• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.497-509
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• 2002

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.

• Journal of Hospice and Palliative Care
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• v.9 no.2
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• pp.67-76
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• 2006

Purpose: The purpose of this study was to develop education program for physicians who work at hospice palliative care settings in Korea, to practice abridged education program extracted from the full contents of the proposed education, and to improve the quality of hospice palliative care service. Methods: To develop the education program, questionnaire for hospice education need assessment (total 79 items) was distributed to 125 organizations practicing hospice service via mail and the data was collected from 1 Sep. to 10 Oct. 2004. Another questionnaire for hospice education importance assessment was asked to the palliative specialists from Sep. 23 to 17 Oct. 2004. Based on the analysis of the questionnaires, and reviewing various references and actual hospice palliative education programs of other countries, the education programs were developed. Results: Ore-day-Hospice education 2004 was conducted based on the suggested education program, and it was practiced four times on a national basis (2 times in Seoul, and once in Busan and Gwangju, respectively). 47 physicians attended the education program. The education program lasted about 7 hours, comprising 5 hours of common lectures for all attendants regardless of their professions and 2 hours of specific seminar for physicians only. Attendants positively responded to the contents of the education program. But they pointed out that the program should be offered on weekday and it should be more in-depth and more discussion based lesson. Conclusion: The suggested education program was not fully conducted yet. After practicing the abridged education program, more in-depth and discussion oriented rather than lecture-based education were suggested. It may be argued that the proposed education, which requires much longer period education, should also reflect the evaluation of the 1-day education program to successfully implement the proposed education program.

• Journal of Preventive Medicine and Public Health
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• v.32 no.4
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• pp.452-458
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• 1999

Objectives: The authors conducted the study to evaluate bias when potentially diseased subjects were included in cohort members while analyzing risk factors of chronic liver diseases. Methods: Total of 14,529 subjects were followed up for the incidence of liver diseases from January 1993 to June 1997. We have used databases of insurance company with medical records, cancer registry, and death certificate data to identify 102 incident cases. The cohort members were classified into potentially diseased group(n=2,217) when they were HBsAg positive, serum GPT levels higher than 40 units, or had or has liver diseases in baseline surveys. Cox's model were used for potentially diseased group, other members, and total subjects, respectively. Results: The risk factors profiles were similar for total and potentially diseased subjects: HBsAg positivity, history of acute liver disease, and recent quittance of smoking or drinking increased the risk. while intake of pork and coffee decreased it. For the potentially diseased, obesity showed marginally significant protective effect. Analysis of subjects excluding the potentially diseased showed distinct profiles: obesity increased the risk, while quitting smoking or drinking had no association. For these intake of raw liver or processed fish or soybean paste stew increased risk; HBsAg positivity, higher levels of liver enzymes and history of acute liver diseases increased the risk. Conclusions: The results suggested the potential bias in risk ratio estimates when potentially diseased subjects were included in cohort study on chronic liver diseases, especially for lifestyles possibly modified after disease onset. The analytic strategy excluding potentially diseased subjects was considered appropriate for identifying risk factors for chronic liver diseases.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1102-1111
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• 2008

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and $30{\mu}g/mL$) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.

• Journal of radiological science and technology
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• v.34 no.3
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• pp.239-244
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• 2011

In this study, we evaluated diffusion weighted imaging (DWI) to investigate whether the DWI parameters can predict characteristic parameters on pathologic specimens of tumor or not. CFPAC-1 was injected subcutaneously on the back flank of athymic nude mice (n=13) then two tumors were initiated on each mouse (2${\times}$13=26 tumors). The mice were sacrificed to make specimen immediately after initial MR imaging then were compared with the MR image. A dedicated high-field (7T) small-animal MR scanner was used for image acquisitions. A T1 and T2 weighted axial image using RARE technique was acquired to measure the T2 values and tumor size. DWI MR was performed for calculating ADC values. To evaluate tumor cellularity and determine the levels of MVD, tumor cells were excised and processed for H-E staining and immunostaining using CD31. T2 values and ADC values were computed and analyzed for each half of the tumors and compared to the correlated specimens slide. Median ADC within each half of mass was compared to the cellularity and MVD in the correlated area of pathologic slide. The mean of ADC value is $0.7327{\times}10^{-3}$ $mm^2/s$ and standard deviation is $0.1075{\times}10^{-3}$ $mm^2/s$. There is a linear relationship between ADC value and tumor necrosis (R2=0.697, p< 0.001). DW image parameters including the ADC values can be utilized as surrogate markers to assess intratumoral neoangiogenesis and change of the internal structure of tumor cells.

• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.50-60
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• 1998

I-123 labelled fatty acids are suitable for investigation of regional myocardial metabolism, so they are on the clinical trial. However, the precise properties of these materials are not characterized yet. We have synthesized phenylpentadecanoic acid and labeled this compound with I-123. The purpose of this study was to examine the stability, biodistribution, metabolism and SPECT imaging of [I-123]15-(p-iodophenyl)pentadecanoic acid(I-123-IPPA) that we made. The stability test of I-123-IPPA in serum of rat, mouse and human showed no free I-123 after 1 hour. In biodistribution study in mice for various time intervals after injection(5, 10, 15, 30, 60 minutes), uptake in myocardium was 14.5%ID/g(5 min), and 1.9%ID/heart(5 min), while uptake in muscles was 2.6%ID/g(5 min). Myocardium to blood ratio and myocardium to lung ratio increased for 5 min after injection and then decreased rapidly. Chromatographic data of rat blood and urine showed that little PPA was found in blood and urine at 15-20 min after injection. The myocardial I-123-IPPA SPECT images of a dog with myocardial infarction showed defects similar to those of Tc-99m-MIBI and F-18-FDG. These data suggest that I-123-IPPA is quite stable in vitro and shows favorable biodistribution in mice. SPECT imaging with I-123-IPPA demonstrated infarct zone as photon defect in dog model of myocardial infarction. I-123-IPPA may be used for the evaluation of fatty acid metabolism in clinical trials in Korea.

• Journal of Nutrition and Health
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• v.42 no.7
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• pp.605-614
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• 2009

Most cancer patients are treated with surgery, chemotherapy or radiation as anticancer therapies. Especially in the case of radiation, these treatments produce adverse effects such as vomiting, weight loss, anorexia, normal cell damage and malabsorption. The major goal of this study was to determine the effect of irradiation on the nutritional and immune status in irradiated rats. A secondary goal was to determine the effectiveness of high protein diet (HP) and resveratrol (Res) in minimizing the adverse effects of radiation. Rats were divided into four groups: normal diet (NP), HP, NP + Res and HP + Res groups. Each group was further divided into subgroups that received radiation (RT group) and one that did not (non-RT group). Each diet was supplied from $12^{th}$ day prior to irradiation treatment with irradiation dose of 17.5 Gy. The diets were continued until 10th day after radiation treatment and animals were sacrificed. The radiation treatment showed decreased body weight, serum protein and HDL levels and increased TG and LDL levels in nutritional status. HP, NP + Res and HP + Res groups reduced the level of serum LDL and TG in irradiated rats. NP + Res and HP + Res groups increased reduced albumin level of serum in RT group. In case of immune status, the radiation treat-ment showed decreased WBC, lymphocytes and increased neutrophil and eosinophil levels. The levels of serum IL-2 and IL-6 were significantly increased by radiation, however the cytokine levels decreased in all dietary treatment groups. These results showed that high protein diet and resveratrol supplementation seem to minimize the adverse effects of radiation on lipid nutritional status and inflammation response in the rat model.

• Journal of Life Science
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• v.19 no.6
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• pp.770-780
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• 2009

A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

• Journal of Life Science
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• v.19 no.6
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• pp.735-743
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• 2009

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.187-194
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• 1999

Purpose : The aim of this study is to look for the possible efficacy of external irradiation for locally advanced papillary thyroid cancers (stage pT4 or Nl ). Methods and Materials : From August 1981 through September 1997, 91 Patients with locally advanced papillary thyroid cancers (stage pT4 or Nl ) have been treated with external irradiation and followed up at our clinic. All of the patients have been treated with surgical resection. After surgery, 23 patients received postoperative external irradiation with or without ablative radioiodine therapy, whereas the other 68 patients were treated with ablative radioiodine therapy alone. Distributions of sex, age, and stage were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence by age, sex, stage, ablative radioiodine therapy and external irradiation on local control were peformed by using Cox's proportional hazard model. Results : Overall survival rates at 7 years were of no significant difference in both groups. There were $98.1\%$ for no RT group and $90\%$ for RT group (p=0.506). 5-year local control rates were significantly different, these were $95.2\%$ for RT group and $67.5\%$ for no RT group (p=0.0408). An analysis of the prognostic factors, age, sex, stage, and RAI were not significant variables, except for the external irradiation. Conclusion : Adjuvant postoperative external irradiation did not affect overall survival, but significantly improved local control in the patients with locally advanced papillary thyroid cancers (stage pT4 or lympy node involvement).