Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo

DEFF Research Database (Denmark)

Ågren, Magnus S; Schnabel, Reinhild; Christensen, Lise H

2015-01-01

Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng/ml) in the a......Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng...... tissue-derived collagenolytic activity with TNF-α exposure was blocked by neutralizing MMP-1 monoclonal antibody and was not due to down-regulation of tissue inhibitor of metalloproteinase-1. TNF-α increased production (pendogenous MMP-1...

Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

Institute of Scientific and Technical Information of China (English)

YAN Chun-fang; YU Xue-wen; JIN Hui; LI Xu

2004-01-01

To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua andconcentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion,threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplainedearly spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortionof pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing arti-ficial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 indecidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was mea-sured with an enzyme-linked immunosorbent assay. Results: The ercentages of membrane tumor necrosis factor receptor 1positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13.14 ±6.30 for healthy pregnant women ( P ＜ 0.05). Serum oncentration of soluble tumor necrosis factor receptor 1 was signifi-cantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women withthreatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion.Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosisfactor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may cont-ribute to the development of early spontaneous abortion.

Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat

NARCIS (Netherlands)

de Vos, A. F.; van Haren, M. A.; Verhagen, C.; Hoekzema, R.; Kijlstra, A.

1995-01-01

Tumor necrosis factor is released in the circulation and aqueous humor during endotoxin-induced uveitis, and induces acute uveitis when injected intraocularly in rats. To elucidate the role of tumor necrosis factor in the development of endotoxin-induced uveitis we analysed the effect of

Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

Science.gov (United States)

Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

2018-03-01

Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

Generation of truncated recombinant form of tumor necrosis factor ...

African Journals Online (AJOL)

7. Original Research Article. Generation of truncated recombinant form of tumor necrosis factor ... as 6×His tagged using E.coli BL21 (DE3) expression system. The protein was ... proapoptotic signaling cascade through TNFR1. [5] which is ...

Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha

DEFF Research Database (Denmark)

Brock, C; Brock, B; Aziz, Q

2017-01-01

-VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which...

Fibrinolytic response to tumor necrosis factor in healthy subjects

NARCIS (Netherlands)

van der Poll, T.; Levi, M. [=Marcel M.; Büller, H. R.; van Deventer, S. J.; de Boer, J. P.; Hack, C. E.; ten Cate, J. W.

1991-01-01

Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men,

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

Science.gov (United States)

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease

DEFF Research Database (Denmark)

El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar

2013-01-01

Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....

Expression of human soluble tumor necrosis factor (TNF)-related ...

African Journals Online (AJOL)

DR NJ TONUKARI

2011-06-06

Jun 6, 2011 ... bio-technique in bacterial (Lin et al., 2007), yeast (Xu et al., 2003) ... biological activity, such as human somatotropin (hST) .... sion way with chloroplast transit peptide (Wang et al., .... chloroplast protein synthesis capacity by massive expression of a ... necrosis factor-related apoptosis-inducing ligand in vivo.

Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Nielsen, Ole Haagen; Ainsworth, Mark Andrew

2013-01-01

A 35-year-old man presents with an exacerbation of Crohn's ileocolitis. He received a diagnosis of Crohn's disease 8 years ago and has been treated on three previous occasions with prednisone. Because of a recurrent need for glucocorticoids, treatment with azathioprine (150 mg per day) was starte...... colonoscopy show acute and chronic granulomatous inflammation, and the gastroenterologist recommends treatment with a tumor necrosis factor (TNF) inhibitor....

Risk factors leading to mucoperiosteal flap necrosis after primary palatoplasty in patents with cleft palate.

Science.gov (United States)

Rossell-Perry, Percy; Figallo-Hudtwalcker, Olga; Vargas-Chanduvi, Roberto; Calderon-Ayvar, Yvette; Romero-Narvaez, Carolina

2017-10-01

Few studies have been published reporting risk factors for flap necrosis after primary palatoplasty in patients with cleft palate. This complication is rare, and the event is a disaster for both the patient and the surgeon. This study was performed to explore the associations between different risk factors and the development of flap necrosis after primary palatoplasty in patients with cleft palate. This is a case-control study. A 20 years retrospective analysis (1994-2015) of patients with nonsyndromic cleft palate was identified from medical records and screening day registries). Demographical and risk factor data were collected using a patient´s report, including information about age at surgery, gender, cleft palate type, and degree of severity. Odds ratios and 95% confident intervals were derived from logistic regression analysis. All cases with diagnoses of flap necrosis after primary palatoplasty were included in the study (48 patients) and 156 controls were considered. In multivariate analysis, female sex, age (older than 15 years), cleft type (bilateral and incomplete), and severe cleft palate index were associated with significantly increased risk for flap necrosis. The findings suggest that female sex, older age, cleft type (bilateral and incomplete), and severe cleft palatal index may be associated with the development of flap necrosis after primary palatoplasty in patients with cleft palate.

Which factors influence radiographic progression during treatment with tumor necrosis factor inhibitors in clinical practice?

DEFF Research Database (Denmark)

Ørnbjerg, Lykke Midtbøll; Østergaard, Mikkel; Bøyesen, Pernille

2014-01-01

OBJECTIVE: To investigate baseline characteristics associated with radiographic progression and the effect of disease activity, drug, switching, and withdrawal on radiographic progression in tumor necrosis factor (TNF) inhibitor-naive patients with rheumatoid arthritis (RA) followed for about 2...

Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis

OpenAIRE

HARRIS, JAMES; HARRIS, JAMES

2008-01-01

PUBLISHED umor necrosis factor (TNF)?? is a proinflammatory cytokine that mediates inflammation in response to various pathogens, including Mycobacterium tuberculosis, but is also a key factor in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. Three TNF???suppressing drugs have been approved to treat selected autoimmune diseases; 2 are monoclonal antibodies against TNF?? (adalimumab and infliximab), and the other is a soluble TNF receptor/Fc fusion protein (etanerce...

Paradoxical Reaction to Golimumab: Tumor Necrosis Factor α Inhibitor Inducing Psoriasis Pustulosa

Directory of Open Access Journals (Sweden)

Marien Siqueira Soto Lopes

2013-11-01

Full Text Available Importance: Golimumab is a human monoclonal antibody, used for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Adverse reactions are increasing with this class of medication (tumor necrosis factor α inhibitors. Observations: The authors present a case of a female patient who presented with psoriasis pustulosa after the use of golimumab for rheumatoid arthritis. Conclusions and Relevance: Paradoxically, in this case, golimumab, which is used for psoriasis, induced the pustular form of this disease. We are observing an increasing number of patients who develop collateral effects with tumor necrosis factor α inhibitors, and the understanding of the mechanism of action and how these adverse reactions occur may contribute to avoid these sometimes severe situations.

Generation of truncated recombinant form of tumor necrosis factor ...

African Journals Online (AJOL)

Purpose: To produce truncated recombinant form of tumor necrosis factor receptor 1 (TNFR1), cysteine-rich domain 2 (CRD2) and CRD3 regions of the receptor were generated using pET28a and E. coli/BL21. Methods: DNA coding sequence of CRD2 and CRD3 was cloned into pET28a vector and the corresponding ...

Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy

NARCIS (Netherlands)

Bremer, Edwin

2013-01-01

The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective

Microglia protect neurons against ischemia by synthesis of tumor necrosis factor

DEFF Research Database (Denmark)

Lambertsen, Kate Lykke; Clausen, Bettina Hjelm; Babcock, Alicia

2009-01-01

Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical...

Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

Energy Technology Data Exchange (ETDEWEB)

Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France); Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr [Institut Gustave Roussy, Department of Epidemiology (France); Tselikas, Lambros, E-mail: lambros.tselikas@gmail.com; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Farouil, Geoffroy, E-mail: g.farouil@gmail.com [Institut Gustave Roussy, Department of Interventional Radiology (France); Boige, Valérie, E-mail: boige@igr.fr; Malka, David, E-mail: david.malka@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Leboulleux, Sophie, E-mail: sophie.leboulleux@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Ducreux, Michel, E-mail: ducreux@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Baudin, Eric, E-mail: baudin@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France)

2015-04-15

PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

Risk Factor Analysis for Mastectomy Skin Flap Necrosis: Implications for Intraoperative Vascular Analysis.

Science.gov (United States)

Reintgen, Christian; Leavitt, Adam; Pace, Elizabeth; Molas-Pierson, Justine; Mast, Bruce A

2016-06-01

Skin flap necrosis after mastectomy can be a devastating complication significantly affecting patient outcomes. Routine vascular analysis (fluorescein or laser angiography) of mastectomy skin flaps in all patients has been advocated but is of questionable cost-effectiveness. The purpose of this study was to identify the incidence and causative risk factors for mastectomy skin flap necrosis and thereby calculate the fiscal reality of intraoperative vascular screening. This is an institutional review board-approved retrospective study of all patients from 2007 to 2013 who underwent mastectomy related to breast cancer. Skin flap necrosis was defined as major if it necessitated return to the operating room. Data analysis was done for determination of causative factors of necrosis, including age, body mass index, smoking, previous irradiation, coronary artery disease, chronic obstructive pulmonary disorder, hypertension, gastroesophageal reflux disease, hyperlipidemia, obstructive sleep apnea, asthma, diabetes, thyroid disease, history of lumpectomy, and breast reduction or augmentation. During this time, intraoperative vascular screening was not done. Five hundred eighty-one patients underwent 616 mastectomies with a total of 34 necrotic events (5.5%)-16 major and 18 minor. Analyses via Student t tests, univariate analyses, χ testing, and logistic regression showed that history of smoking was the only patient factor associated with postoperative necrosis (P = 0.008). More frequently represented in the necrosis group, but without statistical significance, are previous lumpectomy (P = 0.069) and immediate reconstruction (P = 0.078).For the entire study period, the actual cost to the hospital for major necrotic events was $7,123.10 or $445.19 for each of the 16 major necrotic events and $209.50 for all 34 necrotic events. Per-patient cost-effective screening would need to be less than $11.54 for all patients, $100.33 for highest risk patients (smokers), and $21.65 for

MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.

Science.gov (United States)

Tran, An Hue Vy; Han, Se Hee; Kim, Joon; Grasso, Francesca; Kim, In San; Han, Ye Sun

2017-07-01

Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

Science.gov (United States)

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease

NARCIS (Netherlands)

Michelakakis, H.; Spanou, C.; Kondyli, A.; Dimitriou, E.; van Weely, S.; Hollak, C. E.; van Oers, M. H.; Aerts, J. M.

1996-01-01

Tumor necrosis factor-a (TNF-a) levels were measured in the plasma of patients with different types of Gaucher disease (GD) and patients with other lysosomal storage diseases. The highest TNF-a levels were observed in the most severe neuronopathic type of GD, exceeding those found in healthy

Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

DEFF Research Database (Denmark)

Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

1994-01-01

Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...... in cardiac output and was associated with the appearance of areas with myocardial necrosis in the regional left ventricular wall. The myocardial plasma flow rate and maximum plasma flow rate in response to a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease in the myocardial...... ng/kg for 60 min) on myocardial microvascular transport of a small hydrophilic indicator was examined by the single-injection, residue-detection method. Intracoronary infusion of rTNF-alpha increased myocardial microvascular transport after 120 min. This increase was preceded by a sustained decline...

Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

Directory of Open Access Journals (Sweden)

Erol-Demirbilek Melike

2016-09-01

Full Text Available Background: Thioredoxin reductase (TrxR, epidermal growth factor (EGF and tumor necrosis factor-α (TNF-α have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains.

Anti-tumor necrosis factor-alpha therapies attenuate adaptive arteriogenesis in the rabbit

NARCIS (Netherlands)

Grundmann, Sebastian; Hoefer, Imo; Ulusans, Susann; van Royen, Niels; Schirmer, Stephan H.; Ozaki, C. Keith; Bode, Christoph; Piek, Jan J.; Buschmann, Ivo

2005-01-01

The specific antagonists of tumor necrosis factor-alpha (TNF-alpha), infliximab and etanercept, are established therapeutic agents for inflammatory diseases such as rheumatoid arthritis and Crohn's disease. Although the importance of TNF-alpha in chronic inflammatory diseases is well established,

Proteolytic activation of proapoptotic kinase protein kinase Cδ by tumor necrosis factor α death receptor signaling in dopaminergic neurons during neuroinflammation

Directory of Open Access Journals (Sweden)

Gordon Richard

2012-04-01

Full Text Available Abstract Background The mechanisms of progressive dopaminergic neuronal loss in Parkinson’s disease (PD remain poorly understood, largely due to the complex etiology and multifactorial nature of disease pathogenesis. Several lines of evidence from human studies and experimental models over the last decade have identified neuroinflammation as a potential pathophysiological mechanism contributing to disease progression. Tumor necrosis factor α (TNF has recently emerged as the primary neuroinflammatory mediator that can elicit dopaminergic cell death in PD. However, the signaling pathways by which TNF mediates dopaminergic cell death have not been completely elucidated. Methods In this study we used a dopaminergic neuronal cell model and recombinant TNF to characterize intracellular signaling pathways activated during TNF-induced dopaminergic neurotoxicity. Etanercept and neutralizing antibodies to tumor necrosis factor receptor 1 (TNFR1 were used to block TNF signaling. We confirmed the results from our mechanistic studies in primary embryonic mesencephalic cultures and in vivo using the stereotaxic lipopolysaccharide (LPS model of nigral dopaminergic degeneration. Results TNF signaling in dopaminergic neuronal cells triggered the activation of protein kinase Cδ (PKCδ, an isoform of the novel PKC family, by caspase-3 and caspase-8 dependent proteolytic cleavage. Both TNFR1 neutralizing antibodies and the soluble TNF receptor Etanercept blocked TNF-induced PKCδ proteolytic activation. Proteolytic activation of PKCδ was accompanied by translocation of the kinase to the nucleus. Notably, inhibition of PKCδ signaling by small interfering (siRNA or overexpression of a PKCδ cleavage-resistant mutant protected against TNF-induced dopaminergic neuronal cell death. Further, primary dopaminergic neurons obtained from PKCδ knockout (−/− mice were resistant to TNF toxicity. The proteolytic activation of PKCδ in the mouse substantia nigra in the

The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

Science.gov (United States)

Luan, Y Y; Yao, Y M; Sheng, Z Y

2013-01-01

Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

Infective endocarditis following tumor necrosis factor-α antagonist therapy for management of psoriatic erythroderma: a case report.

Science.gov (United States)

Mizuno, Takuro; Kiyosawa, Jun; Fukuda, Akihiro; Watanabe, Seiji; Kurose, Nozomu; Nojima, Takayuki; Kanda, Tsugiyasu

2017-02-09

The introduction of biological agents, such as infliximab, which act against tumor necrosis factor-α was a major advance for the treatment of an increasing number of chronic diseases. Tumor necrosis factor-α antagonists represent a major therapeutic advance for the management of chronic inflammatory diseases, such as psoriasis. Previous studies have reported that the use of tumor necrosis factor-α antagonists increased the risk of opportunistic infections and reactivation of latent bacterial infections. Cardiac involvement, such as infective endocarditis, is very rare in the literature. A 77-year-old Asian man with a 10-year history of psoriatic erythroderma was referred due to high fever and general malaise. He was treated with Predonine (prednisolone) and infliximab. After treatment, cardiac echography showed mitral valve vegetation and brain magnetic resonance imaging indicated multiple fresh infarctions. He died from large brain infarction in October 2013. An autopsy showed fresh thrombosis in his left middle cerebral artery, mitral valve vegetations, and septic micro-embolisms in multiple organs. Lethal bacterial endocarditis was revealed after administration of tumor necrosis factor-α inhibitor, infliximab, for the treatment of psoriatic erythroderma. An autopsy showed vegetation in his mitral valve and brain infarction with fresh purulent embolism in his left middle cerebral artery and septic micro-embolisms.

Herpes Simplex Encephalitis during Treatment with Tumor Necrosis Factor-α Inhibitors

OpenAIRE

Bradford, Russell D.; Pettit, April C.; Wright, Patty W.; Mulligan, Mark J.; Moreland, Larry W.; McLain, David A.; Gnann, John W.; Bloch, Karen C.

2009-01-01

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-α) inhibitors for rheumatologic disorders. Although TNF-α inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti–TNF-α drugs and herpes simplex virus encephalitis has not been previously described.

Proliferative and antiproliferative effects of interferon-gamma and tumor necrosis factor-alpha on cell lines derived from cervical and ovarian malignancies

International Nuclear Information System (INIS)

Mutch, D.G.; Massad, L.S.; Kao, M.S.; Collins, J.L.

1990-01-01

Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed

Tumor necrosis factor alpha gene polymorphism in multiple sclerosis and optic neuritis

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Sandberg-Wollheim, M

1990-01-01

The NcoI tumor necrosis factor (TNF alpha) polymorphism was studied in relapsing/remitting multiple sclerosis and monosymptomatic optic neuritis. The frequency of the NcoI marker phenotypes did not differ between healthy controls and the two disease groups. No extra or missing DNA fragments were...

Role of tumour necrosis factor in pathogenesis of radicular cyst

International Nuclear Information System (INIS)

Qureshi, W.U.R.; Idris, M.; Khan, S.A.

2011-01-01

Background: The radicular cyst is very common odontogenic cyst of the jaws, which is usually associated with a tooth with necrotic pulp. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. The wall of the cyst contains epithelial cells, macrophages, fibroblasts and other cells. TNF is one of inflammatory mediators, which is produced by macrophages and monocytes. This study was carried out to investigate the role of tumour necrosis factor in the pathogenesis of radicular cyst, which is by far the commonest cystic lesion of the jaws. Methods: Explants from 20 radicular cysts were cultured in vitro to grow the epithelial cells. However, the cultures were rapidly contaminated with fibroblasts and it was impossible to grow the epithelial cells separately. Therefore, the proliferative effect of Tumour Necrosis Factor (TNF) was studied on mammalian epithelial cells. Results: TNF at low concentration had a proliferative effect on the epithelial cells, which may play some role in pathogenesis of radicular cyst. Conclusion: TNF stimulated the epithelial cell proliferation in low concentration and inhibit the proliferation in higher concentrations. These two effects may have some implications in the pathogenesis of radicular cyst. (author)

Expression of tumour necrosis factor alpha and accumulation of fibronectin in coronary artery restenotic lesions retrieved by atherectomy.

Science.gov (United States)

Clausell, N.; de Lima, V. C.; Molossi, S.; Liu, P.; Turley, E.; Gotlieb, A. I.; Adelman, A. G.; Rabinovitch, M.

1995-01-01

BACKGROUND--The formation of coronary artery neointima experimentally induced in piglets after cardiac transplantation is related to an immune-inflammatory reaction associated with increased expression of T cells and inflammatory mediators (tumour necrosis factor alpha and interleukin 1 beta) and upregulation of fibronectin. In vivo blockade of tumour necrosis factor alpha in rabbits after cardiac transplantation results in reduced neointimal formation. The objective of this study was to investigate the hypothesis that coronary restenosis after atherectomy or percutaneous balloon angioplasty is associated with a similar inflammatory cascade initiated by mechanical injury. METHODS--Specimens taken at coronary atherectomy were analysed from 16 patients. Nine had had the procedure performed twice, firstly, to remove a primary lesion, and secondly, to remove a restenotic lesion. Seven had percutaneous balloon angioplasty after removal of restenotic tissue. Coronary atherectomy specimens were analysed by immunohistochemistry for the presence of T cells, macrophages, major histocompatibility complex II, interleukin 1 beta, tumour necrosis factor alpha, fibronectin, and the receptor for hyaluronan mediated motility. RESULTS--The groups were clinically and angiographically similar with equivalent lumens before and after atherectomy. Restenotic lesions had increased expression of tumour necrosis factor alpha and fibronectin compared with the primary lesions (P < 0.05 for both). There was also a trend towards a greater number of T cells and increased expression of interleukin 1 beta. CONCLUSIONS--Restenosis is associated with increased expression of tumour necrosis factor alpha and fibronectin, suggesting that an immune-inflammatory reaction probably contributes to neointimal formation and may represent a form of wound healing and repair secondary to mechanical injury. Images PMID:7626352

Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown

International Nuclear Information System (INIS)

Mahadevan, V.; Malik, S.T.; Meager, A.; Fiers, W.; Lewis, G.P.; Hart, I.R.

1990-01-01

Flavone acetic acid (FAA), a novel investigational antitumor agent, has been shown to cause early vascular shutdown in several experimental murine tumors, and this phenomenon is believed to be crucial to FAA's antitumor effects. However, the basis of this FAA-induced tumor vascular shutdown is unknown. In this study a radioactive tracer-clearance technique has been used as an objective indication of tumor blood flow to show that i.p. administered FAA induces a progressive and sustained reduction in blood flow in a colon 26 tumor growing s.c. in syngeneic mice. As early as 1 h after administration, there was a significant increase in the t1/2 clearance value for intratumorally injected 133Xe, reaching a peak at 3 h (117.3 +/- 36.4 versus 7.8 +/- 0.85 min for controls). Significant inhibition of blood flow was still apparent 48 h after a single injection of drug. This FAA-induced vascular shutdown was virtually abolished in tumor-bearing mice pretreated with an antiserum against tumor necrosis factor, while no such effect was observed in controls pretreated with nonimmune serum (t1/2 of 10.8 +/- 1.2 versus 65.6 +/- 8.0 min for controls). Furthermore, in vitro FAA was seen to induce tumor necrosis factor secretion from murine peritoneal cells and splenocytes. These studies suggest that FAA-induced tumor vascular shutdown in the colon 26 tumor is mediated by tumor necrosis factor

Divergent effects of tumor necrosis factor alpha on apoptosis of human neutrophils

NARCIS (Netherlands)

van den Berg, J. M.; Weyer, S.; Weening, J. J.; Roos, D.; Kuijpers, T. W.

2001-01-01

Apoptosis of neutrophils is a key mechanism to control the intensity of the acute inflammatory response. Previously, the cytokine tumor necrosis factor alpha (TNF-alpha) was reported by some to have pro-apoptotic and by others to have antiapoptotic effects on neutrophils. The aim of this study was

Systemic side effects of isolated limb perfusion with tumor necrosis factor alpha

NARCIS (Netherlands)

Zwaveling, Jan Harm

1997-01-01

The main function of tumor necrosis factor alpha (TNF-a), a small polypeptide shared by all mammals, is probably protection against invading bacteria, parasites and viruses; killing of these microorganisms is facilitated in the presence of TNF-a. However, as its name suggest, TNF-a is also capable

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

Science.gov (United States)

Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; ptumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

NARCIS (Netherlands)

Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P.; Petrides, Francine; Cuesta Torres, Luisa F.; Hou, Liming; Cook, Adam; Barter, Philip J.; Weninger, Wolfgang; Rye, Kerry-Anne

2015-01-01

Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo)

Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

DEFF Research Database (Denmark)

Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

2005-01-01

Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type-1 receptor (TNFR1) and type-2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild-type (WT) animals and in mice lacking TNFR1 (TNFR1 KO...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...

Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

Science.gov (United States)

Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

2015-10-01

Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. Copyright © 2015 by the American Society of Nephrology.

Impact of Stopping Tumor Necrosis Factor inhibitors on Rheumatoid Arthritis Patients' Burden of Disease

NARCIS (Netherlands)

Ghiti Moghadam, Marjan; ten Klooster, Peter M.; Vonkeman, Harald Erwin; Kneepkens, Eva L.; Klaasen, Ruth; Stolk, Jan N.; Tchetverikov, Ilja; Vreugdenhil, Simone A.; van Woerkom, Jan M.; Goekoop-Ruiterman, Yvonne P.M.; Landewé, Robert B.M.; van Riel, Piet L.C.M.; van de Laar, Mart A F J; Jansen, Tim L.

OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). METHODS: In the pragmatic

Impact of Stopping Tumor Necrosis Factor-inhibitors on Rheumatoid Arthritis Patients' Burden of Disease

NARCIS (Netherlands)

Ghiti Moghadam, Marjan; ten Klooster, Peter M.; Vonkeman, Harald Erwin; Kneepkens, Eva L.; Klaasen, Ruth; Stolk, Jan N.; Tchetverikov, Ilja; Vreugdenhil, Simone A.; van Woerkom, Jan M.; Goekoop-Ruiterman, Yvonne P.M.; Landewé, Robert B.M.; van Riel, Piet L.C.M.; van de Laar, Mart A F J; Jansen, Tim L.

2017-01-01

OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). METHODS: In the pragmatic

Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in vitro.

Science.gov (United States)

Zinetti, M; Galli, G; Demitri, M T; Fantuzzi, G; Minto, M; Ghezzi, P; Alzani, R; Cozzi, E; Fratelli, M

1995-11-01

Chlorpromazine (CPZ) has been previously shown to protect against endotoxin [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis factor in vivo. We investigated at the cellular level whether this was due to direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP-1 cells in a dose dependent manner by a maximum of 80%. This effect was comparable to that of two well-known inhibitory drugs, dexamethasone and cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis in L929 cells, as detected by analysis of nuclear morphology. However, since we showed that apoptosis was very limited, and was not the main mode of cell death in our conditions, this could not explain the overall protection. Since CPZ did not interfere with either the oligomerization state of TNF-alpha or its receptor binding, our data suggest that it reduced cytotoxicity by inhibiting some steps in the TNF-alpha signalling pathways.

Tumour necrosis factor-α polymorphism as one of the complex inherited factors in pemphigus

Directory of Open Access Journals (Sweden)

Jolanta Dorota Torzecka

2003-01-01

Full Text Available The aim of our study was to analyse a significance of tumour necrosis factor (TNF-α promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-α gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls.

Increased voluntary exercise in mice deficient for tumour necrosis factor-alpha and lymphotoxin-alpha.

NARCIS (Netherlands)

Netea, M.G.; Kullberg, B.J.; Vonk, A.G.; Verschueren, I.; Joosten, L.A.B.; Meer, J.W.M. van der

2007-01-01

BACKGROUND: The endogenous mediators playing a role in the sensing of fatigue and cessation of exercise are yet to be characterized. We hypothesized that proinflammatory cytokines, in particular tumour necrosis factor-alpha (TNFalpha) and lymphotoxin-alpha (LT) transmit signals leading to fatigue.

Impact of Stopping Tumor Necrosis Factor-inhibitors on Rheumatoid Arthritis Patients' Burden of Disease

NARCIS (Netherlands)

Ghiti Moghadam, Marjan; ten Klooster, Peter M.; Vonkeman, Harald E.; Kneepkens, Eva L.; Klaasen, Ruth; Stolk, Jan N.; Tchetverikov, Ilja; Vreugdenhil, Simone A.; van Woerkom, Jan M.; Goekoop-Ruiterman, Yvonne P. M.; Landewé, Robert B. M.; van Riel, Piet L. C. M.; van de Laar, Mart A. F. J.; Jansen, Tim L.

2017-01-01

To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). In the pragmatic 12-month POET trial,

Clinical response, drug survival, and predictors thereof among 548 patients with psoriatic arthritis who switched tumor necrosis factor α inhibitor therapy

DEFF Research Database (Denmark)

Glintborg, Bente; Ostergaard, Mikkel; Krogh, Niels Steen

2013-01-01

To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care.......To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care....

Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells.

NARCIS (Netherlands)

Paleolog, E.M.; Delasalle, S.A.; Buurman, W.A.; Feldmann, M.

1994-01-01

Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion

Radiation necrosis of the mandible: a 10 year study. Part II. Dental factors; onset, duration and management of necrosis

International Nuclear Information System (INIS)

Murray, C.G.; Herson, J.; Daly, T.E.; Zimmerman, S.

1980-01-01

In a review of patients receiving radiation for cancer in the oral region the rate of radiation necrosis of the mandible was found to be similar for patients who had dental extractions before radiation therapy and for the remainder of the dentate population. It was suggested that diseased teeth should be removed prior to irradiation and sufficient healing time should be allowed. Teeth should not be extracted after irradiation. Dental prostheses can be provided for most irradiated patients if adequate care is exercised. The probability of necrosis commencing was highest three to twelve months after the start of therapy; it diminished gradually after that period. The duration of necrosis was depicted as an exponential curve with a constant probability of necrosis termination at each time point after onset. In 46.8% of the patients in study II (1971-1975), the necrosis was healed by conservative means. This was a significant increase over study I (1966-1969), and a complementary reduction in the necessity for surgical intervention was also found

Logistic regression analysis of factors associated with avascular necrosis of the femoral head following femoral neck fractures in middle-aged and elderly patients.

Science.gov (United States)

Ai, Zi-Sheng; Gao, You-Shui; Sun, Yuan; Liu, Yue; Zhang, Chang-Qing; Jiang, Cheng-Hua

2013-03-01

Risk factors for femoral neck fracture-induced avascular necrosis of the femoral head have not been elucidated clearly in middle-aged and elderly patients. Moreover, the high incidence of screw removal in China and its effect on the fate of the involved femoral head require statistical methods to reflect their intrinsic relationship. Ninety-nine patients older than 45 years with femoral neck fracture were treated by internal fixation between May 1999 and April 2004. Descriptive analysis, interaction analysis between associated factors, single factor logistic regression, multivariate logistic regression, and detailed interaction analysis were employed to explore potential relationships among associated factors. Avascular necrosis of the femoral head was found in 15 cases (15.2 %). Age × the status of implants (removal vs. maintenance) and gender × the timing of reduction were interactive according to two-factor interactive analysis. Age, the displacement of fractures, the quality of reduction, and the status of implants were found to be significant factors in single factor logistic regression analysis. Age, age × the status of implants, and the quality of reduction were found to be significant factors in multivariate logistic regression analysis. In fine interaction analysis after multivariate logistic regression analysis, implant removal was the most important risk factor for avascular necrosis in 56-to-85-year-old patients, with a risk ratio of 26.00 (95 % CI = 3.076-219.747). The middle-aged and elderly have less incidence of avascular necrosis of the femoral head following femoral neck fractures treated by cannulated screws. The removal of cannulated screws can induce a significantly high incidence of avascular necrosis of the femoral head in elderly patients, while a high-quality reduction is helpful to reduce avascular necrosis.

Soluble receptors for tumor necrosis factor as markers of disease activity in visceral leishmaniasis

NARCIS (Netherlands)

Zijlstra, E. E.; van der Poll, T.; Mevissen, M.

1995-01-01

Serum concentrations of soluble receptors for tumor necrosis factor (sTNFRs) were measured before and after antimony therapy in 25 Sudanese patients with active visceral leishmaniasis (VL). Both sTNFR types I and II were significantly elevated in patients with VL compared with healthy controls from

Effect of tumor necrosis factor-alpha infusion on the incretin effect in healthy volunteers

DEFF Research Database (Denmark)

Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke

2013-01-01

Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumor necrosis factor-alpha (TNF-α). Whereas TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce...

Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis

NARCIS (Netherlands)

Baert, F. J.; D'Haens, G. R.; Peeters, M.; Hiele, M. I.; Schaible, T. F.; Shealy, D.; Geboes, K.; Rutgeerts, P. J.

1999-01-01

Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. Thirteen patients with steroid-refractory Crohn's

Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection

Directory of Open Access Journals (Sweden)

Nadia Belmellat

2017-11-01

Full Text Available Tumor necrosis factor-alpha (TNF-α blockade is an effective treatment for rheumatoid arthritis (RA and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

Science.gov (United States)

Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

2009-12-01

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker

Directory of Open Access Journals (Sweden)

Agarwal Pankaj

2007-01-01

Full Text Available The development of anti-tumor necrosis factor (TNF therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

What factors determine patients' preference for tumour necrosis factor inhibitors in ankylosing spondylitis?

Science.gov (United States)

Fajri, Dessy W; Brand, Caroline A; Dharmage, Shyamali C; Martin, Belinda J; Buchanan, Russell R C; Schachna, Lionel

2009-05-01

Tumour necrosis factor inhibitor (TNFi) therapy, either intravenous (IV) or subcutaneous (SQ), demonstrates similar efficacy in ankylosing spondylitis (AS). The objective of this study was to examine factors influencing patient preference of TNFi. Fifty-nine (79.7%) participants were male with mean age 43.9 years and disease duration of 22.0 years. Fifty-nine patients (79.7%) agreed with the statement 'My doctor gave me a choice and I made a decision based on my personal preference'. Patients commenced first on IV TNFi most commonly cited reduced frequency of injections (96.6%), administration by a trained professional (89.7%) and use of infusion time for leisure activities (86.2%). Patients commenced on SQ TNFi cited flexibility with timing of treatment (80%), shortened administration time (73.3%) and the convenience of home therapy (73.3%). Shared clinical decision-making between clinicians and patients may be desirable for AS patients commencing TNFi therapy.

Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome

DEFF Research Database (Denmark)

Coenen, Marieke J H; Enevold, Christian; Barrera, Pilar

2010-01-01

Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication.......Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication....

Tumor necrosis factor alpha production in irradiated cells in vitro

International Nuclear Information System (INIS)

Koeteles, G.J.; Bognar, G.; Kubasova, T.

1994-01-01

Normal and tumor cell lines were used to investigate tumor necrosis factor (TNFα) production and its radiation sensitivity. The cells were irradiated with gamma rays using different doses from 0.25 Gy up to 5 Gy. The number of plated cells, changes of proliferation and TNFα production were determined during the following four post-irradiation days. For TNFα quantity measurement immuno-radiometric assay (IRMA) and enzyme amplified sensitivity assay (EASIA) was used. The results suggest that though gamma irradiation decreased cell proliferation in a dose dependent manner, the quantity produced in the post-irradiation period increased considerably in each irradiated sample. (N.T.) 3 refs.; 2 figs.; 1 tab

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

NARCIS (Netherlands)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2010-01-01

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

Nitric oxide-releasing agents enhance cytokine-induced tumor necrosis factor synthesis in human mononuclear cells

NARCIS (Netherlands)

Eigler, A; Sinha, B; Endres, S

1993-01-01

In septic shock tumor necrosis factor (TNF) leads to increased nitric oxide (NO) production by induction of NO synthase. An inverse regulatory effect, the influence of NO on cytokine synthesis, has rarely been investigated. The present study assessed the influence of NO-releasing agents on TNF

Studies on structural features of human tumor necrosis factor

International Nuclear Information System (INIS)

Yin Chuanyuan; Guo Donglin; Xi Tao; Xu Xianxiu; Gu Qingchao

1997-01-01

The microstructure of human tumor necrosis factor alpha (TNF-α) and its mutant (TNF-b) has been investigated by utilizing positron annihilation lifetime spectroscopy, radioiodination of human TNF and L929 cells assay. The experimental results show that the long lifetime (Τ 2 ) and corresponding intensity (I 2 ) of lower ortho-positronium annihilation in TNF-α are longer and less than those in the TNF-b, respectively. It suggests that the TNF-b is smaller in free volume and higher in density than the TNF-α. The TNF-b may maintain a more favorable conformation for binding to TNF receptors, thus increasing its biological activity. It is then concluded that the increases in the cytotoxicity and in the density for the TNF-b result from the decreases in the free volume in the TNF-b

Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

Directory of Open Access Journals (Sweden)

Rena Watanabe

2018-02-01

Full Text Available Tumor necrosis factor-stimulated gene-6 (TSG-6 is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD, plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases

DEFF Research Database (Denmark)

Olesen, Caroline Meyer; Coskun, Mehmet; Peyrin-Biroulet, Laurent

2016-01-01

Biological treatment with tumor necrosis factor (TNF) inhibitors is successful in the management of inflammatory bowel disease (IBD). All TNF inhibitors antagonize the pro-inflammatory cytokine TNF-α but with varying efficacies in IBD. The variations in efficacy probably are caused by structural ...... inhibitors in order to identify mechanisms of importance for their efficacy in IBD. Thus, a better understanding of the mechanistic basis for clinical efficacy can lead to a more rational use of TNF inhibitors in the management of IBD....

Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?

NARCIS (Netherlands)

van der Poll, T.; Lowry, S. F.

1995-01-01

Tumor necrosis factor-alpha (TNF) exerts numerous influences which, in association with severe infection, subserve both detrimental as well as beneficial host responses. The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular

Tumor necrosis factor (TNF) biology and cell death.

Science.gov (United States)

Bertazza, Loris; Mocellin, Simone

2008-01-01

Tumor necrosis factor (TNF) was the first cytokine to be used in humans for cancer therapy. However, its role in the treatment of cancer patients is debated. Most uncertainties in this field stem from the knowledge that the pathways directly activated or indirectly affected upon TNF engagement with its receptors can ultimately lead to very different outcomes in terms of cell survival. In this article, we summarize the fundamental molecular biology aspects of this cytokine. Such a basis is a prerequisite to critically approach the sometimes conflicting preclinical and clinical findings regarding the relationship between TNF, tumor biology and anticancer therapy. Although the last decade has witnessed remarkable advances in this field, we still do not know in detail how cells choose between life and death after TNF stimulation. Understanding this mechanism will not only shed new light on the physiological significance of TNF-driven programmed cell death but also help investigators maximize the anticancer potential of this cytokine.

Parity-Violating Electron Deuteron Scattering and the Proton's Neutral Axial Vector Form Factor

International Nuclear Information System (INIS)

Ito, T.

2003-01-01

The authors report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at the backward angles at electron beam energy of 125 MeV [Q 2 =0.038 (GeV/c) 2 ]. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon. In addition to the tree level amplitude associated with Z-exchange, the neutral weak axial vector form factor as measured in electron scattering can potentially receive large electroweak corrections, including the anapole moment, that are absent in neutrino scattering. The measured asymmetry A -3.51 ± 0.57 (stat) ± 0.58 (sys) ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at 200 MeV [Q 2 = 0.091 (GeV/c) 2 ] on a deuterium target. The updated results are also consistent with theoretical predictions on the neutral weal axial vector form factor

Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts

NARCIS (Netherlands)

García, S.; Bodaño, A.; Pablos, J. L.; Gómez-Reino, J. J.; Conde, C.

2008-01-01

To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were

A study of serum levels of leptin, ghrelin and tumour necrosis factor-alpha in child patients with cyanotic and acyanotic, congenital heart disease

International Nuclear Information System (INIS)

Shahramian, I.; Noori, N.M.

2013-01-01

Objective: To investigate the serum levels of leptin, ghrelin and tumour necrosis factor-alpha in children with cyanotic and acyanotic congenital heart disease. Methods: The prospective cohort study, was conducted at imam Ali Hospital, Zahedan University of Medical Sciences, Iran, in 2009-10 and comprised 64 subjects, including patients and controls. Using enzyme-linked immunosorpent assay kits, serum levels of ghrelin, leptin and tumour necrosis factor-alpha were measured and compared among patients (both cyanotic and acyanotic) and the controls, SPSS version 20 was used for statistical analysis. Results: Of the 64 subjects, 24 (37.5%) were cyanotic, 21(32.8%) were acynotic and 19(29.68%) were healthy controls. The three groups were homogenous in terms of age and gender characteristics. There was no significant difference among the groups leptin, ghrelin and tumour necrosis factor-alpha serum levels (p>0.05). There were also no significant differences in terms of weight, height and body mass index (P>0.05). Conclusion: Serum levels of ghrelin, leptin and tumour necrosis factor-alpha did not change in acyanotic and cyanotic patients with congenital heart disease, suggesting that other crucial factors may regulate individuals' nutrient intake, growth, weight and energy intake and output. (author)

Nonselective matrix metalloproteinase but not tumor necrosis factor-a inhibition effectively preserves the early critical colon anastomotic integrity

DEFF Research Database (Denmark)

Ågren, Magnus S.; Andersen, Thomas L.; Andersen, Line

2011-01-01

Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor-a (TNF-a) induces MMPs and may influence anastomosis repair....

INTRAOCULAR AND SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN ACUTE RETINAL NECROSIS AND OCULAR TOXOPLASMOSIS

NARCIS (Netherlands)

Wiertz, Karin; De Visser, Lenneke; Rijkers, Ger; De Groot-Mijnes, Jolanda; Los, Leonie; Rothova, Aniki

2010-01-01

Purpose: To determine the intraocular and serum vascular endothelial growth factor (VEGF) levels in patients with acute retinal necrosis (ARN) and compare those with VEGF levels found in patients with ocular toxoplasmosis (OT). Methods: Paired intraocular fluid and serum samples of 17 patients with

Skin Flap Necrosis After Mastectomy With Reconstruction: A Prospective Study.

