• Title/Summary/Keyword: Nuclear foci

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BAF53 is Critical for Focus Formation of $\gamma$-H2AX in Response to DNA Damage

  • Park, Pan-Kyu;Kang, Dong-Hyun;Kwon, Hyock-Man
    • Animal cells and systems
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    • v.13 no.4
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    • pp.405-409
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    • 2009
  • When DNA double-strand breaks (DSBs) were induced in mammalian cells, many DNA damage response proteins are accumulated at damage sites to form nuclear foci called IR-induced foci. Although the formation of foci has been shown to promote repair efficiency, the structural organization of chromatin in foci remains obscure. BAF53 is an actin-related protein which is required for maintenance of chromosome territory. In this study, we show that the formation of IR-induced foci by $\gamma$-H2AX and 53BP1 were reduced when BAF53 is depleted, while DSB- activated ATM pathway and the phosphorylation of H2AX remains intact after DNA damage in BAF53 knockdown cells. We also found that DSB repair efficiency was largely compromised in BAF53 knockdown cells. These results indicate that BAF53 is critical for formation of foci by $\gamma$-H2AX decorated chromatin at damage sites and the structural organization of chromatin in foci is an important factor to achieve the maximum efficiency of DNA repair.

Functional Neuroimaging in Epilepsy: FDG-PET and SPECT (간질에서의 기능적 뇌영상:양전자방출단층촬영과 단일광전자방출 단층촬영)

  • Lee, Sang-Kun;Lee, Dong-Soo
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.1
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    • pp.24-33
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    • 2003
  • Finding epileptogenic zone is the most important step for the successful epilepsy surgery. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and single photon emission computed tomography (SPECT) can be used in the localization of epileptogenic foci. In medial temporal lobe epilepsy, the diagnostic sensitivity of FDG-PET and ictal SPECT is excellent. However, detection of hippocampal sclerosis by MRI is so certain that use of FDG-PET and ictal SPECT in medial temporal lobe epilepsy is limited for some occasions. In neocortical epilepsy, the sensitivities of FDG-PET or ictal SPECT are fair. However, FDG-PET and ictal SPECT can have a crucial role in the localization of epileptogenic foci for non-lesional neocortical epilepsy. Interpretation of FDG-PET has been recently advanced by voxel-based analysis and automatic volume of interest analysis based on a population template. Both analytical methods can aid the objective diagnosis of epileptogenic foci. Ictal SPECT was analyzed using subtraction methods and voxel-based analysis. Rapidity of injection of tracers, ictal EEG findings during injection of tracer, and repeated ictal SPECT were important technical issues of ictal SPECT. SPECT can also be used in the evaluation of validity of Wada test.

The Performance of Ictal Brain SPECT for Localizing Epileptogenic Foci in Temporal Lobe Epilepsies (측두엽 간질에서 발작기 뇌관류 SPECT의 간질병소 국소화 성능)

  • Kim, Eun-Sil;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon;Chang, Kee-Hyun;Lee, Sang-Kun;Chung, Chun-Kee
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.3
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    • pp.287-293
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    • 1995
  • Anterior temporal lobectomy has become a widely used resective surgery in patients with medically intractable temporal lobe epilepsies. Prerequisites of this resection include the accurate localization of the epileptogenic focus and the determination that the proposed resection would not result in unacceptable postoperative memory or language deficits. The purpose of this study was to evaluate the performance of ictal SPECT compared to MRI findings for localization of epiletogenic foci in this group of patients. 11 patients who had been anterior temporal lobectomy were evaluated with ictal $^{99m}Tc$-HMPAO SPECT and MRI. MRI showed 8/11(73%) concordant lesion to the side of surgery and ictal SPECT also showed 8/11(73%) concordant hyperperfusion. In 3 cases with incorrect or nonlocalizing findings of MRI, ictal SPECT showed concordant hyperperfusion. In 2 cases confirmed by pre-resectional invasive EEG, MRI showed bilateral and contralateral lesion but ictal SPECT showed concordant hyperperfusion. 3 delayed injection of ictal SPECT showed discordant hyperperfusion. Thus, ictal SPECT was a useful method for localizing epileptogenic foci in temporal lobe epilepsis and appeared complementay to MRI.

