• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.98-108
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• 1994

The etiology and pathophysiology of schizophrenia remain unknown. It has been postulated that infectious-autoimmune process may play a role in the pathogenesis of symptoms in some schizophrenic patients. Findings of altered interleukin(IL) regulation have been regarded as additional proof that schzophrenia has an infectious-autoimmune background. In the present study, we measured mitogen-stimulated production of and serum level of IL-$1{\beta}$, IL-2, IL-6 using ELISA in 16 neuroleptic-free schizophrenic patients and in 16 age, sex matched healthy controls. The results were as follows : 1) There was a significant decrease of IL-2 production in schizophrenic patients than in normal controls(respectively $1.90{\pm}0.13ng/m{\ell}$, $2.79{\pm}0.14ng/m{\ell}$, p<0.001). But there was no significant difference of IL-$1{\beta}$ production and IL-6 production between schizophrenic patients and normal controls. 2) There was a significant increase of serum level of IL-2 in schizophrenic pateitns than in normal controls(respectively $184.8{\pm}12.8pg/m{\ell}$, $104.2{\pm}34.2pg/m{\ell}$, p<0.01). Serum level of IL-$1{\beta}$ was partially detected in both groups and serum level of IL-6 was not detected in both groups. 3) There was no significant differences of IL-$1{\beta}$, -2, -6 production & serum level of IL-2 according to male vs female, paranoid type vs undifferentiated type, drug-naive group vs drug-free group in schizophrenic patients. 4) There was significant correlation between IL-$1{\beta}$ and IL-6 production(r=0.86, p<0.001). No correlation between IL-$1{\beta}$, -2, -6 production, serum level of IL-2 and age, duration of illness, and BPRS score was found. It has been suggested that the low lymphocyte production of IL-2 in the patients with autoimmune disease occurs because the T cells are activated and lymphocyte-derived IL-2 has been released into the serum. The authors suggest that decreased IL-2 production in our schizophrenic patients is due to increased IL-2 serum level in those patients. Thus our finding of low IL-2 production and high serum level of IL-2 in our schizophrenic patients is compatible with the possibility that our patients have an autoimmune process. Further study on relationship between IL alteration and other immunological abnormalities(the presence of serum autoantibody and of anti-brain antibody, $CD4^+$, $CD8^+$ cell index, etc) in schizophrenic patients will be warranted.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.6
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• pp.474-481
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• 2004

Squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its low survival rate, high malignancy, mortality with facial defects, and poor prognosis. Exact cause and pathogenesis of the squamous cell carcinoma is still unknown. Various routes including smoking, radiation, and viral infections predispose its genesis, and recent studies revealed that genetic defects which fail to prevent cancer proliferation play a role. Generally, a cancer develops from the decreased rate of apoptosis which is an active and voluntary cell death, and from the altered cell cycles. Anticancer effect can be obtained by recovering the apoptotic process, and by suppressing the cell cycles. Among the apoptosis related factors, bcl-2, caspase-9, and VDAC (voltage-dependent anion channel)are produced in mitochondria of the cell. Cyclosporin-A is known to induce apoptosis through its activation with VDAC. This study was to reveal the anticancer effect of Cyclosporin A to the oral squamous cell carcinoma. The inverted microscope was used to find alterations in the tissue, and sensitivity test to the anticancer cells was performed with MTT (Tetrazolium-based colorimetric) assay. Following cell line culture of primary and metastastic oral squamous cell carcinoma, electrophoresis was performed with extracted total RNA. Finally, semi-quantitative study was carried out through RT-PCR (Reverse Transcription-Polymerase Chain Reaction). The results of this study are as follows: 1. The inverted microscopic observation revealed a poorly defined cytoplasm at $2000ng{\sim}3000ng/ml$, indistinct nucleus, and apoptosis. 2. The Growth of cancer cells was decreased at 1000ng/ml of cyclosporin-A. No cancer cell growth was observed at over 2000ng/ml concentration of cyclosporin-A, and at one week, growth of cancer cells was ceased. 3. The MTT assays were decreased as cyclosporin-A concentration was increased. This means that the activation of succinyl dehydrogenase in mitochondria was decreased following administration of cyclosporin A. 4. A result of RT-PCR showed that amount of mRNA of VDAC-2 was decreased half times at a cyclosporine-A concentration of 2000ng/ml. In bcl-2, amount of mRNA was significantly decreased 1/5 times at 2000ng/ml. caspase-9, however, showed slight increase compared to the control group. From the results obtained in this study, administration of cyclosporin-A to the cell lines of oral squamous cell carcinoma induced alterations in morphology and growth of the cells as its concentration increased. Since apoptosis related factors such as VDAS-2, bcl-2, and caspase-9 also showed distinct alterations on their mRNAs, further research on cyclosporin A as an anti-cancer agent will be feasible.