Science.gov (United States)

Matsen, Cindy B; Mehrara, Babak; Eaton, Anne; Capko, Deborah; Berg, Anastasia; Stempel, Michelle; Van Zee, Kimberly J; Pusic, Andrea; King, Tari A; Cody, Hiram S; Pilewskie, Melissa; Cordeiro, Peter; Sclafani, Lisa; Plitas, George; Gemignani, Mary L; Disa, Joseph; El-Tamer, Mahmoud; Morrow, Monica

2016-01-01

Rates of mastectomy with immediate reconstruction are rising. Skin flap necrosis after this procedure is a recognized complication that can have an impact on cosmetic outcomes and patient satisfaction, and in worst cases can potentially delay adjuvant therapies. Many retrospective studies of this complication have identified variable event rates and inconsistent associated factors. A prospective study was designed to capture the rate of skin flap necrosis as well as pre-, intra-, and postoperative variables, with follow-up assessment to 8 weeks postoperatively. Uni- and multivariate analyses were performed for factors associated with skin flap necrosis. Of 606 consecutive procedures, 85 (14 %) had some level of skin flap necrosis: 46 mild (8 %), 6 moderate (1 %), 31 severe (5 %), and 2 uncategorized (0.3 %). Univariate analysis for any necrosis showed smoking, history of breast augmentation, nipple-sparing mastectomy, and time from incision to specimen removal to be significant. In multivariate models, nipple-sparing, time from incision to specimen removal, sharp dissection, and previous breast reduction were significant for any necrosis. Univariate analysis of only moderate or severe necrosis showed body mass index, diabetes, nipple-sparing mastectomy, specimen size, and expander size to be significant. Multivariate analysis showed nipple-sparing mastectomy and specimen size to be significant. Nipple-sparing mastectomy was associated with higher rates of necrosis at every level of severity. Rates of skin flap necrosis are likely higher than reported in retrospective series. Modifiable technical variables have limited the impact on rates of necrosis. Patients with multiple risk factors should be counseled about the risks, especially if they are contemplating nipple-sparing mastectomy.

Polymorphisms in tumor necrosis factor genes and susceptibility to visceral leishmaniasis in Moroccan children

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Rajaa Ejghal

2015-05-01

Full Text Available Objective: To examine whether polymorphic alleles at these two loci are involved in the susceptibility to visceral leishmaniasis (VL in Moroccan children. Methods: We have genotyped polymorphisms by PCR-restricted fragment length polymorphisms in 102 patients with VL, 92 asymptomatic carriers [positive skin test delayedtype hypersensitivity (DTH+] and 40 healthy controls (negative skin test delayed-type hypersensitivity, with no history of Leishmania infection. Results: Regression analysis showed no significant association between polymorphisms of tumor necrosis factors-ααwhen comparing VL and DTH + group (P > 0.05. The associations were detected between VL and negative skin test delayed-type hypersensitivity for the heterozygote genotype (P = 0.021, the recessive model: 1/2 + 2/2 (P = 0.044 and the minor allele 2 (P = 0.019. The resistance to VL was found to be under the recessive model 1/2 + 2/2 of tumor necrosis factors-β, when comparing VL and DTH + group (odds ratios: 0.558, 95%; confidence interval: 0.316-0.987; P = 0.044. Conclusions: These results must be regarded to preliminary but suggestive that further study with larger populations is worthwhile.

Arginase-II Promotes Tumor Necrosis Factor-α Release From Pancreatic Acinar Cells Causing β-Cell Apoptosis in Aging.

Science.gov (United States)

Xiong, Yuyan; Yepuri, Gautham; Necetin, Sevil; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2017-06-01

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L -arginine-ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II -/- ) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild-type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II -/- ) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice. © 2017 by the American Diabetes Association.

CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necrosis Factor Inhibitor Therapy in Rheumatoid Arthritis.

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Alessandra Citro

Full Text Available CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control. The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.

The correlation analysis of tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk: A meta-analysis.

Science.gov (United States)

Gao, Quangen; Zhang, Peijin; Wang, Wei; Ma, He; Tong, Yue; Zhang, Jing; Lu, Zhaojun

2016-10-01

Venous thromboembolism is a common complex disorder, being the resultant of gene-gene and gene-environment interactions. Tumor necrosis factor-alpha is a proinflammatory cytokine which has been implicated in venous thromboembolism risk. A promoter 308G/A polymorphism in the tumor necrosis factor-alpha gene has been suggested to modulate the risk for venous thromboembolism. However, the published findings remain inconsistent. In this study, we conducted a meta-analysis of all available data regarding this issue. Eligible studies were identified through search of Pubmed, EBSCO Medline, Web of Science, and China National Knowledge Infrastructure (CNKI, Chinese) databases up to June 2014. Pooled Odd ratios (ORs) with 95% confidence intervals were applied to estimating the strength of the genetic association in the random-effects model or fixed-effects model. A total of 10 studies involving 1999 venous thromboembolism cases and 2166 controls were included in this meta-analysis to evaluate the association between tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk. Overall, no significantly increased risk venous thromboembolism was observed in all comparison models when all studies were pooled into the meta-analysis. However, in stratified analyses by ethnicity, there was a pronounced association with venous thromboembolism risk among West Asians in three genetic models (A vs. G: OR = 1.82, 95%CI = 1.13-2.94; GA vs. GG: OR = 1.82, 95%CI = 1.08-3.06; AA/GA vs. GG: OR = 1.88, 95%CI = 1.12-3.16). When stratifying by source of controls, no significant result was detected in all genetic models. This meta-analysis demonstrates that tumor necrosis factor-alpha 308G/A polymorphism may contribute to susceptibility to venous thromboembolism among West Asians. Studies are needed to ascertain these findings in larger samples and different racial groups. © The Author(s) 2015.

Peculiarities of X-ray appearances of aseptic necrosis of head of the femur in adults and children and their connection with bio mechanical factors

International Nuclear Information System (INIS)

Suslova, O.Ya.; Shargorodskij, C.S.; Antipova, A.A.; Naumenko, N.A.; Kresnyj, D.I.

1987-01-01

260 patients aged from 3 to 56 with aseptic necrosis of head of the femur are examined. Experimental biomechanical simulation of load conditions on femur head and cotyloid cavity was carried out at phantom devices using tensiometry, ichnographic and polarization-optical methods. Peculiarities of X-ray appearances of asceptic necrosis with respect to age are studied. A definite connection between asceptic necrosis and biomechanical factors is established

Anti-Tumor Necrosis Factor With a Glyco-Engineered Fc-Region Has Increased Efficacy in Mice With Colitis

NARCIS (Netherlands)

Bloemendaal, Felicia M.; Levin, Alon D.; Wildenberg, Manon E.; Koelink, Pim J.; Mcrae, Bradford L.; Salfeld, Jochen; Lum, Jenifer; van der Neut Kolfschoten, Marijn; Claassens, Jill W.; Visser, Remco; Bentlage, Arthur; D'Haens, Geert R. A. M.; Verbeek, J. Sjef; Vidarsson, Gestur; van den Brink, Gijs R.

2017-01-01

Although tumor necrosis factor (TNF) antagonists reduce many clinical features of inflammatory bowel disease, complete mucosal healing occurs in fewer than 50% of patients. The Fc-region of monoclonal antibodies against TNF has immunosuppressive properties via effects on macrophage polarization. We

Microglia and macrophages express tumor necrosis factor receptor p75 following middle cerebral artery occlusion in mice

DEFF Research Database (Denmark)

Lambertsen, Kate Lykke; Clausen, Bettina Hjelm; Fenger, Claus

2007-01-01

The proinflammatory and potential neurotoxic cytokine tumor necrosis factor (TNF) is produced by activated CNS resident microglia and infiltrating blood-borne macrophages in infarct and peri-infarct areas following induction of focal cerebral ischemia. Here, we investigated the expression of the ...

Avascular Necrosis

Science.gov (United States)

... Financial Reports Watchdog Ratings Feedback Contact Select Page Avascular Necrosis Home > Cancer Resources > Late Effects of Treatment > Avascular Necrosis Avascular necrosis (AVN) is a disorder resulting from ...

THE USE OF TUMOR NECROSIS FACTOR α INHIBITORS IN PATIENTS WITH WEBER-CHRISTIAN DISEASE

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Olga Nikolayevna Egorova

2013-01-01

Full Text Available Weber-Christian disease (WCD, also known as idiopathic lobular panniculitis, is a rare disease belonging to the group of diffuse connective tissue diseases. No therapy for WCD has been developed; empirical treatment is typically used. The first description of the use of tumor necrosis factor α inhibitors in a female patient with infiltrative WCD is presented. The tactics of managing this patient category are analyzed.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) participates in anti-lipopolysaccharide factors (ALFs) gene expression in mud crab.

Science.gov (United States)

Sun, Wan-Wei; Zhang, Xin-Xu; Wan, Wei-Song; Wang, Shu-Qi; Wen, Xiao-Bo; Zheng, Huai-Ping; Zhang, Yue-Ling; Li, Sheng-Kang

2017-02-01

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key cytoplasm signal adaptor that mediates signals activated by tumor necrosis factor receptor (TNFR) superfamily and the Interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. The full-length 2492 bp TRAF6 (Sp-TRAF6) from Scylla paramamosain contains 1800 bp of open reading frame (ORF) encoding 598 amino acids, including an N-terminal RING-type zinc finger, two TRAF-type zinc fingers and a conserved C-terminal meprin and TRAF homology (MATH) domain. Multiple alignment analysis shows that the putative amino acid sequence of Sp-TRAf6 has highest identity of 88% with Pt-TRAF6 from Portunus trituberculatus, while the similarity of Sp-TRAF6 with other crustacean sequences was 54-55%. RT-PCR analysis indicated that Sp-TRAF6 transcripts were predominantly expressed in the hepatopancreas and stomach, whereas it was barely detected in the heart and hemocytes in our study. Moreover, Sp-TRAF6 transcripts were significantly up-regulated after Vibrio parahemolyticus and LPS challenges. RNA interference assay was carried out used by siRNA to investigate the genes expression patterns regulated by Sp-TRAF6. The qRT-PCR results showed that silencing Sp-TRAF6 gene could inhibit SpALF1, SpALF2, SpALF5 and SpALF6 expression in hemocytes, while inhibit SpALF1, SpALF3, SpALF4, SpALF5 and SpALF6 expression in hepatopancreas. Taken together, the acute-phase response to immune challenges and the inhibition of SpALFs gene expression indicate that Sp-TRAF6 plays an important role in host defense against pathogen invasions via regulation of ALF gene expression in S. paramamosain. Copyright © 2016. Published by Elsevier Ltd.

A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma

NARCIS (Netherlands)

Wenzel, Sally E.; Barnes, Peter J.; Bleecker, Eugene R.; Bousquet, Jean; Busse, William; Dahlén, Sven-Erik; Holgate, Stephen T.; Meyers, Deborah A.; Rabe, Klaus F.; Antczak, Adam; Baker, James; Horvath, Ildiko; Mark, Zsuzsanna; Bernstein, David; Kerwin, Edward; Schlenker-Herceg, Rozsa; Lo, Kim Hung; Watt, Rosemary; Barnathan, Elliot S.; Chanez, Pascal; Chanez, P.; Tunon-de-Lara, M.; Antczak, A.; Pierzchala, W.; Bukowczan, Z.; Trawinska, E.; Baker, J.; Wenzel, S. E.; Katial, R.; Bernstein, D.; Kerwin, E.; Bensch, G.; Castro, M.; Noonan, M.; Nayak, A.; Chupp, G.; Kline, J.; Busse, W.; Kavuru, M. S.; Lang, D.; Wolfe, R.; Baughman, R.; Korenblat, P.; Mansfield, L.; Bleecker, E.; Lisberg, E.; Liu, M.; Panettieri, R.; Spangenthal, S.; Bel, E. H.

2009-01-01

RATIONALE: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. OBJECTIVES: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.

Suppressor of cytokine signalling-3 inhibits Tumor necrosis factor-alpha induced apoptosis and signalling in beta cells

DEFF Research Database (Denmark)

Bruun, Christine; Heding, Peter E; Rønn, Sif G

2009-01-01

Tumor necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine involved in the pathogenesis of several diseases including type 1 diabetes mellitus (T1DM). TNFalpha in combination with interleukin-1-beta (IL-1beta) and/or interferon-gamma (IFNgamma) induces specific destruction...

[Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

Science.gov (United States)

Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

2014-11-18

To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial.

Science.gov (United States)

Scott, David L; Ibrahim, Fowzia; Farewell, Vern; O'Keeffe, Aidan G; Walker, David; Kelly, Clive; Birrell, Fraser; Chakravarty, Kuntal; Maddison, Peter; Heslin, Margaret; Patel, Anita; Kingsley, Gabrielle H

2015-03-13

To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. 24 rheumatology clinics in England. Patients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor strategy and -0.45 with the alternative combined drug strategy. The difference between

Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis

Directory of Open Access Journals (Sweden)

Ruxandra Calin

2017-07-01

Full Text Available A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF therapy is reported here. The patient required prolonged treatment with doxycycline–ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment.

Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

Science.gov (United States)

Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

2011-06-01

Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Investigation of relationship between tumor necrosis factor α in gingival and periodontitis

International Nuclear Information System (INIS)

Zhao Jingjie; Yang Xia; Hou Guihua; Wang Weiyue; Wang Haodan; Jia Hongying; Li Yantao

1999-01-01

42 periodontitis patients and 15 health controls are selected to determine the amount of tumor necrosis factor-α (TNF-α) in inflamed gingival and the normal gingival by RIA. The elations between TNF-α and clinical parameters are analysed. The results show that the level of TNF-α in inflamed gingival is higher than that in the controls (P<0.01). The relationship between TNF-α and clinical parameters indicate that the level of TNF-α positively correlate to the degree of periodontitis and group damage. It indicates TNF-α may be one of the mechanism in the pathogenesis of periodontitis disease

Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients

NARCIS (Netherlands)

Feelders, R. A.; Swaak, A. J.; Romijn, J. A.; Eggermont, A. M.; Tielens, E. T.; Vreugdenhil, G.; Endert, E.; van Eijk, H. G.; Berghout, A.

1999-01-01

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects

Programmed necrosis and necroptosis – molecular mechanisms

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Agata Giżycka

2015-12-01

Full Text Available Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor alpha biomarker in human serum

Energy Technology Data Exchange (ETDEWEB)

Eletxigerra, U. [Micro-NanoFabrication Unit, IK4-Tekniker, Eibar (Spain); CIC microGUNE, Arrasate-Mondragón (Spain); Martinez-Perdiguero, J. [CIC microGUNE, Arrasate-Mondragón (Spain); Merino, S. [Micro-NanoFabrication Unit, IK4-Tekniker, Eibar (Spain); CIC microGUNE, Arrasate-Mondragón (Spain); Villalonga, R.; Pingarrón, J.M. [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, Madrid (Spain); Campuzano, S., E-mail: susanacr@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, Madrid (Spain)

2014-08-01

Highlights: • Electrochemical magnetoimmunosensor for tumor necrosis factor alpha (TNFα) biomarker. • Sensitive and selective detection of TNFα in undiluted serum. • LOD achieved lower than the cut-off value established for relevant illnesses. • Useful and affordable alternative to ELISAs for TNFα determination in serum. - Abstract: An amperometric immunoassay for the determination of tumor necrosis factor alpha (TNFα) protein biomarker in human serum based on the use of magnetic microbeads (MBs) and disposable screen-printed carbon electrodes (SPCEs) has been developed. The specifically modified microbeads were magnetically captured on the working electrode surface and the amperometric responses were measured at −0.20 V (vs. Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as electron transfer mediator and H{sub 2}O{sub 2} as the enzyme substrate. After a thorough optimization of the assay, extremely low limits of detection were achieved: 2.0 pg mL{sup −1} (36 fM) and 5.8 pg mL{sup −1} (105 fM) for standard solutions and spiked human serum, respectively. The simplicity, robustness and this clinically interesting LOD proved the developed TNFα immunoassay as a good contender for real clinical application.

Amperometric magnetoimmunoassay for the direct detection of tumor necrosis factor alpha biomarker in human serum

International Nuclear Information System (INIS)

Eletxigerra, U.; Martinez-Perdiguero, J.; Merino, S.; Villalonga, R.; Pingarrón, J.M.; Campuzano, S.

2014-01-01

Highlights: • Electrochemical magnetoimmunosensor for tumor necrosis factor alpha (TNFα) biomarker. • Sensitive and selective detection of TNFα in undiluted serum. • LOD achieved lower than the cut-off value established for relevant illnesses. • Useful and affordable alternative to ELISAs for TNFα determination in serum. - Abstract: An amperometric immunoassay for the determination of tumor necrosis factor alpha (TNFα) protein biomarker in human serum based on the use of magnetic microbeads (MBs) and disposable screen-printed carbon electrodes (SPCEs) has been developed. The specifically modified microbeads were magnetically captured on the working electrode surface and the amperometric responses were measured at −0.20 V (vs. Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as electron transfer mediator and H 2 O 2 as the enzyme substrate. After a thorough optimization of the assay, extremely low limits of detection were achieved: 2.0 pg mL −1 (36 fM) and 5.8 pg mL −1 (105 fM) for standard solutions and spiked human serum, respectively. The simplicity, robustness and this clinically interesting LOD proved the developed TNFα immunoassay as a good contender for real clinical application

Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway

Directory of Open Access Journals (Sweden)

Ramesh Vijay

2012-05-01

Full Text Available Abstract Background Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice. Methods The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice. In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody. Results Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity. Conclusions Taken together

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

Directory of Open Access Journals (Sweden)

Kadasah S

2017-04-01

Full Text Available Saeed Kadasah,1 Misbahul Arfin,2 Sadaf Rizvi,2 Mohammed Al-Asmari,2 Abdulrahman Al-Asmari2 1Department of Psychiatry, 2Division of Molecular Biology & Genetics, Scientific Research Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Background: Schizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia. Objective: The aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF-α (-308G/A and TNF-β (+252A/G polymorphisms with schizophrenia susceptibility. Subjects and methods: TNF-α and TNF-β genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (-308G/A and TNF-β (+252A/G polymorphisms in patients were compared with those in controls. Results: The frequencies of TNF-α (-308 allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (-308G/A may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-β (+252A/G polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-β (+252A/G was significantly higher in male patients than in female patients. The distribution of TNF-α (-308G/A and TNF-β (+252A/G polymorphisms was almost similar in schizophrenia patients with

Bevacizumab as a treatment option for radiation-induced cerebral necrosis

Energy Technology Data Exchange (ETDEWEB)

Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; Nawatny, Jens [Univ. Hospital Duesseldorf (Germany). Dept. of Radiology; Hoffmann, Thomas K. [Duisburg-Essen Univ., Essen (Germany). Dept. of Otorhinolaryngology; Peiper, Matthias; Orth, Klaus [Hospital Essen-Sued, Essen (Germany). Dept. of Surgery; Gerber, Peter Arne [Univ. Hospital Duesseldorf (Germany). Dept. of Dermatology; Rusnak, Ethelyn [State Univ. of New York, Buffalo, NY (United States). Dept. of Anesthesiology; Lammering, Guido [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; MAASTRO Clinic, Maastricht (Netherlands). Radiation Oncology

2011-02-15

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

Bevacizumab as a treatment option for radiation-induced cerebral necrosis

International Nuclear Information System (INIS)

Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried; Nawatny, Jens; Hoffmann, Thomas K.; Peiper, Matthias; Orth, Klaus; Gerber, Peter Arne; Rusnak, Ethelyn; Lammering, Guido; MAASTRO Clinic, Maastricht

2011-01-01

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

Morphometric findings in avascular necrosis of the femoral head.

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Kamal, Diana; Trăistaru, Rodica; Alexandru, D O; Kamal, C K; Pirici, D; Pop, O T; Mălăescu, D Gh

2012-01-01

Avascular necrosis of the femoral head is an illness with a controversial etiology, the trigger event being the suppression of blood flow to the femoral head. The disease affects mostly young adults within their third and fifth decade, the majority of the patients being men. The main risk factors are trauma, chronic alcohol consumption, smoking, corticotherapy. The main goal of our study is to describe the morphometric changes found in the bone tissue of patients diagnosed with avascular necrosis of the femoral head, with different risk factors, by comparing the area of bone trabeculae inside the area of necrosis with that from the adjacent viable tissue. The morphometric study used biological material from 16 patients with ages between 29 and 57 years, who underwent surgery for avascular necrosis of the femoral head. They were admitted in the Orthopedics Department at the Emergency County Hospital in Craiova between 2010 and 2011 and were split into four groups. Group I presented trauma as the main risk factor, Group II had corticotherapy as the defining risk factor, Group III presented chronic alcohol consumption and Group IV was represented by the patients who smoked and exhibited chronic alcohol consumption. There was not a significant statistical difference between the areas of bone trabeculae of the four groups when we compared viable bone tissue to the necrotized one. Knowing the risk factors of the avascular necrosis of the femoral head is critical to the management of the disease, because diagnosing it in an early stage is a necessity for obtaining a good result for conservative treatment.

Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.

Science.gov (United States)

Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

1995-09-15

Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNF alpha on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compared to control (99 +/- 2%) (P 0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.

The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model

DEFF Research Database (Denmark)

Henriksen, Maiken Lumby; Søgaard Teisner, Ane; Kjeldsen, Jens

2016-01-01

BACKGROUND: Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment. MATERIALS...... AND METHODS: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration...... of functional IFX in the circulation. RESULTS: We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies. CONCLUSION: Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed...

[Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha].

Science.gov (United States)

Landeros-Olvera, Erick; López-Alvarenga, Juan Carlos; Nava-González, Edna J; Gallegos-Cabriales, Esther; Lavalle-González, Fernando; Bastarrachea, Raúl A; Salazar González, Bertha Cecilia

2014-01-01

The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n=17, controls n=17) with a body mass index>27kg/m(2). Molecular analysis was performed by immune-fluorescence. Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2μ/ml (P=.008); leptin 20.0 vs. 28.0μ/L (P=.02); and tumour necrosis factor-alpha 4.7 vs. 5.1pg/ml (P=.05). The established exercise (5 sessions a week of exercise of 40min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Tumor necrosis factor related apoptosis inducing ligand triggers apoptosis in dividing but not in differentiating human epidermal keratinocytes

NARCIS (Netherlands)

Jansen, Bastiaan J. H.; van Ruissen, Fred; Cerneus, Stefanie; Cloin, Wendy; Bergers, Mieke; van Erp, Piet E. J.; Schalkwijk, Joost

2003-01-01

Using serial analysis of gene expression we have previously identified the expression of several pro-apoptotic and anti-apoptotic genes in cultured human primary epidermal keratinocytes, including tumor necrosis factor related apoptosis inducing ligand (TRAIL). TRAIL is a potent inducer of apoptosis

Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis.

Science.gov (United States)

Calin, Ruxandra; Caumes, Eric; Reibel, Florence; Ali Mohamed, Anzime; Brossier, Florence; Foltz, Violaine; Boussouar, Samia; Fautrel, Bruno; Maurin, Max; Katlama, Christine; Pourcher, Valérie

2017-07-01

A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF) therapy is reported here. The patient required prolonged treatment with doxycycline-ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a sensitive ELISA for the quantification of human tumour necrosis factor-alpha using 4 polyclonal antibodies.

NARCIS (Netherlands)

Grebenchtchikov, N.J.; Ven-Jongekrijg, J. van der; Pesman, G.J.; Geurts-Moespot, A.; Meer, J.W.M. van der; Sweep, C.G.J.

2005-01-01

Despite the availability of many assays to measure concentrations of tumour necrosis factor alpha (TNF-alpha) in body fluids, these assays often lack specificity or sensitivity and are often of questionable reliability, resulting in inconsistent results. Therefore, we have developed an ELISA that is

Bunched beam neutralization

International Nuclear Information System (INIS)

Gammel, G.M.; Maschke, A.W.; Mobley, R.M.

1979-01-01

One of the steps involved in producing an intense ion beam from conventional accelerators for Heavy Ion Fusion (HIF) is beam bunching. To maintain space charge neutralized transport, neutralization must occur more quickly as the beam bunches. It has been demonstrated at BNL that a 60 mA proton beam from a 750 kV Cockcroft--Walton can be neutralized within a microsecond. The special problem in HIF is that the neutralization must occur in a time scale of nanoseconds. To study neutralization on a faster time scale, a 40 mA, 450 kV proton beam was bunched at 16 MHz. A biased Faraday cup sampled the bunched beam at the position where maximum bunching was nominally expected, about 2.5 meters from the buncher. Part of the drift region, about 1.8 meters, was occupied by a series of Gabor lenses. In addition to enhancing beam transport by transverse focussing, the background cloud of electrons in the lenses provided an extra degree of neutralization. With no lens, the best bunch factor was at least 20. Bunch factor is defined here as the ratio of the distance between bunches to the FWHM bunch length. With the lens, it was hoped that the increased plasma frequency would decrease the neutralization time and cause an increase in the bunch factor. In fact, with the lens, the instantaneous current increased about three times, but the bunch factor dropped to about 10. Even with the lens, the FWHM of the bunches at the position of maximum bunching was still comparable to or less than the oscillation period of the surrounding electron plasma. Thus, the electron density in the lens must increase before neutralization could be effective in this case, or bunching should be done at a lower frequency

Tumor necrosis factor-alpha expression in peripheral blood mononuclear cells correlates with early childhood social interaction in autism spectrum disorder.

Science.gov (United States)

Makinodan, Manabu; Iwata, Keiko; Ikawa, Daisuke; Yamashita, Yasunori; Yamamuro, Kazuhiko; Toritsuka, Michihiro; Kimoto, Sohei; Okumura, Kazuki; Yamauchi, Takahira; Yoshino, Hiroki; Tsujii, Masatsugu; Sugiyama, Toshiro; Tsuchiya, Kenji; Mori, Norio; Matsuzaki, Hideo; Kishimoto, Toshifumi

2017-03-01

Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines. Since social experience of children with autism spectrum disorder is generally unlike to typically developing children, we hypothesized that social interaction during childhood contribute to pro-inflammatory cytokine expression in subjects with autism spectrum disorder. We compared revised Autism Diagnostic Interview scores and expression levels of pro-inflammatory cytokines in peripheral blood mononuclear cells of subjects with autism spectrum disorder (n = 30). The score of domain A on the revised Autism Diagnostic Interview, indicating social interaction impairment in early childhood, was negatively correlated with tumor necrosis factor-α mRNA expression level in peripheral blood mononuclear cells but not interleukin-1β or -6. Consistently, tumor necrosis factor-α mRNA expression was markedly low in subjects with autism spectrum disorder compared to typically developing children who presumably experienced the regular levels of social interaction. These findings suggest that the low blood levels of tumor necrosis factor-α mRNA in subjects with autism spectrum disorder might be due to impaired social interaction in early childhood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy

NARCIS (Netherlands)

van der Meer, Marrit; Hoving, Jan L.; Vermeulen, Marjolein I. M.; Herenius, Marieke M. J.; Tak, Paul P.; Sluiter, Judith K.; Frings-Dresen, Monique H. W.

2011-01-01

To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with

Regulation of Tumor Progression by Programmed Necrosis

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Su Yeon Lee

2018-01-01

Full Text Available Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1, which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.

The proinflammatory cytokine tumor necrosis factor-α excites subfornical organ neurons.

Science.gov (United States)

Simpson, Nick J; Ferguson, Alastair V

2017-09-01

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNF-α -/- mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNF-α into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNF-α, while direct administration of TNF-α into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNF-α. Therefore, we used patch-clamp techniques to examine both acute and long-term effects of TNF-α on the excitability of Sprague-Dawley rat SFO neurons. It was observed that acute bath application of TNF-α depolarized SFO neurons and subsequently increased action potential firing rate. Furthermore, the magnitude of depolarization and the proportion of depolarized SFO neurons were concentration dependent. Interestingly, following 24-h incubation with TNF-α, the basal firing rate of the SFO neurons was increased and the rheobase was decreased, suggesting that TNF-α elevates SFO neuron excitability. This effect was likely mediated by the transient sodium current, as TNF-α increased the magnitude of the current and lowered its threshold of activation. In contrast, TNF-α did not appear to modulate either the delayed rectifier potassium current or the transient potassium current. These data suggest that acute and long-term TNF-α exposure elevates SFO neuron activity, providing a basis for TNF-α hypertensive and sympathetic effects. NEW & NOTEWORTHY Considerable recent evidence has suggested important links between inflammation and the pathological mechanisms underlying hypertension. The present study describes cellular mechanisms through which acute and long-term exposure of tumor necrosis factor-α (TNF-α) influences the activity of subfornical organ neurons by

Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

Science.gov (United States)

Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

Science.gov (United States)

2008-11-19

Microbiology . All Rights Reserved. Hantaan Virus Nucleocapsid Protein Binds to Importin Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced...Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,1 and Department of Microbiology , Mount Sinai...34–36. 32. Prescott , J., C. Ye, G. Sen, and B. Hjelle. 2005. Induction of innate immune response genes by Sin Nombre hantavirus does not require

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

Energy Technology Data Exchange (ETDEWEB)

Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

2015-03-15

Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

Association of tumor necrosis factor alpha gene polymorphism G-308A with pseudoexfoliative glaucoma in the Pakistani population.

NARCIS (Netherlands)

Khan, M.I.; Micheal, S.; Rana, N.; Akhtar, F.; Hollander, A.I. den; Ahmed, A.; Qamar, R.

2009-01-01

PURPOSE: The purpose of the present study was to determine the role of the tumor necrosis factor alpha (TNF-alpha) gene polymorphism G-308A and total serum immunoglobulin E (TsIgE) levels in the onset of pseudoexfoliation glaucoma (PEXG) in Pakistani patients. METHODS: The TNF-alpha polymorphism

Tumor necrosis factor-α regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells

NARCIS (Netherlands)

Giraudo, E.; Primo, L.; Audero, E.; Gerber, H.-P.; Koolwijk, P.; Soker, S.; Klagsbrun, M.; Ferrara, N.; Bussolino, F.

1998-01-01

Tumor necrosis factor-α (TNF-α) modulates gene expression in endothelial cells and is angiogenic in vivo. TNF-α does not activate in vitro migration and proliferation of endothelium, and its angiogenic activity is elicited by synthesis of direct angiogenic inducers or of proteases. Here, we show

Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection

DEFF Research Database (Denmark)

Shinde, Prashant V; Xu, Haifeng C; Maney, Sathish Kumar

2018-01-01

Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain...... stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF) which signals via TNFR1 and promote "enforced virus replication" in CD169(+) macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance....

Avascular necrosis of the femoral head presenting as trochanteric bursitis.

Science.gov (United States)

Mandell, B F

1990-01-01

Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement. PMID:2241294

Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction.

Science.gov (United States)

Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

2015-09-01

Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab

DEFF Research Database (Denmark)

Bendtzen, Klaus; Geborek, Pierre; Svenson, Morten

2006-01-01

Infliximab, an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial...

Interleukin-4 inhibits both paracrine and autocrine tumor necrosis factor-alpha-induced proliferation of B chronic lymphocytic leukemia cells

NARCIS (Netherlands)

van Kooten, C.; Rensink, I.; Aarden, L.; van Oers, R.

1992-01-01

The proliferative response of purified malignant B cells from 26 patients with chronic lymphocytic leukemia (CLL) was investigated in vitro. In the majority of these patients, a proliferative response could be induced by the combination of tumor necrosis factor (TNF)-alpha and PMA. The concentration

Tumour necrosis factor inhibitor treatment and occurrence of anterior uveitis in ankylosing spondylitis

DEFF Research Database (Denmark)

Lie, Elisabeth; Lindström, Ulf; Zverkova-Sandström, Tatiana

2017-01-01

OBJECTIVES: Tumour necrosis factor-α inhibitor (TNFi) treatment has been shown to reduce the rates of anterior uveitis (AU) in patients with ankylosing spondylitis (AS). Our objective was to compare the effect of adalimumab (ADA), etanercept (ETN) and infliximab (IFX) on AU occurrence in AS, using...... obtained by linkage to the Swedish National Patient Register. For each TNFi, AU rates 2 years before TNFi start and for the first 2 years on TNFi treatment were compared. In the subgroup of patients who were AU-free during the 2 years before TNFi start, we also compared the risk of a first AU event...

Effects of interferon-gamma and tumor necrosis factor-alpha on macrophage enzyme levels

Science.gov (United States)

Pierangeli, Silvia S.; Sonnenfeld, Gerald

1989-01-01

Murine peritoneal macrophages were treated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF). Measurements of changes in acid phosphatase and beta-glucuronidase levels were made as an indication of activation by cytokine treatment. IFN-gamma or TNF-gamma treatment resulted in a significant increase in the activities of both enzymes measured in the cell lysates. This increase was observable after 6 h of incubation, but reached its maximum level after 24 h of incubation. The effect of the treatment of the cell with both cytokines together was additive. No synergistic effect of addition of both cytokines on the enzyme levels was observed.

Effectiveness of anti-tumour necrosis factor-α therapy in Danish patients with inflammatory bowel diseases

DEFF Research Database (Denmark)

Bank, Steffen; Andersen, Paal Skytt; Burisch, Johan

2015-01-01

Introduction: The objective of this study was to evaluate the outcome of anti-tumour necrosis factor-α (anti-TNF) treatment in a large cohort of patients with inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) in clinical practice and to establish a cohort...... in clinical trials. Funding: The work was funded by Health Research Fund of Central Denmark Region, Colitis-Crohn Foreningen and the University of Aarhus (PhD grant). Trial registration: Clinicaltrials NCT02322008....

In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor

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Anne Silvestre

2015-07-01

Full Text Available Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction. The tissue inflammation associated with tumour necrosis factor (TNF secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1 stained the E. histolytica trophozoite surface and (on immunoblots binds to a 150-kDa protein. Proteome screening with the TNFR1 sequence revealed a BspA family protein in E. histolytica that carries a TNFR signature domain and six leucine-rich repeats (named here as "cell surface protein", CSP, in view of its cellular location. Cell surface protein shares structural homologies with Toll-Like receptors, colocalizes with TNF and is internalized in TNF-containing vesicles. Reduction of cellular CSP levels abolished chemotaxis toward TNF and blocked parasite invasion of human colon. Conclusions: there is a clear link between TNF chemotaxis, CSP and pathogenesis.

Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications.

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Anne Chastre

Full Text Available Acute liver failure (ALF due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE, a serious neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM hepatotoxicity.Mice were administered saline or etanercept (10 mg/kg; i.p. 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001 and CD40L levels (3.7-fold; p<0.001 compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05, attenuated microglial activation (assessed by OX-42 immunoreactivity, and increased brain glutathione concentrations.These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting liver transplantation.

Risk factors for tuberculosis in inflammatory bowel disease: anti-tumor necrosis factor and hospitalization

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Sabino Riestra

Full Text Available Aims: To determine risk factors for active tuberculosis in patients with inflammatory bowel diseases. Methods: Retrospective, case-control study at 4 referral hospitals in Spain. Cases developed tuberculosis after a diagnosis of inflammatory bowel disease. Controls were inflammatory bowel disease patients who did not develop tuberculosis. For each case, we randomly selected 3 controls matched for sex, age (within 5 years and time of inflammatory bowel disease diagnosis (within 3 years. Inflammatory bowel disease characteristics, candidate risk factors for tuberculosis and information about the tuberculosis episode were recorded. Multivariate analysis and a Chi-squared automatic interaction detector were used. Results: Thirty-four cases and 102 controls were included. Nine of the 34 cases developed active tuberculosis between 1989 and 1999, and 25 became ill between 2000 and 2012. Multivariate regression showed an association between active tuberculosis and anti-TNF (tumor necrosis factor therapy in the previous 12 months (OR 7.45; 95% CI, 2.39-23.12; p = 0.001; hospitalization in the previous 6 months (OR 4.38; 95% CI, 1.18-16.20; p = 0.027; and albumin levels (OR 0.88; 95% CI, 0.81-0.95; p = 0.001. The median time between the start of biologic therapy and the onset of active tuberculosis was 13 (interquartile range, 1-58 months. Tuberculosis developed after a year of anti-TNF therapy in 53%, and late reactivation occurred in at least 3 of 8 patients. Conclusions: The main risks factors for developing tuberculosis were anti-TNF therapy and hospitalization. Over half the cases related to anti-TNF treatment occurred after a year.

Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.

Science.gov (United States)

Bolkun, Lukasz; Lemancewicz, Dorota; Piszcz, Jaroslaw; Moniuszko, Marcin; Bolkun-Skornicka, Urszula; Szkiladz, Malgorzata; Jablonska, Ewa; Kloczko, Janusz; Dzieciol, Janusz

2015-12-01

Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.

Lipopolysaccharide (LPS) stimulates fresh human monocytes to lyse actinomycin D-treated WEHI-164 target cells via increased secretion of a monokine similar to tumor necrosis factor

International Nuclear Information System (INIS)

Chen, A.R.; McKinnon, K.P.; Koren, H.S.

1985-01-01

The effects of lipopolysaccharide (LPS) on tumoricidal activity of human monocytes freshly isolated from peripheral blood were studied. Actinomycin D-treated WEHI-164 cells were used as targets because they are NK insensitive and are lysed rapidly by monocytes in 6-hr 51 Cr-release assays. Monocytes exhibited significant spontaneous activity without endotoxin. Monocytes either pretreated for 1 hr with LPS or assayed in the presence of LPS exhibited 100- to 1000-fold increased cytolytic activity. Cytolytic activity was heat labile and trypsin sensitive, and was recovered from Sepharose S-200 columns in a single peak with an apparent m.w. between 25,000 and 40,000. Actinomycin D or cycloheximide treatment of monocytes before the addition of LPS inhibited cytolytic monokine production. Cytolytic monokine activity was practically neutralized by specific rabbit antisera to human tumor necrosis factor (TNF). It was concluded that, although fresh human monocytes exhibit spontaneous tumoricidal activity, LPS is a potent activating agent. Its stimulatory effects depend on new transcription and translation and are mediated by enhanced secretion of a cytolytic monokine similar to TNF

Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone.

Science.gov (United States)

Xu, Menglin; Wang, Xiangdong

2017-08-01

Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.

Lack of Evidence for a Direct Interaction of Progranulin and Tumor Necrosis Factor Receptor-1 and Tumor Necrosis Factor Receptor-2 From Cellular Binding Studies

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Isabell Lang

2018-04-01

Full Text Available Progranulin (PGRN is a secreted anti-inflammatory protein which can be processed by neutrophil proteases to various granulins. It has been reported that at least a significant portion of the anti-inflammatory effects of PGRN is due to direct high affinity binding to tumor necrosis factor receptor-1 (TNFR1 and TNFR2 and inhibition of tumor necrosis factor (TNF-induced TNFR1/2 signaling. Two studies failed to reproduce the interaction of TNFR1 and TNFR2 with PGRN, but follow up reports speculated that this was due to varying experimental circumstances and/or the use of PGRN from different sources. However, even under consideration of these speculations, there is still a striking discrepancy in the literature between the concentrations of PGRN needed to inhibit TNF signaling and the concentrations required to block TNF binding to TNFR1 and TNFR2. While signaling events induced by 0.2–2 nM of TNF have been efficiently inhibited by low, near to equimolar concentrations (0.5–2.5 nM of PGRN in various studies, the reported inhibitory effects of PGRN on TNF-binding to TNFR1/2 required a huge excess of PGRN (100–1,000-fold. Therefore, we investigated the effect of PGRN on TNF binding to TNFR1 and TNFR2 in highly sensitive cellular binding studies. Unlabeled TNF inhibited >95% of the specific binding of a Gaussia princeps luciferase (GpL fusion protein of TNF to TNFR1 and TNFR2 and blocked binding of soluble GpL fusion proteins of TNFR1 and TNFR2 to membrane TNF expressing cells to >95%, too. Purified PGRN, however, showed in both assays no effect on TNF–TNFR1/2 interaction even when applied in huge excess. To rule out that tags and purification- or storage-related effects compromise the potential ability of PGRN to bind TNF receptors, we directly co-expressed PGRN, and as control TNF, in TNFR1- and TNFR2-expressing cells and looked for binding of GpL-TNF. While expression of TNF strongly inhibited binding of GpL-TNF to TNFR1/2, co

Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

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Nirmala Chandralega Kampan

2017-11-01

Full Text Available BackgroundEpithelial ovarian cancer (EOC remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2, as well as pro-inflammatory factors such as interleukin 6 (IL-6 and tumor necrosis factor (TNF. IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control. In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β and pro-inflammatory cytokines (IL-6 and TNF were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ production by effector T cells, and was

Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion

NARCIS (Netherlands)

Faas, MM; Bakker, WW; Valkhof, N; Baller, JFW; Schuiling, GA

Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 mu g/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant

El factor de necrosis tumoral-α, la resistencia a la insulina, el metabolismo de lipoproteínas y la obesidad en humanos Tumor necrosis factor-α, insulin resistance, the lipoprotein metabolism and obesity in humans

OpenAIRE

M.ª M. Ramírez Alvarado; C. Sánchez Roitz

2012-01-01

En la obesidad el tejido adiposo produce moléculas proinflamatorias como el Factor de Necrosis tumoral-α, que tiene efectos locales en la fisiología del adipocito y efectos sistémicos en otros órganos. Muchos estudios relacionando TNF-α, obesidad, resistencia a la insulina y metabolismo lipídico se han realizado en ratas, conejos y perros, pero los resultados observados en varios de estos estudios han sido contradictorios y muchos de ellos no se han logrado reproducir en humanos, lo...

