Chang, Yoon Soo;Lee, Ho-Young;Kim, Young Sam;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Kim, Se Kyu
Tuberculosis and Respiratory Diseases
/
v.56
no.5
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pp.465-484
/
2004
Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.
Purpose: Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. Materials and Methods: Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. Results: All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, p=0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT Abuser group had lower basal ganglia DAT SBR than that of control ($2.38{\pm}0.20\;vs\;3.04{\pm}0.27$, p=0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, p=0.012, r=-0.924, p=0.009). Conclusion: These results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers.
Tricuspid regurgitation has been considered as a secondary lesion when it is combined with left valvular heart diseases. However, there have been some reports which show that tricuspid regurgitation keeps going and results in congestive heart failure even after a successful operation for left valvular heart disease. So far, there are no definite operation indications and predictive factors for the tricuspid re-gurgitation which is resulted from the left sided valvular heart disease. We designed this study to evaluate the effects of pulmonary artery pressure and left ventricular ejection fraction on the prognosis of tricuspid regurgitation, and to make an operation indication for the patients with secondary tricuspid regurgitation. Material and Method: We reviewed the medical records of patients who underwent surgery for the left sided valvular heart disease with tricuspid regurgitation and were followed for more than 1 year with echocardiograms. There was a total of 114 cases. We compared the grades of tricuspid regurgitations and pulmonary artery pressures and left ventricular ejection fractions on the basis of echocardiograms which were checked preoperatively and on the last follow up. Result: There were 43 cases of tricuspid an-nuloplasty. In these patients, the grades of tricuspid regurgitations were improved in 42 cases (97.7%). But in 71 cases without annuloplasty, 29 cases (41%) were improved, 32 cases (45%) had no change, and 29 cases (14%) were aggravated. This finding shows significant differences in the prognoses of tricuspid regur-gitations between the two groups (p<0.05). There was no difference in pulmonary artery pressures and ejection fractions between the patients who showed progression of tricuspid regurgitations and those who didn't (p > 0.05). The improvements of tricuspid regurgitations are not statistically related to the changes of pulmonary artery pressures or left ventricular ejection fractions. Conclusion: This study shows that it is impossible to predict the prognoses of tricuspid regurgitations with preoperative pulmonary artery pressures or left ventricular ejection fractions. Also, the excellent results of tricuspid annuloplasty is proven in controlling the secondary tricuspid regurgitations. Therefore, when tricuspid regurgitation is detected preoperatively, the procedures to correct the tricuspid regurgitation at the time of the operation for the left-sided valvular heart disease must be considered positively, regardless of the grades of tricuspid regurgitations, to prevent sig-nificant tricuspid regurgitation that may develop later.
Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.
Background: There are various treatment modalities for atherosclerotic arterial obstructive disease at the lower limbs, for example, conservative physical therapy, medication, operation etc. Yet it has been established that an arterial bypass operation is the most effective treatment. The aim of this study is to evaluate the effect of arterial bypass operation within our experience and to determine the indicators of treatment. Material and Method: Ninety six patients received arterial bypass operation for atherosclerotic arterial obstructive disease from June 2002 to April 2006. We evaluated the feasibility of arterial bypass operation based on the improvement of symptoms and the ankle-brachial index (ABI) and the surgical outcomes, as based on the complications, the amputation rates and the patency rates. We also assessed the possible risk factors such as gender, age, a smoking history, co-morbidities, the anastomotic sites, the graft size and the graft type. We retrospectively reviewed the medical records of the patients. The total mean follow-up period was $29.4{\pm}13.1$ months. Result: The mean age was $65.95{\pm}9.61$ and there were 88 male patients. The most common clinical manifestation was ischemic resting pain in the lower extremities. The underlying combined diseases were hypertension (61%), diabetes (43%), cardiac problems (35%) and smoking (91.7%). The most frequent site of arterial obstruction was the superficial femoral artery (44 cases, 40%). A femoropopliteal artery bypass operation with a Polytetrafluoroethylene(PTFE) synthetic graft was done in 44 cases (40%) and the great saphenous vein graft was used in 11 cases. The postoperative ABI increased significantly from $0.30{\pm}0.11$ preoperatively to $0.63{\pm}0.11$ (p<0.001) postoperatively. In 8 cases, amputations above the ankle level were necessary. The graft patency rates were 86.4% and 68.0% after 1 and 3 years, respectively. There were 29 cases (30.21%) of patency failure; the male gender, smokers and hypertension were significantly more frequent in the failure group. Of these, hypertension was the most powerful risk factor (p=0.042). Conclusion: The arterial bypass operation is an effective treatment modality for controlling the symptoms such as pain and claudication, and for preventing major amputations for the patients with atherosclerotic arterial obstructive disease. This study suggests quitting smoking, strict blood pressure control, selection of an appropriate graft, regular outpatient follow up and proper medication would offer higher patency rates and more favorable outcomes.
