조기분만진통 임산부에서 양수 tumor necrosis factor-α 와 조직학적 융모양막염 및 선천성 패혈증과의 관련성에 관한 연구

박교훈(Kyo Hoon Park),윤보현(Bo Hyun Yoon),전중관(Jong Kwan Jun),박중신(Joong Shin Park),김길자(Gil Ja Kim),이홍균(Hong Kyoon Lee),신희철(Hee Chul Syn) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Objective : Our purposes were (1) to determine whether amniotic fluid concentrations of tumor necrosis factor-α are of value in the diagnosis of histologic chorioamnionitis of preterm placenta and in the prediction of congenital sepsis in patients with preterm labor and intact membranes and (2) to compare the diagnostic performance of placental histologic finding and amniotic fluid culture with that of amniotic fluid tumor necrosis factor-α for this outcome variable. Methods : The relations among placental histologic finding, perinatal outcome, amniotic fluid culture, and amniotic fluid tumor necrosis factor-α concentrations were examined in 61 consecutive patients with preterm labor and intact membranes who delivered preterm neonates within 72 hours after transabdominal amniocentesis. Tumor necrosis factor-α was determined by enzyme-linked immunosorbent assays. Mann-Whitney U test, Fisher's exact test, receiver-operator characteristic curve, and multiple logistic regression were used for analysis. Results : 1) Women with acute histologic chorioamnionitis had significantly higher median amniotic fluid tumor necrosis factor-α concentrations than those without histologic chorioamnionitis (median 83.2 pg/ml, range 1.4 to 7241 pg/ml vs median 1.6 pg/ml, range 0 to 59.9 pg/ml, p <0.0001). Amniotic fluid tumor necrosis factor-α concentrations ≥4.6 pg/ml had a sensitivity of 88% (28/32) and specificity of 80% (23/29) in the diagnosis of acute histologic chorioamnionitis. 2) Amniotic fluid concentrations of tumor necrosis factor-α were significantly higher in neonates with congenital sepsis than in those without congenital sepsis (median 227.5 pg/ml, range 1.2 to 7241 pg/ml vs median 3.8 pg/ml, range 0 to 735 pg/ml, p <0.0005). Amniotic fluid tumor necrosis factor-α concentrations ≥41 pg/ml had a sensitivity of 82% (23/29) and specificity of 79% (38/48) in the prediction of congenital sepsis. 3) Multiple logistic regression indicated that elevated amniotic fluid tumor necrosis factor-α (≥41 pg/ml) was the only independent predictor of congenital sepsis (odd ratio 12.9, 95% confidence interval 1.3 to 125.3, p <0.05) after correction for known confounding variables [i.e., low gestational age at birth (≤32 weeks), positive amniotic fluid culture, histologic or clinical chorioamnionitis, low Apgar score (<7)]. Conclusion : Test of amniotic fluid tumor necrosis factor-α is of value in the antenatal diagnosis of histologic chorioamnionitis and congenital sepsis in patients with preterm labor and intact membranes. Amniotic fluid tumor necrosis factor-α is a better independent predictor of congenital sepsis than placental histologic finding or amniotic fluid culture.

배양된 인체의 거대세포종에 대한 Tumor necrosis factor-alpha의 영향

정도현,장의찬,김현태,강수용,이은우 중앙대학교 의과대학 의과학연구소 1993 中央醫大誌 Vol.18 No.1

In vitro, cell culture techniques have been used to identify and characterize the types of the individual cell presented in human tumors. Using techniques of cell dispersion with mechanical disruption and treatment with proteolytic enzymes, it was possible to obtain heterogenous populations of cells from original tumor tissue and to maintain these cells in cluture. This technique provided a means for more extensive study of the morphologic features and response of these cells to a variety of biochemical stimuli. The author investigated the behavior of the cells in culture of giant cell tumor and it became possible to draw some suggestions concerning possible origin and biologic features of this tumor. In response to a variety of stimuli lymphocytes secrete cytokines that are capable of altering host mechanism. These cytokines include interleukin, interferon and tumor necrosis factor. Tumor necrosis factor(TNF) is able to elicit hemorrhagic necrosis of tumor and interest in TNF has been considerable on account of its possible use in the treatment of neoplastic disease. To investigate the antiproliferative effect of tumor necrosis factor alpha(TNF-alpha), cultured mononuclear cell in the media containing TNF-alpha (100 units/㎖) were observed by light microscopy. The number of viable cells growing in microtiter plate wells were estimated with a colorimetric assay and an automatic microplate scanning spectrophotometer. Also superoxide dismutase was added to see whether it could reverse the inhibitory effects of TNF-alpha in proliferation or not. The results were as follows 1. In vitro cell culture from human giant cell tumor of bone, three cell types were identified based on morphologic characteristics. Among them, multinucleated giant cells and mononuclear cells which resembled monocyte-macrophage cells did not persist in culture. The stromal cells were persistently proliferated, which were positively stained on nonspecific esterase and the staining was inhibited by sodium fluoride. 2. TNF-alpha, 100 units/㎖, induced cell shrinkage, and especially pyknotic and karyorrhectic change in nuclei in many stromal cells in culture. 3. TNF-alpha significantly inhibited cell proliferation and antiproliferative effect was dose dependent. 4. Simultaneous addition of superoxide dismutase with TNF-alpha lessned the antiproliferative effect of TNF-alpha on stromal cell of human giant cell tumor, which suggested that the antiproliferative effect of TNF-alpha on cultured stromal cell was mediated through the superoxide anion. In summry, the stromal cell most likely represented the major neoplastic element of the giant cell tumor and the fact that nonspecific esterases were present in the stromal cell and those enzymes were inhibited by sodium fluoride allowed the possibility that the stromal cells were derived from monocyte. TNF-alpha had antiproliferative effect of the stromal cell and in appeared that TNF-alpha can be used as antitumor agent. The antiproliferative effect of TNF-alpha on the stromal cell may be mediated by the superoxide anion.

