• Journal of Microbiology and Biotechnology
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• v.24 no.5
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• pp.704-713
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• 2014

The highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype infect poultry and have also been spreading to humans. Although new antiviral drugs and vaccinations can be effective, rapid detection would be more efficient to control the outbreak of infections. In this study, a phage-display library was applied to select antibody fragments for HPAI strain A/Hubei/1/2010. As a result, three clones were selected and sequenced. A hemagglutinin inhibition assay of the three scFvs revealed that none exhibited hemagglutination inhibition activity towards the H5N1 virus, yet they showed a higher binding affinity for several HPAI H5N1 strains compared with other influenza viruses. An ELISA confirmed that the HA protein was the target of the scFvs, and the results of a protein structure simulation showed that all the selected scFvs bound to the HA2 subunit of the HA protein. In conclusion, the three selected scFVs could be useful for developing a specific detection tool for the surveillance of HPAI epidemic strains.

• Journal of Preventive Medicine and Public Health
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• v.43 no.2
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• pp.99-104
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• 2010

The World Health Organization (WHO) announced the emergence of a novel influenza on April 24, 2009, and they declared pandemic on June 11. In Korea, the proportion of influenza-like illness and the consumption of antiviral agents peaked in early November. The government established the Central Headquarters for Influenza Control and operated the emergency response system. In the quarantine stations, we checked the body temperature and collected quarantine questionnaires from all the arrivals from infected countries. We also isolated the confirmed cases in the national isolation hospitals. However, as the community outbreaks were reported, we changed strategy from containment to mitigation. We changed the antiviral agent prescription guideline so that doctors could prescribe antiviral agents to all patients with acute febrile respiratory illness, without a laboratory diagnosis. Also the 470 designated hospitals were activated to enhance the efficacy of treatment. We vaccinated about 12 million people and manage the adverse event following the immunization management system. In 2010, we will establish additional national isolation wards and support hospitals to establish fever clinics and isolation intensive care unit (ICU) beds. We will also make a computer program for managing the national isolation hospitals and designated hospitals. We will establish isolation rooms and expand the laboratory in quarantine stations and we will construct a bio-safety level 3 laboratory in each province. In addition, we plan to construct a bio-safety level 4 laboratory at a new Korea Centers for Disease Control and Prevention (KCDC) facilities in Ossong.

• Laboratory Medicine Online
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• v.1 no.1
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• pp.26-34
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• 2011

Background: Laboratory diagnosis of new influenza A (H1N1) is crucial for managing patients and establishing control and prevention measures. We compared the diagnostic accuracies of the real time RT-PCR (rRT-PCR) test recommended for the confirmation of the new flu and the viral culture method used conventionally for viral disease with that of the rapid antigen test (RAT). Methods: We performed RAT, R-mix culture, and real-time PCR by using 861 respiratory samples collected from December 2009 to January 2010 and evaluated the abilities of these methods to detect new influenza A. The relationship among the positive rates of RAT, grades of culture, and the cycle threshold (Ct) values of rRT-PCR was also evaluated. Results: Of the 861 patients, 308 (35.8%) were diagnosed with new influenza A. The sensitivities, specificities, positive predictive values, and negative predictive values of the tests were respectively as follows: 59.7%, 99.5%, 98.4%, and 81.6% for RAT; 93.2%, 100%, 100%, and 96.3% for R-mix culture; and 95.8%, 100%, 100%, and 97.7% for rRT-PCR. Samples with weak positive grade in culture and those with Ct values of 30-37 in rRT-PCR showed positivities as low as 25.3% and 2.3% in RAT, respectively. The hospitalization rate and death rate of the confirmed patients were 3.2% and 0.3%, respectively, and gastrointestinal symptoms were observed in 7.2% of the patients. Conclusions: R-mix culture and rRT-PCR tests showed excellent reliability in the diagnosis of new influenza A and could be very useful, especially for samples with low viral load.

• Mycobiology
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• v.47 no.2
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• pp.256-260
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• 2019

Neuraminidase (NA) cleaves the glycosidic bond linkages of sialic acids to release the mature virions from infected cells and has been an attractive therapeutic target for anti-influenza agents. In our ongoing investigation of NA inhibitors in mushroom extracts, we found that the extract the fruiting body of Glaziella splendens potently inhibited neuraminidase. The fruiting bodies of G. splendens were extracted and partitioned successively with hexane, ethyl acetate, and butanol. The ethyl acetate soluble-layer was subjected to silica gel and Sephadex LH-20 column chromatographies, and MPLC to obtain five compounds (1-5). Their structures were determined by spectroscopic methods. NA inhibitory activity of these compounds was evaluated using NAs from recombinant rvH1N1, H3N2, and H5N1 influenza A viruses. One compound (1) was elucidated as a new azaphilone derivative, and four compounds (2-5) were identified as entonaemin A, comazaphilone D, rubiginosin A, and entonaemin B, respectively. Compounds 3 and 4 showed considerable inhibitory activity against three types of neuraminidases with the $IC_{50}$ values of 30.9, 41.8, and $35.7{\mu}M$ for 3 and 46.5, 50.4, and $29.9{\mu}M$ for 4, respectively. This study reveals that the fruiting bodies of G. splendens possess azaphilone derivatives with the NA inhibitory activity. This is the first report on the isolation of neuraminidase inhibitors from the fruiting bodies of G. splendens.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.280-287
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• 2015

