• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.42-51
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• 2007

Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). Results: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. Conclusion: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.

• Korean Journal of Breeding Science
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• v.41 no.3
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• pp.244-251
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• 2009

This study was carried out to identify useful single gene and gene combination resistant to K1, K2, K3 and 24 bacterial blight(BB) isolates (including K3a, HB01009) breaking down Xa3 gene. Xa3, Xa4, xa5 and Xa7 genes were resistant to K1, K2, K3 of bacterial blight pathogen. Against 24 BB isolates breaking down Xa3 gene, Xa1, Xa2, xa8, Xa10, Xa11, xa13 genes were susceptible, whereas Xa4 gene was moderately resistant and xa5 and Xa21 genes were resistant. IRBB7 having Xa7 gene showed resistance responding to 24 BB isolates, whereas IRBB107 carrying Xa7 gene was susceptible to 10 BB isolates and moderately resistant to 14 BB isolates. Near-isogenic lines (NILs) of Toyonishiki and IR24, both possessing Xa7 gene, showed different resistance response against 24 BB isolates according to genetic background. Xa3+xa5, Xa4+xa5, Xa4+xa13, Xa4+Xa21, xa5+xa13, xa5+Xa21, xa13+Xa21, Xa4+xa5+xa13, Xa4+xa5+Xa21, Xa4+xa13+Xa21, xa5+xa13+Xa21, and Xa4+xa5+xa13+Xa21 were resistant to K1, K2, K3 and 24 isolates breaking down Xa3 gene. When Xa3 and xa13 genes were combined with xa5, Xa4, Xa21, resistance response was enhanced compared with single gene lines containg only Xa3 or xa13. Similarly, when Xa4 gene was combined with xa5 and Xa21, resistance response was improved by the gene combination effect.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.822-835
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• 1997

Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.180-190
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• 2000

Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

• Korean Journal of Breeding Science
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• v.51 no.3
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• pp.263-276
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• 2019

'Sinjinbaek' is a bacterial blight (BB)-resistant, mid-late maturing rice cultivar with high grain quality. To diversify the resistance genes and enhance the resistance of Korean rice cultivars against BB, 'Sinjinbaek' was developed from a cross between 'Iksan493' (cultivar name 'Jinbaek') and the F₁ cross between 'Hopum' and 'HR24670-9-2-1' ('HR24670'). 'Jinbaek' is a BB-resistant cultivar with two BB resistance genes, Xa3 and xa5. 'Hopum' is a high grain quality cultivar with the Xa3 resistance gene. 'HR24670' is a near-isogenic line that carries the Xa21 gene, a resistance gene inherited from a wild rice species O. longistaminata, in the genetic background of japonica elite rice line 'Suweon345'. 'Sinjinbaek' was selected through the pedigree method, yield trials, and local adaptability tests. Using bioassay for BB races and DNA markers for resistance genes, three resistance genes, Xa3, xa5, and Xa21, were pyramided in the 'Sinjinbaek' cultivar. 'Sinjinbaek' exhibited high-level and broad-spectrum resistance against BB, including the K3a race, the most virulent race in Korea. 'Sinjinbaek' is a mid-late maturing rice cultivar tolerant to lodging. It has multiple disease resistance against BB, rice blast, and stripe virus. The yield of 'Sinjinbaek' was similar to that of 'Nampyeong'. 'Sinjinbaek' showed excellent grain appearance, good taste of cooked rice, and enhanced milling performance, and we concluded that it could contribute to improving the quality of BB-resistant cultivars. 'Sinjinbaek' was successfully introgressed with the Xa21 gene without the linkage drag negatively affecting its agronomic characteristics. 'Sinjinbaek' improved the resistance of Korean rice cultivars against BB by introgression of a new resistance gene, Xa21, as well as by pyramiding three resistance genes, Xa3, xa5, and Xa21. 'Sinjinbaek' would be suitable for the cultivation in BB-prone areas since it has been used in breeding programs for enhancing plants' resistance to BB (Registration No. 7273).

