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

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.

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

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.

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

조산아 기관지폐이형성증과 Tumor Necrosis Factor-α 유전자 다 형성과의 연관성

조희승,장윤환,김한석,김병일,최중환 대한신생아학회 2011 Neonatal medicine Vol.18 No.1

Purpose: Several factors including prolonged inflammatory response are thought to contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The clinical findings can be explained by an increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α). We investigated the relationship between susceptibility to BPD and TNF-α promoter polymorphisms to identify genetic factors of the disease. Methods: Thirty-eight preterm infants who had developed BPD and 55 controlled infants with a birth weight <1,500 g were analyzed for TNF-α genotypes. The alleles of five promoter sites (-1031/-863/-857/-308/-238) of TNF-α gene were determined using Taqman^®-based allelic discrimination assays. Results: Gestational age (27^(+5)±2^(+0) wk vs. 29^(+2)±1^(+4) wk, P<0.0001) and birth weight (990±270 g vs. 1,220±230 g, P<0.0001)were lower in the BPD group compared to the control group. The incidence of respiratory distress syndrome (71.1% vs. 49.1%,P=0.035) and patent ductus arteriosus (71.1% vs. 50.9%, P=0.052) was higher in the BPD group compared to the control group. The frequencies of the alleles and genotypes of five promoter sites (-1031/-863/-857/-308/-238) of TNF-α gene did not show differences between the BPD group and the control group. Conclusion: TNF-α promoter polymorphisms are not associated with susceptibility to BPD in Korean preterm infants. 목적: 기관지폐이형성증(bronchopulmonary dysplasia,BPD)의 발생에는 폐의 염증반응이 중요하게 작용한다. Tumor necrosis factor-α (TNF-α)는 대표적인 proinflammatory cytokine으로, TNF-α 고생산 부위의 단일염기다형성과 BPD 발생 사이의 연관성을 알아보고자 하였다. 방법: 2006년 1월부터 12월까지 서울대학교병원에서 출생하여 신생아중환자실에 입원한 재태주령 32주 미만이면서 출생체중 1,500 g 미만의 미숙아 93예를 대상으로, 실시간 중합효소연쇄반응을 이용하여, TNF-α 유전자 촉진자 5개 부위(-1031T/C,-863C/A, -857C/T, -308G/A, -238G/A)의 단일염기다형성을분석하였다. 결과: BPD 군은 전체연구대상93예 중에서 38예로40.9%에해당하였다. BPD 군에서 대조군보다 재태연령(27+5±2+0 wk vs. 29+2±1+4 wk, P<0.0001)과 출생체중(990±270 g vs. 1,220±230 g, P<0.0001)이 낮고, 신생아 호흡곤란증후군(71.1% vs. 49.1%, P=0.035) 과 동맥관개존(71.1% vs. 50.9%, P=0.052) 의발생빈도가 높아서 두 군간의 임상적 특성에는 차이가 있었다. 그러나 TNF-α 유전자 단일염기다형성 분석에서는, 각각의TNF-α 대립유전자의 빈도와 일배체형의 분포 모두가 BPD 군과 대조군 사이에 차이를 보이지 않았다. 결론: 한국인 조산아에서는, TNF-α 유전자 다형성보다는 임상적인 위험인자가 BPD 발생에 중요하게 작용하였다.

종양괴사인자-α로 유발시킨 삼출성 중이염에서 TNF Soluble Receptor TypeⅠ의 역할

이동희,박용수,최영철,전은주,여상원 대한이비인후과학회 2000 대한이비인후과학회지 두경부외과학 Vol.43 No.9

A Novel Herbal Formulation “LiverCare” Differentially Regulates Primary Rat Hepatocyte and Hepatocarcinoma Cell Proliferation In Vitro

Satyakumar Vidyashankar,Sandeep R. Varma,Mohammed Azeemudin,Ashok Godavarthi,Nandakumar S. Krishna,Pralhad Sadashiv Patki 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.9