• Journal of Microbiology and Biotechnology
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• v.21 no.4
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• pp.366-373
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• 2011

We characterized the proteomes of murine N2a cells following infection with three rabies virus (RV) strains, characterized by distinct virulence phenotypes (i.e., virulent BD06, fixed CVS-11, and attenuated SRV9 strains), and identified 35 changes to protein expression using two-dimensional gel electrophoresis in whole-cell lysates. The annotated functions of these proteins are involved in various cytoskeletal, signal transduction, stress response, and metabolic processes. Specifically, a-enolase, prx-4, vimentin, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and prx-6 were significantly up-regulated, whereas Trx like-1 and galectin-1 were down-regulated following infection of N2a cells with all three rabies virus strains. However, comparing expressions of all 35 proteins affected between BD06-, CVS-11-, and SRV9-infected cells, specific changes in expression were also observed. The up-regulation of vimentin, CIAPIN1, prx-4, and 14-3-3 ${\theta}/{\delta}$, and down-regulation of NDPK-B and HSP-1 with CVS and SRV9 infection were ${\geq}2$ times greater than with BD06. Meanwhile, Zfp12 protein, splicing factor, and arginine/serine-rich 1 were unaltered in the cells infected with BD06 and CVS-11, but were up-regulated in the group infected with SRV9. The proteomic alterations described here may suggest that these changes to protein expression correlate with the rabies virus' adaptability and virulence in N2a cells, and hence provides new clues as to the response of N2a host cells to rabies virus infections, and may also aid in uncovering new pathways in these cells that are involved in rabies infections. Further characterization of the functions of the affected proteins may contribute to our understanding of the mechanisms of RV infection and pathogenesis.

• Korean Journal of Veterinary Research
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• v.42 no.1
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• pp.89-100
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• 2002

The nonstructural glycoprotein NSP4, encoded by the 10th gene of rotavirus, has been known to play important roles in viral assembly and pathogenesis. The NSP4 genes of human rotavirus Korean isolates, designated as CBNU/HR-1, CBNU/HR-2, CBNU/HR-3, and CBNU/HR-4, were cloned, sequenced and characterized. Also, the NSP4 gene of the CBNU/HR-1 was expressed in a baculovirus-insect cell system. The sequence data indicated that the NSP4 genes of human rotavirus Korean isolates were 750 or 751 bases in length and encoded one open reading frame of 175 amino acids. Two glycosylation sites were recognized in the NSP4 gene of human rotavirus isolates tested. The NSP4 of CBNU/HR-1, CBNU/HR-3, and CBNU/HR-4 exhibited a high degree of amino acid sequence homology with that of NSP4 genotype B viruses, but a low degree of amino acid sequence homology with that of NSP4 genotype A viruses. However, the NSP4 of CBNU/HR-2 exhibited a high degree of amino acid sequence homology with that of NSP4 genotype A viruses, but a low degree of amino acid sequence homology with that of NSP4 genotype B viruses. The Sf9 cells infected with recombinant baculovirus, inserted with NSP4 gene of CBNU/HR-1, produced specific cytopathic effects and the expressed NSP4 was detected by immunofluorescence staining using NSP4-specific monoclonal antibody(MAb). The expressed NSP4 migrated at 16-26 kDa on SDS-PAGE and reacted with NSP4-specific MAb by Western blotting.

• Journal of Digital Convergence
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• v.18 no.12
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• pp.425-434
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• 2020

Background: Viral infection outbreaks are emerging public health concerns. They often exhibit seasonal patterns that could be predicted by the application of big data and bioinformatic analyses. Purpose: The purpose of this study was to identify trends in diarrhea-causing viruses such as rotavirus (Gr.A), norovirus G-I, and norovirus G-II in Cheonan, Korea. The identified related factors of diarrhea-causing viruses may be used to predict their trend and prevent their infections. Method: A retrospective analysis of 4,009 fecal samples from June 2010 to December 2019 was carried out at Dankook University Hospital in Cheonan. Reverse transcription-PCR (RT-PCR) was employed to identify virus strains. Information about seasonal patterns of infection was extracted and compared with local weather data. Results: Out of the 4,009 fecal samples tested using multiplex RT-PCR (mRT-PCR), 985 were positive for infection with Gr.A, G-I, and G-II. Out of these 985 cases, 95.3% (n = 939) were under 10 years of age. Gr.A, G-I, and G-II showed high infection rates in patients under 10 years of age. Student's t-test showed a significant correlation between the detection rate of Gr.A and the relative humidity. The detection rate of G-II significantly correlated with wind-chill temperature. Conclusion: Climate factors differentially modulate rotavirus and norovirus infection patterns. These observations provide novel insights into the seasonal impact on the pathogenesis of Gr.A, G-I, and G-II.

