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The Role of Heme Oxygenase-1 in Lung Cancer Cells (폐암세포주에서 Heme Oxygenase-1의 역할)

  • Jung, Jong-Hoon;Kim, Hak-Ryul;Kim, Eun-Jung;Hwang, Ki-Eun;Kim, So-Young;Park, Jung-Hyun;Kim, Hwi-Jung;Yang, Sei-Hoon;Jeong, Eun-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.3
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    • pp.304-313
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    • 2006
  • Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.

The Effects of air-borne particulate matters on the Alveolar Macrophages for the iNOS Expression and Nitric Oxide with Nitrotyrosilated-proteins Formation (미세분진이 흰쥐의 폐포대식세포에서 Nitric Oxide 생성 및 iNOS 발현과 Nitrotyrosilated-protein의 형성에 미치는 효과)

  • Cui, Feng Ji;Li, Tian-Zhu;Lee, Soo-Jin;Park, Se-Jong;Lim, Young;Kim, Kyung-A;Chang, Byung-Joon;Lee, Jong-Hwan;Lee, Myoung-Heon;Choe, Nong-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.426-436
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    • 2006
  • Background : Particulate matters (PM) when inhaled is known to induce pulmonary diseases including asthma and chronic bronchitis when inhaled. Despite the epidemiological proofevidence, the pathogenesis of PM-related pulmonary diseases is unclearremain poorly understood. Methods : Primary alveolar macrophages were harvested from the SPF and inflammatory rats by bronchioalveolar lavage (BAL). The cultured primary alveolar macrophages were treated with the medium only, PM only ($5{\sim}40{\mu}g/cm^2$), LPS (5ng/ml) only, and PM with LPS for 24 and 48 hours. The level of secreted nitric oxide (NO) was assayed from the cultured medium by using the Griess reaction. The cultured cells were utilized for the western blotting against the inducible nitric oxide synthase (iNOS) proteins. Immunocyto- chemical staining against the iNOS and NT-proteins were performed in cells that cultured in the $Lab-Tek^{(R)}$ chamber slide after treatments. Results : The PM that utilizein this experiments induced NO formation with iNOS expression in the cultured SPF and inflammatory rats alveolar macrophages, by itself. When the cells were co-treated with PM and LPS, there was a statistically significant synergistic effect on NO formation and iNOS expression over the LPS effect. The cells from the sham control showed minimal immunoreactivity for the NT-proteins. Significantly higher quantities of NT-proteins were detected in the PM and PM with LPS co-treated cells than from the sham control. Conclusion : Increased iNOS expression and NO formation with increased NT-proteins formation might be involved in the pathogenesis of PM-induced lung injury.

Efficacy of Low-dose Hydrocortisone Infusion for Patients with Severe Community-acquired Pneumonia Who Invasive Mechanical Ventilation (기계 환기가 요구된 중증 지역사회 획득 폐렴에서 저용량 하이드로코르티손 주입의 효과)

  • Kim, Ho Cheol;Lee, Seung Jun;Ham, Hyoun Seok;Cho, Yu Ji;Jeong, Yi Yeong;Lee, Jong Deok;Hwang, Young Sil
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.419-425
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    • 2006
  • Background : Severe community-acquired pneumonia (CAP) can develop into respiratory failure that requires mechanical ventilation (MV), which is associated with a higher rate of mortality. It was recently reported that a hydrocortisone infusion in severe CAP patients was associated with a significant reduction in the length of the hospital stay and mortality. This study evaluated efficacy of a hydrocortisone infusion for patients with severe CAP requiring MV. Methods : From February 2005 to July 2005, 13 patients (M : F = 10 : 3, mean age: $68.6{\pm}14.1years$), who were diagnosed with severe CAP and required MV, were enrolled in this study. Hydrocortisone was administered as an intravenous 200mg loading bolus, which was followed by an infusion at a rate of 10mg/hour for 7 days. The control group was comprised of patients with severe CAP requiring MV but in whom corticosteroid was not used before study period. The clinical and physiologic parameters on or by day 8 and the outcome in the hydrocortisone infusion group were compared with those in the control group. Results : 1) There was no significant difference in age, gender ratio, SAPS II, SOFA score, temperature, leukocyte count, PaO2/FiO2 (P/F) ratio, the number of patients with P/F ratio < 200, chest radiograph score, lung injury score and catecholamine-dependent septic shock between the hydrocortisone infusion group and control group at day 1. 2) At day 8, the proportion of patients with an improvement in the P/F ratio ${\geq}100$ and the chest radiograph score was significantly higher in the hydrocortisone infusion group than in the control group (61.5% vs. 15.4%, 76.9% vs. 23.1%, p< 0.05). However, there was no significant difference in the other clinical and physiologic parameters. 3). There was no significant difference in the duration of the MV, ICU stay, hospital stay and 10th and 30th day mortality between the two groups. Conclusion : Hydrocortisone infusion for patients with severe CAP requiring invasive mechanical ventilation may be effective in improving the level of oxygenation and the chest radiograph score.

