는 것이라고 말 할 수 있겠다. 이러한 자료들은 생산계획상 각 단계(stage)에서의 작업량, 예상재료비와 인건비의 산출등이 포함될 수 있으며, 선박이나 해상구조물의 전반적인 설계방법론(design methodology)을 개선코자 한다면 ''생산지향적 설계(Design for Production)''의 근간이 되는 선박건조전략(build strategy), 구매정책(purchasing policy)과 생산기술(production technology)에 대한 폭넓은 지식이 한데 어우러져야 한다. 최근에는 CIMS의 일부분에서 보는 바와 같은 경영관리, 설계 및 생산지원 시스템의 도입으로 이와 같은 설계 프로세스의 추진을 가능케하고 있다. 이와 병행하여 설계를 지원하기 위한 전산기술, 특히 대화형 화상처리기술(interactive graphics)의 발달은 설계자가 선박의 형상이나 구조 배치를 여러 가지로 변화시켜 가면서 눈으로 즉시 확인할 수 있도록 설계자의 능력을 배가시키는데 크게 기여하고 있다. 여러 가지의 설계안(alternative design arrangement)을 신속히 만들어내고 이를 즉시 검토 평가할 수 있는 능력을 초기설계 단계에서 가질 수 있다면 이는 분명히 큰 장점일 것이며, 더구나 설계초기 단계에 생산관련인자를 설계에서 고려할 수 있다면 이는 더욱 두드러진 발전일 것이다. 생산공법과 관련생산 비용을 정확히 반영한 각 가지의 설계안을 짧은 시간내에 검토하고 생산소요 비용을 산출하여 비교함으로써, 수주계약단계에서 실제적인 생산공법과 신뢰성있는 생산실적자료를 기준으로 하여 총 건조비(total production cost)를 최소로 하는 최적의 설계를 선택할 수 있도록 해 줄 것이다. 이제 이와 같은 새로운 설계도구(design tool)를 제공해 주므로써 초기설계에 각종 생산관련 정보나 지식 및 실적자료가 반영가능토록 발전되었다. 본 논문은 영국의 뉴카슬대학교(Univ. of Newcastle upon Type)에서 위에 언급한 특징들을 반영하여 새로운 선박구조 설계 방법을 개발한 연구결과를 보여주고 있다. 본 선계연구는 5단계로 구분되는데; (1) 컴퓨터 그라픽스를 이용하고 생산정보 데이타베이스와 연결시켜 구조형상(geometry)을 정의하고 구조부재 칫수(scantling) 계산/결정 (2) 블럭 분할(block division) 및 강재 배치(panel arrangement)의 확정을 위해 생산기술 및 건조방식에 대한 정보 제공 (3) 상기 (1) 및 (2)를 활용하여 아래 각 생산 단계에서의 생산작업 분석(work content assessment) a) 생산 준비 단계(Preparation) b) 가공 조립 단계(Fabrication/Assembly) c) 탑재 단계(Erection) (4) 각각의 설계(안)에 대하여 재료비(material cost), 인건비(labour cost) 및 오버헤드 비용(overhead cost)을 산출키 위한 조선소의 생산시설 및 각종 품셈 정보 (5) 총 건조 비용(total production cost)을 산출하여 각각의 설계안을 비교 검토. 본 설계 방식을 산적화물선(Bulk Carrier) 설계에 적용하여 구조배치(structural geometry), 표준화의 정도(levels of standardisation), 구조생산공법(structural topology) 등의 변화에 따른 설계 결과의 민감도를 분석(sensitivity studies)하였다. 전산장비는 설계자의 대화형 접근을 용이하도록 하기 위해 VAX의 화상 처리장치를 이용하여 각 설계안에 대한 구조형상과 작업분석, 건조비 현황 등을 제시할 수 있도록 하였다. 결론적으로 본 연구는 설계초기 단계에서 상세한 건조비 모델(detailed production cost model)을 대화형 화상 처리방법에 접합시켜 이를 이용하여 여러가지 설계안의 도출과 비교검토를 신속히 처리할 수 있도록 함은 물론, 각종 생산 실적정보를 초기설계에 반영하는 최초의 시도라고 믿으며, 생산지향적(Design for Production) 최적설계분야의 발전에 많은 도움이 되기를 기대해 마지 않는다. 참고로 본 시스템의 설계 적용결과를 부록에 요약 소개하며, 상세한 내용은 참고문헌 [4] 또는 [7]을 참조 요망한다.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.