Current influenza vaccines are produced in embryonated chicken eggs. However, egg-based vaccines have various problems. To address these problems, recombinant protein vaccines have been developed as new vaccine candidates. Unfortunately, recombinant proteins frequently encounter aggregation and low stability during their biogenesis. It has been previously demonstrated that recombinantly expressed proteins can be greatly stabilized with high solubility by fusing stabilizing peptide (SP) derived from the C-terminal acidic tail of human synuclein (ATS). To investigate whether SP fusion proteins can induce protective immunity in mice, we produced influenza HA and SP fusion protein using a baculovirus expression system. In in vitro tests, SP-fused recombinant HA1 (SP-rHA1) was shown to be more stable than recombinant HA1 (rHA1). Mice were immunized intramuscularly with baculovirus-expressed rHA1 protein or SP-rHA1 protein ($2{\mu}g/mouse$) formulated with aluminum hydroxide. Antibody responses were determined by ELISA and hemagglutination inhibition assay. We observed that SP-rHA1 immunization elicited HA-specific antibody responses that were comparable to rHA1 immunization. These results indicate that fusion of SP to rHA1 does not negatively affect the immunogenicity of the vaccine candidate. Therefore, it is possible to apply SP fusion technology to develop stable recombinant protein vaccines with high solubility.

• Journal of Korean Medical classics
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• v.22 no.4
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• pp.221-239
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• 2009

Background: The recent outbreak of the novel strain of influenza A (H1N1) virus has raised a global concern of the future risk of pandemic. Traditional Korean Medicine(TKM) has been combatting against contagious diseases and developed its own particular and efficient way in treating those diseases. Objectives: Provide a distinctive and effective TKM method in understanding the principles of treatment, prevention, and contraindications against influenza A through case histories. Method: We revised case histories of eminent doctors of Ming and Qing dynasties according to their clinical manifestations similar to those of influenza A. We also verified prescriptions of the "Dong-uibogam(東醫寶鑑)" through examining clinical practices of China today. Results: 1. The subtypes of Warm disease; Wind Warmth and Pestilence has the most similar clinical manifestation in comparison to Influenza A. Specifying these terms is important in recognizing and classifying various diseases under the name of Warm disease. 2. TKM considered not only external factors but also individual factors like general condition, diet, emotion, constitutional types, etc in the treatment of febrile diseases. 3. TKM developed a new way in the treatment of contagious diseases. considering the characteristics of each pathogen. TKM described the Warm pathogen being light as a feather, which enters through the nose, principally affecting the Lung. Therefore, they emphasized treatment with Pungent Sweet Cooling Moistening[辛甘凉潤] method. 4. As the conservation of fluid and humor is the primordial concern in the treatment of Warm disease, they restricted release of the exterior with pungent-warm and purgation method. The purgation methods was used exclusively to decrease fever and preserve fluid and humor. 5. The only differentiating characteristics of Influenza A with seasonal influenza are vomiting and diarrhea. Case research revealed the possibility of these manifestations to be a mechanism of restoration. 6. TKM provides alimento prevention method like Mint Pear Porridge, mung bean, and etc also combination of herbal medicine. Also emphasized in the conservation of essence for the prevention of contagious diseases. Conclusions: TKM developed its unique way in understanding the pathogenesis, diagnosis, treatment, and prevention of contagious diseases and formed its independent scheme of Warm Disease. This knowledge in febrile contagious disease is relevant today in providing diverse treatment and prevention for influenza A.

• Tuberculosis and Respiratory Diseases
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• v.72 no.1
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• pp.1-7
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• 2012

Extracorporeal Membrane Oxygenation (ECMO) support to tissue oxygenation has been shown to improve survival in patients with life threatening respiratory distress syndrome or cardiac failure. Extracorporeal life support such as ECMO, including extracorporeal $CO_2$ removal ($ECCO_2R$), is used as temporary support until successful recovery of organs. A recently published multicentre randomized controlled trial, known as the CESAR (conventional ventilation or extracorporeal membrane oxygenation for severe adult respiratory failure) trial, was the first trial to demonstrate the utility of ECMO in acute respiratory distress syndrome (ARDS). During the 2009 influenza A (H1N1) pandemic, there were many reports of patients with severe ARDS related to H1N1 infection treated with ECMO. These reports revealed a high survival rate and effectiveness of ECMO. In this review, we explain the indication of ECMO clinical application, the practical types of ECMO, and complications associated with ECMO. In addition, we explain recent new ECMO technology and management of patients during ECMO support.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.1-10
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• 2012

Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.138-144
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• 2011

