• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.241-250
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• 1999

Background: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined ; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. Methods: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood and agarose gel electrophoresis. Results: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M : F=24.3% : 75.7%) compared to the non-cough group (M : F=49.7% : 50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D=16.2% : 18.9% : 64.9% in the cough group and 18.9% : 18.2% : 62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7% : 74.3% and 28.0% : 72.0% in the cough and non-cough group respectively and the difference was not significant(p = 0.676). Conclusion: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induced cough. ACE inhibitor-induced dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.451-463
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• 2006

Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

• Journal of agricultural medicine and community health
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• v.25 no.2
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• pp.353-377
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• 2000

This study was performed to investigate the performance state and improvement countermeasure of Primary Health care Posts(PHPs). The operation reports of PHPs(1996 330 PHPs, 1999 313 PHPs) located in Kyongsangbuk-Do and data collected by self-administered questionnaire survey of 280 community health practitioners(CHPs) were analyzed. The major results were as follows: Population per PHP in 1999 decreased in number compared with 1996. But population of the aged increased in number. The performance status of PHP in 1999 increased compared with 1996. A hundred forty one community health practitioners(50.4%) replied that the fiscal standing of PHP was good. Only 1.4% replied that the fiscal standing of PHP was difficult. For the degree of satisfaction in affairs, overall of community health practitioners felt proud. The degree of cooperation between PHP and public health institutions was high and the degree of cooperation of between PHP and private medical institutions was high. The degree of cooperation between PHP and Health Center was significantly different by age of CHP, the service period of CHP, and CHP's service period at present PHP. Over seventy percent of CHPs replied that they had cooperative relationship with operation council, village health workers, community organization. CHPs who drew up the paper on PHP's health activity plan were 96.4 % and only 11.4% of CHPs participated drawing up the report on the second community health plan. CHPs who grasped the blood pressure and smoking status of residents over 70% were 88.2%, 63.9% respectively and the grasp rate of blood pressure fur residents were significantly different according to age and educational level of CHP. CHPs received job education in addition continuous job education arid participated on research program in last 3 years were 27.5%, respectively. CHPs performed the return health program for residents in last 3years were 65.4%. Over 95% of CHPs replied that PHPs might be necessary and 53.9% of CHPs replied that the role of PHPs should be increased. CHPS indicated that major reasons of FHPs lockout were lack of understanding for PHP and administrative convenience, CHPs were officials in special government service governors intention of self-governing body. CHPs suggested number of population in health need such as the aged and patients with chronic disease, opinion of residents, population size, traffic situation and network in order as evaluation criteria for PHP and suggested results of health performance, degree of relationship with residents, results of medical examination anti treatment, ability for administration and affairs in order as evaluation criteria for CHP. CHPs replied that the important countermeasures for PHPs under standard were affairs improvement of PHPs and shifting of location to health weakness area in city. Over 50% of CHPs indicated that the most important thing for improvement of PHPs was affairs adjustment of CLIP. And CHPs suggested that health programs carried out in priority at PHP were management of diabetes mellitus and hypertention. home visiting health care, health care for the aged. The Affairs of BLIP should be adjusted to satisfy community health need and health programs such as management of diabetes mellitus and hypertention, home visiting health care, health care for the aged should be activated in order that PHPs become organization reflecting value system of primary health care.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.486-494
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• 2000

Background : The dominant innervation of airway smooth muscle is parasympathetic fibers which are carried in the vagus nerve. Activation of these cholinergic nerves releases acetylcholine which binds to $M_3$ muscarinic receptors on the smooth muscle causing bronchocontraction. Acetylcholine also feeds back onto neuronal $M_2$ muscarinic receptors located on the postganglionic cholinergic nerves. Stimulation of these receptors further inhibits acetylcholine release, so these $M_2$, muscarinic receptors act as autoreceptors. Loss of function of these $M_2$ receptors, as it occurs in animal models of hyperresponsiveness, leads to an increase in vagally mediated hyperresponsiveness. However, there are limited data pertaining to whether there are dysfunctions of these receptors in patients with asthma. The aim of this study is to determine whether there are dysfunction of $M_2$ muscarinic receptors in asthmatic patients and difference of function of these receptors according to severity of asthma. Method : We studied twenty-seven patients with asthma who were registered at Pulmonology Division of Korea University Hospital. They all met asthma criteria of ATS. Of these patients, eleven patients were categorized as having mild asthma, eight patients moderate asthma and eight patients severe asthma according to severity by NAEPP Expert Panel Report 2(1997). All subjects were free of recent upper respiratory tract infection within 2 weeks and showed positive methacholine challenge test ($PC_{20}$<16mg/ml). Methacholine provocation tests were performed twice on separate days allowing for an interval of one week. In the second test, pretreatment with the $M_2$ muscarinic receptor agonist pilocarpine($180{\mu}g$) through inhalation was performed be fore the routine procedures. Results : Eleven subjects with mild asthma and eight subjects with moderate asthma showed significant increase of $PC_{20}$ from 5.30$\pm$5.23mg/ml(mean$\pm$SD) to 20.82$\pm$22.56mg/ml(p=0.004) and from 2.79$\pm$1.51mg/ml to 4.67$\pm$3.53mg/ml(p=0.012) after pilocarpine inhalation, respectively. However, in the eight subjects with severe asthma significant increase of $PC_{20}$ from l.76$\pm$1.50mg/ml to 3.18$\pm$4.03mg/ml(p=0.161) after pilocarpine inhalation was not found. Conclusion : In subjects with mild and moderate asthma, function of $M_2$ muscarinic receptors was normal, but there was a dysfunction of these receptors in subjects with severe asthma. ηlese results suggest that function of $M_2$ muscarinic receptors is different according to severity of asthma.

