• Tuberculosis and Respiratory Diseases
• /
• v.42 no.2
• /
• pp.184-205
• /
• 1995

Background: Pulmonary toxicity by bleomycin has multiple mechanisms including direct tissue toxicity due to oxygen-derived free radicals and indirect toxicity through amplification of pulmonary inflammation. To evaluate the effect of chelators or free radical scavenger to lung damage induced by bleomycin, penicillamine as a copper chelator, deferoxamine as an iron chelator and vitamin E as a free radical scavenger were administered. Methods: Two hundred Wistar rats were divided into five groups: Control, bleomycin treated, bleomycin-penicillamine treated, bleomycin-deferoxamine treated, and bleomycin-vitamin E treated groups. Rats sacrificed on day 1, day 3, day 4, day 7, day 14, and day 28 after treatment. Bronchoalveolar lavage, light microscopic and immunohistologic studies for type I, III, IV collagens, fibronectin, laminin and NBD phallicidin were evaluated. Results: There was a significant increase in the total cell counts of bronchoalveolar lavage on day 1 from all treated animals and vitamin treated group showed an abrupt decrease in total cell counts with decrease of neutrophils on day 3. Bleomycin-vitamin E treated group had the least histologic changes such as pulmonary fibrosis. The alveolar basement membranes were positive for type IV collegen and laminin. Basement membranes of bleomycin, bleomycin-penicillamine, or bleomycin-deferoxamine treated groups were disrupted and fragmented on day 4 or 7. The bleomycin-vitamin E treated group had intact basement membranes until day 28. Conclusion: Bleomycin-induced pulmonary fibrosis was related to the severity of acute injury to oxygen radicals or activation of neutrophils and disruption of basement membrane. Vitamin E seemed to be the most effective antioxidant in the inhibition of bleomycin-induced pulmonary injury and fibrosis.

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.3
• /
• pp.257-265
• /
• 2005

Background : Rifabutin (ansamycin) is a spiro-piperidyl rifamycin, which is highly active against Mycobacterium tuberculosis. It has been found that some clinical isolates of tubercle bacilli that are resistant to rifampicin are susceptible to rifabutin, with some patients with multi-drug resistant pulmonary tuberculosis having shown favorable clinical and bacteriological responses to the rifabutin. This study was conducted to find the proportion of rifabutin-susceptible strains among rifampicin-resistant isolates from Korean MDR-TB patients, and investigate the presence of specific rpoB mutations, which may confer resistance to rifampicin, but not to rifabutin. Methods : 201 rifampicin-resistant and 50 pan-susceptible M. tuberculosis isolates were randomly selected for this study. The isolates were retested at rifampicin and rifabutin concentrations of 0, 20, 40 and $80{\mu}g/ml$, respectively. The isolates that grew at and/or over a rifabutin concentration of $20{\mu}g/ml$ were judged rifabutin-resistant. The rpoB gene was extracted from the isolates, and then amplified for direct sequencing to investigate specific rpoB mutations that conferred rifabutin- susceptibility but rifampicin-resistance. Results : Out of the 201 rifampicin-resistant M. tuberculosis, 41 strains (20.4%) were susceptible to rifabutin using the absolute concentration method on Lowenstein-Jensen media. The rpoB mutation types that showed susceptibility to rifabutin were Leu511Pro, Ser512Arg, Gln513Glu, Asp516Ala, Asp516Gly, Asp516Val, Asp516Tyr, Ser522Leu, His526Asn, His526Leu, His526Cys, Arg529Pro and Leu533Pro. A reverse hybridization technique was able to detect 92.5% of the rifabutin-susceptible isolates, with a specificity of 96.1% among 195 M. tuberculosis isolates with the rpoB mutation. Conclusions : Around 20% of the rifampicin-resistant isolates in Korea showed susceptibility to rifabutin, which was associated with some specific mutations of rpoB. Rifabutin could be used for the treatment of MDR-TB patients, especially when drug susceptibility testing reveals susceptibility to rifabutin.

• Molecules and Cells
• /
• v.37 no.2
• /
• pp.178-186
• /
• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.

