• The Korean Journal of Physiology and Pharmacology
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• v.13 no.1
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• pp.55-59
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• 2009

Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor($h{\alpha}4{\beta}2$ and $h{\alpha}3{\beta}4$) agonists was studied using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA). From 11 CoMFA and CoMSIA models, CoMSIA with steric and electrostatic fields gave the best predictive models($q^2=0.926$ and 0.945, ${r^2}_{ncv}=0.983$ and 0.988). This study can be used to develop potent $h{\alpha}4{\beta}2$ receptor agonists with low activity on $h{\alpha}3{\beta}4$ subtype.

• Tuberculosis and Respiratory Diseases
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• v.69 no.1
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• pp.24-30
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• 2010

Background: A novel 2009 influenza A (H1N1) virus emerged and disseminated to all over the world. There are few reports on the clinical characteristics of patients with complications. We describe the clinical features of pneumonia in adult patients hospitalized, who have novel influenza infection. Methods: There were 43 adult patients enrolled into the study with pneumonia of 528 hospitalized patients confirmed influenza A (H1N1) virus infection by real-time reverse transcriptase polymerase chain reaction testing, between 24 August 2009 and 31 January 2010. The clinical data of patients with pneumonia were collected retrospectively. Results: There were 22 of 43 (51.2%) influenza patients with pneumonia that had higher risk factors for complications. Compared to 28 patients with influenza A (H1N1) viral pneumonia and 15 patients, who had isolated bacteria from cultures, those with mixed viral and bacterial pneumonia were significantly more likely to have unilobar consolidations on chest radiographs (53.3 vs. 10.7%, p<0.01) and higher scores of pneumonia severity index (PSI; 90 [66~100] vs. 53 [28~90], p=0.04). Six patients required mechanical ventilation support in an Intensive Care Unit and were more likely to have dyspnea (83.3 vs. 29.3%, p=0.02) and low levels of $PaO_2$ (48.3 [37.0~70.5] vs 64.0 [60.0~74.5] mm Hg, p=0.02) and high levels of pneumonia severity index (PSI) score (108.0 [74.5~142.8] vs. 56.0 [40.5~91.0], p=0.03). Conclusion: The majority of pneumonia patients infected with novel influenza improved. Chest radiographic findings of unilobar consolidations suggest that mixed pneumonia is more likely. Initial dyspnea, hypoxemia, and high levels of PSI score are associated with undergoing mechanical ventilation support.

• Tuberculosis and Respiratory Diseases
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• v.72 no.6
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• pp.493-500
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• 2012

Background: This study investigated the clinical characteristics and risk factors of the severity of pandemic influenza A (H1N1) 2009 infection in pediatric patients in Busan and Gyeongsangnam-do. Methods: Cases of influenza A (H1N1) 2009 in patients under the age of 18 years, confirmed by reverse transcription polymerase chain reaction, at Pusan National University Hospital and Pusan National University Yangsan Hospital from the last week of August 2009 through the last week of February 2010 were retrospectively analyzed. Results: Of the 3,777 confirmed cases of influenza A (H1N1) 2009, 2,200 (58.2%) were male and 1,577 (41.8%) were female. The average age of the patients was $8.4{\pm}4.8$ years. The total cases peaked during 44th to 46th week. Most of the patients were in the 5- to 9-year-old age group. Oseltamivir was administered to 2,959 (78.3%) of the patients. 221 patients (5.9%) were hospitalized, age an average of $6.7{\pm}4.5$ years. The average duration of hospitalization was $7.4{\pm}5.6$ days. One hundred cases (45.2%) had pneumonia. Risk factors for hospitalization included male gender, <2 years of age, and underlying disease. Children with asthma were at very high risk of hospitalization, over 20 times the non-asthmatic children (odds ratio [OR], 21.684; confidence interval [CI], 13.295~39.791). Likewise the children with neurologic deficits faced a 16 times higher risk (OR, 15.738; CI, 7.961~31.111). Ten of the patients (4.5%) were admitted to the intensive care unit, and eight (3.6%) required mechanical ventilation. Conclusion: Of the pediatric patients with pandemic influenza A (H1N1) 2009, most of the patients were in the 5- to 9-year-old age group. Risk factors for hospitalization included male gender, <2 years of age, and underlying disease. The most common complication was pneumonia. The very high risk of severe morbidity in children with asthma or neurologic disease shows the critical importance of targeted vaccine coverage, special awareness and swift care by both guardians and primary care providers.

