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Sample records for balance anti-tumour necrosis

  1. What is left when anti-tumour necrosis factor therapy in inflammatory bowel diseases fails?

    PubMed Central

    Lawrance, Ian C

    2014-01-01

    The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient’s life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn’s disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome. PMID:24574799

  2. What is left when anti-tumour necrosis factor therapy in inflammatory bowel diseases fails?

    PubMed

    Lawrance, Ian C

    2014-02-07

    The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient's life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn's disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome.

  3. Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol increases its anti-tumour potency.

    PubMed Central

    Tsutsumi, Y.; Kihira, T.; Tsunoda, S.; Kanamori, T.; Nakagawa, S.; Mayumi, T.

    1995-01-01

    This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use. PMID:7734321

  4. Thalidomide increases both intra-tumoural tumour necrosis factor-α production and anti-tumour activity in response to 5,6-dimethylxanthenone-4-acetic acid

    PubMed Central

    Cao, Z; Joseph, W R; Browne, W L; Mountjoy, K G; Palmer, B D; Baguley, B C; Ching, L-M

    1999-01-01

    5,6-Dimethylxanthenone-4-acetic acid (DMXAA), synthesized in this laboratory and currently in phase I clinical trial, is a low molecular weight inducer of tumour necrosis factor-α (TNF-α). Administration of DMXAA to mice with established transplantable tumours elicits rapid vascular collapse selectively in the tumour, followed by extensive haemorrhagic necrosis mediated primarily through the production of TNF-α. In this report we have investigated the synthesis of TNF-α mRNA in hepatic, splenic and tumour tissue. Co-administration of thalidomide with DMXAA increased anti-tumour activity and increased intra-tumoural TNF-α production approximately tenfold over that obtained with DMXAA alone. Thalidomide increased splenic TNF-α production slightly but significantly decreased serum and hepatic levels of TNF-α induced with DMXAA. Lipopolysaccharide (LPS) induced 300-fold higher serum TNF-α than did DMXAA at the maximum tolerated dose, but induced similar amounts of TNF-α in spleen, liver and tumour. Splenic TNF-α activity induced with LPS was slightly increased with thalidomide, but serum and liver TNF-α levels were suppressed. Thalidomide did not increase intra-tumoural TNF-α production induced with LPS, in sharp contrast to that obtained with DMXAA. While thalidomide improved the anti-tumour response to DMXAA, it had no effect on the anti-tumour action of LPS that did not induce a significant growth delay or cures against the Colon 38 tumour. The increase in the anti-tumour action by thalidomide in combination with DMXAA corresponded to an increase in intra-tumoural TNF-α production. Co-administration of thalidomide may represent a novel approach to improving selective intra-tumoural TNF-α production and anti-tumour efficacy of DMXAA. © 1999 Cancer Research Campaign PMID:10360649

  5. Effect of thalidomide on tumour necrosis factor production and anti-tumour activity induced by 5,6-dimethylxanthenone-4-acetic acid.

    PubMed Central

    Ching, L. M.; Xu, Z. F.; Gummer, B. H.; Palmer, B. D.; Joseph, W. R.; Baguley, B. C.

    1995-01-01

    The investigational anti-tumour agent, 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA), an analogue of flavone acetic acid (FAA), has been scheduled for clinical evaluation. Like FAA, 5,6-MeXAA exhibits excellent experimental anti-tumour activity and is an efficient inducer of cytokines in mice. We have examined the effect of pharmacological suppression of tumour necrosis factor (TNF) production on the anti-tumour activity of 5,6-MeXAA, taking advantage of previous observations that TNF production in response to endotoxin in vitro is inhibited by thalidomide. Thalidomide at doses of between 8 and 250 mg kg-1 efficiently suppressed serum TNF activity in response to 5,6-MeXAA at its optimal TNF inducing dose of 55 mg kg-1. Suppression was achieved when thalidomide was administered at the same time as, or up to 4 h before, 5,6-MeXAA. Under conditions in which TNF activity was suppressed, the degree of tumour haemorrhagic necrosis and the proportion of cures in the subcutaneous Colon 38 tumour were increased. In mice administered thalidomide (100 mg kg-1) together with 5,6-MeXAA (30 mg kg-1), complete tumour regression was obtained in 100% of mice, as compared with 67% in mice receiving 5,6-MeXAA alone. The results suggest a possible new application for thalidomide and pose new questions about the action of 5,6-MeXAA and related compounds. PMID:7640215

  6. Impact of thiopurines and anti-tumour necrosis factor therapy on hospitalisation and long-term surgical outcomes in ulcerative colitis

    PubMed Central

    Alexakis, Christopher; Pollok, Richard CG

    2015-01-01

    Ulcerative colitis (UC) is a chronic inflammatory condition affecting the large bowel and is associated with a significant risk of both requirement for surgery and the need for hospitalisation. Thiopurines, and more recently, anti-tumour necrosis factor (aTNF) therapy have been used successfully to induce clinical remission. However, there is less data available on whether these agents prevent long-term colectomy rates or the need for hospitalisation. The focus of this article is to review the recent and pertinent literature on the long-term impact of thiopurines and aTNF on long-term surgical and hospitalisation rates in UC. Data from population based longitudinal research indicates that thiopurine therapy probably has a protective role against colectomy, if used in appropriate patients for a sufficient duration. aTNF agents appear to have a short term protective effect against colectomy, but data is limited for longer periods. Whereas there is insufficient evidence that thiopurines affect hospitalisation, evidence favours that aTNF therapy probably reduces the risk of hospitalisation within the first year of use, but it is less clear on whether this effect continues beyond this period. More structured research needs to be conducted to answer these clinically important questions. PMID:26730281

  7. Genetic Variants in Toll-Like Receptors Are Not Associated with Rheumatoid Arthritis Susceptibility or Anti-Tumour Necrosis Factor Treatment Outcome

    PubMed Central

    Barrera, Pilar; Schijvenaars, Mascha M. V. A. P.; Toonen, Erik J. M.; Scheffer, Hans; Padyukov, Leonid; Kastbom, Alf; Klareskog, Lars; Barton, Anne; Kievit, Wietske; Rood, Maarten J.; Jansen, Tim L.; Swinkels, Dorine; van Riel, Piet L. C. M.; Franke, Barbara; Bendtzen, Klaus; Radstake, Timothy R. D. J.

    2010-01-01

    Background 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. Methodology and Principal Findings 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population. PMID:21179534

  8. Abatacept (cytotoxic T lymphocyte antigen 4-immunoglobulin) improves B cell function and regulatory T cell inhibitory capacity in rheumatoid arthritis patients non-responding to anti-tumour necrosis factor-α agents.

    PubMed

    Picchianti Diamanti, A; Rosado, M M; Scarsella, M; Germano, V; Giorda, E; Cascioli, S; Laganà, B; D'Amelio, R; Carsetti, R

    2014-09-01

    The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg ) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects. The size of the circulating B and T cell compartments in RA patients was not significantly different from healthy donors, but B cell proliferation and plasma cell differentiation was impaired before therapy and restored by abatacept. While Treg cell frequency was normal, its inhibitory function was absent before therapy and was partially recovered 6 months after abatacept. B and Treg cell function is impaired in RA patients not responding to the first anti-TNF-α agent. Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome, suggesting that RA patients, in whom anti-TNF-α failed, are immunologically prone to benefit from an agent targeting a different pathway.

  9. The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial

    PubMed Central

    Schiff, M; Pritchard, C; Huffstutter, J E; Rodriguez-Valverde, V; Durez, P; Zhou, X; Li, T; Bahrt, K; Kelly, S; Le Bars, M; Genovese, M C

    2009-01-01

    Objective: To assess the safety, tolerability and efficacy of abatacept in patients with rheumatoid arthritis (RA) who had failed anti-tumour necrosis factor (TNF) therapy and were switched to abatacept directly or after completing washout. Methods: In this international, 6-month, open-label trial, patients had active RA, an inadequate response to anti-TNF therapy for 3 months or longer and a disease activity score in 28 joints (DAS28 (C-reactive protein; CRP) of 5.1 or greater. “Washout” patients discontinued anti-TNF therapy 2 months or longer pre-screening; “direct-switch” patients began abatacept (∼10 mg/kg) at their next scheduled anti-TNF therapy dose. Results: 1046 patients were treated (449 washout, 597 direct-switch; baseline characteristics were similar between groups). At 6 months, adverse events (AE; 78.0% vs 79.2%), serious AE (11.1% vs 9.9%) and discontinuations due to AE (3.8% vs 4.0%) and serious AE (2.0% vs 1.3%) were comparable in washout versus direct-switch patients. There were no opportunistic infections. At 6 months, in washout versus direct-switch patients, similar clinically meaningful improvements were seen in DAS28 (CRP) (⩾1.2 unit improvement, 59.5% vs 53.6%, respectively; low disease activity state, 22.5% vs 22.3%; DAS28-defined remission, 12.0% vs 13.7%), physical function (health assessment questionnaire disability index ⩾0.22 improvement; 46.3% vs 47.1%) and health-related quality of life (mean change in short-form 36 scores: physical component summary, 5.5 vs 6.1; mental component summary, 4.8 vs 5.4). Conclusion: Abatacept demonstrated acceptable safety and tolerability and clinically meaningful efficacy over 6 months in patients with inadequate response to anti-TNF therapy. Results were comparable with or without a washout, supporting direct switching from anti-TNF therapy to abatacept as an option in clinical practice. Trial registration number: NCT00124982. PMID:19074911

  10. Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy.

    PubMed

    Iwaszko, M; Świerkot, J; Kolossa, K; Jeka, S; Wiland, P; Bogunia-Kubik, K

    2015-12-01

    Involvement of the non-classical human leucocyte antigen-E (HLA-E) in both innate and acquired immune response suggests its possible role in development of autoimmune pathologies. This study was undertaken to investigate relationships between the HLA-E gene single nucleotide polymorphisms (SNPs) and a risk of rheumatoid arthritis (RA), as well as to evaluate a potential of these polymorphisms to modulate clinical outcome of anti-tumour necrosis factor (TNF) treatment in female patients. A total of 223 female patients with RA receiving anti-TNF biological therapy and 134 female healthy subjects were enrolled into the study. Genotypings for two SNPs within the HLA-E gene (rs1264457 HLA-E*01:01/01:03; rs1059510 HLA-E*01:03:01/01:03:02) were performed using a polymerase chain reaction (PCR) amplification employing LightSNiP assays. Clinical response was evaluated according to the European League Against Rheumatism (EULAR) criteria at 12 and 24 weeks after initiation of the therapy. The frequency of the HLA-E*01:01/01:01 genotype was decreased significantly in RA patients in comparison to controls (P = 0.031). The presence of the HLA-E*01:01/01:01 genotype in patients correlated with better EULAR response after 12 weeks of anti-TNF treatment, while 01:03 allele carriers were generally unresponsive to the treatment (P = 0.014). The HLA-E*01:03/01:03 genotype was also over-represented among non-responding patients in comparison to HLA-E*01:01/01:01 homozygotes (P = 0.021). With respect to the HLA-E rs1059510 variation, a better response after 12 weeks was observed more frequently in patients carrying the HLA-E*01:03:01/01:03:01 genotype than other genotypes (P = 0.009). The results derived from this study imply that HLA-E polymorphisms may influence RA susceptibility and affect clinical outcome of anti-TNF therapy in female RA patients.

  11. Photodynamic therapy and anti-tumour immunity

    PubMed Central

    Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.

    2010-01-01

    Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

  12. Immune stimulatory and anti-tumour properties of haemin.

    PubMed Central

    Tsuji, A; Wang, J; Stenzel, K H; Novogrodsky, A

    1993-01-01

    IL-2 induces tumour regression in some patients with metastatic disease, but the dose of IL-2 is limited by severe toxicity. Agents that increase the expression of IL-2 receptors in the effector cells could be used to improve the effectiveness of IL-2 in mediating its anti-tumour effect. We have reported that haemin increased the expression of IL-2 receptors in human peripheral blood mononuclear cells (PBMC) and synergized with IL-2 in the induction of mitogenicity, cytotoxicity and cytokine production. We now report on haemin-induced immune stimulation and tumour regression in mice. Haemin-induced mitogenicity in mouse splenocytes was potentiated up to two-fold by IL-2. The combination of haemin and IL-2 was also effective in inducing cytotoxicity for natural killer (NK)-resistant target cells. Maximal induction of cytotoxicity was attained at an optimal concentration of haemin of 10 microM. Higher concentrations were less effective. Splenocytes isolated from mice that had been treated in vivo with haemin and IL-2 incorporated twice the amount of 3H-thymidine compared with splenocytes from mice treated with either haemin or IL-2 alone. Cytotoxicity of splenocytes for NK-resistant target cells was not increased following in vivo administration of haemin and IL-2 when fresh splenocytes were tested. Cytotoxicity was enhanced, however, up to five-fold following 48 h in vitro incubation with IL-2. Administration of haemin and IL-2 resulted in a significant decrease (40%) of established hepatic metastases in mice. Either IL-2 or haemin alone at the dose used were ineffective. The anti-tumour effect of haemin and IL-2 was enhanced (63% decrease in metastases) by administration of the thiol compound, N-acetylcysteine. Since haemin can safely be administered to patients, it may represent a new class of biologic response modifiers that could enhance IL-2-mediated anti-tumour effects. PMID:8370158

  13. Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy

    PubMed Central

    Pergola, Carlo; Schubert, Katrin; Pace, Simona; Ziereisen, Jana; Nikels, Felix; Scherer, Olga; Hüttel, Stephan; Zahler, Stefan; Vollmar, Angelika M.; Weinigel, Christina; Rummler, Silke; Müller, Rolf; Raasch, Martin; Mosig, Alexander; Koeberle, Andreas; Werz, Oliver

    2017-01-01

    Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)α release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFκB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFα secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFα. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells. PMID:28134280

  14. Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents.

    PubMed

    Ushio, Soichiro; Egashira, Nobuaki; Sada, Hikaru; Kawashiri, Takehiro; Shirahama, Masafumi; Masuguchi, Ken; Oishi, Ryozo

    2012-06-01

    Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice.

  15. Effects of nandrolone decanoate on the toxicity and anti-tumour action of CCNU and FU in murine tumours.

    PubMed Central

    Bibby, M. C.; Double, J. A.; Mughal, M. A.

    1981-01-01

    Pre-treatment with the anabolic steroid nandrolone decanoate (ND) increases the LD50 of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-Fluorouracil (FU) in NMRI mice. Administration of ND did not affect the anti-tumour action of CCNU against a transplantable mouse adenocarcinoma of the colon (MAC 13) or the anti-tumour action of FU against MAC 26. In both tumour lines ND had no significant effect on tumour growth. These data suggest that an increase in the anti-tumour selectivity of these agents may be produced by pre-treatment with ND. PMID:7295514

  16. Antibodies as an unlimited source of anti-infective, anti-tumour and immunomodulatory peptides.

    PubMed

    Ciociola, Tecla; Magliani, Walter; Giovati, Laura; Sperindé, Martina; Santinoli, Claudia; Conti, Giorgio; Conti, Stefania; Polonella, Luciano

    2014-01-01

    Antibodies (Abs) are emerging as an important class of therapeutic agents for the treatment of various human diseases, often conjugated to drugs or toxic substances. In recent years, the incidence of cancer and infectious diseases has increased dramatically making it imperative to discover new effective therapeutic molecules. Among these, small peptides are arousing great interest. Synthetic peptides, representative of variable and constant region fragments of Abs, were proved to exert in vitro, ex vivo and/or in vivo anti-microbial, anti-viral, anti-tumour and/or immunomodulatory activities, mediated by different mechanisms of action and regardless of the specificity and isotype of the Ab. Some of these synthetic peptides possess the ability to spontaneously and reversibly self-assemble in an organised network of fibril-like structure. Ab fragments may represent a novel model of targeted anti-infective and anti-tumour auto-delivering drugs.

  17. Systemic interleukin 12 displays anti-tumour activity in the mouse central nervous system.

    PubMed Central

    Kishima, H.; Shimizu, K.; Miyao, Y.; Mabuchi, E.; Tamura, K.; Tamura, M.; Sasaki, M.; Hakakawa, T.

    1998-01-01

    In various systemic cancers, interleukin 12 (IL-12) induces anti-tumour immunity mediated by T lymphocytes and natural killer cells. To determine whether IL-12 has anti-tumour activity against malignant gliomas in the central nervous system (CNS), which is considered to be an immunologically privileged site, we treated mice with meningeal gliomatosis by intraperitoneal (i.p.) or intrathecal (i.t.) administration of recombinant murine IL-12. Although untreated mice revealed symptoms, such as body weight loss or paraplegia as a result of the meningeal gliomatosis within 8 days after tumour inoculation, 80% of the mice treated with IL-12 at 0.5 microg i.p. were cured. Many lymphocytes, mostly CD4+ and CD8+ cells, infiltrated to the tumours of IL-12-treated mice. The numbers of these cells increased in the cervical lymph nodes, into which the cerebrospinal fluid drains, and there they secreted a considerable amount of interferon-gamma. Mice cured by IL-12 rejected subcutaneous or i.t. rechallenge with their original glioma cells, but the same mice were not able to reject other syngeneic tumour cells. These results indicate that the immune system recognizes malignant glioma cells in the subarachnoid space of the CNS and that systemic IL-12 may produce effective anti-tumour activity and long-lasting tumour-specific immunity. Images Figure 1 Figure 4 PMID:9716025

  18. Cutting the limits of aminobisphosphonates: new strategies for the potentiation of their anti-tumour effects.

    PubMed

    Marra, M; Abbruzzese, A; Addeo, R; Del Prete, S; Tassone, P; Tonini, G; Tagliaferri, P; Santini, D; Caraglia, M

    2009-11-01

    Therapy with aminobisphosphonate (N-BPs), and zoledronic acid (ZOL) especially, has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that N-BPs exert their direct or indirect anti-tumour effects on cancer growth factor release, cancer cell adhesion, invasion and viability, cancer angiogenesis and cancer cell apoptosis. Here, we will discuss the molecular mechanisms of the antitumour effects induced by ZOL. Despite their well-established in vitro anti-tumour effects N-BPs have not clear in vivo anti-tumour activity in humans. The bases of these discrepancies will be discussed in the text with a special focus on the pharmacokinetic limits of N-BPs. Moreover, the following molecular and pharmacological strategies in order to overcome N-BPs limitations will be described: i) development of pharmacological combinations with other biological agents; ii) finding of new molecular targets of N-BPs; iii) development of new pharmacological formulations of N-BPs. Finally, a new scenario of integrated bio-medicine and pharmacology will be depicted in order to drive the optimization of anti-cancer activity of N-BPs.

  19. Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response

    PubMed Central

    Habets, Thomas H. P. M.; Oth, Tammy; Houben, Ans W.; Huijskens, Mirelle J. A. J.; Senden-Gijsbers, Birgit L. M. G.; Schnijderberg, Melanie C. A.; Brans, Boudewijn; Dubois, Ludwig J.; Lambin, Philippe; De Saint-Hubert, Marijke; Germeraad, Wilfred T. V.; Tilanus, Marcel G. J.; Mottaghy, Felix M.

    2016-01-01

    Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects. PMID:27427766

  20. Tumor necrosis factor-alpha/interleukin-10 balance in normal and cystic fibrosis children.

    PubMed Central

    Shmarina, G V; Pukhalsky, A L; Kokarovtseva, S N; Pukhalskaya, D A; Shabalova, L A; Kapranov, N I; Kashirskaja, N J

    2001-01-01

    BACKGROUND: The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-alpha contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators. AIMS: In the present study, the relationships between TNF-alpha and IL-10 in the plasma of healthy school-children and cystic fibrosis (CF) patients have been investigated. METHODS: Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF-alpha/IL-10 > 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-alpha or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed. CONCLUSIONS: There were no fundamental differences between CF and healthy children in the regulation of TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-alpha, whereas immune disturbance was characterized by IL-10 superiority. The only

  1. Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of Cisplatin with Simultaneous Reduction in its Nephrotoxictiy.

