• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.836-843
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• 2004

Nontypeable H. influenzae (NTHi), a Gram-negative obligate human pathogen, causes pneumonia, chronic bronchitis, and otitis media, and the respiratory epithelium is the first line of defense that copes with the pathogen. In an effort to identify transcriptional responses of human respiratory epithelial cells to infection with NTHi, we examined its differential gene expression using high density cDNA microarrays. BEAS-2B human bronchial epithelial cells were exposed to NTHi for 3 hand 24 h, and the alteration of mRNA expression was analyzed using microarrays consisting of 8,170 human cDNA clones. The results indicated that approximately 2.6% of the genes present on the microarrays increased in expression over 2-fold and 3.8% of the genes decreased during the 24-h infection period. Upregulated genes included cytokines (granulocyte-macrophage colony stimulating factor 2, granulocyte chemotactic protein 2, IL-6, IL-10, IL-8), transcription factors (Kruppel-like factor 7, CCAAT/enhancer binding protein $\beta$, E2F-1, NF-$\kappa$B, cell surface molecules (CD74, ICAM-1, ICAM-2, HLA class I), as well as those involved in signal transduction and cellular transport. Selected genes were further confirmed by reverse-transcription-PCR. These data expand our knowledge of host cellular responses during NTHi infection and should provide a molecular basis for the study of host-NTHi interaction.

• Radiation Oncology Journal
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• 제12권2호
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• pp.209-217
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• 1994

목적 : 1987년 7월부터 1992년 12월까지 가톨릭의과대학 부속 성모병원 치료방사선과에서 만성골수성백혈병으로 진단되어 동종골수이식을 위한 전신방사선치료를 받은 환자 22명을 대상으로 생존율 및 재발율에 영향을 미치는 요소들을 알아보기 위하여 후향분석을 시행하였다. 대상 및 방법 : 22명중 14명은 만성기였으며 8명은 이행기 혹은 급전기였고 진단 후 골수이식까지의 기간은 4-36개월 (중간값, 8개월)이었으며, 모든 환자들은 HLA 완전일치의 동종골수이식을 위한 전처치로 화학요법과 전신방사선조사가 시행되었다. 전신방사선조사는 6예에서는 1200cGy/6 fractions/3days, 16예에서는 1320cGy/8fractions/4days로 시행되었다. 화학요법은 8명에서는 cyclophosphamide(CTX), 5명에서는 CTX과 Daunorubicin, 그리고 9명에서는 CTX과 Adriamycin이 병용되었다. 또한 골수이식전 비장이 절제된 경우는 14예였고 6예에서는 비장에 방사선조사 (250-800 cGy/2-8fractions)가 시행되었으며 2예에서는 비장 방사선조사후 비장절제술이 시행되었다. 이식편대숙주병을 예방하기 위해 4명에서는 cyclosporine A가 단독투여되었고 18명에서는 methotrexate가 추가 투여되었다. 결과 : 전체환자의 4년 생존율은 $58.8\%$였고 22명중 8명이 재발되었으며 4년 무병생존율은 $41.2\%$였다. 생존율 및 재발율, 이식편대숙주병에 있어서 환자의 성별, 연령, 진단에서 골수이식까지의 기간, 골수이식 당시의 병기, 비장상태, 골수공여자와의 성별 혹은 혈액형 일치여부, 골수 공여자의 연령, 전처치 항암제의 종류, 방사선치료방법, 이식편대숙주병의 억제를 위한 화학요법의 방법 등이 어떤 영향을 미치는지 분석한 결과 골수이식당시의 병기만이 생존율에 유의한 차이를 보였다. 또한 이식편대숙주병과 재발율 사이에도 유의한 연관성을 보이지 않았다. 결론적으로 동종골수이식을 위한 전처치 및 면역억제방법에 따라 생존율 및 재발율이 크게 다르지 않았으며 HLA 일치 혈연자중 골수공여자가 있는 만성기의 만성골수성 백혈병 관자에서 동종골수이식을 위한 전처치로서 화학요법과 함께 전신방사선 분할조사는 중요한 역할을 담당함을 알 수 있었으나 보다 많은 환자를 대상으로 한 전향적 연구가 필요할 것으로 사료된다.

