• Title/Summary/Keyword: HLA-I

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Can herbal drug(s) meet the challenges of genomewide screen results on rheumatoid arthritis

  • Paul, Bholanath
    • Advances in Traditional Medicine
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    • v.5 no.4
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    • pp.251-261
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    • 2005
  • Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. RA is characterized by chronic inflammation of the synovial membrane in the joint, which leads to the progressive destruction of articular cartilage, ligament and bone. Several cytokines such as tumor necrosis $factor-{\alpha}\;TNF-{\alpha}\;and\;interleukin-1{\beta}\;(IL-1{\beta})$ and interleukin-6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. Genome wide screening of subjects suffering from autoimmune diseases especially arthritis revealed linkage to inflammatory molecules like $TNF-{\alpha},\;IL-1{\beta}$ and IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB $(NF-{\kappa}B)$ and human leucocyte antigen/major histocompatibility complex (HLA/MHC) locus. The status of the pharmacological mechanism of herbal drugs in the light of genome wide screening results has been discussed to reinforce the therapeutic potential and the pharmacological basis of the herbal drugs.

The Effect of Gefitinib on Immune Response of Human Peripheral Blood Monocyte-Derived Dendritic Cells (인간 말초혈액 단핵구 유래 수지상세포의 면역반응에 미치는 Gefitinib의 영향)

  • Cho, Jin-Hoon;Kim, Mi-Hyun;Lee, Kwang-Ha;Kim, Ki-Uk;Jeon, Doo-Soo;Park, Hye-Kyung;Kim, Yun-Seong;Lee, Min-Ki;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.6
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    • pp.456-464
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    • 2010
  • Background: Synergistic antitumor effects of the combined chemoimmunotherapy based on dendritic cells have been reported recently. The aim of this study is to search new applicability of gefitinib into the combination treatment through the confirmation of gefitinib effects on the monocyte derived dendritic cells (moDCs); most potent antigen presenting cell (APC). Methods: Immature and mature monocyte-derived dendritic cell (im, mMoDC)s were generated from peripheral blood monocyte (PBMC) in Opti-MEM culture medium supplemented with IL-4, GM-CSF and cocktail, consisting of TNF-${\alpha}$ (10 ng/mL), IL-$1{\beta}$ (10 ng/mL), IL-6 (1,000 U/mL) and $PGE_2$ ($1{\mu}/mL$). Various concentrations of gefitinib also added on day 6 to see the influence on immature and mature MoDCs. Immunophenotyping of DCs under the gefitinib was performed by using monoclonal antibodies (CD14, CD80, CD83, CD86, HLA-ABC, HLA-DR). Supernatant IL-12 production and apoptosis of DCs was evaluated. And MLR assay with $[^3H]$-thymidine uptake assay was done. Results: Expression of CD83, MHC I were decreased in mMoDCs and MHC I was decreased in imMoDCs under gefitinib. IL-12 production from mMoDCs was decreased under $10{\mu}M$ of gefitinib sinificantly. Differences of T cell proliferation capacity were not observed in each concentration of geftinib. Conclusion: In spite of decreased expressions of some dendritic cell surface molecules and IL-12 production under $10{\mu}M$ of gefitinib, significant negative influences of gefitinib in antigen presenting capacity and T cell stimulation were not observed.

Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Daniel M. Miller
    • Korean Journal of Microbiology
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    • v.38 no.4
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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.

Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Miller, Daniel M.;Cebulla, Colleen M.;Sedmak, Daniel D.
    • Journal of Microbiology
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    • v.38 no.4
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    • pp.203-208
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    • 2000
  • 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-$\alpha$/$\beta$) 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-$\alpha$ 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.

