Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data, Including Meteorological Factors and Medical Facility Resources / 예방의학회지

OBJECTIVES: This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea. METHODS: We collected and stored 660 000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul. RESULTS: Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient. CONCLUSIONS: In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks.

Regulation of anti-inflammatory cytokines IL-10 and TGF-beta in mouse dendritic cells through treatment with Clonorchis sinensis crude antigen

Dendritic cells (DCs), which are regarded as the most potent antigen-presenting cells, are involved in innate and adaptive immunity. Upon uptake of pathogens, DCs express cell surface markers and secrete cytokines. In this study, we analyzed production of cytokines and found that interleukin (IL)-10 and transforming growth factor (TGF)-beta production significantly increased in bone marrow-derived DCs and a mouse DC line, DC2.4, after treatment with crude antigen (CA) from liver fluke, Clonorchis sinensis. However, expression patterns of several activation molecules did not change. In addition, following treatment of DC2.4 cells with antigen from the lung fluke, Paragonimus westermani, production of IL-10 and TGF-beta significantly increased compared with groups treated with other parasite antigens, Spirometra erinacei plerocercoid CA and Echinococcus granulosus hydatid cystic fluid. We also found that treatment of DC2.4 cells with C. sinensis CA resulted in rapid and significant phosphorylation of extracellular signal-regulated kinase 1/2, a mitogen-activated protein kinase. Following treatment of DC2.4 cells with C. sinensis CA, treatment with an inhibitor specific to an extracellular signal-regulated kinase inhibited production of IL-10 and TGF-beta. Our results suggest that CA from C. sinensis has a role in the anti-inflammatory function of DC cells by inducing IL-10 and TGF-beta through activation of extracellular signal-regulated kinase 1/2.

In Vitro Maintenance of Clonorchis sinensis Adult Worms

Clonorchis sinensis is a biological carcinogen inducing human cholangiocarcinoma, and clonorchiasis is one of the important endemic infectious diseases in East Asia. The present study investigated survival longevity of C. sinensis adult worms in various in vitro conditions to find the best way of keeping the worms longer. The worms were maintained in 0.85% NaCl, 1xPBS, 1xLocke's solution, RPMI-1640, DMEM, and IMDM media, and in 1xLocke's solution with different supplements. All of the worms died within 3 and 7 days in 0.85% NaCl and 1xPBS, respectively, but survived up to 57 days in 1xLocke's solution. The worms lived for 106 days in DMEM, and 114 days in both RPMI-1640 and IMDM media. The survival rate in RPMI-1640 medium was the highest (50%) compared to that in DMEM (20+/-10%) and in IMDM (33.3+/-25.2%) after 3 months. The 1xLocke's solution with 0.005% bovine bile supplement showed increased duration of maximum survival from 42 days to 70 days. Higher concentration of bile supplements than 0.005% or addition of glucose were disadvantageous for the worm survival. The worms died rapidly in solutions containing L-aspartic acid, L-glutamic acid, and adenine compared to L-arginine, L-serine, and L-tryptophan. In conclusion, the 1xLocke's solution best supports the worms alive among inorganic solutions for 57 days, and the RPMI-1640 medium maintains living C. sinensis adults better and longer up to 114 days in vitro than other media.

Effects of Excretory/Secretory Products from Clonorchis sinensis and the Carcinogen Dimethylnitrosamine on the Proliferation and Cell Cycle Modulation of Human Epithelial HEK293T Cells

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.

Infection Status of Freshwater Fish with Metacercariae of Clonorchis sinensis in Korea

This study investigated freshwater fish for their current infection status with metacercariae of Clonorchis sinensis in Korea. Twenty-one species of freshwater fish (n = 677) were collected from 34 regions nationwidely from February 2007 to June 2008. They were individually examined by digestion technique. Eight species of freshwater fish from 17 different regions were recognized positive for the metacercariae of C. sinensis. The positive rates (range of metacercariae number per fish) of fish by the species were as follows: 48% (1-1,142) in Pseudorasbora parva, 60% (1-412) in Pungtungia herzi, 15.7% (1-23) in Pseudogobio esocinus, 29% (1-7) in Acheilognathus intermedia, 21% (1-4) in Odontobutis interrupta, 33% (1-6) in Zacco temmincki, 3.6% (1-4) in Zacco platypus, and 26.3% (1) in Hemibarbus labeo. The two species, P. parva and P. herzi, are able to be the index fish for estimation of C. sinensis transmission in a certain locality. Still several species of freshwater fish are briskly transmitting C. sinensis infection in many riverside areas of southern Korea.