In order to minimize such adverse drug reactions, governments and international organs have been on the watch for them. Also in South Korea, a system has been established in order that adverse drug reactions may be reported to Korea Food and Drug Administration(KFDA). This study is to analyze drugs to cause adverse reactions, the adverse reactions and patients concerned on the authority of the data of Korea FDA, which is expected to be the preliminary data on preventable adverse reactions. This study was conducted on the 74,037 cases of adverse drug reactions reported to Korea FDA between January 2007 and June 2010. Fentanyl, iopromide and tramadol caused adverse reactions with high frequencies. Oseltamivir showed a high frequency between 2009 and 2010 due to the influence of the new influenza A. Also, OTC drugs accounted for approximately 5% of the adverse reactions. In 2009, adverse drug reactions remarkably increased (2,106 cases; 10.1%) in infants and children due to the new influenza-A(H1N1). The patients aged between 31 and 64 accounted for approximately 55% during the given period. There was no significant intergender difference. In relation to regions, the adverse reactions most frequently occurred in the gastrointestinal system and the integumentary system for three and half years. In addition to anticancer drugs and immunosuppressive drugs that are known to cause adverse reactions frequently, not a few of OTC drugs and external preparations caused such reactions. In particular, the drugs containing specific ingredients caused adverse reactions more frequently than others from 2007 until the first half of 2010. It is advisable for prescribers to acquaint themselves with such adverse reactions and to prescribe drugs other than them. They also have need to sensibly cope with adverse drug reactions just in case they have no substitute drugs. In addition, patients also need to be trained to understand possible adverse reactions in order that they can sensibly accommodate them or choose healthcare services. The results of this study are expected to be helpful to minimize adverse drug reactions.

• Journal of Internet Computing and Services
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• v.14 no.5
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• pp.69-76
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• 2013

The incidence of globally infectious and pathogenic diseases such as H1N1 (swine flu) and Avian Influenza (AI) has recently increased. An infectious disease is a pathogen-caused disease, which can be passed from the infected person to the susceptible host. Pathogens of infectious diseases, which are bacillus, spirochaeta, rickettsia, virus, fungus, and parasite, etc., cause various symptoms such as respiratory disease, gastrointestinal disease, liver disease, and acute febrile illness. They can be spread through various means such as food, water, insect, breathing and contact with other persons. Recently, most countries around the world use a mathematical model to predict and prepare for the spread of infectious diseases. In a modern society, however, infectious diseases are spread in a fast and complicated manner because of rapid development of transportation (both ground and underground). Therefore, we do not have enough time to predict the fast spreading and complicated infectious diseases. Therefore, new system, which can prevent the spread of infectious diseases by predicting its pathway, needs to be developed. In this study, to solve this kind of problem, an integrated monitoring system, which can track and predict the pathway of infectious diseases for its realtime monitoring and control, is developed. This system is implemented based on the conventional mathematical model called by 'Susceptible-Infectious-Recovered (SIR) Model.' The proposed model has characteristics that both inter- and intra-city modes of transportation to express interpersonal contact (i.e., migration flow) are considered. They include the means of transportation such as bus, train, car and airplane. Also, modified real data according to the geographical characteristics of Korea are employed to reflect realistic circumstances of possible disease spreading in Korea. We can predict where and when vaccination needs to be performed by parameters control in this model. The simulation includes several assumptions and scenarios. Using the data of Statistics Korea, five major cities, which are assumed to have the most population migration have been chosen; Seoul, Incheon (Incheon International Airport), Gangneung, Pyeongchang and Wonju. It was assumed that the cities were connected in one network, and infectious disease was spread through denoted transportation methods only. In terms of traffic volume, daily traffic volume was obtained from Korean Statistical Information Service (KOSIS). In addition, the population of each city was acquired from Statistics Korea. Moreover, data on H1N1 (swine flu) were provided by Korea Centers for Disease Control and Prevention, and air transport statistics were obtained from Aeronautical Information Portal System. As mentioned above, daily traffic volume, population statistics, H1N1 (swine flu) and air transport statistics data have been adjusted in consideration of the current conditions in Korea and several realistic assumptions and scenarios. Three scenarios (occurrence of H1N1 in Incheon International Airport, not-vaccinated in all cities and vaccinated in Seoul and Pyeongchang respectively) were simulated, and the number of days taken for the number of the infected to reach its peak and proportion of Infectious (I) were compared. According to the simulation, the number of days was the fastest in Seoul with 37 days and the slowest in Pyeongchang with 43 days when vaccination was not considered. In terms of the proportion of I, Seoul was the highest while Pyeongchang was the lowest. When they were vaccinated in Seoul, the number of days taken for the number of the infected to reach at its peak was the fastest in Seoul with 37 days and the slowest in Pyeongchang with 43 days. In terms of the proportion of I, Gangneung was the highest while Pyeongchang was the lowest. When they were vaccinated in Pyeongchang, the number of days was the fastest in Seoul with 37 days and the slowest in Pyeongchang with 43 days. In terms of the proportion of I, Gangneung was the highest while Pyeongchang was the lowest. Based on the results above, it has been confirmed that H1N1, upon the first occurrence, is proportionally spread by the traffic volume in each city. Because the infection pathway is different by the traffic volume in each city, therefore, it is possible to come up with a preventive measurement against infectious disease by tracking and predicting its pathway through the analysis of traffic volume.