• Title/Summary/Keyword: Mononuclear

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A Case of Methotrexate Induced Pneumonitis in a Patient with Rheumatoid Arthritis (류마티스 관절염 환자에서 Methotrexate에 의해 발생한 간질성 폐렴 1예)

  • Park, Chan Seok;Lee, Sang Haak;Shim, Kon Ho;Kim, Wan Uk;Lee, Sook Young;Kim, Seok Chan;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.273-277
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    • 2004
  • Methotrexate is commonly used in rheumatoid arthritis as an anti-inflammatory agent, but treatment with methotrexate can lead to severe side effects, especially pulmonary complication. Interstitial pneumonitis is one of the most important pulmonary adverse effects of methotrexate and most patient present with a subacute febrile illness and peripheral eosinophilia is seen in about a half of patients. Almost all patients have abnormal chest roentgenograms and bibasilar interstitial infiltration with alveolar pulmonary consolidations is the most characteristic finding. Interstitial inflammation with mononuclear cell infiltration is a characteristic pathologic feature and findings that suggest acute hypersensitivity pneumonitis, such as bronchiolitis, granuloma formation with giant cells, and infiltration with eosinophils are often present. Methotrexate-induced pneumonitis is a potentially life threatening and unpredictable complication but it is difficult to make a definite diagnosis in the absence of high index of clinical suspicion. Early recognition and appropriate management may avoid the serious outcome. Herein we report a case of methotrexate-induced pneumonitis in a patient with rheumatoid arthritis.

M. tuberculosis Somatic Antigen Specific CD8+T cell Responses in BCG-Vaccinated Subjects (BCG 예방접종을 받은 개체에서 유도되어 있는 결핵균 균체항원에 특정한 CD8+T 세포의 보호 면역반응)

  • Cho, Jang-Eun;Cho, Sang-Nae;Lee, Kyung Wha;Park, Seung Kyu;Cho, Sungae
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.3
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    • pp.272-278
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    • 2005
  • Background : The immune responses mediated by CD8+T cells are known to be significant in controlling M. tuberculosis infections. In order to determine the role of cytotoxic CD8+T cells in the protective immune mechanism in latently infected subjects, this study examined whether or not the cytotoxic immune responses of CD8+T cells specific to the M. tuberculosis somatic antigens are induced in BCG vaccinated healthy subjects. Methods : Cytotoxicity and $IFN-{\gamma}$ elispot assays were used to investigate the activities of CD8+T cells specific for the $thyA_{30-38}$ peptide epitope in circulating peripheral blood mononuclear cells (PBMC) from BCG-vaccinated HLA-A*0201 and A*0206 subjects. Results : The results indicate the cytotoxic and $IFN-{\gamma}$ immune responses of CD8+T cells specific for $thyA_{30-38}$ were induced in BCG vaccinated healthy subjects. Conclusion : The cytotoxic and $IFN-{\gamma}$ responses by CD8+T cells specific for the M. tuberculosis somatic antigens are induced in BCG-vaccinated subjects, and appear to be involved in the protective immune mechanism in latently infected people against a M. tuberculosis infection.

Effects of Concurrent Administration of JaUmJeSeupTangKaKam(JUJSTK) and Atopy Cream, Jawoongo(AJ) on Atopic Dermatitis-like Skin Lesions in NC/Nga Mouse (아토피양(樣)피부염 NC/Nga 생쥐에서 자음제습탕가감(滋陰除濕湯加減)과 아토피 크림-자운고(紫雲膏)의 병용투여가 피부염에 미치는 영향)