자궁내막증의 존재유무에 따른 혈장과 복강액내의 TNF - α 농도 ; TNF - α 가 자궁내막증의 병인인가 ?

김호성(Ho Sung Kim),이수미(Soo Mi Lee),신희경(Hee Gung Shin),문혜경(Hye Kyoung Mun),조태일(Tae Il Cho),강정배(Jeong Bae Kang),이영경(Young Kyeong Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.9

N/A Objective : Our purpose of study was to investigate whether in vivo levels of tumor necrosis factor-α in plasma and peritoneal fluid (PF) differ in women with and without endometriosis. Design : Prospective and case-control study. Methods : Fifty-seven women with laparotomy or laparoscopic findings of minimal to severe endometriosis, and forty-two women with no visual evidence of pelvic endometriosis and with benign gynecologic disease. Tumor necrosis factor-α levels in plasma and PF were determined using commercial ELISA. Tumor necrosis factor-α concentrations were compared among women with and without endometriosis, and then also were compared according to the revised American Fertility Society classification. Results : Tumor necrosis factor-α concentrations were not significantly increased in the plasma and PF of women with endometriosis than in matched normal controls. Tumor necrosis factor-α concentrations in endometriosis stage III and IV were sightly increased, which were not increased statistically significant. Conclusions : Plasma and PF tumor necrosis factor-α levels were not different between women with and without endometriosis. Our results do not rule out the hypothesis that tumor necrosis factor-α may be involved in the pathogenesis of some features of endometriosis.

Tumor Necrosis Factor와 Interleukin - 2가 신세포암환자의 종양침윤림프구 세포독성 활성화에 미치는 영향

이춘용,최홍용,우영남 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.1

In an attempt to increase the potency of tumor infiltrating lymphocytes(TIL) in immunotherapy, the effect of tumor necrosis factor(TNF) and interleukin-2(IL-2) were investigated in vitro on proliferation and cytotoxic effect of TIL to the vatious kinds of tumor lines and fresh frozen tumor cells from renal cell carcinoma patient. The dosage of TNF was 500 unit/ml and IL-2 was 1000 Cetus unit/ml. The cytotoxicity of TIL was checked with 4 hour Chromium release cytotoxicity of TIL was checked with 4 hour Chromium release cytotoxicity assay and its proliferatio was checked by {³H} thymidine uptake assay. For the target cell of the TIL cytotoxicity was used M-14(melanoma cell line) as a lymphokine activated killer(LAK) cell sensitive cell line for investigation of LAK activity and K562(erythroleukemic cell line) for investigation of natural killer(NK) cell activity. To investigate the specific cytotoxicity on renal cell carcinoma, autologous tumor cell line was used as the autologous target. To investigate the non specific cytotoxicity on renal cell carcinoma, allogeneic fresh frozen renal carcinoma cells and renal cell carcinoma cell line(444) were used as the allogeneic target cells. The proliferation effect of TIL, treated with IL-2 at 20th day of culture was 11486±591 cpm and 23871±1069 cpm with combination of TNF and IL-2. The nonspectific cytotoxicity of TIL for the 444 at 20th day of culture was 8.2 LU in IL-2 only and 19.0 LU with combination of TNF and IL-2. The cytotoicity of TIL for the K562 at 20th day of culture was 37.3 LU in IL-2 only and 60.4 LU with combination of TNF and IL-2. These result suggest that the combination of TNF and IL-2 has a synergistic effect on proliferation and nonspectific cytotoxicity of TIL at 20th day of culture in vitro. THese results bear important practical implication for clinical trials of TIL in adoptive immunotherapy for metastatic renal cell carcinoma.

