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Is the BRCA Germline Mutation a Prognostic Factor in Korean Patients with Early-onset Breast Carcinomas? (한국의 젊은 여성유방암 환자에서 BRCA 배선유전자 돌연변이는 예후인자인가?)

  • Choi Doo Ho;Lee Min Hyuk;Haffty Bruce G.
    • Radiation Oncology Journal
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    • v.21 no.2
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    • pp.149-157
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    • 2003
  • Purpose: The purpose of this study was to determine if there were prognostic differences between BRCA related and BRCA non-related Korean patients with early-onset breast carcinomas. Materials and Methods: Sixty women who had developed breast cancers before the age of 40, and who were treated at the Soonchunhyang University Hospital, were studied independently of their family histories. The age range was 18 to 40 with a median of 34.5 years. Lymphocyte specimens from peripheral blood were studied for the heterozygous mutations of BRCA1 and BRCA2 using direct sequencing methods. Immunohistochemistry was peformed on the paraffin-embedded tissue blocks that were available. Results: Eleven deleterious mutations (18.3%, 6 in BRCA1 and 5 in BRCA2) and 7 missense mutations of unknown significance (11.7%), were found among the 60 patients. More than half of the mutation were novel, and were not reported in the database. Most of the BRCA-associated patients had no history of breast cancer. No treatment related failures were observed in the BRCA carriers, with the exception of one patient that had experienced a new primary tumor of the contralateral breast. The seven year relapse free survival rate were 50 and 79% In the BRCA carrier and BRCA negative patients, respectively. Although the expression of estrogen and progesterone receptors were less common, and histological features more aggressive, in the BRCA associated tumors, the outcome of the patients with BRCA mutations was not poorer than that on the patients without deleterious mutations. Conclusion.: Despite the BRCA mutation carriers having adverse prognostic features, the recurrence rate was relatively lower than that in the BRCA non-carrying Korean patients wi4h early-onset breast carcinomas. In addition, although the prevalence of the BRCA mutation in Korean patients was higher than that in white patients, the penetrance of the cancer seemed to be relatively low in Korean women carrying BRCA mutations. A large population based study of the BRCA mutation, with a long-term follow-up of the study patients will be required to confirm these results.

The vacuolar processing enzyme (VPE) mutation suppresses an HR-like cell death induced by the double knockout mutant of vacuolar Ca2+-ATPases in Arabidopsis (애기장대에서 두 액포막 칼슘펌프 돌연변이에 의하여 유도되는 세포사멸 표현형의 액포수식효소(VPE) 돌연변이에 의한 억제)

  • Park, Hyeong-Cheol;Lee, Sang-Min;Kim, Ho-Soo;Chung, Woo-Sik
    • Journal of Plant Biotechnology
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    • v.38 no.2
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    • pp.169-175
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    • 2011
  • Calcium ($Ca^{2+}$) signals have been implicated in regulating plant development and responses to the environmental stresses including a programmed cell death pathway. In animals and plants, cytosolic $Ca^{2+}$ signals have been involved in the activation of programmed cell death (PCD). Recently, we reported that disruption of Arabidopsis vacuolar $\b{A}$utoinhibited $\underline{C}a^{2+}$-$\b{A}$TPases (ACAs), ACA4 and ACA11, resulted in the activation of a salicylic acid-dependent programmed cell death pathway. Although extensive studies have revealed various components of a PCD in plants, executors to directly induce PCD are well unknown. Here, we provide that the vacuolar processing enzymes (VPEs) are involved in a PCD induced by the double knockout mutant of vacuolar $Ca^{2+}$-ATPases in Arabidopsis. The gene expression of VPE was rapidly up-regulated and the enzyme activity of VPE was increased in the double mutant plants. We also generated aca4/aca11/avpe, aca4/aca11/${\gamma}$vpe and aca4/aca11/avpe/${\gamma}$vpe mutant plants. Although cell death phenotype of the double mutant plants was not completely disappeared in the triple and quadruple mutant plants, the triple and quadruple mutant plants showed to significantly delay cell death phenotype of the double mutant plants. These results suggest that the VPE is involved in the HR-like cell death in the double mutant of vacuolar $Ca^{2+}$-ATPases in Arabidopsis.