• Asia pacific journal of information systems
• /
• v.21 no.3
• /
• pp.71-96
• /
• 2011

Within the traditional medical delivery system, patients residing in medically vulnerable areas, those with body movement difficulties, and nursing facility residents have had limited access to good healthcare services. However, Information and Communication Technology (ICT) provides us with a convenient and useful means of overcoming distance and time constraints. ICT is integrated with biomedical science and technology in a way that offers a new high-quality medical service. As a result, rapid technological advancement is expected to play a pivotal role bringing about innovation in a wide range of medical service areas, such as medical management, testing, diagnosis, and treatment; offering new and improved healthcare services; and effecting dramatic changes in current medical services. The increase in aging population and chronic diseases has caused an increase in medical expenses. In response to the increasing demand for efficient healthcare services, a telehealth service based on ICT is being emphasized on a global level. Telehealth services have been implemented especially in pilot projects and system development and technological research. With the service about to be implemented in earnest, it is necessary to study its overall acceptance by consumers, which is expected to contribute to the development and activation of a variety of services. In this sense, the study aims at positively examining the structural relationship among the acceptance factors for telehealth services based on the Technology Acceptance Model (TAM). Data were collected by showing audiovisual material on telehealth services to online panels and requesting them to respond to a structured questionnaire sheet, which is known as the information acceleration method. Among the 1,165 adult respondents, 608 valid samples were finally chosen, while the remaining were excluded because of incomplete answers or allotted time overrun. In order to test the reliability and validity of the assessment scale items, we carried out reliability and factor analyses, and in order to explore the causal relation among potential variables, we conducted a structural equation modeling analysis using AMOS 7.0 and SPSS 17.0. The research outcomes are as follows. First, service quality, innovativeness of medical technology, and social influence were shown to affect perceived ease of use and perceived usefulness of the telehealth service, which was statistically significant, and the two factors had a positive impact on willingness to accept the telehealth service. In addition, social influence had a direct, significant effect on intention to use, which is paralleled by the TAM used in previous research on technology acceptance. This shows that the research model proposed in the study effectively explains the acceptance of the telehealth service. Second, the research model reveals that information privacy concerns had a insignificant impact on perceived ease of use of the telehealth service. From this, it can be gathered that the concerns over information protection and security are reduced further due to advancements in information technology compared to the initial period in the information technology industry, and thus the improvement in quality of medical services appeared to ensure that information privacy concerns did not act as a prohibiting factor in the acceptance of the telehealth service. Thus, if other factors have an enormous impact on ease of use and usefulness, concerns over these results in the initial period of technology acceptance may become irrelevant. However, it is clear that users' information privacy concerns, as other studies have revealed, is a major factor affecting technology acceptance. Thus, caution must be exercised while interpreting the result, and further study is required on the issue. Numerous information technologies with outstanding performance and innovativeness often attract few consumers. A revised bill for those urgently in need of telehealth services is about to be approved in the national assembly. As telemedicine is implemented between doctors and patients, a wide range of systems that will improve the quality of healthcare services will be designed. In this sense, the study on the consumer acceptance of telehealth services is meaningful and offers strong academic evidence. Based on the implications, it can be expected to contribute to the activation of telehealth services. Further study is needed to assess the acceptance factors for telehealth services, such as motivation to remain healthy, health care involvement, knowledge on health, and control of health-related behavior, in order to develop unique services according to the categorization of customers based on health factors. In addition, further study may focus on various theoretical cognitive behavior models other than the TAM, such as the health belief model.

• Asia pacific journal of information systems
• /
• v.19 no.3
• /
• pp.99-124
• /
• 2009