Granulomatous salmonella osteomyelitis associated with anti-tumor necrosis factor therapy in a non-sickle cell patient: a case report

Energy Technology Data Exchange (ETDEWEB)

Gould, Elaine S.; Gilet, Anthony G. [State University of New York at Stony Brook, Department of Radiology, Stony Brook, NY (United States); Vigorita, Vincent J. [SUNY Health Sciences Center Brooklyn, Department of Pathology and Orthopedics, Brooklyn, NY (United States)

2010-08-15

Salmonella osteomyelitis is seen most commonly in patients with sickle cell disease and in those with compromised immune systems. We report on the clinical, histological and imaging findings of salmonella osteomyelitis with intraosseous abscess formation occurring in a non-sickle cell patient receiving anti-tumor necrosis factor (TNF) alpha therapy. (orig.)

Granulomatous salmonella osteomyelitis associated with anti-tumor necrosis factor therapy in a non-sickle cell patient: a case report

International Nuclear Information System (INIS)

Gould, Elaine S.; Gilet, Anthony G.; Vigorita, Vincent J.

2010-01-01

Salmonella osteomyelitis is seen most commonly in patients with sickle cell disease and in those with compromised immune systems. We report on the clinical, histological and imaging findings of salmonella osteomyelitis with intraosseous abscess formation occurring in a non-sickle cell patient receiving anti-tumor necrosis factor (TNF) alpha therapy. (orig.)

Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients

International Nuclear Information System (INIS)

Gatanaga, Tetsuya; Whang, Chenduen; Cappuccini, F.; Lucci, J.A. III; Jeffes, E.W.B.; Kohr, W.; Lentz, R.; Tomich, J.; Yamamoto, R.S.; Granger, G.A.

1990-01-01

Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor α (TNF-α) in vitro. BF is a protein with a molecular mass of 28kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-α and recombinant human lymphotoxin activity of TNF-α and recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-α more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-α when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-α and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-α in clinical trials with human cancer patients

'Femoral head necrosis' in metabolic and hormonal osteopathies

International Nuclear Information System (INIS)

Heuck, F.H.W.; Treugut, H.

1984-01-01

The pathogenesis of bone necrosis is discussed with special attention and with respect to metabolic, hormonal, and vascular factors. The influence of statics and dynamics of the hip joint bones for the development of aseptic necrosis are discussed. 45 patients with ''idiopathic femoral head necroses'' were observed, including 6 cases of renal osteopathy following renal transplantation and immune suppression therapy, 14 cases of long term corticoid therapy, and 11 cases of liver diseases of different genesis. The femoral head necrosis understood as complication of an osteopathy. In our patients there were 31 males and 14 females - which means higher involvement of males. Plain radiological findings and CT-findings of changes of the femoral heat structure in different stages of the disease are described. Early diagnosis of metabolic and hormonal osteopathies is demanded for a joint keeping therapy of the beginning femoral head necrosis. (orig.) [de

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

Science.gov (United States)

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

2015-12-01

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

A Computational Study of the Oligosaccharide Binding Sites in the Lectin-Like Domain of Tumor Necrosis Factor and the TNF-derived TIP Peptide

Czech Academy of Sciences Publication Activity Database

Dulebo, A.; Ettrich, Rüdiger; Lucas, R.; Kaftan, D.

2012-01-01

Roč. 18, č. 27 (2012), s. 4236-4243 ISSN 1381-6128 Institutional support: RVO:67179843 Keywords : lectin-like domain * tumor necrosis factor * TIP peptide * oligosaccharides * molecular docking * molecular dynamics simulation * alveolar liquid clearance Subject RIV: CE - Biochemistry Impact factor: 3.311, year: 2012

Neutral π decay and transition form-factor in the light-cone

International Nuclear Information System (INIS)

Tomio, L.; Melo, J.P.B.C. De; Frederico, T.

2001-01-01

Full text: Considering phenomenological wave-functions in the light-cone, we obtain the neutral pion (π 0 ) decay and the electromagnetic transition form-factor. The form-factor is obtained from the one-loop quark-diagrams projected on the null plane. By studying different models for the π 0 → γ * γ process, it is found out a strong model sensitivity of the π 0 width. This result suggests that such observable should be used as an important constraint to the model wave function. The relativistic approach to the wave-function based only on constituents quarks is possible in the light-cone due to the suppression of pair creation process. This property arises from the particular choice of the light-cone coordinates. Also the center of mass coordinate is easily separated. In specific processes involving a bound-state, the internal loop-momentum is integrated first in the light-cone energy, then the wave-function of the bound-state appears naturally. This procedure is the essence of the diagrammatic approach that was applied to obtain the weak decay constant and electromagnetic form-factor of the charged pion. In this reference, it was used one-loop dia- grams, the triangle diagram for the form-factor and the bubble diagram which expresses the Partial Conservation of the Axial Current (PCAC). The integration over the light-cone energy in the triangle diagram is per- formed and the asymptotic wave-function of the bound quark-antiquark pair is replaced by phenomenological pion wave-functions. We use three distinct model wave-functions: the Gaussian; the hydrogen-atom; and the wave-function model. This last model has the two characteristics that one believes belongs to Quantum Chromodynamics, i.e., confinement and short distance one gluon exchange. The Gaussian model has only the property of confinement and the Hydrogen model mimics the one gluon exchange at short distances. It is observed that the neutral pion radius presents a correlation with the quark mass. The

Synthesis of tumor necrosis factor α for use as a mirror-image phage display target.

Science.gov (United States)

Petersen, Mark E; Jacobsen, Michael T; Kay, Michael S

2016-06-21

Tumor Necrosis Factor alpha (TNFα) is an inflammatory cytokine that plays a central role in the pathogenesis of chronic inflammatory disease. Here we describe the chemical synthesis of l-TNFα along with the mirror-image d-protein for use as a phage display target. The synthetic strategy utilized native chemical ligation and desulfurization to unite three peptide segments, followed by oxidative folding to assemble the 52 kDa homotrimeric protein. This synthesis represents the foundational step for discovering an inhibitory d-peptide with the potential to improve current anti-TNFα therapeutic strategies.

PROGNOSTIC VALUE OF TUMOR NECROSIS FACTOR-ALPHA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

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E. N. Zotina

2016-01-01

Full Text Available The prognostic value of tumor necrosis factor-alfa (TNFα, a pro-inflammatory cytokine was studied in 140 patients with a newly diagnosed chronic lymphocytic leukemia (CLL. TNFα contents in blood serum was determined using ELISA method. A significant increase of serum TNFα was shown in patients with newly diagnosed CLL, as compared to healthy individuals. Dependence of the cytokine concentration on clnical stage and course of disease was revealed: the highest levels of serum TNFα were registered in patients with advanced disease and/or CLL progression. Distinct correlations were revealed between the studied cytokine amounts and clinical laboratory parameters reflecting the cell proliferative activity and tumor clone size. Immunochemotherapy was accompanied by a significant reduction of TNFα levels. According to the data from multivariate regression analysis. TNFα level of at the time of the diagnosis was an independent predictor of overall survival. Hence, TNFα plays an important role in CLL pathogenesis and may be used as an additional predictive factor for CLL outcomes.

Tumor necrosis factor-α inhibits effects of aryl hydrocarbon receptor ligands on cell death in human lymphocytes.

Science.gov (United States)

Ghatrehsamani, Mahdi; Soleimani, Masoud; Esfahani, Behjat A Moayedi; Shirzad, Hedayatollah; Hakemi, Mazdak G; Mossahebimohammadi, Majid; Eskandari, Nahid; Adib, Minoo

2015-01-01

Activation of aryl hydrocarbon receptor (AhR) leads to diverse outcome in various kinds of cells. AhR activation may induce apoptosis or prevent of apoptosis and cell death. Recent studies suggest that apoptosis effects of AhR can be modulated by inflammatory cytokine like tumor necrosis factor alpha (TNF-α). In this study, we try to investigate the possible interaction of TNF-α with the 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR, on peripheral lymphocytes. Human peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood by discontinuous density gradient centrifugation on ficoll. Isolated PBMCs were divided into four groups: Control group, TNF-α administered group, TCDD administered group, co-administered group with TCDD and TNF-α. Cells were maintained for a week in lymphocyte culture condition. Then, TNF-α was added to group 2 and 4. Finally, apoptosis and necrosis were analyzed in all samples using flowcytometry. In group 4, the mean percent of necrosis and apoptosis in TCDD treatment groups was significantly larger than other groups; (P 0.05). However, the mean percent of cell death in co-administered group with TCDD and TNF-α was significantly lower than other groups; (P < 0.05). TNF-α could significantly inhibit effects of TCDD on lymphocytes apoptosis. Combination effects of TNF-α and TCDD on lymphocyte increase cell survival.

Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo

NARCIS (Netherlands)

Hinsbergh, V.W.M. van; Kooistra, T.; Berg, E.A. van den; Princen, H.M.G.; Fiers, W.; Emeis, J.J.

1988-01-01

The vascular endothelium plays an important role in fibrinolysis by producing tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). The monokine tumor necrosis factor (human recombinant TNF) increased the production of PAI by cultured human endothelial cells from

Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

Science.gov (United States)

Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

1997-01-01

We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

Interleukin-6 and tumor necrosis factor-alpha values in elk neonates

Science.gov (United States)

Barber-Meyer, S. M.; Johnson, C.R.; Murtaugh, M.P.; Mech, L.D.; White, P.J.

2007-01-01

Serological indicators of general condition would be helpful for monitoring or assessing ungulate wildlife. Toward that end, we report the 1st reference values for 2 cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-??), in neonatal elk (Cervus elaphus). We obtained blood samples from 140 calves ??? 6 days old in Yellowstone National Park during summer 2003-2005. TL-6 values ranged from 0 to 1.21 pg/ml with a median of 0.03 pg/ml. TNF-?? values ranged from 0 to 225.43 pg/ml with a median of 1.85 pg/ml. IL-6 and TNF-?? concentrations were not significant predictors of elk calf survival through 21 days. Development of ungulate-based IL-6 and TNF-?? assays that provide greater sensitivity than cross-reacting human-based assays could be helpful in monitoring ungulate condition and health status comparisons among herds. Such information could provide indirect assessments of range quality or environmental influences among herds. 

Elevated levels of tumor necrosis factor alpha and mortality in centenarians

DEFF Research Database (Denmark)

Bruunsgaard, Helle; Andersen-Ranberg, Karen; Hjelmborg, Jacob v B

2003-01-01

BACKGROUND: Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) alpha initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-alpha was also a prognostic marker for all......-cause mortality in these persons. METHODS: We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-alpha, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during...... the subsequent 5 years. RESULTS: Only 9 subjects were alive after 5 years. Elevated levels of TNF-alpha were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C...

Tumor necrosis factor-alpha and its receptors in epithelial ovarian cancer.

Directory of Open Access Journals (Sweden)

Jacek Nikliński

2010-05-01

Full Text Available The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF-alpha and its receptors (TNF-Rs in the epithelial ovarian cancer (EOC and compare these results with the outcome of 126 patients. Presence of TNF-alpha, TNFR-1 and TNFR-2 were studied by Western blotting and immunohistochemistry. The proportion of samples positive for TNF-alpha and TNF-R2 was higher in epithelial ovarian cancer patients than in benign ovarian diseases (p<0.001 and p=0.016, respectively. Immunostaining intensity of TNF-R2 were correlated with tumor stage (p<0.001 and with reduced mean survival time (MST (p=0.002. The results of the present study suggested that tissue expression of TNF-R2 in epithelial ovarian cancer was correlated with the highest risk of cancer progression. Thus, the clinical value of activated TNF system in epithelial ovarian cancer needs to be further investigated.

Paradoxical response with increased tumor necrosis factor-α levels to anti-tuberculosis treatment in a patient with disseminated tuberculosis

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Sho Watanabe

2017-01-01

Full Text Available It has been reported that tuberculosis (TB worsens after cessation of tumor necrosis factor-α inhibitors and starting anti-TB treatment. Little is known about the immunological pathogenesis of this paradoxical response (PR. We report the first case of a TB patient in whom PR occurred concurrently with elevation of circulating tumor necrosis factor-α (TNFα levels. A 75-year-old woman, who had been treated with adalimumab for SAPHO syndrome, developed disseminated TB. Soon after administration of anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol, and after discontinuation of adalimumab, a PR occurred. Serial testing of serum cytokine levels revealed a marked increase in TNFα, and a decline in interferon-γ levels. Despite intensive treatment with antibiotics, prednisolone, noradrenaline, and mechanical ventilation, acute respiratory distress syndrome developed and she died. Thus, overproduction of TNFα after cessation of TNFα inhibitors may partially account for the pathogenesis of a PR. This supports preventative or therapeutic reinitiation of TNFα inhibitors when PR occurs. Serial monitoring of circulating inflammatory cytokine levels could lead to earlier identification of a PR.

Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1.

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Dinarello, C A; Cannon, J G; Wolff, S M; Bernheim, H A; Beutler, B; Cerami, A; Figari, I S; Palladino, M A; O'Connor, J V

1986-06-01

Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the fever produced by rIL-1. On a weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce the same amount of fever and induce comparable levels of PGE2 in rabbit hypothalamic cells in vitro; like IL-1, TNF fever is blocked by drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) rTNF alpha produces biphasic fevers. The first fever reaches peak elevation 45-55 min after bolus injection and likely represents a direct action on the thermoregulatory center. During the second fever peak (3 h later), a circulating endogenous pyrogen can be shown present using passive transfer of plasma into fresh rabbits. This likely represents the in vivo induction of IL-1. In vitro, rTNF alpha induces the release of IL-1 activity from human mononuclear cells with maximal production observed at 50-100 ng/ml of rTNF alpha. In addition, rTNF alpha and rIFN-gamma have a synergistic effect on IL-1 production. The biological activity of rTNF alpha could be distinguished from IL-1 in three ways: the monophasic pyrogenic activity of rIL-1 was destroyed at 70 degrees C, whereas rTNF alpha remained active; anti-IL-1 neutralized IL-1 but did recognize rTNF alpha or natural cachectin nor neutralize its cytotoxic effect; and unlike IL-1, rTNF alpha was not active in the mitogen-stimulated T cell proliferation assay. The possibility that endotoxin was responsible for rTNF alpha fever and/or the induction of IL-1 was ruled-out in several studies: rTNF alpha produced fever in the endotoxin-resistant C3H/HeJ mice; the IL-1-inducing property of rTNF alpha was destroyed either by heat (70 degrees C) or trypsinization, and was unaffected by polymyxin B; pyrogenic tolerance to daily injections of rTNF alpha did not occur; levels of endotoxin, as determined in the Limulus amebocyte lysate, were below the minimum rabbit pyrogen dose; and

Implication of snail in metabolic stress-induced necrosis.

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Cho Hee Kim

2011-03-01

Full Text Available Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

Renal papillary necrosis

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... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

Early Diagnosis of Avascular Necrosis of Bone Following Renal Transplantation By Bone Scan

International Nuclear Information System (INIS)

Shin, Hyun Ho; Kim, Han Su; Ihn, Chun Gyoo; Kim, Myung Jae

1982-01-01

Avascular necrosis of bone has become a well-recognized complication of renal transplantation. While preexisting metabolic bone disease, especially hyperparathyroidism, and metabolic disturbances induced by steroids have been implicated as etiological factors, the pathogenesis is controversial. The diagnosis of avascular necrosis of bone had been based on a history of joint pain and radiographic demonstration of bone necrosis. Recently the bone scan using 99m Tc-methylene diphosphonate is helpful in determining the early stage of bone necrosis. We report two cases of avascular necrosis of femur head, of which diagnosis was made by the bone scan using 99m Tc-methylene diphosphonate.

Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through the Toll-like receptor 4-nuclear factor-κB signaling pathway and myoblast-derived tumor necrosis factor-α.

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Yuko Ono

Full Text Available Circulating lipopolysaccharide (LPS concentrations are often elevated in patients with sepsis or with various endogenous diseases that are associated with metabolic endotoxemia. Involuntary loss of skeletal muscle, termed muscle wasting, is commonly observed in these conditions, suggesting that circulating LPS might play an essential role in its development. Although impairment of muscle regeneration is an important determinant of skeletal muscle wasting, it is unclear whether LPS affects this process and, if so, by what mechanism. Here, we used the C2C12 myoblast cell line to investigate the effects of LPS on myogenesis.C2C12 myoblasts were grown to 80% confluence and induced to differentiate in the absence or presence of LPS (0.1 or 1 μg/mL; TAK-242 (1 μM, a specific inhibitor of Toll-like receptor 4 (TLR4 signaling; and a tumor necrosis factor (TNF-α neutralizing antibody (5 μg/mL. Expression of a skeletal muscle differentiation marker (myosin heavy chain II, two essential myogenic regulatory factors (myogenin and MyoD, and a muscle negative regulatory factor (myostatin was analyzed by western blotting. Nuclear factor-κB (NF-κB DNA-binding activity was measured using an enzyme-linked immunosorbent assay.LPS dose-dependently and significantly decreased the formation of multinucleated myotubes and the expression of myosin heavy chain II, myogenin, and MyoD, and increased NF-κB DNA-binding activity and myostatin expression. The inhibitory effect of LPS on myogenic differentiation was reversible, suggesting that it was not caused by nonspecific toxicity. Both TAK-242 and anti-TNF-α reduced the LPS-induced increase in NF-κB DNA-binding activity, downregulation of myogenic regulatory factors, and upregulation of myostatin, thereby partially rescuing the impairment of myogenesis.Our data suggest that LPS inhibits myogenic differentiation via a TLR4-NF-κB-dependent pathway and an autocrine/paracrine TNF-α-induced pathway. These pathways

Tumor Necrosis Factors, Interferons and Matrix Metalloproteinase-9 in Sera of Non-Hodgkin's Lymphoma Patients

International Nuclear Information System (INIS)

Abdel Malak, C.A.; Karawya, E.M.; Hammouda, G.A.; Zakhary, N.I.

2003-01-01

In the present study, the serum levels of some cytokines and the matrix metalloproteinase-9 (MMP-9) were studied in an attempt to find suitable markers for early diagnosis of non- Hodgkin's lymphoma (NHL) and to assess their role in differentiating between disseminated and non disseminated cases. The present study was conducted on 60 patients with non disseminated NHL, 14 patients with disseminated NHL, in addition to 10 healthy controls. Their sera were used to determine tumor necrosis factor-α (TNF--α), tumor necrosis factor--β (TNF-β), interferon---α), (IFN--α), interferon-γ (IFN--γ) and Matrix Metalloproteinase-9 (MMP-9) using the ELISA technique. The results showed that the serum level of TNF---α), and IFN---α), can be used to differentiate between the control group and the group of NHL patients. However, they could not differentiate between non disseminated NHL (nd- NHL) and disseminated NHL (d- NHL). On the other hand, the serum level of TNF-β) can be used to differentiate between nd- NHL and d- NHL, but not between the control group and nd-NHL. Each of [FN--γ and MMP-9 were not useful in discrimination between the control group and the diseased ones. Our data revealed no correlation between serum level of the parameters investigated and the gender of the patients. The present results revealed that TNF-α) and INF-α), can be used as diagnostic tools for NHL. On the other hand, TNF-β) is useful in the differentiation between nd-NHL and d-NHL

Levels of inhibitors of tumor necrosis factor alpha and interleukin 1beta in urine and sera of patients with urosepsis

NARCIS (Netherlands)

Olszyna, D. P.; Prins, J. M.; Buis, B.; van Deventer, S. J.; Speelman, P.; van der Poll, T.

1998-01-01

The antiinflammatory cytokine response during urosepsis was determined by measurement of concentrations of soluble tumor necrosis factor receptor (sTNFR) types I and II, interleukin 1 receptor antagonist (IL-1ra), soluble IL-1 receptor type II (sIL-1RII), and interleukin 10 in sera and urine of 30

Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma : The value of adjuvant radiotherapy

NARCIS (Netherlands)

Thijssens, KMJ; van Ginkel, RJ; Pras, E; Suurmeijer, AJH; Hoekstra, HJ

Background: The aim was to investigate the value of adjuvant radiotherapy for locally advanced soft tissue sarcoma after hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan followed by limb-saving surgery. Methods: From 1991 to 2003, 73 patients (median age, 54

Molecular and functional characterization of pigeon (Columba livia) tumor necrosis factor receptor-associated factor 3.

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Zhou, Yingying; Kang, Xilong; Xiong, Dan; Zhu, Shanshan; Zheng, Huijuan; Xu, Ying; Guo, Yaxin; Pan, Zhiming; Jiao, Xinan

2017-04-01

Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays a key antiviral role by promoting type I interferon production. We cloned the pigeon TRAF3 gene (PiTRAF3) according to its predicted mRNA sequence to investigate its function. The 1704-bp full-length open reading frame encodes a 567-amino acid protein. One Ring finger, two TRAF-type Zinc fingers, one Coiled coil, and one MATH domain were inferred. RT-PCR showed that PiTRAF3 was expressed in all tissues, with relatively weak expression in the heart and liver. In HEK293T cells, over-expression of wild-type, △Ring, △Zinc finger, and △Coiled coil PiTRAF3, but not a △MATH form, significantly increased IFN-β promoter activity. Zinc finger and Coiled coil domains were essential for NF-κB activation. In chicken HD11 cells, PiTRAF3 increased IFN-β promoter activity and four domains were all contributing. R848 stimulation of pigeon peripheral blood mononuclear cells and splenocytes significantly increased expression of PiTRAF3 and the inflammatory cytokine genes CCL5, IL-8, and IL-10. These data demonstrate TRAF3's innate immune function and improve understanding of its involvement in poultry antiviral defense. Copyright © 2016 Elsevier Ltd. All rights reserved.

Post Traumatic Avascular Necrosis of the Proximal Carpal Row--A Case Report.

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Manohara, Ruben; Sebastin, Sandeep Jacob; Puhaindran, Mark Edward

2015-10-01

We report a case of avascular necrosis of the scaphoid, lunate and triquetrum in a young 21-year-old patient, after a purely ligamentous peri-lunate dislocation of the wrist. He presented with a Mayfield III peri-lunate dislocation after a road traffic accident and underwent an open reduction and internal fixation. Post-operatively, the scapho-lunate gap widened after removal of the temporary K-wires, and he gradually developed avascular necrosis of the scaphoid, lunate and triquetrum, and osteoarthritis of his wrist. We present this unusual case of simultaneous avascular necrosis of multiple carpal bones and discuss the possible risk factors and subsequent management plans for this complex injury. Our patient has no identifiable contributing factors to developing avascular necrosis. We suspect that the violence of the injury and surgery may have compromised the circulation, and advise caution when treating and counseling these patients pre-operatively.

United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

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Rogers, S N; Palmer, N O A; Lowe, D; Randall, C

2015-02-01

We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Atraumatic Pantalar Avascular Necrosis in a Patient With Alcohol Dependence.

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Callachand, Fayaz; Milligan, David; Wilson, Alistair

2016-01-01

In the United States, an estimated 10,000 to 20,000 new cases of avascular necrosis are diagnosed each year. We present an unusual case of atraumatic avascular necrosis with widespread hindfoot and midfoot involvement. A 62-year-old female with a history of alcohol dependence and smoking, who had previously been treated for avascular necrosis of the knee, presented with right-sided foot pain and difficulty weightbearing. Imaging studies revealed extensive avascular necrosis of the hindfoot and midfoot, which precluded simple surgical intervention. The patient was followed up for 18 months. In the last 8 months of the 18-month period, the patient managed her symptoms using an ankle-foot orthosis. A diagnosis of avascular necrosis should be considered in patients with atraumatic foot and ankle pain, especially in the presence of risk factors such as alcohol excess and smoking. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Tumor necrosis factor and its receptors in the neuroretina and retinal vasculature after ischemia-reperfusion injury in the pig retina

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Gesslein, Bodil; Håkansson, Gisela; Gustafsson, Lotta

2010-01-01

Numerous studies have been performed aimed at limiting the extent of retinal injury after ischemia, but there is still no effective pharmacological treatment available. The aim of the present study was to examine the role of tumor necrosis factor (TNF)α and its receptors (TNF-R1 and TNF-R2), espe...

Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

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Rutault, K; Hazzalin, C A; Mahadevan, L C

2001-03-02

Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

Early Diagnosis of Avascular Necrosis of Bone Following Renal Transplantation By Bone Scan

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Shin, Hyun Ho; Kim, Han Su; Ihn, Chun Gyoo; Kim, Myung Jae [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

1982-09-15

Avascular necrosis of bone has become a well-recognized complication of renal transplantation. While preexisting metabolic bone disease, especially hyperparathyroidism, and metabolic disturbances induced by steroids have been implicated as etiological factors, the pathogenesis is controversial. The diagnosis of avascular necrosis of bone had been based on a history of joint pain and radiographic demonstration of bone necrosis. Recently the bone scan using {sup 99m}Tc-methylene diphosphonate is helpful in determining the early stage of bone necrosis. We report two cases of avascular necrosis of femur head, of which diagnosis was made by the bone scan using {sup 99m}Tc-methylene diphosphonate.

Avascular necrosis of the femoral head after osteosynthesis of femoral neck fracture.

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Min, Byung-Woo; Kim, Sung-Jin

2011-05-18

The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. We evaluated the incidence of avascular necrosis of the femoral head with the use of contemporary techniques for femoral neck fracture fixation. We then sought to determine what potential risk factors influenced the development of avascular necrosis.Between 1990 and 2005, one hundred sixty-three intracapsular femoral neck fractures in 163 patients were treated with internal fixation at our level-I trauma center. All patients were monitored until conversion to total hip arthroplasty or for a minimum of 2 years postoperatively. Ten patients (10 hips) died and 7 patients (7 hips) were lost to follow-up. The remaining 146 patients (146 hips) had a mean 5.2 years of follow-up (range, 3 months to 17 years). The incidence of avascular necrosis was 25.3% (37 hips). The average time to diagnosis of avascular necrosis was 18.8 months (range, 3-47 months). Patient sex, age, interval from injury to surgery, and mechanism of injury were statistically not associated with the development of avascular necrosis. The quality of fracture reduction, adequacy of fixation, degree of displacement, and comminution of the posterior cortex were significantly associated. After we controlled for patient and radiographic characteristics, multivariate analyses indicated that the important predictors for avascular necrosis are poor reduction (odds ratio=13.889) and initial displacement of the fracture (odds ratio=4.693). Copyright 2011, SLACK Incorporated.

Choice of therapeutic tactics after failure of the first tumor necrosis factor-α inhibitor

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N. V. Chichasova

2017-01-01

Full Text Available The paper discusses whether the effect of different biological agents (BAs can be achieved in patients with active rheumatoid arthritis (RA when they inadequately respond to therapy with tumor necrosis factor-α (TNF-α inhibitors. It gives data on the efficacy of BAs with another mechanism of action (abatacept, tocilizumab, and rituximab and on the comparable efficacy of golimumab (GLM in this group of patients. It is shown that the effect of GLM therapy does not depend on the reasons for discontinuation of a previously used TNF-α inhibitors (inefficacy, adverse events, etc.. It is conclusion that GLM is effective after failure of one or two TNF-α inhibitors.

Vasculitis Associated With Tumor Necrosis Factor-α Inhibitors

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Sokumbi, Olayemi; Wetter, David A.; Makol, Ashima; Warrington, Kenneth J.

2012-01-01

Objective To describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors. Patients and Methods This is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti–TNF-α therapy. Results Of 8 patients with vasculitis associated with anti–TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti–TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation. Conclusion Cutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed. PMID:22795634

Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity

DEFF Research Database (Denmark)

Engelmann, H; Holtmann, H; Brakebusch, C

1990-01-01

Immunological cross-reactivity between tumor necrosis factor (TNF) binding proteins which are present in human urine (designated TBPI and TBPII) and two molecular species of the cell surface receptors for TNF is demonstrated. The two TNF receptors are shown to be immunologically distinct, to differ....... These antibodies are cytotoxic to cells which are sensitive to TNF toxicity, induce resistance to TNF toxicity, enhance the incorporation of thymidine into normal fibroblasts, inhibit the growth of chlamydiae, and induce the synthesis of prostaglandin E2. Monovalent F(ab) fragments of the polyclonal antibodies...

Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

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Joseph Kwong

2009-06-01

Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

The dual role of tumor necrosis factor (TNF) in cancer biology.

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Bertazza, Loris; Mocellin, Simone

2010-01-01

Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the cascade of molecular events underlying TNF-mediated tumor regression observed in vivo is still incompletely elucidated. Furthermore, some preclinical findings suggest that TNF may even promote cancer development and progression. With this work we intend to summarize the molecular biology of TNF (with particular regard to its tumor-related activities) and review the experimental and clinical evidence currently available describing the complex and sometime apparently conflicting relationship between this cytokine, cancer biology and antitumor therapy. We also propose a model to explain the dual effect of TNF based on the exposure time and cytokine levels reached within the tumor microenvironment. Finally, we overview recent research findings that might lead to new ways for exploiting the anticancer potential of TNF in the clinical setting.

[Avascular necrosis of the femoral head in a patient with severe aplastic anaemia].

Science.gov (United States)

Plichta, Piotr; Pawelec, Katarzyna

2011-01-01

Avascular necrosis (AVN) is a pathological condition associated with numerous processes. Most frequent causes of ischaemia of the femoral head include trauma, corticosteroid therapy, radiation therapy, alcoholism, Gaucher's disease, systemic lupus erythematosus, rheumatoid arthritis. Corticosteroid therapy is considered the most frequent risk factor for developing avascular necrosis. In this paper we report a case of a 19-year old female patient who developed avascular necrosis of the right femoral head following treatment of severe aplastic anaemia. Clinical symptoms included groin pain and fever, painful abduction and internal rotation, tenderness over the right hip joint. The plain X-ray was not specific. However magnetic resonance imaging of the hip revealed changes characteristic for avascular necrosis. Conservative treatment was administrated. Two years after the onset of first clinical symptoms the patient is able to walk without pain, although the range of motion of the right hip joint is partially diminished. We evaluated the possible risk factors of AVN, diagnostic methods and prognosis. The onset of avascular necrosis should be considered as one of the relevant complications in patients with severe aplastic anaemia following immunosuppressive treatment.

Management of infected pancreatic necrosis: state of the art

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Roberto Rasslan

Full Text Available ABSTRACT Pancreatic necrosis occurs in 15% of acute pancreatitis. The presence of infection is the most important factor in the evolution of pancreatitis. The diagnosis of infection is still challenging. Mortality in infected necrosis is 20%; in the presence of organic dysfunction, mortality reaches 60%. In the last three decades, there has been a real revolution in the treatment of infected pancreatic necrosis. However, the challenges persist and there are many unsolved questions: antibiotic treatment alone, tomography-guided percutaneous drainage, endoscopic drainage, video-assisted extraperitoneal debridement, extraperitoneal access, open necrosectomy? A step up approach has been proposed, beginning with less invasive procedures and reserving the operative intervention for patients in which the previous procedure did not solve the problem definitively. Indication and timing of the intervention should be determined by the clinical course. Ideally, the intervention should be done only after the fourth week of evolution, when it is observed a better delimitation of necrosis. Treatment should be individualized. There is no procedure that should be the first and best option for all patients. The objective of this work is to critically review the current state of the art of the treatment of infected pancreatic necrosis.

Effects of neutral gas collisions on the power transmission factor at the divertor sheath

International Nuclear Information System (INIS)

Futch, A.H.; Matthews, G.F.; Buchenauer, D.; Hill, D.N.; Jong, R.A.; Porter, G.D.

1992-01-01

We show that charge-exchange and other ion-neutral collision can reduce the power transmission factor of the plasma sheath, thereby lowering the ion impact energy and target plate sputtering. The power transmission factor relates the heat flux reaching the divertor target to the plasma density and temperature just in front of the surface: δ=Q surf /J ew k T e . Experimental data from the DIII-D tokamak suggests that δ could be as low as 2-3 near the region of peak divertor particle flux, instead of the 7-8 expected from usual sheath theory. Several effects combine to allow ion-neutral interactions to be important in the divertor plasma sheath. The shallow angle of incidence of the magnetic field (1-3deg in DIII-D) leads to the spatial extension of the sheath from approximately ρ i ∝1 mm normal to the plate to several centimeters along the field lines. Ionization reduces the sheath potential, and collisions reduce the ion impact energy. (orig.)

Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide

DEFF Research Database (Denmark)

Bendtzen, K; Morling, N; Fomsgaard, A

1988-01-01

The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF be...

Granulocyte-Macrophage Colony-Stimulating Factor Amplification of Interleukin-1β and Tumor Necrosis Factor Alpha Production in THP-1 Human Monocytic Cells Stimulated with Lipopolysaccharide of Oral Microorganisms

OpenAIRE

Baqui, A. A. M. A.; Meiller, Timothy F.; Chon, Jennifer J.; Turng, Been-Foo; Falkler, William A.

1998-01-01

Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1β and TNF-α production following GM-CSF suppl...

Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

DEFF Research Database (Denmark)

Clausen, Bettina H; Lambertsen, Kate L; Babcock, Alicia A

2008-01-01

BACKGROUND: Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We inv...

Airway necrosis after salvage esophagectomy

International Nuclear Information System (INIS)

Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

2010-01-01

Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

Science.gov (United States)

Cates, Justin Mm; Dupont, William D

2017-01-01

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

Tumor necrosis factor alpha inhibitors in the treatment of toxic epidermal necrolysis.

Science.gov (United States)

Woolridge, Katelyn F; Boler, Patrick L; Lee, Brian D

2018-01-01

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction for which there is no standardized or consistently effective treatment. Due to a greater understanding of disease pathogenesis and the identification of tumor necrosis factor (TNF) α as a mediator of keratinocyte death, TNF-α antagonists have been used in the treatment of TEN. Specifically, infliximab and etanercept have been shown to be effective at halting disease progression. The objective of this study is to review published case reports and case series using anti-TNF-α medications in the treatment of TEN. Results of many of the articles reviewed support the use of TNF-α inhibitors in TEN in both adult and pediatric populations; however, the risks caused by these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

Tumor necrosis factor alpha of teleosts: in silico characterization and homology modeling

Directory of Open Access Journals (Sweden)

Tran Ngoc Tuan

2016-10-01

Full Text Available Tumor necrosis factor alpha (TNF- is known to be crucial in many biological activities of organisms. In this study, physicochemical properties and modeling of TNF- protein of fish was analyzed using in silico approach. TNF- proteins selected from fish species, including grass carp (Ctenopharyngodon idella, zebra fish (Danio rerio, Nile tilapia (Oreochromis niloticus, goldfish (Carassius auratus, and rainbow trout (Oncorhynchus mykiss were used in this study. Physicochemical characteristics with molecular weight, theoretical isoelectric point, extinction coefficient, aliphatic index, instability index, total number of negatively charged residues and positively charged residues, and grand average of hydropathicity were computed. All proteins were classified as transmembrane proteins. The “transmembrane region” and “TNF” domain were identified from protein sequences. The function prediction of proteins was also performed. Alpha helices and random coils were dominating in the secondary structure of the proteins. Three-dimensional structures were predicted and verified as good structures for the investigation of TNF- of fish by online server validation.

UVEITIS INA RHEUMATOLOGISTS PRACTICE: A ROLE OF TUMOR NECROSIS FACTOR-а INHIBITORS

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Sergey Valentinovich Moiseyev

2009-01-01

Full Text Available Uveitis frequently develops in patients with ankylosing spondylitis (AS and other autoimmune diseases. It is occasionally characterized by a severe recurrent course and untreatable with systemic glucocorticoids (GC and standard immunosuppressive agents. The results of (mainly small clinical trials, as well as some observations suggest that therapy with tumor necrosis factor-а (TNF-а inhibitors is effective in such patients. There is the strongest evidence that they are beneficial in treating recurrent uveitis in patients with AS, infliximab having some efficacy advantages over etanercept and adalimumab. Accordingly, chronic uveitis in AS can be considered as an additional argument in favor of the use of TNF-а inhibitors. Furthermore, treatment with drugs of this group is warranted in severe uveitis refractory to GC and immunosuppressants. It is conceivable that in some forms of uveitis, for example, in patients with Behcet's disease, treatment with TNF-а inhibitors should be initiated at an earlier stage as the efficacy of standard immunosuppressants is generally limited

[Effects of occupational stress on serum tumor necrosis factor-α and interleukins].

Science.gov (United States)

Zhou, Wen-Hui; Yu, Shan-Fa; Jiang, Kai-You

2010-12-01

To explore the effect of occupational stress on serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-2 and IL-4. A cross-sectional epidemiological study was conducted in 200 workers from the refrigerator assembly line in Henan province in China. Psychosocial work conditions were measured by using the job demand-control model, the effort-reward imbalance model questionnaires and occupational stress measurement scale. Serum TNF-α, IL-1β, IL-2, and IL-4 concentrations were measured by radioimmunoassay or immunoradiometric assay method respectively. Serum TNF-α concentration was statistically significantly different between workers with higher affective balance level and control groups [(1.947 ± 0.173) and (2.029 ± 0.240) fmol/ml] (P life stress level and control groups [(1.759 ± 0.361) and (1.606 ± 0.381) ng/ml] (P life stress and role ambiguity were the predictors of serum IL-2 (R(2) was 0.040, 0.078 and 0.104, respectively). Reward was the predictor of serum IL-4 (R(2) = 0.030). Unhealthy psychological stress factor might be induce a marked increase in the concentrations of serum TNF-α, IL-1β, IL-2, as well as IL-4.

Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy

DEFF Research Database (Denmark)

Larsson, S; Englund, M; Struglics, A

2015-01-01

concentrations of interleukin (IL)-6, -8 and tumor necrosis factor (TNF)-α by multiplex immunoassay, graded radiographic features of tibiofemoral and patellofemoral OA according to the Osteoarthritis Research Society International (OARSI) atlas, scored patient-reported outcomes using the Knee Injury...

Autocrine secretion of tumor necrosis factor under the influence of interferon-γ amplifies HLA-DR gene induction in human monocytes

International Nuclear Information System (INIS)

Arenzana-Seisdedos, F.; Mogensen, S.C.; Vuillier, F.; Fiers, W.; Virelizier, J.L.

1988-01-01

Recombinant interferon-γ (IFN-γ) induced HLA-DR gene expression in both U937 and THP-1 human monocytic cell lines, although the former was only very weakly inducible. Combination of recombinant tumor necrosis factor (TNF) and IFN-γ resulted in a synergistic enhancement of DR mRNA and protein induction in both cell lines. TNF alone increased the constitutive expression of the DR gene in THP-1 cells. In the HLA class II-negative U937 cells, TNF used alone was not able to induce DR gene expression. Such a negative result was not due to a lack of TNF receptor expression in U937 cells, since TNF clearly induced HLA class I and TNF gene expression in this cell line. THP-1, but not U937, cells secreted TNF under the influence of IFN-γ. Neutralization of TNF by a specific antibody decreased IFN-γ-induced DR antigen expression in THP-1 cultures. These observations indicate that TNF is not able to directly induce DR gene expression, but rather amplifies ongoing expression of this gene, whether constitutive or induced by IFN-γ. In the two cell lines tested, the level of DR inducibility under the influence of IFN-γ used alone depended on a different inducibility of TNF secretion by IFN-γ. Altogether, the observations indicate that TNF, whether exogenous or endogenously produced under the influence of IFN-γ, amplifies DR gene expression in monocytes, a phenomenon that may provide to such antigen-presenting cells a selective sensitivity to the DR-inducing effects of IFN-γ

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

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Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

2017-09-01

Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

Science.gov (United States)

Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

2005-05-01

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

'Femoral head necrosis' in metabolic and hormonal osteopathies

Energy Technology Data Exchange (ETDEWEB)

Heuck, F.H.W.; Treugut, H.

1984-07-01

The pathogenesis of bone necrosis is discussed with special attention and with respect to metabolic, hormonal, and vascular factors. The influence of statics and dynamics of the hip joint bones for the development of aseptic necrosis are discussed. 45 patients with ''idiopathic femoral head necroses'' were observed, including 6 cases of renal osteopathy following renal transplantation and immune suppression therapy, 14 cases of long term corticoid therapy, and 11 cases of liver diseases of different genesis. The femoral head necrosis understood as complication of an osteopathy. In our patients there were 31 males and 14 females - which means higher involvement of males. Plain radiological findings and CT-findings of changes of the femoral heat structure in different stages of the disease are described. Early diagnosis of metabolic and hormonal osteopathies is demanded for a joint keeping therapy of the beginning femoral head necrosis. 90 refs.

Regulatory role of tumor necrosis factor receptor-associated factor 6 in breast cancer by activating the protein kinase B/glycogen synthase kinase 3β signaling pathway.