The Role and Significance of Biomarker for Plasma G-CSF in Patients with Primary Lung Cancer (원발성 폐암에서 혈장 과립구 자극인자의 암표지자로서의 역할과 의의)

  • Song, Jung Sub;Kim, So Young;Jo, Hyang Jeong;Lee, Kang Kyoo;Shin, Jeong Hyun;Shin, Seong Nam;Kim, Dong;Park, Seong Hoon;Lee, Young Jin;Ko, Chang Bo;Lee, Mi Kung;Choi, Soon Ho;Jeong, Jong Hoon;Park, Jung Hyun;Kim, Hui Jung;Kim, Hak Ryul;Jeong, Eun Taik;Yang, Sei Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.6
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    • pp.444-450
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    • 2009
  • Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

Soluble Triggering Receptor Expressed on Myeloid cells-1: Role in the Diagnosis of Pleural Effusions (흉수의 감별 진단 시 Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)의 유용성)

  • Kim, Jung-Hyun;Park, Eun-Young;Kim, Won-Hee;Park, Woong;Jeong, Hye-Cheol;Lee, Ji-Hyun;Kim, Eun-Kyung
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.4
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    • pp.290-298
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    • 2007
  • Background: The currently available diagnostic markers for pleural effusion have a limited role. The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a molecule recently reported to play an important role in the myeloid cell mediated inflammatory response, and is up regulated in the body fluid by bacterial or fungal products. This study examined the expression of sTREM-1 in pleural effusion. Methods: Between April 2004 and December 2005, 48 patients with pleural effusions were enrolled in this study. The pleural fluids were taken and analyzed for the total protein, glucose, lactate dehydrogenase (LDH), adenosine deaminase (ADA), and sTREM-1. Bacterial cultures and cytology tests were also performed. Results: The clinical diagnoses were 17 parapneumonic, 14 tuberculous, and 13 malignant effusions. Four patients presented with transudates. The mean ages of the parapneumonic, tuberculous and malignant effusion groups were $57.1{\pm}19.7$, $49.5{\pm}18.6$, $66.9{\pm}15.5$, and $76.0{\pm}18.1$. respectively. The level of sTREM-1 expression was significantly higher in the parapneumonic effusions ($344.0{\pm}488.7$) than in the tuberculous effusions ($81.7{\pm}56.6$) and malignant effusions ($39.3{\pm}19.6$). With a cut-off value of 55.4pg/ml, the sensitivity and specificity for a parapneumonic effusion was 70.6% and 74.1%. Conclusion: sTREM-1 expression is significantly higher in parapneumonic effusions, suggesting its potential role as an additional diagnostic marker for pleural effusions.

The Evaluation of Image Correction Methods for SPECT/CT in Various Radioisotopes with Different Energy Levels (SPECT/CT에서 서로 다른 에너지의 방사성동위원소 사용시 영상보정기법의 유용성 평가)

  • Shin, Byung Ho;Kim, Seung Jeong;Yun, Seok Hwan;Kim, Tae Yeop;Lim, Jung Jin;Woo, Jae Ryong;Oh, So Won;Kim, Yu Kyeong
    • The Korean Journal of Nuclear Medicine Technology
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    • v.17 no.2
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    • pp.53-58
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    • 2013
  • Purpose: To optimize correction method for SPECT/CT, image quality consisting of resolution and contrast was evaluated using three radioisotopes ($^{99m}Tc$, $^{201}Tl$ and $^{131}I$) and three different correction methods; attenuation correction (AC), scatter correction (SC) and both attenuation and scatter correction (ACSC). Materials and Methods: Images were acquired with a SPECT/CT scanner and a conventional CT protocol with an OESM reconstruction algorithm (2 iterations and 10 subsets). For resolution measurement, fixed radioactivity (2.22 kBq) was infused into a spatial resolution phantom and full width at half maximum (FWHM) was measured using a vendor-provided software. For contrast evaluation, radioactive source with a ratio of 1:8 to background was filled in a Flanged Jaszczak phantom and percent contrast (%) were calculated. All the parameters for image quality were compared with non-correction (NC) method. Results: As compared with NC, image resolution of all three isotopes were significantly improved by AC and ACSC, not by SC. In particular, ACSC showed better resolution than AC alone for $^{99m}Tc$ and $^{201}Tl$. Image contrast of all three radioisotopes in a sphere with the largest diameter were enhanced by all correction methods. ACSC showed the highest contrast in all three radioisotopes, which was the most accurate in $^{99m}Tc$ (85.9%). Conclusion: Image quality of SPECT/CT was improved in all the radioisotopes by CT-based attenuation correction methods, except SC alone. SC failed to improve resolution in any radioisotopes, but it was effective in contrast enhancement. ACSC would be the best correction method as it improved resolution in radioisotopes with low energy levels and contrast in radioisotope with low energy levels. However, in radioisotope with high energy level, AC would be better than ACSC for resolution improvement.