Many firms in Korea have adopted and used advanced information technology in an effort to boost efficiency. The process of adapting to the new technology, at the same time, can vary from one firm to another. As such, this research focuses on several relevant factors, especially the roles of social interaction as a key variable that influences the technology adaptation process and the outcomes. Thus far, how a firm goes through the adaptation process to the new technology has not been yet fully explored. Previous studies on changes undergone by a firm or an organization due to information technology have been pursued from various theoretical points of views, evolved from technological and institutional views to an integrated social technology views. The technology adaptation process has been understood to be something that evolves over time and has been regarded as cycles between misalignments and alignments, gradually approaching the stable aligned state. The adaptation process of the new technology was defined as "appropriation" process according to Poole and DeSanctis (1994). They suggested that this process is not automatically determined by the technology design itself. Rather, people actively select how technology structures should be used; accordingly, adoption practices vary. But concepts of the appropriation process in these studies are not accurate while suggested propositions are not clear enough to apply in practice. Furthermore, these studies do not substantially suggest which factors are changed during the appropriation process and what should be done to bring about effective outcomes. Therefore, research objectives of this study lie in finding causes for the difference in ways in which advanced information technology has been used and adopted among organizations. The study also aims to explore how a firm's interaction with social as well as technological factors affects differently in resulting organizational changes. Detail objectives of this study are as follows. First, this paper primarily focuses on the appropriation process of advanced information technology in the long run, and we look into reasons for the diverse types of the usage. Second, this study is to categorize each phases in the appropriation process and make clear what changes occur and how they are evolved during each phase. Third, this study is to suggest the guidelines to determine which strategies are needed in an individual, group and organizational level. For this, a substantially grounded theory that can be applied to organizational practice has been developed from a longitudinal comparative case study. For these objectives, the technology appropriation process was explored based on Structuration Theory by Giddens (1984), Orlikoski and Robey (1991) and Adaptive Structuration Theory by Poole and DeSanctis (1994), which are examples of social technology views on organizational change by technology. Data have been obtained from interviews, observations of medical treatment task, and questionnaires administered to group members who use the technology. Data coding was executed in three steps following the grounded theory approach. First of all, concepts and categories were developed from interviews and observation data in open coding. Next, in axial coding, we related categories to subcategorize along the lines of their properties and dimensions through the paradigm model. Finally, the grounded theory about the appropriation process was developed through the conditional/consequential matrix in selective coding. In this study eight hypotheses about the adaptation process have been clearly articulated. Also, we found that the appropriation process involves through three phases, namely, "direct appropriation," "cooperate with related structures," and "interpret and make judgments." The higher phases of appropriation move, the more users represent various types of instrumental use and attitude. Moreover, the previous structures like "knowledge and experience," "belief that other members know and accept the use of technology," "horizontal communication," and "embodiment of opinion collection process" are evolved to higher degrees in their dimensions of property. Furthermore, users continuously create new spirits and structures, while removing some of the previous ones at the same time. Thus, from longitudinal view, faithful and unfaithful appropriation methods appear recursively, but gradually faithful appropriation takes over the other. In other words, the concept of spirits and structures has been changed in the adaptation process over time for the purpose of alignment between the task and other structures. These findings call for a revised or extended model of structural adaptation in IS (Information Systems) literature now that the vague adaptation process in previous studies has been clarified through the in-depth qualitative study, identifying each phrase with accuracy. In addition, based on these results some guidelines can be set up to help determine which strategies are needed in an individual, group, and organizational level for the purpose of effective technology appropriation. In practice, managers can focus on the changes of spirits and elevation of the structural dimension to achieve effective technology use.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.10 no.1
• /
• pp.50-63
• /
• 1999

Introduction：Test anxiety is a pervasive problem among high school students in Korea. While anxiety in test situations may actually facilitate the performance of some students, more often it is disruptive and leads to performance decrements. Over the past years, many child psychiatrists have become concerned with understanding the nature of test anxiety, but it is not clearly understood yet. In order to understand the nature of test anxiety, the relationship between test anxiety and depression, state anxiety, trait anxiety, temperament and family environment were examined. Methods：The Test Anxiety Inventory, Chidlren's Depression Inventory, State-Trait Anxiety Inventory, Temperamnet and Family Environment Scale Scale were administered to 576 high school students in Seoul. The relationships between test anxiety and other measures were tested using Pearson correlation coefficients and to test the causal relationship among the variables, regression analysis was performed. Results：The correlation coefficients between test anxiety and depression, state anxiety, trait anxiety, temperament and family environment scale were 0.42(p<0.01), 0.34(p<0.05), 0.38(p<0.05), 0.36(p<0.05) and -0.23(p<0.01), respectively. Regression analysis showed that only state and trait anxiety had direct causal relationship with test anxiety. Depression, temperament and family environment were indirecly related with test anxiety. Conclusions：This study indicates that the level of state and trait anxiety are directly related with test anxiety, and other variables such as temperament, family environment and depression are indirectly related with test anxiety. Thus, in order to develop the effective methods for treatment, these psychopathological characteristics should be kept in mind and the most important factors are the levels of state and trait anxiety.