Mitral Valve Repair for Active and Healed Endocarditis (급성 혹은 치유된 심내막염 환자에서의 승모판막성형술)

  • Baek, Man-Jong;Na, Chan-Young;Oh, Sam-Sae;Kim, Woong-Han;Whang, Sung-Wook;Lee, Cheol;Kang, Chang-Hyun;Chang, Yun-Hee;Jo, Won-Min;Kim, Jae-Hyun;Seo, Hong-Ju;Kim, Wook-Sung;Lee, Young-Tak;Kim, Chong-Whan
    • Journal of Chest Surgery
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    • v.36 no.11
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    • pp.820-827
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    • 2003
  • Background: Mitral valve repair rather than replacement for mitral regurgitation (MR) offers a number of well-accepted benefits. However, the surgical results of repair for mitral valve endocarditis remain largely unknown. Material and Method: Fourteen patients who underwent mitral valve repair for MR caused by mitral valve endocarditis from April 1995 through October 2001 were reviewed retrospectively. There were 9 male patients and mean age was 32$\pm$10 years. Four patients had previous embolism and 2 had active infections. The grade of MR were III in 6 patients and IV in 8. Operatively, mitral annuloplasty was performed in 12 patients and various valvuloplasty techniques were applied in all patients. One patient had immediate valve replacement due to residual MR after weaning of cardiopulmonary bypass. Result: There was no early operative death. Early postoperative transthoracic echocardiography revealed no or grade I of MR and no or mild mitral stenosis in 13 patients. After the mean follow-up of 36 months, there was no late death, and no or grade I of MR in 11 patients (84.6%) and no or mild mitral stenosis in 12 patients (92.3%). Reoperation required in one patient (7.1%). The cumulative freedom from recurrent MR and valve-related reoperation at 5 years were 91$\pm$9% and 75$\pm$22%, respectively. Conclusion: This study suggests that mitral valve repair for mitral regurgitation caused by endocarditis offers good early and intermediate survival and functional improvement without reinfection, and it is an attractive alternative to valve replacement in selective patients with bacterial endocariditis.

Clinical Significance of Segmental Parenchymal Excretion Delay on Tc-99m DISIDA Hepatobiliary Scan (Tc-99m DISIDA 간담도 신티그라피에서 간 실질의 분절형 배설지연의 임상적 의의)

  • Kang, Do-Young;Ryu, Jin-Sook;Moon, Dae-Hyuk;Lee, Sung-Koo;Kim, Myung-Hwan;Lee, Hee-Kyung
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.2
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    • pp.161-167
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    • 1998
  • Purpose: Segmental parenchymal excretion delay on Tc-99m DISIDA scan is caused by intrahepatic bile duct obstruction. However, the diagnostic value for intrahepatic bile duct obstruction is unknown. We conducted this study to assess the positive predictive value of segmental excretion delay for the diagnosis of intrahepatic bile duct obstruction, and additional benefit over other noninvasive radiologic studies. Materials and Methods: The study population consisted of 43 patients (48 scans) who showed segmental parenchymal excretion delay on Tc-99m DISIDA scan. The results of abdominal CT or ultrasonography, which was done within 1 month of Tc-99m DISIDA scan, were compared with scintigraphic findings. Results: The etiology of segmental parenchymal excretion delay was determined by ERC or PTC in 31 scans, and follow-up studies in 13 scans. No causes were identified in 4 scans. The positive predictive value of segmental parenchymal excretion delay for intrahepatic bile ductobstruction was 92% (44/48). On the other hand, 13% (5/38) of CT and 28% (5/18) of ultrasonography were normal. In 18% (7138) of CT and 17% (3/18) of ultrasonography, only intraheipatic bile duct dilatation was noted without any diagnostic findings of intrahepatic bile duct obstruction. Conclusion: Segmental parenchymal excretion delay on Tc-99m DISIDA scan had a high positive predictive value for the diagnosis of intrahepatic bile duct obstruction. Tc-99m DISIDA scan may be useful for the diagnosis of intrahepatic bile duct obstruction, especially in patients with nondiagnostic CT or ultrasonography. The diagnostic usefulness need to be confirmed by further prospective studies.

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[ $^{99m}Tc-DISIDA$ ] Scintigraphic Diagnosis Of Extrahepatic Hepatocellular Carcinoma Metastasis : Comparison with Primary Hepatocellular Carcinoma ($^{99m}Tc-DISIDA$ 신티그래피를 이용한 간세포암 간외 전이의 진단 : 원발 간세포암과의 비교)