    PubMed

    Jamdade, Vinayak Sudhir; Mundhe, Nitin A; Kumar, Parveen; Tadla, Venkatesh; Lahkar, Mangala

    2016-01-01

    Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as chemotherapeutic agent. However, it remains as most widely employed anticancer agent to treat various solid tumours like head-neck, testicular, ovarian and mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as well as anti-cancer agent. The present study was carried out to explore the effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its anti-tumour activity in 7, 12 dimethyl benz [a] anthracene induced mammary tumour in animal model. Renal damage was accessed by measuring serum level of creatinine, blood urea nitrogen and albumin whereas systemic inflammation was accessed by measuring level of pro-inflammatory cytokines like tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) and nuclear factor kappa B (NFκB). Moreover, assessment of tumour reduction was done by measuring tumour volume and percentage tumour reduction. A single dose of cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood urea nitrogen, NF-kB, TNF-α and IL-6 levels along with decrease in albumin and IL-10 levels. However, there were no significant changes in raloxifene (8 mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked decrease in serum creatinine, blood urea nitrogen, TNF-α and IL-6 levels whereas increase in albumin and IL-10 levels. However, pre-treatment of raloxifene showed maximum tumour reduction as compared to cisplatin and raloxifene treated groups. The present study demonstrates that raloxifene potentiates anti-tumour activity of cisplatin with simultaneous reduction in its nephrotoxicity, and this effect is attributed to its direct anti-inflammatory activity.

  2. Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules

    PubMed Central

    Shimokawa, T; Seike, M; Soeno, C; Uesaka, H; Miyanaga, A; Mizutani, H; Kitamura, K; Minegishi, Y; Noro, R; Okano, T; Yoshimura, A; Gemma, A

    2012-01-01

    Background: Enzastaurin, an oral serine–threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. Methods: We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. Results: We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. Conclusion: Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules. PMID:22333600

  3. [Certain results of the investigations into the anti-tumour action of the magnetic field under experimental conditions].

    PubMed

    Ulashchik, V S

    2015-01-01

    This paper summarizes the results of the application of thr magnetic fields for the treatment of experimental tumours, such as sarcoma M-1, alveolar liver cancer PC-1, and Erlich's carcinoma. The evidence of the anti-tumour action of both strong (1200 mTI) and weak (5 to 100 mTI) magnetic fields has been obtained. The author describes the modulating effect of the magnetic fields on the anti-tumour potency of photodynamic therapy and chemotherapy. The data concerning the impact of ferromagnetic hyperthermal therapy on the tumour growth and the survival rate among the tumour-bearing animals are presented.

  4. Could plant lectins become promising anti-tumour drugs for causing autophagic cell death?

    PubMed

    Liu, Z; Luo, Y; Zhou, T-T; Zhang, W-Z

    2013-10-01

    Plant lectins, a group of highly diverse carbohydrate-binding proteins of non-immune origin, are ubiquitously distributed through a variety of plant species, and have recently drawn rising attention due to their remarkable ability to kill tumour cells using mechanisms implicated in autophagy. In this review, we provide a brief outline of structures of some representative plant lectins such as concanavalin A, Polygonatum cyrtonema lectin and mistletoe lectins. These can target autophagy by modulating BNIP-3, ROS-p38-p53, Ras-Raf and PI3KCI-Akt pathways, as well as Beclin-1, in many types of cancer cells. In addition, we further discuss how plant lectins are able to kill cancer cells by modulating autophagic death, for therapeutic purposes. Together, these findings provide a comprehensive perspective concerning plant lectins as promising new anti-tumour drugs, with respect to autophagic cell death in future cancer therapeutics.

  5. Evidence for anti-tumour effect of allogeneic haematopoietic SCT in cases without sustained donor engraftment.

    PubMed

    Daguindau, E; Lioure, B; Buzyn, A; Robin, M; Faucher, C; Kuentz, M; Tiberghien, P; Deconinck, E

    2010-01-01

    Remissions of haematological malignancies have been reported after allo-SCT, despite donor cell rejection, suggesting that sustained allogeneic engraftment is not mandatory to obtain a lasting anti-tumour effect. To evaluate the potential benefit from transient post-allo-SCT alloreactivity, we took advantage of the Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC) registry to colligate 14 patients with an efficient and long-lasting allogeneic (GVL) effect after allo-SCT for haematological malignancies, despite transient or absent engraftment. None received a second allogeneic graft after autologous recovery. The median duration of remission after autologous reconstitution was 118 (12-252) months. Although we cannot exclude the possibility that some patients were cured before allo-SCT, this retrospective analysis does strongly suggest that an efficient GVL effect can be observed without sustained donor engraftment, and that the transient presence of donor T cells might be sufficient to induce a powerful GVL effect.

  6. Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer.

    PubMed

    Li, Zhenfei; Bishop, Andrew C; Alyamani, Mohammad; Garcia, Jorge A; Dreicer, Robert; Bunch, Dustin; Liu, Jiayan; Upadhyay, Sunil K; Auchus, Richard J; Sharifi, Nima

    2015-07-16

    Prostate cancer resistance to castration occurs because tumours acquire the metabolic capability of converting precursor steroids to 5α-dihydrotestosterone (DHT), promoting signalling by the androgen receptor and the development of castration-resistant prostate cancer. Essential for resistance, DHT synthesis from adrenal precursor steroids or possibly from de novo synthesis from cholesterol commonly requires enzymatic reactions by 3β-hydroxysteroid dehydrogenase (3βHSD), steroid-5α-reductase (SRD5A) and 17β-hydroxysteroid dehydrogenase (17βHSD) isoenzymes. Abiraterone, a steroidal 17α-hydroxylase/17,20-lyase (CYP17A1) inhibitor, blocks this synthetic process and prolongs survival. We hypothesized that abiraterone is converted by an enzyme to the more active Δ(4)-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor, providing an additional explanation for abiraterone's clinical activity. Here we show that abiraterone is converted to D4A in mice and patients with prostate cancer. D4A inhibits CYP17A1, 3βHSD and SRD5A, which are required for DHT synthesis. Furthermore, competitive androgen receptor antagonism by D4A is comparable to the potent antagonist enzalutamide. D4A also has more potent anti-tumour activity against xenograft tumours than abiraterone. Our findings suggest an additional explanation-conversion to a more active agent-for abiraterone's survival extension. We propose that direct treatment with D4A would be more clinically effective than abiraterone treatment.

  7. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer

    PubMed Central

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-01-01

    Background and Purpose The psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. Experimental Approach To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. Key Results CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. Conclusions and Implications O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. PMID:24910342

  8. Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG.

    PubMed Central

    Castés, M.; Lynch, N. R.; Lespinats, G.; Orbach-Arbouys, S.

    1981-01-01

    The i.v. injection of high doses (3 mg) of BCG into C3H mice bearing a transplantable 3-methylcholanthrene-induced fibrosarcoma caused the regression of a significant proportion. This effect was most evident when the BCG was injected on the day of the graft, or 7 days later. The injection of this agent either 14 days before the graft, or in low doses (0.1 or 0.5 mg), or directly into the tumour (i.t.) only prolonged the survival of the animals. Spleen cells from systemic high-dose BCG-treated mice were found to exert a strong nonspecific cytostatic effect in vitro that was not an artefact of the test conditions, and was not expressed by cells from low-dose animals. The cytostatic effect was shown to be caused by cells with the characteristics of macrophages, i.e. they were strongly adherent, unaffected by treatment with anti-Thy 1.2 + C', radioresistant but heat-sensitive, and were detected in BCG-treated "B" mice. The spleens of high-dose BCG-treated mice also contained suppressor cells that were capable of inhibiting the in vitro reactivity of normal T cells to PHA. Like the cytostatic effect, this suppressor activity was not detected in low-dose mice, and the cells responsible had the properties of macrophages; the effect was lost after the removal of adherent cells by sequential exposure to plastic and colloidal iron, but was conserved after treatment with anti-Thy 1.2 + C'. T-cell-deprived animals, such as "B" or nude mice, also developed suppressor-cell activity when treated with systemic high-dose BCG. Close parallels became evident between the in vivo anti-tumour activity of BCG, the in vitro cytostatic effect, and the suppressor-cell activity. We here discuss the possible role of suppressor cells in the mechanism of action of this agent. PMID:6459797

  9. Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

    PubMed Central

    Martins-Marques, Tania; Pinho, Maria Joao; Zuzarte, Monica; Oliveira, Carla; Pereira, Paulo; Sluijter, Joost P. G.; Gomes, Celia; Girao, Henrique

    2016-01-01

    Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43) in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects. PMID:27702427

  10. Induction of anti-tumour lymphocytes in cancer patients after brief exposure to supernatants from cultures of anti-CD3-stimulated allogeneic lymphocytes.

    PubMed Central

    Baxevanis, C. N.; Tsiatas, M. L.; Cacoullos, N. T.; Spanakos, G.; Liacos, C.; Missitzis, I.; Papadhimitriou, S. I.; Papamichail, M.

    1997-01-01

    The present study investigated the ability of supernatants collected from cultures of healthy donor-derived peripheral blood mononuclear cells (HD-PBMCs) stimulated with anti-CD3 monoclonal antibody (MAb) (allogeneic CD3 supernatants; ACD3S) to induce, upon brief exposure, tumour-reactive cytotoxic lymphocytes in cancer patients' PBMCs. ACD3S enhanced natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxicity. ACD3S contained increased levels of interleukins (IL) 1, 2, 6, 7 and 12, as well as of granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma-interferon (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). MAbs against these cytokines significantly reduced the ACD3S-induced cytotoxicity. ACD3S-induced cytotoxicity was not inhibited by anti-CD4, CD8 and MHC class I MAbs, but was markedly reduced in the presence of MAb against CD18. In contrast to HD-PBMC, ACD3S derived from cancer patients' lymphocytes exhibited lower levels of the above-mentioned cytokines and exerted reduced biological activity. In conclusion, ACD3S are able to activate, upon short-term incubation, tumour-reactive lymphocytes from cancer patients' PBMCs that lyse a variety of tumour targets, including autologous tumours. ACD3S contain high levels of certain cytokines that positively influence the induction of autologous tumour-reactive lymphocytes. Such supernatants can be collected easily from healthy donors and stored until use in clinical trials for adoptive cellular therapy of cancer. They may also be indicated in the construction of cytokine cocktails that have the ability to induce anti-tumour cytotoxicity. PMID:9376269

  11. Design, characterization and anti-tumour cytotoxicity of a panel of recombinant, mammalian ribonuclease-based immunotoxins.

    PubMed Central

    Deonarain, M. P.; Epenetos, A. A.

    1998-01-01

    Bovine seminal ribonuclease (BSRNase) is an unusual member of the ribonuclease superfamily, because of its remarkable anti-tumour and immunosuppressive properties. We describe here the construction, expression, purification and characterization of a panel of six immunotoxins based upon this enzyme and show that we can increase its anti-tumour activity by over 2 x 10(4)-fold. This is achieved by improving tumour cell targeting using a single-chain Fv (scFv) directed against the oncofetal antigen placental alkaline phosphatase. As well as the simple scFv-BSRNase fusion protein, we have constructed five other derivatives with additional peptides designed to improve folding and intracellular trafficking and delivery. We find that the molecule most cytotoxic to antigen (PLAP)-positive cells in vitro is one that contains a C-terminal 'KDEL' endoplasmic reticulum retention signal and a peptide sequence derived from diphtheria toxin. All these molecules are produced in Escherichia coli (E. coli) as insoluble inclusion bodies and require extensive in vitro processing to recover antigen binding and ribonuclease activity. Despite incomplete ribonuclease activity and quaternary assembly, these molecules are promising reagents for specific chemotherapy of cancer and are potentially less harmful and immunogenic than current immunotoxins. Images Figure 2 PMID:9484808

  12. Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells

    PubMed Central

    Momeny, Majid; Sabourinejad, Zahra; Zarrinrad, Ghazaleh; Moghaddaskho, Farima; Eyvani, Haniyeh; Yousefi, Hassan; Mirshahvaladi, Shahab; Poursani, Ensieh M.; Barghi, Farinaz; Poursheikhani, Arash; Dardaei, Leila; Bashash, Davood; Ghazi-Khansari, Mahmoud; Tavangar, Seyyed M.; Dehpour, Ahmad R.; Yaghmaie, Marjan; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H.

    2017-01-01

    Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and succumb to chemoresistant disease. Overcoming drug resistance is the key to successful treatment of EOC. Members of vascular endothelial growth factor (VEGF) family are overexpressed in EOC and play key roles in its malignant progression though their contribution in development of the chemoresistant disease remains elusive. Here we show that expression of the VEGF family is higher in therapy-resistant EOC cells compared to sensitive ones. Overexpression of VEGFR2 correlated with resistance to cisplatin and combination with VEGFR2-inhibitor apatinib synergistically increased cisplatin sensitivity. Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death. Tivozanib decreased invasive potential of these cells, concomitant with reduction of intercellular adhesion molecule-1 (ICAM-1) and diminishing the enzymatic activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). Moreover, tivozanib synergistically enhanced anti-tumour effects of EGFR-directed therapies including erlotinib. These findings suggest that the VEGF pathway has potential as a therapeutic target in therapy-resistant EOC and VEGFR blockade by tivozanib may yield stronger anti-tumour efficacy and circumvent resistance to EGFR-directed therapies. PMID:28383032

  13. Novel anti-tumour barringenol-like triterpenoids from the husks of Xanthoceras sorbifolia Bunge and their three dimensional quantitative structure activity relationships analysis.

    PubMed

    Wang, Da; Su, Dan; Yu, Bin; Chen, Chuming; Cheng, Li; Li, Xianzhe; Xi, Ronggang; Gao, Huiyuan; Wang, Xiaobo

    2017-01-01

    The high edible oil content of Xanthoceras sorbifolia Bunge seeds contributes to its economic value. In this study, we analysed the barrigenol-like triterpenoids derived from X. sorbifolia husks. We also identified anti-tumour agents that could enhance the health benefits and medicinal value of X. sorbifolia. We isolated 10 barrigenol triterpenoids, including six new compounds (1-6) and four known compounds (7-10). New compounds 3 and 5 showed significant inhibitory activity against the proliferation of three human tumour cell lines, namely, HepG2, HCT-116 and U87-MG. We determined the relationship between the structures and inhibitory activity of 25 barrigenol triterpenoids and 15 penta-cyclic triterpenoids through analysis of three-dimensional quantitative structure activity relationships (3D-QSAR). The isolation of novel barrigenol derivatives with anti-tumour activity from X. sorbifolia implied that husks of this plant may be a good source of anti-tumour agents.

  14. Enhanced oral bioavailability and anti-tumour effect of paclitaxel by 20(s)-ginsenoside Rg3 in vivo.

    PubMed

    Yang, Lei-Qiong; Wang, Bin; Gan, Hui; Fu, Shou-Ting; Zhu, Xiao-Xia; Wu, Zhuo-Na; Zhan, Da-Wei; Gu, Ruo-Lan; Dou, Gui-Fang; Meng, Zhi-Yun

    2012-11-01

    The purpose of this study was to investigate the effect of paclitaxel in combination with 20(s)-ginsenoside Rg3 on its anti-tumour effect in nude mice. In the Caco-2 transport assay, the apparent permeability from the apical side to the basal side (P(app)) (A-B) and P(app) (B-A) of paclitaxel were measured when co-incubated with different concentrations of 20(s)-ginsenoside Rg3. The results indicated that the penetration of paclitaxel through the Caco-2 monolayer from the apical side to the basal side was facilitated by 20(s)-ginsenoside Rg3 in a concentration-dependent manner. Meanwhile, 20(s)-ginsenoside Rg3 inhibited P-glycoprotein (P-gp), and the maximum inhibition was achieved at 80 µM (p < 0.05). The pharmacokinetic parameters of paclitaxel after oral co-administration of paclitaxel (40 mg/kg) with various doses of 20(s)-ginsenoside Rg3 in rats were investigated by an in vivo pharmacokinetic experiment. The results showed that the AUC of paclitaxel co-administered with 20(s)-ginsenoside Rg3 was significantly higher (p < 0.001 at 10 mg/kg) compared with the control. The relative bioavailability (RB) % of paclitaxel with 20(s)-ginsenoside Rg3 was 3.4-fold (10 mg/kg) higher than that of the control. The effect of paclitaxel orally co-administered with 20(s)-ginsenoside Rg3 against human tumour MCF-7 xenografts in nude mice was also evaluated. Paclitaxel (20 mg/kg) co-administered with 20(s)-ginsenoside Rg3 (10 mg/kg) exhibited an effective anti-tumour activity with the relative tumor growth rate (T/C) values of 39.36% (p <0.05). The results showed that 20(s)-ginsenoside Rg3 enhanced the oral bioavailability of paclitaxel in rats and improved the anti-tumour activity in nude mice, indicating that oral co-administration of paclitaxel with 20(s)-ginsenoside Rg3 could provide an effective strategy in addition to the established i.v. route.

  15. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity

    PubMed Central

    Leal, JFM; Martínez-Díez, M; García-Hernández, V; Moneo, V; Domingo, A; Bueren-Calabuig, JA; Negri, A; Gago, F; Guillén-Navarro, MJ; Avilés, P; Cuevas, C; García-Fernández, LF; Galmarini, CM

    2010-01-01

    BACKGROUND AND PURPOSE PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that is currently in phase I clinical development for the treatment of solid tumours. In this study we have characterized the interactions of PM01183 with selected DNA molecules of defined sequence and its in vitro and in vivo cytotoxicity. EXPERIMENTAL APPROACH DNA binding characteristics of PM01183 were studied using electrophoretic mobility shift assays, fluorescence-based melting kinetic experiments and computational modelling methods. Its mechanism of action was investigated using flow cytometry, Western blot analysis and fluorescent microscopy. In vitro anti-tumour activity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the in vivo activity utilized several human cancer models. KEY RESULTS Electrophoretic mobility shift assays demonstrated that PM01183 bound to DNA. Fluorescence-based thermal denaturation experiments showed that the most favourable DNA triplets providing a central guanine for covalent adduct formation are AGC, CGG, AGG and TGG. These binding preferences could be rationalized using molecular modelling. PM01183–DNA adducts in living cells give rise to double-strand breaks, triggering S-phase accumulation and apoptosis. The potent cytotoxic activity of PM01183 was ascertained in a 23-cell line panel with a mean GI50 value of 2.7 nM. In four murine xenograft models of human cancer, PM01183 inhibited tumour growth significantly with no weight loss of treated animals. CONCLUSIONS AND IMPLICATIONS PM01183 is shown to bind to selected DNA sequences and promoted apoptosis by inducing double-strand breaks at nanomolar concentrations. The potent anti-tumour activity of PM01183 in several murine models of human cancer supports its development as a novel anti-neoplastic agent. PMID:20977459

  16. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters

    PubMed Central

    Nancolas, Bethany; Guo, Lili; Zhou, Rong; Nath, Kavindra; Nelson, David S.; Leeper, Dennis B.; Blair, Ian A.; Glickson, Jerry D.; Halestrap, Andrew P.

    2016-01-01

    Lonidamine (LND) is an anti-tumour drug particularly effective at selectively sensitising tumours to chemotherapy, hyperthermia and radiotherapy, although its precise mode of action remains unclear. It has been reported to perturb the bioenergetics of cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggests it may also inhibit L-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Here we test these possibilities directly. We demonstrate that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki 2.5 μM) and cooperatively inhibits L-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K0.5 and Hill Coefficient values of 36–40 μM and 1.65–1.85. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50 ~7 μM) than other substrates including glutamate (IC50 ~20 μM). In isolated DB-1 melanoma cells 1–10 μM LND increased L-lactate output, consistent with MPC inhibition, but higher concentrations (150 μM) decreased L-lactate output while increasing intracellular [L-lactate] > five-fold, consistent with MCT inhibition. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated L-lactic acid efflux and glutamine/glutamate oxidation. Together these actions can account for published data on the selective tumour effects of LND on L-lactate, intracellular pH (pHi) and ATP levels that can be partially mimicked by the established MPC and MCT inhibitor α-cyano-4-hydroxycinnamate. PMID:26831515

  17. Zoledronic acid has differential anti-tumour activity in the pre-and post-menopausal bone microenvironment in vivo

    PubMed Central

    Ottewell, Penelope D; Wang, Ning; Brown, Hannah K; Reeves, Kimberly J; Fowles, C Anne; Croucher, Peter I; Eaton, Colby L; Holen, Ingunn

    2014-01-01

    Purpose Clinical trials in early breast cancer have suggested that benefits of adjuvant bone targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and post-menopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumour cells. Here we report a differential anti-tumour effect of zoledronic acid (ZOL) in these two settings. Experimental design 12-week old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumour cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and post-menopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100ug/kg ZOL weekly. Tumour growth was assessed by in vivo imaging and effects on bone by RT-PCR, microCT, histomorphometry and measurements of bone markers. Disseminated tumour cells were detected by two-photon microscopy. Results OVX increased bone resorption and induced growth of disseminated tumour cells in bone. Tumours were detected in 83% of animals following OVX (post-menopausal model) compared to 17% following sham operation (pre-menopausal model). OVX had no effect on tumours outside of bone. OVX-induced tumour growth was completely prevented by ZOL, despite the presence of disseminated tumour cells. ZOL did not affect tumour growth in bone in the sham-operated animals. ZOL increased bone volume in both groups. Conclusions This is the first demonstration that tumour growth is driven by osteoclast-mediated mechanisms in models that mimic post-but not pre-menopausal bone, providing a biological rationale for the differential anti-tumour effects of ZOL reported in these settings. PMID:24687923

  18. Molecular investigation of the direct anti-tumour effects of nonsteroidal anti-inflammatory drugs in a panel of canine cancer cell lines.