  • Lee, Nam-Yerl;Kim, Yun-Hee;Han, Jae-Kyung
    • The Journal of Pediatrics of Korean Medicine
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    • v.23 no.3
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    • pp.9-36
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    • 2009
  • Objectives The purpose of this study is to examine the effect of a concurrent administration of JUJSTK and AJ on atopic dermatitis in an in-vivo experiment. Thus, this study is expressed by using NC/Nga atopic dermatitis mice which have histological and clinical similarities to that of humans have been used. Methods Clinical skin score, hematology, serum total IgE and IgG1 of the mouse was evaluated, and cytokine levels, total number of the cells, immunohistochemical staining, histological features of axillary lymph node(ALN), peripheral blood mononuclear cells(PBMCs), and a dorsal skin tissue of the mouse were analyzed. Results Oral administration of JUJSTK and concurrent administration of JUJSTK and AJ lowered the clinical skin score, total cell number of WBC, eosinophils in blood, and serum total of IgE & IgG1, IFN-$\gamma$, IL-5, IL-13, IL-17. In addition, total cell number of ALN and dorsal skin tissue, absolute cell number of $CD3e^+$ T cell, $CD4^+$ Th cell, $CD8^+$ c/sT cell, $CD3^+CCR3^+$ cell, $CCR3^+$ cell, $CD3^+CD69^+$, $CD4^+CXCR5^+$ in ALN, PBMCs, absolute cell number of $CCR3^+$, $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$, $CD11b^+/Gr-1^+$ in dorsal skin tissue, Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue and gene expression of IL-5 mRNA, IL-13 mRNA in ALN were significantly decreased. Furthermore, thickness of epidermis infiltrated inflammatory immune cell & mast cell in dermis, histological infiltration of mast cell, the size of inflammatory lymphocytes cells & plasma cells in ALN and histological infiltration of $CD4^+$ & $CCR3^+$ in ALN and dorsal skin tissue were significantly decreased as well. Conclusions Concurrent administration of JUJSTK and AJ on atopic dermatitis in an in-vivoexperiment by using an NC/Nga atopic dermatitis mouse was very effective as an atopic dermatitis treatment.

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Effect of Jeseupwiryeongtang-gagam on Atopic Dermatitis-like Skin NC/Nga Mouse Induced by Dermatophagoides Farinae Crude Extract (제습위령탕가감이 집 먼지 진드기 추출물로 유도된 NC/Nga mouse의 아토피 피부염에 미치는 영향)

  • Na, Dong-Gyu;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.22 no.2
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    • pp.81-114
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    • 2008
  • Objectives : The purpose of this study is to investigate the effect of Jeseupwiryeongtang-gagam(JWTG) on atopic dermatitis by in vivo experiment using NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the atopic dermatitis of human. Methods : To investigate the effect of JWTG on AD, we evaluated atopic dermatitis-like skin lesions by clinical skin index and analyzed immunological parameters in peripheral blood mononuclear cells(PBMCs), splenocytes, draining lymph node(DLN) and performed skin histology in ears and dorsal skin of atopic dermatitis-like skin NC/Nga mouse in vivo. Results and Conclusions : In vivo, clinical skin severity score were significantly lower in JWTG group than control group. IgE, IL-6, $TNF-{\alpha}$, IgM, IgG2a and IgG2b levels in serum were decreased remarkably in JWTG group than control group and $IFN-{\gamma}$ production, secreted in Th1 cell were increased by JWTG. After experiment ended, we analyzed immunological cells ($CD3^+$, $CD19^+$, $CD4^+$, $CD8^+$, $CD3^+$$CD69^+$, $CD4^+$$CD25^+$ and $CD49b^+$) by flow cytometry. It resulted that total absolute number of $CD3^+$, $CD19^+$, $CD4^+$ and $CD8^+$ cells were recovered as normal and $CD3^+$$CD69^+$ were decreased significantly compared with control group in isolated DLN and PBMCs from NC/Nga mouse and total absolute number of $Gr-1^+$, $CD11b^+$ and $CD3^+$ in dorsal skin of NC/Nga mouse were decreased by JWTG. We analyzed ear, DLN, and neck-back skin after biopsy and dyeing by hematoxyline/eosin(H&E) and toluidine staining (mast cells marker) and obtained results that JWTG were effective to histological symptoms (dermal and epidermal thickening, hyperkeratosis and inflammatory cell infiltration). Ear thickness was decreased significantly than the control group and the size of inflammatory lymphocytes cells(ILC) and plasma cells(PC) in DLN were also decreased.

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A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in Hunter syndrome patients

  • Lee, Ok-Jeong;Kim, Su-Jin;Sohn, Young-Bae;Park, Hyung-Doo;Lee, Soo-Youn;Kim, Chi-Hwa;Ko, Ah-Ra;Yook, Yeon-Joo;Lee, Su-Jin;Park, Sung-Won;Kim, Se-Hwa;Cho, Sung-Yoon;Kwon, Eun-Kyung;Han, Sun-Ju;Jin, Dong-Kyu
    • Clinical and Experimental Pediatrics
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    • v.55 no.3
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    • pp.88-92
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    • 2012
  • Purpose: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II. Methods: We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl- ${\alpha}$-iduronate 2-sulphate. Results: Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type ($p$=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 $nmol{\cdot}4hr^{-1}{\cdot}mL^{-1}$. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; $p$=0.003). Conclusion: These results show that the mild phenotype may be related to residual lysosomal enzyme activity.

