• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.310-322
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• 2000

Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.323-331
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• 2000

Purpose: Brain metastases are present in approximately 10-16% of small cell lung cancer patients at diagnosis. Brain metastasis is an important clinical problem associated with increasing the survival rate, with a cumulative incidence of up to 80% in patients surviving 2 years. Prophylactic cranial irradiation(PCI) reduces the incidence of brain matastasis and may prolong survival in patients with limited small-cell lung cancer who achieved complete remission. This study was performed to analyze the incidence of brain metastasis, survival and clinical aspects after PCI in patients with limited small-cell lung cancer who achieved complete remission. Methods : Between 1989 and 1999, forty-two patients with limited small-cell lung cancer who achived achieved complete remission after therapy were enrolled into this study retrospectively. All patients received etoposide and cisplatin(VPP) alternating with cytoxan, adriamycin, and vincristine(CAV) every 3 weeks for at least 6 cycles initially. All patients received thoracic radiotherapy: concurrent(38.1%) and sequential(61.9%). All patients received late PCI. Results : Most patients(88.1%) were men, and the median age was 58 years. The median follow-up duration was 18.1 months. During the follow-up period, 57.1% of the patients developed relapse. The most frequent site of relapse was chest(35.7%), followed by brain(14.3%), liver(11.9%), adrenal gland(44%), and bone(2.2%). With the Kaplan-Meier method, the average disease-free interval was 1,090 days(median 305 days). The average time to development of brain relapse after PCI and other sites relapse(except brain) were 2,548 days and 1,395 days(median 460 days), respectively. The average overall survival was 1,233 days(median 634 days, 21.1 months), and 2-year survival rates was 41.7%. The average overall survival in the relapse group was 642 days(median 489 days) and in the no relapse group was 2,622 days(p<0.001). The average overall survival in the brain relapse group was 928 days(median 822 days) and in the no brain relapse group was 1,308 days(median 634 days)(p=0.772). In most patients(85.7%), relapse(except brain) or systemic disease was the usual cause of death. Brain matastasis was the cause of death in 14.3% of the cases. Conclusions : We may conclude that PCI reduces and delays brain metastasis in patients with limited small cell lung cancer who achieved complete remission. We found decreased survival in relapse group but, no significant survival difference was noted according to brain matastasis. And relapse(except brain) or systemic disease was the usual cause of death. In order to increase survival, new treatment strategies for control methods for relapse and systemic disease are required.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.557-566
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• 2004

Background : To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC Methods : From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results : Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41%. In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion : Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.241-250
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• 1997

Objective : Although the prevalence of pulmonary tuberculosis has decreased progressively after the national control program for tuberculosis began, nowadays the number of MDRTB is increasing seriously. MDRTB tends to be poor responsive to current antituberculosis regimens. It is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. The purpose of present study is to evaluate the clinical features of pulmonary tuberculosis patients admitted in one national tuberculosis hospital and to expose the problems pertaining to current remedies, to increase the treatment efficacy for pulmonary tuberculosis including MDRTB in the end. Method : Retrospective analysis of 336 pulmonary tuberculosis patients admitted in National Masan Tuberculosis Hospital was done. Contents of analysis were patients profile, the first diagnosed time and medical institutes, family history, residence, previous treatment history, chief complaints at the time of admission, lesion site on chest X -ray film, combined deseases, side reaction to antibuberculosis drugs, used drugs before admission and the results of drug sensitivity test. Results : The ratio between male and female was 4 : 1. Age showed relatively even distribution from 3rd to 6 th decades. 64.6% of the patients was diagnosed at public health center. Weight loss was the most common complaint at admission. Bilateral lesions on chest X-ray films were 59.8%. 130patients had combined desease, of which DM was the most common(37.7%). 95patients had family history, of which parents were the most common(41.7%). According to the time of first diagnosis, 31 patients were diagnosed before 1980, and after then the number of patients was increased by degrees. Residence overwhelmed in pusan and gyung-nam province. 258 patients got previous treatment history, of which 112 patients(43.4%) had more than 3 times and only 133 patients(51.6%)got regular medication. 97 patients used more than other 3 drugs in addition to INH, EMB, RFP and PZA before admission. 154 patients were informed with the results of drug sensitivity test. of which 77 patients had resistance to more than 5 drugs. Gastrointestinal problem was the most common in side reaction to drugs. Conclusion : In the case of weight loss of unknown cause, tuberculosis should be suspected. In first treatment, sufficient and satisfactory explanation for tuberculosis is necessary and treatment period should not be stict to 6 month-short term therapy. In retreatment, new drugs should not be added to used drugs even though drug sensitivity results show sensitivity to some of them. Proper time for surgical intervention should not be delayed.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.379-390
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• 1997

Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.945-953
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• 1996