• Tuberculosis and Respiratory Diseases
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• v.68 no.3
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• pp.162-167
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• 2010

Background: To date, there are few data on the risk factors for severe cases and deaths associated with the 2009 pandemic H1N1 influenza A. Here, we describe the clinical and epidemiologic characteristics of patients hospitalized for pneumonia and identify those factors associated with the development of major complications (MC). Methods: We reviewed the medical records of 41 cases of pneumonia admitted to a university-affiliated tertiary hospital between Aug 26 and Dec 10, 2009, and who had confirmed H1N1 influenza A based on real-time reverse transcriptase-polymerase-chain-reaction assay. There were 7,962 patients that fit these criteria. We compared the clinical features and demographic characteristics of patients who developed MC to with those who did not develop MC. Results: During the study period, 10 patients developed MC (required admission to the intensive care unit, n=10; required ventilator therapy, n=6; death, n=4). Patients with MC were significantly older than those without MC and more frequently had underlying medical conditions (90.0% vs 41.9%, p-value <0.01). In the patients with developed MC, the median $PaO_2/FiO_2$ ratio of 230.0 (145.0~347.3) at admission and pneumonia severity index (PSI) score of 141.5 (88.3~158.5) were higher than patients without MC. However, no differences were observed in laboratory findings or in viral shedding between the 2 groups. Conclusion: In hospitalized pneumonia patients of 2009 H1N1 influenza, old age, a history of malignancy, initial hypoxemia, $PaO_2/FiO_2$ ratio, and PSI score appear to be risk factor significantly related to developing MC. These findings might be the basis to influence strategies for admitting patients to an intensive or intermediate care unit and for pre-emptive antiviral therapy.

• Korean Journal of Veterinary Research
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• v.52 no.4
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• pp.223-230
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• 2012

The worldwide distribution and continuing genetic mutation of avian influenza virus (AIV) has been posed a great threat to human and animal health. A comparison of 3 isolates of AIV H9N2, A/chicken/Korea/KBNP-0028/00 (H9N2) (KBNP-0028), A/chicken/Korea/SNU8011/08 (H9N2) (SNU 8011) and an inactivated oil vaccine strain A/chicken/Korea/01310/01 (H9N2) (01310), was performed. The former 2 AIVs were isolated from field cases before and after the application of an inactivated H9N2 vaccine in 2007, respectively. The antigenic relationship, viral shedding, tissue tropism and genetic analysis were examined. The comparison of virus shedding from the cloaca and the oropharynx revealed that both isolates were more frequently isolated from the upper respiratory tract (90~100%) 1 day post inoculation (DPI) compared with isolation 5 DPI from gastrointestinal tracts (10~60%). Moreover, the isolate KBNP-0028 were recovered from all organs including bone marrow, brain and kidneys, indicating higher ability for broad tissue dissemination than that of SNU 8011. KBNP-0028 replicated earlier than other strains and with a higher titer than SNU 8011. In full-length nucleotide sequences of the NA gene and a partial sequence of the HA gene of SNU 8011, we found that there might be significant changes in tissue tropism, virus replication and genetic mutation in AIV H9N2 isolates.

• Korean Journal of Veterinary Service
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• v.38 no.2
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• pp.107-116
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• 2015

In this study, we developed a rapid, sensitive and specific reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for detection of swine influenza viruse (SIV) including major subtypes of swine influenza viruses H1N1, H1N2 and H3N2, and a novel subtype of influenza A virus that accidentally infected in pig population. The RT-LAMP was completed in 40 min at $58^{\circ}C$ and the sensitivity of the RT-LAMP ($1copy/{\mu}L$) was 10-fold higher than conventional reverse transcription-polymerase chain reaction (RT-PCR) ($10copy/{\mu}L$) and the same to real time RT-PCR ($1copy/{\mu}L$). Also, the result of the RT-LAMP can be confirmed without any detection system. Therefore, the RT-LAMP could be a alternative diagnostic method for SIV detection in national SIV monitoring system and clinical diagnostic laboratory in the future.

• Korean Journal of Poultry Science
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• v.31 no.2
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• pp.119-128
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• 2004

Highly Pathogenic Avian Influenza (HPAI) is a very acute systemic disease in poultry, particularly in chickens and turkeys caused by HPAI viruses. An outbreak of HPAI caused by subtype H5N1, was first reported in a broiler breeder farm on December 10, 2003 in Korea, although there had been twenty one outbreaks of the disease reported in the world before. Since mid-December 2003, eight Asian countries have confirmed outbreaks of HPAI due to the same subtype. The outbreak has also resulted in at least twenty three fatal human cases in Vietnam and Thailand as of May 17, 2004 according to the WHO. Regarding the first outbreak of recent Asian HPAI, it has been suspected that some Asian countries with the exception of Korea and Japan veiled the fact of HPAI outbreaks since the last half of 2003, even though it was first reported in Korea. There have been total nineteen outbreaks of HPAI among chicken and duck farms in 10 provinces in Korea since Dec. 2003 and approximately 5,280,000 birds were slaughtered from 392 farms for eradication of the disease and preemptive culling. The origin of the H5Nl HPAI virus introduced into the country are unknown and still under epidemiological investigation. Current status of outbreaks and characteristics of HPAI will be reviewed and discussed on the basis of genetic, virological, clinicopathological, and ecological aspect, as well as future measures for surveillance and prevention of the disease in Korea.