  • Chung, Soo-Kyo;Kim, Sung-Hoon;Baik, Joon-Hyun;Kim, Young-Joo;Chun, Kyung-Ah;Park, Seog-Hee;Bahk, Yong-Whee;Shin, Kyung-Sub
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.4
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    • pp.484-491
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    • 1995
  • It is well known that hepatobiliary agent are taken up by metastatic hepatocellular carcinoma(HCC) as well as primary HCC. But the reported cases of the extrahepatic metastasis of HCC diagnosed by hepatobiliary scintigraphy are for the most part hematogenous ones. The relation of the uptake pattern of hepatobiliary agent in the primary and metastatic HCC is also still remains unknown. So we undertook this study to evaluate the relation of the hepatobiliary scintigraphic patterns of primary and metastatic HCC with different metastatic routes. Nine patients with primary HCC and twelve cases of metastatic HCC including four lung metastases, one bone metastasis, one right atrial metastasis, one peritoneal wall metastasis, and five lymph node metastases were studied with $^{99m}Tc-DISIDA$ scintigraphy. The images were taken on 10, 30 minutes, 1, 2, 4-6 hours. The overall detection rates of hematogenous metastases(lung and bone) is 60%(3 of 5), direct metastasis(right atrium and peritoneal wall), 100%(2 of 2) and lymphatic metastases, 0%(0 of 5). In four of five metastatic cases demonstrated with hepatobiliary scintigraphy, biliary agent is also taken up by primary HCC lesions. And the appearing time of the radioactivity in the direct metastatic HCC lesioin is same as that of primary HCC and in the cases of hematogenous metastasis, earlier than that of primary HCC. Hepatobiliary scintigraphy is more useful in the diagnosis of the metastatic HCC than primary HCC, in the cases of hematogenous and direct metastasis.

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Detection of Spinal Metastases: Comparison of Bone Scan and MR Imaging (전이성 척추 악성 종양의 진단 : 골스캔과 자기공명영상의 비교)

  • Kim, Ki-Jun;Sohn, Hyung-Sun;Park, Jeong-Mi;Chung, Soo-Kyo;Lee, Jae-Moon;Kim, Choon-Yul;Bahk, Yong-Whee;Shinn, Kyung-Sub
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.3
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    • pp.384-390
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    • 1994
  • Authors retrospectively compared the 99mTc MDP bone scans and corresponding MR imagings in 20 patients with histologically proven malignancy, Mean interval of the two studies was 16.6 days, Cancer diagnosis Included 8 lung, 2 each of colon, breast, stomach, 1 each of prostate, thyroid, malignant lymphoma and 3 adenocarcinoma of unknown primary site. Of the 105 regions compared, :t6 regions were positive for metastases in bone scans or MR imagings. 30 regions(65.2%) were positive by bone scan and 44 regions(95.7%) by MR imaging. 87 regions(82.9%) were concordantly positive or negative by bone scan and MR imaging, but 18 regions(17.1%) were discordant. In the discordant regions, 16 regions positive in MR imaging were negative in bone scan. The greatest number of discordant findings occured in the cervical region and in the patient with stomach cancer. Our results suggest that the sensitivity of MR Imaging is greater than that of bone scan in detecting spinal metastases. And bone scan is useful screening test of metastasis for evaluating entire skeleton including spine.

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Clinical Significance of Incidental Asymmetric Palatine Tonsillar Uptake on $^{18}F$-FDG PET/CT ($^{18}F$-FDG PET/CT에서 우연히 관찰되는 구개편도의 비대칭적 섭취증가의 임상적 의의)

  • Chae, Sun-Young;Baek, So-Ra;Ryu, Jin-Sook;Moon, Dae-Hyuk;Kim, Jae-Seung
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.5
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    • pp.402-410
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    • 2009
  • Purpose: The aim of this study was to determine the incidence and malignant rate of incidental asymmetric palatine tonsillar uptake (ATU) on $^{18}F$-FDG PET/CT in various clinical indications and to evaluate the clinical and PET/CT findings suggesting malignancy. Materials and Methods: We retrospectively reviewed a total of 2,901 patients ($58.4{\pm}12.3$ yrs, range 20~88 yrs, M:F = 1,841:1,060) who underwent $^{18}F$-FDG PET/CT during an 1-year period with various indications except primary tonsillar cancer and lymphoma evaluation. On $^{18}F$-FDG PET/CT, metabolic abnormality of the palatine tonsil and cervical lymph node were visually assessed. ATU was defined as increased palatine tonsillar uptake with diffuse, focal, or irregular pattern compared to contralateral side. The incidence and malignant ratio of ATU were evaluated according to clinical and PET/CT findings. Results: Of 2,901 cases, 290(10,0%) showed ATU. The incidence of ATU showed seasonal variation and was high in the winter (12.1%). Of 209 cases with ATU confirmed pathologically and/or clinically, five (2.4%) were malignant lesions. ATU with irregular uptake pattern (2/2) and in cases referred for cervical lymph node metastasis of unknown origin (3/5) were frequently associated with malignant lesion (p<0.05). Conclusion: ATU was not infrequently observed on $^{18}F$-FDG PET/CT, and the malignant risk of ATU was low. However, ATU with cervical lymph node metastasis or with irregular pattern on PET/CT would be further evaluated by the histopathologic examination.