$RpoB_{127-135}$ Peptide Derived from Mycobacterium tuberculosis is Processed and Presented to HLA-$A^*0201$ Restricted CD8+ T Cells via an Alternate HLA-I Processing Pathway

  • Cho, Jang-Eun;Cho, Sang-Nae;Cho, Sungae
    • Biomedical Science Letters
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    • v.20 no.4
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    • pp.250-255
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    • 2014
  • Mycobacterium tuberculosis (MTB) resides and replicates inside macrophages. In our previous report, we reported that CD8+ T cell-mediated immune responses specific for the peptide derived from MTB RNA polymerase beta-subunit ($RpoB_{127-135}$) could be induced in TB patients expressing HLA-$A^*0201$ subtype. In order to examine whether $RpoB_{127-135}$ specific CD8+ T cells can recognize MTB infected macrophages in vitro, CD8+ T cell lines specific for $RpoB_{127-135}$ peptide were generated from peripheral blood mononuclear cells (PBMCs) of healthy HLA-$A^*0201$ subjects by in vitro immunization technique. In this study, we observed $RpoB_{127-135}$ specific CD8+ T cells could recognize and destroy macrophages infected with MTB for 2 to 4 days. $RpoB_{127-135}$ specific CD8+ T cell immune response was inducible from PBMC of healthy subjects expressing HLA-$A^*0206$ subtype, one of HLA-A2 supertype members. Next, we investigated the HLA-I processing mechanism of $RpoB_{127-135}$ peptide in MTB infected macrophages. As a result, the presentation of the MTB derived epitope peptide, $RpoB_{127-135}$, to CD8+ T cells was not inhibited by the treatment with brefeldin-A (ER-Golgi transport inhibitor) or lactacystin (proteasome inhibitor), which blocks the classical HLA-I processing pathway. However, $RpoB_{127-135}$ specific CD8+ T cell activity was blocked either by the blocking agent for the endocytosis (cytochalasin D) or by the blocking antibody (W6/32) for HLA-I molecules. Therefore, the $RpoB_{127-135}$ peptide may be processed by accessing the alternate HLA-I processing pathway. Understanding the processing and presentation mechanisms of the MTB derived proteins will help to improve the efficacy of vaccines and the efficiency of therapeutic agents for TB.

Regulatory effects of Seogakjihwang-tang on Cytokines and Growth Factor Production in PBMC from the Patient with Cerebral infarction under Consciousness Disorders

  • Kim Yo Han;Sung Kang Keyng;Lee Kwang Ro;Lee Sang Kwan;Cheong Sang Su;Kang Sei Young;Lee So Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.3
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    • pp.829-836
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    • 2003
  • Seogakjihwang-tang (SJT) was widely used to treat patients suffering from cerebral infarction. But scientific investigation has been carried out very little. The aim of the present study is to investigate the effect of SJT on the production of various cytokines in the patients with cerebral infarction (CI). We investigated interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-1 in the sera of 27 patients with cerebral infarction under consciousness disorders and 10 normal controls using an originally devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA). We found that plasma levels of IL-4 were slightly elevated in patients with cerebral infarction, whereas plasma levels of IL-10 (P<0.001) and TGF-1 were reduced. Peripheral blood mononuclear cells (PBMC) obtained from the patient with CI were cultured for 24 h in the presence or absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA). The amount of IL-4, IL-10 and TGF-1, in culture supernatant, was significantly increased in the LPS or PHA treated cells compared to unstimulated cells (P<0.05), We also show that increased cytokines IL-4, and IL-10 level was significantly inhibited by SJT in a dose-dependent manner. Maximal inhibition rate of IL-4 and IL-10 production by SJT was 45.63.3% and 614.7% for LPS-stimulated cell and 27.31.2% and 83.62% for PHA-stimulated cells, respectively (P<0.05). On the other hand, SJT significantly increased the LPS or PHA-induced TGF-1 production (P<0.05). These data suggest that SJT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of CI.

