• 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 Service
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• v.36 no.3
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• pp.163-169
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• 2013

Both of avian influenza (AI) and Newcastle disease (ND) can cause mild to severe diease in poultry. In this study, clinical signs, macro, and micro lesions were studied. Eighteen six-week-old SPF chicks were divided into 4 groups (E1, E2, E3 and C1) and housed in different rooms of the isolation facility at CAVAC (Daejeon, Korea). The control group (C1) of 3 chicks was housed separately as uninoculated. Experimental groups (E1, E2 and E3) challenged with H9N2 and/or NDV. E1 group was challenged with 0.1 mL A/Kr/Ck/01310/01 (H9N2) $10^{5.6}$ $EID_{50}$ by intranasal, E2 group was challenged with 0.5 mL Kyojeongwon (KJW) $10^{5.0}{\sim}10^{6.0}$ $ELD_{50}$ by intramuscular, and E3 group was challenged with 0.1 mL A/Kr/Ck/01310/01 $10^{5.6}$ $EID_{50}$ by intranasal and 0.5 mL KJW $10^{5.0}{\sim}10^{6.0}$ $ELD_{50}$ by intramuscular 7 days after H9N2 challenge. In clinical signs and gross findings, E1 group showed 0% mortality, anorexia, and hemorrhage of proventriculus and thymus, E2 group showed 100% mortality within 3~5 days after challenge, anorexia, green diarrhea, hemorrhage of proventriculus, proximal esophagus and thymus, enlargement of kidney, and bronze liver, and E3 group showed 100% mortality within 24~36 hours after NDV challenge, depression, anorexia, green diarrhea, hemorrhage of proventriculus, spleen, and lung, enlargement of kidney, and reduction of thymus size and number. In histopathological examination, E1 group showed depletion and necrosis in bursa of Fabricius, thymus, and spleen, and E2 and E3 group showed severe lymphocyte depletion and necrosis with destruction of lymphoid organ structures. In conclusion, co-infection of H9N2 with ND virus causes acute disease with high mortality than single infection and the pathologic lesions were more severe.

• Korean Journal of Microbiology
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• v.45 no.3
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• pp.286-290
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• 2009

The transcription of mRNA of avian influenza virus is regulated temporally during infection. Therefore, the measurement of transcript level in host cells should be performed before viral release from host cells because errors can occur in the analysis of the transcript levels if the viruses released from the infected cells re-infect cells. In this study, the timing of viral release was determined by measuring the level of viral RNA from viruses released from H9N2-infected chicken fibroblast cell line UMNSAH/DF-1 by semi-quantitative RT-PCR. The viral genomic RNA was isolated together with mouse total RNA which was added to the collected medium as carrier to monitor the viral RNA recovery and to use its GAPDH as an internal control for normalizing reverse transcription reaction as well as PCR reaction. It was found that viral release of H9N2 in the chicken fibroblast cell line UMNSAH/DF-1 took between 16 and 20 h after infection. We measured all 8 viral mRNA levels. Of the 8 transcripts, 7 species of viral mRNAs (each encoding HA, NA, PB1, PB2, NP, M, NS, respectively) except PA mRNA showed robust amplification, indicating these mRNA can be used as targets for amplification to measure transcript levels. These results altogether suggest that the method in this study can be used for screening antiviral materials against viral RNA polymerase as a therapeutic target.

• Clinical and Experimental Pediatrics
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• v.54 no.5
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• pp.207-211
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• 2011