• Journal of Preventive Medicine and Public Health
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• v.7 no.1
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• pp.1-28
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• 1974

The writers have conducted the investigation to assess the nutritional status of young rural Korean children aged from 0 to 4 years old in August 1971. The survey areas were Kaejong-myon. Daeya-myon, Okku-gun, Jeonra-bukdo, Korea. These survey areas were typical agricultural plain areas. The total numbers of children examined were 2,706 comprising 1,394 male and 1,312 female. The weight, height, and chest circumference of children were measured and means and standard deviations. were calculated for each measurement. In addition, the nutritional status of each child was classified by the four levels of malnutrition and the Gomez classification, The examination of red blood cell count, haematocrit value, and intestinal parasite infection were carried out at the same time. In general, recent work tend to suggest that environmental influences, especially nutrition, are of great importance than genetic background or other biological factors for physical growth and development. Certainly the physical dimensions of the body are much influenced by nutrition, particularly in the rapidly growing period of early childhood. Selected body measurements can therefore give valuable information concerning protein-calory malnutrition. Growth can also be affected by bacterial, viral, and parasitic infection. For the field workers in a developing country, therefore, nutritional anthropometry appears to be of greatest value in the assessment of growth failure and undernutrition, principally from lack of protein and calories. In order to compare and evaluate the data obtained, the optimal data of growth from the off-spring of the true well-fed, medically and socially protected are needed. So-called 'Standards' that have been compiled for preschool children in Korea, however, are based on measurement of children from middle or lower socio-economic groups, who are, in fact, usually undernourished from six months of age onwards and continuously exposed to a succession of infective and parasitic diseases. So that, the Harvard Standards which is one of the international reference standards was used as the reference standards in this study. Findings of the survey were as follows: A. Anthropometric data: 1) Comparing the mean values for body weight obtained with the Korean standard weight of the same age, the rural Korean children were slightly haevier than the Korean standard values in both sexes. Comparing with the Japanese children values, the rural Korean children were slightly haevier in male and in the infant period of female but lighter in female of the period of 1 to 4 years old than Japanese children. 2) Comparing the mean values for height obtained with the Korean standard height of the same age, the rural Korean children were taller than the Korean standard values except the second half of infatn period in both sexes. Comparing with the Japanese children, the rural Korean children were slightly smaller than Japanese children except the first half of infant peroid in both sexes. 3) Mear values of chest circumference of rural Korean children obtained were less than the Korean standard values of the same ages in both sexes. B. Prevalence of Protein-Calory Malnutrition: Children examined were devided into two groups, i. e., infant(up to the first birthday) and toddler (1 to 4 fears old). 1) Percentages of four levels of malnutrition: a) When the nutrtional status of each child was classified (1) by body weight value, the percentages for male and female of children attained standard growth were 52.8%(infant 83.3%, toddler 44.4%) and 39.7% (infant 74.5%. toddler 30.5%), the first level of malnutrition were 31.9%(infant 13.7%, toddler 36.9%) and 31.7%(infant 15.3%, toddler 36,0%), the second level of malnutrition were 12.3%(infant 1.7%, toddler 15.3%) and 23.3% (infant 7.7%, fodder 27.5%), the third level of malnutrition were 2.7%(infant 0.7%, toddler 3.2%) and 4.6%(infant 1.8%, toddler 5.3%) the fourth level of malnutrition were 0.3% (infant 0.7%, toddler 0.2%) and 0.7% (0.7% for infant and toddler) respectively. (2) by height value, the percentages for male and female of children attained standard growth were 80.3% (infant 97.3%, toddler 75.6%) and 