Hepatocyte growth factor (HGF) plays an important role in hepatocyte proliferation. HGF expression is regulated by various signaling molecules and nuclear receptors. In the present study, LiverCare^ⓡ (LC), a novel polyherbal formulation (The Himalaya Drug Company, Bangalore, India), was evaluated for its efficacy, using co-cultures of primary rat hepatocytes–non-parenchymal cells (NPCs) and human hepatocellular carcinoma cells (HepG2). The rate of primary hepatocyte co-culture proliferation was significantly and dose-dependently increased by LC as determined by [3H]thymidine incorporation into newly synthesized DNA and cell proliferation assay. LC also increased HGF expression in primary hepatocyte co-culture. Albumin and urea content remained constant during proliferation of hepatocyte co-cultures in the presence of LC with decreased activity of alanine aminotransferase. It is interesting that LC inhibited incorporation of [3H]thymidine into DNA in HepG2 cells. LC enhanced peroxisome proliferator-activated receptor-α expression during hepatocyte proliferation, whereas tumor necrosis factor-α expression remained unaffected. In conclusion, our study clearly showed that LC differentially regulates primary rat hepatocytes and human hepatocarcinoma cell proliferation. LC may be a promising candidate for treating degenerative liver diseases by enhancing liver regeneration.

난포액내에 존재하는 TNF - α 와 NO 의 농도가 난자의 질에 미치는 영향에 관한 연구

이규섭 ( K . S . Lee ) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.7

Objective: Our objective was to explain a relationship between concentrations of tumor necrosis factor- α (TNF- α) and nitric oxide (NO) in follicular fluid, oocyte quality, and outcomes of in vitro fertilization- embryo transfer 0VF-ET). Method: The concentrations of TNF- α and NO were measured in 115 follicular fluid samples collected from 43 patients undergoing IVF-ET program, due to tubal obstruction, some with endometriosis (8 patients) or hydrosalpinx (5 patients). A correlation of these factors concentrations and the oocyte quality, the oocyte marurity, and infertility associated disease was analyzed Result: No correlation was found between concentrations of NO and TNF- α in follicular fluid. NO concentrations in follicular fluids were significantly higher in patients with endometriosis (P<0.001) or hydrosalpinx (P<0.01) compared to the patients with just tubal obstruction. Follicular NO concentration differences according to oocyte maturity and oocyte quality were not found. In contrast, TNF- α concentrations in follicular fluids were significantly higher in poor quality oocytes (P<0.05) but were not associated with infertility-associated diseases, such as hydrosalpinx or endometriosis, and the oocyte maturity. No significant differences in follicular levels of NO and TNF- α as well as IVF-ET parameters of pregnant and nonpregnant groups were revealed. Conclusions: There is no significant correlation between the concentrations of NO and TNF- α in follicular fluid. NO levels in follicular fluid are altered in infertility-associated disease. However, TNF- α levels but not NO levels influence oocyte quality. These results suggest that the production of NO and TNF- α in follicular fluid may be regulated via different pathways and can be tempered with infertility-associated disease, thereby influencing oocyte quality locally.

건선 병변에서 Interleukin-8 과 Tumor necrosis factor - α 발현에 대한 면역조직화학적 연구

원덕환(Duck Hwan Won),김영근(Young Keun Kim),최광성(Gwang Sung Choi) 대한피부과학회 2001 大韓皮膚科學會誌 Vol.39 No.5

N/A Background: Psoriasis is a chronic skin disease characterized histologically by prominent keratinocyte hyperplasia and an early inflammatory cell infiltrate. However, the pathogenesis is not fully understood yet. Recently, there has been growing interest in the probable role of a T cell mediated immune response in the pathogenesis. Especially, cytokine network involved in psoriasis has been studied. Objective : This study was done to investigate the role of Interleukin-8(IL-8) and its inducer, Tumor necrosis factor-a(TNF-a) for pathogenesis of psoriasis. Methods: We performed immunohistochemical staining using antibodies for IL-8 and TNF- a in frozen skin samples of 14 psoriatic patients who had not been treated for psoriatic lesion for 1 month and 3 normal skin samples as controls. Results : There was no detectable discrete immunoreactivity for either TNF-a and IL-8 in epidermis and dermis of normal controls. In psoriatic lesions, the expression of TNF-a was found in dermal cells within the papillary dermis, particularly around blood vessels. The expression of IL-8 was presented on suprabasal keratinocytes above TNF- a-positive dermal tissue. Conclusion : Our results strongly suggest that histologic expression and functional interaction between IL-8 and its inducer, TNF- a have significant roles in the pathogenesis of psoriasis.