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$^{99m}Tc-HMPAO$ Brain SPECT in Medically Intraetable Epilepsy; Ictal Study (간질증후군의 $^{99m}Tc-HMPAO$ Brain SPECT; Ictal Study)

  • Chung, Tae-Sub;Suh, Jung-Ho;Kim, Dong-Ik;Lee, Jong-Doo;Park, Chang-Yun;Hong, Yong-Kook;Lee, Byung-In;Huh, Kyun
    • The Korean Journal of Nuclear Medicine
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    • v.26 no.2
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    • pp.244-250
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    • 1992
  • Both interictal and ictal $^{99m}Tc-HMPAO$ brain SPECT were performed in 22 patients with medically intractable epilepsy. Localization of epileptic foci in our patients was made by combined results of EEG and other tests, including Wada test, magnetic resonance imaging, and neuropsychometric test. Among them, ictal $^{99m}Tc-HMPAO$ SPECT, localized epilptic foci in 20 of 22 patients and provided evidence of epileptic focus in 12 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci during the ictal study with decreased rCP in interictal study. Ictal $^{99m}Tc-HMPAO$ SPECT was particularly useful for investigating epileptic foci, and when correlated with simultaneously recorded ictal EEG, provided further insight for localizing epileptic foci. Conclusively, $^{99m}Tc-HMPAO$ SPECT is. a useful, noninvasive method of localizing epileptic activity which may be particularly important for presurgical investigations, especially in those patients without large morphological lesions.

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BMI-1026 treatment can induce SAHF formation by activation of Erk1/2

  • Seo, Hyun-Joo;Park, Hye-Jeong;Choi, Hyung-Su;Hwang, So-Yoon;Park, Jeong-Soo;Seong, Yeon-Sun
    • BMB Reports
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    • v.41 no.7
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    • pp.523-528
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    • 2008
  • BMI-1026 is a synthetic aminopyrimidine compound that targets cyclin dependent kinases (cdks) and was initially designed as a potential anticancer drug. Even though it has been well documented that BMI-1026 is a potent cdk inhibitor, little is known about the cellular effects of this compound. In this study, we examined the effects of BMI-1026 treatment on inducing premature senescence and then evaluated the biochemical features of BMI-1026-induced premature senescence. From these experiments we determined that BMI-1026 treatment produced several biochemical features of premature senescence and also stimulated expression of mitogen activated protein kinase (MAPK) family proteins. BMI-1026 treatment caused nuclear translocation of activated Erk1/2 and the formation of senescence associated heterochromatin foci in 5 days. The heterochromatin foci formation was perturbed by inhibition of Erk1/2 activation.

Diagnosis of Ictal Hyperperfusion Using Subtraction Image of Ictal and Interictal Brain Perfusion SPECT (발작기와 발작간기 뇌 관류 SPECT 감산영상을 이용한 간질원인 병소 진단)

  • Lee, Dong Soo;Seo, Jong-Mo;Lee, Jae Sung;Lee, Sang-Kun;Kim, Hyun Jip;Chung, June-Key;Lee, Myung Chul;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.1
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    • pp.20-31
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    • 1998
  • A robust algorithm to disclose and display the difference of ictal and interictal perfusion may facilitate the detection of ictal hyperfusion foci. Diagnostic performance of localizing epileptogenic zones with subtracted SPECT images was compared with the visual diagnosis using ictal and interictal SPECT, MR, or PET. Ietal and interictal Tc-99m-HMPAO cerebral perfusion SPECT images of 48 patients(pts) were processed to get parametric subtracted images. Epileptogenic foci of all pts were diagnosed by seizure free state after resection of epileptogenic zones. In subtraction SPECT, we used normalized difference ratio of pixel counts(ictal-interictal)/interictal ${\times}100%$) after correcting coordinates of ictal and interictal SPECT in semi-automatized 3-dimensional fashion. We found epileptogenic zones in subtraction SPECT and compared the performance with visual diagnosis of ictal and interictal SPECT, MR and PET using post-surgical diagnosis as gold standard. The concordance of subtraction SPECT and ictal-interictal SPECT was moderately good(kappa=0.49). The sensitivity of ictal-interictal SPECT was 73% and that of subtraction SPECT 58%. Positive predictive value of ictal-interictal SPECT was 76% and that of subtraction SPECT was 64%. There was no statistical difference between sensitivity or positive predictive values of subtraction SPECT and ictal-interictal SPECT, MR or PET. Such was also the case when we divided patients into temporal lobe epilepsy and neocortical epilepsy. We conclude that subtraction SPECT we produced had equivalent diagnostic performance compared with ictal-interictal SPECT in localizing epileptogenic zones. Additional value of these subtraction SPECT in clinical interpretation of ictal and interictal SPECT should be further evaluated.