• Journal of Distribution Science
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• v.9 no.1
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• pp.17-27
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• 2011

As the world becomes more globalized, business competition becomes fiercer, while consumers' needs for less expensive quality products are on the increase. Business operations make an effort to secure a competitive edge in costs and services, and the logistics industry, that is, the industry operating the storing and transporting of goods, once thought to be an expense, begins to be considered as the third cash cow, a source of new income. Logistics centers are central to storage, loading and unloading of deliveries, packaging operations, and dispensing goods' information. As hubs for various deliveries, they also serve as a core infrastructure to smoothly coordinate manufacturing and selling, using varied information and operation systems. Logistics centers are increasingly on the rise as centers of business supply activities, growing beyond their previous role of primarily storing goods. They are no longer just facilities; they have become logistics strongholds that encompass various features from demand forecast to the regulation of supply, manufacturing, and sales by realizing SCM, taking into account marketability and the operation of service and products. However, despite these changes in logistics operations, some centers have been unable to shed their past roles as warehouses. For the continuous development of logistics centers, various measures would be needed, including a revision of current supporting policies, formulating effective management plans, and establishing systematic standards for founding, managing, and controlling logistics centers. To this end, the research explored previous studies on the use and effectiveness of logistics centers. From a theoretical perspective, an evaluation of the overall introduction, purposes, and transitions in the use of logistics centers found issues to ponder and suggested measures to promote and further advance logistics centers. First, a fact-finding survey to establish demand forecast and standardization is needed. As logistics newspapers predicted that after 2012 supply would exceed demand, causing rents to fall, the business environment for logistics centers has faltered. However, since there is a shortage of fact-finding surveys regarding actual demand for domestic logistic centers, it is hard to predict what the future holds for this industry. Accordingly, the first priority should be to get to the essence of the current market situation by conducting accurate domestic and international fact-finding surveys. Based on those, management and evaluation indicators should be developed to build the foundation for the consistent advancement of logistics centers. Second, many policies for logistics centers should be revised or developed. Above all, a guideline for fair trade between a shipper and a commercial logistics center should be enacted. Since there are no standards for fair trade between them, rampant unfair trades according to market practices have brought chaos to market orders, and now the logistics industry is confronting its own difficulties. Therefore, unfair trade cases that currently plague logistics centers should be gathered by the industry and fair trade guidelines should be established and implemented. In addition, restrictive employment regulations for foreign workers should be eased, and logistics centers should be charged industry rates for the use of electricity. Third, various measures should be taken to improve the management environment. First, we need to find out how to activate value-added logistics. Because the traditional purpose of logistics centers was storage and loading/unloading of goods, their profitability had a limit, and the need arose to find a new angle to create a value added service. Logistic centers have been perceived as support for a company's storage, manufacturing, and sales needs, not as creators of profits. The center's role in the company's economics has been lowering costs. However, as the logistics' management environment spiraled, along with its storage purpose, developing a new feature of profit creation should be a desirable goal, and to achieve that, value added logistics should be promoted. Logistics centers can also be improved through cost estimation. In the meantime, they have achieved some strides in facility development but have still fallen behind in others, particularly in management functioning. Lax management has been rampant because the industry has not developed a concept of cost estimation. The centers have since made an effort toward unification, standardization, and informatization while realizing cost reductions by establishing systems for effective management, but it has been hard to produce profits. Thus, there is an urgent need to estimate costs by determining a basic cost range for each division of work at logistics centers. This undertaking can be the first step to improving the ineffective aspects of how they operate. Ongoing research and constant efforts have been made to improve the level of effectiveness in the manufacturing industry, but studies on resource management in logistics centers are hardly enough. Thus, a plan to calculate the optimal level of resources necessary to operate a logistics center should be developed and implemented in management behavior, for example, by standardizing the hours of operation. If logistics centers, shippers, related trade groups, academic figures, and other experts could launch a committee to work with the government and maintain an ongoing relationship, the constraint and cooperation among members would help lead to coherent development plans for logistics centers. If the government continues its efforts to provide financial support, nurture professional workers, and maintain safety management, we can anticipate the continuous advancement of logistics centers.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.510-516
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• 2005

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine $1000mg/m^2$ and intravenous vinorelbine $25mg/m^2$ on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.231-238
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• 1994

Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.77-89
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• 1998

Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.372-385
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• 1999

Background: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. Method: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. Results: The experimental group was divided into two subgroups-those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 $cells/mm^3$ while control group's mean was 0.4 $cells/mm^2$(p=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 $cells/mm^2$ with 28.4 $cells/mm^2$ of control group(P=0.026). In addition, the mean thickness of the basement membrane of experimental group was $14.20{\pm}5.20{\mu}m$ in contrast of control group whose mean was $3.50{\pm}1.37{\mu}m$(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough variant asthma ; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive (21.4%) with the skin prick test In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). Conclusion: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.