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Treatment and Follow-up of Human Papillomavirus Infected Women in a Municipality in Southern Brazil

  • Ruggeri, Joao Batista;Agnolo, Catia Millene Dell;Gravena, Angela Andreia Franca;Demitto, Marcela de Oliveira;Lopes, Tiara Cristina Romeiro;Delatorre, Silvana;Carvalho, Maria Dalva de Barros;Consolaro, Marcia Edilaine Lopes;Pelloso, Sandra Marisa
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6521-6526
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    • 2015
  • Background: This study aimed toanalyze the risk behavior for cervical cancer (CC) and the human papillomavirus (HPV) prevalence and resolution among women who received care through the private healthcare network of a municipality in southern Brazil. Materials and Methods: This descriptive and retrospective study was conducted with 25 women aged 20 to 59 years who received care through the private healthcare network and were treated at a specialty clinic in the period from January to December 2012 in a municipality in Northwest Parana, Southern Brazil. Data from medical records with cytological and HPV results were used. Following treatment, these women were followed-up and reassessed after 6 months. Data were statistically analyzed using the t-test and chi-squared test at a 5% significance level. Results: The mean age of the studied women was $27.8{\pm}7.75$ years old, and the majority were married, with paid employment and were non-smokers. The mean age at menarche was $13.0{\pm}0.50$ years old, and the mean age at first intercourse was $17.5{\pm}1.78$ years, with only 8.0% (2) initiating sexual activity at an age ${\leq}15$ years old. The majority had 1 to 2 children (60.0%), while 88.0% reported having had one sexual partner in their lifetime, and all the women were sexually active. A total of 68.0% used a hormonal contraceptive method. All the women had leukorrhea and pain and were infected by a single HPV type. Regarding the lesion grade, 80.0% showed high risk and 20.0% low risk. The most prevalent high-risk HPV strain was 16. Conclusions: These findings provide relevant information on HPV risk factors and infection, as well as the treatment and 6-month follow-up results, in economically and socially advantaged women with no traditional risk factors, corroborating previous reports that different risk factors may be described in different populations. Thus, this study reinforces the fact that even women without the traditional risk factors should undergo HPVmonitoring and assessment to determine the persistence of infection, promoting early diagnosis of the lesions presented and appropriate treatment to thus prevent the occurrence of CC.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

  • Zhang, Yu-Rong;Xu, Yong;Yang, Kuo;Liu, Ming;Wei, Dong;Zhang, Yao-Guang;Shi, Xiao-Hong;Wang, Jian-Ye;Yang, Fan;Wang, Xin;Liang, Si-Ying;Zhao, Cheng-Xiao;Wang, Fei;Chen, Xin;Sun, Liang;Zhu, Xiao-Quan;Zhu, Ling;Yang, Yi-Ge;Tang, Lei;Jiao, Hai-Yan;Huo, Zheng-Hao;Yang, Ze
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6273-6276
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    • 2012
  • Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

The Health Status of Rural Farming Women (농촌여성(農村女性)의 건강실태(健康實態)에 관한 연구(硏究))