Tissue parasitic helminthiases are prevalent at Cheongjin, North Korea

We investigated a small-scale serological survey to screen tissue-parasitic helminthiases of North Koreans as one of research programs for re-unification of Korea. Soil-transmitted helminthiases were found highly prevalent among North Korean residents at the border with China. ELISA using 4 tissue-parasitic helminth antigens was applied to 137 residents living in Cheongjin-shi, Hamgyeongbuk-do, North Korea and 133 female refugees in South Korea in 2004-2005. Among a total of 270 samples, 31 (11.5%), 25 (9.3%), and 11 (4.1%) were positive for specific IgG antibodies to antigens of Clonorchis sinensis, Taenia solium metacestode, and sparganum, respectively. The overall positive rate was 21.5%; 38.2% in males and 15.8% in females. The present finding suggests that tissue parasites, such as C. sinensis, T. solium metacestode and sparganum are highly prevalent in some limited areas of North Korea. These foodborne tissue-parasitic helminthiases should be considered for future control measures of parasitic diseases in North Korea.

Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment

A cohort was established for evaluation of cancer risk factors in Sancheong-gun, Gyeongsangnam-do, Korea. As one of the cohort studies, stools of 947 residents (403 males and 544 females, age range: 29-86 years) were screened for Clonorchis sinensis eggs using both Kato-Katz method and formalin-ether sedimentation technique. The overall egg positive rate of C. sinensis was 37.7% and individual EPG (eggs per gram of feces) counts ranged from 24 to 28,800. Eight egg positive residents voluntarily joined a process of collection of the passed worms after praziquantel treatment. A total of 158 worms were recovered from 5 of the 8 treated persons, ranged from 3 to 108 in each individual. The worms were 15-20 mm x 2-3 mm in size, and showed brown-pigmented, red, or white body colors. This is the first collection record of C. sinensis adult worms from humans through anthelmintic treatment and purgation. The adult worms of C. sinensis may be paralyzed by praziquantel and then discharged passively through bile flow in the bile duct and by peristaltic movement of the bowel.

Status of intestinal helminthic infections of borderline residents in North Korea

The present authors investigated intestinal parasitic infections among North Korean residents and refugees in China in 2003. The Kato-Katz method was applied to 236 residents and soldiers in a town on the North Korea-China border and to 46 people at a refugee camp in China. Only eggs of Ascaris and Trichuris were detected, with egg positive rates of 41.1% and 37.6%, respectively. The total egg positive rate was 55.0% and most of those who were egg positive were only lightly infected. Women of 61.2% and men of 53.1% were egg positive. The refugees from rural areas showed higher egg positive rates than those from urban areas. The present investigation confirmed high prevalence of soil-transmitted intestinal helminths in rural borderline areas of North Korea.

Immunoreactivity of CD99 in Stomach Cancer

CD99 is characteristically expressed in Ewing's sarcoma/primitive neuroectodermal tumor. Recently its immunoreactivity has also been reported in other tumors. However, the significance of CD99 isoforms expressed in these tumors has not been elucidated. In this study, we evaluated the expression of CD99 isoforms and its relationship with histopathologic parameters in gastric adenocarcinomas. Paraffin sections of 46 gastric adenocarcinomas were stained with an anti-CD99 monoclonal antibody, YG32. Twelve (26.1%) cases of 46 gastric adenocarcinomas showed immunoreactivity to YG32. The CD99 expression was also seen both in non-neoplastic foveolar epithelial cells and infiltrating lymphocytes. In addition, Western blot and RT-PCR analyses revealed that the type I is the predominant isoform of CD99 in non-neoplastic and neoplastic gastric tissues. The CD99 expression was usually seen in the intestinal type adenocarcinoma, while rarely in the diffuse type. The CD99 immunoreactivity decreased in MMP-2-overexpressing adenocarcinomas (p=0.028). Our results suggest that the type I is the major isoform of CD99 expressed in non-neoplastic gastric mucosa and gastric adenocarcinomas and its downregulation in gastric adenocarcinoma may be associated with cellular dedifferentiation and/or MMP-2 overexpression.