    PubMed

    Yoshitake, R; Saeki, K; Watanabe, M; Nakaoka, N; Ong, S M; Hanafusa, M; Choisunirachon, N; Fujita, N; Nishimura, R; Nakagawa, T

    2017-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested as effective adjunctive anti-tumour agents in human and veterinary medicine. However, the molecular mechanisms associated with their anti-tumour effects and correlations with the expression of cyclooxygenase (COX) and related molecules in tumours remain controversial. The objective of this study was to compare the expression profiles of COX and related molecules with NSAID sensitivity and to explore the molecular mechanisms of anti-tumour effects. The expression profiles of COXs, prostaglandins (PGs), PGD2 synthases, and PGE2 synthases were obtained, and their correlations with in vitro sensitivity to the NSAIDs piroxicam, carprofen, and robenacoxib were examined, using 26 canine cancer cell lines. Subsequently, microarray analysis was performed using one melanoma cell line to gain insight into mechanisms by which NSAIDs could exert cytotoxic effects. No strong correlation was observed between the cellular expression of COX and related molecules and sensitivity to NSAID treatment. Additionally, NSAIDs inhibited cell growth only at considerably higher concentrations than those required for functional COX inhibition. Microarray data demonstrated that five genes (SLC16A6, PER2, SLC9A8, HTR2B, and BRAF) were significantly upregulated and that four genes (LOC488305, H2AFJ, LOC476445, and ANKRD43) were significantly downregulated by NSAID exposure to the melanoma cell line. These results suggest that the direct in vitro anti-tumour effects of NSAIDs might be mediated by COX/PG-independent pathways. Novel candidate genes that could potentially be involved in the anti-tumour effects of NSAIDs were identified. Further validation and elucidation of their associated mechanisms will contribute to patient selection in clinical settings and the development of effective combination therapies.

  19. Dendritic cell-based immunotherapy induces transient clinical response in advanced rat fibrosarcoma - comparison with preventive anti-tumour vaccination.

    PubMed

    Kucera, A; Pýcha, K; Pajer, P; Spísek, R; Skába, R

    2009-01-01

    In this study we present the models of preventive and therapeutic vaccination of sarcoma-bearing rats with dendritic cells that present tumour antigens from killed tumour cells. We present the characteristics of dendritic cell-based vaccine and its capacity to induce anti-tumour immune response both in vitro and in vivo. We show that preventive vaccination efficiently prevents tumour growth. On the other hand, vaccination of rats with established tumours did not lead to eradication of the tumours. Despite the induction of a vigorous immune response after administration of dendritic cell-based vaccine and transient decrease in tumour progression, tumours eventually resumed their growth and animals vaccinated with dendritic cells succumbed to cancer. In both settings, preventive and therapeutic, dendritic cell-based vaccination induced a vigorous tumour-specific T-cell response. These results argue for the timing of cancer immunotherapy to the stages of low tumour load. Immunotherapy initiated at the stage of minimal residual disease, after reduction of tumour load by other modalities, will have much better chance to offer a clinical benefit to cancer patients than the immunotherapy at the stage of metastatic disease.

  20. Anti-tumour activity of photodynamic therapy in combination with mitomycin C in nude mice with human colon adenocarcinoma.

    PubMed Central

    Ma, L. W.; Moan, J.; Steen, H. B.; Iani, V.

    1995-01-01

    The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug, mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT alone, MMC alone or with both. It was found that the combined treatment produced a greater retardation in the growth of the WiDr tumour than monotherapy with MMC or PDT. The synergistic effect was especially prominent when PDT was used in combination with a low dose of MMC (1 mg kg-1), since treatment of 1 mg kg-1 MMC alone had no effect on the tumour. The anti-tumour activity of PDT was found to be increased with MMC of 5 mg kg-1. The response of normal skin on mice feet to PDT slightly greater when PDT was combined with 5 mg kg-1 MMC than when PDT was applied alone, while no detectable additional effect on skin photosensitivity was observed when PDT was combined with 1 mg kg-1 MMC. An enhanced uptake of Photofrin in tumours was found 12 h and 24 h after administration of MMC. The effect of MMC on the cell cycle distribution of cell dissociated directly from the tumours was studied. The results suggest that the increased susceptibility to photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase. PMID:7734319

  1. Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma

    NASA Astrophysics Data System (ADS)

    Dai, Jie; Wu, Shan; Kong, Yan; Chi, Zhihong; Si, Lu; Sheng, Xinan; Cui, Chuanliang; Fang, Jing; Zhang, Jue; Guo, Jun

    2017-01-01

    The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the pro-apoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma.

  2. Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma

    PubMed Central

    Dai, Jie; Wu, Shan; Kong, Yan; Chi, Zhihong; Si, Lu; Sheng, Xinan; Cui, Chuanliang; Fang, Jing; Zhang, Jue; Guo, Jun

    2017-01-01

    The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the pro-apoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma. PMID:28054548

  3. Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity

    PubMed Central

    Zamarin, Dmitriy; Holmgaard, Rikke B.; Ricca, Jacob; Plitt, Tamar; Palese, Peter; Sharma, Padmanee; Merghoub, Taha; Wolchok, Jedd D.; Allison, James P.

    2017-01-01

    Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL). In the bilateral flank tumour models, intratumoral administration of NDV-ICOSL results in enhanced infiltration with activated T cells in both virus-injected and distant tumours, and leads to effective rejection of both tumours when used in combination with systemic CTLA-4 blockade. These findings highlight that intratumoral immunomodulation with an oncolytic virus expressing a rationally selected ligand can be an effective strategy to drive systemic efficacy of immune checkpoint blockade. PMID:28194010

  4. Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion

    PubMed Central

    Jiang, G; Yang, C-S; Xu, D; Sun, C; Zheng, J-N; Lei, T-C; Liu, Y-Q

    2014-01-01

    Background: Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells. Methods: Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT–PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay. Results: Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice. Conclusions: This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma. PMID:24714752

  5. Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells

    PubMed Central

    Momeny, Majid; Moghaddaskho, Farima; Gortany, Narges K.; Yousefi, Hassan; Sabourinejad, Zahra; Zarrinrad, Ghazaleh; Mirshahvaladi, Shahab; Eyvani, Haniyeh; Barghi, Farinaz; Ahmadinia, Leila; Ghazi-Khansari, Mahmoud; Dehpour, Ahmad R.; Amanpour, Saeid; Tavangar, Seyyed M.; Dardaei, Leila; Emami, Amir H.; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H.

    2017-01-01

    Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM. PMID:28287096

  6. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity

    PubMed Central

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  7. Natural products from aquatic eukaryotic microorganisms for cancer therapy: Perspectives on anti-tumour properties of ciliate bioactive molecules.

    PubMed

    Catalani, Elisabetta; Proietti Serafini, Francesca; Zecchini, Silvia; Picchietti, Simona; Fausto, Anna Maria; Marcantoni, Enrico; Buonanno, Federico; Ortenzi, Claudio; Perrotta, Cristiana; Cervia, Davide

    2016-11-01

    Several modern drugs, including those for cancer therapy, have been isolated from natural sources, are based on natural products and its derivatives, or mime natural products. Some of them are in clinical use, others in clinical trials. The success of natural products in drug discovery is related to their biochemical characteristics and to the technologic methods used to study their feature. Natural compounds may acts as chemo-preventive agents and as factors that increase therapeutic efficacy of existing drugs, thus overcoming cancer cell drug resistance that is the main factor determining the failure in conventional chemotherapy. Water environment, because of its physical and chemical conditions, shows an extraordinary collection of natural biological substances with an extensive structural and functional diversity. The isolation of bioactive molecules has been reported from a great variety of aquatic organisms; however, the therapeutic application of molecules from eukaryotic microorganisms remains inadequately investigated and underexploited on a systematic basis. Herein we describe the biological activities in mammalian cells of selected substances isolated from ciliates, free-living protozoa common almost everywhere there is water, focusing on their anti-tumour actions and their possible therapeutic activity. In particular, we unveil the cellular and molecular machine mediating the effects of cell type-specific signalling protein pheromone Er-1 and secondary metabolites, i.e. euplotin C and climacostol, in cancer cells. To support the feasibility of climacostol-based approaches, we also present novel findings and report additional mechanisms of action using both in vitro and in vivo models of mouse melanomas, with the scope of highlighting new frontiers that can be explored also in a therapeutic perspective. The high skeletal chemical difference of ciliate compounds, their sustainability and availability, also through the use of new organic synthesis

  8. 2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity.

    PubMed Central

    Bradshaw, T. D.; Wrigley, S.; Shi, D. F.; Schultz, R. J.; Paull, K. D.; Stevens, M. F.

    1998-01-01

    2-(4-Aminophenyl)benzothiazole (CJM 126) elicits biphasic growth-inhibitory effects against a panel of oestrogen receptor-positive (ER+) and oestrogen receptor-negative (ER-) human mammary carcinoma cell lines in vitro, yielding IC50 values in the nM range. Substitutions adjacent to the amino group in the 2-phenyl ring with a halogen atom or methyl group enhance potency in sensitive breast lines (pM IC50 values). Transient biphasic dose responses were induced but rapidly eradicated after specific drug exposure periods. Two human prostate carcinoma cell lines were refractory to the growth-inhibitory properties of 2-(4-aminophenyl)benzothiazoles; IC50 values > 30 microM were obtained. Potency and selectivity were confirmed when compounds were examined in the National Cancer Institute's Developmental Therapeutics screen; the spectrum of activity included specific ovarian, renal, colon as well as breast carcinoma cell lines. Moreover, comparing 6-day and 48-h incubations, the exposure time-dependent nature of the biphasic response was corroborated. Differential perturbation of cell cycle distribution followed treatment of MCF-7 and MDA 468 cells with substituted 2-(4-aminophenyl)benzothiazoles. In MDA 468 populations only, accumulation of events in G2/M phase was observed. Two MCF-7 cell lines were established with acquired resistance to CJM 126 (IC50 values > 20 microM), which exhibit cross-resistance to substituted benzothiazoles, but equal sensitivity to tamoxifen and doxorubicin. Compared with standard anti-tumour agents evaluated in the National Cancer Institute in vitro cell panel, benzothiazoles revealed unique profiles of growth inhibition, suggesting a mode(s) of action shared with no known clinically active class of chemotherapeutic agents. PMID:9514053

  9. Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

    PubMed Central

    den Brok, M H M G M; Sutmuller, R P M; Nierkens, S; Bennink, E J; Frielink, C; Toonen, L W J; Boerman, O C; Figdor, C G; Ruers, T J M; Adema, G J

    2006-01-01

    Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-γ upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, ‘in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens. PMID:16953240

  10. Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway

    PubMed Central

    Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

    2013-01-01

    BACKGROUND AND PURPOSE We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. EXPERIMENTAL APPROACH Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. KEY RESULTS While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. CONCLUSIONS AND IMPLICATIONS Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of ‘fanconizing’ cancer cells in order to make them more sensitive to other anti-tumour drugs. PMID:23937566

  11. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study

    PubMed Central

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-01-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n=101) or placebo (n=103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n=41; placebo, n=47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. PMID:26743120

  12. Mesenchymal stromal cells (MSCs) and colorectal cancer: a troublesome twosome for the anti-tumour immune response?

    PubMed Central

    O'Malley, Grace; Heijltjes, Madelon; Houston, Aileen M.; Rani, Sweta; Ritter, Thomas; Egan, Laurence J.; Ryan, Aideen E.

    2016-01-01

    The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis. PMID:27542276

  13. Mesenchymal stromal cells (MSCs) and colorectal cancer: a troublesome twosome for the anti-tumour immune response?

    PubMed

    O'Malley, Grace; Heijltjes, Madelon; Houston, Aileen M; Rani, Sweta; Ritter, Thomas; Egan, Laurence J; Ryan, Aideen E

    2016-09-13

    The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis.

  14. Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis.

    PubMed

    Verwoerd, A; Hijdra, D; Vorselaars, A D M; Crommelin, H A; van Moorsel, C H M; Grutters, J C; Claessen, A M E

    2016-08-01

    Sarcoidosis is a systemic granulomatous disease of unknown aetiology that most commonly affects the lungs. Although elevated levels of regulatory T cells (Tregs ) have been reported, the extent to which they play a role in sarcoidosis pathogenesis remains unclear. Tumour necrosis factor (TNF) is thought to be one of the driving forces behind granuloma formation, illustrated by the efficacy of infliximab in severe sarcoidosis. Tregs express TNF receptor 2 (TNFR2) highly. Here, we examined the influence of infliximab therapy on Tregs and (soluble) TNFR2 levels in sarcoidosis, and correlated these with response to therapy. We observed that relative frequencies of Tregs were significantly higher in patients (n = 54) compared to healthy controls (n = 26; median 6·73 versus 4·36%; P < 0·001) and decreased following therapy (4·95; P < 0·001). Baseline TNFR2 expression on Tregs was increased significantly in patients versus controls (99·4 versus 96·2%; P = 0·031), and also in responders to therapy versus non-responders (99·6 versus 97·3%; P = 0·012). Furthermore, baseline soluble TNFR2 (sTNFR2) was higher in responders than in non-responders (mean 174 versus 107 pg/ml; P = 0·015). After treatment, responders showed a significant reduction in sTNFR2 levels in peripheral blood (-44·7 pg/ml; P < 0·001), in contrast to non-responders (+3·59 pg/ml). Our results demonstrated that Treg frequencies and TNFR2 expression on Tregs are increased in sarcoidosis, followed by a decline during infliximab therapy, suggesting a pathophysiological role of this T cell subset. Interestingly, sTNFR2 levels at baseline differed significantly between responders and non-responders, making it a potential marker in predicting which patients might benefit from infliximab.

  15. BALANCE

    DOEpatents

    Carmichael, H.

    1953-01-01

    A torsional-type analytical balance designed to arrive at its equilibrium point more quickly than previous balances is described. In order to prevent external heat sources creating air currents inside the balance casing that would reiard the attainment of equilibrium conditions, a relatively thick casing shaped as an inverted U is placed over the load support arms and the balance beam. This casing is of a metal of good thernnal conductivity characteristics, such as copper or aluminum, in order that heat applied to one portion of the balance is quickly conducted to all other sensitive areas, thus effectively preventing the fornnation of air currents caused by unequal heating of the balance.

  16. Multi-scale modeling predicts a balance of tumor necrosis factor-α and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection.

    PubMed

    Cilfone, Nicholas A; Perry, Cory R; Kirschner, Denise E; Linderman, Jennifer J

    2013-01-01

    Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) are key anti- and pro-inflammatory mediators elicited during the host immune response to Mycobacterium tuberculosis (Mtb). Understanding the opposing effects of these mediators is difficult due to the complexity of processes acting across different spatial (molecular, cellular, and tissue) and temporal (seconds to years) scales. We take an in silico approach and use multi-scale agent based modeling of the immune response to Mtb, including molecular scale details for both TNF-α and IL-10. Our model predicts that IL-10 is necessary to modulate macrophage activation levels and to prevent host-induced tissue damage in a granuloma, an aggregate of cells that forms in response to Mtb. We show that TNF-α and IL-10 parameters related to synthesis, signaling, and spatial distribution processes control concentrations of TNF-α and IL-10 in a granuloma and determine infection outcome in the long-term. We devise an overall measure of granuloma function based on three metrics - total bacterial load, macrophage activation levels, and apoptosis of resting macrophages - and use this metric to demonstrate a balance of TNF-α and IL-10 concentrations is essential to Mtb infection control, within a single granuloma, with minimal host-induced tissue damage. Our findings suggest that a balance of TNF-α and IL-10 defines a granuloma environment that may be beneficial for both host and pathogen, but perturbing the balance could be used as a novel therapeutic strategy to modulate infection outcomes.

  17. Fat necrosis.

    PubMed

    Canteli, B; Saez, F; de los Ríos, A; Alvarez, C

    1996-04-01

    We report the MR appearance of a case of subcutaneous fat necrosis, which is a previously unreported etiology for knee mass. The role of MR imaging in differentiating fat necrosis from other causes of soft tissue masses is discussed. We conclude that MR characteristics of subcutaneous fat necrosis are typical and allow its differentiation from other types of soft tissue lesions.

  18. Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity.

    PubMed Central

    Vizler, C.; Rosato, A.; Calderazzo, F.; Quintieri, L.; Fruscella, P.; Wainstok de Calmanovici, R.; Mantovani, A.; Vecchi, A.; Zanovello, P.; Collavo, D.

    1998-01-01

    In syngeneic mice, the H5V polyoma middle-T oncogene-transformed endothelioma cell line induces Kaposi's sarcoma-like cavernous haemangiomas that regress transiently, probably because of an anti-tumour immune response, but eventually grow progressively and kill the host. To evaluate the generation of tumour-specific cytotoxic T lymphocytes (CTLs), spleen cells of tumour-bearing mice were restimulated with irradiated H5V cells in mixed leucocyte-tumour cell cultures. Tumour-specific CTLs were demonstrable only when low numbers of H5V stimulator cells were used (<1 H5V cell per 50 splenocytes). We found that H5V cells secrete immunosuppressive mediators because CTL generation was blocked when H5V cells culture supernatants were added to allogeneic mixed leucocyte cultures. As numerous tumour-derived immunosuppressive mediators may interfere with interleukin 12 (IL-12) production, we tested whether IL-12 treatment of the tumour-bearing mice would augment their immune response and thus suppress tumour growth. Indeed, IL-12 inhibited tumour growth and prevented mortality, but did not increase anti-H5V CTL generation either in vitro or in vivo. Moreover, the anti-tumour activity in IL-12-treated mice was abrogated by anti-interferon (IFN)-gamma monoclonal antibody (MAb) co-administration. These results strongly suggest that the anti-tumour effect of IL-12 is principally mediated by IFN-gamma release that in turn blocks H5V cell proliferation and induces the release of factors that suppress angiogenesis. PMID:9484826

  19. Targeting colon cancer cell NF-κB promotes an anti-tumour M1-like macrophage phenotype and inhibits peritoneal metastasis.

    PubMed

    Ryan, A E; Colleran, A; O'Gorman, A; O'Flynn, L; Pindjacova, J; Lohan, P; O'Malley, G; Nosov, M; Mureau, C; Egan, L J

    2015-03-19

    In a model of peritoneal metastasis in immune-competent mice, we show that nuclear factor (NF)-κB inhibition in CT26 colon cancer cells prevents metastasis. NF-κB inhibition, by stable overexpression of IκB-α super-repressor, induced differential polarization of co-cultured macrophages to an M1-like anti-tumour phenotype in vitro. NF-κB-deficient cancer cell-conditioned media (CT26/IκB-α SR) induced interleukin (IL)-12 and nitric oxide (NO) synthase (inducible NO synthase (iNOS)) expression in macrophages. Control cell (CT26/EV) conditioned media induced high levels of IL-10 and arginase in macrophages. In vivo, this effect translated to reduction in metastasis in mice injected with CT26/ IκB-α SR cells and was positively associated with increased CD8(+)CD44(+)CD62L(-) and CD4(+)CD44(+)CD62L(-) effector T cells. Furthermore, inhibition of NF-κB activity induced high levels of NO in infiltrating immune cells and decreases in matrix metalloproteinase-9 expression, simultaneous with increases in tissue inhibitor of metalloproteinases 1 and 2 within tumours. CT26/IκB-α SR tumours displayed increased pro-inflammatory gene expression, low levels of angiogenesis and extensive intratumoral apoptosis, consistent with the presence of an anti-tumour macrophage phenotype. Macrophage depletion reduced tumour size in CT26/EV-injected animals and increased tumour size in CT26/IκB-α SR cells compared with untreated tumours. Our data demonstrate, for the first time, that an important implication of targeting tumour cell NF-κB is skewing of macrophage polarization to an anti-tumour phenotype. This knowledge offers novel therapeutic opportunities for anticancer treatment.

  20. Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis.