According to the '2013 Performance Assessment Report on the Financial Program' from the National Assembly Budget Office, the unfilled recruitment ratio of Software(SW) Developers in South Korea was 25% in the 2012 fiscal year. Moreover, the unfilled recruitment ratio of highly-qualified SW developers reaches almost 80%. This phenomenon is intensified in small and medium enterprises consisting of less than 300 employees. Young job-seekers in South Korea are increasingly avoiding becoming a SW developer and even the current SW developers want to change careers, which hinders the national development of IT industries. The Korean government has recently realized the problem and implemented policies to foster young SW developers. Due to this effort, it has become easier to find young SW developers at the beginning-level. However, it is still hard to recruit highly-qualified SW developers for many IT companies. This is because in order to become a SW developing expert, having a long term experiences are important. Thus, improving job continuity intentions of current SW developers is more important than fostering new SW developers. Therefore, this study surveyed the job continuity intentions of SW developers and analyzed the factors associated with them. As a method, we carried out a survey from September 2014 to October 2014, which was targeted on 130 SW developers who were working in IT industries in South Korea. We gathered the demographic information and characteristics of the respondents, work environments of a SW industry, and social positions for SW developers. Afterward, a regression analysis and a decision tree method were performed to analyze the data. These two methods are widely used data mining techniques, which have explanation ability and are mutually complementary. We first performed a linear regression method to find the important factors assaociated with a job continuity intension of SW developers. The result showed that an 'expected age' to work as a SW developer were the most significant factor associated with the job continuity intention. We supposed that the major cause of this phenomenon is the structural problem of IT industries in South Korea, which requires SW developers to change the work field from developing area to management as they are promoted. Also, a 'motivation' to become a SW developer and a 'personality (introverted tendency)' of a SW developer are highly importantly factors associated with the job continuity intention. Next, the decision tree method was performed to extract the characteristics of highly motivated developers and the low motivated ones. We used well-known C4.5 algorithm for decision tree analysis. The results showed that 'motivation', 'personality', and 'expected age' were also important factors influencing the job continuity intentions, which was similar to the results of the regression analysis. In addition to that, the 'ability to learn' new technology was a crucial factor for the decision rules of job continuity. In other words, a person with high ability to learn new technology tends to work as a SW developer for a longer period of time. The decision rule also showed that a 'social position' of SW developers and a 'prospect' of SW industry were minor factors influencing job continuity intensions. On the other hand, 'type of an employment (regular position/ non-regular position)' and 'type of company (ordering company/ service providing company)' did not affect the job continuity intension in both methods. In this research, we demonstrated the job continuity intentions of SW developers, who were actually working at IT companies in South Korea, and we analyzed the factors associated with them. These results can be used for human resource management in many IT companies when recruiting or fostering highly-qualified SW experts. It can also help to build SW developer fostering policy and to solve the problem of unfilled recruitment of SW Developers in South Korea.
Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.