Science.gov (United States)

Shen, Hongyu; Li, Liangpeng; Yang, Sujin; Wang, Dandan; Zhou, Siying; Chen, Xiu; Tang, Jinhai

2017-08-01

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples. Compared with adjacent healthy tissues, TRAF6 protein expression levels were significantly upregulated in breast cancer tissues. Reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant upregulation of the cellular proliferative marker Ki‑67 and proliferation cell nuclear antigen expression levels in breast carcinoma specimens. Furthermore, protein expression levels of the accessory molecule, transforming growth factor β‑activated kinase 1 (TAK1), were significantly increased in breast cancer patients, as detected by western blot analysis. As determined by MTT assay, TRAF6 exerted profoundly proliferative effects in the MCF‑7 breast cancer cell line; however, these detrimental effects were ameliorated by TAK1 inhibition. Notably, protein kinase B (AKT)/glycogen synthase kinase (GSK)3β phosphorylation levels were markedly upregulated in breast cancer samples, compared with adjacent healthy tissues. In conclusion, an altered TRAF6‑TAK1 axis and its corresponding downstream AKT/GSK3β signaling molecules may contribute to breast cancer progression. Therefore, TRAF6 may represent a potential therapeutic target for the treatment of breast cancer.

Tumor necrosis factor-alpha induces activation of coagulation and fibrinolysis in baboons through an exclusive effect on the p55 receptor

NARCIS (Netherlands)

van der Poll, T.; Jansen, P. M.; van Zee, K. J.; Welborn, M. B.; de Jong, I.; Hack, C. E.; Loetscher, H.; Lesslauer, W.; Lowry, S. F.; Moldawer, L. L.

1996-01-01

Tumor necrosis factor-alpha (TNF-alpha) can bind to two distinct transmembrane receptors, the p55 and p75 TNF receptors. We compared the capability of two mutant TNF proteins with exclusive affinity for the p55 or p75 TNF receptor with that of wild type TNF, to activate the hemostatic mechanism in

Increased expression of vascular endothelial growth factor attenuates contusion necrosis without influencing contusion edema after traumatic brain injury in rats.

Science.gov (United States)

Tado, Masahiro; Mori, Tatsuro; Fukushima, Masamichi; Oshima, Hideki; Maeda, Takeshi; Yoshino, Atsuo; Aizawa, Shin; Katayama, Yoichi

2014-04-01

To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (pnecrosis at 21 days (pnecrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.

Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

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Tetsuya Ishida

2014-01-01

Full Text Available We report a 45-year-old female patient who developed acute hepatic disorder during anti-tumor necrosis factor α therapy for the treatment of Crohn's disease (CD. She was diagnosed as colonic CD and placed on infliximab (IFX. She was negative for hepatitis B surface antigen at the initiation of IFX therapy, but developed acute hepatitis after the 30th administration of IFX 4 years and 1 month after the first administration. She was suspected to have had occult hepatitis B virus infection before IFX therapy, and de novo hepatitis B was considered the most likely diagnosis. Hepatitis subsided after discontinuation of anti-tumor necrosis factor α therapy and initiation of treatment with entecavir. She started to receive adalimumab to prevent relapse of CD. She has continued maintenance therapy with entecavir and adalimumab and has since been asymptomatic. As de novo hepatitis B may be fatal, virological testing for hepatitis B is essential for patients who are being considered for treatment that may weaken the immune system.

Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study.

Science.gov (United States)

Rosen, Lauren E; Karrison, Theodore; Ananthanarayanan, Vijayalakshmi; Gallan, Alexander J; Adusumilli, Prasad S; Alchami, Fouad S; Attanoos, Richard; Brcic, Luka; Butnor, Kelly J; Galateau-Sallé, Françoise; Hiroshima, Kenzo; Kadota, Kyuichi; Klampatsa, Astero; Stang, Nolween Le; Lindenmann, Joerg; Litzky, Leslie A; Marchevsky, Alberto; Medeiros, Filomena; Montero, M Angeles; Moore, David A; Nabeshima, Kazuki; Pavlisko, Elizabeth N; Roggli, Victor L; Sauter, Jennifer L; Sharma, Anupama; Sheaff, Michael; Travis, William D; Vigneswaran, Wickii T; Vrugt, Bart; Walts, Ann E; Tjota, Melissa Y; Krausz, Thomas; Husain, Aliya N

2018-04-01

A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple

Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

DEFF Research Database (Denmark)

Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj

2003-01-01

BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin....../or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow....... Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (Palpha...

Characterization of receptors for recombinant human tumor necrosis factor-alpha from human placental membranes

International Nuclear Information System (INIS)

Aiyer, R.A.; Aggarwal, B.B.

1990-01-01

High affinity receptors for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) were identified on membranes prepared from full term human placenta. Highly purified rhTNF-alpha iodinated by the iodogen method was found to bind placental membranes in a displaceable manner with an approximate dissociation constant (KD) of 1.9 nM. The membrane bound TNF-alpha receptor could be solubilized by several detergents with optimum extraction being obtained with 1% Triton X-100. The binding of 125I-rhTNF-alpha to the solubilized receptor was found to be time and temperature dependent, yielding maximum binding within 1 h, 24 h and 48 h at 37 degrees C, 24 degrees C and 4 degrees C, respectively. However, the maximum binding obtainable at 4 degrees C was only 40% of that at 37 degrees C. The binding 125I-rhTNF-alpha to solubilized placental membrane extracts was displaceable by unlabeled rhTNF-alpha, but not by a related protein recombinant human tumor necrosis factor-beta (rhTNF-beta; previously called lymphotoxin). This is similar to the behavior of TNF-alpha receptors derived from detergent-solubilized cell extracts, although on intact cells, both rhTNF-alpha and rhTNF-beta bind with equal affinity to TNF receptors. The Scatchard analysis of the binding data of the solubilized receptor revealed high affinity binding sites with a KD of approximately 0.5 nM and a receptor concentration of about 1 pmole/mg protein. Gel filtration of the solubilized receptor-ligand complexes on Sephacryl S-300 revealed two different peaks of radioactivity at approximate molecular masses of 50,000 Da and 400,000 Da. The 400,000 dalton peak corresponded to the receptor-ligand complex. Overall, our results suggest that high affinity receptors for TNF-alpha are present on human placental membranes and provide evidence that these receptors may be different from that of rhTNF-beta

MR imaging of avascular necrosis of the femoral head: Evaluation of the prognostic factors

Energy Technology Data Exchange (ETDEWEB)

Jin, Uk; Ryu, Kyung Nam; Yoo, Myung Chul; Yoon, Yup [Kyung Hee University Hospital, Seoul (Korea, Republic of)

1994-07-15

To evaluate the factors influencing the prognosis in avascular necrosis(AVN) of the femoral head by MR. Radiographic and MRI findings of twenty-three patients(30 cases, aged 23-67 years) with AVN identified clinically and radiologically were evaluated. The radiography included follow up study for at least 6 months. The mean age of these patients was 43 years and M : F ratio was 20 : 3. MR imaging was performed at 1.5 T unit using T1- and T2-weighted coronal and T1-weighted sagittal and axial spin echo sequences. We categorized the changes of the femoral head on radiographic follow-ups to three grades of mild , moderate and severe. We also analyzed the changes of the signal intensity and sizes of the lesion at sagittal and coronal MR images. On MR imaging we classified the extent of AVN of the femoral head to 2 grades according to the size of lesion. In the cases of mild changes in femoral head on radiography, the mean age of the patient was 37 years and the extent of AVN was below 1/2 in eleven out of seventeen cases. In the cases of moderate changes, the mean age was 43 years and the extent was above 1/2 in five out of seven cases. In the cases of severe changes, the mean age was 60 years and the extent was above 1/2 in all 6 cases. With 95% confidence coefficient, comparisons in the age and necrosis extent revealed statistical significance in severe versus moderate changes and in severe versus mild changes. Comparisons in the change of signal intensity on T1 and T2 weighted images showed no statistical relationship between each other. We conclude that if patient is younger and has smaller extent of the AVN, bone destruction is slower that these factors may be helpful in predicting the prognosis of AVN. However, the modes of the changes of the signal intensity on T1- and T2-weighted images may not be useful in predicting the prognosis of AVN.

Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors

DEFF Research Database (Denmark)

Pedersen, Susanne Juhl; Sørensen, Inge Juul; Lambert, Robert G W

2011-01-01

To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix...... metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy....

P55 tumour necrosis factor receptor in bone marrow-derived cells promotes atherosclerosis development in low-density lipoprotein receptor knock-out mice

NARCIS (Netherlands)

Xanthoulea, Sofia; Gijbels, Marion J. J.; van der Made, Ingeborg; Mujcic, Hilda; Thelen, Melanie; Vergouwe, Monique N.; Ambagts, Matheus H. C.; Hofker, Marten H.; de Winther, Menno P. J.

2008-01-01

Tumour necrosis factor (TNF) is a pivotal pro-inflammatory cytokine with a clear pathogenic role in many chronic inflammatory diseases, and p55 TNF receptor (TNFR) mediates the majority of TNF responses. The aim of the current study was to investigate the role of p55 TNFR expression in bone

Tumor Necrosis Factor-α-Induced Ototoxicity in Mouse Cochlear Organotypic Culture.

Directory of Open Access Journals (Sweden)

Qian Wu

Full Text Available Tumor necrosis factor (TNF-α is a cytokine involved in acute inflammatory phase reactions, and is the primary upstream mediator in the cochlear inflammatory response. Treatment of the organ of Corti with TNF-α can induce hair cell damage. However, the resulting morphological changes have not been systematically examined. In the present study, cochlear organotypic cultures from neonatal mice were treated with various concentrations and durations of TNF-α to induce inflammatory responses. Confocal microscopy was used to evaluate the condition of hair cells and supporting cells following immunohistochemical staining. In addition, the ultrastructure of the stereocilia bundle, hair cells, and supporting cells were examined by scanning and transmission electron microscopy. TNF-α treatment resulted in a fusion and loss of stereocilia bundles in hair cells, swelling of mitochondria, and vacuolation and degranulation of the endoplasmic reticulum. Disruption of tight junctions between hair cells and supporting cells was also observed at high concentrations. Hair cell loss was preceded by apoptosis of Deiters' and pillar cells. Taken together, these findings detail the morphological changes in the organ of Corti after TNF-α treatment, and provide an in vitro model of inflammatory-induced ototoxicity.

Radioprotection by murine and human tumor-necrosis factor; Dose-dependent effects on hematopoiesis in the mouse

Energy Technology Data Exchange (ETDEWEB)

Sloerdal, L; Muench, M O; Warren, D J; Moore, M A.S. [James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York (USA)

1989-01-01

Tumor-necrosis factor (TNF) has been shown to confer significant radioprotection in murine models. Herein, we demonstrate a dose-dependent enhancement of hematological recovery when single doses of either murine or human recombinant TNF are administered prior to irradiation. In addition to its action upon leukocytes and erythocytes, TNF also alleviates radiation-induced thrombocytopenia in the mouse. These effects on circulating blood constituents are further reflected in increased numbers of both primitive (CFU-S) and more differentiated (CFU-GM, CFU-Mega) hematopoietic progenitors in TNF-treated animals. This suggests that TNF exerts it radioprotective effects on a pool of primitive multi-potential hematopoietic cells. (author).

Tumor Necrosis Factor-α Produced in Cardiomyocytes Mediates a Predominant Myocardial Inflammatory Response to Stretch in Early Volume Overload

OpenAIRE

Chen, Yuanwen; Pat, Betty; Zheng, Junying; Cain, Laura; Powell, Pamela; Shi, Ke; Sabri, Abdelkarim; Husain, Ahsan; Dell’Italia, Louis J

2010-01-01

Acute stretch caused by volume overload (VO) of aorto-caval fistula (ACF) induces a variety of myocardial responses including mast cell accumulation, matrix metalloproteinase (MMP) activation and collagen degradation, all of which are critical in dictating long term left ventricle (LV) outcome to VO. Meanwhile, these responses can be part of myocardial inflammation dictated by tumor necrosis factor-α (TNF-α) which is elevated after acute ACF. However, it is unknown whether TNF-α mediates a ma...

Characterization of a Canine Tetranucleotide Microsatellite Marker Located in the First Intron of the Tumor Necrosis Factor Alpha Gene

OpenAIRE

WATANABE, Masashi; TANAKA, Kazuaki; TAKIZAWA, Tatsuya; SEGAWA, Kazuhito; NEO, Sakurako; TSUCHIYA, Ryo; MURATA, Michiko; MURAKAMI, Masaru; HISASUE, Masaharu

2013-01-01

ABSTRACT A polymorphic tetranucleotide (GAAT)n microsatellite in the first intron of the canine tumor necrosis factor alpha (TNFA) gene was characterized in this study; 139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24 Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the presence of the 4 alleles (GAAT)5, (GAAT)6, (GAAT)7 and (GAAT)8, including 9 of the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic informatio...

Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

DEFF Research Database (Denmark)

Dominguez, Helena; Storgaard, Heidi; Rask-Madsen, Christian

2005-01-01

OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic...... glucose uptake remained unchanged as well. Beta-cell function tended to improve. CONCLUSION: Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed....

Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma : Three time periods at risk for amputation

NARCIS (Netherlands)

van Ginkel, Robert J.; Thijssens, Katja M. J.; Pras, Elisabeth; van der Graaf, Winette T. A.; Suurmeijer, Albert J. H.; Hoekstra, Harald J.

Background: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS). Methods: From 1991 to 2003, 73 patients (36 men, 37 women,

Soluble tumor necrosis factor receptor-I in preterm infants with chorioamnionitis.

Science.gov (United States)

Sato, Miho; Nishimaki, Shigeru; An, Hiromi; Shima, Yoshio; Naruto, Takuya; Sugai, Toshiyuki; Iwasaki, Shiho; Seki, Kazuo; Imagawa, Tomoyuki; Mori, Masaaki; Yokota, Shumpei

2009-04-01

The aim of our study was (i) to determine whether chorioamnionitis (CAM) is associated with an elevated soluble tumor necrosis factor receptor I (sTNFR-I) level and (ii) to examine the time course of the concentration of sTNFR-I in preterm infants after birth. We measured sTNFR-I levels in the cord blood of 112 preterm infants (gestational age < or =34 weeks), and those in peripheral blood of 30 preterm infants on days 7, 14, 21 and 28. The median value for the sTNFR-I was significantly elevated in 33 infants with CAM at stage 3 (4618 pg/mL) compared with the 52 infants without CAM (2866 pg/mL), or the 13 infants with CAM at stage 1 (3638 pg/mL) and the 14 infants at stage 2 (3242 pg/mL). The severity of CAM is an independent factor for the elevation of cord blood sTNFR-I. The sTNFR-I level on day 0 was significantly higher in eight infants with CAM at stage 3 than in the 22 infants without CAM or with CAM at stage 1 and 2; however there were no significant differences on days 7, 14, 21 and 28. The serum level of sTNFR-I showed a significant gradual decline with time. We suggest that there is an association between elevated sTNFR-I levels in cord blood and maternal CAM, and this elevation may reflect the fetal inflammation. However the elevation of sTNFR-I could not persist postnatally for a long time.

Vitamin C deficiency aggravates tumor necrosis factor α-induced insulin resistance.

Science.gov (United States)

Qing, Zhou; Xiao-Hui, Wu; Xi-Mei, Wu; Chao-Chun, Zou

2018-06-15

Chronic low-grade inflammation plays a major role in the development of insulin resistance. The potential role and underlying mechanism of vitamin C, an antioxidant and anti-inflammatory agent, was investigated in tumor necrosis factor-α (TNF-α)-induced insulin resistance. Gulonolactone oxidase knockout (Gulo -/- ) mice genetically unable to synthesize vitamin C were used to induce insulin resistance by continuously pumping small doses of TNF-α for seven days, and human liver hepatocellular carcinoma cells (HepG2 cells) were used to induce insulin resistance by treatment with TNF-α. Vitamin C deficiency aggravated TNF-α-induced insulin resistance in Gulo -/- mice, resulting in worse glucose tolerance test (GTT) results, higher fasting plasma insulin level, and the inactivation of the protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β) pathway in the liver. Vitamin C deficiency also worsened liver lipid accumulation and inflammation in TNF-α-treated Gulo -/- mice. In HepG2 cells, vitamin C reversed the TNF-α-induced reduction of glucose uptake and glycogen synthesis, which were mediated by increasing GLUT2 levels and the activation of the insulin receptor substrate (IRS-1)/AKT/GSK3β pathway. Furthermore, vitamin C inhibited the TNF-α-induced activation of not only the mitogen-activated protein kinase (MAPKs), but also nuclear factor-kappa B (NF-κB) signaling. Taken together, vitamin C is essential for preventing and improving insulin resistance, and the supplementing with vitamin C may be an effective therapeutic intervention for metabolic disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased risk of post-operative complications in patients with Crohn's disease treated with anti-tumour necrosis factor α agents - a systematic review

DEFF Research Database (Denmark)

El-Hussuna, Alaa; Theede, Klaus; Olaison, Gunnar

2014-01-01

INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

Science.gov (United States)

Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

1997-05-23

Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

Anorectal stenosis after treatment with tumor necrosis factor α antibodies: a case series

Directory of Open Access Journals (Sweden)

Keegan Denise

2010-07-01

Full Text Available Abstract Introduction We identified three patients who developed anorectal stenosis after successful treatment with anti-tumor necrosis factor α (anti-TNF-α agents. Case presentation Two patients, a 24-year-old Irish Caucasian man and a 64-year-old Irish Caucasian woman, developed symptoms attributable to anorectal stenosis four to six weeks after treatment. A further patient, a 25-year-old Irish Caucasian male, presented three years after treatment with anorectal stenosis, having been asymptomatic with his stenosis for the preceding three years. No patients had evidence of active inflammation at time of representation or had previous anal canal surgery. Conclusion Anorectal stenosis in these patients appears to be independent of active inflammation. No other cause of new stenosis could be identified. We postulate that rapid clinical response to anti-TNF-α agents led to aberrant mucosal healing. This in turn led to anorectal stenosis. This is the first report of this complication in association with the use of biologic agents.

Feline Toxoplasmosis: Tumor Necrosis Factor, Nitric Oxide, and Free Radicals in Seropositive Cats.

Science.gov (United States)

Faria, Joice L M; Couto, Caroline do; Wierzynski, Sheron L; Bottari, Nathieli B; Baldissera, Matheus D; Pereira, Wanderson A B; Da Silva, Aleksandro S

2018-02-01

Toxoplasma gondii is a cosmopolitan protozoan that causes disease in several species, including humans. In cats, these infections are usually asymptomatic, but in other species they can lead to high levels of inflammatory and cell damage markers, causing cellular damage. Therefore, the aim of this study was to measure levels of tumor necrosis factor (TNF-α), reactive oxygen species (ROS), and nitric oxide (nitrite/nitrate-NO x ) in the serum of cats seropositive for T. gondii. Initially, we investigated the presence of antibodies against T. gondii in cats in the city of Concordia, Santa Catarina, Brazil, with the use of indirect immunofluorescence (IFA), and found 30 cats seropositive for T. gondii and 30 seronegative cats. In this study, seropositive cats showed higher levels of TNF-α, ROS, and NO x compared to seronegative cats. Although cats do not show clinical signs of disease, constant inflammatory response can cause cell damage, which over time may adversely affect the animal.

Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

Science.gov (United States)

Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

2015-07-01

Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tumor necrosis factor receptor associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system

Science.gov (United States)

Walsh, Matthew C.; Lee, JangEun; Choi, Yongwon

2016-01-01

Summary Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of IL-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor (IRF) pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system, but also for maintaining immune tolerance, and more recent works have begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. PMID:26085208

In vitro cytotoxicity of human recombinant tumor necrosis factor alpha in association with radiotherapy in a human ovarian carcinoma cell line

International Nuclear Information System (INIS)

Manetta, A.; Lucci, J.; Soopikian, J.; Granger, G.; Berman, M.L.; DiSaia, P.J.

1990-01-01

It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors

Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

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Manetta J

2014-08-01

Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

Closed reduction of slipped capital femoral epiphysis: high-risk factor for avascular necrosis.

Science.gov (United States)

Kitano, Toshio; Nakagawa, Keisuke; Wada, Mayuko; Moriyama, Michiko

2015-07-01

How should we treat acute/unstable slipped capital femoral epiphysis (SCFE) without the development of avascular necrosis (AVN)? To answer this question, we investigated the risk factors of AVN development after SCFE. Seventy-six hips of 64 patients were classified using two kinds of classification systems, Loder's classification based on instability and the conventional classification based on the duration of symptom, because both classifications are related to AVN development. Of 21 unstable SCFEs, seven hips developed AVN. Of 35 hips defined as acute or acute on chronic, nine hips developed AVN. Two stable SCFEs of Loder's classification developed AVN, one was acute and the other was acute on chronic. No hips of chronic SCFE developed AVN. The factor that had influenced AVN development was only closed reduction, whether purposefully or inadvertently, in an acute or unstable SCFE. On the basis of the findings of this study, one should not embark on any modality of closed reduction for an unstable or acute form of SCFE, as there is a high risk for occurrence of AVN. For the same reason, a traction table should not be used for SCFE fixation, so as to avoid an inadvertent reduction or force that can lead to AVN.

Treatment of therapy-resistant perineal metastatic Crohn's disease after proctectomy using anti-tumor necrosis factor chimeric monoclonal antibody, cA2 - Report of two cases

NARCIS (Netherlands)

van Dullemen, HM; de Jong, E; Slors, F; Tytgat, GNJ; van Denventer, SJH

PURPOSE: Two young females with well-documented Crohn's disease and nonhealing perineal wounds following proctectomy compatible with "metastatic Crohn's disease" are described, We hypothesized that metastatic Crohn's disease would be a tumor necrosis factor-dependent inflammatory-reaction and have

Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

NARCIS (Netherlands)

Bos, W.H.; Bartelds, G.M.; Vis, M.; van der Horst, A.R.; Wolbink, G.J.; van de Stadt, R.J.; van Schaardenburg, D.; Dijkmans, B.A.C.; Lems, W.F.; Nurmohamed, M.T.; Aarden, L.; Hamann, D.

2009-01-01

Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody ( ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis ( RA). Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated

Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

NARCIS (Netherlands)

Bos, W.H.; Bartelds, G.M.; Vis, M.; Horst, A.; Wolbink, G.; van de Stadt, R.J.; van Schaardenburg, D.; Dijkmans, B.A.C.; Lems, W.F.; Nurmohamed, M.T.; Aarden, L.; Hamann, D.

2009-01-01

Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated

NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1989-01-01

The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5...

New Onset Autoimmune Hepatitis during Anti-Tumor Necrosis Factor-Alpha Treatment in Children.

Science.gov (United States)

Ricciuto, Amanda; Kamath, Binita M; Walters, Thomas D; Frost, Karen; Carman, Nicholas; Church, Peter C; Ling, Simon C; Griffiths, Anne M

2018-03-01

To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use. We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center. Patients with alanine aminotransferase (ALT) ≥×2 the upper limit of normal were included. The incidence, evolution, and risk factors for liver injury were examined with univariate and multivariable proportional hazards regression. Causality was assessed using the Roussel-Uclaf Causality Assessment Method. The index case, a teenage girl with Crohn's disease, developed elevated liver enzymes and features of autoimmune hepatitis on liver biopsy 23 weeks after starting infliximab. The injury resolved entirely within 4 months of withdrawing infliximab without additional therapy. Overall, 7.7% of our cohort developed new ALT elevations while on anti-TNF. Most ALT elevations were mild and transient and attributable to alternate etiologies. No additional clear cases of autoimmune hepatitis were identified. Transient liver enzyme abnormalities are relatively common among anti-TNF-treated children. Anti-TNF-related DILI with autoimmune features is rare but must be recognized so that therapy can be stopped. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

Czech Academy of Sciences Publication Activity Database

Weber, T.; Lu, M.; Anděra, Ladislav; Lahm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, A.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neuzil, J.

2002-01-01

Roč. 8, - (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA ČR GA312/99/0348 Institutional research plan: CEZ:AV0Z5052915 Keywords : Vitamin E, Antineoplastic Agent, Tumor Necrosis Factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

Differential Effects of Self-Reported Lifetime Marijuana Use on Interleukin-1 Alpha and Tumor Necrosis Factor in African American Adults

OpenAIRE

Keen, Larry; Turner, Arlener D.; Callender, Clive; Campbell, Alfonso

2015-01-01

It is unknown how lifetime marijuana use affects different proinflammatory cytokines. The purpose of the current study is to explore potential differential effects of lifetime marijuana use on interleukin-1 alpha (IL-1α) and tumor necrosis factor (TNF) in a community based sample. Participants included 168 African American adults (51% female, median age= 47 years). Upon study entry, blood was drawn and the participants completed questions regarding illicit drug use history whose answers were ...

A comment on form factor mass singularities in flavor-changing neutral currents

International Nuclear Information System (INIS)

Sanchis, M.A.; Centro Mixto Valencia Univ./CSIC, Valencia

1991-01-01

Flavor-changing effective vertices q l q h V 0 , where V 0 represents a neutral gauge boson (γ,Z 0 ,g), involving a heavy external quark, are discussed within the standard model at one-loop level and second-order approximation in external momenta and masses: the logarithmic singular terms in the form factors at vanishing mass of the internal quark in the loop have to be replaced by pieces coming from next order in external momenta. Implications in the b→d+X penguin transitions are commented. (orig.)

Prognostic factors for survival and radiation necrosis after stereotactic radiosurgery alone or in combination with whole brain radiation therapy for 1–3 cerebral metastases

International Nuclear Information System (INIS)

Schüttrumpf, Lars Hendrik; Niyazi, Maximilian; Nachbichler, Silke Birgit; Manapov, Farkhad; Jansen, Nathalie; Siefert, Axel; Belka, Claus

2014-01-01

In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. 340 patients with 1–3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS ≤ 70: 122 days; KPS > 70: 342 days), for RPA (recursive partitioning analysis) class (RPA class I: 1800 days; RPA class II: 281 days; RPA class III: 130 days), irradiated volume (≤2.5 ml: 354 days; > 2.5 ml: 234 days), prescribed dose (≤18 Gy: 235 days; > 18 Gy: 351 days), gender (male: 235 days; female: 327 days) and whole brain radiotherapy (+WBRT: 341 days/-WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA class and gender. MRI and clinical symptoms suggested radiation necrosis in 21 patients after SRS +/− whole brain radiotherapy (WBRT). In five patients clinically relevant radiation necrosis was confirmed by PET imaging. SRS alone or in combination with WBRT represents a feasible option as initial treatment for patients with brain metastases; however a significant subset of patients may develop neurological complications. Performance status, RPA class and gender were identified to predict improved survival in cerebral metastasized patients

Chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab in psoriasis

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Sridhar J

2006-01-01

Full Text Available Background: Insights into the pathogenesis of psoriasis have provided opportunities to target key steps in the disease process. Tumor necrosis factor-alpha (TNF-a being crucial to the pathogenesis of psoriasis, monoclonal antibodies against this cytokine have proved useful in its treatment. Aim: To study the efficacy of chimeric monoclonal antibody to TNF-a (infliximab in Indian patients with recalcitrant psoriasis vulgaris. Materials and Methods: Three patients with recalcitrant psoriasis vulgaris were studied. Baseline haemogram, biochemical parameters, chest radiograph and Mantoux skin test were performed. A loading dose regimen of 5 mg/kg infliximab was administered at weeks 0, 2 and 6. PASI assessment, adverse drug event monitoring and laboratory assessments were carried out at 2-week intervals until week 10. Patients were followed up until week 22 for relapse. Results: Infliximab was well tolerated. The mean PASI was 25.4 at presentation and declined to 5.5 at 10 weeks. PASI 75 was attained at a mean of 9.6 weeks. Relapse occurred at a mean of 18.6 weeks after the first infusion. Conclusions: This study on Indian patients brings out the importance of cytokine-based therapies in psoriasis. Indigenous production could make these therapies a viable therapeutic option for psoriasis patients in the near future.

Targeting of regulated necrosis in kidney disease

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Diego Martin-Sanchez

2018-03-01

Full Text Available The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention. Resumen: La idea de que el término necrosis tubular aguda supone una denominación inapropiada se deriva de estudios morfológicos de necropsias humanas. La opinión generalizada ha sido que la necrosis representa una forma pasiva de muerte celular no regulada que no es susceptible de manipulación terapéutica. Los recientes avances han mejorado nuestra comprensión de la muerte celular en la lesión renal aguda. En primer lugar, la apoptosis origina una pérdida celular, pero no desencadena una respuesta inflamatoria. Sin embargo, los intentos rudimentarios de interferir en la apoptosis

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

2016-04-29

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

International Nuclear Information System (INIS)

Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

2016-01-01

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

The tumor necrosis factor alpha - 308G>A polymorphism is associated with dementia in the oldest-old

DEFF Research Database (Denmark)

Bruunsgaard, Helle; Benfield, Thomas L; Andersen-Ranberg, Karen

2004-01-01

OBJECTIVES: To test the hypothesis that the tumor necrosis factor (TNF) -308 G>A promoter gene polymorphism is a risk factor in age-related dementia and longevity. DESIGN: A cross-sectional and a longitudinal study. SETTING: A population-based sample of Danish centenarians. PARTICIPANTS: One...... was investigated (Fischer exact test). Furthermore, whether the TNF -308 G>A polymorphism was associated with the prevalence of dementia (logistic regression analysis), the plasma level of TNF-alpha (analysis of variance), and mortality in the following 5 years (Cox regression analysis) within the cohort...... higher plasma levels of TNF-alpha, but the significance was questionable due to a low number of subjects with this genotype. CONCLUSION: It is possible that the TNF -308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism possess the optimal inflammatory...

Effect of bevacizumab on radiation necrosis of the brain

International Nuclear Information System (INIS)

Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A.

2007-01-01

Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% (±22 SD), and the average change in the FLAIR images was 60% (±18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg (±3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment

Regulation of bitter taste responses by tumor necrosis factor.

Science.gov (United States)

Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

2015-10-01

Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

International Nuclear Information System (INIS)

Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

1991-01-01

We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

DNA fragmentation and cytotoxicity by recombinant human tumor necrosis factor in L929 fibroblast cells

International Nuclear Information System (INIS)

Kosaka, T.; Kuwabara, M.; Koide, F.

1992-01-01

Induction of cell DNA fragmentation by treatment of recombinant human Tumor Necrosis Factor alpha (rhTNF alpha) was examined by using mouse L929 cells derived from mouse fibroblast cells. The amount of DNA fragments derived from rhTNF alpha-treated cells, detected by alkaline elution technique, was smaller than that derived from X-irradiated cells. The rhTNF alpha caused the DNA fragmentation depending on its incubation time and concentration. The DNA damage caused by rhTNF alpha treatment correlated with its cytotoxicity. This result suggested that the DNA fragmentation is one of causes of cell death. The treatment with proteinase K of DNA obtained from rhTNF alpha-treated cells did not increase the amount of DNA fragmentation, which indicates that rhTNF alpha causes DNA-fragmentation but not DNA-protein cross-linking

Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

NARCIS (Netherlands)

Bos, W. H.; Bartelds, G. M.; Vis, M.; van der Horst, A. R.; Wolbink, G. J.; van de Stadt, R. J.; van Schaardenburg, D.; Dijkmans, B. A. C.; Lems, W. F.; Nurmohamed, M. T.; Aarden, L.; Hamann, D.

2009-01-01

To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 :

Pediatric Digital Necrosis Secondary to Dressing Application: A Case Series.

Science.gov (United States)

Bjorklund, Kim A; Rice, Dahlia M; Amalfi, Ashley N

2018-04-01

Pediatric digital necrosis resulting in revision amputation is a devastating outcome following digital dressing application. We report a series of 4 pediatric patients (age: 21 months-11 years) who presented for surgical consultation related to digital ischemia and irreversible necrosis following the application of Coban digital dressings. A review of the literature demonstrated that such injuries had not previously been described. In our case series, Coban dressing was utilized as a deterrent for thumb sucking, fingertip tuft fractures with nail bed lacerations, and a phalanx fracture secondary to crush injury. All 4 children suffered digital necrosis secondary to Coban dressings and ultimately required revision amputation. We discuss risks factors, application practices, and strategies to minimize complications with digital dressings in the pediatric population with the intent of creating awareness among hand surgeons to help promote safe practices and improve patient outcomes.

Increased risk of post-operative complications in patients with Crohn’s disease treated with anti-tumour necrosis factor α agents - a systematic review

DEFF Research Database (Denmark)

El-Hussuna, Alaa; Theede, Klaus; Olaison, Per Olov Gunnar

2014-01-01

INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

Effect of disrupted mitochondria as a source of damage-associated molecular patterns on the production of tumor necrosis factor α by splenocytes from dogs.

Science.gov (United States)

Friedenberg, Steven G; Strange, Heather R; Guillaumin, Julien; VanGundy, Zachary C; Crouser, Elliott D; Papenfuss, Tracey L

2016-06-01

OBJECTIVE To evaluate the effects of damage-associated molecular patterns (DAMPs) derived from disrupted mitochondria on canine splenocytes and other immune cells. SAMPLES Liver, spleen, and bone marrow samples obtained from 8 cadavers of healthy research Beagles that had been euthanized for other purposes. PROCEDURES Mitochondria were obtained from canine hepatocytes, and mitochondrial DAMPs (containing approx 75% mitochondrial proteins) were prepared. Mitochondrial DAMPs and the nuclear cytokine high-mobility group box protein 1 were applied to splenocytes, bone marrow-differentiated dendritic cells, and a canine myelomonocytic cell (DH82) line for 6 or 24 hours. Cell culture supernatants from splenocytes, dendritic cells, and DH82 cells were assayed for tumor necrosis factor α with an ELISA. Expression of tumor necrosis factor α mRNA in splenocytes was evaluated with a quantitative real-time PCR assay. RESULTS In all cell populations evaluated, production of tumor necrosis factor α was consistently increased by mitochondrial DAMPs at 6 hours (as measured by an ELISA). In contrast, high-mobility group box protein 1 did not have any independent proinflammatory effects in this experimental system. CONCLUSIONS AND CLINICAL RELEVANCE The study revealed an in vitro inflammatory effect of mitochondrial DAMPs (containing approx 75% mitochondrial proteins) in canine cells and validated the use of an in vitro splenocyte model to assess DAMP-induced inflammation in dogs. This experimental system may aid in understanding the contribution of DAMPs to sepsis and the systemic inflammatory response syndrome in humans. Further studies in dogs are needed to validate the biological importance of these findings and to evaluate the in vivo role of mitochondrial DAMPs in triggering and perpetuating systemic inflammatory states.

Is tumor necrosis factor - 376a promoter polymorphism associated with susceptibility to multiple sclerosis? ¿El polimorfismo-376A del promotor del gen del factor de necrosis tumoral se asocia con una mayor susceptibilidad a padecer esclerosis múltiple?

Directory of Open Access Journals (Sweden)

Marcelo A. Kauffman

2007-10-01

Full Text Available A single nucleotide polymorphism (SNP at position -376 of the tumor necrosis factor á gene (TNFA has been associated with susceptibility to multiple sclerosis (MS in Spain. However, no association was found in populations from the USA and The Netherlands. Here we investigate the association between the TNFA - 376A SNP and MS susceptibility in Argentinean patients with MS. The A/G genotype was found in 4.4% of patients (n=90 and in 4.8% of healthy individuals (n=84; p=0.92; odds ratio=0.93; confidence interval: 0.23- 3.84. Thus, no significant differences in genotype and allele frequencies were found between healthy individuals and patients with MS in Argentina.Un polimorfismo de nucleótido único (SNP, por sus iniciales en inglés en la posición -376 del gen codificante del factor de necrosis tumoral á (TNFA ha sido asociado en España con un mayor riesgo a padecer esclerosis múltiple (EM. Sin embargo, esta asociación no fue encontrada en estudios hechos en poblaciones provenientes de los EE.UU. y Holanda. Aquí investigamos la asociación entre el SNP TNFA -376A y el desarrollo de EM en una población de pacientes argentinos con EM. El genotipo A/G fue encontrado en 4.4% de los pacientes (n=90 y en 4.8% de los controles sanos (n=84; p=0.92; odds ratio=0.93; intervalo de confianza: 0.23-3.84. En consecuencia, no encontramos diferencias en las frecuencias alélicas y genotípicas entre los sujetos enfermos y los controles sanos en Argentina.

The influence of X-radiation on production of interleukin-6 and alpha-tumor necrosis factor by perepheral blood mononuclears

International Nuclear Information System (INIS)

Komarovskaya, M.E.; Dryk, S.I.; Krivenko, S.I.; Karkanitsa, L.V.

1993-01-01

The influence of X-radiation on production of interleurin-6 (IL-6) and α-tumor necrosis factor (TNF) has been investigated. Irradiation with doses of 45, 90 and 900 cGy was shown to increase considerably TNF and IL-6 production both in intact mononuclear cultures of human peripheral blood and in cultures stimulated by phytohemagglutinin. In addition to an absolute increase in the production, the stimulatory effect was manifested by earlier accumulation of IL-6 and TNF activities in supernatant fractions of the cultures under study

Pathological investigation of radiation necrosis

International Nuclear Information System (INIS)

Nakamura, Nishio; Yoshimura, Noriaki; Ikuta, Fusahiro

1975-01-01

The brain and spinal cord of an 18-year-old male, who suffered from cerebellar medulloblastoma with subarachnoid spread, had been irradiated by a large amount of Linac X-ray: 14,450 rads to the lower thoracic segments and 7,400 rads to the lumbar segments. The tumor at the roof of the 4th ventricle had disseminated along the ventricular system but was limited to the subarachnoid space of the cervical spinal cord. No remarkable changes were found in the volume or consistency of the thoracic and lumbar cord. Elasticity of the lower thoracic segment was greatly diminished and the cut surfaces were yellowish white and fragile. Microscopically extensive coagulation necrosis was observed with complete disintegration of myelin and axon. Vascular changes were most prominent in the smaller vessels, eg. hyalinous thickening, concentric cleavage, adventitial fibrosis and edema of small artery perivascular spaces, fibrin thrombi occulusion of arterioles and capillaries, and telangiectasia. In the lumbar spinal cord, moderate neuronal degeneration and protoplasmic astrocytosis were observed. Changes in the lumbar posterior white column were considered to be not only secondary degeneration but also a primary lesion caused by irradiation. Liquefactive necrosis in the gray matter of the cervical cord was thought to be a nonspecific circulatory disturbance because of the absence of vascular changes. Vascular changes were thought to be very important in the histological diagnosis of radiation myelopathy and it was supposed that increased permeability of the vessel walls was a factor in coagulation necrosis. They considered this case to have typical histology of radiation myelopathy. (Evans, J.)

MRI study of avascular necrosis of the knee

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Simizu, Koh; Suguro, Toru; Tsuchiya, Akihiro; Moriya, Hideshige; Nishikawa, Satoru; Arimizu, Noboru [Chiba Univ. (Japan). School of Medicine

1990-10-01

Magnetic resonance (MR) images of 70 joints were reviewed in 38 patients with avascular necrosis of the knee or hip joint, whose ages ranged from 19 to 62 years with an average of 41 years. According to causes, steroid induced avascular necrosis was the commonest, accounting for 87% of cases. The remainer of the cases were alcoholic avascular necrosis (8%) and idiopathic avascular necrosis (5%). Steroid induced avascular necrosis was greatly different from idiopathic avascular necrosis in view of clinical manifestations, common sites, and complications of femur head necrosis. Idiopathic avascular necrosis was common in the central part of internal condyle and was confined to one joint. Steroid induced avascular necrosis was common in the posterior part of external condyle and was frequently associated with multiple necroses of the diaphysis. Seventy five percent of the cases were associated with avascular necrosis of the knee. The diagnostic accuracy of the other imaging modalities in avascular necrosis was low (33% for plain roentgenography and 50% for RI examination). Thus, MR was the imaging procedure of choice for detecting avascular necrotic lesions. (N.K.).

MRI study of avascular necrosis of the knee

International Nuclear Information System (INIS)

Simizu, Koh; Suguro, Toru; Tsuchiya, Akihiro; Moriya, Hideshige; Nishikawa, Satoru; Arimizu, Noboru

1990-01-01

Magnetic resonance (MR) images of 70 joints were reviewed in 38 patients with avascular necrosis of the knee or hip joint, whose ages ranged from 19 to 62 years with an average of 41 years. According to causes, steroid induced avascular necrosis was the commonest, accounting for 87% of cases. The remainer of the cases were alcoholic avascular necrosis (8%) and idiopathic avascular necrosis (5%). Steroid induced avascular necrosis was greatly different from idiopathic avascular necrosis in view of clinical manifestations, common sites, and complications of femur head necrosis. Idiopathic avascular necrosis was common in the central part of internal condyle and was confined to one joint. Steroid induced avascular necrosis was common in the posterior part of external condyle and was frequently associated with multiple necroses of the diaphysis. Seventy five percent of the cases were associated with avascular necrosis of the knee. The diagnostic accuracy of the other imaging modalities in avascular necrosis was low (33% for plain roentgenography and 50% for RI examination). Thus, MR was the imaging procedure of choice for detecting avascular necrotic lesions. (N.K.)

Ischemic necrosis and osteochondritis

International Nuclear Information System (INIS)

Weissman, S.D.