  • Park, Jung-Eun
    • Journal of agricultural medicine and community health
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    • v.15 no.2
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    • pp.97-106
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    • 1990
  • 1. Background Women's health and their involvement in health care are essential to health for everyone. If they are ignorant, malnourished or over-worked, the health &-their families as well as their own health will suffer. Women's health depends on broad considerations beyond medicine. Among other things, it depends upon their work in farming. their subordination to their families, their accepted roles, and poor hygiene with poorly equipped housing and environmental sanitation. 2. Objectives and Contents a. The health status of rural women : physical and mental complaints, experience of pesticides intoxication, Farmer's syndrome, experiences of reproductive health problems. b. participation in and attitudes towards housework and farming c. accessibility of medical care d. status of maternal health : fertility, family planning practice. induced abortion, and maternal care 3. Research method A nationwide field survey, based on stratified random sampling, was conducted during July, 1986. Revised Cornell Medical index(68 out of 195 items). Kawagai's Farmers Syndrome Scale, and self-developed structured questionnaires were used to rural farming wives(n=2.028). aged between 26-55. 4. Characteristics of the respondents mean age : 40.2 marital status : 90.8% married mean no. of household : 4.9 average years of education : 4.7 yrs. average income of household : \235,000 average years of residence in rural area : 36.4 yrs average Working hours(household and farming) : 11 hrs. 23 min 5. Health Status of rural women a. The average number of physical and mental symptoms were 12.4, 4.7, and the rate of complaints were 22.1%, 38.8% each. revealing complaints of mental symptomes higher than physical ones. b. 65.4% of rural women complained of more than 4 symptoms out of 9, indicating farmer's syndrome. 11.9 % experienced pesticide overdue syndrome c. 57.6% of respondents experienced women-specific health problems. d. Age and education of respondents were the variables which affect on the level of their health 6. Utilization of medical services a. The number of symptoms and complaints of respondents were dependent on the distance to where the health-care service is given b. Drug store was the most commonly utilized due to low price and the distance to reach. while nurse practitioners were well utilized when there were nurse practitioner's office in their villages. c. Rural women were internalized their subordination to husbands and children, revealing they are positive(93%) in health-care demand for-them but negative(30%) for themselves d. 33.0% of respondents were habitual drug users, 4.5% were smokers and 32.3% were alcohol drinkers. and 86.3% experienced induced-abortion. But most of them(77.6%) knew that those had negative effects on health. 7. Maternal Health Care a. Practice rate of contraception was 48.1% : female users were 90.9% in permanent and 89.6% in temporary contraception b. Induced abortions were taken mostly at hospital(86.3%), while health centers(4.7%), midwiferies(4.3%). and others(4.5%) including drug stores were listed a few. The repeated numbers of induced abortion seemed affected on the increasing numbers of symptoms and complaints. c. The first pre-natal check-up during first trimester was 41.8%, safe delivery rate was 15.6%, post-natal check-up during two months after delivery. Rural women had no enough rest after delivery revealing average days of rest from home work and farming 8.3 and 17.2. d. 86.6% practised breast feeding, showing younger and more educated mothers depending on artificial milk 8. Recommendations a. To lessen the multiple role over burden housing and sanitary conditions should be improved, and are needed farming machiner es for women and training on the use of them b. Health education should begin at primary school including health behavior and living environment. c. Women should be encouraged to become policy-makers as well as administrators in the field of women specific health affairs. d. Women's health indicators should be developed and women's health surveillance system too.

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Chemical Age Dating of Zircon and Monazite by E1ectron Microprobe (전자현미분석기를 이용한 저어콘 및 모나자이트의 화학적 연대 측정법)

  • 이석훈
    • The Journal of the Petrological Society of Korea
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    • v.10 no.3
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    • pp.179-189
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    • 2001
  • The determination of trace concentration of U, Th and Pb was carried out for chemical dating of zircon and monazite by electron microprobe. Detection limit and error range should be considered to measure characteristic X-rays of M-line from those minerals, which are low in the ionization of atom and low peak intensity in the spectrum. The element of U, Th and Pb were simultaneously measured with 3 spectrometers equipped with PET crystal to reduce a total counting time and error due to drift of instrumental operating condition. Detection limit could be improved from increase of the peak/background ratio through adjusting pulse height analyzer about 1000 mv baseline. Under permissible maximum analytical conditions, theoretical detection limit of U, Th and Pb is down to 30 ppm (99% confidence level). The analytical result was maintained at a relative error $\pm$10% ($2{\sigma}$) in 800 ppm Pb, $\pm$5% ($2{\sigma}$) in 2330 ppm U and $\pm$10% ($2{\sigma}$) in dating from a single measurement of zircon at 15 keV and 100 nA. However, for the precise dating of zircon and monazite, if it is considered a 3 $\mu\textrm{m}$ spatial resolution, <100 ppm ($3{\sigma}$) detection limit and <$\pm$10% ($2{\sigma}$) relative error, optimum analytical conditions are given as 15~20 keV accelerating voltage, 100~200 nA beam current and 300~1200 sec total counting time. To reduce material damage by high current, there is need to be up to 3~5 $\mu\textrm{m}$ of electron beam diameter, or to use arithmetic average of multiple measuring at a shorter counting time. A younger or relatively low concentration rocks can be dated chemically by lower detection limit and improved precision resulted from increase of current and measuring time.

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