    PubMed

    Zheng, Yu; Zhou, Hong; Brennan, Karen; Blair, Julie M; Modzelewski, James R K; Seibel, Markus J; Dunstan, Colin R

    2007-02-01

    Inhibition of bone resorption either by bisphosphonate (BP) treatment or by blocking RANKL signalling with osteoprotegerin (OPG) has been shown to reduce tumour burden in bone and inhibit bone destruction in murine xenograft models of breast cancer. However, whether the anti-tumour effect of OPG or BP in bone is mediated by inhibition of bone resorption or by direct effects on tumour cells is uncertain. The current study is designed to investigate anti-tumour effects of OPG and ibandronate (IBN), dosed alone or in combination, on tumour growth to determine if there is experimental support for combination treatments and to provide evidence for the presence of direct anti-tumour effects. To this aim, 10 microl (5 x 10(6) cells/ml) of the bone-seeking MDA-MB-231 (Tx-SA) cell line was injected intra-tibially into nude mice. After 10 days, when the tumours were evident radiologically, mice were treated with vehicle, OPG (1 mg/kg/day), ibandronate (IBN) (160 microg/kg/day) or IBN and OPG at the same doses (IBN+OPG) for a week, and the effects of each treatment on lytic lesions, tumour cell growth, cell apoptosis and proliferation were measured by radiography, immunohistochemistry and histomorphometry. Compared to vehicle controls, in vivo treatment with OPG, IBN, or IBN+OPG, each prevented the expansion of osteolytic bone lesions (increase in lytic lesion area day 10 to day 17: OPG -3.2%, IBN 6.6%, IBN+OPG 3.6%, Vehicle 232.5%; p<0.01). Treatment with OPG, IBN or IBN+OPG each produced similar reductions in tumour area relative to vehicle-treated mice (OPG 52%, IBN 54%, IBNp and OPG 48%, p<0.01 vs. vehicle) OPG and IBN alone and in combination each produced a similar increase in cancer cell apoptosis (OPG 330%, IBN 342%, IBN and OPG 347%, p<0.01 vs. vehicle) and a decrease in cancer cell proliferation (OPG 59%, IBN 62%, IBN and OPG 58%, p<0.05 vs. vehicle). Our findings indicate that (i) combined treatment with OPG and a bisphosphonate is not significantly more effective

  1. Activated microglia provide a neuroprotective role by balancing glial cell-line derived neurotrophic factor and tumor necrosis factor-α secretion after subacute cerebral ischemia.

    PubMed

    Wang, Jianping; Yang, Zhitang; Liu, Cong; Zhao, Yuanzheng; Chen, Yibing

    2013-01-01

    Microglia are the major immune cells in the central nervous system and play a key role in brain injury pathology. However, the role of activated microglia after subacute cerebral ischemia (SCI) remains unknown. To address this issue, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and treated pMCAO rats with N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (an inhibitor of microglial activation), or with vehicle alone. Finally, we determined the differences between the PJ34-and vehicle-treated rats with respect to neurological deficits, infarct volume, neuronal loss and the expression of CD11b (a marker of microglial activation), glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-α (TNF-α) at 1, 3 and 7 days after treatment. We found that the PJ34-treated rats had more severe neurological deficits and a larger infarct volume and exhibited a decreased CD11b expression, more neuronal loss, decreased expression of GDNF mRNA and protein but increased expression of TNF-α mRNA and protein compared with the vehicle-treated rats at 3 and 7 days after treatment. These results indicate that activated microglia provide a neuroprotective role through balancing GDNF and TNF-α expression following SCI.

  2. Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.

    PubMed

    Ito, Hiroyasu; Ando, Tatsuya; Arioka, Yuko; Saito, Kuniaki; Seishima, Mitsuru

    2015-04-01

    Toll-like receptor (TLR) agonists have been shown to have anti-tumour activity in basic research and clinical studies. However, TLR agonist monotherapy does not sufficiently eliminate tumours. Activation of the innate immune response by TLR agonists is effective at driving adaptive immunity via interleukin-12 (IL-12) or IL-1, but is counteracted by the simultaneous induction of immunosuppressive cytokines and other molecules, including IL-10, transforming growth factor-β, and indoleamine 2,3-dioxygenase (IDO). In the present study, we evaluated the anti-cancer effect of the TLR7 agonist, imiquimod (IMQ), in the absence of IDO activity. The administration of IMQ in IDO knockout (KO) mice inoculated with tumour cells significantly suppressed tumour progression compared with that in wild-type (WT) mice, and improved the survival rate. Moreover, injection with IMQ enhanced the tumour antigen-specific T helper type 1 response in IDO-KO mice with tumours. Combination therapy with IMQ and an IDO inhibitor also significantly inhibited tumour growth. Our results indicated that the enhancement of IDO expression with TLR agonists in cancer treatment might impair host anti-tumour immunity while the inhibition of IDO could enhance the therapeutic efficacy of TLR agonists via the increase of T helper type 1 immune response.

  3. Smac is another pathway in the anti-tumour activity of Trichosanthin and reverses Trichosanthin resistance in CaSki cervical cancer cells.

    PubMed

    Cui, Lei; Song, Jian; Wu, Liting; Huang, Liming; Wang, Yanlin; Huang, Yingdi; Yu, Han; Huang, Yiling; You, C C; Ye, Jiayou

    2015-02-01

    Trichosanthin (TCS), or Tin Hua Fen, is a renowned traditional Chinese medicine and is still used in Chinese clinics for midterm abortion and the treatment of choriocarcinoma. Many studies have demonstrated that TCS has anti-tumour action as a type I ribosome-inactivating protein. We hypothesized that there is another pathway of the anti-tumour activity of TCS. cDNA array analysis was applied to profile changes in gene expression of human CaSki in response to TCS stimulation. Smac, a mitochondrial protein, was identified as the highly upregulated protein in response to TCS treatment. The mRNA and protein levels of Smac were determined by real-time RT-PCR and Western blotting respectively. We analysed the methylation status of Smac using methylation-specific PCR (MSP) and indicates that TCS promotes Smac demethylation and increases its expression in cervical CaSki cells. Tumour cells develop resistance to TCS during prolonged treatment, as with other classic chemotherapeutic agents. Smac expression was downregulated and Twist was upregulated in TCS-resistant cells. These results indicate that TCS has demethylating activity and that Smac is involved in both TCS response and TCS resistance.

  4. Balancing

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    At many occasions we are asked to achieve a “balance” in our lives: when it comes, for example, to work and food. Balancing is crucial in game design as well as many have pointed out. In games with a meaningful purpose, however, balancing is remarkably different. It involves the balancing of three different worlds, the worlds of Reality, Meaning, and Play. From the experience of designing Levee Patroller, I observed that different types of tensions can come into existence that require balancing. It is possible to conceive of within-worlds dilemmas, between-worlds dilemmas, and trilemmas. The first, the within-world dilemmas, only take place within one of the worlds. We can think, for example, of a user interface problem which just relates to the world of Play. The second, the between-worlds dilemmas, have to do with a tension in which two worlds are predominantly involved. Choosing between a cartoon or a realistic style concerns, for instance, a tension between Reality and Play. Finally, the trilemmas are those in which all three worlds play an important role. For each of the types of tensions, I will give in this level a concrete example from the development of Levee Patroller. Although these examples come from just one game, I think the examples can be exemplary for other game development projects as they may represent stereotypical tensions. Therefore, to achieve harmony in any of these forthcoming games, it is worthwhile to study the struggles we had to deal with.

  5. Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis.

    PubMed Central

    Liew, F Y; Parkinson, C; Millott, S; Severn, A; Carrier, M

    1990-01-01

    Genetically resistant CBA mice developed significantly larger lesions to Leishmania major infection when they were injected with rabbit anti-tumour necrosis factor (TNF)-specific antibodies compared to control mice injected with normal rabbit immunoglobulin. BALB/c mice recovered from a previous infection following prophylactic sublethal irradiation also developed exacerbated lesions when treated with the anti-TNF antibody. Injection of TNF into the lesion of infected CBA mice significantly reduced the lesion development. Furthermore, TNF activates macrophages to kill Leishmania in vitro. These data demonstrate that TNF plays an important role in mediating host-protection against cutaneous leishmaniasis. PMID:2335376

  6. Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

    PubMed

    García-Rivera, Dagmar; Delgado, René; Bougarne, Nadia; Haegeman, Guy; Berghe, Wim Vanden

    2011-06-01

    Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network.

  7. Pro- and anti-tumour effects of B cells and antibodies in cancer: a comparison of clinical studies and preclinical models.

    PubMed

    Guy, Thomas V; Terry, Alexandra M; Bolton, Holly A; Hancock, David G; Shklovskaya, Elena; Fazekas de St. Groth, Barbara

    2016-08-01

    The primary immune role of B cells is to produce antibodies, but they can also influence T cell function via antigen presentation and, in some contexts, immune regulation. Whether their roles in tumour immunity are similar to those in other chronic immune responses such as autoimmunity and chronic infection, where both pro- and anti-inflammatory roles have been described, remains controversial. Many studies have aimed to define the role of B cells in antitumor immune responses, but despite this considerable body of work, it is not yet possible to predict how they will affect immunity to any given tumour. In many human cancers, the presence of tumour-infiltrating B cells and tumour-reactive antibodies correlates with extended patient survival, and this clinical observation is supported by data from some animal models. On the other hand, T cell responses can be adversely affected by B cell production of immunoregulatory cytokines, a phenomenon that has been demonstrated in humans and in animal models. The isotype and concentration of tumour-reactive antibodies may also influence tumour progression. Recruitment of B cells into tumours may directly reflect the subtype and strength of the anti-tumour T cell response. As the response becomes chronic, B cells may attenuate T cell responses in an attempt to decrease host damage, similar to their described role in chronic infection and autoimmunity. Understanding how B cell responses in cancer are related to the effectiveness of the overall anti-tumour response is likely to aid in the development of new therapeutic interventions against cancer.

  8. Avascular Necrosis

    MedlinePlus

    ... blood flow and leading to avascular necrosis. Excessive alcohol use. Consuming several alcoholic drinks a day for several years also can cause fatty deposits to form in your blood vessels. Bisphosphonate ...

  9. A randomised controlled phase II trial of pre-operative celecoxib treatment reveals anti-tumour transcriptional response in primary breast cancer

    PubMed Central

    2013-01-01

    Introduction Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. In transgenic breast cancer models, over-expression of COX-2 leads to tumour formation while COX-2 inhibition exerts anti-tumour effects in breast cancer cell lines. To further determine the effect of COX-2 inhibition in primary breast cancer, we aimed to identify transcriptional changes in breast cancer tissues of patients treated with the selective COX-2 inhibitor celecoxib. Methods In a single-centre double-blind phase II study, thirty-seven breast cancer patients were randomised to receive either pre-operative celecoxib (400 mg) twice daily for two to three weeks (n = 22) or a placebo according to the same schedule (n = 15). Gene expression in fresh-frozen pre-surgical biopsies (before treatment) and surgical excision specimens (after treatment) was profiled by using Affymetrix arrays. Differentially expressed genes and altered pathways were bioinformatically identified. Expression of selected genes was validated by quantitative PCR (qPCR). Immunohistochemical protein expression analyses of the proliferation marker Ki-67, the apoptosis marker cleaved caspase-3 and the neo-angiogenesis marker CD34 served to evaluate biological response. Results We identified 972 and 586 significantly up- and down-regulated genes, respectively, in celecoxib-treated specimens. Significant expression changes in six out of eight genes could be validated by qPCR. Pathway analyses revealed over-representation of deregulated genes in the networks of proliferation, cell cycle, extracellular matrix biology, and inflammatory immune response. The Ki-67 mean change relative to baseline was -29.1% (P = 0.019) and -8.2% (P = 0.384) in the treatment and control arm, respectively. Between treatment groups, the change in Ki-67 was statistically significant (P = 0.029). Cleaved caspase-3 and CD34 expression were not significantly different between the celecoxib-treated and placebo-treated groups

  10. The novel atypical retinoid ST5589 down-regulates Aurora Kinase A and has anti-tumour activity in lymphoma pre-clinical models.

    PubMed

    Bernasconi, Elena; Gaudio, Eugenio; Kwee, Ivo; Rinaldi, Andrea; Cascione, Luciano; Tarantelli, Chiara; Mensah, Afua Adjeiwaa; Stathis, Anastasios; Zucca, Emanuele; Vesci, Loredana; Giannini, Giuseppe; Bertoni, Francesco

    2015-11-01

    Despite the marked improvements in the treatment of lymphomas, there is still a need for new therapeutic agents. Synthetic retinoids represent a class of compounds with anti-cancer activity. Here, we report the preclinical activity of a new member of this class, the ST1926-derivative ST5589, in lymphomas. ST5589 presented a dose-dependent anti-proliferative activity in almost all of the 25 lymphoma cell lines analysed, with a median 50% inhibitory concentration of 433 nM. Apoptosis was observed in 8/11 cell lines. ST5589 induced changes in the gene expression profiles of the cell lines, including the down-regulation of Aurora Kinase A (AURKA). Specific gene expression signatures were associated with a higher sensitivity to the compound and combination of ST5589 with carfilzomib revealed the importance of proteasome activity in mediating the anti-tumour activity of ST5589. In conclusion, we have identified a new mechanism of action of atypical retinoids as anti-cancer compounds, and the encouraging results obtained with the new ST1926-derivative ST5589 provide the basis for further developments of the compound.

  11. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.

    PubMed

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita; Azogui, Orly

    2016-01-01

    Natural regulatory T (Treg) cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs) subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy.

  12. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells

    PubMed Central

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita

    2016-01-01

    Natural regulatory T (Treg) cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs) subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy. PMID:27341421

  13. Dinuclear ruthenium complexes display loop isomer selectivity to c-MYC DNA G-quadriplex and exhibit anti-tumour activity.

    PubMed

    Zheng, Chuping; Liu, Yanan; Liu, Ying; Qin, Xiuying; Zhou, Yanhui; Liu, Jie

    2016-03-01

    G-quadruplex DNA, especially the cellular-myelocytomatosis viral oncogene (c-MYC) is closely associated with cell-cycle regulation, proliferation of tumour cells. In this work, the interaction between the c-MYC and two dinuclear Ru(II) complexes [(bpy)2Ru(bpibp)Ru(bpy)2](ClO4)4 (compound 1) and [(phen)2Ru(bpibp)Ru(phen)2](ClO4)4 (compound 2) have been studied. The data from UV-Visible, PCR-stop and Fluorescence resonance energy transfer (FRET) showed that two complexes can stabilize the structure of G-quadruplex in the c-MYC promoter and targeting the G-quadruplex loop isomers. Interestingly, the complex 2 has a greater effect on the 1:2:1 and 2:1:1 loop isomers while the 1 prefers to the 1:2:1 isomers. The mechanism studies revealed that complexes can induce apoptosis in HepG2 cells by generating ROS metabolites, triggering mitochondrial membrane potential loss and down-regulation of P-Akt (Akt also known as protein kinase B), P-p44/42 MAP kinase protein (P-p44/42), and c-MYC. Taken together, these results suggested that the two dinuclear complexes may both be candidates as anti-tumour agents as they may reduce the c-MYC gene expression. {bpibp: 4, 4'-bis (1, 10-phenanthroline-[5, 6-d] imidazole-2-yl)-biphenyl, bpy: 2,2-bipyridine, phen: 1,10-phenanthroline}.

  14. Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up.

    PubMed Central

    Bontenbal, M.; Foekens, J. A.; Lamberts, S. W.; de Jong, F. H.; van Putten, W. L.; Braun, H. J.; Burghouts, J. T.; van der Linden, G. H.; Klijn, J. G.

    1998-01-01

    Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti

  15. Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming

    PubMed Central

    2011-01-01

    Background As well as inducing direct oncolysis, reovirus treatment of melanoma is associated with activation of innate and adaptive anti-tumour immune responses. Results Here we characterise the effects of conditioned media from reovirus-infected, dying human melanoma cells (reoTCM), in the absence of live virus, to address the immune bystander potential of reovirus therapy. In addition to RANTES, IL-8, MIP-1α and MIP-1β, reovirus-infected melanoma cells secreted eotaxin, IP-10 and the type 1 interferon IFN-β. To address the mechanisms responsible for the inflammatory composition of reoTCM, we show that IL-8 and IFN-β secretion by reovirus-infected melanoma cells was associated with activation of NF-κB and decreased by pre-treatment with small molecule inhibitors of NF-κB and PKR; specific siRNA-mediated knockdown further confirmed a role for PKR. This pro-inflammatory milieu induced a chemotactic response in isolated natural killer (NK) cells, dendritic cells (DC) and anti-melanoma cytotoxic T cells (CTL). Following culture in reoTCM, NK cells upregulated CD69 expression and acquired greater lytic potential against tumour targets. Furthermore, melanoma cell-loaded DC cultured in reoTCM were more effective at priming adaptive anti-tumour immunity. Conclusions These data demonstrate that the PKR- and NF-κB-dependent induction of pro-inflammatory molecules that accompanies reovirus-mediated killing can recruit and activate innate and adaptive effector cells, thus potentially altering the tumour microenvironment to support bystander immune-mediated therapy as well as direct viral oncolysis. PMID:21338484

  16. Anti-interleukin-10R1 monoclonal antibody in combination with bacillus Calmette–Guérin is protective against bladder cancer metastasis in a murine orthotopic tumour model and demonstrates systemic specific anti-tumour immunity

    PubMed Central

    Newton, M R; Askeland, E J; Andresen, E D; Chehval, V A; Wang, X; Askeland, R W; O'Donnell, M A; Luo, Y

    2014-01-01

    Effective treatment of bladder cancer with bacillus Calmette–Guérin (BCG) depends on the induction of a T helper type (Th) 1 immune response. Interleukin (IL)-10 down-regulates the Th1 response and is associated with BCG failure. In this study, we investigated whether blocking IL-10 signalling could enhance the BCG-induced Th1 response and anti-tumour immunity in a murine orthotopic tumour model. Treatment with BCG and anti-IL-10 receptor 1 monoclonal antibody (anti-IL-10R1 mAb) increased the interferon (IFN)-γ to IL-10 ratio in both splenocyte cultures and urine. Mice bearing luciferase-expressing MB49 (MB49-Luc) tumours were treated and followed for tumour growth by bioluminescent imaging, bladder weight and histology. Mice treated with phosphate-buffered saline (PBS) (group 1), BCG plus control immunoglobulin (Ig)G1 (group 2) or BCG plus anti-IL-10R1 mAb (group 3) showed 0, 6 and 22% tumour regression, respectively. The mean bladder weight of group 3 mice was substantially lower than those of groups 1 and 2 mice. Remarkably, 36% of group 1 and 53% of group 2 mice but no group 3 mice developed lung metastasis (P = 0·02). To investigate the mechanisms underlying the effect of combination therapy, splenocytes were stimulated with S12 peptide (serine mutation at codon 12 of the K-ras oncogene) known to be expressed in MB49-Luc cells. Induction of ras mutation-specific IFN-γ and cytotoxicity was observed in mice treated with combination therapy. These observations indicate that BCG, in combination with anti-IL-10R1 mAb, induces enhanced anti-tumour immunity that is protective against lung metastasis. Anti-IL-10R1 mAb demonstrates systemic effects and may prove useful in clinical practice for treating bladder cancer in high-risk patients. PMID:24593764

  17. Anti-interleukin-10R1 monoclonal antibody in combination with bacillus Calmette--Guérin is protective against bladder cancer metastasis in a murine orthotopic tumour model and demonstrates systemic specific anti-tumour immunity.

    PubMed

    Newton, M R; Askeland, E J; Andresen, E D; Chehval, V A; Wang, X; Askeland, R W; O'Donnell, M A; Luo, Y

    2014-07-01

    Effective treatment of bladder cancer with bacillus Calmette-Guérin (BCG) depends on the induction of a T helper type (Th) 1 immune response. Interleukin (IL)-10 down-regulates the Th1 response and is associated with BCG failure. In this study, we investigated whether blocking IL-10 signalling could enhance the BCG-induced Th1 response and anti-tumour immunity in a murine orthotopic tumour model. Treatment with BCG and anti-IL-10 receptor 1 monoclonal antibody (anti-IL-10R1 mAb) increased the interferon (IFN)-γ to IL-10 ratio in both splenocyte cultures and urine. Mice bearing luciferase-expressing MB49 (MB49-Luc) tumours were treated and followed for tumour growth by bioluminescent imaging, bladder weight and histology. Mice treated with phosphate-buffered saline (PBS) (group 1), BCG plus control immunoglobulin (Ig)G1 (group 2) or BCG plus anti-IL-10R1 mAb (group 3) showed 0, 6 and 22% tumour regression, respectively. The mean bladder weight of group 3 mice was substantially lower than those of groups 1 and 2 mice. Remarkably, 36% of group 1 and 53% of group 2 mice but no group 3 mice developed lung metastasis (P = 0·02). To investigate the mechanisms underlying the effect of combination therapy, splenocytes were stimulated with S12 peptide (serine mutation at codon 12 of the K-ras oncogene) known to be expressed in MB49-Luc cells. Induction of ras mutation-specific IFN-γ and cytotoxicity was observed in mice treated with combination therapy. These observations indicate that BCG, in combination with anti-IL-10R1 mAb, induces enhanced anti-tumour immunity that is protective against lung metastasis. Anti-IL-10R1 mAb demonstrates systemic effects and may prove useful in clinical practice for treating bladder cancer in high-risk patients.