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A Method of Integration Testing for Federation using Mock Object Patterns (모형 객체 패턴을 이용한 Federation 통합시험 방법)

  • Shim, Jun-Yong;Lee, Young-Heon;Lee, Seung-Young;Kim, Seh-Hwan
    • Journal of the Korea Society for Simulation
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    • v.20 no.4
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    • pp.41-48
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    • 2011
  • The act of writing a unit test is more an act of design than of verification. It is also more an act of documentation than of verification. The act of writing a unit test closes a remarkable number of feedback loops, the least of which is the one pertaining to verification of function. Unit testing is a fundamental practice in Extreme Programming, but most non-trivial code is difficult to test in isolation. Normal unit testing is hard because It is trying to test the code from outside. On the other hand, developing unit tests with Mock Objects leads to stronger tests and to better structure of both domain and test code. In this paper, I first describe how Mock Objects are used for unit testing of federation integration. Then I describe the benefits and costs of Mock Objects when writing unit tests and code. Finally I describe a design of Mock federate for using Mock objects.

A CASE OF NARCOLEPSY IN A 11 YEAR-OLD BOY (소아 기면증 1예)

  • Choi, Bo-Moon
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.4 no.1
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    • pp.173-178
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    • 1993
  • Narcolepsy's age at onset is reported to be relatively homogeneous, occuring usually after the onset of puberty, although most cases are diagnosed when the patients are in their late teens to late 20s. It is very unusual for a patient to develop narcolepsy before 15 years of age or after 30 years of age. A 11-year old boy who has developed excessive daytime sleepiness since age of 7 and has all the four major features of narcolepsy by the time of evaluation is presented. On polysomnographic examination, the patient showed two sleep onset REM periods in the three latency test of the multiple sleep latency test and the nocturnal polysomnogram. In addition, the findings of typing HLA class I and II of the patient's family are presented. Reports of pediatric narcolepsy previously reported are reviewed.

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Transcriptional Responses of Human Respiratory Epithelial Cells to Nontypeable Haemophilus influenzae Infection Analyzed by High Density cDNA Microarrays

  • Lee, Ji-Yeon;Lee, Na-Gyong
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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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.

Immunochemical study on the Role of ${\beta}_2$ Integrin in the Activation of Monocytes Upon Direct Contact with T Lymphocytes (T 세포 접촉에 의한 단핵구 활성화에서 ${\beta}_2$ Integrin의 역할에 관한 면역화학적 연구)

  • Lee, Suck-Cho;Lee, Ho;Oh, Kwi-Ok;Kim, Hyung-Seop
    • Journal of Periodontal and Implant Science
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    • v.29 no.2
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    • pp.333-350
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    • 1999
  • The modulation of leukocyte cell surface adhesion molecules may influence the development of cellular events that determine the course of the inflammatory process. Direct interaction between activated T cells and monocytes resulted in a large production of $IL-1{\beta}$ by monocytes. In this reactions, adhesion molecules play an important part, yet the role of them in Tmonocytes interaction remain unclear. This study was undertaken in an effort to elucidate, 1) the influence of 1.25(OH)$_2D_3-induced$ differentiation on the monocyte responsiveness to direct contact with T lymphocytes, and 2) the role of adhesion molecules on the T-monocyte direct interaction. Initially, I observed that direct contact of monocyte cell line THP-1 with stimulated fixed T cell line HuT78 markedly induces IL-1${\beta}$ production by THP-1. $IL-1{\beta}$ production was higher when THP-1 had been previously exposed to 1.25(OH)$_2D_3$ as compared to control, with ${\alpha}$- 1.25(OH)$_2D_3$ dose-dependent and exposure time-dependent manner. It was shown that 1.25(OH)$_2D_3$ also increased the expression of ${\beta}_2$ integrin adhesion receptor Mac-1(CD11b/CD18) dose- and timedependently, but did not increase the expression of human leukocyte antigen- D(HLA-D) and intercellular adhesion molecule-1(ICAM-1). The $IL-1{\beta}$ producing activity of THP-1 cells correlated well with the ability to induce the Mac-1 expression on THP-1 surface. Monoclonal antibody raised against relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibody to Mac-1 only partially blocked $IL-1{\beta}$ production by THP-1, whereas antibodies to ICAM-1 and HLA-D did not. These data indicate that regulation of Mac-1 expression on THP-1 cells can alter the responsiveness of these cells to contact by activated T cells, however other unknown structures on the THP-1 cells may be involved in this process also.