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Clinical Application of PET in Abdominal Cancers (소화기 암에서 PET의 임상적 의의)

  • Choi, Chang-Woon
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.39-45
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    • 2002
  • Clinical application of positron emission tomography (PET) is rapidly increasing for the defection and staging of cancer at whole-body studios performed with the glucose analogue tracer 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in the liver and the other abdominal organs, it is particularly useful for identification and characterization of the entire body simultaneously. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterizing of indeterminate soft-tissue masses. Most abdominal cancer requires surgical management. FDG PET can improve the selection of patients for surgical treatment and thereby reduce the morbidity and mortality associated with inappropriate surgery. FDG PET is also useful for the early detection of recurrence and the monitoring of therapeutic effect. The abdominal cancers, such as gastroesophageal cancer, colorectal cancer, liver cancer and pancreatic cancer, are common malignancies in Korea, and PET is one of the most promising and useful methodologies for the management of abdominal cancers.

The Actin-Related Protein BAF53 Is Essential for Chromosomal Subdomain Integrity

  • Lee, Kiwon;Kim, Ji Hye;Kwon, Hyockman
    • Molecules and Cells
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    • v.38 no.9
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    • pp.789-795
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    • 2015
  • A chromosome territory is composed of chromosomal subdomains. The internal structure of chromosomal subdomains provides a structural framework for many genomic activities such as replication and DNA repair, and thus is key to determining the basis of their mechanisms. However, the internal structure and regulating proteins of a chromosomal subdomain remains elusive. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. Because the integrity of chromosomal subdomains is a deciding factor of the volume of a chromosome territory, we examined here the effect of BAF53 knockdown on chromosomal subdomains. We found that BAF53 knockdown led to the disintegration of histone H2B-GFP-visualized chromosomal subdomains and BrdU-labeled replication foci. In addition, the size of DNA loops measured by the maximum fluorescent halo technique increased and became irregular after BAF53 knockdown, indicating DNA loops were released from the residual nuclear structure. These data can be accounted for by the model that BAF53 is prerequisite for maintaining the structural integrity of chromosomal subdomains.

The Preventive Effects of Colon Cancer and Imflammatory Bowel Disease of Supercritical Heat-Treated Radish Extracts

  • Kim, Hyun-Kyoung
    • International Journal of Internet, Broadcasting and Communication
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    • v.12 no.2
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    • pp.98-112
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    • 2020
  • There is a strong connection between the diet rich in antioxidants and the decreased incidence of inflammatory bowel disease and cancerous diseases. Diets that are rich in anti-oxidants particularly include fruits and vegetables containing the high amounts of vitamin A-E, carotenoids, and minerals. The supercritical heat-treated radish extracts of the research result had an inhibitory effect on the development of aberrant crypt foci (ACF), namely, preneoplastic lesions having a potential to become cancer cells and reduced the number of the aberrant crypt foci (ACF) consisting of four or more aberrant crypts (AC) having high risk to become tumors by about half. The supercritical heat-treated radish extracts can reduce the incidence of preneoplastic lesions having a high risk of developing cancer by about 28 %. DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. Supercritical heat-treated radish extracts, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, supercritical heat-treated radish extracts treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways, and prevented the apoptosis of colon. Moreover, supercritical heat-treated radish extracts administration significantly led to the up-regulation of anti-oxidant enzyme including SOD and Catalase.

Downregulation of JMJD2a and LSD1 is involved in CK2 inhibition-mediated cellular senescence through the p53-SUV39h1 pathway

  • Park, Jeong-Woo;Bae, Young-Seuk
    • BMB Reports
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    • v.55 no.2
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    • pp.92-97
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    • 2022
  • Lysine methylation is one of the most important histone modifications that modulate chromatin structure. In the present study, the roles of the histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence were investigated. The ectopic expression of JMJD2a and LSD1 suppressed the induction of senescence-associated β-galactosidase activity and heterochromatin foci formation as well as the reduction of colony-forming and cell migration ability mediated by CK2 knockdown. CK2 downregulation inhibited JMJD2a and LSD1 expression by activating the mammalian target of rapamycin (mTOR)-ribosomal p70 S6 kinase (p70S6K) pathway. In addition, the down-regulation of JMJD2a and LSD1 was involved in activating the p53-p21Cip1/WAF1-SUV39h1-trimethylation of the histone H3 Lys9 (H3K9me3) pathway in CK2-downregulated cells. Further, CK2 downregulation-mediated JMJD2a and LSD1 reduction was found to stimulate the dimethylation of Lys370 on p53 (p53K370me2) and nuclear import of SUV39h1. Therefore, this study indicated that CK2 downregulation reduces JMJD2a and LSD1 expression by activating mTOR, resulting in H3K9me3 induction by increasing the p53K370me2-dependent nuclear import of SUV39h1. These results suggest that CK2 is a potential therapeutic target for age-related diseases.