  18. Photodynamic therapy with recombinant adenovirus AdmIL-12 enhances anti-tumour therapy efficacy in human papillomavirus 16 (E6/E7) infected tumour model

    PubMed Central

    Park, Eun Kyung; Bae, Su-Mi; Kwak, Sun-Young; Lee, Sung Jong; Kim, Yong-Wook; Han, Chan-Hee; Cho, Hyun-Jung; Kim, Kyung Tae; Kim, Young-Jae; Kim, Hyun-Jung; Ahn, Woong Shick

    2008-01-01

    Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. Here we investigated the utility of adenoviral delivery of interleukin-12 (AdmIL-12) as an adjuvant for PDT in mouse tumour challenge model. PDT was performed by irradiating Radachlorin in C57BL/6 mice transplanted with TC-1 cells. PDT plus AdmIL-12 treatment for tumour suppression as well as specific immune responses were evaluated with the following tests: in vitro and in vivo tumour growth inhibition, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) assay, and cytotoxic T lymphocyte (CTL) assay. Direct intratumoral injection of AdmIL-12 resulted in a significant suppression of tumour growth compared to the control group. Treatment of PDT along with AdmIL-12 further enhanced antitumour effects significantly higher than either AdmIL-12 or PDT alone. This combined treatment resulted in complete regression of 9-mm sized tumour in every animal. We also evaluated immune responses induced by these treatments. Combined treatment significantly increased the production level of IFN-γ and TNF-α compared with that by AdmIL-12 or PDT alone. PDT plus AdmIL-12 enhanced antitumour immunity through increased expansion of the CTL subset mediated by CD8+ T cells. Taken together, these results indicate that the high anti-cancer activity of PDT with AdmIL-12 is a powerful tool against cancer therapy and is a promising subject for further investigation. PMID:18397271

  19. Renal papillary necrosis

    MedlinePlus

    ... ureters. Causes Renal papillary necrosis often occurs with analgesic nephropathy . This is damage to one or both ... Treatment depends on the cause. For example, if analgesic nephropathy is the cause, your doctor will recommend ...

  20. Tumor necrosis factor.

    PubMed

    Chu, Wen-Ming

    2013-01-28

    Tumor necrosis factor (TNF) is a critical cytokine, which contributes to both physiological and pathological processes. This mini-review will briefly touch the history of TNF discovery, its family members and its biological and pathological functions. Then, it will focus on new findings on the molecular mechanisms of how TNF triggers activation of the NF-κB and AP-1 pathways, which are critical for expression of pro-inflammatory cytokines, as well as the MLKL cascade, which is critical for the generation of ROS in response to TNF. Finally, this review will briefly summarize recent advances in understanding TNF-induced cell survival, apoptosis and necrosis (also called necroptosis). Understanding new findings and emerging concepts will impact future research on the molecular mechanisms of TNF signaling in immune disorders and cancer-related inflammation.

  1. Necrosis in yeast.

    PubMed

    Eisenberg, Tobias; Carmona-Gutierrez, Didac; Büttner, Sabrina; Tavernarakis, Nektarios; Madeo, Frank

    2010-03-01

    Necrosis was long regarded as an accidental cell death process resulting from overwhelming cellular injury such as chemical or physical disruption of the plasma membrane. Such a definition, however, proved to be inapplicable to many necrotic scenarios. The discovery that genetic manipulation of several proteins either protected or enhanced necrotic cell death argued in favor of a regulated and hence programmed process, as it is the case for apoptosis. For more than a decade, yeast has served as a model for apoptosis research; recently, evidence accumulated that it also harbors a necrotic program. Here, we summarize the current knowledge about factors that control necrotic cell death in yeast. Mitochondria, aging and a low pH are positive regulators of this process while cellular polyamines (e.g. spermidine) and endonuclease G as well as homeostatic organelles like the vacuole or peroxisomes are potent inhibitors of necrosis. Physiological necrosis may stimulate intercellular signaling via the release of necrotic factors that promote viability of healthy cells and, thus, assure survival of the clone. Together, the data obtained in yeast argue for the existence of a necrotic program, which controls longevity and whose physiological function may thus be aging.

  2. Arthroscopic assessment of avascular necrosis.

    PubMed

    Bain, Gregory I; Durrant, Adam W

    2011-08-01

    Avascular necrosis of the lunate is a process that is not well understood. The cause is uncertain, but a common theory persists that it is caused by disruption of the vascular supply to the lunate. This article discusses an approach to assessment that respects the articular cartilage and places at the front of the decision-making process the pathoanatomic components of the articular cartilage. It primarily respects the articular cartilage in the patient with avascular necrosis. This approach was developed for avascular necrosis of the lunate, but in principle applies to other joints with avascular necrosis as well.

  3. Balance Problems

    MedlinePlus

    ... version of this page please turn Javascript on. Balance Problems About Balance Problems Have you ever felt dizzy, lightheaded, or ... dizziness problem during the past year. Why Good Balance is Important Having good balance means being able ...

  4. Balance Problems

    MedlinePlus

    ... often, it could be a sign of a balance problem. Balance problems can make you feel unsteady or as ... fall-related injuries, such as hip fracture. Some balance problems are due to problems in the inner ...

  5. Spontaneous Necrosis of Choroidal Melanoma

    PubMed Central

    Thareja, Shalini; Rashid, Alia; Grossniklaus, Hans E.

    2014-01-01

    Background/Aims The purpose of this study was to examine the clinical presentations and pathological features of spontaneously necrotic choroidal melanomas. Methods The clinical and histological features of patients who underwent enucleation for uveal melanoma from 1989 to 2012 at Emory University and were found to have spontaneously necrotic choroidal melanomas were retrospectively analyzed. Results A total of 6 cases were identified. All cases had 90-100% tumor necrosis and also exhibited marked ischemic necrosis of the iris and ciliary body; 5 of 6 cases exhibited marked ischemic necrosis of the retina. The tumor consisted of melanoma ghost cells often surrounded by a zone of pigmented macrophages. Thrombi were not found in any of the cases. All of the tumors in our cases were centered around the equatorial choroid and 2 extended into the ciliary body. One of the cases exhibited a wedge-shaped infarct in a lateral aspect of the tumor. In most of the cases, microscopic areas of intact tumor cells were present in the peripheries of the tumors. Conclusions Spontaneous necrosis may occur in uveal melanoma. We believe that this occurs secondary to tumor hypoxia in the center of the tumor, followed by secondary inflammation, generalized ischemia and finally complete tumor necrosis. PMID:27175363

  6. Therapy for acute retinal necrosis.

    PubMed

    Kawaguchi, Tatsushi; Spencer, Doran B; Mochizuki, Manabu

    2008-01-01

    Acute retinal necrosis is a progressive necrotizing retinopathy caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The mainstay of its treatment is antiviral therapy against these pathogenic organisms, such as intravenous acyclovir or oral valacyclovir. Systemic and topical corticosteroids together with antiviral therapy are used as an anti-inflammatory treatment to minimize damages to the optic nerve and retinal blood vessels. Because the majority of severe cases of the disease show occlusive retinal vasculitis, a low dosage of aspirin is used as anti-thrombotic treatment. Vitreo-retinal surgery is useful to repair rhegmatogenous retinal detachment, one of the main late-stage complications. Moreover, recent articles have reported some encouraging results of prophylactic vitrectomy before rhegmatogenous retinal detachment occurs. The efficacy of laser photocoagulation to prevent the development or extension of rhegmatogenous retinal detachment is controversial. Despite these treatments, the visual prognosis of acute retinal necrosis is still poor, in particular VZV-induced acute retinal necrosis.

  7. [Nephrocalcinosis and subcutaneous fat necrosis].

    PubMed

    Gomes, Cláudia; Lobo, Luísa; Azevedo, António Siborro; Simão, Carla

    2015-01-01

    Subcutaneous fat necrosis of the newborn is an uncommon, transient and self-healing panniculits. This entity generally follows an uncomplicated course, however there are rare and important complications. The authors present a case of a newborn with subcutaneous fat necrosis complicated by hypercalcemia and nephrocalcinosis. The pathogenesis of hypercalcemia is not fully understood and the nephrocalcinosis can evolve to chronic kidney disease. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor for hypercalcemia and patients should have serial serum and urinary calcium determinations for up to 6 months after the appearance of the skin lesions. The early diagnosis and prompt treatment of hypercalcemia are essential to prevent severe complications.

  8. Avascular necrosis of carpal bones.

    PubMed

    Golimbu, C N; Firooznia, H; Rafii, M

    1995-05-01

    MR imaging is extremely well suited to detection of early phases of avascular necrosis, permitting diagnosis before collapse of the carpal bones has occurred. The sensitivity of this imaging modality allows differentiation of subtle changes in the bone marrow signal. This is used as criteria for a new stage classification of Kienböck's disease based on MR imaging appearance. The prognosis of scaphoid fractures and estimation of likelihood of avascular necrosis of the proximal fragment can be inferred by using gadolinium enhancement to evaluate the bone marrow vascularity.

  9. Inflammatory duodenal necrosis complicating gastroschisis

    PubMed Central

    Fouad, Dina; Lee, Geraint J.; Upadhyaya, Manasvi; Drake, David

    2016-01-01

    Babies with gastroschisis have an increased risk of necrotizing enterocolitis (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition requirement, and its associated complications. To our knowledge, this is the first case report of recurrent duodenal ischemia and necrosis associated with gastroschisis in the absence of NEC totalis. PMID:27695214

  10. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  11. Enzymic degradation of plasma arginine using arginine deiminase inhibits nitric oxide production and protects mice from the lethal effects of tumour necrosis factor alpha and endotoxin.

    PubMed Central

    Thomas, J Brandon; Holtsberg, Frederick W; Ensor, C Mark; Bomalaski, John S; Clark, Mike A

    2002-01-01

    Septic shock is mediated in part by nitric oxide (NO) and tumour necrosis factor alpha (TNFalpha). NO is synthesized primarily from extracellular arginine. We tested the ability of an arginine-degrading enzyme to inhibit NO production in mice and to protect mice from the hypotension and lethality that occur after the administration of TNFalpha or endotoxin. Treatment of BALB/c mice with arginine deiminase (ADI) formulated with succinimidyl succinimide polyethylene glycol of M(r) 20000 (ADI-SS PEG(20000)) eliminated all measurable plasma arginine (from normal levels of approximately 155 microM arginine to 2 microM). In addition, ADI-SS PEG(20000) also inhibited the production of NO, as quantified by plasma nitrate+nitrite. Treatment of mice with TNFalpha or endotoxin resulted in a dose-dependent increase in NO production and lethality. Pretreatment of mice with ADI-SS PEG(20000) resulted in increased resistance to the lethal effects of TNFalpha and endotoxin. These observations are consistent with NO production resulting, to some extent, from the metabolism of extracellular arginine. The toxic effects of TNFalpha and endotoxin may be partially inhibited by enzymic degradation of plasma arginine by ADI-SS PEG(20000). Interestingly, pretreatment with ADI-SS PEG(20000) did not inhibit the anti-tumour activity of TNFalpha in vitro or in vivo. This treatment may allow greater amounts of TNFalpha, as well as other cytokines, to be administered while abrogating side effects such as hypotension and death. PMID:11964159

  12. Acute oesophageal necrosis (black oesophagus).

    PubMed

    Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles

    2016-03-01

    A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident.

  13. Laser Balancing

    NASA Astrophysics Data System (ADS)

    1981-01-01

    Mechanical Technology, Incorporated developed a fully automatic laser machining process that allows more precise balancing removes metal faster, eliminates excess metal removal and other operator induced inaccuracies, and provides significant reduction in balancing time. Manufacturing costs are reduced as a result.

  14. Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists.

    PubMed

    Hamdi, Haïfa; Mariette, Xavier; Godot, Véronique; Weldingh, Karin; Hamid, Abdul Monem; Prejean, Maria-Victoria; Baron, Gabriel; Lemann, Marc; Puechal, Xavier; Breban, Maxime; Berenbaum, Francis; Delchier, Jean-Charles; Flipo, René-Marc; Dautzenberg, Bertrand; Salmon, Dominique; Humbert, Marc; Emilie, Dominique

    2006-01-01

    Reactivation of latent Mycobacterium tuberculosis (Mtb) infection is a major complication of anti-tumour necrosis factor (TNF)-alpha treatment, but its mechanism is not fully understood. We evaluated the effect of the TNF antagonists infliximab (Ifx), adalimumab (Ada) and etanercept (Eta) on anti-mycobacterial immune responses in two conditions: with ex vivo studies from patients treated with TNF antagonists and with the in vitro addition of TNF antagonists to cells stimulated with mycobacterial antigens. In both cases, we analysed the response of CD4+ T lymphocytes to purified protein derivative (PPD) and to culture filtrate protein (CFP)-10, an antigen restricted to Mtb. The tests performed were lymphoproliferation and immediate production of interferon (IFN)-gamma. In the 68 patients with inflammatory diseases (rheumatoid arthritis, spondylarthropathy or Crohn's disease), including 31 patients with a previous or latent tuberculosis (TB), 14 weeks of anti-TNF-alpha treatment had no effect on the proliferation of CD4+ T lymphocytes. In contrast, the number of IFN-gamma-releasing CD4+ T lymphocytes decreased for PPD (p < 0.005) and CFP-10 (p < 0.01) in patients with previous TB and for PPD (p < 0.05) in other patients (all vaccinated with Bacille Calmette-Guérin). Treatments with Ifx and with Eta affected IFN-gamma release to a similar extent. In vitro addition of TNF antagonists to CD4+ T lymphocytes stimulated with mycobacterial antigens inhibited their proliferation and their expression of membrane-bound TNF (mTNF). These effects occurred late in cultures, suggesting a direct effect of TNF antagonists on activated mTNF+ CD4+ T lymphocytes, and Ifx and Ada were more efficient than Eta. Therefore, TNF antagonists have a dual action on anti-mycobacterial CD4+ T lymphocytes. Administered in vivo, they decrease the frequency of the subpopulation of memory CD4+ T lymphocytes rapidly releasing IFN-gamma upon challenge with mycobacterial antigens. Added in vitro, they

  15. Balancing Acts

    MedlinePlus

    ... a new type of balance therapy using computerized, virtual reality. UPMC associate professor Susan Whitney, Ph.D., ... involves simulated trips down the aisles of a virtual grocery store in the university's Medical Virtual Reality ...

  16. Thermal inactivation of infectious hematopoietic necrosis and infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Gosting, L.; Gould, R.W.

    1981-01-01

    A plaque assay was used to follow the inactivation kinetics of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in cell culture media at various temperatures. Inactivation of infectious hematopoietic necrosis virus in a visceral organ slurry was compared with that in culture media.

  17. Renal papillary necrosis: an update.

    PubMed

    Eknoyan, G; Qunibi, W Y; Grissom, R T; Tuma, S N; Ayus, J C

    1982-03-01

    The clinical and diagnostic features of renal papillary necrosis (RPN) of 27 patients were studied. Diabetes mellitus was the most frequent (56%) condition associated with RPN. Analgesic abuse, sickle hemoglobinopathy and urinary tract obstruction were present in 4 patients each; in 6 of these 12 patients these conditions were present as a coexistent disease with diabetes mellitus. There was evidence of an acute or chronic infection of the urinary tract in 18 patients, as a coexistent condition with another underlying disease that itself can cause RPN in 14 patients and as the only cause of RPN in another 4. Thus, the presence of more than one diagnostic condition which might be implicated in the causation of RPN was present in 15 patients or 55% of the cases in this series. When infection was excluded, six patients or 22% of the cases had two coexisting diseases, each of which has been implicated as a cause of RPN. This observation underlines the multifactorial nature of this entity and might explain why RPN is not encountered more frequently in each of the various primary diseases with which it has been associated. The average age of the patients at the time of diagnosis was 53 years for women and 56 years for men. Only six of the patients were younger than 40 years, and three of these had sickle hemoglobinopathy. The diagnosis of RPN was based on x-ray findings in eight patients, on the histologic examination of papillary tissue in urine in one, and on autopsy findings in the rest. Papillary necrosis was bilateral in three-fourths of the cases. The clinical picture varied. Most of the patients (67%) presented with chills and fever. Flank pain and dysuria were present in 11 patients (41%). As a rule oliguria was rare and progressive uremia was uncommon. In cases diagnosed at post-mortem, the patients had succumbed to infection or to a primary severe extrarenal disorder with the possibility of RPN having been entertained clinically in only half these cases prior

  18. Nucleotide carriers for anti-tumour actinomycin antibiotics.

    PubMed

    Vekshin, N L; Kovalev, V I

    2016-01-01

    We have investigated a number of complexes of 7-aminoactinomycin D (7AAMD), with its potential carriers: caffeine, folic acid (FA), purine bases-guanine and adenine, pyrimidine base-thymine and with fragmented DNA to determine more stable and suitable complex. The process of binding of the fluorescent antibiotic with clusters of caffeine, guanine, adenine, thymine and with fragmented DNA was accompanied by a considerable long-wavelength shift in excitation spectrum. The energy of interaction between phenoxazine hetero-cycle of 7AAMD and chromophores of the carriers studied has been found. In the case of 7AAMD with guanine, adenine, thymine and caffeine, the energy is about of 7 kcal/mol, which is a little lower than in the case with DNA (7.7 kcal/mol). On the basis of emission spectra, in all examined compounds, with the exception DNA, the 7AAMD molecule emits photons from water phase, not from a cluster, since photo-excitation leads to desorption of the antibiotic from a cluster surface. We observed also the mutual fluorescence quenching of 7AAMD and FA in their complex. It may well be that this complex forms due to interaction of peptide-lactone rings of 7AAMD with system of FA. In the case of DNA, the complex with 7AAMD has very high stability that is determined not only by interaction between phenoxazine of 7AAMD and the DNA bases, but it is largely owing to the interaction between two peptide-lactone rings of 7AAMD and the DNA deoxyribose-phosphate chains.

  19. Anti-tumour activity of Digitalis purpurea L. subsp. heywoodii.

    PubMed

    López-Lázaro, Miguel; Palma De La Peña, Nieves; Pastor, Nuria; Martín-Cordero, Carmen; Navarro, Eduardo; Cortés, Felipe; Ayuso, María Jesús; Toro, María Victoria

    2003-08-01

    Recent research has shown the anticancer effects of digitalis compounds suggesting their possible use in medical oncology. Four extracts obtained from the leaves of Digitalis purpurea subsp. heywoodii have been assessed for cytotoxic activity against three human cancer cell lines, using the SRB assay. All of them showed high cytotoxicity, producing IC50 values in the 0.78 - 15 microg/mL range with the methanolic extract being the most active, in non toxic concentrations. Steroid glycosides (gitoxigenin derivatives) were detected in this methanolic extract. Gitoxigenin and gitoxin were evaluated in the SRB assay using the three human cancer cell lines, showing IC50 values in the 0.13 - 2.8 microM range, with the renal adenocarcinoma cancer cell line (TK-10) being the most sensitive one. Morphological apoptosis evaluation of the methanolic extract and both compounds on the TK-10 cell line showed that their cytotoxicity was mediated by an apoptotic effect. Finally, possible mechanisms involved in apoptosis induction by digitalis compounds are discussed.

  20. Balance System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    TherEx Inc.'s AT-1 Computerized Ataxiameter precisely evaluates posture and balance disturbances that commonly accompany neurological and musculoskeletal disorders. Complete system includes two-strain gauged footplates, signal conditioning circuitry, a computer monitor, printer and a stand-alone tiltable balance platform. AT-1 serves as assessment tool, treatment monitor, and rehabilitation training device. It allows clinician to document quantitatively the outcome of treatment and analyze data over time to develop outcome standards for several classifications of patients. It can evaluate specifically the effects of surgery, drug treatment, physical therapy or prosthetic devices.

  1. Balancing Eggs

    ERIC Educational Resources Information Center

    Mills, Allan

    2014-01-01

    Theory predicts that an egg-shaped body should rest in stable equilibrium when on its side, balance vertically in metastable equilibrium on its broad end and be completely unstable on its narrow end. A homogeneous solid egg made from wood, clay or plastic behaves in this way, but a real egg will not stand on either end. It is shown that this…

  2. Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

    PubMed

    Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

    2008-01-01

    Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

  3. Acute Necrotizing Esophagitis Followed by Duodenal Necrosis.

    PubMed

    Del Hierro, Piedad Magdalena

    2011-12-01

    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.