75.1% (infant 96.4%, toddler 69.5), the first level of malnutrition were 17.9% (infant 2.0%, toddler 22.3%) and 23.6% (infants 3.6%, toddler 28.8%), the second level of malnutrition were 1.2% (infant 0.3%, toddler 1.5%) and 1.1% (infant 0%, toddler 1.4%), the third level of malnutrition were 0.4%(infant 0.3%, toddler 0.5%) and 0.2%(infant 0%, toddler 0.3%), the fourth level of malnutrition were 0.1%(infant 0%, toddler 0.1%) and 0% respectively. (3) by body weight in relation to height, the percentages for male and female of children attained standard growth were 87.9% (infant 77.6%, toddler 87.9%) and 78.2% (infant 77.4%, toddler 78.2%), the first level of malnutrition were 12.2% (infant 18.4%, toddler 10.6%) and 18.2% (infant 17.9%, toddler 18.3%), the second level of malnutrition were 1.9%(infant 3.3%, toddler 1.5%) and 3.0%(infant 3.3%, toddler 2.9%), the third level of malnutrition were 0.1%(infant 0%. toddler 0.1%) and 0.5% (infant 0%, toddler 0.6%), the fourth level of malnutrition were 0.1%(infant 0.7%, toddler 0%) and 0.3% (infant 1.5%, toddler 0%) respectively. b) When the nutritional status of each child according to the mother's age at perturition, i. e., young aged mother (up to 30 years old), middle aged mother (31 to 40 years old) and old aged mother (41 years or above) was classified (1) by body weight, among infants and toddlers, at each year of age, with increasing the mother's age, there was an increase in percentage of subjects underweight. This tendency of increasing percentage of underweight was more significant in the infant period than the toddler period. (2) by height value, no significant differences between each mother's age group were found. c) When the nutritional status of each child according to the birth rank, i. e., lower birth rank (first to third) and higher birth rank (fourth or above) was classified (1) by weight value, children of higher birth rank were slightly more often underweight than those of lower birth rank, but not significant. (2) by height value, no differences were found between children of lower and higher birth rank. 2) Gomez Classification: When the nutritional status of each child was classified a) by body weight value, the percentages for male and female of children. attained standard growth were 53.1% (infant 82.6%, toddler 44.9%) and 39.2% (infant 73.4%, toddler 30.1%), the first degree of malnutrition were 39.4% (infant 14.7%, toddler 46.2%) and 47.1% (infant 21.9%, toddler 53.8%), the second degree of malnutrition were 7.3%(infant 2.3%, toddler 8.6%) and 12.9% (infant 4.0%, toddler 15.2%). and the third degree of malnutrition were 0.2%. (infant 0.3%, toddler 0.2%) and 0.8% (infant 0.7%, toddler 0.9%) respectively. b) by height value, the percentages for male and female of children attained standard growth were 80.8% (infant 97.0%, toddler 76.3%) and 73.8%(infant 95.6%, toddler 68.0%), the first degree of malnutrition were 18.5% (infant 2.7%, toddler 22.9%) and 24.6% (infant 4.4%, toddler 30.0%), the second degree of malnutrition were 0.6%(infant 0.3%, toddler 0.7%) and 0.5% (infant 0.1%, toddler 0.7%), and the third degree of malnutrition were 0.1%(infant 0%, toddler 0.1%) and 1.1% (infant 0%, toddler 1.3%) respectively. C. Results of clinical laboratory examination: 1) Red blood cells: The ranges of mean red blood cell counts for male and female were $3,538,000/mm^3\;to\;4,403,000/mm^3\;and\;3,576,000/mm^3\;to\;4,483,000/mm^3$ respectively. The lowest red cell counts were seen at the age of 0-3 months for male and 1-2 months for female. 2) Haematocrit value : The ranges of haematocrit value of male and female were 35.1% to 38.8% and 34.7% to 38.8% respectively. The lowest haematocrit values were seen at the age of 2-3 months for male and 1-2, months for female. 3) The prevalence rates of intestinal parasites for male and female children with Ascaris lumbricoides were 34.1% (infant 18.8%, toddler 38.1%) and 36.0%(infant 18.4%, toddler 40.7%), with Trichocephalus trichiuris were 6.8% (infant 2.9%, toddler 7.9%) and 9.0% (infant 3.0%, toddler 10.6%), with Hookworm were 0.3% (infant 0.5%, toddler 0.2%) and 0.3% (infant 0.5%, toddler 0.3%), with Clonorchis sinensis were 0.4%(infant 0%, toddler 0.5%) and 0.1%(infant 0%, toddler 0.1%) respectively.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.534-546
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• 1997

Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.