Anti-Tumor Necrosis Factor Therapy in Intestinal Behcet’s Disease

( Jihye Park ),( Jae Hee Cheon ) 대한소화기학회 2018 Gut and Liver Vol.12 No.6

Intestinal Behcet’s disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behcet’s disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor-α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behcet’s disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor-α for the treatment of intestinal Behcet’s disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behcet’s disease. This review also discusses safety issues associated with anti-tumor necrosis factor-α, including vulnerability to infections and malignancy. (Gut Liver 2018;12:623-632)

Tumor Necrosis Factor와 Interleukin-2가 신세포암환자의 종양침윤림프구 세포독성 활성화에 미치는 영향

최홍용,이춘용,우영남 大韓泌尿器科學會 1998 Korean Journal of Urology Vol.39 No.7

Interferon-gamma, Tumor Necrosis Factor-alpha및 Transforming Growth Factor-beta(1)에 의한 골수세포의 유착분자 발현 및 Stromal Cell-Derived Factor-1 생성의 조절

조덕연,황진희,정효균,박수진,박상은,곽승근,윤환중,성주명,김삼용 大韓血液學會 2003 大韓血液學會誌 Vol.38 No.2

Receptor Interacting Protein 3 Kinase Regulates Caspase-independent Programmed Necrosis

조영식 계명대학교 자연과학연구소 2013 Quantitative Bio-Science Vol.32 No.1

Programmed necrosis is a specialized cell death that is distinct from apoptosis in morphology and mechanism. Unlike apoptosis, caspases are not required in programmed necrosis. In fact, programmed necrosis occurs optimally when caspases are inactivated, such as infections with viruses that encode caspase inhibitors. Thus, programmed necrosis may be an important anti-viral host defense strategy. The serine/threonine kinase receptor interacting protein1 (RIP1/RIPK1) plays an essential role in programmed necrosis and other caspase-independent cell death programs. However, the molecular basis by which RIP1 mediates caspase independent cell death is poorly understood. Here, we show that the kinase activity of RIP1 is induced in a cytoplasmic signaling complex termed Complex II during tumor necrosis factor alpha (TNF)- induced programmed necrosis. Using a RNA interference (RNAi) screen, we identified RIP3 as a crucial downstream regulator for RIP1-mediated programmed necrosis. RIP3 binds to Complex II and undergoes phosphorylation in a RIP1-dependent manner. RIP3 triggers programmed necrosis by regulating downstream reactive oxygen species (ROS) production. Our results provide significant mechanistic insight on the molecular regulation of TNF-induced programmed necrosis and reveal a physiological clue for RIP3-dependent programmed necrosis in a range of biological events.

원인 불명 반복유산 환자에서 태반 항원에 대한 말초혈액 단핵구의 반응에 대한 연구

이순곤 순천향의학연구소 1998 Journal of Soonchunhyang Medical Science Vol.4 No.2

Peripheral blood mononuclear cells(PBMCs) from many women with unexplained recurrent abortion(URA) respond to trophoblast extracts in vitro by both proliferating and releasing soluble factors that adversely affect embryo and trophoblast viability, while PBMCs from parous women with a history of normal pregnancies and women with recurrent abortion due to maternal chromosomal or anatomic causes do not commonly show this response. Other studies have demonstrated that TH1-type cytokines, especially IFN-r and tumor necrosis factor-α, impair early embeyo development and trophoblast growth and function in vitro, and cause abortion in mice. In contrast, TH2-type cytokines are secreted at the maternal-fetal interface during normal murine pregnancy and may play an important role in normal pregnancy by suppressing cellular immune responses that could endanger the fetus, while maintaining humoral immunity vital for maternal defense against pathogens. Therefore, reproductive success may depend on cytokine regulation of the maternal immune response. In this study, we investigated whether or not PBMCs from women with a history of URA produce TH 1-type cytokines, IL-2 and tumor necrosis factor-α, following exposure to trophoblast extracts. We detected tumor necrosis factor-α(mean, 33±19.8pg/mL) in trophoblast-activated PBMC culture supernatants from URA patients. None of the trophoblast-activated PBMC culture supernatants from reproductively normal women contained tumor necrosis factor-α. None of the trophoblast-activated PBMC culture supernatants from URA patients and reproductively normal women contained IL-2. Supernatants from unstimulated cultures contained neither IL-2 nor tumor necrosis factor-α.

실험동물에서 Lipopolysaccharide와 Thalidomide에 의한 Vascular Endothelial Growth Factor와 Tumor Necrosis Factor-α 발현의 변화

최동락,조창호,정진숙,홍숙희,윤길숙 대한대장항문학회 2004 Annals of Coloproctolgy Vol.20 No.3