Purpose: This study was conducted to investigate the immune responses of children with moderate and severe novel influenza A virus (H1N1) pneumonia, and to compare their clinical and immunological findings with those of control subjects. Methods: Thirty-two admitted patients with H1N1 pneumonia were enrolled in the study. The clinical profiles, humoral and cell-mediated immune responses of the 16 H1N1 pneumonia patients who were admitted to the pediatric intensive care unit (severe pneumonia group), 16 H1N1 pneumonia patients admitted to the pediatric general ward (moderate pneumonia group) and 13 control subjects (control group) were measured. Results: Total lymphocyte counts were significantly lower in patients with H1N1 pneumonia than in the control group (P=0.02). The number of CD4+ T lymphocytes was significantly lower in the severe pneumonia group ($411.5{\pm}253.5/{\mu}L$) than in the moderate pneumonia ($644.9{\pm}291.1/{\mu}L$, P=0.04) and control ($902.5{\pm}461.2/{\mu}L$, P=0.01) groups. However, the number of CD8+ T lymphocytes was significantly higher in the severe pneumonia group ($684.2{\pm}420.8/{\mu}L$) than in the moderate pneumonia ($319.7{\pm}176.6/{\mu}L$, P=0.02) and control ($407.2{\pm}309.3/{\mu}L$, P=0.03) groups. The CD4+/CD8+ T lymphocytes ratio was significantly lower in the severe pneumonia group ($0.86{\pm}0.24$) than in the moderate pneumonia ($1.57{\pm}0.41$, P=0.01) and control ($1.61{\pm}0.49$, P=0.01) groups. The serum levels of immunoglobulin G, immunoglobulin M and immunoglobulin E were significantly higher in the severe pneumonia group than in the 2 other groups. Conclusion: The results of this study suggest that increased humoral immune responses and the differences in the CD4+ and CD8+ T lymphocyte profiles, and imbalance of their ratios may be related to the severity of H1N1 pneumonia in children.

• IMMUNE NETWORK
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• v.13 no.1
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• pp.34-41
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• 2013

Interleukin-18 (IL-18) has been known to induce interferon-${\gamma}$ (IFN-${\gamma}$) production and promote Th1 immunity. Although mammalian IL-18 has been characterized in great detail, the properties and application of chicken IL-18 remain largely uninvestigated as of yet. In this study, we evaluated the immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza (AI) and Newcastle disease (ND) vaccines. After oral administration of S. enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted using the same protocol 7 days later. Humoral and cell-mediated immune responses were evaluated in terms of HI antibody titers and proliferation and mRNA expression of IFN-${\gamma}$ and IL-4 of peripheral blood mononuclear cells (PBMC) in response to specific antigen stimulation. According to our results, oral administration of S. enterica serovar Typhimurium expressing chIL-18 induced enhanced humoral and Th1-biased cell-mediated immunity against AI and ND vaccines, compared to that of chickens received S. enterica serovar Typhimurium harboring empty vector. Therefore, we conclude that our proposed vaccination regimen using inactivated AI and ND viruses along with oral administration of S. enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in protecting chicken from currently circulating AI and ND virus strains.

• Plant Breeding and Biotechnology
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• v.6 no.4
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• pp.404-412
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• 2018

The influenza neuraminidase (NA, E.C. 3.2.1.18), an antiviral, has been the target of high pharmaceutical companies due to its essential role in viral replication cycle. Perilla frutescens (P. frutescens) is used in traditional Chinese medicine for various diseases, such as cold due to wind-cold, headache and cough. In this context, four major polyphenolic compounds including rosmarinic acid-3-O-glucoside (1), rosmarinic acid (2), luteolin (3), and apigenin (4) isolated from P. frutescens were evaluated for their inhibitory effect on recombinant virus H1N1 neuraminidase (rvH1N1 NA). Among the test compounds, rosmarinic acid and luteolin inhibited the rvH1N1 NA with an $IC_{50}$ of 46.7 and $8.4{\mu}M$, respectively. The inhibition kinetics analyzed by the Dixon plots indicated that rosmarinic acid and luteolin were noncompetitive inhibitors and that the inhibition constant, $K_I$, was established as 43.9 and $14.3{\mu}M$, respectively. In addition, 578 genetically diverse accessions and 39 cultivars of P. frutescens were analyzed using HPLC to characterize the diversity of polyphenolic composition and concentration. The individual and total compositions exhibited significant difference (P < 0.05), especially rosmarinic acid which was detected as the predominant metabolite in all accessions (58.8%) and cultivars (62.8%). Yeupsil and Sangback cultivars exhibited the highest rosmarinic acid ($3,393.5{\mu}g/g$) and luteolin ($383.3{\mu}g/g$) content respectively. YCPL177-2 with the high concentration ($889.8{\mu}g/g$) of luteolin may be used as a genetic resource for breeding elite cultivars.