Background : Many acute and chronic lung diseases including pneumoconiosis are characterized by the presence of increased numbers of activated macrophages. These macrophages generate several inflammatory cell chemoattractants, by which neutrophil migrate from vascular compartment to the alveolar space. Recruited neutrophils secrete toxic oxygen radicals or proteolytic enzymes and induce inflammatory response. Continuing inflammatory response results in alteration of the pulmonary structure and irreversible fibrosis. Recently, a polypeptide with specific neutrophil chemotactic activity, interleukin-8(IL-8), has been cloned and isolated from a number of cells including : monocytes, macrophages and fibroblasts. IL-1 and/or TNF-${\alpha}$ preceded for the synthesis of IL-8, and we already observed high level of IL-1 and TNF-${\alpha}$ in the pneumoconioses. So we hypothesized that IL-8 may be a central role in the pathogenesis of pneumoconiosis. In order to evaluate the clinical utility of IL-8 as a biomarker in the early diagnosis of pneumoconiosis, we investigated the increase of IL-8 in the pneumoconiotic patient and the correlation between IL-8 level and progression of pneumoconiosis. Method : We measured IL-8 in the serum of 48 patients with pneumoconiosis and 16 persons without dust exposure history as a control group. Pneumoconiotic cases were divided into 3 groups according to ILO Classification : suspicious group(n=16), small opacity group(n=16) and large opacity group(n=16). IL-8 was measured by a sandwich enzytne immunoassay technique. All data were expressed as the $mean{\pm}standard$ deviation. Results: 1) The mean value of age was higher in the small opacity and large opacity group than comparison group, but smoking history was even. Duration of dust exposure was not different among 3 pneumoconiosis groups. 2) IL-8 level was $70.50{\pm}53.63pg/m{\ell}$ in the suspicious group, $107.50{\pm}45.88pg/m{\ell}$ in the small opacity group, $132.50{\pm}73.47pg/m{\ell}$ in the large opacity group and $17.85{\pm}33.85pg/m{\ell}$ in the comparison group. IL-8 concentration in all pneumoconiosis group was significant higher than that in the comparison group(p<0.001). 3) IL-8 level tended to increase with the progression of pneumoconiosis. Multiple comparison test using Anova/Scheffe analysis showed a significant difference between suspicious group and large opacity group(p<0.05). 4) The level of IL-8 was correlated with the progression of pneumoconiosis(r=0.4199, p<0.05). Conclusion : IL-8 is thought to be a good biomarker for the early diagnosis of pneumoconiosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.290-300
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• 1998

Background: CYFRA 21-1 is a tumor marker which measures a fragment of cytokeratin 19 expressed by epithelial cells in bronchus. It is known that cytokeratin 19 is abundant in squamous epithelial cell cancer of the lung. However, if the incidence of elevated serum CYFRA 21-1 level in patients with benign lung diseases or pulmonary tuberculosis with severe parenchymal damage is high the specificity of CYFRA 21-1 could be decreased. The purpose of this study is to investigate the changes of serum CYFRA 21-1 according to the degree of parenchymal damage and the usefulness of CYFRA 21-1 for diagnosing possibly combined lung cancer in patients with pulmonary tuberculosis. Method: We studied the changes of serum CYFRA 21-1 according to the sputum AFB stain, radiologic manifestation and history of treatment in 81 patients with pulmonary tuberculosis, and 20 healthy persons, 25 patients with lung cancer, as a control group. CYFRA 21-1 concentration in serum was quantified by the immunoradiometry assay(Centocor$^{(R)}$). Result: The results were as follow; Serum CYFRA 21-1 level was significantly lower in patients with pulmonary tuberculosis($1.54{\pm}1.19ng/mL$, p<0.01) as compared to patients with lung cancer($12.25{\pm}15.97ng/mL$), and was slightly higher than the level in heathy persons($0.90{\pm}0.49ng/mL$) but there was no significant difference. Serum CYFRA 21-1 level was below the cut-off value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis but it was above the cut-off value in 64 percent of patients with lung cancer. Serum CYFRA 21-1 level was significantly higher in the initial treatment group($1.91{\pm}1.55ng/mL$, p<0.05) as compared to the treatment. failure group ($0.92{\pm}0.30ng/mL$). According to the sputum AFB smear, serum CYFRA 21-1 level in patients with negative result was slightly higher than the level in patients with positive result but there was no significant difference. According to the radiologic manifestation, serum CYFRA 21-1 level was significantly higher in patients with infiltrative lesion ($2.15{\pm}1.63ng/mL$, p<0.01) as compared to patients with destructive lesion ($l.04{\pm}0.54ng/mL$). As the size of cavity or destructive lesion was larger, the level was significantly lower(p<0.05). Conclusion: As serum CYFRA 21-1 level was significantly higher in the initial treatment group and patients with infiltrative lesion, it suppose to be closely related with the degree of parenchymal damage of the lung of the pulmonary tuberculosis. However CYFRA 21-1 could be useful method for diagnosing lung cancer even in patients with pulmonary tuberculosis combined with lung cancer because of the fact that it was below the cutoff value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis.