1989-01-01

Osteonecrosis indicates that ischemic death of the cellular constituents of bone and marrow has occurred. Historically, this first was thought to be related to sepsis in the osseous segments. However, continued studies led to the use of the term aseptic necrosis. Subsequent observations indicated that the necrotic areas of bone were not only aseptic, but were also avascular. This led to the terms ischemic necrosis, vascular necrosis and bone infarction. Ischemic necrosis of bone is discussed in this chapter. It results from a significant reduction in or obliteration of blood supply to the affected area. The various bone cells, including osteocytes, osteoclasts, and osteoblasts, usually undergo anoxic death in 12 to 48 hours after blood supply is cut off. The infarct that has thus developed in three-dimensional and can be divided into a number of zones: a central zone of cell death; an area of ischemic injury, most severe near the zone of cell death, and lessening as it moves peripherally; an area of active hyperemia and the zone of normal unaffected tissue. Once ischemic necrosis has begun, the cellular damage provokes an initial inflammatory response, which typically is characterized by vasodilatation, transudation of fluid and fibrin, and local infiltration of flammatory cells. This response can be considered the first stage in repair of the necrotic area

Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study.

Science.gov (United States)

Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

2011-02-01

Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ≥ 25 kg/m(2): N=27) individuals with normal weight (NW: BMI<18.5-24.9 kg/m(2): N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity.

Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head

Science.gov (United States)

2012-01-01

Avascular necrosis (AVN) of the femoral head is a debilitating disease of multifactorial genesis, predominately affects young patients, and often leads to the development of secondary osteoarthritis. The evolving field of regenerative medicine offers promising treatment strategies using cells, biomaterial scaffolds, and bioactive factors, which might improve clinical outcome. Early stages of AVN with preserved structural integrity of the subchondral plate are accessible to retrograde surgical procedures, such as core decompression to reduce the intraosseous pressure and to induce bone remodeling. The additive application of concentrated bone marrow aspirates, ex vivo expanded mesenchymal stem cells, and osteogenic or angiogenic growth factors (or both) holds great potential to improve bone regeneration. In contrast, advanced stages of AVN with collapsed subchondral bone require an osteochondral reconstruction to preserve the physiological joint function. Analogously to strategies for osteochondral reconstruction in the knee, anterograde surgical techniques, such as osteochondral transplantation (mosaicplasty), matrix-based autologous chondrocyte implantation, or the use of acellular scaffolds alone, might preserve joint function and reduce the need for hip replacement. This review summarizes recent experimental accomplishments and initial clinical findings in the field of regenerative medicine which apply cells, growth factors, and matrices to address the clinical problem of AVN. PMID:22356811

Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

Science.gov (United States)

Lavazza, Cristiana; Carlo-Stella, Carmelo; Giacomini, Arianna; Cleris, Loredana; Righi, Marco; Sia, Daniela; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Francolini, Maura; Gloghini, Annunziata; Carbone, Antonino; Formelli, Franca; Gianni, Alessandro M

2010-03-18

Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.

Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation.

Science.gov (United States)

Duan, Chong; Perez-Torres, Carlos J; Yuan, Liya; Engelbach, John A; Beeman, Scott C; Tsien, Christina I; Rich, Keith M; Schmidt, Robert E; Ackerman, Joseph J H; Garbow, Joel R

2017-05-01

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P < 0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P < 0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation.

Low level tumor necrosis factor-alpha protects cardiomyocytes against high level tumor necrosis factor-alpha: brief insight into a beneficial paradox.

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Cacciapaglia, Fabio; Salvatorelli, Emanuela; Minotti, Giorgio; Afeltra, Antonella; Menna, Pierantonio

2014-12-01

Whether tumor necrosis factor-alpha (TNFα) caused beneficial or detrimental cardiovascular effects remains poorly defined. Anti-TNFα agents improved cardiac end points in chronic rheumatic diseases characterized by progressive deterioration of cardiac function. In contrast, anti-TNFα agents did not always improve but actually worsened cardiac function in non-rheumatic patients with heart failure (HF), in spite of that HF usually accompanies with high circulating levels of TNFα. To shed light on these mixed findings, we characterized the effects of TNFα in H9c2 cardiomyocytes. Cells were incubated for 24 h with increasing concentrations of TNFα, hydrogen peroxide, aminotriazole, or etoposide. Posttreatment cell viability was assessed by antimycin A-inhibitable reduction of 3-(4,dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and the IC50 value of each test compound was defined. H9c2 cells were also preconditioned with a low non-toxic concentration of TNFα and then re-challenged with increasing concentrations of TNFα and other stressor agents. In re-challenge experiments, all of the IC50 values increased significantly, with the IC50 value of TNFα increasing approximately 16-fold. TNFα preconditioning increased cardiomyocytes shedding of the external portion of transmembrane type 1 and type 2 TNFα receptors [(soluble TNFα receptors (sTNFR)]. Levels of survival-oriented soluble TNFR2 (sTNFR2) always exceeded those of death-oriented sTNFR1. When exposed to TNFα at its IC50 value, preconditioned cardiomyocytes showed an increased release of sTNFR2 but not sTNFR1. These results denoted that preconditioning by "low TNFα" helped cardiomyocyte to withstand toxicity from "high TNFα" or other agents. These results also suggested that beneficial or detrimental effects of anti-TNFα agents might well depend on whether these agents spared or intercepted discrete amounts of TNFα that preconditioned cardiomyocytes and made them more resistant to high

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

OpenAIRE

Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

2017-01-01

Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL)....

Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheumatoid arthritis patients in clinical practice

DEFF Research Database (Denmark)

Ornbjerg, Lykke Midtbøll; Østergaard, Mikkel; Bøyesen, Pernille

2013-01-01

radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated.RESULTS: 517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21......OBJECTIVES: To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice.METHODS: Conventional radiographs (x......-1002) and the median TNF-I period was 562 days (IQR 405-766). The median radiographic progression rate decreased from 0.7 (IQR 0-2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0-0.9) units/year in the TNF-I period (p0) in the DMARD period compared with 158 patients in the TNF-I period (p...

Necrosis related HIF-1α expression predicts prognosis in patients with endometrioid endometrial carcinoma

International Nuclear Information System (INIS)

Seeber, Laura MS; Horrée, Nicole; Groep, Petra van der; Wall, Elsken van der; Verheijen, René HM; Diest, Paul J van

2010-01-01

Hypoxia inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27 kip1 , which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1α and p27 kip expression in patients with endometrioid endometrial cancer. Expression levels of HIF-1α, CAIX, Glut-1, and p27 kip1 were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted. Necrosis was correlated with shortened disease free survival (DFS) (p = 0.008) and overall survival (OS) (p = 0.045). For DFS, perinecrotic HIF-1α expression was also prognostic (p = 0.044). Moreover, high p27 kip1 expression was an additional prognostic factor for these patients with perinecrotic HIF-1α expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1α expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1. In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1α are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics

Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus

Science.gov (United States)

Lin, Marie C; Lee, Nikki P; Zheng, Ning; Yang, Pai-Hao; Wong, Oscar G; Kung, Hsiang-Fu; Hui, Chee-Kin; Luk, John M; Lau, George Ka-Kit

2005-01-01

AIM: To compare the gene expression profile in a pair of HBV-infected twins. METHODS: The gene expression profile was compared in a pair of HBV-infected twins. RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV, whereas the other became a chronic HBV carrier. Eighty-eight and forty-six genes were found to be up- or down-regulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen stimulation, TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+ channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins. CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV. PMID:16437679

Tumor Necrosis Factor-Alpha in Peripical Tissue Exudates of Teeth with Apical Periodontitis

Directory of Open Access Journals (Sweden)

Sonja Pezelj-Ribaric

2007-01-01

Full Text Available Aim. The aim of this study was to determine tumor necrosis factor-alpha (TNF-α levels in periapical exudates and to evaluate their relationship with radiological findings. Methodology. Periapical exudates were collected from root canals of 60 single-rooted teeth using absorbent paper points. TNF-α levels were determined by enzyme-linked immunosorbent assays. The samples were divided into three groups according to the periapical radiolucent area. Results. Nonparametric Kruskal-Wallis test revealed significant differences between TNF-α concentrations in control group (40, 57±28, 15 pg/mL and group with larger radiolucent areas (2365, 79±582, 95 pg/mL, as well as between control and canals with small radiolucent areas (507, 66±278, 97 (P<.05. Conclusions. The levels of TNF-α increase significantly in teeth with periapical pathosis, from smaller to bigger lesions. This research and its results have shown that objective analysis of the TNF-α levels enables establishment of a relationship between different concentrations of TNF-α and different radiological changes.

Parapoxvirus orf virus infection induces an increase in interleukin-8, tumour necrosis factor-α, and decorin in goat skin fibroblast cells

Directory of Open Access Journals (Sweden)

Wang Lingling

2016-09-01

Full Text Available Introduction: Orf virus (ORFV is a prototype Parapoxvirus species in the Poxviridae family that causes serious zoonotic infectious disease. Goat skin fibroblast (GSF cells are the major host targets of ORFV. Interleukin 8 (IL-8 and tumour necrosis factor (TNF-α are known to play a vital role in immune response during viral infections. However, the manner of variation over time of their level of expression in GSF cells remains unclear.

Macrophages control vascular stem/progenitor cell plasticity through tumor necrosis factor-α-mediated nuclear factor-κB activation.

Science.gov (United States)

Wong, Mei Mei; Chen, Yikuan; Margariti, Andriani; Winkler, Bernhard; Campagnolo, Paola; Potter, Claire; Hu, Yanhua; Xu, Qingbo

2014-03-01

Vascular lineage differentiation of stem/progenitor cells can contribute to both tissue repair and exacerbation of vascular diseases such as in vein grafts. The role of macrophages in controlling vascular progenitor differentiation is largely unknown and may play an important role in graft development. This study aims to identify the role of macrophages in vascular stem/progenitor cell differentiation and thereafter elucidate the mechanisms that are involved in the macrophage- mediated process. We provide in vitro evidence that macrophages can induce endothelial cell (EC) differentiation of the stem/progenitor cells while simultaneously inhibiting their smooth muscle cell differentiation. Mechanistically, both effects were mediated by macrophage-derived tumor necrosis factor-α (TNF-α) via TNF-α receptor 1 and canonical nuclear factor-κB activation. Although the overexpression of p65 enhanced EC (or attenuated smooth muscle cell) differentiation, p65 or TNF-α receptor 1 knockdown using lentiviral short hairpin RNA inhibited EC (or rescued smooth muscle cell) differentiation in response to TNF-α. Furthermore, TNF-α-mediated EC differentiation was driven by direct binding of nuclear factor-κB (p65) to specific VE-cadherin promoter sequences. Subsequent experiments using an ex vivo decellularized vessel scaffold confirmed an increase in the number of ECs and reduction in smooth muscle cell marker expression in the presence of TNF-α. The lack of TNF-α in a knockout mouse model of vein graft decreased endothelialization and significantly increased thrombosis formation. Our study highlights the role of macrophages in directing vascular stem/progenitor cell lineage commitment through TNF-α-mediated TNF-α receptor 1 and nuclear factor-κB activation that is likely required for endothelial repair in vascular diseases such as vein graft.

Tumor necrosis factor (TNF-alpha) and C-reactive protein (CRP) are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes.

Science.gov (United States)

Yeo, Eun-Sil; Hwang, Ji-Yun; Park, Ji Eun; Choi, Young Ju; Huh, Kap Bum; Kim, Wha Young

2010-07-01

Chronic low-grade inflammation may induce chronic kidney disease in patients with type 2 diabetes. This study investigated the relation between inflammatory biomarkers and chronic kidney disease in patients with type 2 diabetes, which has not yet been reported in Asian populations. A cross-sectional study was performed in 543 patients recruited from diabetic clinics for an ongoing, prospective study. Multivariate logistic regression was used to evaluate the association between inflammatory biomarkers and the presence of chronic kidney disease (estimated glomerular filtration rate Disease equation using plasma creatinine). The risk of chronic kidney disease increased in the highest quartiles of C-reactive protein (CRP) [multivariate odds ratio (OR) = 3.73; 95% CI = 1.19-1.70] and tumor necrosis factor-alpha (multivariate OR = 4.45; 95% CI = 1.63-12.11) compared to the lowest quartiles after adjustments for age, sex, zinc intake, and other putative risk factors for chronic kidney disease. Our results suggest that CRP and tumor necrosis factor-alpha may be independent risk factors for chronic kidney disease in patients with type 2 diabetes. A causal mechanism of this association should be evaluated in a followup study of Korean patients with type 2 diabetes.

Golimumab and certolizumab: The two new anti-tumor necrosis factor kids on the block

Directory of Open Access Journals (Sweden)

Mittal Mohit

2010-01-01

Full Text Available Anti-tumor necrosis factor (anti-TNF agents have revolutionized treatment of psoriasis and many other inflammatory diseases of autoimmune origin. They have considerable advantages over the existing immunomodulators. Anti-TNF agents are designed to target a very specific component of the immune-mediated inflammatory cascades. Thus, they have lower risks of systemic side-effects. In a brief period of 10 years, a growing number of biological therapies are entering the clinical arena while many more biologicals remain on the horizon. With time, the long-term side-effects and efficacies of these individual agents will become clearer and help to determine which ones are the most suitable for long-term care. Golimumab (a human monoclonal anti-TNF-α antibody and Certolizumab (a PEGylated Fab fragment of humanized monoclonal TNF-α antibody are the two latest additions to the anti-TNF regimen. Here, we are providing a brief description about these two drugs and their uses.

Systemic use of tumor necrosis factor alpha as an anticancer agent

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Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

Molecular Basis for the Neutralization of Tumor Necrosis Factor α by Certolizumab Pegol in the Treatment of Inflammatory Autoimmune Diseases

Directory of Open Access Journals (Sweden)

Jee Un Lee

2017-01-01

Full Text Available Monoclonal antibodies against TNFα, including infliximab, adalimumab, golimumab, and certolizumab pegol, are widely used for the treatment of the inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Recently, the crystal structures of TNFα, in complex with the Fab fragments of infliximab and adalimumab, have revealed the molecular mechanisms of these antibody drugs. Here, we report the crystal structure of TNFα in complex with the Fab fragment of certolizumab pegol to clarify the precise antigen-antibody interactions and the structural basis for the neutralization of TNFα by this therapeutic antibody. The structural analysis and the mutagenesis study revealed that the epitope is limited to a single protomer of the TNFα trimer. Additionally, the DE loop and the GH loop of TNFα play critical roles in the interaction with certolizumab, suggesting that this drug exerts its effects by partially occupying the receptor binding site of TNFα. In addition, a conformational change of the DE loop was induced by certolizumab binding, thereby interrupting the TNFα-receptor interaction. A comprehensive comparison of the interactions of TNFα blockers with TNFα revealed the epitope diversity on the surface of TNFα, providing a better understanding of the molecular mechanism of TNFα blockers. The accumulation of these structural studies can provide a basis for the improvement of therapeutic antibodies against TNFα.

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.

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Skansing, Daniel Bräuner; Londero, Stefano Christian; Asschenfeldt, Pia; Larsen, Stine Rosenkilde; Godballe, Christian

2017-06-01

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles

NARCIS (Netherlands)

Wilson, A. G.; de Vries, N. [=Niek; Pociot, F.; di Giovine, F. S.; van der Putte, L. B.; Duff, G. W.

1993-01-01

The tumor necrosis factor (TNF) alpha gene lies within the class III region of the major histocompatibility complex (MHC), telomeric to the class II and centromeric to the class I region. We have recently described the first polymorphism within the human TNF-alpha locus. This is biallelic and lies

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

Science.gov (United States)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Progressive skin necrosis of a huge occipital encephalocele

Science.gov (United States)

Andarabi, Yasir; Nejat, Farideh; El-Khashab, Mostafa

2008-01-01

Objects: Progressive skin necrosis of giant occipital encephalocoele is an extremely rare complication found in neonates. Infection and ulceration of the necrosed skin may lead to meningitis or sepsis. We present here a neonate with giant occipital encephalocoele showing progressive necrosis during the first day of his life. Methods: A newborn baby was found to have a huge mass in the occipital region, which was covered by normal pink-purplish skin. During the last hours of the first day of his life, the sac started becoming ulcerated accompanied with a rapid color change in the skin, gradually turning darker and then black. The neonate was taken up for urgent excision and repair of the encephalocele. Two years after the operation, he appears to be well-developed without any neurological problems. Conclusion: Necrosis may have resulted from arterial or venous compromise caused by torsion of the pedicle during delivery or after birth. The high pressure inside the sac associated with the thin skin of the encephalocoele may be another predisposing factor. In view of the risk of ulceration and subsequent infection, urgent surgery of the necrotizing encephalocele is suggested. PMID:19753210

Progressive skin necrosis of a huge occipital encephalocele

Directory of Open Access Journals (Sweden)

Andarabi Yasir

2008-01-01

Full Text Available Objects: Progressive skin necrosis of giant occipital encephalocoele is an extremely rare complication found in neonates. Infection and ulceration of the necrosed skin may lead to meningitis or sepsis. We present here a neonate with giant occipital encephalocoele showing progressive necrosis during the first day of his life. Methods: A newborn baby was found to have a huge mass in the occipital region, which was covered by normal pink-purplish skin. During the last hours of the first day of his life, the sac started becoming ulcerated accompanied with a rapid color change in the skin, gradually turning darker and then black. The neonate was taken up for urgent excision and repair of the encephalocele. Two years after the operation, he appears to be well-developed without any neurological problems. Conclusion: Necrosis may have resulted from arterial or venous compromise caused by torsion of the pedicle during delivery or after birth. The high pressure inside the sac associated with the thin skin of the encephalocoele may be another predisposing factor. In view of the risk of ulceration and subsequent infection, urgent surgery of the necrotizing encephalocele is suggested.

Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta

DEFF Research Database (Denmark)

Issazadeh-Navikas, Shohreh; Ljungdahl, A; Höjeberg, B

1995-01-01

in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes. Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (= lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical...... signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting...... proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression...

Supernatants from Staphylococcus epidermidis grown in the presence of different antibiotics induce differential release of tumor necrosis factor alpha from human monocytes.

OpenAIRE

Mattsson, E; Van Dijk, H; Verhoef, J; Norrby, R; Rollof, J

1996-01-01

Bacterial products from gram-positive bacteria, such as peptidoglycan, teichoic acid, and toxins, activate mononuclear cells to produce tumor necrosis factor alpha (TNF). The present study evaluated the release of soluble cell wall components from Staphylococcus epidermidis capable of inducing TNF after exposure of the bacteria to various antibiotics. A clinical S. epidermidis isolate (694) was incubated with either penicillin, oxacillin, vancomycin, or clindamycin at five times the MIC. Supe...

Intermitted pharmacologic pretreatment by xenon, isoflurane, nitrous oxide, and the opioid morphine prevents tumor necrosis factor alpha-induced adhesion molecule expression in human umbilical vein endothelial cells

NARCIS (Netherlands)

Weber, Nina C.; Kandler, Jennis; Schlack, Wolfgang; Grueber, Yvonne; Frädorf, Jan; Preckel, Benedikt

2008-01-01

BACKGROUND: The barrier properties of the endothelium are of critical importance during pathophysiologic processes. These barrier properties depend on an intact cytoskeleton and are regulated by cell adhesion molecules. Tumor necrosis factor alpha (TNF-alpha) is known to induce cell adhesion

Cost of tumor necrosis factor blockers per patient with rheumatoid arthritis in a multistate Medicaid population

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Bonafede M

2014-09-01

Full Text Available Machaon Bonafede,1 George J Joseph,2 Neel Shah,2 Nicole Princic,1 David J Harrison2 1Truven Health Analytics, Cambridge, MA, 2Amgen Inc., Thousand Oaks, CA, USA Background: The purpose of this study was to estimate the annual cost per treated patient for the tumor necrosis factor (TNF blockers, etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA patients covered by Medicaid. Methods: The MarketScan Medicaid Multistate Database was used to identify adult RA patients who used etanercept, adalimumab, or infliximab (index agents from 2007 to 2011. The index date was the first claim preceded by 180 days and followed by 360 days of continuous enrollment. Patients with other conditions for which these agents are approved by the US Food and Drug Administration were excluded. “Continuing” patients had one or more pre-index claim for their index biologic, and "new" patients did not. Cost per treated patient was calculated in the 360 day post-index period for each index agent as the total index drug and administration cost to the payer and the costs of switched-to agents divided by the number of patients who received the index agent. Results: A total of 1,085 patients met the study criteria. Forty-eight percent received etanercept (n=521; 37% received adalimumab (n=405; and 15% received infliximab (n=159. Patient characteristics were similar across groups (mean age 47.4 years, 83% female. The annual cost per treated patient was lowest for etanercept ($18,466, followed by adalimumab ($20,983 and infliximab ($26,516. For all agents, annual costs were lower for new patients ($17,996 for etanercept, $18,992 for adalimumab, and $24,756 for infliximab than for continuing patients ($19,004 for etanercept, $24,438 for adalimumab, and $28,127 for infliximab. Conclusion: Etanercept had lower costs per treated patient than adalimumab or infliximab in both new and continuing Medicaid enrollees with RA. Keywords: cost, tumor necrosis factor

Avascular Necrosis of the Capitate

OpenAIRE

Bekele, Wosen; Escobedo, Eva; Allen, Robert

2011-01-01

Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma.

Macroscopic and microscopic findings in avascular necrosis of the femoral head.

Science.gov (United States)

Kamal, Diana; Alexandru, D O; Kamal, C K; Streba, C T; Grecu, D; Mogoantă, L

2012-01-01

The avascular necrosis of the femoral head is an illness induced by the cutoff of blood flow to the femoral head and it affects mostly young adults between the ages of 30 and 50 years, raising therapeutic and diagnostic issues. Many risk factors are incriminated in the development of avascular necrosis of the femoral head like: trauma, chronic alcohol consumption, smoking, administration of corticosteroid drugs, most of the cases are considered to be idiopathic. The main goal of our paper is to describe the macroscopic and microscopic variations of the bone structure, which occur in patients with avascular necrosis of the femoral head. The biological material needed for our study was obtained following hip arthroplasty surgery in 26 patients between the ages of 29 and 59 years, which previously were diagnosed with avascular necrosis of the femoral head and admitted in the Orthopedics Department of the Emergency County Hospital of Craiova (Romania) between 2010 and 2011. From a macroscopic point of view, we found well defined areas of necrosis, most of which were neatly demarcated of the adjacent viable tissue by hyperemic areas, loss of shape and contour of the femoral head and transformations of the articular cartilage above the area of necrosis. When examined under the microscope, we found vast areas of fibrosis, narrow bone trabeculae, obstructed blood vessels or blood vessels with clots inside, hypertrophic fat cells, bone sequestration but also small cells and pyknotic nuclei. The microscopic and macroscopic findings on the femoral head sections varied with the patients and the stage of the disease.

Effects of Tumor Necrosis Factor Blocker on Salicylate-Induced Tinnitus in Mice.

Science.gov (United States)

Hwang, Juen-Haur; Huang, David Chang-Wei; Lu, Yin-Chang; Yang, Wei-Shiung; Liu, Tien-Chen

2017-06-01

Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control. The tinnitus score significantly decreased in the Enbrel® treated group. The mRNA levels of both TNFR1 and TNFR2 were significantly lower in the treatment than in the control group. The mRNA levels of NR2B and DREAM followed a similar trend. we found that treatment with 30 mg/ kg Enbrel® decreased salicylate-induced behavior associated with tinnitus and reduced the mRNA expression levels of TNFR1/R2, NR2B, and DREAM in the cochlea of mice. These findings supported the hypothesis that neuroinflammation might be a novel mechanism for salicylate-induced tinnitus.

Avascular Necrosis of the Capitate

Science.gov (United States)

Bekele, Wosen; Escobedo, Eva; Allen, Robert

2011-01-01

Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma. PMID:22470799

Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

NARCIS (Netherlands)

Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

Method to Minimize the Low-Frequency Neutral-Point Voltage Oscillations With Time-Offset Injection for Neutral-Point-Clamped Inverters

DEFF Research Database (Denmark)

Choi, Ui-Min; Blaabjerg, Frede; Lee, Kyo-Beum

2015-01-01

time of small- and medium-voltage vectors. However, if the power factor is lower, there is a limitation to eliminate neutral-point oscillations. In this case, the proposed method can be improved by changing the switching sequence properly. Additionally, a method for neutral-point voltage balancing......This paper proposes a method to reduce the low-frequency neutral-point voltage oscillations. The neutral-point voltage oscillations are considerably reduced by adding a time offset to the three-phase turn-on times. The proper time offset is simply calculated considering the phase currents and dwell...

Inflammatory cytokine tumor necrosis factor α suppresses neuroprotective endogenous erythropoietin from astrocytes mediated by hypoxia-inducible factor-2α.

Science.gov (United States)

Nagaya, Yoshiaki; Aoyama, Mineyoshi; Tamura, Tetsuya; Kakita, Hiroki; Kato, Shin; Hida, Hideki; Saitoh, Shinji; Asai, Kiyofumi

2014-12-01

Interest in erythropoietin (EPO) as a neuroprotective mediator has grown since it was found that systemically administered EPO is protective in several animal models of disease. However, given that the blood-brain barrier limits EPO entry into the brain, alternative approaches that induce endogenous EPO production in the brain may be more effective clinically and associated with fewer untoward side-effects. Astrocytes are the main source of EPO in the central nervous system. In the present study we investigated the effect of the inflammatory cytokine tumor necrosis factor α (TNFα) on hypoxia-induced upregulation of EPO in rat brain. Hypoxia significantly increased EPO mRNA expression in the brain and kidney, and this increase was suppressed by TNFα in vivo. In cultured astrocytes exposed to hypoxic conditions for 6 and 12 h, TNFα suppressed the hypoxia-induced increase in EPO mRNA expression in a concentration-dependent manner. TNFα inhibition of hypoxia-induced EPO expression was mediated primarily by hypoxia-inducible factor (HIF)-2α rather than HIF-1α. The effects of TNFα in reducing hypoxia-induced upregulation of EPO mRNA expression probably involve destabilization of HIF-2α, which is regulated by the nuclear factor (NF)-κB signaling pathway. TNFα treatment attenuated the protective effects of astrocytes on neurons under hypoxic conditions via EPO signaling. The effective blockade of TNFα signaling may contribute to the maintenance of the neuroprotective effects of EPO even under hypoxic conditions with an inflammatory response. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

DEFF Research Database (Denmark)

Bruunsgaard, H; Ladelund, S; Pedersen, A N

2003-01-01

Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality...... in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...

Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

DEFF Research Database (Denmark)

Bruunsgaard, H.; Ladelund, S.; Pedersen, Agnes Nadelmann

2003-01-01

Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha ) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality...... in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...

Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

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Borkowski, Brian J.; Cheema, Yaser; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Weber, Karl T.

2011-01-01

An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca2+ accumulation (EICA), and mitochondrial Ca2+ overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal–transducer–effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria. PMID:21398641

The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

DEFF Research Database (Denmark)

Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

2011-01-01

Tumour necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

DEFF Research Database (Denmark)

Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

2011-01-01

Tumour necrosis factor-a (TNF-a) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-a acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-a and TNF-a receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

NecroQuant: quantitative assessment of radiological necrosis

Science.gov (United States)

Hwang, Darryl H.; Mohamed, Passant; Varghese, Bino A.; Cen, Steven Y.; Duddalwar, Vinay

2017-11-01

Clinicians can now objectively quantify tumor necrosis by Hounsfield units and enhancement characteristics from multiphase contrast enhanced CT imaging. NecroQuant has been designed to work as part of a radiomics pipelines. The software is a departure from the conventional qualitative assessment of tumor necrosis, as it provides the user (radiologists and researchers) a simple interface to precisely and interactively define and measure necrosis in contrast-enhanced CT images. Although, the software is tested here on renal masses, it can be re-configured to assess tumor necrosis across variety of tumors from different body sites, providing a generalized, open, portable, and extensible quantitative analysis platform that is widely applicable across cancer types to quantify tumor necrosis.

Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells.

Science.gov (United States)

Ma, Hak-Ling; Napierata, Lee; Stedman, Nancy; Benoit, Stephen; Collins, Mary; Nickerson-Nutter, Cheryl; Young, Deborah A

2010-02-01

Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor alpha (TNFalpha) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNFalpha blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNFalpha blockade-induced exacerbation of skin inflammation in murine psoriasis-like skin disease. Skin inflammation was induced in BALB/c scid/scid mice after they received CD4+CD45RB(high)CD25- (naive CD4) T cells from donor mice. These mice were treated with either anti-interleukin-12 (anti-IL-12)/23p40 antibody or murine TNFRII-Fc fusion protein and were examined for signs of disease, including histologic features, various cytokine levels in the serum, and cytokine or FoxP3 transcripts in the affected skin and draining lymph node (LN) cells. In a separate study, naive CD4+ T cells were differentiated into Th1 or Th17 lineages with anti-CD3/28 magnetic beads and appropriate cytokines in the presence or absence of TNFalpha. Cytokine gene expression from these differentiated cells was also determined. Neutralization of TNFalpha exacerbated skin inflammation and markedly enhanced the expression of the proinflammatory cytokines IL-1beta, IL-6, IL-17, IL-21, and IL-22 but suppressed FoxP3 expression in the skin and reduced the number of FoxP3-positive Treg cells in the draining LNs. TNFalpha also demonstrated a divergent role during priming and reactivation of naive T cells. These results reveal a novel immunoregulatory role of TNFalpha on Th17 and Treg cells in some individuals, which may account for the exacerbation of skin inflammation in some patients who receive anti-TNF treatments.

Evaluation of tumor necrosis factor alpha serum level in obese and lean women with clomiphene citrate resistant polycystic ovary disease

OpenAIRE

Seyam, Emaduldin; Hasan, Momen; Khalifa, Eissa M.; Ramadan, Ahmad; Hefzy, Enas

2017-01-01

Objective: The aim of this work was to investigate the level of the serum level of tumor necrosis factor alpha (TNF-α) as an inflammatory biomarker in lean and obese women with polycystic ovary disease (PCOD), who are resistant to clomiphene citrate (CCR-PCOD). Patients and design: It is a case controlled study, where one hundred and fifty (n = 150) PCOD women (study group), who are resistant to clomiphene citrate (CCR-PCOD) had been recruited, in addition to one hundred (n = 100) women wi...

A prognostic model for soft tissue sarcoma of the extremities and trunk wall based on size, vascular invasion, necrosis, and growth pattern

DEFF Research Database (Denmark)

Carneiro, Ana; Bendahl, Par-Ola; Engellau, Jacob

2011-01-01

type, necrosis, and grade. METHODS:: Whole-tumor sections from 239 soft tissue sarcomas of the extremities were reviewed for the following prognostic factors: size, vascular invasion, necrosis, and growth pattern. A new prognostic model, referred to as SING (Size, Invasion, Necrosis, Growth...

Angiogenesis and expression of vascular endothelial growth factor, tumour necrosis factor-α and hypoxia inducible factor-1α in canine renal cell carcinoma.

Science.gov (United States)

Yhee, J Y; Yu, C H; Kim, J H; Im, K S; Kim, N H; Brodersen, B W; Doster, A R; Sur, J-H

2012-01-01

The aim of the present study was to determine the distribution and characteristics of microvessels in various histological types of canine renal cell carcinoma (RCC). The study compared microvessel density (MVD) and distribution of blood vessels according to histological type and evaluated the presence of angiogenesis-related proteins. Nine archival samples of canine RCC were studied. MVD was calculated as the mean number of blood vessels per mm(2). The diameter of blood vessels was calculated by determining either the length of the long axis of blood vessels (diameter(max)) or the mean distance from the centre of each blood vessel to the tunica adventia (diameter(mean)). A significant difference in MVD was evident between RCCs and normal kidneys (46.6 ± 28.0 versus 8.4 ± 2.2 microvessels/mm(2)). Diameter(max) in canine RCCs (34.1 ± 14.7 μm) was also significantly different from normal canine kidney (23.2 ± 3.4 μm). Vascular endothelial growth factor (VEGF) was expressed by tumour cells and vascular endothelial cells and tumour necrosis factor (TNF)-α expression was observed in vascular endothelial cells in both neoplastic and normal kidney. Although VEGF is involved in angiogenesis and correlates with tumour stage of development, no correlation was found between VEGF expression and MVD. Tumour-associated macrophages expressing TNF-α and hypoxia inducible factor 1α were identified in peritumoural tissue and may play an important role in angiogenesis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reactivation of pulmonary tuberculosis (TBC) with the use of antagonist of the tumor necrosis factor alpha (FNTα) in rheumatoid arthritis: On purpose of a case

International Nuclear Information System (INIS)

Martinez V, Jose B; Medina V, Yimy F; Parga, Roberto; Restrepo, Jose Felix; Iglesias G, Antonio; Rondon, Federico

2005-01-01

Woman 56 years old, with history of rheumatoid arthritis who develops reactivation of pulmonary tuberculosis (TBC) after 1 year of treatment with biological therapy (antagonist of the tumor necrosis factor alpha). It is discussed pathophysiologic mechanisms, diagnostic approach, treatment of TBC and some recommendations for the use of biological therapy in patients with rheumatic disease

Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt

DEFF Research Database (Denmark)

Trebicka, Jonel; Krag, Aleksander; Gansweid, Stefan

2011-01-01

In cirrhosis portal hypertension can promote bacterial translocation and increase serum endotoxin levels. Vice versa, endotoxin aggravates portal hypertension by induction of systemic and splanchnic vasodilation, and by triggering hepatic inflammatory response via tumor necrosis factor α (TNFα......). However, the hepatic elimination of endotoxin in cirrhotic patients with severe portal hypertension, in the absence of acute complications, has not been investigated so far....

Molecular modeling of human neutral sphingomyelinase provides insight into its molecular interactions.

Science.gov (United States)

Dinesh; Goswami, Angshumala; Suresh, Panneer Selvam; Thirunavukkarasu, Chinnasamy; Weiergräber, Oliver H; Kumar, Muthuvel Suresh

2011-01-01

The neutral sphingomyelinase (N-SMase) is considered a major candidate for mediating the stress-induced production of ceramide, and it plays an important role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress responses. Recent studies have identified a small region at the very N-terminus of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced activation of N-SMase. There is no direct association between TNF-R55 NSD and N-SMase; instead, a protein named factor associated with N-SMase activation (FAN) has been reported to couple the TNF-R55 NSD to N-SMase. Since the three-dimensional fold of N-SMase is still unknown, we have modeled the structure using the protein fold recognition and threading method. Moreover, we propose models for the TNF-R55 NSD as well as the FAN protein in order to study the structural basis of N-SMase activation and regulation. Protein-protein interaction studies suggest that FAN is crucially involved in mediating TNF-induced activation of the N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses. Inhibition of N-SMase may lead to reduction of ceramide levels and hence may provide a novel therapeutic strategy for inflammation and autoimmune diseases. Molecular dynamics (MD) simulations were performed to check the stability of the predicted model and protein-protein complex; indeed, stable RMS deviations were obtained throughout the simulation. Furthermore, in silico docking of low molecular mass ligands into the active site of N-SMase suggests that His135, Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based on our results, these ligands are proposed to be potent and selective N-SMase inhibitors, which may ultimately prove useful as lead compounds for drug development.

A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

DEFF Research Database (Denmark)

Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

2014-01-01

When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...

Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.

Science.gov (United States)

Robinson, Antwon D; Ramanathan, Kodangudi B; McGee, Jesse E; Newman, Kevin P; Weber, Karl T

2011-08-01

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation

Energy Technology Data Exchange (ETDEWEB)

Saber, Anne T.; Bornholdt, Jette; Dybdahl, Marianne; Sharma, Anoop K.; Vogel, Ulla; Wallin, Haakan [National Institute of Occupational Health, Copenhagen (Denmark); Loft, Steffen [Copenhagen University, Institute of Public Health, Copenhagen (Denmark)

2005-03-01

Particle-induced carcinogenicity is not well understood, but might involve inflammation. The proinflammatory cytokine tumor necrosis factor (TNF) is considered to be an important mediator in inflammation. We investigated its role in particle-induced inflammation and DNA damage in mice with and without TNF signaling. TNF-/- mice and TNF+/+ mice were exposed by inhalation to 20 mg m{sup -3} carbon black (CB), 20 mg m{sup -3} diesel exhaust particles (DEP), or filtered air for 90 min on each of four consecutive days. DEP, but not CB particles, induced infiltration of neutrophilic granulocutes into the lung lining fluid (by the cellular fraction in the bronchoalveolar lavage fluid), and both particle types induced interleukin-6 mRNA in the lung tissue. Surprisingly, TNF-/- mice were intact in these inflammatory responses. There were more DNA strand breaks in the BAL cells of DEP-exposed TNF-/- mice and CB-exposed mice compared with the air-exposed mice. Thus, the CB-induced DNA damage in BAL-cells was independent of neutrophil infiltration. The data indicate that an inflammatory response was not a prerequisite for DNA damage, and TNF was not required for the induction of inflammation by DEP and CB particles. (orig.)

Mastectomy skin necrosis after microsurgical breast reconstruction.

Science.gov (United States)

Vargas, Christina R; Koolen, Pieter G; Anderson, Katarina E; Paul, Marek A; Tobias, Adam M; Lin, Samuel J; Lee, Bernard T

2015-10-01

Mastectomy skin necrosis represents a significant clinical morbidity after immediate breast reconstruction. In addition to aesthetic deformity, necrosis of the native mastectomy skin may require debridement, additional reconstruction, or prolonged wound care and potentially delay oncologic treatment. This study aims to evaluate patient and procedural characteristics to identify predictors of mastectomy skin necrosis after microsurgical breast reconstruction. A retrospective review was performed of all immediate microsurgical breast reconstructions performed at a single academic center. Patient records were queried for age, diabetes, active smoking, previous breast surgery, preoperative radiation, preoperative chemotherapy, body mass index, mastectomy type, mastectomy weight, flap type, autologous flap type, and postoperative mastectomy skin flap necrosis. There were 746 immediate autologous microsurgical flaps performed by three plastic surgeons at our institution during the study period. The incidence of mastectomy skin flap necrosis was 13.4%. Univariate analysis revealed a significantly higher incidence of mastectomy skin necrosis in patients with higher mastectomy weight (P mastectomy type. Multivariate analysis demonstrated statistically significant associations between mastectomy skin necrosis and both increasing mastectomy weight (odds ratio 1.348 per quartile increase, P = 0.009) and diabetes (odds ratio 2.356, P = 0.011). Increasing mastectomy weight and coexisting diabetes are significantly associated with postoperative mastectomy skin necrosis after microsurgical reconstruction. These characteristics should be considered during patient counseling, procedure selection, operative planning, and intraoperative tissue viability assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular imaging of tumor photoimmunotherapy: Evidence of photosensitized tumor necrosis and hemodynamic changes

DEFF Research Database (Denmark)

Kishimoto, Shun; Oshima, Nobu; Yamamoto, Kazutoshi

2018-01-01

Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode of cytotox......Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode...... of cytotoxicity based mainly on in vitro studies. To better understand the acute effects of NIR PIT, molecular imaging studies were performed to assess its cellular and vascular effects.In addition to in vitro studies for cytotoxicity of NIR PIT, the in vivo tumoricidal effects and hemodynamic changes induced....... Following NIR PIT, metabolic MRI using hyperpolarized fumarate showed the production of malate in EGFR-expressing A431 tumor xenografts, providing direct evidence for photosensitized tumor necrosis induced by NIR PIT. R2* mapping studies showed temporal changes in oxygenation, with an accompanying increase...

Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

International Nuclear Information System (INIS)

Wang Weimin; Li Jinliang; Huang Yongqiang

2010-01-01

Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors.

Directory of Open Access Journals (Sweden)

Jennifer M Binning

2018-01-01

Full Text Available The lentiviral protein Viral Infectivity Factor (Vif counteracts the antiviral effects of host APOBEC3 (A3 proteins and contributes to persistent HIV infection. Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. Here, we describe a degradation-independent mechanism of Vif-mediated antagonism that was revealed through detailed structure-function studies of antibody antigen-binding fragments (Fabs to the Vif complex. Two Fabs were found to inhibit Vif-mediated A3 neutralization through distinct mechanisms: shielding A3 from ubiquitin transfer and blocking Vif E3 assembly. Combined biochemical, cell biological and structural studies reveal that disruption of Vif E3 assembly inhibited A3 ubiquitination but was not sufficient to restore its packaging into viral particles and antiviral activity. These observations establish that Vif can neutralize A3 family members in a degradation-independent manner. Additionally, this work highlights the potential of Fabs as functional probes, and illuminates how Vif uses a multi-pronged approach involving both degradation dependent and independent mechanisms to suppress A3 innate immunity.