  4. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Solez, K.; Miller, M.; Quarles, P. A.; Finer, P. M.; Heptinstall, R. H.

    1974-01-01

    To test the thesis that vasoconstriction plays a significant role in the pathogenesis of papillary necrosis caused by bromoethylamine hydrobromide (BEA), medullary plasma flow was determined in rats treated with BEA. Medullary blood flow was normal ½ to 1 hour after BEA treatment, and was actually elevated 6 hours after BEA. There was no increase in plasma levels of prostaglandins A and E, which would have been expected if there had been medullary ischemia. Pretreatment with reserpine, which inhibited the development of papillary necrosis, had little effect on medullary plasma flow. These observations do not support the notion that vasoconstriction is the mechanism by which BEA causes papillary necrosis. PMID:4472110

  5. Balance (or Vestibular) Rehabilitation

    MedlinePlus

    ... the Public / Hearing and Balance Balance (or Vestibular) Rehabilitation Audiologic (hearing), balance, and medical diagnostic tests help ... whether you are a candidate for vestibular (balance) rehabilitation. Vestibular rehabilitation is an individualized balance retraining exercise ...

  6. Cortical necrosis in a renal transplant

    SciTech Connect

    Blumhardt, R.; Growcock, G.; Lasher, J.C.

    1983-07-01

    The /sup 99m/Tc-DTPA renogram is a well extabished noninvasive method for evaluating and following transplanted kidneys. The examination is useful in distinguishing rejection from acute tubular necrosis as well as demonstrating several less common complications such as vascular occlusion, urinary extravasation, obstruction, and lymphocele. A previously unreported condition involving a transplant kidney (i.e., renal cortical necrosis) is described which was diagnosed with renal scintigraphy in combination with sonography.

  7. Intracellular serpins, firewalls and tissue necrosis.

    PubMed

    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.

  8. Renal Papillary Necrosis: Role of Radiology

    PubMed Central

    Pandya, Vaidehi K.

    2016-01-01

    Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID:26894147

  9. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry

    PubMed Central

    Tubach, Florence; Salmon, Dominique; Ravaud, Philippe; Allanore, Yannick; Goupille, Philippe; Bréban, Maxime; Pallot-Prades, Béatrice; Pouplin, Sophie; Sacchi, Antoinette; Chichemanian, Rose Marie; Bretagne, Stéphane; Emilie, Dominique; Lemann, Marc; Lorthololary, Olivier; Mariette, Xavier

    2009-01-01

    Background Tuberculosis (TB) is associated with anti-tumour necrosis factor (TNF) therapy but whether it is drug-specific remains a concern. Our objective was to describe cases of tuberculosis associated with anti-TNF therapy, identify risk factors and estimate the incidence. Methods An incidence study with the French population as reference and a case-control analysis. We collected, for 3 years, cases of TB among French patients receiving anti-TNF therapy, whatever the indication, with two controls treated with anti-TNF agents per case. Results We collected 69 cases of TB in patients treated for rheumatoid arthritis (n=40), spondylarthropathies (n=18), inflammatory colitis (n=9), psoriasis (n=1) and Behçet’s disease (n=1) treated with infliximab (n=36), adalimumab (n=28) and etanercept (n=5). None of the cases had received correct chemoprophylaxis treatment. The sex and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The SIR was 12.2 (95% confidence interval 9.7–15.5) and was higher for therapy with infliximab and adalimumab than for that with etanercept: 18.6 (13.4–25.8) and 29.3 (20.2–42.4) versus 1.8 (0.7–4.3), respectively. In the case-control analysis, the exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB: odds ratio=13.3 (2.6–69.0) and 17.1 (3.6–80.6), respectively. Other risk factors were age, the first year of anti-TNF treatment, and being born in an endemic area. Conclusions The risk of TB is higher for patients receiving monoclonal-antibody than soluble-receptor anti-TNF therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylaxis treatment favours the reactivation of latent TB. PMID:19565495

  10. Shaft balancing

    DOEpatents

    Irwin, John A.

    1979-01-01

    A gas turbine engine has an internal drive shaft including one end connected to a driven load and an opposite end connected to a turbine wheel and wherein the shaft has an in situ adjustable balance system near the critical center of a bearing span for the shaft including two 360.degree. rings piloted on the outer diameter of the shaft at a point accessible through an internal engine panel; each of the rings has a small amount of material removed from its periphery whereby both of the rings are precisely unbalanced an equivalent amount; the rings are locked circumferentially together by radial serrations thereon; numbered tangs on the outside diameter of each ring identify the circumferential location of unbalance once the rings are locked together; an aft ring of the pair of rings has a spline on its inside diameter that mates with a like spline on the shaft to lock the entire assembly together.

  11. Infectious pancreatic necrosis: its detection and identification

    USGS Publications Warehouse

    Wolf, K.

    1965-01-01

    Ultimate control of infectious pancreatic necrosis (IPN) in hatcheries depends largely upon learning where the virus occurs. To detect the presence of virus either susceptible fish or susceptible fish cell cultures may be used as test systems. In modern virology, it is generally agreed that cell cultures are more convenient, are usually a much more sensitive test system, and allow more rapid determinations.

  12. [Acral necrosis as a complication of urosepsis].

    PubMed

    Blarer, J; Pfister, D; Jandali, A R; Gutzeit, A; John, H; Horstmann, M

    2014-06-01

    Sepsis is the third most common cause of death in Germany. Every fourth patient with sepsis has urosepsis. Even if substantial therapeutic progress has been made, sepsis remains a severe condition with high morbidity and mortality that requires rapid interdisciplinary measures. Besides life-threatening complications, acral necrosis as presented here can occur as a result of disseminated intravascular coagulation and severe microcirculatory disorders.

  13. Oligodendroglial degeneration in distemper: apoptosis or necrosis?

    PubMed

    Schobesberger, M; Zurbriggen, A; Summerfield, A; Vandevelde, M; Griot, C

    1999-03-01

    Canine distemper virus (CDV) causes a multifocal demyelinating disease in dogs. It was previously shown that the initial demyelinating lesions are directly virus induced since a correlation between the occurrence of demyelination and CDV replication in white matter cells was observed. During the course of infection oligodendrocytes undergo distinct morphological alterations, partly due to a restricted CDV infection of these cells, and eventually disappear from the lesions. This phenomenon has been described in vivo as well as in vitro. However, the reason for the morphological alterations and the following oligodendroglial depletion remained unclear. Since virus infection can induce cell death, it was investigated whether apoptosis or necrosis plays a role in the pathogenesis of demyelination in canine distemper. In brain tissue sections from dogs with acute distemper apoptotic cells were not detected within the demyelinating lesions using morphological and biochemical cell death criteria. In chronic distemper, apoptotic cells - presumably inflammatory cells - were seen within the perivascular cuffs. These in vivo findings were correlated to the in vitro situation using CDV-infected primary dog brain cell cultures as well as Vero cells. Infection with culture-adapted CDV lead to massive necrosis but not to apoptosis. After infection with virulent CDV neither apoptosis nor necrosis was a predominant feature in either culture system. These findings suggest that virus-induced demyelination in canine distemper is not the direct consequence of apoptosis or necrosis. It is speculated that another mechanism must be responsible for the observed morphological alterations of oligodendrocytes, ultimately leading to demyelination.

  14. Excitotoxins in neuronal apoptosis and necrosis.

    PubMed

    Nicotera, P; Lipton, S A

    1999-06-01

    Neuronal loss is common to many neurodegenerative diseases. Although necrosis is a common histopathologic feature observed in neuropathologic conditions, evidence is increasing that apoptosis can significantly contribute to neuronal demise. The prevalence of either type of cell death, apoptosis or necrosis, and the relevance for the progression of disease is still unclear. The debate on the occurrence and prevalence of one or the other type of death in pathologic conditions such as stroke or neurotoxic injury may in part be resolved by the proposal that different types of cell death within a tissue reflect either partial or complete execution of a common death program. Apoptosis is an active process of cell destruction, characterized morphologically by cell shrinkage, chromatin aggregation with extensive genomic fragmentation, and nuclear pyknosis. In contrast, necrosis is characterized by cell swelling, linked to rapid energy loss, and generalized disruption of ionic and internal homeostasis. This swiftly leads to membrane lysis, release of intracellular constituents that evoke a local inflammatory reaction, edema, and injury to the surrounding tissue. During the past few years, our laboratories have studied the signals and mechanisms responsible for induction or prevention of apoptosis/necrosis in neuronal injury and this is the subject of this review.

  15. Snapshot in surgery: intraperitoneal encapsulated fat necrosis

    PubMed Central

    Oh, Han Boon; Arab, Nahlah; Teo, Lynette; Lieske, Bettina

    2015-01-01

    Key Clinical Message A 66-year-old man with rectal cancer was found to have an incidental ring-like lesion in the left rectovesical pouch. Histology revealed an encapsulated fat necrosis. Intraperitoneal encapsulated fat necroses are postulated to be a result of infarcted epiploic appendages resulting in a free-floating lesion. PMID:25767714

  16. Hepatic necrosis following halothane anesthesia in goats.

    PubMed

    O'Brien, T D; Raffe, M R; Cox, V S; Stevens, D L; O'Leary, T P

    1986-12-15

    One goat anesthetized with thiamylal sodium, xylazine, and halothane for repair of an abominal hernia, and 7 of 29 goats similarly anesthetized for an experiment unrelated to considerations of anesthesia, developed signs of hepatic failure within 24 hours of anesthesia. Affected goats had high values for serum aspartate transaminase and serum total bilirubin by 12 to 24 hours after induction of anesthesia. Necropsy of the 8 affected goats revealed centrilobular to massive hepatic necrosis (8 of 8), brain lesions consistent with hepatic encephalopathy (3 of 4), and acute renal tubular necrosis (6 of 6). Two unaffected goats had no hepatic necrosis. Causes of hepatic necrosis other than those related to anesthesia (eg, infectious agents, toxins) were ruled out by lack of supporting necropsy findings or were considered unlikely because of lack of opportunity for exposure. Hepatic lesions in these goats closely resembled those described in human beings with halothane-associated hepatic injury, although in both species these lesions are nonspecific at the gross and light microscopic levels. The pathogenesis of halothane-associated hepatic injury in goats, as in human beings, remains to be determined.

  17. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-07-07

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness.

  18. Imaging Manifestations of Mediastinal Fat Necrosis

    PubMed Central

    Bhatt, Malay Y.; Martínez-Jiménez, Santiago; Rosado-de-Christenson, Melissa L.; Watson, Kenneth R.; Walker, Christopher M.; Kunin, Jeffrey R.

    2013-01-01

    Mediastinal fat necrosis (MFN) or epipericardial fat necrosis, as it is commonly referred to in the literature, is a rare self-limiting cause of chest pain of unclear etiology. MFN affects previously healthy individuals who present with acute pleuritic chest pain. Characteristic computed tomography (CT) findings include a fat attenuation lesion with intrinsic and surrounding increased attenuation stranding. There is often associated thickening of the adjacent pericardium and/or pleural effusions. We present two cases of MFN manifesting as ovoid fat attenuation lesions demarcated by a soft tissue attenuation rim with intrinsic and surrounding soft tissue attenuation stranding and review the clinical and pathologic features of these lesions. Knowledge of the clinical presentation of patients with MFN and familiarity with the characteristic imaging findings of these lesions should allow radiologists to prospectively establish the correct diagnosis and suggest conservative management and follow-up. PMID:24369521

  19. Balance Food and Activity

    MedlinePlus

    ... eNewsletters Calendar Balance Food and Activity What is Energy Balance? Energy is another word for "calories." Your ... adults, fewer calories are needed at older ages. Energy Balance in Real Life Think of it as ...

  20. Dizziness and Balance

    MedlinePlus

    AUDIOLOGY Dizziness and Balance Inform ation Seri es Our balance system helps us walk, run, and move without falling. ... if I have a problem with balance or dizziness? It is important to see your doctor if ...

  1. Peripheral fat necrosis after penetrating pancreatic trauma: a case report.

    PubMed

    Adams, D B

    1993-11-01

    Peripheral fat necrosis (PFN), a rare complication of pancreatitis, has been reported previously in association with blunt pancreatic trauma. A patient who developed peripheral fat necrosis after penetrating pancreatic trauma and needed bilateral above-the-knee amputations to treat complications of lower extremity fat necrosis is reported.

  2. Balance in Assessment

    ERIC Educational Resources Information Center

    White, Richard

    2007-01-01

    The review by Black and Wiliam of national systems makes clear the complexity of assessment, and identifies important issues. One of these is "balance": balance between local and central responsibilities, balance between the weights given to various purposes of schooling, balance between weights for various functions of assessment, and balance…

  3. A Question of Balance

    ERIC Educational Resources Information Center

    Claxton, David B.; Troy, Maridy; Dupree, Sarah

    2006-01-01

    Most authorities consider balance to be a component of skill-related physical fitness. Balance, however, is directly related to health, especially for older adults. Falls are a leading cause of injury and death among the elderly. Improved balance can help reduce falls and contribute to older people remaining physically active. Balance is a…

  4. Dynamic balance improvement program

    NASA Technical Reports Server (NTRS)

    Butner, M. F.

    1983-01-01

    The reduction of residual unbalance in the space shuttle main engine (SSME) high pressure turbopump rotors was addressed. Elastic rotor response to unbalance and balancing requirements, multiplane and in housing balancing, and balance related rotor design considerations were assessed. Recommendations are made for near term improvement of the SSME balancing and for future study and development efforts.

  5. Effects of tumour necrosis factor on protein metabolism.

    PubMed

    Evans, D A; Jacobs, D O; Wilmore, D W

    1993-08-01

    Increased skeletal muscle breakdown and negative nitrogen balance are features of sepsis that may be mediated by cytokines. The effects of tumour necrosis factor (TNF) on protein metabolism were studied. When administered to anaesthetized dogs (0.57 x 10(5) units per kg body-weight over 6h), TNF caused urinary nitrogen excretion to increase (mean(s.e.m.) 165(15) mg kg-1 for dogs that received TNF versus 113(8) mg kg-1 for control animals, P < 0.01). Amino acid nitrogen release from the hindlimbs showed no change over the study period, indicating that the additional urinary nitrogen was not derived from peripheral protein stores. In a second study the same dose of TNF or saline was infused after the intestine had been removed. The mean(s.e.m.) urinary nitrogen excretion in control dogs that had undergone enterectomy (101(7) mg kg-1) was similar to that of intact animals, and addition of TNF did not significantly increase nitrogen excretion (86(18) mg kg-1). The results suggest that nitrogen excreted in the urine during administration of TNF is derived, at least initially, from the intestinal tract.

  6. Apoptosis and Necrosis in the Liver

    PubMed Central

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  7. Endothelial cell effects of cytotoxics: balance between desired and unwanted effects.

    PubMed

    de Vos, F Y F L; Willemse, P H B; de Vries, E G E; Gietema, J A

    2004-10-01

    Since Folkman defined angiogenesis more than 25 years ago as the most important process in tumour growth and metastasis, specific anti-angiogenic agents have been developed. One obvious route to block this process was until recently overlooked, however. Tumour endothelial cells are different from normal endothelial cells and may respond differently to conventional cytotoxics. Chemotherapeutic-induced vascular toxicity has been observed in various clinical studies and seems to be based on endothelial cell damage as seen in vitro in human umbilical vein endothelial cells (HUVEC) models with protracted low-dose cytostatic exposure. Translated into the clinical setting, such "metronomically" administered chemotherapy could lead to anti-angiogenesis enhancing anti-tumour efficacy of cytostatic drugs. This paper reviews the desired anti-tumour endothelial activity versus the unwanted general vascular toxicity of cytostatic drugs. Several ways to enhance the anti-tumour activity and to circumvent the unwanted vascular toxicity of these "accidental" anti-angiogenic drugs will be discussed.

  8. Cystic avascular necrosis of the triquetrum.

    PubMed

    Albtoush, Omar M; Esmadi, Mohammad; Al-Omari, Mamoon H

    2013-01-01

    Carpal bones are rarely affected by avascular necrosis (AVN) in the absence of fractures. The lunate is the most frequently affected carpal bone, followed by the scaphoid and the capitate. The triquetrum is rarely affected by AVN. We report a case of multiple cystic changes in the triquetrum in a patient with a history of trauma. He was treated by below elbow Colles plaster cast for 3 months, with no improvement. Cystic changes resulted from irreversible AVN of the triquetrum. This is the first case to be reported in the literature with cystic AVN changes in the triquetrum.

  9. Balancing Vanguard Satellites

    NASA Technical Reports Server (NTRS)

    Simkovich, A.; Baumann, Robert C.

    1961-01-01

    The Vanguard satellites and component parts were balanced within the specified limits by using a Gisholt Type-S balancer in combination with a portable International Research and Development vibration analyzer and filter, with low-frequency pickups. Equipment and procedures used for balancing are described; and the determination of residual imbalance is accomplished by two methods: calculation, and graphical interpretation. Between-the-bearings balancing is recommended for future balancing of payloads.

  10. Mastectomy skin flap necrosis: challenges and solutions

    PubMed Central

    Robertson, Stuart A; Jeevaratnam, Johann A; Agrawal, Avi; Cutress, Ramsey I

    2017-01-01

    Introduction Mastectomy skin flap necrosis (MSFN) has a reported incidence of 5%–30% in the literature. It is often a significant and underappreciated problem. The aim of this article was to review the associated challenges and possible solutions. Methods A MEDLINE search was performed using the search term “mastectomy skin flap necrosis”. Titles and abstracts from peer-reviewed publications were screened for relevance. Results MSFN is a common complication and may present as partial- or full-thickness necrosis. Predictive patient risk factors include smoking, diabetes, obesity, radiotherapy, previous scars and severe medical comorbidity. MSFN leads to a number of challenges, including wound management problems, delays to adjuvant therapy, esthetic compromise, implant extrusion, patient distress and financial loss. Careful preoperative planning and meticulous surgical technique may reduce the incidence of MSFN. A number of intraoperative techniques are available to try and predict skin flaps at risk of MSFN. MSFN may be managed operatively or nonoperatively. Early intervention may reduce the morbidity of MSFN in selected cases. Topical nitroglycerin ointment may be beneficial in reducing MSFN following immediate reconstruction, but the evidence base is still limited. Conclusion MSFN can result in considerable challenges for the patient and the health care service. This review discusses the management options for this problem. PMID:28331365

  11. Epipericardial fat necrosis: an underdiagnosed condition

    PubMed Central

    Costa, A N; Bachion, G H; Apanavicius, A; Filho, J R P; Kairalla, R A; Lynch, D A

    2014-01-01

    Objective: Epipericardial fat necrosis (EFN) is an uncommon benign and self-limited condition that leads patients to the emergency department (ED) owing to the onset of acute pleuritic chest pain. The aim of this study was to describe the cases of this disease in our institution and to illustrate the associated clinical and radiological findings. Methods: We reviewed 3604 chest scans referred by the ED from November 2011 to July 2013. Patients diagnosed with epipericardial necrosis had their medical records and original tomography reports analysed. Results: Chest pain was the primary complaint in 426 patients; 11 of them had definitive EFN findings characterized by a round soft-tissue attenuation lesion with a varying degree of strands. All patients presented with pleuritic chest pain on the same side as the lesion. Pericardial thickening, pleural effusion and mild atelectasis were the associated tomography findings. Cardiac enzyme and D-dimer tests performed during the episode were normal in all cases. 27% of the cases only were correctly diagnosed with EFN at the time of presentation. Conclusion: EFN is a benign inflammatory condition frequently overlooked in the ED by physicians and radiologists but is an important factor in the differential diagnosis of patients with acute chest pain. Advances in knowledge: The article adds clinically and radiologically useful information about the condition and displays the importance of making the correct diagnosis to avoid unnecessary examinations. PMID:24707937

  12. Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

    PubMed Central

    Jiang, Binghu; Wang, Jichen; Ni, Yicheng; Chen, Feng

    2013-01-01

    Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin. PMID:24052807

  13. Avascular necrosis of bone complicating corticosteroid replacement therapy.

    PubMed Central

    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. Images PMID:6859959

  14. Concomitant avascular necrosis of the scaphoid and lunate.

    PubMed

    Bhardwaj, Praveen; Sharma, Chetna; Sabapathy, S Raja

    2012-01-01

    Simultaneous avascular necrosis of multiple carpal bones is rare. Concomitant avascular necrosis of scaphoid and lunate has been reported only once. We report one more case of this rare condition which can be a cause of wrist pain. Steroid intake is a known risk factor for avascular necrosis but in our case the patient had been taking herbal medicines for joint pain the composition of which was not known. Probably the presence of steroid in these medicines was the cause of avascular necrosis in this case.

