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Effect of cAMP on the Replication of Human Cytomegalovirus (Human cytomegalovirus 증식에 미치는 cAMP의 영향)

  • 지용훈;윤주현;이찬희
    • Korean Journal of Microbiology
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    • v.31 no.1
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    • pp.72-78
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    • 1993
  • Since the 'promoter/enhancer region of the major immediate early (IE) ~ene of human cytomegalovirus (HCMV) contains the cyclic AMP (cAMP) response element (CRE) consensus sequence, it was reasonable to hypothesize that cAMP might affect HCMV replication. Cyclic AMP modulating drugs such as 8-bromoadenosine 3',5'-cyclic monophosphate (BrA), and papaverine were used to affect the intracellular levels of cAMP, and the effects of the drugs on HCMV replication were studied. While papaverine effectively inhibited HCMV multiplication and DNA synthesis, BrA exerted little effect on the production of infectious HCMV yields. The synthesis of DNA in HCMV-infected cells appeared to be stimulated by BrA In order to understand the effect of cAMP on the expression of HCMV major IE gene, plasmid (pCMVIE/CAT) containing a reporter gene driven by HCMV IE promoter was transfected into either permissive human embryo lung (HEL) cells or nonpermissive cells. PL,Javerine, which has been reported to block the HCMV-induced increase in cAMP, reduced the expression of pCMVIE/CA T in permissive HEL cells. Treatment of transfected cells with BrA increased the expression of HCMV major IE promoter not only in HEL cells, but also in nonpermissive HeLa and Vero cells. Therefore, it seems that the expression of HCMV major IE gene is regulated by cAMP.

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Fracture Behaviors of Jointed Rock Model Containing an Opening Under Biaxial Compression Condition (이축압축 조건에서 공동이 존재하는 유사 절리암반 모델의 파괴 거동)

  • SaGong, Myung;Yoo, Jea-Ho;Park, Du-Hee;Lee, J.S.
    • Journal of the Korean Geotechnical Society
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    • v.25 no.10
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    • pp.17-30
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    • 2009
  • Underground construction such as tunneling can induce damages on the surrounding rock mass, due to the stress concentration of in situ stresses and excessive energy input during construction sequence, such as blasting. The developed damage on the rock mass can have substantial influence on the mechanical and hydraulic behaviors of the rock masses around a tunnel. In this study, investigation on the generation of damage around an opening in a jointed rock model under biaxial compression condition was conducted. The joint dip angles employed are 30, 45, and 60 degrees to the horizontal, and the synthetic rock mass was made using early strength cement and water. From the biaxial compression test, initiation and propagation of tensile cracks at norm to the joint angle were found. The propagated tensile cracks eventually developed rock blocks, which were dislodged from the rock mass. Furthermore, the propagation process of the tensile cracks varies with joint angle: lower joint angle model shows more stable and progressive tensile crack propagation. The development of the tensile crack can be explained under the hypothesis that the rock segment encompassed by the joint set is subjected to the developing moment, which can be induced by the geometric irregularity around the opening in the rock model. The experiment results were simulated by using discrete element method PFC 2D. From the simulation, as has been observed from the test, a rock mass with lower joint angle produces wider damage region and rock block by tensile cracks. In addition, a rock model with lower joint angle shows progressive tensile cracks generation around the opening from the investigation of the interacted tensile cracks.

Phase Image Analysis in Conduction Disturbance Patients (심실내 전도장애 환자에서의 $^{99m}Tc$-RBC Gated Blood-Pool Scintigraphy을 통한 Phase Image Analysis)

  • Kwak, Byeng-Su;Choi, Si-Wan;Kang, Seung-Sik;Park, Ki-Nam;Lee, Kang-Wook;Jeon, Eun-Seok;Park, Chong-Hun
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.1
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    • pp.44-51
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    • 1994
  • It is known that the normal His-Purkinje system provides for nearly synchronous activation of right (RV) and left (LV) ventricles. When His-Purkinje conduction is abnormal, the resulting sequence of ventricular contraction must be correspondingly abnormal. These abnormal mechanical consequences were difficult to demonstrate because of the complexity and the rapidity of it's events. To determine the relationship of the phase changes and the abnormalities of ventricular conduction, we performed phase image analysis of $^{99m}Tc$-RBC gated blood pool scintigrams in patients with intraventricular conduction disturbances (24 complete left bundle branch block (C-LBBB), 15 complete right bundle branch block (C-RBBB), 13 Wolff-Parkinson-White syndrome (WPW), 10 controls). The results were as follows; 1) The ejection fraction (EF), peak ejection rate (PER), and peak filling rate (PFR) of LV in gated blood pool scintigraphy (GBPS) were significantly lower in patients with C-LBBB than in controls ($44.4{\pm}13.9%$ vs $69.9{\pm}4.2%,\;2.48{\pm}0.98$ vs $3.51{\pm}0.62,\;1.76{\pm}0.71$ vs $3.38{\pm}0.92$, respectively, p<0.05). 2) In the phase angle analysis of LV, Standard deviation (SD), width of half maximum of phase angle (FWHM), and range of phase angle were significantly increased in patients with C-LBBB than in controls ($20.6{\pm}18.1$ vs $8.6{\pm}1.8,\;22.5{\pm}9.2$ vs $16.0{\pm}3.9,\;95.7{\pm}31.7$ vs $51.3{\pm}5.4$, respectively, p<0.05). 3) There was no significant difference in EF, PER, PFR between patients with the Wolff-parkinson-White syndrome and controls. 4) Standard deviation and range of phase angle were significantly higher in patients with WPW syndrome than in controls ($10.6{\pm}2.6$ vs $8.6{\pm}1.8$, p<0.05, $69.8{\pm}11.7$ vs $51.3{\pm}5.4$, p<0.001, respectively), however, there was no difference between the two groups in full width of half maximum. 5) Phase image analysis revealed relatively uniform phase across the both ventricles in patients with normal conduction, but markedly delayed phase in the left ventricle of patients with LBBB. 6) In 13 cases of WPW syndrome, the site of preexcitation could be localized in 10 cases (77%) by phase image analysis. Therefore, it can be concluded that phase image analysis can provide an accurate noninvasive method to detect the mechanical consequences of a wide variety of abnormal electrical activation in ventricles.

