• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.24-32
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• 2000

Purpose: Microsatellite instability(MSI) is frequently used as an indicator of microsatellite mutator phenotype(MMP) tumors. MSI has been observed in a percentage of non-small cell lung cancer(NSCLC). However, its role in tumorigenesis of NSCLC remains unknown. The frequency and pattern of MSI in NSCLC were evaluated and clinical parameters of MSI-positive tumors with those of MSS(microsatellite stable) tumors were compared. Materials and Methods: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosomes 3p and 9p. The peripheral blood lymphocytes of patients were used as the source of the normal DNA. Results: 1) Of 20 cases, 8(40%) demonstrated MSI. 2) Instability was observed more frequently in tri- and tetra-nucleotide repeats than in dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LDH was observed in 10(50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor(showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors(showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI-negative tumors in terms of clinicopathologic features such as pack-year history of smoking, histologic subtype, and(delete) stage of disease. There was also no significant difference in the incidence of LDH in relation to the status of MSI. Conclusion: These data strongly suggest that MSI plays different roles in lung and colon cancer. MMP pathway appears to be far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1343-1352
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• 1997

Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

• Journal of Nutrition and Health
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• v.9 no.2
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• pp.68-86
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• 1976

The primary purpose of this study is to evaluate the correct nutritional status on pre-school children in Korea. Furthermore, it made an attempt to find and define nutrional problems, and assist in establishment on their nutritional improvement plan. For this, food intake and health condition (physical, clinical, biochemical and parasitological) survey on 109 Pre-school children in both sexes, randomly selected from Yang-Gu area in Gang-Won province and Rea-ju area in Kyong-gy Province, were conducted by means of three-day records, during the two periods of Spring and Fall season in 1975. The results obtained are summerized as follows: 1. The food intake; Average food intake of the subjects per day were $508{\sim}647g$ ($83{\sim}91%$ in vegetable foods and $5.5{\sim}11.7%$ in animal foods) in Yang-gu area, and $587{\sim}698g$ ($88{\sim}89%$ in vegetable foods and $6.3{\sim}7.6%$ in animal foods) in Rea-ju area. 2. The intake of energy and nutrients; a) Calory intake. Average energy intake of subjects per day in Yang-gu area$(1120{\sim}1415kcal)$ were all lower than the Korean Recommended Dietary Allowances (RDA) in either Spring and Fall survey, whereas the subjects in Rea-ju area were lower intake $(1213{\sim}1418kcal)$ than the RDA in the Spring but higher intake$(1516{\sim}1755kcal)$ than the RDA in the Fall, and the average intake were similar level with that of RDA. b) Protein intake. Average protein intake of the subjects per day in Yang-gu area $(33{\sim}43g)$ girl subjects in Rea-ju area $(35{\sim}39g)$ were lower than the RDA in either Spring and Fall survey, whereas the boy subjects in Rea-ju area$(36{\sim}38g)$ were lower in Spring and higher $(49{\sim}57g)$ in the Fall than that of the RDA, but the average $(43{\sim}47g)$ were similar level with the RDA. The protein intake from animal sources in all subjects were much lower $(5.5{\sim}11.7\;of\;total\;protein)$ than the RDA. c) Fat intake. Average fat intake were very lower in all subjects of both area $(14{\sim}24g\;in\;Yang-gu,\;10{\sim}12g\;in\;Rea-ju)$ than that of RDA which is recommended $12{\sim}14%$ of total energy to be supplied from fat. d) Calcium intake. Average calcium intake were very low in all subjects of both area $(264{\sim}355mg\;in\;Yang-gu\;and\;283{\sim}429mg\;in\;Rea-ju)$, especially, these in Spring were about a half level of the RDA, and it was much increased in the Fall due to increased intake of milk, but it was still not enough than the RDA. e) Vitamin A intake. Average intake of V.A ($703{\sim}1465\;IU$ in Ynag-gu and $750{\sim}1521\;IU$ in Rea-ju) were also lower than the RDA, moreover their V-A sources were mainly vegetable, so that the V-A supply might be critical one for the subjected. f) Riboflavin intake. Average riboflavin intake on all subjects in both area except boys in Rea-ju area in Fall, were very lower than the RDA. 3. The physical status; a) Average weight and height of boys aged 4 and 5 in Yang-gu area and girls of aged 5 in Rea-ju area were lower than those of Korean Standard of 1967 report, but those by age of girls in Yang-gu area and boys in Rea-ju area were a little heigher than the Korean Standard. It is, hower, present Korean standard of physical status might be somehow heigher than the 1967, since the socio-economical situation has been much improved during past a decade. So that, if one considered on this sense, the physical status of the subjects on this survey might be somehow lower than those of present Korean standard. b) Average upper arm circumference in both area were no difference each other, and their mean values of age 4, 5 and 6 in boy and girl were 15.6, 16.5, 16.4 and 15.5, 16.5, 16.4cm respectively. c) Average chest girth of boys were similar to those of Korean standard whereas the girls were smaller than the Korea standard. The average head circumference also showed similar tendency with the chest girth. 4. The clinical findings; The most popular clinical signs were angular stomatitis and dental caries, and boys had more heigher incidence then the girls. 5. The biochemical findings; a) Hemoglobin and anemia Average Hb value of boys and girls were 11.4 and 10.9g per 100 ml of blood respectively. The incidence of anemia (Hb value below 11 g/100 ml, by WHO) was increased by age, and girls had more heigher incidence than the boy (34% : 48%). The incidence of anemia in age of 4,5, and 6 in boys and girls were 28%, 41% 34%, and 33%, 50%, 49% respectively. The degree of the anemia was not severe, and the anemia of there subjects may be caused mainly low intake of better quality protein and low iron intake as well. b) Hematocrit. Average Ht value of whole subject were $39.9{\sim}41.6%$. c) Blood plasma protein. Average blood plasma protein contents of whole subjects were $6.6{\sim}7.4gm$ per 100 ml. The incidence of deficient range (<6.0g%, by ICNND) was only one girl of age 4 in yang Gu area. 6. Parasitological findgs; The most popular parasitism were asicris lumbicoides and trichocephalus trichiura, and about 2/3 of the whole subjects were suffering one or more of these parasitism.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.