  15. Definition of bone necrosis by the pathologist

    PubMed Central

    Fondi, Cristina; Franchi, Alessandro

    2007-01-01

    Osteonecrosis is a common disorder that may go clinically unrecognized or may result in the collapse of the architecture of bone, determining severe anatomic alterations of the involved site. Osteonecrosis is not a specific disease entity, but rather the result of a number of conditions ultimately leading to an impairment of blood supply to the bone tissue, although there is evidence that modifications of bone remodelling activity and weakening of bone structure with formation of microfractures are implicated as well. According to the site involved and to the factors promoting its development, the morbid anatomy and histopathology of osteonecrosis show a different appearance. This review discusses the main skeletal manifestations of osteonecrosis, including subarticular avascular necrosis of the femoral head and of the knee, as well as osteonecrosis of the jaw. PMID:22460748

  16. Cortical bone allografting in femoral head necrosis.

    PubMed

    Delloye, C; Cornu, O

    1999-01-01

    Ten femoral heads (six patients) with avascular necrosis were operated on using a fibular allograft. The procedure included core decompression followed by insertion of a cortical bone graft in order to relieve mechanical stresses from the overlying subchondral bone. The presence of the supporting graft should avoid an expected collapse or prevent its worsening if already present. A freeze-dried and processed cortical bone allograft was preferred to an autograft. Weightbearing was normally and fully resumed at the second postoperative month. There were three failures within the first year, four satisfactory results, in which the hip was replaced after 4 years while there are still 3 hips that have been preserved from arthroplasty in young patients after 5 years. The technique is easy and able to substantially delay an arthroplasty in an active patient.

  17. Occlusal cranial balancing technique.

    PubMed

    Smith, Gerald H

    2007-01-01

    The acronym for Occlusal Cranial Balancing Technique is OCB. The OCB concept is based on the architectural principle of a level foundation. The principles of Occlusal Cranial Balancing are a monumental discovery and if applied will enhance total body function.

  18. Skylab water balance analysis

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1977-01-01

    The water balance of the Skylab crew was analyzed. Evaporative water loss using a whole body input/output balance equation, water, body tissue, and energy balance was analyzed. The approach utilizes the results of several major Skylab medical experiments. Subsystems were designed for the use of the software necessary for the analysis. A partitional water balance that graphically depicts the changes due to water intake is presented. The energy balance analysis determines the net available energy to the individual crewman during any period. The balances produce a visual description of the total change of a particular body component during the course of the mission. The information is salvaged from metabolic balance data if certain techniques are used to reduce errors inherent in the balance method.

  19. Polarization-balanced beamsplitter

    DOEpatents

    Decker, Derek E.

    1998-01-01

    A beamsplitter assembly that includes several beamsplitter cubes arranged to define a plurality of polarization-balanced light paths. Each polarization-balanced light path contains one or more balanced pairs of light paths, where each balanced pair of light paths includes either two transmission light paths with orthogonal polarization effects or two reflection light paths with orthogonal polarization effects. The orthogonal pairing of said transmission and reflection light paths cancels polarization effects otherwise caused by beamsplitting.

  20. Polarization-balanced beamsplitter

    DOEpatents

    Decker, D.E.

    1998-02-17

    A beamsplitter assembly is disclosed that includes several beamsplitter cubes arranged to define a plurality of polarization-balanced light paths. Each polarization-balanced light path contains one or more balanced pairs of light paths, where each balanced pair of light paths includes either two transmission light paths with orthogonal polarization effects or two reflection light paths with orthogonal polarization effects. The orthogonal pairing of said transmission and reflection light paths cancels polarization effects otherwise caused by beamsplitting. 10 figs.

  1. Wind Tunnel Balances

    NASA Technical Reports Server (NTRS)

    Warner, Edward P; Norton, F H

    1920-01-01

    Report embodies a description of the balance designed and constructed for the use of the National Advisory Committee for Aeronautics at Langley Field, and also deals with the theory of sensitivity of balances and with the errors to which wind tunnel balances of various types are subject.

  2. Coaching for Balance.

    ERIC Educational Resources Information Center

    Larson, Bonnie

    2001-01-01

    Discusses coaching for balance the integration of the whole self: physical (body), intellectual (mind), spiritual (soul), and emotional (heart). Offers four ways to identify problems and tell whether someone is out of balance and four coaching techniques for creating balance. (Contains 11 references.) (JOW)

  3. Human Balance System

    MedlinePlus

    ... and vision problems, and difficulty with concentration and memory. What is balance? Balance is the ability to maintain the body’s center of mass over its base of support. 1 A properly functioning balance system allows humans to see clearly while moving, identify orientation with ...

  4. Reconceptualizing balance: attributes associated with balance performance.

    PubMed

    Thomas, Julia C; Odonkor, Charles; Griffith, Laura; Holt, Nicole; Percac-Lima, Sanja; Leveille, Suzanne; Ni, Pensheng; Latham, Nancy K; Jette, Alan M; Bean, Jonathan F

    2014-09-01

    Balance tests are commonly used to screen for impairments that put older adults at risk for falls. The purpose of this study was to determine the attributes that were associated with balance performance as measured by the Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) balance test. This study was a cross-sectional secondary analysis of baseline data from a longitudinal cohort study, the Boston Rehabilitative Impairment Study of the Elderly (Boston RISE). Boston RISE was performed in an outpatient rehabilitation research center and evaluated Boston area primary care patients aged 65 to 96 (N=364) with self-reported difficulty or task-modification climbing a flight of stairs or walking 1/2 of a mile. The outcome measure was standing balance as measured by the FICSIT-4 balance assessment. Other measures included: self-efficacy, pain, depression, executive function, vision, sensory loss, reaction time, kyphosis, leg range of motion, trunk extensor muscle endurance, leg strength and leg velocity at peak power. Participants were 67% female, had an average age of 76.5 (±7.0) years, an average of 4.1 (±2.0) chronic conditions, and an average FICSIT-4 score of 6.7 (±2.2) out of 9. After adjusting for age and gender, attributes significantly associated with balance performance were falls self-efficacy, trunk extensor muscle endurance, sensory loss, and leg velocity at peak power. FICSIT-4 balance performance is associated with a number of behavioral and physiologic attributes, many of which are amenable to rehabilitative treatment. Our findings support a consideration of balance as multidimensional activity as proposed by the current International Classification of Functioning, Disability, and Health (ICF) model.

  5. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

    PubMed Central

    Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

    2016-01-01

    Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

  6. Avascular necrosis of multiple carpal bones. A case report.

    PubMed

    De Smet, L

    1999-01-01

    A case of a 66-year-old female patient with hyperlipaemia, corticosteroid osteoporosis and chronic obstructive lung disease with avascular necrosis of the proximal row of the carpus and hamate is described. No other sites of avascular bone necrosis were found. A proximal row carpectomy was performed with an excellent outcome.

  7. [Myocellular necrosis by cathecolamines in pheochromocytoma (author's transl)].

    PubMed

    Thiene, G; Valente, M; Cecchetto, A; Giordano, R; Pennelli, N

    1975-01-01

    A case of myocellular necrosis by cathecholamines in a patient presenting pheocromocytoma is reported. Death was due to cerbral apoplexy. The histological findings are quite specific and show myofibrillar degeneration with substitution of the normal striation by coarse sarcomeric transversal bands. The possible role of necrosis by catecholamines in sudden deaths and non-coronary myocardiosclerosis is emphasized.

  8. Black esophagus (acute esophageal necrosis) after spinal anesthesia.

    PubMed

    Román Fernández, A; López Álvarez, A; Fossati Puertas, S; Areán González, I; Varela García, O; Viaño López, P M

    2014-01-01

    Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms.

  9. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

    PubMed

    Felipo, F; Vaquero, M; del Agua, C

    2004-09-01

    An extraordinary case of encapsulated fat necrosis characterized by its large size, diffuse formation of pseudomembranes, and tendency to recur after excision is reported. A 67-year-old Caucasian woman suffering from morbid obesity was admitted for diagnosis and surgical treatment of a soft tissue mass showing a longest diameter of 14 cm and lying adjacently to the scar from previous appendicectomy. Histopathologic features were consistent with a nodular-cystic encapsulated fat necrosis with diffuse pseudomembranous transformation. Eight months after surgery, a new larger mass (longest diameter of 18 cm) sharing identical histopathologic features appeared in the same location. Encapsulated fat necrosis is a well-defined entity even though several names have been proposed for this condition, including mobile encapsulated lipoma, encapsulated necrosis, or nodular-cystic fat necrosis. Its pathogenesis seems to be related to ischemic changes secondary to previous trauma. It may occasionally show degenerative changes, including dystrophic calcifications and presence of pseudomembranes. To our knowledge, these are the first reported cases of encapsulated fat necrosis presenting as lesions of such size and showing diffuse formation of pseudomembranes; these particular features made diagnosis difficult and led to consideration of a wide range of potential diagnostic possibilities. This case expands the clinico-pathologic spectrum of membranocystic fat necrosis, including the potential ability of this subcutaneous fatty tissue abnormality to recur after surgical excision. Felipo F, Vaquero M, del Agua C. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

  10. Disseminated intravascular coagulation and acute myocardial necrosis caused by lightning.

    PubMed

    Ekoé, J M; Cunningham, M; Jaques, O; Balague, F; Baumann, R P; Humair, L; de Torrenté, A

    1985-01-01

    A 24-year-old woman was struck by lightning and suffered 20% second degree burns. She was admitted after cardiac and respiratory arrest. Despite intensive supportive care she died 24 h later of cardiogenic shock complicated by disseminated intravascular coagulation. At autopsy there was myocardial necrosis. Disseminated intravascular coagulation and myocardial necrosis are only rarely described as complications of lightning.

  11. Prognostic significance of differentiating necrosis from fluid collection on endoscopic ultrasound in patients with presumed isolated extrapancreatic necrosis

    PubMed Central

    Rana, Surinder S.; Chhabra, Puneet; Sharma, Ravi; Sharma, Vishal; Gupta, Rajesh; Bhasin, Deepak K.

    2017-01-01

    Background Extrapancreatic necrosis is diagnosed on computed tomography (CT) as extrapancreatic changes that are more than fat stranding; both fluid collections and necrosis would have a similar appearance. The aim of this study was to determine the prognostic significance of differentiating peripancreatic necrosis from fluid collection on endoscopic ultrasound (EUS) in patients with presumed isolated extrapancreatic necrosis. Methods We carried out a retrospective analysis of prospectively collected data from 36 patients (25 males; age range 19-65 years) with acute pancreatitis (AP) and isolated extrapancreatic necrosis. On EUS, peripancreatic anechoic areas were labeled as peripancreatic fluid collections and peripancreatic heterogeneously echotextured areas as peripancreatic necrosis. Results The etiology of AP was alcohol in 16 (44.4%) patients, gallstone disease in 13 (36.1%), and other in 7 (19.4%). On EUS, 25 (69.4%) patients had peripancreatic necrosis and 11 (30.6%) patients had peripancreatic fluid collections. Compared with patients who had peripancreatic fluid collections, patients with peripancreatic necrosis had a significantly higher frequency of pleural effusion (88% vs. 55%; P=0.04), organ failure (OF) (68% vs. 27%; P=0.03), and persistent OF (48% vs. 9%; P=0.03). The patients with peripancreatic necrosis also had a higher frequency of ascites (20% vs. 9%), need for intervention (20% vs. nil), surgery (8% vs. nil) and mortality (8% vs. nil), but these differences were not statistically significant. Conclusion Isolated extrapancreatic necrosis on contrast-enhanced CT comprises a heterogeneous group, with patients who show peripancreatic fluid collections on EUS having a less severe disease course compared to patients with peripancreatic necrosis. PMID:28243045

  12. Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain.

    PubMed

    Miyatake, Shin-Ichi; Nonoguchi, Noasuke; Furuse, Motomasa; Yoritsune, Erina; Miyata, Tomo; Kawabata, Shinji; Kuroiwa, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient's quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.

  13. Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain.

    PubMed

    Miyatake, Shin-Ichi; Nonoguchi, Noasuke; Furuse, Motomasa; Yoritsune, Erina; Miyata, Tomo; Kawabata, Shinji; Kuroiwa, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.

  14. Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

    PubMed Central

    Osterberg, E. Charles; Elliott, Sean P.; Hittelman, Adam B.

    2016-01-01

    We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting. PMID:27656309

  15. Immunization with viral antigens: Infectious haematopoietic necrosis

    USGS Publications Warehouse

    Winton, J.R.

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

  16. Stimulation of neutrophils by tumor necrosis factor

    SciTech Connect

    Klebanoff, S.J.; Vadas, M.A.; Harlan, J.M.; Sparks, L.H.; Gamble, J.R.; Agosti, J.M.; Waltersdorph, A.M.

    1986-06-01

    Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H/sub 2/O/sub 2/ production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation.

  17. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

  18. Inactivated infectious haematopoietic necrosis virus (IHNV) vaccines.

    PubMed

    Anderson, E; Clouthier, S; Shewmaker, W; Weighall, A; LaPatra, S

    2008-10-01

    The inactivation dynamics of infectious haematopoietic necrosis virus (IHNV) by b-propiolactone (BPL), binary ethylenimine (BEI), formaldehyde or heat and the antigenic and immunogenic properties of the inactivated vaccines were evaluated. Chemical treatment of IHNV with 2.7 mm BPL, 1.5 mm BEI or 50 mm formaldehyde abolished virus infectivity within 48 h whereas heat treatment at 50 or 100 degrees C rendered the virus innocuous within 30 min. The inactivated IHNV vaccines were recognized by rainbow trout, Oncorhynchus mykiss, IHNV-specific antibodies and were differentially recognized by antigenic site I or antigenic site II IHNV glycoprotein-specific neutralizing monoclonal antibodies. The BPL inactivated whole virus vaccine was highly efficacious in vaccinated rainbow trout challenged by waterborne exposure to IHNV 7, 28, 42 or 56 days (15 degrees C) after immunization. The formaldehyde inactivated whole virus vaccine was efficacious 7 or 11 days after vaccination of rainbow trout but performed inconsistently when tested at later time points. The other vaccines tested were not efficacious.

  19. Great Toe Necrosis Predicts an Unfavorable Limb Salvage Prognosis

    PubMed Central

    Ichioka, Shigeru

    2014-01-01

    Summary: The initial location of necrosis may affect the limb salvage rate. This study of 130 patients with chronic toe ulcers or gangrene was performed to assess whether the location of initial necrosis in the toes affected limb salvage prognosis. The patients were divided into 2 groups according to whether the initial necrosis was in the great toe or in other toes. Limb salvage prognosis was determined retrospectively. In the great toe group, the rates of total toe loss and major amputation were 50.0% and 24.4%, respectively. When the initial necrosis was in other toes, these rates were 27.3% and 9.3%, respectively. Great toe necrosis is associated with significantly higher rates of total toe loss (odds ratio = 3.10; P = 0.003; 95% confidence interval, 1.43−6.68) and major amputation (odds ratio = 3.66; P = 0.007; 95% confidence interval, 1.37−9.79). The great toe is supplied by 3 source arteries, whereas the lesser toes are fed by 1 or 2 arteries. Therefore, necrosis initiating from the great toe may reflect the presence of severe vascular disorders. The great toe is also anatomically connected to much of the foot via the tendons. Infection is more likely to spread along these tendons, which may reduce limb prognosis. Thus, the initial location of necrosis may be predictive of limb prognosis. PMID:25426399

  20. [Torsion and necrosis of epiploic appendices of the large bowel].

    PubMed

    Timofeev, M E; Fedorov, E D; Krechetova, A P; Shapoval'iants, S G

    2014-01-01

    The features of the clinical symptoms was studied, the possibility of laparoscopy in modern diagnosis and treatment of epiploic appendices torsion and necrosis of the large bowel was assessed in the article. It was done the retrospective analysis of the medical records of 87 patients with a diagnosis of epiploic appendices torsion and necrosis of the large bowel. The patients had laparoscopic operations in our hospital in the period from January 1995 to December 2012. The clinical picture, laboratory and instrumental datas in cases of epiploic appendices torsion and necrosis were scarce and nonspecific. An abdominal pain preferentially localized in the lower divisions was the main symptom (97.7%). The instrumental methods did not allow to diagnose the torsion and necrosis of epiploic appendices in the majority of cases and all these techniques were used for the differential diagnosis with other diseases. The assumption of the presence of appendices torsion and necrosis occured just in 34.5% of cases before the operation. Diagnosis of epiploic appendices torsion and necrosis present significant difficulties on prehospital and preoperative stages. The diagnostic laparoscopy is the method of choice in unclear situations and it allows to diagnose the torsion and necrosis of epiploic appendices in 96.6% of cases. Successful surgical treatment by using laparoscopic approach is possible in 90.8% of cases.

  1. Tumor necrosis factor interaction with gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Tsai, De-Hao; Elzey, Sherrie; Delrio, Frank W.; Keene, Athena M.; Tyner, Katherine M.; Clogston, Jeffrey D.; Maccuspie, Robert I.; Guha, Suvajyoti; Zachariah, Michael R.; Hackley, Vincent A.

    2012-05-01

    We report on a systematic investigation of molecular conjugation of tumor necrosis factor-α (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis, attenuated total reflectance-Fourier transform infrared spectroscopy, fluorescence assay, and enzyme-linked immunosorbent assay. The native TNF used in this study exists in the active homotrimer configuration prior to conjugation. After binding to AuNPs, the maximum surface density of TNF is (0.09 +/- 0.02) nm-2 with a binding constant of 3 × 106 (mol L-1)-1. Dodecyl sulfate ions induce desorption of monomeric TNF from the AuNP surface, indicating a relatively weak intermolecular binding within the AuNP-bound TNF trimers. Anti-TNF binds to both TNF-conjugated and citrate-stabilized AuNPs, showing that non-specific binding is significant. Based on the number of anti-TNF molecules adsorbed, a substantially higher binding affinity was observed for the TNF-conjugated surface. The inclusion of thiolated polyethylene glycol (SH-PEG) on the AuNPs inhibits the binding of anti-TNF, and the amount of inhibition is related to the number ratio of surface bound SH-PEG to TNF and the way in which the ligands are introduced. This study highlights the challenges in quantitatively characterizing complex hybrid nanoscale conjugates, and provides insight on TNF-AuNP formation and activity.We report on a systematic investigation of molecular conjugation of tumor necrosis factor-α (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis

  2. Plaquing procedure for infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Burke, J.A.; Mulcahy, D.

    1980-01-01

    A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.

  3. Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

    SciTech Connect

    Chao, Samuel T.; Ahluwalia, Manmeet S.; Barnett, Gene H.; Stevens, Glen H.J.; Murphy, Erin S.; Stockham, Abigail L.; Shiue, Kevin; Suh, John H.

    2013-11-01

    The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

  4. Mandibular bone necrosis after use of paraformaldehyde-containing paste

    PubMed Central

    Lee, Chi-hwan; Choi, Yoorina

    2016-01-01

    Paraformaldehyde has been used in the past as a pulpotomy agent. However, it has a severe cytotoxic effect and may cause alveolar bone necrosis. Depulpin, a devitalizing agent containing 49% paraformaldehyde, is no longer used frequently due to its severe side effects. In the two cases described in the present study, Depulpin was used as a devitalizing agent during root canal treatment. It caused a gradual loss of sensibility in adjacent teeth, gingival necrosis, and osteomyelitis. This case report demonstrates the serious side effects of using a paraformaldehyde-containing paste as a devitalizing agent for pulp, particularly mandibular bone necrosis. PMID:27847756

  5. Breast lipoma with central fat necrosis: case report

    PubMed Central

    Bouroumane, Mohamed Reda; Khalil, Reda; Khalil, Hind; Jalal, Hicham

    2016-01-01

    Fat necrosis of the breast is a benign non-suppurative inflammatory process of adipose tissue that most commonly occurs as the result of minor breast trauma. We present a case of a 40-years-old female with fat necrosis in a breast lipoma. She presented with an overlapping mass on the lateral quadrants. Mammography showed Well delineated radiolucent mass with peripheral “egg-shell” calcifications, that appeared an hypoechoic mass with posterior shadowing on ultrasonography. A history of accidental trauma raises the suspicion of fat necrosis. Pathology is necessary when radiological findings simulate malignancy.

  6. Identifying Balance in a Balanced Scorecard System

    ERIC Educational Resources Information Center

    Aravamudhan, Suhanya; Kamalanabhan, T. J.