• 미생물학회지
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• 제38권4호
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• pp.203-203
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• 2002

Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

• 한국시뮬레이션학회논문지
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• 제22권4호
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• pp.11-19
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• 2013

해군 무기체계 전투실험은 미래 새로운 무기체계의 소요를 창출하고 운용개념을 정립하며, 작전운용성능을 실험하고 검증할 뿐 아니라 나아가 교리발전 및 훈련에 이르기까지 폭넓게 실험을 수행하고 있다. 한국 해군은 전투실험을 효과적으로 지원할 수 있는 도구는 물론 전용의 실험 시설을 통해서 효율적, 효과적인 모의기반획득 지원환경을 구축하기 위해 노력하고 있다. 본 논문에서는 해군 전투실험의 훈련 및 전술발전 지원을 위한 C2 가상모의 연동 시뮬레이터를 개발하고 연동을 위한 아키텍처를 설계하였다. 대함전/대공전 시뮬레이션은 교전급 모델인 SADM을 이용하고 대잠전 시뮬레이션은 공학급 모델인 교전분석 시뮬레이터를 재사용하여 운용자 참여가 가능한 전투실험을 수행하였다. 전투실험을 통해 나온 결과를 분석, 훈련 전술에 반영하고 운용자 참여를 통해서 훈련 현실감을 높였다. C2 가상모의 연동 아키텍처는 전투실험 교전에 대한 연동 및 C2 훈련이 가능한 구성의 아키텍처로 설계되었다. 또한 서로 다른 운용개념의 시스템을 통합하고 연동하기 위한 아키텍처이다.

• 대한핵의학회지
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• 제35권5호
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• pp.313-323
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• 2001

목적: 저선량 방사선에 의해 그 이후의 고선량 방사선에 저항이 생기는 유익한 반응을 보인다는 방사선적응반응이라는 현상이 알려져 있지만, 저선량 방사선이 어떤 기작에 의해 이런 반응을 일으키는지에 대해서는 아직 알려지지 않고 있다. 본 연구에서는 정상 인체세포주에서 저선량 $^{99m}Tc$에 의해 방사선적응반응이 유도되는지를 확인하고, 이 때 활성화되는 유전자를 찾아보고자 하였다. 대상 및 방법: 인체 정상 림프구 세포주인 NC-37 세포주 $2{\times}10^6mL$개의 세포에 $^{99m}Tc$을 148 MBq/mL로부터 148 Bq/mL의 농도가 되도록 10배씩 희석하여 첨가하고 44시간동안 배양하였다. 결과: 각각의 군에 대해 이상 염색체를 계수하여 148 KBq/mL의 $^{99m}Tc$을 첨가한 군에서 방사선적응반응이 가장 현저하게 유도되었음을 확인하였다. 이 세포군에서 mRNA를 추출하고 여기에서 cDNA를 만든 후 gene discovery array (GDA) 여과기를 이용하여 대조군에 비해 발현이 증가된 casein kinase II beta chain, immunoglobulin, HLA-B 그리고 아직 알려지지 않은 2개의 유전자 등 6개의 유전자를 찾아내었다. Representational difference analysis (RDA)법을 통해서는 대조군에 비해 발현이 증가된 유전자 클론을 20개 찾아내었다. 결론: 인체세포주 NC-37에서 저선량의 $^{99m}Tc$에 의해 방사선적응반응이 유도된다는 사실을 밝혔으며, 이때 다수의 유전자가 발현된다는 사실을 알 수 있었다.

• IMMUNE NETWORK
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• 제4권1호
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• pp.31-37
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• 2004

Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and is shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy of these peptides we established an adoptive transfer model. $D^{b-/-}{\times}{\beta}2$ microglobulin (${\beta}2m$) null mice transgenic for a chimeric HLA-A2.1/$D^b-{\beta}2m$ single chain (HHD mice) were immunized with irradiated peptide-loaded RMA-S/HHD/B7.1 transfectants. Spleens were removed after last immunization, and splenocytes were re-stimulated in vitro. Lymphocytes from vaccinated HHD mice were transferred together with IL-2 to the tumor bearing nude mice that were challenged S.C. with the HCT/HHD/B7 colon carcinoma cell line that was found to grow in these mice. Results: Peptide 3-5 was found to be highly effective in CTL activity. Adoptively transferred anti-peptide 3-5 cytolytic T lymphocytes caused significant retardation in tumor growth. Conclusion: This study shows that peptide 3-5 can be the most effective candidate for the vaccine of adoptive immunotherapy against colon cancer.