• Tuberculosis and Respiratory Diseases
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• v.69 no.2
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• pp.103-107
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• 2010

Background: The aim of the present study was to evaluate whether findings on initial chest computed tomography (CT) of influenza pneumonia can help predict clinical outcome. Methods: We reviewed all adult patients admitted to the Emergency Department (ED) with a confirmed diagnosis of novel influenza A H1N1 virus (2009 H1N1) pneumonia, who underwent chest CT upon admission between Aug 26, 2009 and Jan 31, 2010. Radiologic findings were characterized by type and pattern of opacities and zonal distribution. Clinical outcome measures were intensive care unit (ICU) admission, mechanical ventilation, and inhospital death. Results: Of 59 patients diagnosed with 2009 H1N1 pneumonia, 41 (69.5%) underwent chest CT on admission into ED. Nine (22%) of these patients developed adverse clinical outcomes requiring the following treatments: 9 (22.0%) ICU admissions, 5 (12.2%) mechanical ventilation, and 3 (7.3%) inhospital deaths. Counting the number of patients with more than 4 involved lobes, the sensitivity, specificity, positive predictive value, and negative predictive value for detection of adverse clinical outcome were 67%, 84%, 55% and 80%, respectively. Conclusion: Extensive involvement of both lungs (over 4 lobes) is related to ICU admission, mechanical ventilation, and inhospital death. Initial chest CT may help predict an adverse clinical outcome of patients with 2009 H1N1 influenza pneumonia.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.08a
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• pp.273-273
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• 2013

Recently, Point-of-care (POC) testing microdevices enable to do the patient monitoring, drug screening, pathogen detection in the outside of hospital. Immunochromatographic strip (ICS) is one of the diagnostic technologies which are widely applied to POC detection. Relatively low cost, simplicity to use, easy interpretations of the diagnostic results and high stability under any circumstances are representative advantages of POC diagnosis. It would provide colorimetric results more conveniently, if the genetic analysis microsystem incorporates the ICS as a detector part. In this work, we develop a reverse transcriptase-polymerase chain reaction (RT-PCR) microfluidic device integrated with a ROSGENE strip for colorimetric influenza H1N1 virus detection. The integrated RT-PCR- ROSGENE device is consist of four functional units which are a pneumatic micropump for sample loading, 2 ${\mu}L$ volume RT-PCR chamber for target gene amplification, a resistance temperature detector (RTD) electrode for temperature control, and a ROSGENE strip for target gene detection. The device was fabricated by combining four layers: First wafer is for RTD microfabrication, the second wafer is for PCR chamber at the bottom and micropump channel on the top, the third is the monolithic PDMS, and the fourth is the manifold for micropump operation. The RT-PCR was performed with subtype specific forward and reverse primers which were labeled with Texas-red, serving as a fluorescent hapten. A biotin-dUTP was used to insert biotin moieties in the PCR amplicons, during the RT-PCR. The RT-PCR amplicons were loaded in the sample application area, and they were conjugated with Au NP-labeled hapten-antibody. The test band embedded with streptavidins captures the biotin labeled amplicons and we can see violet colorimetric signals if the target gene was amplified with the control line. The off-chip RT-PCR amplicons of the influenza H1N1 virus were analyzed with a ROSGENE strip in comparison with an agarose gel electrophoresis. The intensities of test line was proportional to the template quantity and the detection sensitivity of the strip was better than that of the agarose gel. The test band of the ROSGENE strip could be observed with only 10 copies of a RNA template by the naked eyes. For the on-chip RT-PCR-ROSGENE experiments, a RT-PCR cocktail was injected into the chamber from the inlet reservoir to the waste outlet by the micro-pump actuation. After filling without bubbles inside the chamber, a RT-PCR thermal cycling was executed for 2 hours with all the microvalves closed to isolate the PCR chamber. After thermal cycling, the RT-PCR product was delivered to the attached ROSGENE strip through the outlet reservoir. After dropping 40 ${\mu}L$ of an eluant buffer at the end of the strip, the violet test line was detected as a H1N1 virus indicator, while the negative experiment only revealed a control line and while the positive experiment a control and a test line was appeared.

• Animal Bioscience
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• v.35 no.3
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• pp.367-376
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• 2022

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection. Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx dynamin like GTPase (Mx) and major histocompatibility complex class I antigen BF2 genes. These chickens were then infected with influenza A virus subtype H5N1, and their lung tissues were collected for RNA sequencing. Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the gene ontology and Kyoto encyclopedia of genes and genomes pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and IL-18), chemokines (C-C Motif chemokine ligand 4 [CCL4] and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, 2'-5'-oligoadenylate synthase-like, and protein kinase R) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens. Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.