• Journal of Life Science
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• v.30 no.3
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• pp.285-290
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• 2020

Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.55-66
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• 1998

Pathophysiological mechanism of hemorrhagic fever with renal syndrome (HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla shows focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at the injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known to be good host cells for the hantaan virus. It is possible that not only the endothelial cell but also the fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are adhesion molecules, and act as receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The ${\alpha}_5{\beta}_1$ integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of ${\alpha}_5{\beta}_1$ integrin in the infection of Hantaan virus was examined by using anti-${\alpha}_5{\beta}_1$, integrin, anti-${\alpha}_5$ integrin and anti-${\beta}_1$, integrin antibodies in chicken embryo fibroblasts (CEF) and Mongolian gerbil fibroblasts(MGF). The treatment of anti-${\alpha}_5{\beta}_1$, integrin antibody in CEF reduced the virion titers 26.8% and the amount of nucleocapsid N protein 32.6% when compared with control CEF. When MGF were treated with anti-${\alpha}_5$, anti-${\beta}_1$ and anti-${\alpha}_5{\beta}_1$ integrin antibodies, virion titers were reduced by 26.5%, 29.4% and 28.7% and the amount of nucleocapsid N protein were reduced by 65.2%, 59.7% and 72.6%. These results suggested that ${\alpha}_5{\beta}_1$ integrin might act as a receptor for the Hantaan virus or blocking of ${\alpha}_5{\beta}_1$ integrin influences on the viral replication in CEF and MGF. It is also possible that the blocking of only one subunit of integrin represents similar results in that of whole molecule.

• Tuberculosis and Respiratory Diseases
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• v.85 no.1
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• pp.37-46
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• 2022

Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma-COPD (ACO) and pure COPD was performed. Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion: Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.58-66
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• 1995

Background: Acute interstitial pneumonia is a relatively rare form of interstitial pneumonia, since the vast majority of interstitial pneumonia have a more chronic course. It corresponds to the lesion described by Hamman and Rich, as Hamman-Rich disease in 1944. Another name in the clinical literature is accelerated interstitial pneumonia, idiopathic acute respiratory distress syndrome (idiopathic ARDS), and the organizing stage of diffuse alveolar damage. Acute interstitial pneumonia differs from chronic interstitial pneumonia by clinical and pathologic features. Clinically, this disease is characterized by a sudden onset and a rapid course, and reversible disease. Method and Purpose: Five cases of pathologically proven acute interstitial pneumonia were retrospectively studied to define the clinical, radiologic, and pathologic features. Results: 1) The five cases ranged in age from 31 to 77 years old. The onset of illness was acute in all patients, it began with viral-like prodrome 6~40 days prior to shortness of breath, and respiratory failure eventually developed in all patients. In 2 cases, generalized skin rash was accompanied with flu-like symptoms. Etiologic agent could not be identified in any case. 2) All patients had leukocytosis and severe hypoxemia. Pulmonary function test of 3 available cases shows restrictive ventilatory defect, and one survived patient(case 5) has a complete improvement of pulmonary function after dismissal. 3) Diffuse bilateral chest infiltrates were present radiologically. Theses were the ground-glass, consolidation, and reticular densities without honeycomb fibrosis in all patients. The pathologic abnormalities were the presence of increased numbers of macrophages and the formation of hyaline membranes within alveolar spaces. There was also interstitial thickening with edema, proliferation of immature fibroblast, and hyperplasia of type II pneumocyte. In the survived patient(case5), pathologic findings were relatively early stage of acute interstitial pneumonia, such as hyaline membrane with mild interstitial fibrosis. 4) Of the 5 patients, four patients died of respiratory failure 14~90 days after onset of first symptom, and one survived and recovered in symptoms, chest X ray, and pulmonary function test Conclusion: These results emphasize that acute interstitial pneumonia is clinically, radiologically, and pathologically distinct form of interstitial pneumonia and should be separated from the group of chronic interstitial pneumonia. Further studies will be needed to evaluate the pathogenesis and the treatment of acute interstitial pneumonia.