• Journal of Ginseng Research
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• 제43권4호
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• pp.666-675
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• 2019

Background: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. Methods: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. Results: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. Conclusion: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.

• Radiation Oncology Journal
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• 제10권2호
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• pp.247-253
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• 1992

1987년 8월부터 1991년 7월까지 급성골수성 백혈병으로 가톨릭의대 치료방사선과에서 동종골수이식을 위한 전신방사선치료를 받은 22명의 환자를 대상으로 성별, 연령, 골수이식당시병기, FAB 아형, 초기말초혈액백혈구수, 항암치료방법, 방사선치료방법에 따라 2년 생존율, 2년무병생존율, 재발율과 간질성폐염 및 이식편대숙주병 (GVHD)의 발생빈도를 후향분석하였다. 22명중 12명은 제 1 완전관해기, 10명은 제 2 완전관해기이후 혹은 재발기였으며, 모든 환자들은 HLA 완전일치의 동종골수이식을 위한 전처치로 다제병용화학요법과 전신방사선조사가 시행되었다. 화학요법은 13명에서는 cyclophosphamide (60 mg/kg) 단독으로, 9명에서는 복합화학요법으로 시행되었으며 전신방사선조사는 8명에서는 850 cGy를 1일 1회로 단일조사되었고, 14명에서는 $150\~200$ cGy를 1일 2회 분할조사하여 $3\~4$일간 총 $1200\~1320$ cGy로 치료되었다. 추적관찰기간은 8개월에서 64.5개월로 중간값은 24개월이었다. 전체 환자의 2년 생존율은 $58\%$였으며 중간생존기간은 31개월이었고 평균 생존기간은 23.2개월이었다. 2년 생존율은 환자의 연령이 20세 이상인 경우가 20세 미만인 경우보다 높게 나타났으며 ($79.4\%\;vs\;14.3\%$, p=0.0008), 전신방사선치료 및 골수이식이 완전관해기에 시행된 경우가 제 2관해기 이후 혹은 재발기에 시행된 경우보다 2년 생존율이 높게 나타났다($83.3\%\;vs\;30\%$, p=0.01). 화학요법이 cyclophosphamide 단독으로 시행된 경우 병용화학요법이 시행된 경우보다 2년 생존율이 더 좋았으며 ($76.9\%\;vs\;33.3\%$, p=0.04), 전신방사선조사는 분할조사로 치료된 군에서 1일 1회 단일조사를 받은 군보다 2년 생존율이 높게 나타났다($70.7\%\;vs\;37.5\%$, p=0.05). 재발율에 있어서 FAB 아형은 유의한 차이를 보이지 않았으나, 초기말초혈액 백혈구 수는 20000/$mm^3$ 이상인 경우 이하인 경우보다 재발율이 높게 나타났다($42.9\%\;vs\;22.0\%$). 또한 방사선치료방법에 따라 재발율과 방사선폐렴 및 이식편대숙주병 빈도를 조사한 결과 분할조사시 재발율이 낮게 나타났으며 ($21.4\%\;vs\;50.0\%$), 방사선에 의한 폐렴 및 이식편대 숙주병의 빈도도 낮게 나타났다($14.3\%\;vs\;25.0\%,\;14.3\%\;vs\;50.0\%$). 이로써 HLA 일치혈연자중 골수공여자가 있는 제 1완전관해기의 급성골수성백혈병환자에서 동종골수이식을 위한 전처치로써 화학요법과 함께 전신방사선 분할조사는 중요한 역할을 담당함을 알 수 있었으나 보다 많은 환자를 대상으로 한 전향적 연구가 필요할 것으로 사료된다.

• International Journal of Stem Cells
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• 제16권4호
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• pp.425-437
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• 2023

Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68⁺/FXIII-A^- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α⁺ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.