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Stratigraphic response to tectonic evolution of sedimentary basins in the Yellow Sea and adjacent areas (황해 및 인접 지역 퇴적분지들의 구조적 진화에 따른 층서)

  • Ryo In Chang;Kim Boo Yang;Kwak won Jun;Kim Gi Hyoun;Park Se Jin
    • The Korean Journal of Petroleum Geology
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    • v.8 no.1_2 s.9
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    • pp.1-43
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    • 2000
  • A comparison study for understanding a stratigraphic response to tectonic evolution of sedimentary basins in the Yellow Sea and adjacent areas was carried out by using an integrated stratigraphic technology. As an interim result, we propose a stratigraphic framework that allows temporal and spatial correlation of the sedimentary successions in the basins. This stratigraphic framework will use as a new stratigraphic paradigm for hydrocarbon exploration in the Yellow Sea and adjacent areas. Integrated stratigraphic analysis in conjunction with sequence-keyed biostratigraphy allows us to define nine stratigraphic units in the basins: Cambro-Ordovician, Carboniferous-Triassic, early to middle Jurassic, late Jurassic-early Cretaceous, late Cretaceous, Paleocene-Eocene, Oligocene, early Miocene, and middle Miocene-Pliocene. They are tectono-stratigraphic units that provide time-sliced information on basin-forming tectonics, sedimentation, and basin-modifying tectonics of sedimentary basins in the Yellow Sea and adjacent area. In the Paleozoic, the South Yellow Sea basin was initiated as a marginal sag basin in the northern margin of the South China Block. Siliciclastic and carbonate sediments were deposited in the basin, showing cyclic fashions due to relative sea-level fluctuations. During the Devonian, however, the basin was once uplifted and deformed due to the Caledonian Orogeny, which resulted in an unconformity between the Cambro-Ordovician and the Carboniferous-Triassic units. The second orogenic event, Indosinian Orogeny, occurred in the late Permian-late Triassic, when the North China block began to collide with the South China block. Collision of the North and South China blocks produced the Qinling-Dabie-Sulu-Imjin foldbelts and led to the uplift and deformation of the Paleozoic strata. Subsequent rapid subsidence of the foreland parallel to the foldbelts formed the Bohai and the West Korean Bay basins where infilled with the early to middle Jurassic molasse sediments. Also Piggyback basins locally developed along the thrust. The later intensive Yanshanian (first) Orogeny modified these foreland and Piggyback basins in the late Jurassic. The South Yellow Sea basin, however, was likely to be a continental interior sag basin during the early to middle Jurassic. The early to middle Jurassic unit in the South Yellow Sea basin is characterized by fluvial to lacustrine sandstone and shale with a thick basal quartz conglomerate that contains well-sorted and well-rounded gravels. Meanwhile, the Tan-Lu fault system underwent a sinistrai strike-slip wrench movement in the late Triassic and continued into the Jurassic and Cretaceous until the early Tertiary. In the late Jurassic, development of second- or third-order wrench faults along the Tan-Lu fault system probably initiated a series of small-scale strike-slip extensional basins. Continued sinistral movement of the Tan-Lu fault until the late Eocene caused a megashear in the South Yellow Sea basin, forming a large-scale pull-apart basin. However, the Bohai basin was uplifted and severely modified during this period. h pronounced Yanshanian Orogeny (second and third) was marked by the unconformity between the early Cretaceous and late Eocene in the Bohai basin. In the late Eocene, the Indian Plate began to collide with the Eurasian Plate, forming a megasuture zone. This orogenic event, namely the Himalayan Orogeny, was probably responsible for the change of motion of the Tan-Lu fault system from left-lateral to right-lateral. The right-lateral strike-slip movement of the Tan-Lu fault caused the tectonic inversion of the South Yellow Sea basin and the pull-apart opening of the Bohai basin. Thus, the Oligocene was the main period of sedimentation in the Bohai basin as well as severe tectonic modification of the South Yellow Sea basin. After the Oligocene, the Yellow Sea and Bohai basins have maintained thermal subsidence up to the present with short periods of marine transgressions extending into the land part of the present basins.

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Correlation of p53 Protein Overexpression, Gene Mutation with Prognosis in Resected Non-Small Cell Lung Cancer(NSCLC) Patients (비소세포폐암에서 p53유전자의 구조적 이상 및 단백질 발현이 예후에 미치는 영향)

  • Lee, Y.H.;Shin, D.H.;Kim, J.H.;Lim, H.Y.;Chung, K.Y.;Yang, W.I.;Kim, S.K.;Chang, J.;Roh, J.K.;Kim, S.K.;Lee, W.Y.;Kim, B.S.;Kim, B.S.
    • 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.

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