• Microbiology and Biotechnology Letters
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• v.39 no.1
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• pp.29-36
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• 2011

Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections on urinary track, cornea, respiratory track, and burn wound site, and mainly relies on quorum sensing (QS) for its virulence. To control the infectivity of P. aeruginosa, we previously synthesized the structural analogues of a major QS signal, N-3-oxododecanoyl homoserine lactone (3OC12-HSL) to use as a QS inhibitor. Two of them (5b and 5f) had been confirmed to have an inhibitory effect on LasR, a major QS signal receptor of P. aeruginosa in the screening by the recombinant Escherichia coli reporter. To further evaluate these compounds, we tested their efficacy to control the QS and virulence of P. aeruginosa. Unlike the result from E. coli reporter, both 5b and 5f failed to affect the LasR activity in P. aeruginosa, but instead they selectively affected the activity of QscR, another 3OC12-HSL receptor of P. aeruginosa. Interestingly, their effect on QscR was complex and opposite to what we obtained with E. coli system. Both 5b and 5f enhanced the QscR activity at the low concentration range (< 10 ${\mu}m$), but high concentration of 5f (${\approx}$1 mM) strongly inhibited QscR. While 5b and 5f didn't affect the production of proteases, the key virulence factor, they significantly reduced the biofilm formation that is important in mediating chronic infections. Especially, 5f inhibited the initial attachment of P. aeruginosa, rather than the biofilm maturation. Based on our results, we suggest that 5f can be applied for an anti-biofilm agent without increasing virulence of P. aeruginosa.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.788-795
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• 2002

This study described the effect of levan (9-2,6-linked fructose polymer) feeding on serum lipids, adiposity and uncoupling protein (UCP) expression in growing rats. Levan was synthesized from sucrose using bacterial levansucrase. UCP is a mitochondrial protein that uncouples the respiratory chain from oxidative Phosphorylation and generates heat instead of ATP, thereby increase energy expenditure. We observed that 3% or 5% levan containing diet reduced serum triglyceride levels, visceral and peritoneal fat mass and induced the UCP expression in rats fed high fat diet in previous study. To determine whether the intake of low level of levan may have the hypolipidemic and anti-obesity effect, 4 wk old Sprague Dawley male rats were fed AIN-76A diet for 6 wk, and sub-sequently fed 1% or 2% levan solution for further 5 wk. Intake of 1% levan in liquid form reduced serum triglyceride and serum total cholesterol levels to 50% and 66% of control group, respectively. Although epididymal and peritoneal fat masses were not affected by levan feeding, visceral fat mass was lower in 1% levan group compared to control group. The expression of UCP2 mRNA in brown adipose tissue, skeletal muscle and hypothalamus and UCP3 mRNA in skeletal muscle were not changed by levan feeding, while the UCP2 mRNA in white adipose tissue was up-regulated by levan feeding. In conclusions, intake of low level of levan solution reduced serum triglyceride and total cholesterol, restrained the visceral fat accumulation and increased UCP expression in white adipose tissue in rats. This study suggests that hypolipidemic and anti-obesity effect of levan attributed to anti-lipogenesis and inefficeint energy utilization by up-regulation of UCPs.

• Neonatal Medicine
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• v.16 no.1
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• pp.47-54
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• 2009

Purpose: Present evidences suggest that Ureaplasma urealyticum is a cause of pneumonia, septicemia, and bronchopulmonary dysplasia (BPD) in newborn infants, particularly those born prematurely. The purpose of this work was to examine the relationship between Ureaplasma urealyticum in the tracheal aspirates and adverse outcomes, such as BPD and early onset neonatal sepsis in premature infants. Methods: A polymerase chain reaction (PCR) was performed on tracheal aspirates collected within 24 hour after birth in 176 premature infants less than 35 weeks of gestation and admitted to the neonatal intensive care unit of Bundang CHA Hospital. Results: U. urealyticum was detected in 37 of 176 preterm infants (21.0%). Gestational age ($29^{+5}{\pm}2^{+5}$ wk vs. $30^{+6}{\pm}2^+{-5}$ wk, P=0.0l3) and birth weight (1.39${\pm}$0.44 kg vs. 1.59${\pm}$0.55 kg, P=0.037) were lower in the U urealyticum-positive group compared to the control group. The incidence of early onset neonatal sepsis (16.2% vs. 6.5%, P=0.045) and BPD (45.9% vs. 29.5%, P=0.047) was higher in the U urealyticum-positive group compared to the control group, but the severity of BPD was not different between two groups. However, multiple logistic regression analysis revealed that the presence of U. urealyticum was not independently related to the development of early onset neonatal sepsis and BPD. Conclusion: The results suggest that colonization of the lower respiratory tract by U. urealyticum might not be related to the development of neonatal sepsis and BPD directly in preterm infants.