Clinical Features of Non-A, B, C Viral Hepatitis in Children (소아에서 발생한 비-A, B, C형 바이러스성 간염의 임상 고찰)

  • Son, Seung Kook;Park, Jae Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.1
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    • pp.41-48
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    • 2005
  • Purpose: Non-A, B, C viral hepatitis is the name given to the disease with clinical viral hepatitis, but in which serologic evidence of A, B, C hepatitis has not been found. Little is known about the etiology and clinical features of non-A, B, C viral hepatitis in children. Methods: A clinical analysis of 45 cases with non-A, B, C viral hepatitis who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 2001 to June 2004 was carried out retrospectively. Patients who were positive for HBsAg, anti-HAV and anti-HCV and had toxic, metabolic, autoimmune, or neonatal hepatitis were excluded in this study. Results: Among 45 cases of non-A, B, C viral hepatitis, the etiology was unknown in 26 (57.8%), CMV (cytomegalovirus) in 14 (31.1%), EBV (Epstein Barr virus) in 2 (4.4%), HSV (herpes simplex virus) in 2 (4.4%) and RV (rubella virus) in 1 (2.2%). Twenty seven out of 45 (60.0%) patients were under 1 year of age. Sixteen (33.3%) patients had no specific clinical symptoms and were diagnosed incidentally. On physical examination, twenty seven out of 45 patients (60.0%) had no abnormal findings. Forty three out of 45 patients (95.6%) showed classic clinical course of acute viral hepatitis, whereas fulminant hepatitis developed in two patients. Mean serum ALT (alanine aminotransferase) level was $448.7{\pm}771.9IU/L$. Serum ALT level was normalized in 31 out of 45 patients (81.6%) within 6 months and all patients within 18 months. Aplastic anemia was complicated in a case. Conclusion: Although most patients with non-A, B, C viral hepatitis showed a good prognosis, a careful follow-up would be necessary because some of them had a clinical course of chronic hepatitis, fulminant hepatitis and severe complication such as aplastic anemia.

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Is Preventive Bilateral Surgery Needed in Case of Bilateral Bullae on HRCT at Unilateral Primary Spontaneous Pneumothorax (일차성 자연기흉의 고해상 CT에서 보이는 반대편 기포의 예방적 기포절제술이 필요한가?)

  • Han, Jong-Hee;Kang, Min-Woong;Yu, Jeong-Hwan;Kim, Yong-Ho;Na, Myung-Hoon;Lim, Seung-Pyung;Lee, Young;Yu, Jae-Hyeon
    • Journal of Chest Surgery
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    • v.40 no.3 s.272
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    • pp.215-219
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    • 2007
  • Background: Due to the advancement of video assisted thoracoscopic techniques, an operation for primary spontaneous pneumothorax is now considered a common procedure. However, whether a preventive operation is necessary when a contralateral bulla is found on High Resolution Computed Tomography (HRCT) at the time of the first primary spontaneous pneumothorax attack is still unknown. In this retrospective study, it was our intension to find whether contralateral bullae are related to the occurrence of pneumothorax. Material and Method: Between January 1999 and April 2006, 550 patients were admitted to the Chungnam University hospital with primary spontaneous pneumothorax, which was confirmed by the HRCT scans in 190 patents. In these 190 patients, 159 had not received a bilateral operation after their first primary spontaneous pneumothorax attack. In these 159 patients, the relationship between the presence of contralateral bullae and the occurrence of pneumothorax was measured. Result: In these 159 patients, 67 had contralateral bullae confirmed inform the HRCT scan, and 92 had no visible contralateral bullae, During the follow up period, 6 patients (8.9%) with contralateral bullae had an occurrence of contralateral pneumothorax, and 5 patients (5.4%) without contralateral bullae had an occurrence of contralateral pneumothorax. (p=0.529 [Fisher's exact test]) Conclusion: In patients with unilateral primary pneumothorax, an HRCT scan is a useful way of confirming contralateral pulmonary bullae. However, the presence of bullae is not a significant predictive sign of an occurrence of contralateral pneumothorax. Also, surgery for pneumothorax is not completely uncomplicated, and bilateral surgery is still doubtful. A further prospective study will be required to find the relationship between the bullae found on HRCT and the occurrence of pneumothorax.

Alteration of Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1 in Human Mon-small Cell Lung Cancer (비소세포 폐암조직에시 Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1의 발현변화)

  • Yoo, Dae-Goon;Song, Yun-Jeong;Cho, Eun-Jung;Kang, Min-Woong;Han, Jong-Hee;Na, Myung-Hoon;Lim, Seung-Pyung;Yu, Jae-Hyeon;Jeon, Byeong-Hwa;Lee, Young
    • Journal of Chest Surgery
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    • v.40 no.8
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    • pp.529-535
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    • 2007
  • Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.