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.

Pertussis toxin-induced hyperacute autoimmune encephalomyelitis in Lewis rats is correlated with increased expression of inducible nitric oxide synthase and tumor necrosis factor alpha

Ahn, Meejung,Kang, Jongchul,Lee, Yongduk,Riu, Keyzung,Kim, Yong-sik,Jee, Youngheun,Matsumoto, Yoh,Shin, Taekyun 제주대학교 방사능이용연구소 2001 연구보고 Vol.15 No.-

자기면역성 뇌척수염(experimental autoimmune encephalomyelitis, EAE)은 뇌조직항원을 면역한 후 야기되는 염증성 질병으로 사람 다발성결화증의 한 모델로 연구되고 있다. 자기면역성 뇌염의 시작은 뇌조직항원에 반응하는 림프구가 중추신경계에 침윤되면서 마비를 나타내는데 이 과정 중에는 여러 종류의 pro-inflammatory mediator (tumor necrosis factor-alpha (TNF-α)와 inducible nitric oxide synthase (iNOS)등)가 관여하는 것으로 알려지고 있다. 이 연구에서는 염증의 진행 단계에 따라 염증 유도 또는 염증 억제의 상반된 기능을 갖는 것으로 알려진 TNF-α와 iNOS가 심급성 뇌척수염 진행에 어떠한 영향을 미치는지를 조사하였다. 뇌염을 유도하기 위한 항원으로는 랫트 척수 조직 유제를 complete Freund adjuvant와 혼합하여 뒷 발바닥에 주사하였으며 심한 뇌척수염을 유도하기 위하여 pertussis toxin(500ng/ea)을 면역하는 날 복강내로 주사하고 매일 체중과 마비 정도를 확인하였다. 독소를 주사한 실험군에서는 대조군(11일)에 비해 마비의 시작이 빨랐으며(9일), 대조군은 자연 회복하는 반면 독소룰 주사한 실험군에서는 모두 폐사하였다. 척수 조직 내 TNF-α 와 iNOS의 양적인 변화를 조사하기 위하여 Competitive PCR과 Western blot를 이용하였으며, 세포형을 구분하기 위하여 면역염색을 이용하였다. Competitive PCR결과 TNF-α는 PT를 투여한 자기면역성뇌척수염의 심한 마비기(EAE,G3)에서 PT를 투여하지 않은 대조군보다 약 5배가 증가하였으며(p<0.01), Western blot결과 iNOS는 PT를 투여한 군에서 정상조직에 비해 약 6배가 증가하였고, PT를 투여하지 않은 군에 비해서는 약 3개바 증가하였다(p<0.01). 면역염색결과 PT를 투여하지 않은 랫트보다 투여한 랫트의 척수조직에서 iNOS 양성 세포가 약 15배가 증가하였으며(p<0.01), 또한 연속절편에서 이들 세포가 큰포식세포임을 확인하였다. 이상의 결과를 종합해 볼 때, 자기면역성 뇌척수염의 초기 유도과정에서는 TNF-α와 iNOS는 염증의 약화에 관여됨을 알 수 있었다. The involvement of inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α), which have diverse roles in the progression of autoimmune disease models, was studied in pertussis toxin (PT-induced hyperacute experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The expression of TNF-α mRNA(increased 5 fold, p<0.01) and iNOS protein (3 fold, p<0.01) was much greater in the spinal cords with PT(+) EAE at the peak stage of EAE than in those with PT(-) EAE, as shown by competitive PCR and Western blot analysis, respectively. Immunohistochemistry showed that the majority of EDI-positive macrophages in EAE lesions contained iNOS, and that three were many more iNOS-positive cells in the CNS lesions of PT(+) rats than in those of PT(-) rats. These findings suggest that PT-induced hyperacute EAE is partly mediated by the enhanced expression of iNOS and TNF-α in the early stages of rat EAE.