Seo, Ji-Young;Yoon, In-Suk;Shin, Choong-Ho;Yang, Sei-Won
Clinical and Experimental Pediatrics
/
v.49
no.3
/
pp.305-311
/
2006
Purpose : GnRH analogues(GnRHa) are used to treat central precocious puberty(CPP). However, in some patients, the GV decrease is so remarkable that it impairs predicted adult height(PAH); and there fore, the addition of growth hormone(GH) is suggested. We analysed the growth changes during two years and final adult height(FAH) in girls with idiopathic CPP treated with combined therapy, compared with those of girls treated with GnRHa alone. Methods : For the analysis, we classified the patients, who was treated for longer than two years, into three groups depending on the initial PAH and combination of GH; PAH_L, treated with GnRHa and PAH less than midparental height(MPH) - 5 cm. PAH_H, treated with GnRHa and PAH greater than MPH - 5 cm. GnRHa+GH, combined GH treatment, regardless of PAH before treatment. We analysed the GV and PAH change during the first two years and FAH. Results : In PAH_L, the PAH(SDS) at first year of therapy was significantly increased to $153.5{\pm}6.5cm(-1.4{\pm}1.3)$ from $149.7{\pm}6.4cm(-2.1{\pm}1.3)$ before treatment(P=0.004). In PAH_H, there was no significant increase in PAH during the two years of treatment. During the first year of combination of GH and GnRHa, GV and PAH increased significantly. We observed significant increases in FAH, comparing to the initial PAH in the PAH_L and GnRHa+GH groups. The height gains(FAH - initial PAH) were significantly higher in the PAH_L and GnRHa+GH groups than that in the PAH_H group. Conclusion : This study suggests the FAH and height gains are improved in patients, whose predicted adult height before treatment was shorter than those with higher predicted adult height, with the treatment of GnRHa alone or in combination with GH. GH could not improve the final adult height, but compensated the growth in patients whose growth velocity was decelerated by GnRHa alone.
Purpose: Radioiodine (I-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age $50{\pm}11$ years) of papillary thyroid cancer. Among them 43 patients were treated with ${\Leq}7.4GBq$, while 15 patients with ${\geq}9.25GBq$. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up I-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were $13.3{\pm}1.9\;and\;13.8{\pm}2.1GBq$, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were $1.54{\pm}0.03\;and\;1.78{\pm}0.03Gy$ (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-dose group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose I-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.
Purpose: A duplicated ureter is congenital renal malformations with ureter in two. Patients with duplicated ureter are in force to $^{99m}Tc-DMSA$ scan at surgery before and after. In existing examination, at produce result after $^{99m}Tc-DMSA$ scan, didn't compare to upper pole and lower pole with malformed kidney and compared to only relative uptake ratio. Therefore, this study will examine about utility of set a partial region of interest and to functional recovery of renal cell through change of upper pole uptake ratio of malformed kidney by setting each partial region of interest in upper pole and lower pole of malformed kidney in $^{99m}Tc-DMSA$ examination in surgery before and after. Materials and Methods: Pediatric patients with malformed kidney of incomplete duplicated ureter, 15 patients were enrolled in this study. Scanning were scan 3 to 4 hours after injection of $^{99m}Tc-DMSA$ 1.5 ~ 1.9 MBq/kg. Region of interest were each set in normal kidney, upper pole and lower pole with malformed kidney. Region of interest were set with same condition and method to images of surgery before and after that radio technologist 1 person, resident of nuclear medicine 1 person and doctor of urology together. Therefore, this study were compared to uptake ratio (A: B: C) that normal kidney (A), lower pole of malformed kidney (B) and upper pole of malformed kidney (C) about uptake ratio changes of malformed kidney in follow-up examination of surgery before and after. Results: When compared to 15 patients, uptake ratios were increased 7 persons and decreased 8 persons. Among increased 7 persons, it were periods of follow-up examination that 2 persons were 14 months, 4 persons were 12 months and 1 person was 8 months after surgery. Among decreased 8 persons, it were periods of follow-up examination that 4 persons were 12 months 3 persons were 6 months and 1 persons were 4 months after surgery. Conclusion: Existing study could not see the exact uptake ratio changes of malformed kidney because using only the overall Left-Right kidney uptake ratios. But a setting partial region of interest was able to see exactly what changes in the uptake of each upper pole and lower pole of malformed kidney. Because recovery of renal parenchymal cells is difficult in an evaluation of short period of time, follow-up examination should be made in long period of time. How to set up partial region of interest be thought that it would be useful.
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