• Journal of Chest Surgery
• /
• v.35 no.5
• /
• pp.356-364
• /
• 2002

Background: This study was undertaken to investigate the outcome of composite graft aortic root replacement using coronary button reimplantation technique for the treatment of aneurysms of the ascending aorta involving the aortic root. Material and Method: Between April 1995 and September 2001, 54 patients having aortic root replacement with a composite valve graft using direct coronary button reimplantation were reviewed retrospectively. Left ventricular dysfunction was present in 14 patients(25.9%), aortic regurgitation in 48(89%), and Marfan's syndrome in 17(31.5%). The indications for operation were annuloaortic ectasia in 29 patients(53.7%), aortic dissection in 11(20.4%), aneurysms of the ascending aorta involving aortic root in 12(22.2%), and aortitis in 2(3.7%). Six patients(11.1%) had previous cardiac or ascending aortic operations. Concomitant procedures were arch replacement in 21 patients(38.9%), coronary artery bypass graft in 7(13%), mitral valve repair or replacement in 4(7.4%), and others in 6. The mean time of circulatory arrest, total bypass, and aortic crossclamp were 18 $\pm$ 9 minutes, 177 $\pm$ 42 minutes, and 127 $\pm$ 31 minutes, respectively. Result: There was 1 early death(1.9%). Mean follow-up was 24.6$\pm$ 19.5 months. There were two late deaths(3.8%) including one death due to the traumatic cerebral hemorrhage. The Kaplan-Meier survival rate was 98.0 $\pm$ 2.0% and 93.1 $\pm$ 5.1% at 1 and 6 years, respectively. Two patients required reoperation owing to a false aneurysm at the root anastomosis site and a malfunction of prosthetic aortic valve(3.8%). Staged operation for dissection of the remaining thoracoabdominal aorta was performed in 1 patient. The freedom rate from reoperation was 97.8 $\pm$ 2.0% and 65.3 $\pm$ 26.7% at 1 and 6 years, respectively.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.4
• /
• pp.319-327
• /
• 1994

Background: The pathogenetic mechanism of adult respiratory distress syndrome(ARDS) is not clearly defined yet, but it is well known that increased pulmonary capillary permeabilty is characteristic feature of ARDS. The increased alveolar-capillary permeability is usually preceded by damage of pulmonary artery endothelial cells. The released enzymes and oxygen free radicals from the activated neutrophils seem to play a predominant role in endothelial cell cytotoxicity. The activated neutrophils, however, probably are not the sole contributing factor in this type of damage because many cases of ARDS have been reported in severe neutropenia. Bacterial endotoxin perse and/or oxygen free radicals released from endothelial cells are suggested to be possible factors that contribute to the development of ARDS. The purpose of this study is to investigate the direct cytotoxicity of endotoxin and the role of oxygen free radicals released from the endothelial cells in endotoxin-induced endothelial cell cytotoxicity. Methods: First, to investigate whether endotoxin is cytotoxic to HUVE by itself, various doses of endotoxin were added to culture medium and cytotoxicity was measured. Second, to evaluate the possible role of oxygen free radical in endotoxin-induced HUVE cytotoxicity, various antioxidants were added on the endotoxin-induced HUVE cytotoxicity and cytotoxicity was measured. Third, to verify the release of oxygen free radicals from HUVE, the concentrations of hydrogen peroxide in the endotoxin-treated culture supernatant were measured. Finally, to observe the cytotoxic effect of hydrogen peroxide, HUVE cytotoxicity in the presence of various doses of hydrogen peroxide was measured. The fourth generations of subcultured HUVE from primary culture were used. The cell cytotoxicity was quantified by the chromium-51 release assay. Results: 1) Endotoxin alone showed HUVE cytotoxicity in a dose-dependent fashion. 2) Endotoxin-induced HUVE cytotoxicity was significantly attenuated by the pretreatment of catalase and DMTU. 3) Hydrogen peroxide was released from HUVE after endotoxin treatment in a dose-dependent fashion. 4) Exogenous hydrogen peroxide also showed HUVE cytotoxicity in a dose-dependent fashion. Conclusion: These results suggest that endotoxin alone can directly injure HUVE, and, oxygen-free radicals released from HUVE in response to endotoxin may also participate in the endotoxin-induced HUVE cytotoxicity.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.3
• /
• pp.298-309
• /
• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.6
• /
• pp.476-486
• /
• 2008

Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.