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Mycobacterium tuberculosis Derived Epitope Peptide Specific CD8+T Cell Responses in Tuberculous Pleurisy

  • Cho, Jang-Eun;Kim, Young-Sam;Park, Moo-Suk;Lee, Kyung-Wha;Lee, Eun-Hee;Cho, Sang-Nae;Cho, Sung-Ae
    • Biomedical Science Letters
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    • v.13 no.4
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    • pp.325-332
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    • 2007
  • Cell-mediated immune response (CMI) is a major immune protective mechanism against tuberculosis (TB) infection. Among several components involved in CMI, recent studies suggest that CD8+ T cells are important in controlling TB infection. In our previous report, we defined four Mycobacterium tuberculosis (MTB) derived epiotpe peptides specific for HLA-A*0201-restricted CD8+ T cells. These four peptides are $PstAl_{75-83}$, $ThyA_{30-38}$, $RpoB_{127-135}$ and $85B_{15-23}$. In this study, these epitope peptides specific CD8+ T cell responses in tuberculous pleurisy were investigated using ex vivo $IFN-\gamma$ elispot assay and intracellular $IFN-\gamma$ staining method. As a result, we observed these epitope peptide specific CD8+ T cell responses are induced in all three patients with tuberculous pleurisy suggesting that CD8+ T cells are involved in protective immune mechanism against MTB infection in tuberculous pleurisy. However, the CMI to mitogens and MTB antigens from pleural fluids of patients with tuberculous pleurisy does not seem to correlate with that from peripheral blood, although the sample size is too small to make any conclusion. In sum, the MHC I restricted CD8+ T cell responses seem to be induced efficiently in the pleural fluids, at the site of TB infection, in which the CMI is actively induced. In addition, these experiments suggest that MHC I restricted CD8+ T cell mediated immune responses are also involved in protective mechanism against MTB infection in extra-pulmonary TB.

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The Relationship between Conical Pap. Smear Findings and Related Factors for Uterine Cervical Cancer in Ullungdo Females (울릉도 여성들의 자궁경부 세포학적 검사소견과 관련요인과의 관계)

  • 윤인숙;이혜자
    • Biomedical Science Letters
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    • v.4 no.2
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    • pp.143-151
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    • 1998
  • To study the incidence and epidemiological factors of uterine cervical cancer in medical underserved area females, the questionnaire survey and Pap. smear for uterine cervical cancer was done on total 330 women who lived in Ullungdo from 5th to 12th August, 1998. The results were summarized as follows: The age distribution of subjects was 50s (24.5%), 60s (24.5%) and their educational level was “no schooling” (14.2%) and “elementary school” (42.7%). The first coital age of subjects was 19∼21yrs (30.0%), 16∼18yrs (13.9%) and the first pregnancy age was 22∼24yrs (36.7%) and 19∼21yrs (30.0%). The frequency of total pregnancy of subjects was over 5 times (52.1%). The frequency of total delivery was “3∼4 times” (35.5%) and “5∼6 times” (15.2%). 68.8% of subjects had experience of abortion and 80.0% of their husband were on the phimosis. 172 (52.1%) subjects had gynecological symptoms, their symptoms were leukorrhea (48.3%), pruritus (21.5%) and leukorrhea with pruritus (20.3%). 63.9% of total subjects have been received Pap. smear and the frequency of their Pap. smear was “only 1 time” (44.1 %), “irregularly” (30.3%) and the reason of respondents who have not been received Pap. smea. was “no specific symptom” (51.3%). Among the 330 women screened there were negative (45.8%), inflammation (47.3%), trichomoniasis and candidiasis (1.8%), atypical cells (4.5%) and dysplasia (0.6%).

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