Genetically engineered bacteriophage delivers a tumor necrosis factor alpha antagonist coating on neural electrodes

International Nuclear Information System (INIS)

Kim, Young Jun; Nam, Chang-Hoon; Jin, Young-Hyun; Stieglitz, Thomas; Salieb-Beugelaar, Georgette B

2014-01-01

This paper reports a novel approach for the formation of anti-inflammatory surface coating on a neural electrode. The surface coating is realized using a recombinant f88 filamentous bacteriophage, which displays a short platinum binding motif and a tumor necrosis factor alpha antagonist (TNF-α antagonist) on p3 and p8 proteins, respectively. The recombinant bacteriophages are immobilized on the platinum surface by a simple dip coating process. The selective and stable immobilization of bacteriophages on a platinum electrode is confirmed by quartz crystal microbalance with dissipation monitoring, atomic force microscope and fluorescence microscope. From the in vitro cell viability test, the inflammatory cytokine (TNF-α) induced cell death was prevented by presenting recombinant bacteriophage coating, albeit with no significant cytotoxic effect. It is also observed that the bacteriophage coating does not have critical effects on the electrochemical properties such as impedance and charge storage capacities. Thus, this approach demonstrates a promising anti-apoptotic as well as anti-inflammatory surface coating for neural implant applications. (paper)

The effect of Atorvastatin therapy tumour necrosis factor- and vascular adhesion molecules in patients with type 2 diabetes mellitus with no prior history of coronary heart disease

NARCIS (Netherlands)

Soedamah-Muthu, S.S.; Charlton-Menys, V.; Bao, W.; Schalkwijk, C.G.; Stehouwer, C.D.A.; Colhoun, H.M.; Betteridge, D.J.; Durrington, P.; Hitman, G.; Neil, H.A.W.; Livingstone, S.J.; Fuller, J.H.; DeMicco, D.A.; Preston, G.M.

2011-01-01

We examined the effect of atorvastatin (and placebo) on tumour necrosis factor (TNF)a, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular cell adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes without prior cardiovascular disease (CVD) and investigated whether

Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells

DEFF Research Database (Denmark)

Ortis, Fernanda; Naamane, Najib; Flamez, Daisy

2010-01-01

by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. RESEARCH DESIGN AND METHODS: Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h......-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression...... of genes involved in the maintenance of beta-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-alpha, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine...

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

Directory of Open Access Journals (Sweden)

Way-Seah Lee

2017-10-01

Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

Directory of Open Access Journals (Sweden)

Jackson Lauren R

2012-03-01

Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

Are "Market Neutral" Hedge Funds Really Market Neutral?

OpenAIRE

Andrew J. Patton

2009-01-01

Using a variety of different definitions of "neutrality," this study presents significant evidence against the neutrality to market risk of hedge funds in a range of style categories. I generalize standard definitions of "market neutrality," and propose five different neutrality concepts. I suggest statistical tests for each neutrality concept, and apply these tests to a database of monthly returns on 1423 hedge funds from five style categories. For the "market neutral" style, approximately o...

Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression.

Science.gov (United States)

Gupta, Rachna; Gupta, Keshav; Tripathi, A K; Bhatia, M S; Gupta, Lalit K

2016-01-01

This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression. Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels. HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels. © 2016 S. Karger AG, Basel.

Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial

NARCIS (Netherlands)

Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie K.; Landewé, Robert; Matteson, Eric L.; Wollenhaupt, Jürgen; Gaylis, Norman; Murphy, Frederick T.; Neal, Jeffrey S.; Zhou, Yiying; Visvanathan, Sudha; Hsia, Elizabeth C.; Rahman, Mahboob U.; Ahern, Michael John; Hall, Stephen; Nash, Peter Thomas; Graninger, Winfried; Ebner, Wolfgang; Machold, Klaus; Zamani, Omid; Atkins, Christopher; Beaulieu, André; Bell, Mary; Fitzcharles, Mary Ann; Keystone, Edward; Khraishi, Majed; McKendry, Robert J. R.; Rahman, Proton; Thomason, Glen T. D.; Thorne, J. Carter; Bookman, Arthur; Faraawi, Rafat; Hannonen, Pekka; Leirisalo-Repo, Marjetta; Järvinen, Pentti; Braun, Jürgen; Burmester, Gerd; Fiehn, Christoph; Gruenke, Mathias; Bäuerle, Michael; Hauer, Rolf-Walter; Kellner, Herbert; Rubbert, Andrea; Schewe, Stefan; Sieper, Joachim; Tony, Hans-Peter; Kekow, Jörn; Ching, Daniel Wai Tho; Jones, Peter Brian Barrie; Singh, Gagrath Pradeep

2009-01-01

Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid

Experimental and clinical stuties on microcirculation disturbance in the hormonal avascular necrosis of femoral head

International Nuclear Information System (INIS)

Shen Xiaowen

2007-01-01

Objective: To find the correlation factors with microcirculation disturbance by animal and clinic exprements; making clear of the pathogenetic mechanism; and providing theoritical evidence for prevention and treatment of the disease. Methods: The rabbits femoral head avascular necrosis models were induced and created by corticoid steroids. The microcirculation including capillary blood flow rate, blood viscosity, blood ingredients and histopathologic change were studied comparatively between the experimental and the control groups in order to explore the correlative factors of the incidence and proper clinical treatment. Results: The expremental group showed intracappillary blood cells aggregation, obviously slow down of blood flow, increase of serum cholesterol and protein, together with decrease of femoral head capillary vasculation. The effective rate for hormone induced femoral head avaseular necrosis through anticoagulation and promotion of microvascular circulation reached 93.75%. Conclusion: Hormone induced femoral head avascular necrosis is a kind of microcirculation disturbance disease. (authors)

The repeatability of interleukin-6, tumor necrosis factor-α, and C-reactive protein in COPD patients over one year

Directory of Open Access Journals (Sweden)

Umme Kolsum

2009-04-01

Full Text Available Umme Kolsum, Kay Roy, Cerys Starkey, Zoë Borrill, Nick Truman, Jørgen Vestbo, Dave SinghNorth West Lung Research Centre, University of Manchester, South Manchester University Hospitals Trust, Wythenshawe, Manchester, UKBackground: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and C-reactive protein (CRP over one year and examined the relationships between these systemic markers in COPD.Methods: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-α were measured. Repeatability was expressed by intraclass correlation coefficient (Ri and the Bland–Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits.Results: There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001 between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α. CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively. There were no other significant associations between the systemic markers at either of the visits.Conclusions: Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.Keywords: interleukin-6, tumor necrosis factor-α, C-reactive protein, repeatability, COPD   

Induction and regulation of tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand-mediated apoptosis in renal cell carcinoma.

Science.gov (United States)

Griffith, Thomas S; Fialkov, Jonathan M; Scott, David L; Azuhata, Takeo; Williams, Richard D; Wall, Nathan R; Altieri, Dario C; Sandler, Anthony D

2002-06-01

The lack of effective therapy for disseminated renal cell carcinoma (RCC) has stimulated the search for novel treatments including immunotherapeutic strategies. However, poor therapeutic responses and marked toxicity associated with immunological agents has limited their use. The tumor necrosis factor family member tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2 ligand induces apoptosis in a variety of tumor cell types, while having little cytotoxic activity against normal cells. In this study the activation and regulation of TRAIL-induced apoptosis and TRAIL receptor expression in human RCC cell lines and pathologic specimens was examined. TRAIL induced caspase-mediated apoptotic death of RCC cells with variable sensitivities among the cell lines tested. Compared with TRAIL-sensitive RCC cell lines (A-498, ACHN, and 769-P), the TRAIL-resistant RCC cell line (786-O) expressed lesser amounts of the death-inducing TRAIL receptors, and greater amounts of survivin, an inhibitor of apoptosis. Incubation of 786-O with actinomycin D increased the expression of the death-inducing TRAIL receptors and, concomitantly, decreased the intracellular levels of survivin, resulting in TRAIL-induced apoptotic death. The link between survivin and TRAIL regulation was confirmed when an increase in TRAIL resistance was observed after overexpression of survivin in the TRAIL-sensitive, survivin-negative RCC line A-498. These findings, along with our observation that TRAIL receptors are expressed in RCC tumor tissue, suggest that TRAIL may be useful as a therapeutic agent for RCC and that survivin may partially regulate TRAIL-induced cell death.

Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein

International Nuclear Information System (INIS)

Gray, P.W.; Barrett, K.; Chantry, D.; Turner, M.; Feldmann, M.

1990-01-01

The cDNA for one of the receptors for human tumor necrosis factor (TNF) has been isolated. This cDNA encodes a protein of 455 amino acids that is divided into an extracellular domain of 171 residues and a cytoplasmic domain of 221 residues. The extracellular domain has been engineered for expression in mammalian cells, and this recombinant derivative binds TNFα with high affinity and inhibits its cytotoxic activity in vitro. The TNF receptor exhibits similarity with a family of cell surface proteins that includes the nerve growth factor receptor, the human B-cell surface antigen CD40, and the rat T-cell surface antigen OX40. The TNF receptor contains four cysteine-rich subdomains in the extracellular portion. Mammalian cells transfected with the entire TNF receptor cDNA bind radiolabeled TNFα with an affinity of 2.5 x 10 -9 M. This binding can be competitively inhibited with unlabeled TNFα or lymphotoxin (TNFβ)

Cloning of Human Tumor Necrosis Factor (TNF) Receptor cDNA and Expression of Recombinant Soluble TNF-Binding Protein

Science.gov (United States)

Gray, Patrick W.; Barrett, Kathy; Chantry, David; Turner, Martin; Feldmann, Marc

1990-10-01

The cDNA for one of the receptors for human tumor necrosis factor (TNF) has been isolated. This cDNA encodes a protein of 455 amino acids that is divided into an extracellular domain of 171 residues and a cytoplasmic domain of 221 residues. The extracellular domain has been engineered for expression in mammalian cells, and this recombinant derivative binds TNFα with high affinity and inhibits its cytotoxic activity in vitro. The TNF receptor exhibits similarity with a family of cell surface proteins that includes the nerve growth factor receptor, the human B-cell surface antigen CD40, and the rat T-cell surface antigen OX40. The TNF receptor contains four cysteine-rich subdomains in the extra-cellular portion. Mammalian cells transfected with the entire TNF receptor cDNA bind radiolabeled TNFα with an affinity of 2.5 x 10-9 M. This binding can be competitively inhibited with unlabeled TNFα or lymphotoxin (TNFβ).

Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

Energy Technology Data Exchange (ETDEWEB)

Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: Mario.rebecchi@SBUmed.org [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)

2012-10-01

Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

Tumor necrosis factor-alpha modulates effects of aryl hydrocarbon receptor ligands on cell proliferation and expression of cytochrome P450 enzymes in rat liver "stem-like" cells

Czech Academy of Sciences Publication Activity Database

Umannová, Lenka; Zatloukalová, Jiřina; Machala, M.; Krčmář, P.; Májková, Z.; Hennig, B.; Kozubík, Alois; Vondráček, Jan

2007-01-01

Roč. 99, č. 1 (2007), s. 79-89 ISSN 0388-1350 R&D Projects: GA ČR(CZ) GA524/05/0595 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : tumor necrosis factor-alpha * xenobiotic metabolizing enzymes * dioxin Subject RIV: BO - Biophysics

IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes

DEFF Research Database (Denmark)

Falkencrone, Sidsel; Poulsen, Lars K.; Bindslev-Jensen, Carsten

2013-01-01

IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have...

The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence.

Science.gov (United States)

Forde, Hannah; Harper, Emma; Davenport, Colin; Rochfort, Keith D; Wallace, Robert; Murphy, Ronan P; Smith, Diarmuid; Cummins, Philip M

2016-04-01

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that belongs to the tumour necrosis factor (TNF) cytokine superfamily. TRAIL is expressed by numerous cell types including vascular cells, immune cells and adipocytes. Although originally thought to induce apoptosis in malignant or transformed cells only, it is now known that TRAIL can bind up to 5 distinct receptors to activate complex signalling pathways, and is capable of exerting pleiotropic effects in non-transformed cells. In this respect, a number of clinical and animal studies point to the potential vasoprotective influence of TRAIL, with TRAIL deficiency being linked to accelerated atherosclerosis and vascular calcification. Moreover, exogenous TRAIL administration has been shown to exhibit anti-atherosclerotic activity in-vivo. In-vitro studies on TRAIL in this context have yielded conflicting results however, with evidence of both pro-atherogenic and vasoprotective effects ascribed to TRAIL. Notwithstanding these various studies, mechanistic information on the precise nature of TRAIL-mediated injury/protection within the vasculature, as well as the identity of the downstream molecular/cellular targets of TRAIL, is still quite limited. In this review, we will summarize our current knowledge of TRAIL regulation, signalling mechanisms, and its apparent involvement in CVD pathogenesis as a prelude to examining the existing evidence for TRAIL-mediated vasoprotection. To this end, extensive in vitro, in vivo, and clinical studies will be reviewed and critical findings highlighted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tumor necrosis factor: specific binding and internalization in sensitive and resistant cells

International Nuclear Information System (INIS)

Tsujimoto, M.; Yip, Y.K.; Vilcek, J.

1985-01-01

Highly purified, Escherichia coli-derived recombinant human tumor necrosis factor (TNF) was labeled with 125 I and employed to determine receptor binding, internalization, and intracellular degradation in murine L929 cells (highly sensitive to the cytotoxic action of TNF) and in diploid human FS-4 cells (resistant to TNF cytotoxicity). 125 I-labeled TNF bound specifically to high-affinity receptors on both L929 and FS-4 cells. Scatchard analysis of the binding data indicated the presence of 2200 binding sites per L929 cell and 7500 binding sites per FS-4 cell. The calculated dissociation constants are 6.1 x 10 -10 M and 3.2 x 10 -10 M for L929 and FS-4 cells, respectively. In both L929 and FS-4 cells, incubation at 37 0 C resulted in a rapid internalization of the bulk of the cell-bound TNF, followed by the appearance of trichloroacetic acid-soluble 125 I radioactivity in the tissue culture medium, due to degradation of TNF. Degradation but not cellular uptake of TNF was inhibited in the presence of chloroquine (an inhibitor of lysosomal proteases) in both L929 and FS-4 cells, suggesting that degradation occurs intracellularly, probably within lysosomes. These results show that resistance of FS-4 cells to TNF cytotoxicity is not due to a lack of receptors or their inability to internalize and degrade TNF

Effects of a Tumor Necrosis Factor-α Antagonist on Experimentally Induced Rhinosinusitis

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Dong-Hyun Kim

2011-01-01

Full Text Available This prospective, randomized, and controlled study examined the effects of tumor necrosis factor soluble receptor type I (sTNFRI, a TNF-α antagonist on experimentally induced rhinosinusitis in rats. The experimental groups received an instillation of lipopolysaccharide (LPS plus an intramuscular injection of amoxicillin/clavulanate (antibiotic group, an instillation of sTNFRI (sTNFRI group, an instillation of sTNFRI and an injection of amoxicillin/clavulanate (sTNFRI/antibiotic group, or no additional treatment (LPS group. Histopathological changes were determined using hematoxylin-eosin and periodic acid-Schiff (PAS staining. Leakage of exudate was determined using fluorescence microscopy. Vascular permeability was measured using the Evans blue dye technique. Expression of MUC5AC was measured using reverse transcriptase PCR. The sTNFRI, antibiotic, and sTNFRI/antibiotic groups had significantly less capillary permeability, mucosal edema, PAS staining, and expression of MUC5AC than the LPS group. There were no differences in capillary permeability, mucosal edema, PAS staining, and MUC5AC expression between the sTNFRI and sTNFRI/antibiotic groups. The antibiotic group had PAS staining similar to that of the sTNFRI and sTNFRI/antibiotic groups but had a greater increase in capillary permeability, mucosal edema, and MUC5AC expression. This study shows that sTNFRI reduces inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats.

Production of tumor necrosis factor-a is increased in urinary tract infections

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Neni Susilaningsih

2015-12-01

Full Text Available BACKGROUND Urinary tract infection (UTI is a common source of bacteriemia. The most common cause of UTI is Escherichia coli (E. coli. Tumor Necrosis Factor (TNF-á gene polymorphism has been reported to be responsible for an excessive production of TNF-á and eventual disruption of pro-inflammatory cytokine regulation. The aim of this study was to compare TNF-á serum levels and TNF-á allele polymorphisms in patients with UTI due to E.coli and in non- UTI controls. METHODS A cross-sectional study was conducted at Dr. Kariadi Central Hospital and the Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang. In 68 patients with UTI the TNF-á serum levels were determined by means of ELISA and compared to those of non-UTI controls (n=55. TNFá- 308G>A gene polymorphism was analyzed by polymerase chain reaction restriction fragment length using the NcoI enzyme. Fragments were visualized on polyacrylamide gel with silver staining. RESULTS TNF-á serum level in patients with UTI had a median of 8.9 pg/mL, which was significantly higher than the median of 3.7 pg/mL in the control group (pA gene polymorphisms found in the patient group were G/G=61 (90%, G/A=7(10% and A/A=0, while in the control group were G/G=48 (87%, G/A=7 (13% and A/A =0. There was no significant differences (p=0.578 in gene polymorphisms between the two groups. CONCLUSIONS TNF-á serum levels in patients with UTI due to E. coli were significantly higher than in non-UTI controls, but for the TNF-á-380 gene polymorphisms no significant difference was found between the two groups. There are presumably more important factors than host genotype that influence UTI pathogenesis.

Production of tumor necrosis factor-á is increased in urinary tract infections

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Neni Susilaningsih

2012-12-01

Full Text Available Background Urinary tract infection (UTI is a common source of bacteriemia. The most common cause of UTI is Escherichia coli (E. coli. Tumor Necrosis Factor (TNF-á gene polymorphism has been reported to be responsible for an excessive production of TNF-á and eventual disruption of pro-inflammatory cytokine regulation. The aim of this study was to compare TNF-á serum levels and TNF-á allele polymorphisms in patients with UTI due to E.coli and in non-UTI controls. Methods A cross-sectional study was conducted at Dr. Kariadi Central Hospital and the Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang. In 68 patients with UTI the TNF-á serum levels were determined by means of ELISA and compared to those of non-UTI controls (n=55. TNF-á-308G>A gene polymorphism was analyzed by polymerase chain reaction restriction fragment length using the NcoI enzyme. Fragments were visualized on polyacrylamide gel with silver staining. Results TNF-á serum level in patients with UTI had a median of 8.9 pg/mL, which was significantly higher than the median of 3.7 pg/mL in the control group (pA gene polymorphisms found in the patient group were G/G=61 (90%, G/A=7(10% and A/A=0, while in the control group were G/G=48 (87%, G/A=7 (13% and A/A =0. There was no significant differences (p=0.578 in gene polymorphisms between the two groups. Conclusions TNF-á serum levels in patients with UTI due to E. coli were significantly higher than in non-UTI controls, but for the TNF-á-380 gene polymorphisms no significant difference was found between the two groups. There are presumably more important factors than host genotype that influence UTI pathogenesis.

FACTORES PARA LA NO NEUTRALIDAD DE LA EVALUACIÓN DE LA CALIDAD DE LA EDUCACIÓN SUPERIOR (FACTORS FOR NON-NEUTRALITY OF THE EVALUATION OF THE HIGHER EDUCATION QUALITY

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Vizcarra Herles Nina Eleonor

2011-08-01

Full Text Available Resumen:En el presente ensayo, los autores con base en la revisión de fuentes bibliográficas, abordan el tema de la no neutralidad de la evaluación de la calidad de la educación superior, se identifican factores de la no neutralidad en la evaluación y en la calidad relacionados con: el referente (modelo de referencia utilizado para la evaluación, las dimensiones explicativo-relacionales de la calidad y las demandas de calidad formuladas por actores sociales; estos factores expresan el propósito del evaluador, componente ideológico que determina la no neutralidad de la evaluación de la calidad. Se infiere que para los sistemas nacionales de evaluación la definición y la mejora de la calidad de la educación superior compromete la participación multisectorial.Abstract: In this essay, the authors based on a review of literature sources, address the issue of non-neutrality of the evaluation of the quality of higher education, identify factors of non-neutrality in the evaluation and quality related to: the reference model used for evaluation, the explanatory-relational dimensions of quality and quality demands made by social actors; these factors express the purpose of evaluator, ideological component that determines the non-neutrality of quality assessment. It is inferred that for the national assessment systems; the definition and the improving of the quality of higher education undertake multi-stakeholder participation.

Histopathological investigation of radiation necrosis. Coagulation necrosis in the irradiated and non-irradiated brain tumors and in the normal brain tissue

Energy Technology Data Exchange (ETDEWEB)

Nakamura, N [Niigata Univ. (Japan). Brain Research Inst.

1977-01-01

Eighty four irradiated tumors (including 59 gliomas) and the surrounding brain tissue were analyzed. In 'normal' brain tissue, typical coagulation necrosis attributable to irradiation was observed in the cerebral white matter, presenting a whitish-yellow color but no remarkable changes in volume. Histologically there was complete desintegration of myelin and axon. Vascular changes included hyalinous thickening, concentric cleavage, fibrinoid degeneration, adventitial fibrosis and edema of small arteries, fibrin thrombi or occlusion of arterioles and capillaries, and telangiectasia of small veins and venules. While other tumors showed hyalinous or fibrous scar tissue and decrease in volume, the gliomas maintained their original volume without residual tumor cells. Massive coagulation necrosis was occasionally found even in full volume, non-irradiated gliomas (controls), although the changes were fewer and not so varied as in typical radiation necrosis. With small dosages, it was difficult to judge whether the necrosis was caused by irradiation or occurred spontaneously. Coagulation necrosis in tumor tissue was found in 25 of 59 cases (42%) of irradiated gliomas, but in only 2 of 49 cases (4%) of the nonirradiated gliomas. In 49 cases no coagulation necrosis of the surrounding tissue was found. Although histopathological judgement is difficult, it is suggested that there is a significant correlation between coagulation necrosis and irradiation. Discussion of the relationship between coagulation necrosis and NSD (nominal standard dose) led to the conclusion that coagulation necrosis will not be caused by irradiation of less than 1400 rets in NSD.

Clinical and CT imaging features of abdominal fat necrosis

International Nuclear Information System (INIS)

Zhao Jinkun; Bai Renju

2013-01-01

Fat necrosis is a common pathological change at abdominal cross-sectional imaging, and it may cause abdominal pain, mimic pathological change of acute abdomen, or be asymptomatic and accompany other pathophysiologic processes. Fat necrosis is actually the result of steatosis by metabolism or mechanical injury. Common processes that are present in fat necrosis include epiploic appendagitis, infarction of the greater omentum, pancreatitis, and fat necrosis related to trauma or ischemia. As a common fat disease, fat necrosis should be known by clinicians and radiologists. Main content of this text is the clinical symptoms and CT findings of belly fat necrosis and related diseases. (authors)

Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum

NARCIS (Netherlands)

Prins, J. M.; Kuijper, E. J.; Mevissen, M. L.; Speelman, P.; van Deventer, S. J.

1995-01-01

The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production

Evolutionary advantage via common action of recombination and neutrality

Science.gov (United States)

Saakian, David B.; Hu, Chin-Kun

2013-11-01

We investigate evolution models with recombination and neutrality. We consider the Crow-Kimura (parallel) mutation-selection model with the neutral fitness landscape, in which there is a central peak with high fitness A, and some of 1-point mutants have the same high fitness A, while the fitness of other sequences is 0. We find that the effect of recombination and neutrality depends on the concrete version of both neutrality and recombination. We consider three versions of neutrality: (a) all the nearest neighbor sequences of the peak sequence have the same high fitness A; (b) all the l-point mutations in a piece of genome of length l≥1 are neutral; (c) the neutral sequences are randomly distributed among the nearest neighbors of the peak sequences. We also consider three versions of recombination: (I) the simple horizontal gene transfer (HGT) of one nucleotide; (II) the exchange of a piece of genome of length l, HGT-l; (III) two-point crossover recombination (2CR). For the case of (a), the 2CR gives a rather strong contribution to the mean fitness, much stronger than that of HGT for a large genome length L. For the random distribution of neutral sequences there is a critical degree of neutrality νc, and for μmutations affect the mean-field-like and fluctuation-like factors similarly. Consequently, recombination can accelerate the non-mean-field (fluctuation) type dynamics without considerably affecting the mean-field-like factors.

The tumor necrosis factor-α inhibitor golimumab in the treatment of rheumatoid arthritis

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Natalia Vladimirovna Chichasova

2014-01-01

Full Text Available The tumor necrosis factor-α (TNF-α golimumab (GLM, that is a fully human monoclonal anti-body, was registered in Russia in 2012 to treat rheumatic diseases, such as rheumatoid arthritis (RA, ankylosing spondylitis, and psoriatic arthritis. Its distinguishing characteristics are a high affinity for TNF-α and easiness-to-use: the drug as a 0.5-ml solution is injected subcutaneously once monthly. The registration of the medication was followed by the implementation of a massive program of clinical trials. The randomized placebo-controlled GO-FORWARD, GO-BEFORE, and GO-AFTER studies have indicated that GLM is effective in patients with RA from different subgroups and has a favorable safety profile as compared to that of the entire class of biological agents. According to the data of these studies, GLM had a positive effect on the functional status and quality of life in patients with RA: there was a significantly greater decrease in HAQ scores in both the early and long open treatment phases (to 5 years and in fatigability than in the control group (p=0.032, physical and mental health improvements, as shown by the SF-36 questionnaire, and a significant reduction in disability.

Outcome of pinning in patients with slipped capital femoral epiphysis: risk factors associated with avascular necrosis, chondrolysis, and femoral impingement.

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Ulici, Alexandru; Carp, Madalina; Tevanov, Iulia; Nahoi, Catalin Alexandru; Sterian, Alin Gabriel; Cosma, Dan

2018-06-01

Objective This study aimed to assess the principal risk factors that could lead to the most common long-term complications of slipped capital femoral epiphysis, such as avascular necrosis, chondrolysis, and hip impingement. Methods We conducted a single-centre, retrospective study and evaluated patients (70 patients, 81 hips) who were treated for slipped capital femoral epiphysis from 2010 to 2015 and who underwent pinning. We measured the severity of displacement radiologically using the Southwick angle. Postoperative radiographs were evaluated for the most frequent long-term complications of avascular necrosis (AVN), chondrolysis, and femoral acetabular impingement (FAI). Results We found seven cases of AVN, 14 cases of chondrolysis, and 31 hips had an α angle of 60°. Sex, ambulation, and symptoms did not affect development of these complications. Patients with a normal weight were almost two times more likely to develop FAI. Patients with moderate and severe slips had a similar percentage of AVN. In severe slips, 85.7% of patients had an α angle higher than 60°. Conclusions This study shows that severe slips have a higher risk of developing AVN and hip impingement. Every patient who suffers from SCFE (even the mildest forms) should be regularly checked for FAI.

Intestinal volvulus with coagulative hepatic necrosis in a chicken.

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Haridy, Mohie; Goryo, Masanobu; Sasaki, Jun; Okada, Kosuke

2010-04-01

A 7-week-old SPF chicken inoculated at 4 weeks of age with chicken anemia virus was puffed up depressed and had ruffled feathers and a good body condition. Intestinal volvulus involving the jejunum and part of the duodenum forming two loops with one knob was observed. Microscopically, venous infarction of the obstructed loops, periportal and sublobular multifocal coagulative hepatic necrosis and granulomatous inflammation of the cecal tonsils were observed. Gram staining revealed no bacteria in hepatic tissue; however, gram-positive bacilli were detected in the necrotic debris in the intestinal lumen. Immunosuppression might have predisposed the chicken to intestinal and cecal tonsil infection that then progressed to volvulus. Loss of the mucosal barrier in infarction might allow bacterial toxins and vasoactive factors to escape into the systemic circulation (toxemia) and be responsible for the hepatic necrosis.

[C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

Science.gov (United States)

Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

2016-11-01

Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

El factor de necrosis tumoral-α, la resistencia a la insulina, el metabolismo de lipoproteínas y la obesidad en humanos

OpenAIRE

M.ª M. Ramírez Alvarado; C. Sánchez Roitz

2012-01-01

En la obesidad el tejido adiposo produce moléculas proinflamatorias como el Factor de Necrosis tumoral-α, que tiene efectos locales en la fisiología del adipocito y efectos sistémicos en otros órganos. Muchos estudios relacionando TNF-α, obesidad, resistencia a la insulina y metabolismo lipídico se han realizado en ratas, conejos y perros, pero los resultados observados en varios de estos estudios han sido contradictorios y muchos de ellos no se han logrado reproducir en humanos, lo que hace ...

Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α.

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Berlec, Aleš; Perše, Martina; Ravnikar, Matjaž; Lunder, Mojca; Erman, Andreja; Cerar, Anton; Štrukelj, Borut

2017-02-01

TNFα has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L. lactis NZ9000 alleviated the colitis severity one week after colitis induction with DSS, more effectively when administered in preventive fashion prior to, during and after DSS administration. TNFα-binding L. lactis was less effective than control L. lactis, particularly when TNFα-binding L. lactis was administered in preventive fashion. Similarly, an apparently detrimental effect of TNFα neutralization was observed in mice that were intraperitoneally administered anti-TNFα monoclonal antibody infliximab prior to colitis induction. The highest concentrations of tissue TNFα were observed in groups without DSS colitis that were treated either with TNFα-binding L. lactis or infliximab. To conclude, we have confirmed that L. lactis exerts a protective effect on DSS-induced colitis in mice. Contrary to expectations, but in line with some reports, the neutralization of TNFα aggravated disease symptoms in the acute phase of colitis and increased TNFα concentration in colon tissue of healthy mice. Nevertheless, we have demonstrated that oral administration of bacteria with surface displayed TNFα-binding affibody can interfere significantly with TNFα signaling and mimic the infliximab response in the given animal model of colitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Indomethacin induced avascular necrosis of head of femur

Science.gov (United States)

Prathapkumar, K; Smith, I; Attara, G

2000-01-01

Chemically induced avascular necrosis of bone is a well documented entity. Indomethacin is one of the causes of this condition but is often difficult to recognise. Review of the literature shows that only one case of indomethacin induced avascular necrosis has been reported in the English language between 1966 and the present.
The case of a young healthy man, who developed avascular necrosis of head of femur after prolonged administration of indomethacin, is reported here.


Keywords: indomethacin; avascular necrosis PMID:10964124

Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey.

Science.gov (United States)

Aggarwal, Bharat B; Gupta, Subash C; Kim, Ji Hye

2012-01-19

Although activity that induced tumor regression was observed and termed tumor necrosis factor (TNF) as early as the 1960s, the true identity of TNF was not clear until 1984, when Aggarwal and coworkers reported, for the first time, the isolation of 2 cytotoxic factors: one, derived from macrophages (molecular mass 17 kDa), was named TNF, and the second, derived from lymphocytes (20 kDa), was named lymphotoxin. Because the 2 cytotoxic factors exhibited 50% amino acid sequence homology and bound to the same receptor, they came to be called TNF-α and TNF-β. Identification of the protein sequences led to cloning of their cDNA. Based on sequence homology to TNF-α, now a total of 19 members of the TNF superfamily have been identified, along with 29 interacting receptors, and several molecules that interact with the cytoplasmic domain of these receptors. The roles of the TNF superfamily in inflammation, apoptosis, proliferation, invasion, angiogenesis, metastasis, and morphogenesis have been documented. Their roles in immunologic, cardiovascular, neurologic, pulmonary, and metabolic diseases are becoming apparent. TNF superfamily members are active targets for drug development, as indicated by the recent approval and expanding market of TNF blockers used to treat rheumatoid arthritis, psoriasis, Crohns disease, and osteoporosis, with a total market of more than US $20 billion. As we learn more about this family, more therapeutics will probably emerge. In this review, we summarize the initial discovery of TNF-α, and the insights gained regarding the roles of this molecule and its related family members in normal physiology and disease.

The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis.

NARCIS (Netherlands)

Blom, M.; Kievit, W.; Fransen, J.; Kuper, I.H.; Broeder, A. den; Gendt, C.M. de; Jansen, T.L.Th.A.; Brus, H.L.; Laar, M.A. van der; Riel, P.L.C.M. van

2009-01-01

OBJECTIVE: To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS: Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking

The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis

NARCIS (Netherlands)

Blom, Marlies; Kievit, Wietske; Fransen, Jaap; Kuper, Ina H.; den Broeder, Alfons A.; De Gendt, Carla M.A.; Jansen, Tim L.; Brus, Herman L.M.; van de Laar, Mart A.F.J.; van Riel, Piet L.C.M.

2009-01-01

OBJECTIVE:To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS:Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking

Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

Science.gov (United States)

Kamarashev, J; Lor, P; Forster, A; Heinzerling, L; Burg, G; Nestle, F O

2002-01-01

We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents. Copyright 2002 S. Karger AG, Basel

Functional discrepancies between tumor necrosis factor and lymphotoxin alpha explained by trimer stability and distinct receptor interactions

DEFF Research Database (Denmark)

Schuchmann, M; Hess, S; Bufler, P

1995-01-01

Tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) are closely related cytokines which bind with nearly identical affinities to the same pair of cell surface receptors, p55 and p75TNFR. Therefore it is assumed that TNF and LT alpha are redundant cytokines. This study, however......, demonstrates that TNF and LT alpha differ significantly with regard to their mitogenic and cytotoxic potentials. LT alpha's superior mitogenic effect could be explained by its formation of a more stable trimer. In contrast to the TNF trimer, which disintegrated under physiological conditions into biologically...... inactive monomers, the LT alpha trimer remained stable for several days. Accordingly, LT alpha more effectively induced fibroblast growth which demands long-term presence of the cytokine. TNF's superior cytotoxicity, which requires only short-term impact of the cytokine, could be attributed to a distinct...

Neutral injection experiments on the ISX-B tokamak

International Nuclear Information System (INIS)

Scott, S.D.

1983-01-01

The following topics are described: (1) review of confinement scaling in ISX-B with strong neutral injection in clean plasmas, (2) discussion of observed energy confinement improvement in slightly contaminated discharges (factor less than or equal to 2), and (3) preliminary evaluation of confinement with balanced neutral beam injection

Development of delayed radiation necrosis

International Nuclear Information System (INIS)

Ohara, ShigFeki; Takagi, Terumasa; Shibata, Taichiro; Nagai, Hajime.

1983-01-01

The authors discussed the developing process of delayed radiation necrosis of the brain from the case of a 42-year-old female who developed intracranial hypertension and left hemiparesis 5 and a half years after radiotherapy for pituitary adenoma. The initial sign of radiation necrosis was from a CT scan taken 3 and a half years after radiotherapy showing an irregular low density lesion in the right temporal lobe. CT scan 2 years later demonstrated displacement of the midline structures to the left and a larger low density lesion with partially high density in the right MCA territory that was enhanced with intravenous contrast medium. Recovery after a right temporal lobectomy and administration of steroid hormone were uneventful. Eight months later there were no signs of raised intracranial pressure nor of neurological deficits. Tissues obtained from the right temporal lobe at lobectomy revealed the characteristic changes of delayed radiation necrosis; a mixture of fresh, recent, and old vascular lesions in the same specimen. From these findings, it was speculated that delayed radiation necrosis might initially occur within several years after radiotherapy and might gradually take a progressive and extended course, even in cases whose clinical symptoms develop much later. (author)

Expression of tumor necrosis factor receptor-associated protein 1 and its clinical significance in kidney cancer.

Science.gov (United States)

Si, Tong; Yang, Guosheng; Qiu, Xiaofu; Luo, Youhua; Liu, Baichuan; Wang, Bingwei

2015-01-01

To investigate the expression and clinical significance of TRAP1 (tumor necrosis factor receptor-associated protein 1) in kidney cancer. TRAP1 expression was detected in kidney cancer and normal kidney tissues by qRT-PCR and immunohistochemistry (IHC), respectively. Then, the correlation of TRAP1 expression with clinicopathological characters and patients' prognosis was evaluated in kidney cancer. IHC results revealed that the high-expression rates of TRAP1 in kidney cancer tissues and normal kidney tissues were 51.3% (41/80), 23.3% (7/30), and the difference was statistically significant (P=0.01). Also, TRAP1 mRNA level in kidney cancer was found to be significantly greater compared with those in normal kidney by qRT-PCR. In addition, TRAP1 expression in kidney cancer significantly correlated with lymph node metastasis and clinical stage (Pkidney cancer and correlates with patients prognosis, which may be served as a potential marker for the diagnosis and treatment of kidney cancer.

10-Year Associations Between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients With Stable Coronary Heart Disease

DEFF Research Database (Denmark)

Carlsson, Axel C; Ruge, Toralph; Kjøller, Erik

2018-01-01

BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease. METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality...... and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all...... factors improved prediction only modestly (concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk...

Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank Interaction

Science.gov (United States)

Kobayashi, Kanichiro; Takahashi, Naoyuki; Jimi, Eijiro; Udagawa, Nobuyuki; Takami, Masamichi; Kotake, Shigeru; Nakagawa, Nobuaki; Kinosaki, Masahiko; Yamaguchi, Kyoji; Shima, Nobuyuki; Yasuda, Hisataka; Morinaga, Tomonori; Higashio, Kanji; Martin, T. John; Suda, Tatsuo

2000-01-01

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF–dependent bone marrow macrophages (M-BMMφ) appeared within 3 d. Tartrate-resistant acid phosphatase–positive osteoclasts were also formed when M-BMMφ were further cultured for 3 d with mouse tumor necrosis factor α (TNF-α) in the presence of M-CSF. Osteoclast formation induced by TNF-α was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti–RANK (ODF/RANKL receptor) antibody. Experiments using M-BMMφ prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-α. Osteoclasts induced by TNF-α formed resorption pits on dentine slices only in the presence of IL-1α. These results demonstrate that TNF-α stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL–RANK system. TNF-α together with IL-1α may play an important role in bone resorption of inflammatory bone diseases. PMID:10637272

Risk factors for avascular necrosis after closed reduction for developmental dysplasia of the hip.

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Schur, Mathew D; Lee, Christopher; Arkader, Alexandre; Catalano, Anthony; Choi, Paul D

2016-06-01

The purpose of this study was to identify and evaluate risk factors of avascular necrosis (AVN) after closed treatment for developmental dysplasia of the hip (DDH). A retrospective review of children diagnosed with DDH at a tertiary-care children's hospital between 1986 and 2009 was performed. The presence of AVN was assessed according to Salter's classification system. Eighty-two affected hips in 70 children with an average age of 10 months at closed reduction (range 1-31 months) and 5 years (range 2-19 years) of follow-up met the inclusion criteria. Twenty-nine (of 82, 35 %) affected hips developed AVN. The use of pre-reduction traction (p = 0.019) increased the risk of AVN, while preoperative Pavlik harness or brace trial (p = 0.28), presence of ossific nucleus at the time of closed reduction (p = 0.16), and adductor tenotomy (p = 0.37) were not significant factors. Laterality (right vs. left) was also not a significant risk factor (p = 0.75), but patients who underwent closed reduction for bilateral DDH were less likely to develop AVN (p = 0.027). Overall, the degree of abduction did not affect the rate of AVN (p = 0.87). However, in patients treated with closed reduction younger than 6 months of age, the rate of AVN was increased with abduction ≥50° (9/15, 60 %) compared to abduction AVN were more likely to require subsequent surgery (p = 0.034) and more likely to report a fair/poor clinical outcome (p = 0.049). The risk of AVN (35 %) following closed reduction and spica casting for DDH is high. The degree of abduction in spica casts appears to be a risk factor in patients ≤6 months old. The authors recommend that abduction in spica casts should be limited to <50° in children younger than 6 months of age. IV.

Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation

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Jian Shang

2016-01-01

Full Text Available Tumor necrosis factor (TNF receptor-associated factor 5 (TRAF5 is a key mediator of TNF receptor superfamily members and is important in both T helper (Th cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5’s influence on inflammatory bowel diseases (IBDs, we investigated TRAF5 deficiency’s effect on dextran sulfate sodium- (DSS- induced colitis. Colitis was induced in TRAF5 knockout (KO mice and their wild-type (WT littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4+ T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4+ T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.

Combined Stimulation with the Tumor Necrosis Factor α and the Epidermal Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured Slices

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Francis Finot

2012-01-01

Full Text Available The culture liver slices are mainly used to investigate drug metabolism and xenobiotic-mediated liver injuries while apoptosis and proliferation remain unexplored in this culture model. Here, we show a transient increase in LDH release and caspase activities indicating an ischemic injury during the slicing procedure. Then, caspase activities decrease and remain low in cultured slices demonstrating a low level of apoptosis. The slicing procedure is also associated with the G0/G1 transition of hepatocytes demonstrated by the activation of stress and proliferation signalling pathways including the ERK1/2 and JNK1/2/3 MAPKinases and the transient upregulation of c-fos. The cells further progress up to mid-G1 phase as indicated by the sequential induction of c-myc and p53 mRNA levels after the slicing procedure and at 24 h of culture, respectively. The stimulation by epidermal growth factor induces the ERK1/2 phosphorylation but fails to activate expression of late G1 and S phase markers such as cyclin D1 and Cdk1 indicating that hepatocytes are arrested in mid-G1 phase of the cell cycle. However, we found that combined stimulation by the proinflammatory cytokine tumor necrosis factor α and the epidermal growth factor promotes the commitment to DNA replication as observed in vivo during the liver regeneration.