Effects of Exogenous Nitric Oxide on the Ischemic Damage of H9c2 Cardiac Myoblast Cells

BACKGROUND: Nitric oxide(NO) is known to have protective effects on an ischemic heart and to exert triggering effects on ischemic preconditioning. However, the effects of NO during the ischemic period have not been investigated. To investigate the role of exogenous nitric oxide in a model of ischemic heart cell death, we studied the effects of ischemic preconditioning and ischemia in a normal and an ischemic buffer. METHODS: Rat cardiac myoblast cells(H9c2) were cultured in a normal and an ischemic buffered medium. For the ischemic culture of heart cells, the cells were cultured in a dessicator with GasPak for 5 hrs. In ischemic preconditioning, the cells were pretreated with ischemic buffer for 5 min and then perfused with normal medium for 30 min. For the measurement of the cytotoxicity, a MTT(3-4-5dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay was performed. A DAPI(4',6-diamidino-2-phenylindole dihydrochloride) staining procedure and a flow cytometry analysis were performed to confirm apoptotic cell death by ischemia. RESULTS: Cell viability, as determined by using a MTT assay, showed that the preconditioned group treated with NO showed more cell death than with the not-preconditioned groups in both normal and ischemic buffers. But, In normal medium and not-preconditioned groups, NO showed protective effect according to the concentrations(100, 1000 microM) . No treatment with NO produced the different results. In normal medium, the protective effect of ischemic preconditioning was demonstrated, but no protective effect of ischemic preconditioning could be seen in the case of the ischemic buffer. The DAPI staining and flow cytometry analysis of heart cells showed characteristic apoptotic features. CONCLUSION: NO added in the ischemic phase had deterious effects on heart cells. Ischemic preconditioning was more harmful than ischemia alone. The toxicity of the cells was characteristic apoptosis.

A monoclonal antibody to cell surface antigen of human thymic epithelial cell

The cell surface molecule identified by a monoclonal antibody(TE-1) to human thymic epithelial cell showed the specificity for thymic epithelial cells of both the cortex and medulla. TE-1 reacted with the epithelial cells of normal thymus and thymoma in fresh frozen tissues. The antigen recognized by TE-1 was mostly confined to the cell surface membrane and arranged in reticular network with long processes between thymocytes. On immunohistochemical analysis, TE-1 did not recognize normal epithelial cells of the uterine cervix, skin and stomach, and neoplastic cells of squamous cell carcinoma and gastric adenocarcinoma, all of which were stained with anti-cytokeratin monoclonal antibody. Among the tumor cell lines tested with flow cytometry, most of epithelial and all of hematopoietic cell origin were not labeled with TE-1. In summary, TE-1 appears to be a monoclonal antibody against a surface antigen of human thymic epithelial cell that is immunohistologically different from known epithelial cell surface antigens reported so far.

A monoclonal antibody to common acute lymphoblastic leukemia antigen (CALLA) and its expression on several human tumor cell lines

We describe a newly-made murine monoclonal antibody to the common acute lymphoblastic leukemia antigen (CALLA), named SHB-10. The antigen detected by SHB-10 has a molecular weight of about 105 kDa. This antibody is very similar to that of conventional anti-CD10 Ab on indirect flowcytometric analysis using lymphoid malignant cell lines and peripheral lymphocytes of acute lymphoblastic leukemia (ALL) patients. The binding of anti-CD10 to Daudi cell and peripheral lymphocytes of ALL patients is blocked by SHB-10. Thus this monoclonal antibody is thought to detect the CALLA. The distribution of antigen detected by SHB-10 on several cell lines of neuroectodermal tumor and lymphoid malignancy was analysed and a slight difference in their cell surface expression is observed when compared with that by conventional anti-CD10. Further biochemical analysis is now under way for a better characterization of this antigen.

Requirements for in vitro growth of human thymocytes

Since it is difficult to study human thymocyte maturation in vitro, we have developed an in vitro thymocyte culture system which has allowed us to select the optimal growth conditions for thymocyte subpopulations. Three thymocyte subpopulations (CD3-CD1-, CD1+CD3-, and CD3+CD1-) were isolated by a single step percoll density gradient centrifugation and indirect panning procedure using anti-CD1 and anti-CD3 monoclonal antibodies, and their purity was checked by flow cytometry. The combination of concanavalin A (Con A), tetradecanoylphorbol acetate (TPA), and IL-2 was shown to be the most reliable stimulus for the proliferation of CD3-CD1- thymocytes for up to 15 days in a culture system in vitro. Flow cytometric analysis for the phenotypic change of CD3-CD1- thymocytes revealed a steady increase of CD3 antigen after a 3-day cultivation, whereas there was no change in CD1 antigen intensity. A combination of Con A and IL-2 was both sufficient and necessary to induce growth of CD3+CD1- thymocytes. The major population of immature cortical thymocytes (CD3-CD1+ or CD3+CD1+), which are considered to be the most unresponsive dead-end cells, could not be maintained or stimulated with any combination used in this experiment, even in the presence of thymic accessory cells.