Effects of Mori Ramulus on Collagen-induced Arthritis Rat - Expression of Immunocells in Draining Lymph Node - (상지가 콜라겐 유발 관절염 랫트에 미치는 영향 - 배액림프절의 면역세포 발현 -)

  • Roh, Seong-Soo;Ku, Sae-Kwang;Seo, Young-Bae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.1106-1115
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    • 2009
  • Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th1 7 cells. DBA/1OlaHsd mice were immunized with bovine type II collagen (CII). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-$\alpha$, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-$\alpha$, IL-6, IL-17 and collagen II-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 mg/kg or 200 mg/kg) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 mg/kg) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma

  • Surapaitoon, Arpa;Suttiprapa, Sutas;Mairiang, Eimorn;Khuntikeo, Narong;Pairojkul, Chawalit;Bethony, Jeffrey;Brindley, Paul J.;Sripa, Banchob
    • Parasites, Hosts and Diseases
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    • v.55 no.3
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    • pp.295-304
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    • 2017
  • Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

Histopathological Studies of Mice after Administration of Radioactive Iodine($^{131}I$) (방사성동위원소옥소(放射性同位元素沃素)($^{131}I$)가 "마우스"의 주요장기(主要臟器)의 병리조직상(病理組織像)에 미치는 영향(影響)에 관(關)한 연구(硏究))

  • Ro, Chae-Song;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.1 no.2
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    • pp.85-97
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    • 1967
  • Histopathological changes of various organs of the mice after intra-peritoneal injections of radioactive iodine ($^{131}I$) were experimentally observed. Sixity healthy female mice, weighing average 25 gm, devided into 6 groups, were used. The various doses of $^{131}I$ were injected intraperitoneally at different intervals. The histopathological changes after these treatments were observed in organs such as thyroids, parathyroids, livers, kidneys and gonads. Following were the results; 1) Thyroid: In the group A given $^{131}I$ with a single dose of $10{\mu}C$ per gm body weight, it was observed that the protoplasms of follicular epithelial cells were destroyed, the nuclei were expanded or dissoluted, showing pyknotic changes of nuclei and vacuolizations of protoplasms. In the group B given $^{131}I$ with a single dose of $5{\mu}C$ per gm body weight, hyperemias, hemorrhages and hyaline degenerations in the whole area were observed. In the group C given $^{131}I$ with 3 doses of $2.5{\mu}C$ per gm body weight every week, the thyroid parenchyms were destroyed and epithelial cells of varing size were observed in the fibrinous tissues. In the group D given $^{131}I$ with 6 doses of $0.5{\mu}C$ per gm body weight every week, some destroyed follicles and new borne follicles were observed. But the histopathological changes resemble the follicles of the normal thyroid gland. In the group E and F given $^{131}I$ with 8 and 10 doses of $0.2{\mu}C\;and\;0.01{\mu}C$ for each group per gm body weight every two days, both pyknotic changes of nuclei and cytoplasmic vacuolizations of the follicular epithelia, hypertrophies of follicles and abnormal irregular follicular structures were observed, and in the group F, lymphocytes appeared around the thyroid glands. 2) Parathyroid: In the group A, hyperemia, proliferations of connective tissues, karyorrhexes and vacuolizations were observed. In other experimental groups, no particular pathological change was observed. 3) Liver: The degnerative changes and acute or chronic inflammatory changes were observed in proportion to the amount of $^{131}I$ injected. Atrophies of the liver cells, dilatations of sinusoids, hyaline degenerations and necrotic pictures were observed. 4) Kidney: In the group A, congestions and infiltrations of mononuclear cells and granulocytes were observed around the cortical arteries, and in the group B, the degenerative changes of cortexes, and, in the group C and D, hydronephrotic changes were observed respectively, and hyaline degenerations were partially observed. 5) Gonad: In the group A, the follicles were degenerated. The ova in the follicles showed irregular figures. The changes in the group B were almost the same as in the group A, but the changes were mild. In the group C, the destructions of whole ova, the hypertrophies of ovarian follicular membranes and pyknotic changes of nuclei were observed. In the group D, the pathological changes were similar to that of group C, but mild in the grade. In the group E, almost none of ovarian follicular fluid was observed, and in the group F, the tissue pictures were almost similar to that of the normal group.

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