A prognostic model for soft tissue sarcoma of the extremities and trunk wall based on size, vascular invasion, necrosis, and growth pattern

DEFF Research Database (Denmark)

Carneiro, Ana; Bendahl, Par-Ola; Engellau, Jacob

2011-01-01

type, necrosis, and grade. METHODS:: Whole-tumor sections from 239 soft tissue sarcomas of the extremities were reviewed for the following prognostic factors: size, vascular invasion, necrosis, and growth pattern. A new prognostic model, referred to as SING (Size, Invasion, Necrosis, Growth......), was established and compared with other clinically applied systems. RESULTS:: Size, vascular invasion, necrosis, and peripheral tumor growth pattern provided independent prognostic information with hazard ratios of 2.2-2.6 for development of metastases in multivariate analysis. When these factors were combined...... into the prognostic model SING, high risk of metastasis was predicted with a sensitivity of 74% and a specificity of 85%. Moreover, the prognostic performance of SING compared favorably with other widely used systems. CONCLUSIONS:: SING represents a promising prognostic model, and vascular invasion and tumor growth...

Association Study of Tumor Necrosis Factor Receptor 1 (TNFR1 Gene Polymorphisms with Schizophrenia in the Polish Population

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Renata Suchanek-Raif

2017-01-01

Full Text Available Schizophrenia is a devastating mental disorder with undetermined aetiology. Previous research has suggested that dysregulation of proinflammatory cytokines and their receptors plays a role in developing schizophrenia. We examined the association of the three single nucleotide polymorphisms (SNPs; rs4149576, rs4149577, and rs1860545 in the tumor necrosis factor receptor 1 (TNFR1 gene with the development and psychopathology of paranoid schizophrenia in the Polish Caucasian sample consisting of 388 patients and 657 control subjects. The psychopathology was assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS. SNPs were genotyped using the TaqMan 5′-exonuclease allelic discrimination assay. The SNPs tested were not associated with a predisposition to paranoid schizophrenia in either the entire sample or after stratification according to gender. However, rs4149577 and rs1860545 SNPs were associated with the intensity of the PANSS excitement symptoms in men, which may contribute to the risk of violent behavior. Polymorphisms in the TNFR1 gene may have an impact on the symptomatology of schizophrenia in men.

Prediction of post-operative necrosis after mastectomy: A pilot study utilizing optical diffusion imaging spectroscopy

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Xie Xian-Jin

2009-11-01

Full Text Available Abstract Introduction Flap necrosis and epidermolysis occurs in 18-30% of all mastectomies. Complications may be prevented by intra-operative detection of ischemia. Currently, no technique enables quantitative valuation of mastectomy skin perfusion. Optical Diffusion Imaging Spectroscopy (ViOptix T.Ox Tissue Oximeter measures the ratio of oxyhemoglobin to deoxyhemoglobin over a 1 × 1 cm area to obtain a non-invasive measurement of perfusion (StO2. Methods This study evaluates the ability of ViOptix T.Ox Tissue Oximeter to predict mastectomy flap necrosis. StO2 measurements were taken at five points before and at completion of dissection in 10 patients. Data collected included: demographics, tumor size, flap length/thickness, co-morbidities, procedure length, and wound complications. Results One patient experienced mastectomy skin flap necrosis. Five patients underwent immediate reconstruction, including the patient with necrosis. Statistically significant factors contributing to necrosis included reduction in medial flap StO2 (p = 0.0189, reduction in inferior flap StO2 (p = 0.003, and flap length (p = 0.009. Conclusion StO2 reductions may be utilized to identify impaired perfusion in mastectomy skin flaps.

Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

International Nuclear Information System (INIS)

Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

1994-01-01

Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig

Research on Stress Neutral Layer Offset in the Straightening Process

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Hailian Gui

2015-01-01

Full Text Available The stress neutral layer offset is analyzed by theoretical and numerical calculation methods. In traditional straightening theory, the stress neutral layer was consistent with the geometric central layer. However, there is a phenomenon that the stress neutral layer has some offset with the geometric neutral layer. This offset is a very important factor for improving the precision of the straightening force. The formula of the stress neutral layer offset is obtained by a theoretical method and the change law is given by numerical calculation method. The neutral layer offset theory provides the theoretical basis for establishing the model of straightening force precisely.

Reversal of cerebral radiation necrosis with bevacizumab treatment in 17 Chinese patients

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Wang Yang

2012-08-01

Full Text Available Abstract Background Bevacizumab has been suggested as a new treatment modality for cerebral radiation necrosis due to its ability to block the effects of vascular endothelial growth factor (VEGF in leakage-prone capillaries, though its use still remains controversial in clinical practice. Methods The use of bevacizumab in 17 patients with symptomatic cerebral radiation necrosis poorly controlled with dexamethasone steroid treatments was examined between March 2010 and January 2012. Bevacizumab therapy was administered for a minimum of two cycles (7.5 mg/kg, at two-week interval with a median of four bevacizumab injections. Changes in bi-dimensional measurements of the largest radiation necrosis lesions were observed by gadolinium-enhanced and T2-weighted magnetic resonance imaging (MRI. Additionally, dexamethasone dosage, Karnofsky performance status (KPS, adverse event occurrence and associated clinical outcomes were recorded for each patient. Results MRI analysis revealed that the average reduction was 54.9% and 48.4% in post-gadolinium and T2-weighted sequence analysis, respectively. Significant clinical neurological improvements were expressed in 10 patients according to KPS values. Dexamethasone reduction was achieved four weeks after initiation of bevacizumab in all patients, with four patients successfully discontinuing dexamethasone treatment. Mild to moderate bevacizumab-related adverse events, such as fatigue, proteinuria and hypertension were observed in three patients. Upon follow-up at 4 to 12 months, 10 patients showed clinical improvement, and 7 patient deaths occurred from tumor progression (5 patients, recurrent necrosis (1 patient, and uncontrolled necrosis-induced edema (1 patient. Conclusions These findings suggest bevacizumab as a promising treatment for cerebral radiation necrosis induced by common radiation therapies, including external beam radiotherapy (EBRT, stereotactic radiosurgery (SRS, and fractionated stereotactic

Interleukin-10 to tumor necrosis factor-alpha ratio is a predictive biomarker in nonalcoholic fatty liver disease: interleukin-10 to tumor necrosis factor-alpha ratio in steatohepatitis.

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Hashem, Reem M; Mahmoud, Mona F; El-Moselhy, Mohamed A; Soliman, Hala M

2008-10-01

Fatty liver disease is commonly associated with diabetes mellitus (DM). Insulin resistance (IR) as an investigative biomarker is only concerned with fatty liver that results from DM type 2 associated with metabolic syndrome. Irrespective of IR, DM is generally characterized by overproduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), whereas action of the latter is modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). The aim of this study was to investigate the efficacy of using TNF-alpha alone or IL-10/TNF-alpha ratio compared to IR, as a promising biomarker for fatty liver assessment in DM. Furthermore, we hypothesized that using garlic as an immunomodulator may decrease TNF-alpha and increase IL-10 production to improve steatohepatitis. DM was induced metabolically by a high-fat diet to bring about IR, or chemically by alloxan, producing insulin deficiency, in male albino rats. Garlic powder was supplemented (15 mg/kg per day) for 3 weeks. Fatty liver was depicted histologically and biochemically (aspartic aminotransferase, alanine aminotransferase, HOMA-IR, TNF-alpha, IL-10, IL-10/TNF-alpha ratio). We found that, in contrast to obese rats, garlic decreased IL-10/TNF-alpha ratio, despite decreasing TNF-alpha in alloxan diabetic rats in agreement with the histology, which revealed more prominent improvement in the obese group. Moreover, the effect of garlic was not linked to improvement of IR in obese rats. We conclude that IL-10/TNF-alpha ratio may be considered as a convenient biomarker for investigation of fatty liver of different grades, apart from being associated with IR, and immunomodulation of this ratio in favor of increasing it may exert significant improvement.

Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

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Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

2001-06-01

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

Avascular necrosis of bone complicating corticosteroid replacement therapy.

OpenAIRE

Williams, P L; Corbett, M

1983-01-01

Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement.

Tracheal stoma necrosis: a case repor

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Pak S

2017-04-01

Full Text Available Acute tracheal dilatation, due to an overinflated cuff, has been reported early in the course of mechanical ventilation through an endotracheal tube. Tracheal stoma necrosis is a rare complication, but such can accompany acute tracheal dilation. Herein, we report a case of tracheal necrosis 9 days following tracheostomy placement in a 71-year old woman associated with overinflation of the tracheal tube cuff. This case report aims to 1 add to the scant body of knowledge about the diagnosis and management for the patients with tracheal stoma necrosis and 2 raise awareness for error-traps in interpreting diagnostic images, specifically satisfaction of search error, inattentional blindness error, and alliterative error.

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

OpenAIRE

Ibrahim, Fowzia; Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-01-01

Objectives: RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response.Methods: We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups...

On becoming neutral: effects of experimental neutralizing reconsidered.

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van den Hout, M; van Pol, M; Peters, M

2001-12-01

Behaviour Research and Therapy 34 (1996) 889-898 found that writing out a negative thought produced anxiety and an urge to neutralize the thought, that instructing participants to neutralize the thought reduced anxiety/neutralization urge in the short run (i.e. within 2 min), but that in the control group 20 min without instruction was attended by the same reduction in anxiety/urge to neutralize ("natural decay"). The observations were made with pariticipants who scored high on "thought action fusion" and the experiment was set up as exerimental model of obsessions. We repeated the study with participants that were not selected on thought action fusion. All the findings reported by Behaviour Research and Therapy 34 (1996) 889-898 were replicated. Correlational analysis indicated that the strength of the effect was not related to scores on scales measuring "thought action fusion". Behaviour Research and Therapy 34 (1996) 889-898 did not assess whether non-neutralizing was followed by immediate reductions in distress. We did assess this and found that the larger part of the immediate reduction of distress after neutralization also occurs when no neutralization instruction is given. The effects of neutralization instructions in the present type of experiment are considerably less powerful than suggested earlier.

A comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

International Nuclear Information System (INIS)

Chang, M.P.

1988-01-01

The mechanism by which tumor necrosis factor-alpha (TNF) initiates tumor cell destruction is unknown. We have approached this problem by comparing the biological properties of TNF with diphtheria toxin (DTx), a well-characterized cytotoxin. Initial studies with human U937 cells revealed that a transient exposure to low pH enhances the cytotoxic activity of TNF. Detailed studies on the interaction of TNF with pure lipid vesicles revealed that the acid-enhanced cytolytic activity of this cytokine is correlated with the acquisition of membrane binding and insertion properties. Significantly, an increase in target membrane stabilization was observed in the presence of TNF; hence, TNF is not directly lytic for membranes. In susceptible target cells, DTx induces the release of 51 Cr- and 75 Se-labeled proteins within 7 h. Although DTx-triggered cell death has generally been accepted as a straightforward effect of translation inhibition, little or no cell lysis was observed over a 20-30 h period when target cells were exposed to cycloheximide, amino acid deficient medium or metabolic poisons even though protein synthesis was inhibited to levels observed with DTx. The protein synthesis inhibition and cytolytic activities of DTx showed similar dose-dependencies, target cell specificities, and sensitivities to NH 4 Cl inhibition. DTx-induced DNA fragmentation preceded cells lysis and did not occur in cells that were treated with the other protein synthesis inhibitors

The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

DEFF Research Database (Denmark)

Kolsum, Umme; Roy, Kay; Starkey, Cerys

2009-01-01

BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

DEFF Research Database (Denmark)

Kolsum, Umme; Roy, Kay; Starkey, Cerys

2009-01-01

BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

Skin Necrosis from Intra-articular Hyaluronic Acid Injection.

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Kim, Whan B; Alhusayen, Raed O

2015-01-01

Tissue necrosis is a rare yet potentially serious complication of intra-articular (IA) hyaluronic acid (HA) injections for treatment of knee osteoarthritis. To report a case of a patient with cutaneous necrosis after IA HA injection for treatment of knee osteoarthritis, presenting as a livedoid violaceous patch on the right knee. We report a case of cutaneous necrosis as a rare complication of IA HA injection for treatment of knee osteoarthritis. A literature review was undertaken of similar cases. Use of HA IA injections in the treatment of osteoarthritis can result in similar skin necrosis at uncommon anatomic locations corresponding to the site of HA injection. Although tissue necrosis is a rare complication, physicians need to be aware of this possibility as a complication of HA IA injections in the treatment of osteoarthritis and should be mindful of potential treatment options to manage this adverse event. © 2014 Canadian Dermatology Association.

Avascular necrosis of the femoral head in HIV positive patients-an ...

African Journals Online (AJOL)

26 consecutive patients (37 hips) with avascular necrosis (AVN) of the femoral head treated surgically at our institution from 1999 to 2008 were reviewed . The aims of the study were to evaluate the risk factors associated with AVN in HIV positive and HIV negative individuals, and assess early response to total hip ...

Correlation between electrical conductivity and apparent diffusion coefficient in breast cancer: effect of necrosis on magnetic resonance imaging.

Science.gov (United States)

Kim, Soo-Yeon; Shin, Jaewook; Kim, Dong-Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; You, Jai Kyung; Kim, Min Jung

2018-03-06

To investigate the correlation between conductivity and ADC in invasive ductal carcinoma according to the presence of necrosis on MRI. Eighty-one women with invasive ductal carcinoma ≥1 cm on T2-weighted fast spin echo sequence of preoperative MRI were included. Phase-based MR electric properties tomography was used to reconstruct conductivity. Mean ADC was measured. Necrosis was defined as an area with very high T2 signal intensity. The relationship between conductivity and ADC was examined using Spearman's correlation coefficient (r). Multiple linear regression analysis was performed to identify factors associated with conductivity or ADC. In the total group, conductivity showed negative correlation with ADC (r = -0.357, p = 0.001). This correlation was maintained in the subgroup without necrosis (n = 53, r = -0.455, p = 0.001), but not in the subgroup with necrosis (n = 28, r = -0.080, p = 0.687). The correlation between the two parameters was different according to necrosis (r = -0.455 vs -0.080, p = 0.047). HER2 enriched subtype was independently associated with conductivity (p = 0.029). Necrosis on MRI was independently associated with ADC (p = 0.027). Conductivity shows negative correlation with ADC that is abolished by the presence of necrosis on MRI. • Electric conductivity showed negative correlation with ADC • However, the correlation was abolished by the presence of necrosis on MRI • HER2-enriched subtype was independently associated with conductivity • Necrosis on MRI was independently associated with ADC.

Association between Interleukin-10-1082 G/A and Tumor Necrosis Factor-α 308 G/A Gene Polymorphisms and Respiratory Distress Syndrome in Iranian Preterm Infants

OpenAIRE

Khoshdel, Abolfazl; Kheiri, Soleiman; Omidvari, Peyman; Moradi, Fahimeh; Hamidi, Majid; Teimori, Hossein

2017-01-01

Cytokine polymorphisms may contribute to the prevalence of respiratory distress syndrome. The present study was done to investigate the frequency of interleukin- (IL-) 10 and tumor necrosis factor- (TNF-) ? gene polymorphisms and their association with the risk of RDS in preterm infants. One-hundred and nineteen patients with RDS and 119 healthy preterm infants were enrolled. PCR restriction fragment length polymorphism was used to determine the frequency of IL-10 and TNF-? genotypes at -1082...

Leonurine protects against tumor necrosis factor-α-mediated inflammation in human umbilical vein endothelial cells.

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Liu, Xinhua; Pan, Lilong; Wang, Xianli; Gong, Qihai; Zhu, Yi Zhun

2012-05-01

Leonurine, a bioactive alkaloid compound in Herba leonuri, has various pharmacological activities, including antioxidant and anti-apoptotic capacities. This study was conducted to test the hypothesis that leonurine was able to attenuate tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVEC) activation and the underlying molecular mechanisms. Mitogen-activated protein kinases (MAPK) activation, nuclear factor-κB (NF-κB) activation, and inflammatory mediators expression were detected by Western blot or enzyme-liked immunosorbent assay, intracellular reactive oxygen species (ROS) and NF-κB p65 translocation were measured by immunofluorescence, endothelial cell-monocyte interaction was detected by microscope. Leonurine inhibited U937 cells adhesion to TNF-α-activated HUVEC in a concentration dependent manner. Treatment with leonurine blocked TNF-α-induced mRNA and protein expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), cyclooxygenase-2, and monocyte chemoattractant protein-1 in endothelial cells. In addition, leonurine attenuated TNF-α-induced intracellular ROS production in HUVEC. Furthermore, leonurine also suppressed the TNF-α-activated p38 phosphorylation and IκBα degradation. Subsequently, reduced NF-κB p65 phosphorylation, nuclear translocation, and DNA-binding activity were also observed. Our results demonstrated for the first time that the anti-inflammatory properties of leonurine in endothelial cells, at least in part, through suppression of NF-κB activation, which may have a potential therapeutic use for inflammatory vascular diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Prevalence and risk factor for symptomatic avascular necrosis development in Thai systemic lupus erythematosus patients.

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Kunyakham, Wichak; Foocharoen, Chingching; Mahakkanukrauh, Ajanee; Suwannaroj, Siraphop; Nanagara, Ratanavadee

2012-06-01

Avascular necrosis (AVN) has been reported in systemic lupus erythematosus (SLE) and most SLE patients suffer from this problem. To study the prevalence of AVN in Thai SLE patients and to determine the risk factors for developing AVN. A retrospective study was performed, between January 1, 1995 and August 31, 2005, on patients over 15 years of age in Khon Kaen, Thailand. The medical records of 736 SLE patients were reviewed. The female to male ratio was 15.4:1. The prevalence of AVN was 8.8%. The average age at the time of AVN detection was 27 years (range, 18-54) and the average duration of disease 69 months (range, 12-112). All cases were AVN of the hip joint. The factors correlated with AVN included: long duration of disease, history of previous septic arthritis in the ipsilateral hip to the AVN development, hematological involvement, gastrointestinal involvement, arthritis and cutaneous vasculitis. After regression analysis, hematological involvement and long duration of disease were associated with AVN with a respective odds ratio of 3.13 (95% CI 1.13-8.54) and 1.01 (95% CI 1.00-1.02). Neither high-dose steroid nor antimalarial treatment were correlated with AVN in our study and 4.6% (n = 3) of patients had never received steroid therapy during the follow-up period. Prevalence of symptomatic AVN was 8.8% in our SLE patients. A longer duration of disease and hematological involvement were associated with AVN development.

Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralizing Potency and Multifunctionality, Generated for Therapeutic Development

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Obinna C. Ubah

2017-12-01

Full Text Available The management of chronic inflammatory diseases, such as inflammatory bowel disease, psoriasis, and rheumatoid arthritis has significantly improved over the last decade with the clinical availability of anti-TNF-α biologics. Despite this undoubted treatment success, a combination of acquired resistance together with an increased risk of systemic complications, means that a significant number of patients either fail to find a suitable targeted therapy or frustratingly discover that an approach that did work is no longer efficacious. Here, we report the isolation and characterization of a new class of super-neutralizing anti-TNF-α biologics formats, the building blocks of which were originally derived as variable new antigen receptor (VNAR domains from an immunized nurse shark. These parental small, stable VNAR monomers recognize and neutralize tumor necrosis factor (TNF-α, in cell-based assays, at nanomolar concentrations. However, the simple, single-chain molecular architecture of VNARs allows for easy and multiple reformatting options. Through reformatting, we achieved a 50,000-fold enhancement in in vitro efficacy with super-neutralizing fusion proteins able to block TNF-α induced cytotoxicity in the 2–5 pM range while retaining other functionality through the addition of fusion proteins known to extend serum half-life in vivo. In an in vitro intestinal epithelial barrier dysfunction efficacy model, the lead VNAR domains, restored barrier function and prevented paracellular flux with comparable efficacy to adalimumab (Humira®. In addition, all multivalent VNAR constructs restored trans-epithelial electrical resistance (TEER to approximately 94% of the untreated control. Reformatted VNAR domains should be considered as a new class of biologic agents for the treatment of hTNF-α driven diseases; either used systemically with appropriate half-life extension or alternatively where site-specific delivery of small and stable neutralizers

Evaluation of angiopoietin 1 and 2, vascular endothelial growth factor, and tumor necrosis factor alpha levels in asthmatic children.

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Köksal, Burcu Tahire; Ozbek, Ozlem Yilmaz; Bayraktar, Nilufer; Yazici, Ayse Canan

2014-01-01

Asthma is characterized by chronic airway inflammation that is associated with structural changes termed airway remodeling. Recently, cytokines/mediators that augment inflammation have been attracting attention in this field. The aim of this study was to evaluate serum angiopoietin (Ang)-1, Ang-2, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) alpha values, which have important roles in inflammation, angiogenesis, and remodeling in asthmatic children. We also documented correlations between demographic features, duration of asthma, and pulmonary function test (PFT) parameters. Randomly selected 40 children (20 male and 20 female children, aged 6-16 years) with mild or moderate persistent asthma and 32 healthy children (15 male and 17 female children, aged 6-16 years) enrolled in the study. All asthmatic children had been using inhaled corticosteroids at least for the last 3 months. Serum Ang-1 levels were significantly lower in asthmatic children than those in normal controls. The Ang-1/Ang-2 ratio was also significantly lower in asthmatic children compared with those in normal controls (p < 0.01). However, serum Ang-2, VEGF, and TNF-alpha levels were similar in the two groups. A significant positive correlation was found between VEGF and duration of asthma. No correlation between serum Ang-1, Ang-2, VEGF values, and PFT parameters was obtained. On the other hand, significant negative correlation was detected between serum TNF-alpha and forced expiratory volume in 1 second. We have shown that serum Ang-1 levels and Ang-1/Ang-2 ratio were significantly reduced and balance was toward Ang-2 in asthmatics children. This process may lead to inflammation, destabilization of blood vessels, and trigger remodeling.

The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

Science.gov (United States)

Takahashi, N; Yoshizaki, T; Hiranaka, N; Kumano, O; Suzuki, T; Akanuma, M; Yui, T; Kanazawa, K; Yoshida, M; Naito, S; Fujiya, M; Kohgo, Y; Ieko, M

2015-05-01

A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes. Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.

Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

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Kathryn S. Brown

2014-01-01

Full Text Available Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1 mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

Science.gov (United States)

Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

2006-04-11

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

Soluble Prokaryotic Expression and Purification of Bioactive Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand.

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Do, Bich Hang; Nguyen, Minh Tan; Song, Jung-A; Park, Sangsu; Yoo, Jiwon; Jang, Jaepyeong; Lee, Sunju; So, Seoungjun; Yoon, Yejin; Kim, Inki; Lee, Kyungjin; Jang, Yeon Jin; Choe, Han

2017-12-28

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as an antitumor agent owing to its ability to induce apoptosis of cancer cells without imparting toxicity toward most normal cells. TRAIL is produced in poor yield because of its insoluble expression in the cytoplasm of E. coli . In this study, we achieved soluble expression of TRAIL by fusing maltose-binding protein (MBP), b'a' domain of protein disulfide isomerase (PDIb'a'), or protein disulfide isomerase at the N-terminus of TRAIL. The TRAIL was purified using subsequent immobilized metal affinity chromatography and amylose-binding chromatography, with the tag removal using tobacco etch virus protease. Approximately 4.5 mg of pure TRAIL was produced from 125 ml flask culture with a purification yield of 71.6%. The endotoxin level of the final product was 0.4 EU/μg, as measured by the Limulus amebocyte lysate endotoxin assay. The purified TRAIL was validated and shown to cause apoptosis of HeLa cells with an EC₅₀ and Hill coefficient of 0.6 ± 0.03 nM and 2.41 ± 0.15, respectively. The high level of apoptosis in HeLa cells following administration of purified TRAIL indicates the significance and novelty of this method for producing high-grade and high-yield TRAIL.

Curcumin Requires Tumor Necrosis Factor α Signaling to Alleviate Cognitive Impairment Elicited by Lipopolysaccharide

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E.M. Kawamoto

2012-05-01

Full Text Available A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor α receptor 2 (TNFR2 signaling. In vivo, the ability of curcumin to counteract hippocampus-dependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl-D-aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se.

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

Science.gov (United States)

Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

2006-01-01

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive Disorder

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N. Konuk

2007-01-01

Full Text Available Aim. Recent research implicated place of an immune mechanism in the pathophysiology of obsessive-compulsive disorder (OCD. Despite increasing evidence involvement of cytokine release in OCD, results of the studies are inconsistent. The aim of this study was to evaluate the plasma levels of the cytokines; tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 in OCD patients. Methods. Plasma concentrations of TNF-α and IL-6 were measured in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy controls. TNF-α and IL-6 concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA. Results. Both TNF-α and IL-6 levels showed statistically significant increases in OCD patients compared to controls (P<.000, P<.001, resp.. In addition, the age of onset was negatively correlated with TNF-α level (r=−.402, P=.025 and duration of illness was weakly correlated with IL-6 levels (r:.357; P:.048 in patients group. Conclusion. OCD patients showed increases in TNF-α and IL-6 levels compared to the healthy controls. This study provides evidence for alterations in the proinflamatory cytokines which suggest the involvement of the immune system in the pathophysiology of OCD.

Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

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Fumiaki Obata

2014-05-01

Full Text Available Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM levels due to glycine N-methyltransferase (Gnmt upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.

Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

DEFF Research Database (Denmark)

Fluhr, Herbert; Krenzer, Stefanie; Stein, Gerburg M

2007-01-01

The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas......-mediated signaling during early implantation. Here we show that ESCs are primarily resistant to Fas-mediated apoptosis independently of their state of hormonal differentiation. Pre-treatment of ESCs with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha sensitizes them to become apoptotic upon stimulation...... of Fas by an agonistic anti-Fas antibody. Incubation of ESCs with the early embryonic signal human chorionic gonadotropin (hCG, CGB) does not influence their reaction to Fas stimulation. The sensitizing effect of IFN-gamma and TNF-alpha was accompanied by a significant upregulation of Fas and FLICE...

Recurrent abdominal pain as the presentation of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in an Asian girl: a case report and review of the literature.

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Chen, Yun-Ju; Yu, Hsin-Hui; Yang, Yao-Hsu; Lau, Yu-Lung; Lee, Wen-I; Chiang, Bor-Luen

2014-12-01

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is characterized by periodic fever, cutaneous rash, conjunctivitis, lymphadenopathy, abdominal pain, myalgia, and arthralgia. It is a rare autosomal dominant disease and strongly associated with heterozygous mutations in the tumor necrosis factor (TNF) receptor super family 1A (TNFRSF1A) gene. It is believed to be more common in Western countries than in Asian countries. Here, we present the case of a 14-year-old girl with periodic fever and abdominal pain with elevation of inflammatory markers for 2 years. After extensive work-up of infectious etiology with negative results, the diagnosis of TRAPS was made although no gene mutations were identified in the TNFRSF1A gene, MVK gene, and NALP3/CIAS1 gene. She had partial clinical response to corticosteroids and immunomodulatory agents. However, the treatment response to TNF-α inhibitor etanercept was dramatic. She has remained symptom free under regular weekly to biweekly etanercept treatment for 2 years. We also reviewed the related literature and summarized the data of 10 Asian cases of TRAPS. Copyright © 2012. Published by Elsevier B.V.

Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study

NARCIS (Netherlands)

Smolen, Josef S.; Kay, Jonathan; Matteson, Eric L.; Landewé, Robert; Hsia, Elizabeth C.; Xu, Stephen; Zhou, Yiying; Doyle, Mittie K.

2014-01-01

Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) inhibitor use. Patients (n=461) previously receiving ≥1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint

ROLE OF THE MITOCHONDRION IN PROGRAMMED NECROSIS

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Christopher eBaines

2010-11-01

Full Text Available In contrast to the programmed nature of apoptosis and autophagy, necrotic cell death has always been believed to be a random, uncontrolled process that leads to the accidental death of the cell. This dogma, however, is being challenged and the concept of necrosis also being programmed is gaining ground. In particular, mitochondria appear to play a pivotal role in the mediation of programmed necrosis. The purpose of this review, therefore, is to appraise the current concepts regarding the signaling mechanisms of programmed necrosis, with specific attention to the contribution of mitochondria to this process.

Piroxicam induced submassive necrosis of the liver.

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Paterson, D; Kerlin, P; Walker, N; Lynch, S; Strong, R

1992-01-01

Several widely used non-steroidal anti-inflammatory drugs have been reported as causing severe hepatitis. Three cases of severe acute hepatitis have been reported in association with piroxicam. A fatal submassive necrosis that occurred in a 68 year old lady who had received piroxicam for 15 months is described. A 48 year old man who developed submassive hepatic necrosis six weeks after beginning piroxicam but was successfully treated with orthotopic liver transplantation is also reported. Piroxicam may induce submassive necrosis of the liver, probably as an idiosyncratic reaction. Images Figure 1 Figure 2 Figure 3 PMID:1446877

Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

National Research Council Canada - National Science Library

Behbakht, Kian

2008-01-01

.... More effective therapies are urgently needed. One of the most promising therapies in development for ovarian cancer is the use of either the Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL...

Predictive value of histologic tumor necrosis after radiation.

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Chen, Y; Taghian, A G; Rosenberg, A E; O'Connell, J; Okunieff, P; Suit, H D

2001-12-20

Postsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS-26, SCC-21, and HGL-21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One-half of the tumor was divided into 1-mm(3) fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCD(p) (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. Copyright 2001 Wiley-Liss, Inc.

[S3 Guideline. Part 3: Non-Traumatic Avascular Necrosis in Adults - Surgical Treatment of Atraumatic Avascular Femoral Head Necrosis in Adults].

Science.gov (United States)

Maus, U; Roth, A; Tingart, M; Rader, C; Jäger, M; Nöth, U; Reppenhagen, S; Heiss, C; Beckmann, J

2015-10-01

with avascular necrosis should be seen as the main risk factor for higher revision rate. The results after resurfacing (today with known restricted indications) and cemented as well as cementless THA in aFKN are comparable for the appropriate indication to those in coxarthrosis or other diagnoses. Regardless of the underlying disease endoprosthetic treatment in aFKN leads to good results. Both cemented and cementless fixation techniques can be recommended. Georg Thieme Verlag KG Stuttgart · New York.

Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head

Science.gov (United States)

Ma, Xiao-Wei; Cui, Da-Ping; Zhao, De-Wei

2015-01-01

Vascular endothelial cell growth factor (VEGF) combined with bone morphogenetic protein (BMP) was used to repair avascular necrosis of the femoral head, which can maintain the osteogenic phenotype of seed cells, and effectively secrete VEGF and BMP-2, and effectively promote blood vessel regeneration and contribute to formation and revascularization of tissue engineered bone tissues. To observe the therapeutic effect on the treatment of avascular necrosis of the femoral head by using bone marrow mesenchymal stem cells (BMSCs) modified by VEGF-165 and BMP-2 in vitro. The models were avascular necrosis of femoral head of rabbits on right leg. There groups were single core decompression group, core decompression + BMSCs group, core decompression + VEGF-165/BMP-2 transfect BMSCs group. Necrotic bone was cleared out under arthroscope. Arthroscopic observation demonstrated that necrotic bone was cleared out in each group, and fresh blood flowed out. Histomorphology determination showed that blood vessel number and new bone area in the repair region were significantly greater at various time points following transplantation in the core decompression + VEGF-165/BMP-2 transfect BMSCs group compared with single core decompression group and core decompression + BMSCs group (P < 0.05). These suggested that VEGF-165/BMP-2 gene transfection strengthened osteogenic effects of BMSCs, elevated number and quality of new bones and accelerated the repair of osteonecrosis of the femoral head. PMID:26629044

Peri-implant parameters, tumor necrosis factor-alpha, and interleukin-1 beta levels in vaping individuals.

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Al-Aali, Khulud A; Alrabiah, Mohammed; ArRejaie, Aws S; Abduljabbar, Tariq; Vohra, Fahim; Akram, Zohaib

2018-03-25

To the author's knowledge, there has been no study that has assessed clinical, radiographic, and immunological peri-implant parameters among individuals vaping e-cigarette (e-cig). This pilot study aimed to compare clinical and radiographic peri-implant parameters and levels of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β levels among individuals vaping e-cigs and never smoker (NS). Forty-seven individuals vaping e-cigs (group-1) and 45 NS (group-2) were included. Demographic and implant-related data were collected using a structured baseline questionnaire. Peri-implant plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded and peri-implant bone loss (PIBL) were assessed using standardized digital radiographs. Enzyme-linked immunosorbent assay was used to assess the levels of TNF-α and IL-1β in peri-implant sulcular fluid. Bleeding on probing showed statistically significantly higher values in group-2 patients as compared to group-1 patients (P vaping individuals. Increased levels of proinflammatory cytokines in peri-implant sulcular fluid may suggest greater local inflammatory response in vaping individuals for peri-implant inflammation. © 2018 Wiley Periodicals, Inc.

Widespread marrow necrosis during pregnancy

International Nuclear Information System (INIS)

Knickerbocker, W.J.; Quenville, N.F.

1982-01-01

Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported. (orig.)

Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

DEFF Research Database (Denmark)

Rontved, C. M.; Tjørnehøj, Kirsten; Viuff, B.

2000-01-01

, of which 23 were experimentally infected with BRSV and five were given a mock inoculum. The presence of the cytokine tumor necrosis factor alpha (TNF-alpha) in the BAL fluids was detected and quantified by a capture ELISA. TNF-alpha was detected in 21 of the infected animals. The amount of TNF-alpha...... in the BAL fluid of calves killed post inoculation day (PID) 2 and 4 was at the same very low level as in the uninfected control animals. Large amounts of TNF-alpha were detected on PID 6, maximum levels of TNF-alpha were reached on PID 7, and smaller amounts of TNF-alpha were seen on PID 8. The high levels...... of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period...

Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

Energy Technology Data Exchange (ETDEWEB)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Indiana University Health Proton Therapy Center, Bloomington, Indiana (United States); Linton, Okechukwu R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Calley, Cynthia S.J. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States)

2015-02-01

Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving

Recombinant tumor necrosis factor alpha inhibits growth of methylcholanthrene-induced sarcoma and enhances natural killer activity of tumor-infiltrating lymphocytes in aging rats

International Nuclear Information System (INIS)

Ziolkowska, Maria; Nowak Joanna, J.; Janiak, Marek; Ryzewska, Alicja

1994-01-01

The effect of recombinant human tumor necrosis factors alpha (rHuTNF-α) on the growth of immunogenic, methylcholanthrene-induced sarcoma (MC-Sa) and natural killer (NK) cell activity of tumor-infiltrating lymphocytes (TIL) in adult and aging rats was investigated. In both groups of animals the growth of transplantable MC-Sa was markedly and similarly inhibited by multiple intratumoral (i.t.) injections of rHuTF-α. This effect was accompanied by stimulation of NK activity of tumor-infiltrating lymphocytes in adult as well as in aging rats. Studies ''in vitro'' demonstrated additionally that rHuTNF-α was a potent stimulator of NK but not of ADCC (antibody-dependent cellular cytotoxicity) activity of spleen lymphocytes from healthy animals. Our results indicate that the antitumor effect of TNF-α is comparable in adult and in aging rats bearing immunogenic MC-Sa. The inhibition of MC-Sa growth may be attributed not only to the TNF-α-induced necrosis of the neoplastic tissue but also to the ''in vivo'' stimulatory effect of this cytokine upon the NK-type function of lymphocytes infiltrating the tumor mass. (author). 31 refs, 5 figs, 2 tabs

Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.

Science.gov (United States)

Kobayashi, Tetsuo; Yokoyama, Tomoko; Ito, Satoshi; Kobayashi, Daisuke; Yamagata, Akira; Okada, Moe; Oofusa, Ken; Narita, Ichiei; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

2014-11-01

Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy. The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases. The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

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Alessandra Costa

2014-01-01

Full Text Available Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novel in vivo role for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies.

MRI Findings of Pericardial Fat Necrosis: Case Report

International Nuclear Information System (INIS)

Lee, Hyo Hyeok; Ryu, Dae Shick; Jung, Sang Sig; Jung, Seung Mun; Choi, Soo Jung; Shin, Dae Hee

2011-01-01

Pericardial fat necrosis is an infrequent cause of acute chest pain and this can mimic acute myocardial infarction and acute pericarditis. We describe here a patient with the magnetic resonance imaging (MRI) findings of pericardial fat necrosis and this was correlated with the computed tomography (CT) findings. The MRI findings may be helpful for distinguishing pericardial fat necrosis from other causes of acute chest pain and from the fat-containing tumors in the cardiophrenic space of the anterior mediastinum.

Characterization of a canine tetranucleotide microsatellite marker located in the first intron of the tumor necrosis factor alpha gene.

Science.gov (United States)

Watanabe, Masashi; Tanaka, Kazuaki; Takizawa, Tatsuya; Segawa, Kazuhito; Neo, Sakurako; Tsuchiya, Ryo; Murata, Michiko; Murakami, Masaru; Hisasue, Masaharu

2014-01-01

A polymorphic tetranucleotide (GAAT)n microsatellite in the first intron of the canine tumor necrosis factor alpha (TNFA) gene was characterized in this study; 139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24 Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the presence of the 4 alleles (GAAT)5, (GAAT)6, (GAAT)7 and (GAAT)8, including 9 of the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic information content (PIC) value of this microsatellite locus varied from 0.389 to 0.749 and from 0.333 to 0.682, respectively, among the 6 breeds. The allelic frequency differed greatly among breeds, but this microsatellite marker was highly polymorphic and could be a useful marker for the canine TNFA gene.

Coordinate viral induction of tumor necrosis factor α and interferon β in human B cells and monocytes

International Nuclear Information System (INIS)

Goldfeld, A.E.; Maniatis, T.

1989-01-01

Human tumor necrosis factor α (TNF-α) gene expression can be induced primarily in cells of the monocyte/macrophage lineage by a variety of inducers, including lipopolysaccharide, phorbol esters such as phorbol 12-myristate 13-acetate, and virus or synthetic double-stranded RNA [poly(I)·poly(C)]. In this paper the authors show that the TNF-α gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF-α mRNA in both monocyte and B-cell lines. In addition, they show that viral infection coinduces the expression of TNF-α and interferon β mRNA and that viral induction of both genes is blocked by the kinase inhibitor 2-aminopurine. Inhibition of protein synthesis with cycloheximide had no effect on mRNA expression of the genes in one of three cell lines tested (U937) but blocked the viral induction of both genes in another (Namalwa). Thus, the regulatory factors required for mRNA induction of both genes are present prior to the addition of virus in U937 but not in Namalwa cells. However, in a third cell line (JY), cycloheximide blocked viral induction of the interferon β gene but not the TNF-α gene. Taken together, these observations suggest that viral induction of TNF-α and interferon β gene expression may involve overlapping pathways with both common and distinct regulatory factors

Symptomatic Avascular Necrosis: An Understudied Risk Factor for Acute Care Utilization by Patients with SCD

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Yu, Tiffany; Campbell, Timothy; Ciuffetelli, Isabella; Haywood, Carlton; Carroll, C. Patrick; Resar, Linda M.S.; Strouse, John J.; Lanzkron, Sophie

2016-01-01

Objectives Sickle cell disease (SCD) is associated with high healthcare utilization rates and poor outcomes in a subset of patients, although the underlying factors that predict this phenotype are poorly understood. Prior studies suggest that comorbid avascular necrosis (AVN) contributes to high healthcare utilization. We sought to clarify whether AVN independently predicts acute care utilization in adults with SCD and to identify characteristics of those with AVN that predict higher utilization. Methods We reviewed the medical records of 87 patients with SCD with symptomatic AVN and compared acute care utilization and clinical characteristics with 87 sex- and age-matched patients with SCD without symptomatic AVN. Patients with ≥2 years of follow-up were included. Outcomes were compared using bivariate analysis and multivariate regression. Results Our study included 1381 follow-up years, with a median of 7 years per patient. The AVN cohort had greater median rates of urgent care visits (3.2/year vs 1.3/year; P = 0.0155), admissions (1.3/year vs 0.4/year; P = 0.0002), and admission days (5.1 days/year vs 1.8 days/year; P = 0.0007). History of high utilization (odds ratio [OR] 4.28; P = 0.001), acute chest syndrome (OR 3.12; P = 0.005), pneumonia (OR 3.20; P = 0.023), hydroxyurea therapy (OR 2.23; P = 0.0136), and long-term transfusion (OR 2.33; P = 0.014) were associated with AVN. In a median regression model, AVN, acute chest syndrome, and pneumonia were independently associated with greater urgent care visits and admissions. Conclusions Symptomatic AVN was found to be an independent risk factor for acute care utilization in patients with SCD. Because this is a potentially modifiable factor, further studies are urgently needed to determine whether AVN prevention/early treatment interventions will alter utilization and improve outcomes for patients with SCD. PMID:27598353

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-α-induced vascular endothelial dysfunction

International Nuclear Information System (INIS)

Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.; Chen, J.-W.; Chiang, H.-C.

2007-01-01

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-α)-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-α induces various biological effects on vascular cells, TNF-α dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-α concentrations, we adopted the lower TNF-α (0.2 ng/ml) to rule out the possible involvement of other TNF-α-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-α-induced adhesion molecule expression and monocyte-endothelial monolayer binding. BSO attenuated the TNF-α-induced nuclear factor-kappaB (NF-κB) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-α. Inhibition of ERK, JNK, or NF-κB attenuates TNF-α-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-α induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-κB in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-α. Although AP-1 activation by the lower TNF-α was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-α-induced adhesion molecule expression

Feline Immunodeficiency Virus (FIV Neutralization: A Review

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Margaret J. Hosie

2011-10-01

Full Text Available One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env, a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3 of Env. For feline immunodeficiency virus (FIV, as well as the related human immunodeficiency virus-1 (HIV-1, little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1.

Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

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Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

2015-05-06

We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. 2015 BMJ Publishing Group Ltd.

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

Science.gov (United States)

Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

2003-08-01

The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis.

Science.gov (United States)

Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P; Petrides, Francine; Cuesta Torres, Luisa F; Hou, Liming; Cook, Adam; Barter, Philip J; Weninger, Wolfgang; Rye, Kerry-Anne

2015-11-01

Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature. © 2015 American Heart Association, Inc.

Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

International Nuclear Information System (INIS)

Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu; Kohara, Junko; Hirata, Toh-ichi; Okada, Kosuke; Ohashi, Kazuhiko; Onuma, Misao

2005-01-01

Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-α and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-α-induced responses, in this study we examined the TNF-α-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-α (rTNF-α) was significantly higher than those from AL cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5 + or sIgM + cells and these cells showed resistance to TNF-α-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-α-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection

Resistin, interleukin-6, tumor necrosis factor-alpha, and human semen parameters in the presence of leukocytospermia, smoking habit, and varicocele.

Science.gov (United States)

Moretti, Elena; Collodel, Giulia; Mazzi, Lucia; Campagna, MariaStella; Iacoponi, Francesca; Figura, Natale

2014-08-01

To explore the relationships between resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and semen parameters, sperm apoptosis, and necrosis in infertile patients and in control subjects with unknown reproductive potential with/without smoking habits, leukocytospermia, and varicocele. Prospective study. Sperm laboratory. A total of 110 selected men. Family history, clinical/physical examination, ELISA determination (resistin, IL-6, TNF-α), semen analysis, annexin V/propidium iodide assay. Relationships among resistin, IL-6, and TNF-α and semen parameters in the presence of smoking habits, varicocele, leukocytospermia, and in infertile subjects. Resistin level was higher in semen than in serum. Resistin semen levels showed negative correlations with sperm motility and positive correlations with apoptotic, necrotic sperm and TNF-α and IL-6 levels. Resistin, TNF-α, and IL-6 levels were higher in smokers compared with nonsmokers and in cases with leukocytospermia, in which an increase in necrotic sperm and a decrease in the number of sperm with normal morphology and motility were observed. Cytokine levels were significantly higher in infertile patients compared with control subjects with unknown reproductive potential. A total of 74.5% of infertile patients showed leukocytospermia. Semen resistin correlated with IL-6, TNF-α, and sperm quality; in cases of leukocytospermia and smoking habits, resistin concentrations were increased, suggesting that resistin may play a regulatory role in inflammation of the male reproductive system. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Net Neutrality in the Netherlands

NARCIS (Netherlands)

van Eijk, N.

2014-01-01

The Netherlands is among the first countries that have put specific net neutrality standards in place. The decision to implement specific regulation was influenced by at least three factors. The first was the prevailing social and academic debate, partly due to developments in the United States. The

Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH

Energy Technology Data Exchange (ETDEWEB)

Cingolani, Gino, E-mail: cingolag@upstate.edu; Andrews, Dewan [Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States); Casjens, Sherwood [Department of Pathology, Division of Cell Biology and Immunology, University of Utah Medical School, Salt Lake City, UT 84112 (United States); Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States)

2006-05-01

The crystallogenesis of bacteriophage P22 tail-fiber gp26 is described. To study possible pH-induced conformational changes in gp26 structure, native trimeric gp26 has been crystallized at acidic pH (4.6) and a chimera of gp26 fused to maltose-binding protein (MBP-gp26) has been crystallized at neutral and alkaline pH (7-10). Gp26 is one of three phage P22-encoded tail accessory factors essential for stabilization of viral DNA within the mature capsid. In solution, gp26 exists as an extended triple-stranded coiled-coil protein which shares profound structural similarities with class I viral membrane-fusion protein. In the cryo-EM reconstruction of P22 tail extracted from mature virions, gp26 forms an ∼220 Å extended needle structure emanating from the neck of the tail, which is likely to be brought into contact with the cell’s outer membrane when the viral DNA-injection process is initiated. To shed light on the potential role of gp26 in cell-wall penetration and DNA injection, gp26 has been crystallized at acidic, neutral and alkaline pH. Crystals of native gp26 grown at pH 4.6 diffract X-rays to 2.0 Å resolution and belong to space group P2{sub 1}, with a dimer of trimeric gp26 molecules in the asymmetric unit. To study potential pH-induced conformational changes in the gp26 structure, a chimera of gp26 fused to maltose-binding protein (MBP-gp26) was generated. Hexagonal crystals of MBP-gp26 were obtained at neutral and alkaline pH using the high-throughput crystallization robot at the Hauptman–Woodward Medical Research Institute, Buffalo, NY, USA. These crystals diffract X-rays to beyond 2.0 Å resolution. Structural analysis of gp26 crystallized at acidic, neutral and alkaline pH is in progress.

Are Moral Disengagement, Neutralization Techniques, and Self-Serving Cognitive Distortions the Same? Developing a Unified Scale of Moral Neutralization of Aggression

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Denis Ribeaud

2010-12-01

Full Text Available

Negative Regulation of Interferon-β Production by Alternative Splicing of Tumor Necrosis Factor Receptor-Associated Factor 3 in Ducks

Directory of Open Access Journals (Sweden)

Xiaoqin Wei

2018-03-01

Full Text Available Tumor necrosis factor receptor-associated factor 3 (TRAF3, an intracellular signal transducer, is identified as an important component of Toll-like receptors and RIG-I-like receptors induced type I interferon (IFN signaling pathways. Previous studies have clarified TRAF3 function in mammals, but little is known about the role of TRAF3 in ducks. Here, we cloned and characterized the full-length duck TRAF3 (duTRAF3 gene and an alternatively spliced isoform of duTRAF3 (duTRAF3-S lacking the fragment encoding amino acids 217–319, from duck embryo fibroblasts (DEFs. We found that duTRAF3 and duTRAF3-S played different roles in regulating IFN-β production in DEFs. duTRAF3 through its TRAF domain interacted with duMAVS or duTRIF, leading to the production of IFN-β. However, duTRAF3-S, containing the TRAF domain, was unable to bind duMAVS or duTRIF due to the intramolecular binding between the N- and C-terminal of duTRAF3-S that blocked the function of its TRAF domain. Further analysis identified that duTRAF3-S competed with duTRAF3 itself for binding to duTRAF3, perturbing duTRAF3 self-association, which impaired the assembly of duTRAF3-duMAVS/duTRIF complex, ultimately resulted in a reduced production of IFN-β. These findings suggest that duTRAF3 is an important regulator of duck innate immune signaling and reveal a novel mechanism for the negative regulation of IFN-β production via changing the formation of the homo-oligomerization of wild molecules, implying a novel regulatory role of truncated proteins.

Aseptic necrosis of the femoral head after pregnancy: a case report.

Science.gov (United States)

Nassar, Kawtar; Rachidi, Wafae; Janani, Saadia; Mkinsi, Ouafa

2016-01-01

A documented case of beginning aseptic necrosis of the femoral head associated with pregnancy together with a review of the literature about this rare complication of pregnancy is presented. The known risk factors of osteonecrosis are; steroid use, alcoholism, organ transplantation, especially after kidney transplant or bone marrow transplantation bone, systemic lupus erythematosus, dyslipidemia especially hypertriglyceridemia, dysbaric decompression sickness, drepanocytosis and Gaucher's disease. Among the less established factors, we mention procoagulations abnormalities, HIV infection, chemotherapy. We report a case of osteonecrosis of femoral head after pregnancy.

Differential effect of glucocorticoids on tumour necrosis factor production in mice: up-regulation by early pretreatment with dexamethasone.

Science.gov (United States)

Fantuzzi, G; Demitri, M T; Ghezzi, P

1994-04-01

Glucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF) production. We investigated the role of endogenous GC in the regulation of TNF production in mice treated with lipopolysaccharide (LPS) using a pretreatment with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary-adrenal axis (HPA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF production, but earlier (24-48 h) pretreatments potentiated it. This up-regulating effect was not observed in adrenalectomized mice or when GC synthesis was inhibited with cyanoketone (CK). This effect could not be explained only by the suppression of LPS-induced corticosterone (CS) levels induced by DEX, since a 48-h pretreatment potentiated TNF production without affecting LPS-induced CS levels. On the other hand, mice chronically pretreated with DEX were still responsive to its inhibitory effect on TNF production, thus ruling out the possibility of a decreased responsiveness to GC.

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

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Nadra, Imad; Boccaccini, Aldo R; Philippidis, Pandelis; Whelan, Linda C; McCarthy, Geraldine M; Haskard, Dorian O; Landis, R Clive

2008-01-01

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.

Free hemoglobin enhances tumor necrosis factor-alpha production in isolated human monocytes.

Science.gov (United States)

Carrillo, Eddy H; Gordon, Laura E; Richardson, J David; Polk, Hiram C

2002-03-01

A systemic inflammatory response (SIR) is seen in approximately 75% of patients with complex blunt liver injuries treated nonoperatively. Many feel this response is caused by blood, bile, and necrotic tissue accumulation in the peritoneal cavity. Our current treatment for these patients is a delayed laparoscopic washout of the peritoneal cavity, resulting in a dramatic resolution of the SIR. Spectrophotometric analysis of the intraperitoneal fluid has confirmed the presence of high concentrations of free hemoglobin (Hb). We hypothesize that free Hb enhances the local peritoneal response by increasing tumor necrosis factor-alpha (TNF-alpha) production by monocytes, contributing to the local inflammatory response and SIR. Monocytes from five healthy volunteers were isolated and cultured in RPMI-1640 for 24 hours. Treatment groups included saline controls, lipopolysaccharide ([LPS], 10 ng/mL, from Escherichia coli), human Hb (25 microg/mL), and Hb + LPS. Supernatants were analyzed by enzyme-linked immunosorbent assay. Student's t test with Mann-Whitney posttest was used for statistical analysis with p < or = 0.05 considered significant. Free Hb significantly increased TNF-alpha production 915 +/- 223 pg/mL versus saline (p = 0.02). LPS and Hb + LPS further increased TNF-alpha production (2294 pg/mL and 2501 pg/mL, respectively, p < 0.001) compared with saline controls. These data confirm that free Hb is a proinflammatory mediator resulting in the production of significant amounts of TNF-alpha. These in vitro findings support our clinical data in which timely removal of intraperitoneal free hemoglobin helps prevent its deleterious local and systemic inflammatory effects in patients with complex liver injuries managed nonoperatively.

Risk Factors for Symptomatic Avascular Necrosis in Childhood-onset Systemic Lupus Erythematosus.

Science.gov (United States)

Yang, Yelin; Kumar, Sathish; Lim, Lily Siok Hoon; Silverman, Earl D; Levy, Deborah M

2015-12-01

To examine the frequency and risk factors for symptomatic avascular necrosis (AVN) in childhood-onset systemic lupus erythematosus (cSLE). A single-center, nested, matched, case-control design was used. There were 617 patients with cSLE followed at the Hospital for Sick Children (SickKids) Lupus Clinic between July 1982 and June 2013 included in the study. The AVN cohort consisted of 37 patients identified with clinical findings of symptomatic AVN and diagnosis was confirmed by 1 or more imaging modalities. Three controls were matched to each patient with AVN by date and age at diagnosis. Baseline clinical, laboratory, and treatment characteristics were compared between patients with AVN and controls by univariable analyses and if statistically significant, were included in a multivariable logistic regression model. A total of 37/617 patients (6%) developed symptomatic AVN in 91 joints during followup at SickKids. The mean duration to disease was 2.3 years. The hip was the most commonly involved joint (26/37, 70%). Compared with the matched non-AVN cohort, patients with AVN had a higher incidence of central nervous system (CNS) involvement and nephritis, required greater cumulative prednisone (PRED) from cSLE diagnosis to AVN, received a greater maximal daily PRED dose, and had more frequent use of pulse methylprednisolone therapy. Multivariable regression analysis confirmed major organ involvement (CNS disease and/or nephritis) and maximal daily PRED dose as significant predictors of symptomatic AVN development. Patients with cSLE with severe organ involvement including nephritis and CNS disease and higher maximal daily dose of PRED are more likely to develop symptomatic AVN.

Aseptic necrosis of the femoral head after pregnancy: a case report

OpenAIRE

Nassar, Kawtar; Rachidi, Wafae; Janani, Saadia; Mkinsi, Ouafa

2016-01-01

A documented case of beginning aseptic necrosis of the femoral head associated with pregnancy together with a review of the literature about this rare complication of pregnancy is presented. The known risk factors of osteonecrosis are; steroid use, alcoholism, organ transplantation, especially after kidney transplant or bone marrow transplantation bone, systemic lupus erythematosus, dyslipidemia especially hypertriglyceridemia, dysbaric decompression sickness, drepanocytosis and Gaucher's dis...

PLT neutral beam injection systems

International Nuclear Information System (INIS)

Menon, M.M.; Barber, G.C.; Blue, C.W.

1979-01-01

A brief description of the Princeton Large Torus (PLT) neutral beam injection system is given and its performance characteristics are outlined. A detailed operational procedure is included, as are some tips on troubleshooting. Proper operation of the source is shown to be a crucial factor in system performance

Selective cytotoxicity of transformed cells but not normal cells by a sialoglycopeptide growth regulator in the presence of tumor necrosis factor

Science.gov (United States)

Woods, K. M.; Fattaey, H.; Johnson, T. C.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

The tumor necrosis factor-alpha (TNF)-resistant, SV40-transformed, murine fibroblast cell lines, F5b and F5m, became sensitive to TNF-mediated cytolysis after treatment with a biologically active 18 kDa peptide fragment (SGP) derived from a 66-kDa parental cell surface sialoglycoprotein. Neither TNF nor the SGP alone exhibited cytotoxicity to the two SV40-transformed cell lines. However, Balb/c 3T3 cells, incubated with SGP alone or with SGP and TNF, were not killed. Therefore, SGP can selectively sensitize cells for TNF alpha-mediated cytotoxicity. This selective sensitization may be due to the previously documented ability of the SGP to selectively mediate cell cycle arrest.

Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus.

Science.gov (United States)

Garcia, J A; Ferreira, H L; Vieira, F V; Gameiro, R; Andrade, A L; Eugênio, F R; Flores, E F; Cardoso, T C

2017-06-01

Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy. © 2015 John Wiley & Sons Ltd.

Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report.

Science.gov (United States)

Deleanu, Bogdan; Prejbeanu, Radu; Vermesan, Dinu; Honcea, Lucian; Mioc, Mihail Lazar; Tsiridis, Eleftherios; Predescu, Vlad

2016-02-01

The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution and left untreated leads to femoral head collapse and severe arthritis. We present a case of a pertrochanteric fracture which has been successfully operated with a dynamic interlocking trochanteric gamma nail on the right hip. At 2 years after surgery the patient developed an incipient avascular necrosis of the femoral head. Despite the good positioning of the implant, we considered that the source of the pain was an intolerance of the implant, and thus we removed it. After implant removal, the patient was kept under observation and conservative treatment, to prevent further damage to the right hip and allow the healing to occur. At 6 months after the gamma nail was removed the X-rays revealed advanced avascular necrosis of the femoral head and secondary osteoarthritis on the right hip. The patient underwent surgery with an uncemented total hip arthroplasty. There are a few discussions regarding the avascular necrosis of the femoral head. These discussions may include the predisposing risk factors, the treatment of choice and the postoperative complications. The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty.

Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

Science.gov (United States)

del Hierro, Piedad Magdalena

2011-01-01

Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

Intracellular serpins, firewalls and tissue necrosis.

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Marciniak, Stefan J; Lomas, David A

2008-02-01

Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.

The Effect of Aerobic Training and Arbotin on Cardiac Nitric Oxide, Tumor Necrosis Factor alpha, and Vascular Endothelial Growth Factor in Male Diabetic Rats

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Rahemeh Jahangiri Jahangiri

2017-07-01

Full Text Available Background and Objectives: Diabetes is one of the most important metabolic diseases, which its incidence rate has increased in recent years. In this disease, the insulin function is impaired, leading to several complications. Physical exercise and medicinal plants are considered as a way to control diabetes along with nutrition and medicine. The present study was conducted with the purpose of determining the effect of aerobic training and use of arbutin on cardiac nitric oxide, tumor necrosis factor-α and vessel endothelial growth factor in male diabetic rats. Methods: In this experimental study, 42 male adult Wistar rats (age, 8 weeks; weight, 190-220g, were randomly divided into 6 groups of 7 each (control, arbutin, diabetic, diabetic+training, diabetic+arbutin, and diabetic+training+arbutin. Training programs included 5 days of swimming per week for 6 weeks. Sampling from the heart was performed 72 hours after the last training session and arbutin consumption to analyze NO, TNF-α and VEGF. Data were analyzed using one-way ANOVA at the significance level p≤0.05. Results: Aerobic training along with use of arbutin led to increased levels of NO and VEGF and decreased level of TNF-α in cardiac tissue of diabetic rats (p<0.001. Conclusion: The results indicated that a period of regular aerobic training and use of arbutin can be considered as an appropriate non-medicinal method to control diabetes mellitus type 2 through decrease in inflammatory factors.

Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients with unipolar depression

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Bizik G

2014-04-01

Full Text Available Gustav Bizik,1 Petr Bob,1 Jiri Raboch,1 Josef Pavlat,1 Jana Uhrova,2 Hana Benakova,2 Tomas Zima2 1Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry and UHSL, 2Department of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic Abstract: Recent evidence indicates that the nature of interactions between the nervous system and immune system is important in the pathogenesis of depression. Specifically, alterations in pro-inflammatory cytokines have been related to the development of several psychological and neurobiological manifestations of depressive disorder, as well as to stress exposure. A number of findings point to tumor necrosis factor alpha (TNF-α as one of the central factors in these processes. Accordingly, in the present study, we test the hypothesis that specific influences of chronic stressors related to traumatic stress and dissociation are related to alterations in TNF-α levels. We performed psychometric measurement of depression (Beck Depression Inventory [BDI]-II, traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40, and psychological and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform Dissociation Questionnaire [SDQ]-20, respectively, and immunochemical measure of serum TNF-α in 66 inpatients with unipolar depression (mean age 43.1 ± 7.3 years. The results show that TNF-α is significantly related to DES (Spearman R=−0.42, P<0.01, SDQ-20 (Spearman R=−0.38, P<0.01, and TSC-40 (Spearman R=−0.41, P<0.01, but not to BDI-II. Results of the present study suggest that TNF-α levels are related to dissociative symptoms and stress exposure in depressed patients. Keywords: depression, dissociation, TNF-alpha, traumatic stress

Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

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Khoshnaw Najmaddin SH

2012-10-01

Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

Bilateral acute retinal necrosis after herpetic meningitis

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Katsura T

2012-04-01

Full Text Available Keisho Hirota1,2, Masayuki Akimoto1,3, Toshiaki Katsura21Department of Ophthalmology, Kyoto Medical Center, National Hospital Organization, 2Internal Medicine, Kyoto Medical Center, 3Clinical Research Center, Kyoto Medical Center, Kyoto, JapanPurpose: The report of a case of bilateral acute retinal necrosis after herpetic meningitis.Case report: A 47-year-old man was admitted with the chief complaint of persistent high fever and transient loss of consciousness. Although his general condition improved after intravenous acyclovir administration, the patient presented with visual loss in both eyes 4 days after admission. Visual acuity in his right eye was 20/200 and his left eye had light perception alone. Both eyes showed panretinal arteritis diagnosed as acute retinal necrosis. Panretinal photocoagulation was performed for both eyes. Progression of retinal detachment was prevented in both eyes; however, visual acuity of the left eye was totally lost because of neovascular glaucoma. Visual acuity of the right eye recovered to 20/20.Conclusion: Although cases of bilateral acute retinal necrosis have been reported after herpetic encephalitis, this condition is rare after herpetic meningitis. Prophylactic acyclovir therapy and early panretinal photocoagulation may prevent retinal detachment and improve the prognosis. Neurologists and ophthalmologists should be aware that not only herpetic encephalitis but also herpetic meningitis can lead to acute retinal necrosis within a very short interval.Keywords: acute retinal necrosis, herpetic meningitis, herpes simplex, varicella zoster virus

Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.

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Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

2016-09-01

Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. The purpose of this study was to evaluate skin barrier function during chronic liver injury. Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.

High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

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Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre

2003-01-01

BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity...... and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly...... humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age...

Generation of intense polarized beams by selective neutralization of negative ions

International Nuclear Information System (INIS)

Hershcovitch, A.I.; Hinds, E.A.

1983-01-01

A novel scheme is proposed. This method is based on selective neutralization by laser negative hydrogen ions in a magnetic field. This selectivity is based on the fact that the final state of the neutralized atom depends on nuclear polarization in the magnetic field. A two-scenario approach is to be followed: one in which the resulting neutral atom is in the ground state, and in the other the neutral atom is in the n = 2 level. Limiting factors are discussed. The main advantages of this scheme are the availability of multi-ampere negative ion sources and the possibility to neutralize negative ions with very high efficiency. 15 references, 2 figures

Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

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Kusmiyati Tjahjono DK

2013-04-01

Full Text Available Background The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. Methods A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. Results After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p=0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. Conclusion TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells.

Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

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Kusmiyati Tjahjono DK

2015-12-01

Full Text Available BACKGROUND The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. METHODS A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. RESULTS After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p= 0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. CONCLUSION TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells

Biomechanical comparisons between a new avascular necrosis of femaral head stem based on Chinese patients with avascular necrosis and two other designs.

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Zhang, Qiang; Cheng, Cheng-Kung; Wei, Hung-Wen; Dong, Xiang; Chen, Yi-Ting; Lai, Yu-Shu; Wang, Yan

2013-01-01

There is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis. We designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems. The morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)). This is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

B-lymfocytdepletring og andre biologiske behandlingsmuligheder ved Graves' oftalmopatiTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

DEFF Research Database (Denmark)

El, Fassi D.; Hegedus, L.; Nielsen, Claus Henrik

2008-01-01

The current medical treatment options for Graves' ophthalmopathy (GO) are unsatisfactory. Recent treatment of GO patients with the B-lymphocyte depleting monoclonal antibody rituximab or with the anti-tumor necrosis factor-alpha agents etanercept and infliximab has shown promising results. We...

Subcutaneous fat necrosis of the newborn.

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Oswalt, G C; Montes, L F; Cassady, G

1978-08-01

Subcutaneous fat necrosis of the newborn (SFNN) developed in a 1-week-old black boy. His mother had received numerous medications for eclampsia. Birth was by Caesarean section and complicated by meconium aspiration. There were numerous nodules over the back, buttocks and extremities that yielded a caseous-like material. Microscopically, these nodules showed crystallization and necrosis of the fat. Hypoglycemia, pneumonia, oliguria, thrombocytopenia, seizures and urinary infection were associated with the cutaneous problem and led to a fatal outcome 2 weeks after birth.

Effect of the strange axial form factor on structure functions for neutral current neutrino scattering in the quasielastic region

International Nuclear Information System (INIS)

Kim, Kyungsik

2011-01-01

We study the effect of the strange axial form factor on various structure functions for the neutral reaction of neutrino-nucleus scattering in the quasielastic region within the framework of a relativistic single particle model. We use 12 C as the target nucleus, and the incident neutrino energy range is between 150 MeV and 1.5 GeV. The structure functions are extracted at a fixed three momentum transfer and energy transfer by using the intrinsic helicity of neutrino. While the effect of the strange axial form factor is very small, the effect on various structure functions is exhibited explicitly.

Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

International Nuclear Information System (INIS)

Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W.

1991-01-01

Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma

Polysaccharide peptide induces a tumor necrosis factor-α-dependent drop of body temperature in rats.

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Jedrzejewski, Tomasz; Piotrowski, Jakub; Wrotek, Sylwia; Kozak, Wieslaw

2014-08-01

Polysaccharide peptide (PSP) extracted from the Coriolus versicolor mushroom is frequently suggested as an adjunct to the chemo- or radiotherapy in cancer patients. It improves quality of the patients' life by decreasing pain, fatigue, loss of appetite, nausea, and vomiting. However, the effect of PSP on body temperature has not thus far been studied, although it is well known that treatment with other polysaccharide adjuvants, such as lipopolysaccharides, may induce fever. The aim of the present study, therefore, was to investigate the influence of PSP on temperature regulation in rats. We report that intraperitoneal injection of PSP provoked a dose-dependent decrease of temperature in male Wistar rats equipped with biotelemetry devices to monitor deep body temperature (Tb). The response was rapid (i.e., with latency of 15-20min), transient (lasting up to 5h post-injection), and accompanied by a significant elevation of the blood tumor necrosis factor-α (TNF-α) level. Pretreatment of the rats with anti-TNF-α antibody prevented the PSP-induced drop in Tb. Based on these data, we conclude that rats may develop an anapyrexia-like response to the injection of peptidopolysaccharide rather than fever, and the response was TNF-α-dependent. Copyright © 2014 Elsevier Ltd. All rights reserved.

The tumor necrosis factor-α-238 polymorphism and digestive system cancer risk: a meta-analysis.

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Hui, Ming; Yan, Xiaojuan; Jiang, Ying

2016-08-01

Many studies have reported the association between tumor necrosis factor-α (TNF-α)-238 polymorphism and digestive system cancer susceptibility, but the results were inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship between TNF-α-238 G/A polymorphism and digestive system cancer risk. Pooled analysis for the TNF-α-238 G/A polymorphism contained 26 studies with a total of 4849 cases and 8567 controls. The meta-analysis observed a significant association between TNF-α-238 G/A polymorphism and digestive system cancer risk in the overall population (GA vs GG: OR 1.19, 95 % CI 1.00-1.40, P heterpgeneity = 0.016; A vs G: OR 1.19, 95 % CI 1.03-1.39, P heterpgeneity = 0.015; dominant model: OR 1.20, 95 % CI 1.02-1.41, P heterpgeneity = 0.012). In the analysis of the ethnic subgroups, however, similar results were observed only in the Asian population, but not in the Caucasian population. Therefore, this meta-analysis suggests that TNF-α-238 G/A polymorphism is associated with a significantly increased risk of digestive system cancer. Further large and well-designed studies are needed to confirm these findings.

Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat

International Nuclear Information System (INIS)

Flores, E.A.; Istfan, N.; Pomposelli, J.J.; Blackburn, G.L.; Bistrian, B.R.

1990-01-01

We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D-[U- 14 C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection

Evaluation of salivary tumor necrosis factor-alpha in patients with the chronic periodontitis: A case-control study.

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Yousefimanesh, Hojatollah; Maryam, Robati; Mahmoud, Jahangirnezhad; Mehri, Ghafourian Boroujerdnia; Mohsen, Taghipour

2013-11-01

Periodontitis is a chronic infectious disease that leads to inflammation of the tissues supporting the teeth, bone loss, attachment loss progressively. In chronic periodontitis for starting the host response and inflammatory reaction, the presence of the infectious agent is necessary. One of inflammatory factors is tumor necrosis factor-alpha (TNF-α) that appear to be important in the destruction of periodontal tissues that were examined in this study. This study was performed in the laboratory and case-control study. The samples of study collected from 30 individuals with chronic periodontitis and 30 healthy controls that matched for age and sex, together. Unstimulated saliva samples were collected from patients and then TNF-α level were measured by enzyme-linked immunosorbent assay and were compared with the control group. In this study for statistical analysis, Mann-Whitney was used. There were differences in mean salivary concentrations of TNF-α in controls and patients. The average concentration in the case group was 9.1 (pg/ml) and the control group was 8.7 (pg/ml), but there was no significant difference between case and control groups (P > 0.05). The results of this analysis showed no significant relationship between two groups TNF-α concentration. This biomarker can not seem to be a good index to evaluate or predict periodontal disease.

Evaluation of salivary tumor necrosis factor-alpha in patients with the chronic periodontitis: A case-control study

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Hojatollah Yousefimanesh

2013-01-01

Full Text Available Context: Periodontitis is a chronic infectious disease that leads to inflammation of the tissues supporting the teeth, bone loss, attachment loss progressively. In chronic periodontitis for starting the host response and inflammatory reaction, the presence of the infectious agent is necessary. Aims: One of inflammatory factors is tumor necrosis factor-alpha (TNF-α that appear to be important in the destruction of periodontal tissues that were examined in this study. Materials and Methods: This study was performed in the laboratory and case-control study. The samples of study collected from 30 individuals with chronic periodontitis and 30 healthy controls that matched for age and sex, together. Unstimulated saliva samples were collected from patients and then TNF-α level were measured by enzyme-linked immunosorbent assay and were compared with the control group. Statistical Analysis Used: In this study for statistical analysis, Mann-Whitney was used. Results: There were differences in mean salivary concentrations of TNF-α in controls and patients. The average concentration in the case group was 9.1 (pg/ml and the control group was 8.7 (pg/ml, but there was no significant difference between case and control groups (P > 0.05. Conclusions: The results of this analysis showed no significant relationship between two groups TNF-α concentration.This biomarker can not seem to be a good index to evaluate or predict periodontal disease.

Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.

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Liu, Chao; Ouyang, Wei; Xia, Jingyan; Sun, Xiaoru; Zhao, Liying; Xu, Feng

2018-05-08

Mast cells (MCs) play a key role in immune process response to invading pathogens. This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice. KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. The present study identifies the critical role of MCs in the host defense against S. aureus infection.

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

International Nuclear Information System (INIS)

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-01-01

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

Energy Technology Data Exchange (ETDEWEB)

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-12-01

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

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R. Dong

2007-08-01

Full Text Available The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a. To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB inhibitor aspirin while not affected by the reactive oxygen species (ROS scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

Development of delayed radiation necrosis. Case report

Energy Technology Data Exchange (ETDEWEB)

Ohara, ShigFeki; Takagi, Terumasa [Meitetsu Hospital, Nagoya (Japan); Shibata, Taichiro; Nagai, Hajime

1983-04-01

The authors discussed the developing process of delayed radiation necrosis of the brain from the case of a 42-year-old female who developed intracranial hypertension and left hemiparesis 5 and a half years after radiotherapy for pituitary adenoma. The initial sign of radiation necrosis was from a CT scan taken 3 and a half years after radiotherapy showing an irregular low density lesion in the right temporal lobe. CT scan 2 years later demonstrated displacement of the midline structures to the left and a larger low density lesion with partially high density in the right MCA territory that was enhanced with intravenous contrast medium. Recovery after a right temporal lobectomy and administration of steroid hormone were uneventful. Eight months later there were no signs of raised intracranial pressure nor of neurological deficits. Tissues obtained from the right temporal lobe at lobectomy revealed the characteristic changes of delayed radiation necrosis; a mixture of fresh, recent, and old vascular lesions in the same specimen. From these findings, it was speculated that delayed radiation necrosis might initially occur within several years after radiotherapy and might gradually take a progressive and extended course, even in cases whose clinical symptoms develop much later.

Response of tumour necrosis factor alpha (TNF ) in blood and spleen mice that vaccinated with P.berghei radiation

International Nuclear Information System (INIS)

Darlina; Tur R; Teja K

2015-01-01

Tumor necrosis factor is a glycoprotein derived from helper T lymphocytes that play an important role in the body's response against malaria infection. However, TNF-α has double play that is on appropriate levels will provide protection and healing, while at excessive levels which may be a response to hyperparasitemia. Thus investigated the expression of TNF alpha secreted blood lymphocytes and spleen cells the mice that's infected with 1 x 10 7 P.berghei infectious or inactivated by radiation. Levels of TNF alpha serum and spleen cell culture medium was monitored on days 2, 7, 14 post infection. Monitoring of parasite growth every two days for 60 days. Determination of TNF alpha levels were measure using ELISA. The results showed parasitaemia mice infected with 175 Gy irradiated parasites have pre patent period of 16 days longer than the control (non-irradiated parasites) with low parasitaemia. TNF alpha concentration that secreted spleen cells of mice vaccinated higher than control mice. Concentration of TNF alpha that secreted blood lymphocyte of mice vaccinated lower than control mice. It was concluded that the secretion of TNF alpha by blood lymphocytes caused more pathogenic factors of the parasite, while the secretion of TNF alpha in spleen due to an immune response against the parasite. (author)

Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy.

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Van der Meer, Marrit; Hoving, Jan L; Vermeulen, Marjolein I M; Herenius, Marieke M J; Tak, Paul P; Sluiter, Judith K; Frings-Dresen, Monique H W

2011-01-01

To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with respect to work participation. Experiences regarding work participation varied and ranged from fatigue at work, having no job control, not being understood by the work environment or difficulty dealing with emotions as a result of interaction within the work environment. Support by health care professionals for work participation was considered important, especially concerning social or psychological issues. Advice in becoming aware of one's changes in abilities was highly appreciated, as was the availability of professional advice in times of an urgent work issue due to RA. Employees mentioned an increase in social support at work and job control as important facilitating factors for work participation. Although patients with RA report improvement in their work functioning after starting anti-TNF therapy, employees continue facing challenges in working life due to RA. For support concerning work participation, it is recommended that health care professionals are more aware of work-related problems in patients with RA treated with anti-TNF therapy.

Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice.

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Fujita, Masaki; Ouchi, Hiroshi; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Nakanishi, Yoichi; Watanabe, Kentaro

2016-01-01

COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

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Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C. (Univ. of California, San Francisco (USA))

1990-06-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

International Nuclear Information System (INIS)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C.

1990-01-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection

Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.

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Hero, M; Suomalainen, A; Hagström, J; Stoor, P; Kontio, R; Alapulli, H; Arte, S; Toiviainen-Salo, S; Lahdenne, P; Mäkitie, O

2013-01-01

Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype. We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism. Copyright © 2012 Elsevier Inc. All rights reserved.

Multigroup calculations of low-energy neutral transport in tokamak plasmas

International Nuclear Information System (INIS)

Gilligan, J.G.; Gralnick, S.L.; Price, W.G. Jr.; Kammash, T.

1978-01-01

Multigroup discrete ordinates methods avoid many of the approximations that have been used in previous neutral transport analyses. Of particular interest are the neutral profiles generated as an integral part of larger plasma system simulation codes. To determine the appropriateness of utilizing a particular multigroup code, ANISN, for this purpose, results are compared with the neutral transport module of the Duechs code. For a typical TFTR plasma, predicted neutral densities differ by a maximum factor of three on axis and outfluxes at the plasma boundary by approximately 40%. This is found to be significant for a neutral transport module. Possible sources of the observed discrepancies are indicated from an analysis of the approximations used in the Duechs model. Recommendations are made concerning the future application of the multigroup method. (author)

A Case of Trapezium Avascular Necrosis Treated Conservatively.

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Petsatodis, Evangelos; Ditsios, Konstantinos; Konstantinou, Panagiotis; Pinto, Iosafat; Kostretzis, Lazaros; Theodoroudis, Ioannis; Pilavaki, Mayia

2017-01-01

Avascular necrosis (AVN) of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option.

Pathological features of cerebral radiation necrosis - Part I

International Nuclear Information System (INIS)

Lefaix, J.L.

1992-01-01

Cerebral radiation necrosis is a major hazard of radiation therapy involving delivery of high doses of radiation to the brain. It is generally irreversible and frequently leads to death from brain necrosis. Necrosis has been reported with total doses of 50-60 Gy, delivered in conventional fractions of 1.7 to 2 Gy daily. Signs and symptoms depend upon the volume of brain irradiated and are frequently those of an intracranial mass. Injury tends to be more severe in white matter and may be present as an area of gliosis or frank necrosis. Possible causes include some direct effect of radiation on glial cells, vascular changes and the action of an immunological mechanism. The weight of evidence suggests that demyelination is important in the early delayed reaction, and that vascular changes gradually become more important in the late delayed reactions, several months to years after treatment. Late delayed radiation injuries of the brain and spinal cord are reviewed in man, dog, monkey and rat

A Case of Trapezium Avascular Necrosis Treated Conservatively

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Evangelos Petsatodis

2017-01-01

Full Text Available Introduction. Avascular necrosis (AVN of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. Case Presentation. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. Conclusion. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option.

Serum levels of tumor necrosis factor-α and soluble adhesion molecules in relation to magnetic resonance imaging results and clinical activity in multiple sclerosis

International Nuclear Information System (INIS)

Millers, A.; Metra, M.; Mastina, M.; Platkajis, A.; Kukaine, R.

2001-01-01

One direction of research in pathogenesis of multiple sclerosis (MS) has been to identify immunological markers associated with disease activity that are capable of predicting subsequent course of disease and are sensitive to intervention by immunomodulatory therapies. Adhesion molecules and tumor necrosis factor-α of the cytokine superfamily are associated with inflammation-mediated blood-brain barrier dysfunction and demyelination in the central nervous system (CNS). This study investigates the relationship between the serum level of soluble vascular adhesion molecule-1 (sVCAM), soluble intercellular adhesion molecule-1 (alCAM), tumor necrosis factor-α (TNF-α) and magnetic resonance imaging (MRI) activity in 18 patients with relapsing-remitting (RR) MS with different clinical activity. Patients with active gadolinium (Gd)-enhanced lesions on MRI showed a higher serum level of TNF-α, sVCA-1, slCAM-1 than RR MS patients without Gd-enhanced lesions. Control individuals (n=10) without MRI abnormalities had significantly lower serum levels of the above immunological parameters. These results suggest that serum levels of TNF-α and adhesion molecules slCAM-1 in RR MS patients are correlated with Gd-enhanced MRI and disease clinical activity and that they can be used as biological markers of disease activity. The soluble form of VCAM levels in peripheral blood did not correlate with disease activity and Gd-enhanced lesions of MRI. sVCAM as an early indicator of blood-brain barrier dysfunction may also serve as marker of beneficial activity in the relapsing phase of MS course. (authors)

High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

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Nishimon, Shohei; Ohnuma, Tohru; Takebayashi, Yuto; Katsuta, Narimasa; Takeda, Mayu; Nakamura, Toru; Sannohe, Takahiro; Higashiyama, Ryoko; Kimoto, Ayako; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

2017-06-02

Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice. Copyright © 2017

Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression

International Nuclear Information System (INIS)

Krutmann, J.; Koeck, A.S.; Schauer, E.; Parlow, F.; Moeller, A.K.; Kapp, A.; Foerster, E.S.; Schoepf, E.L.; Luger, T.A.

1990-01-01

Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC

Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.

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Sun, Junjiang; Hua, Baolai; Chen, Xiaojing; Samulski, Richard J; Li, Chengwen

2017-08-01

While therapeutic expression of coagulation factors from adeno-associated virus (AAV) vectors has been successfully achieved in patients with hemophilia, neutralizing antibodies to the vector and inhibitory antibodies to the transgene severely limit efficacy. Indeed, approximately 40% of mice transduced with human factor VIII using the AAV8 serotype developed inhibitory antibodies to factor VIII (FVIII inhibitor), as well as extremely high titers (≥1:500) of neutralizing antibodies to AAV8. To correct hemophilia in these mice, AAV9, a serotype with low in vitro cross-reactivity (≤1:5) to anti-AAV8, was used to deliver mouse-activated factor VII (mFVIIa). It was found that within 6 weeks of systemic administration of 2 × 10 13 particles/kg of AAV9/mFVIIa, hemophiliac mice with FVIII inhibitors and neutralizing antibodies (NAb) to AAV8 achieved hemostasis comparable to that in wild-type mice, as measured by rotational thromboelastometry. A level of 737 ng/mL mFVIIa was achieved after AAV9/mFVIIa adminstration compared to around 150 ng/mL without vector treatment, and concomitantly prothrombin time was shortened. Tissues collected after intra-articular hemorrhage from FVIII-deficient mice and mice with FVIII inhibitors were scored 4.7 and 5.5, respectively, on a scale of 0-10, indicating significant pathological damage. However, transduction with AAV9/mFVIIa decreased pathology scores to 3.6 and eliminated hemosiderin iron deposition in the synovium in most mice. Collectively, these results suggest that application of alternative serotypes of AAV vector to deliver bypassing reagents has the potential to correct hemophilia and prevent hemoarthrosis, even in the presence of FVIII inhibitor and neutralizing antibodies to AAV.