    2007-01-01

    In recent years, strategic management concepts seem to be gaining greater attention from the academicians and the practitioner's alike. Balanced Scorecard (BSC) concept is one such management concepts that has spread in worldwide business and consulting communities. The BSC translates mission and vision statements into a comprehensive set of…

  7. Judicial Checks and Balances

    ERIC Educational Resources Information Center

    La Porta, Rafael; Lopez-de-Silanes, Florencio; Pop-Eleches, Cristian; Shleifer, Andrei

    2004-01-01

    In the Anglo-American constitutional tradition, judicial checks and balances are often seen as crucial guarantees of freedom. Hayek distinguishes two ways in which the judiciary provides such checks and balances: judicial independence and constitutional review. We create a new database of constitutional rules in 71 countries that reflect these…

  8. Leadership: A Balancing Act

    ERIC Educational Resources Information Center

    Hines, Thomas E.

    2011-01-01

    Maintaining balance in leadership can be difficult because balance is affected by the personality, strengths, and attitudes of the leader as well as the complicated environment within and outside the community college itself. This article explores what being a leader at the community college means, what the threats are to effective leadership, and…

  9. A Balance of Power?

    ERIC Educational Resources Information Center

    Mosey, Edward

    1991-01-01

    The booming economy of the Pacific Northwest region promotes the dilemma of balancing the need for increased electrical power with the desire to maintain that region's unspoiled natural environment. Pertinent factors discussed within the balance equation are population trends, economic considerations, industrial power requirements, and…

  10. Chemical Equation Balancing.

    ERIC Educational Resources Information Center

    Blakley, G. R.

    1982-01-01

    Reviews mathematical techniques for solving systems of homogeneous linear equations and demonstrates that the algebraic method of balancing chemical equations is a matter of solving a system of homogeneous linear equations. FORTRAN programs using this matrix method to chemical equation balancing are available from the author. (JN)

  11. A smartphone inertial balance

    NASA Astrophysics Data System (ADS)

    Barrera-Garrido, Azael

    2017-04-01

    In order to measure the mass of an object in the absence of gravity, one useful tool for many decades has been the inertial balance. One of the simplest forms of inertial balance is made by two mass holders or pans joined together with two stiff metal plates, which act as springs.

  12. Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb necrosis?

    PubMed

    Warkentin, T E; Pai, M

    2016-02-01

    For unknown reasons, a small minority of critically ill patients with septic or cardiogenic shock, multiorgan failure, and disseminated intravascular coagulation develop symmetrical acral (distal extremity) limb loss due to microvascular thrombosis ('limb gangrene with pulses'). Case reports have described preceding 'shock liver' in some critically ill patients who developed such a picture of ischemic limb necrosis. This suggests that profoundly disturbed procoagulant-anticoagulant balance featuring uncontrolled generation of thrombin-resulting from failure of the protein C and antithrombin natural anticoagulant systems due to insufficient hepatic synthesis of these crucial proteins-could explain the microvascular thrombosis and associated limb loss. We hypothesize that shock liver is the key predisposing risk factor underlying ischemic limb necrosis in the majority of patients who develop this complication in the setting of acute disseminated intravascular coagulation complicating septic or cardiogenic shock. As shock liver precedes onset of limb ischemia by several days, therapeutic intervention may be possible.

  13. Toe Necrosis, Etiologies and Management, a Case Series

    PubMed Central

    Issa, Abdelfatah Abou; Newman, Mackenzie; Simman, Richard

    2014-01-01

    Toe necrosis may have vast different etiologies. These include ischemia, embolus, and others. (1) The most common etiology is ischemia. It is a reduction in blood supply to a viable tissue that can lead to susceptibility to infection and tissue death. Peripheral ischemia, which is rooted in the lower limbs, is a major risk factor for toe necrosis because the basal metabolic requirements of tissue are not being sufficiently met. As a result, pain, ulcers, and gangrene commonly occur. (2) Other causes of direct and indirect toe necrosis and related lower limb gangrene include mechanical trauma, infectious, pharmacological sensitivity, cancer, blue toe syndrome, and other granulomatous diseases, such as Churg-Strauss syndrome. We present a case series of toes necrosis which resulted from different etiologies and their management. PMID:26199887

  14. Cerebral radiation necrosis: diagnostic challenge and clinical management.

    PubMed

    Eisele, S C; Dietrich, J

    2015-09-01

    Cerebral radiation is an indispensable cornerstone in the treatment of many primary and metastatic brain tumors. However, besides its desired therapeutic effect on tumor cells, a significant proportion of patients will experience neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis can result in progressive neurological symptoms and radiographic changes. To differentiate radiation necrosis from progressive tumor based on imaging can pose a diagnostic challenge because the MRI characteristics may be similar in both situations. Therefore, surgical biopsy and pathological confirmation is sometimes necessary to guide further management. Effective treatment options for cerebral radiation necrosis exist and should be offered to symptomatic patients. A better understanding of the cellular and molecular processes underlying the development of radiation necrosis is necessary to prevent and minimize radiation-associated morbidity and to improve treatment strategies.

  15. Renal papillary necrosis and pyelonephritis accompanying fenoprofen therapy.

    PubMed

    Husserl, F E; Lange, R K; Kantrow, C M

    1979-10-26

    Renal papillary necrosis occurred after fenoprofen calcium administration in a patient with systemic lupus erythematosus and urinary tract infection. Possible mechanisms of renal damage may be hypersensitivity, decreased blood flow, and decreased production of a prostaglandin E-like substance.

  16. Recommendations from the INHAND Apoptosis/Necrosis Working Group.

    PubMed

    Elmore, Susan A; Dixon, Darlene; Hailey, James R; Harada, Takanori; Herbert, Ronald A; Maronpot, Robert R; Nolte, Thomas; Rehg, Jerold E; Rittinghausen, Susanne; Rosol, Thomas J; Satoh, Hiroshi; Vidal, Justin D; Willard-Mack, Cynthia L; Creasy, Dianne M

    2016-02-01

    Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:Use necrosis and apoptosis as separate diagnostic terms.Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).Use the combined term apoptosis/single cell necrosis whenThere is no requirement or need to split the processes, orWhen the nature of cell death cannot be determined with certainty, orWhen both

  17. Coexisting avascular necrosis of the scaphoid and lunate.

    PubMed

    Park, Il-Jung; Lee, Sang-Uk; Kim, Hyoung-Min

    2010-11-01

    Reports of coexisting avascular necrosis of more than one carpal bone are rare. We report coexisting avascular necrosis of the scaphoid and lunate in a 56-year-old woman with no history of using steroids or injury. We treated her with a radioscapholunate fusion with two angled 2.4 mm distal radius plates to stabilise the locking plate. At her 12-month follow up there was no evidence of non-union.

  18. [The asterisk sign and adult ischemic femur head necrosis].

    PubMed

    Dihlmann, W; Heller, M

    1985-04-01

    The asterisk sign is a stellate density, which is seen normally in the femoral head on computed tomography. It is due to the demonstration of the trabeculae in the femoral head. In adult ischaemic necrosis of the femoral head, there are characteristic changes in the asterisk sign at an early stage, even before there is collapse of the head. The changes are described and the indications for performing CT of the hip for diagnosing adult ischaemic necrosis are discussed.

  19. Renal cortical necrosis: A rare complication of Plasmodium vivax malaria.

    PubMed

    Kumar, R; Bansal, N; Jhorawat, R; Kimmatkar, P D; Malhotra, V

    2014-11-01

    A young female with Plasmodium vivax malaria presented with anemia, hyperbilirubinemia, thrombocytopenia, and advanced renal failure. She remained anuric for more than 3 weeks. Kidney biopsy confirmed the diagnosis of acute cortical necrosis. During follow-up, she became dialysis independent, but remained in stage 4 chronic kidney disease (CKD) at 3 month. P. vivax is supposed to be benign in nature, but can lead to rare and severe complication like renal cortical necrosis and progress to CKD.

  20. Relationship between dental disease and radiation necrosis of the mandible

    SciTech Connect

    Murray, C.G.; Daly, T.E.; Zimmerman, S.O.

    1980-02-01

    Preirradiation panoramic radiographs of forty-six dentate patients were examined for the presence of significant dental disease. Evidence of a positive association between dental disease present before radiation therapy and subsequent necrosis of the mandible was found leading to a recommendation that significant disease be eradicated before irradiation of oral tissues. Considerable suffering results from bone necrosis, which can be reduced by careful and rational dental diagnosis and treatment.

  1. Intestinal Necrosis due to Sodium Polystyrene Sulfonate (Kayexalate) in Sorbitol

    PubMed Central

    McGowan, C. E.; Saha, S.; Chu, G.; Resnick, M. B.; Moss, S. F.

    2013-01-01

    Background Sodium polystyrene sulfonate (SPS, Kayexalate) has been implicated in the development of intestinal necrosis. Sorbitol, added as a cathartic agent, may be primarily responsible. Previous studies have documented bowel necrosis primarily in postoperative, dialysis, and transplant patients. We sought to identify additional clinical characteristics among patients with probable SPS-induced intestinal necrosis. Methods Rhode Island Hospital surgical pathology records were reviewed to identify all gastrointestinal specimens reported as containing SPS crystals from December 1998 to June 2007. Patient demographics, medical comorbidities, and hospital courses of histologically verified cases of intestinal necrosis were extracted from the medical records. Results Twenty-nine patients with reports of SPS crystals were identified. Nine cases were excluded as incidental findings with normal mucosa. Nine patients were excluded as their symptoms began before SPS administration or because an alternate etiology for bowel ischemia was identified. Eleven patients had confirmed intestinal necrosis and a temporal relationship with SPS administration suggestive of SPS-induced necrosis. Only 2 patients were postoperative, and only 4 had end-stage renal disease (ESRD). All patients had documented hyperkalemia, received oral SPS, and developed symptoms of intestinal injury between 3 hours and 11 days after SPS administration. Four patients died. Conclusion Intestinal ischemia is a recognized risk of SPS in sorbitol. Our series highlights that patients may be susceptible even in the absence of ESRD, surgical intervention, or significant comorbidity. PMID:19373153

  2. Serum transaminase levels after experimental paracetamol-induced hepatic necrosis.

    PubMed Central

    Dixon, M F; Fulker, M J; Walker, B E; Kelleher, J; Losowsky, M S

    1975-01-01

    The relationship between serum transaminase levels and the extent of paracetamol-induced liver necrosis has been investigated in the rat. Three methods of histological quantitation were used to assess of necrosis--arbitrary grading, point counting, and the image-analysis computer. Highly significant correlations were obtained between the three methods and all were found to be reproducible. A close correlation was found between the extent of hepatic necrosis and the serum ASAT and ALAT 24 hours after a large dose (4 g/kg) of paracetamol. Likewise, the mean grade of necrosis correlated reasonably well with the serum enzyme levels in the recovery phase at 36 and 72 hours, although the transaminase level for a given degree of necrosis was considerably lower at 72 hours than at 24 hours. These findings suggest that serum transaminase levels gives a reliable indication of the severity of hepatic necrosis if the time of ingestion of the paracetamol is known and taken into account. Images Fig 1 Fig 2 PMID:1205274

  3. Active balance system and vibration balanced machine

    NASA Technical Reports Server (NTRS)

    Qiu, Songgang (Inventor); Augenblick, John E. (Inventor); Peterson, Allen A. (Inventor); White, Maurice A. (Inventor)

    2005-01-01

    An active balance system is provided for counterbalancing vibrations of an axially reciprocating machine. The balance system includes a support member, a flexure assembly, a counterbalance mass, and a linear motor or an actuator. The support member is configured for attachment to the machine. The flexure assembly includes at least one flat spring having connections along a central portion and an outer peripheral portion. One of the central portion and the outer peripheral portion is fixedly mounted to the support member. The counterbalance mass is fixedly carried by the flexure assembly along another of the central portion and the outer peripheral portion. The linear motor has one of a stator and a mover fixedly mounted to the support member and another of the stator and the mover fixedly mounted to the counterbalance mass. The linear motor is operative to axially reciprocate the counterbalance mass.

  4. Load Balancing Scientific Applications

    SciTech Connect

    Pearce, Olga Tkachyshyn

    2014-12-01

    The largest supercomputers have millions of independent processors, and concurrency levels are rapidly increasing. For ideal efficiency, developers of the simulations that run on these machines must ensure that computational work is evenly balanced among processors. Assigning work evenly is challenging because many large modern parallel codes simulate behavior of physical systems that evolve over time, and their workloads change over time. Furthermore, the cost of imbalanced load increases with scale because most large-scale scientific simulations today use a Single Program Multiple Data (SPMD) parallel programming model, and an increasing number of processors will wait for the slowest one at the synchronization points. To address load imbalance, many large-scale parallel applications use dynamic load balance algorithms to redistribute work evenly. The research objective of this dissertation is to develop methods to decide when and how to load balance the application, and to balance it effectively and affordably. We measure and evaluate the computational load of the application, and develop strategies to decide when and how to correct the imbalance. Depending on the simulation, a fast, local load balance algorithm may be suitable, or a more sophisticated and expensive algorithm may be required. We developed a model for comparison of load balance algorithms for a specific state of the simulation that enables the selection of a balancing algorithm that will minimize overall runtime.

  5. Consideration of Dynamical Balances

    NASA Technical Reports Server (NTRS)

    Errico, Ronald M.

    2015-01-01

    The quasi-balance of extra-tropical tropospheric dynamics is a fundamental aspect of nature. If an atmospheric analysis does not reflect such balance sufficiently well, the subsequent forecast will exhibit unrealistic behavior associated with spurious fast-propagating gravity waves. Even if these eventually damp, they can create poor background fields for a subsequent analysis or interact with moist physics to create spurious precipitation. The nature of this problem will be described along with the reasons for atmospheric balance and techniques for mitigating imbalances. Attention will be focused on fundamental issues rather than on recipes for various techniques.

  6. Balance Evaluation Systems

    NASA Technical Reports Server (NTRS)

    1996-01-01

    NeuroCom's Balance Master is a system to assess and then retrain patients with balance and mobility problems and is used in several medical centers. NeuroCom received assistance in research and funding from NASA, and incorporated technology from testing mechanisms for astronauts after shuttle flights. The EquiTest and Balance Master Systems are computerized posturography machines that measure patient responses to movement of a platform on which the subject is standing or sitting, then provide assessments of the patient's postural alignment and stability.

  7. Errors in potassium balance

    SciTech Connect

    Forbes, G.B.; Lantigua, R.; Amatruda, J.M.; Lockwood, D.H.

    1981-01-01

    Six overweight adult subjects given a low calorie diet containing adequate amounts of nitrogen but subnormal amounts of potassium (K) were observed on the Clinical Research Center for periods of 29 to 40 days. Metabolic balance of potassium was measured together with frequent assays of total body K by /sup 40/K counting. Metabolic K balance underestimated body K losses by 11 to 87% (average 43%): the intersubject variability is such as to preclude the use of a single correction value for unmeasured losses in K balance studies.

  8. Programmed necrosis in the Cross Talk of Cell Death and Inflammation

    PubMed Central

    Chan, Francis Ka-Ming; Luz, Nivea Farias; Moriwaki, Kenta

    2015-01-01

    Cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. Disease pathologies ensue when these processes are disturbed. A plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity or immuno-deficiency. Programmed necrosis or necroptosis is a form of non-apoptotic cell death driven by the receptor interacting protein kinase 3 (RIPK3) and its substrate mixed lineage kinase domain-like (MLKL). RIPK3 partners with its upstream adaptors RIPK1, TRIF or DAI to signal for necroptosis in response to death receptor or toll-like receptor stimulation, pathogen infection, or sterile cell injury. Necroptosis promotes inflammation through leakage of cellular contents from damaged plasma membrane. Intriguingly, many of the signal adaptors of necroptosis have dual functions in innate immune signaling. This unique signature illustrates the cooperative nature of necroptosis and innate inflammatory signaling pathways in managing cell and organismal stresses from pathogen infection and sterile tissue injury. PMID:25493335

  9. Mars Balance Challenge

    NASA Video Gallery

    The Challenge is to develop ideas for how NASA can turn available entry, descent, and landing balance mass on a future Mars mission into a scientific or technological payload. Proposed concepts sho...

  10. Strength and Balance Exercises

    MedlinePlus

    ... Venous Thromboembolism Aortic Aneurysm More Strength and Balance Exercises Updated:Sep 8,2016 If you have medical ... if you have been inactive and want to exercise vigorously, check with your doctor before beginning a ...

  11. Balancing Work & Family.

    ERIC Educational Resources Information Center

    Lee, Chris

    1991-01-01

    Describes the responses of some companies to increasing demands for family-work balance in terms of flexibility in working hours and leave policies, child care, and fringe benefits. Identifies some of the effects on the "bottom line." (SK)

  12. The Balanced Literacy Diet.

    ERIC Educational Resources Information Center

    Willows, Dale

    2002-01-01

    Describes professional development program in Ontario school district to improve student reading and writing skills. Program used food-pyramid concepts to help teacher learn to provide a balanced and flexible approach to literacy instruction based on student needs. (PKP)

  13. Balance Function Disorders

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Researchers at the Balance Function Laboratory and Clinic at the Minneapolis (MN) Neuroscience Institute on the Abbot Northwestern Hospital Campus are using a rotational chair (technically a "sinusoidal harmonic acceleration system") originally developed by NASA to investigate vestibular (inner ear) function in weightlessness to diagnose and treat patients with balance function disorders. Manufactured by ICS Medical Corporation, Schaumberg, IL, the chair system turns a patient and monitors his or her responses to rotational stimulation.

  14. Energy Balance and Obesity

    PubMed Central

    Hill, James O.; Wyatt, Holly R.; Peters, John C.

    2012-01-01

    This paper describes the interplay among energy intake, energy expenditure and body energy stores and illustrates how an understanding of energy balance can help develop strategies to reduce obesity. First, reducing obesity will require modifying both energy intake and energy expenditure and not simply focusing on either alone. Food restriction alone will not be effective in reducing obesity if human physiology is biased toward achieving energy balance at a high energy flux (i.e. at a high level of energy intake and expenditure). In previous environments a high energy flux was achieved with a high level of physical activity but in today's sedentary environment it is increasingly achieved through weight gain. Matching energy intake to a high level of energy expenditure will likely be more a more feasible strategy for most people to maintain a healthy weight than restricting food intake to meet a low level of energy expenditure. Second, from an energy balance point of view we are likely to be more successful in preventing excessive weight gain than in treating obesity. This is because the energy balance system shows much stronger opposition to weight loss than to weight gain. While large behavior changes are needed to produce and maintain reductions in body weight, small behavior changes may be sufficient to prevent excessive weight gain. In conclusion, the concept of energy balance combined with an understanding of how the body achieves balance may be a useful framework in helping develop strategies to reduce obesity rates. PMID:22753534

  15. Watt and joule balances

    NASA Astrophysics Data System (ADS)

    Robinson, Ian A.

    2014-04-01

    The time is fast approaching when the SI unit of mass will cease to be based on a single material artefact and will instead be based upon the defined value of a fundamental constant—the Planck constant—h . This change requires that techniques exist both to determine the appropriate value to be assigned to the constant, and to measure mass in terms of the redefined unit. It is important to ensure that these techniques are accurate and reliable to allow full advantage to be taken of the stability and universality provided by the new definition and to guarantee the continuity of the world's mass measurements, which can affect the measurement of many other quantities such as energy and force. Up to now, efforts to provide the basis for such a redefinition of the kilogram were mainly concerned with resolving the discrepancies between individual implementations of the two principal techniques: the x-ray crystal density (XRCD) method [1] and the watt and joule balance methods which are the subject of this special issue. The first three papers report results from the NRC and NIST watt balance groups and the NIM joule balance group. The result from the NRC (formerly the NPL Mk II) watt balance is the first to be reported with a relative standard uncertainty below 2 × 10-8 and the NIST result has a relative standard uncertainty below 5 × 10-8. Both results are shown in figure 1 along with some previous results; the result from the NIM group is not shown on the plot but has a relative uncertainty of 8.9 × 10-6 and is consistent with all the results shown. The Consultative Committee for Mass and Related Quantities (CCM) in its meeting in 2013 produced a resolution [2] which set out the requirements for the number, type and quality of results intended to support the redefinition of the kilogram and required that there should be agreement between them. These results from NRC, NIST and the IAC may be considered to meet these requirements and are likely to be widely debated

  16. The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

    PubMed

    Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction.

  17. Apoptosis, oncosis, and necrosis. An overview of cell death.

    PubMed Central

    Majno, G.; Joris, I.

    1995-01-01

    The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7856735

  18. Effect of bevacizumab on radiation necrosis of the brain

    SciTech Connect

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A. . E-mail: vlevin@mdanderson.org

    2007-02-01

    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.

  19. Cavendish Balance Automation

    NASA Technical Reports Server (NTRS)

    Thompson, Bryan

    2000-01-01

    This is the final report for a project carried out to modify a manual commercial Cavendish Balance for automated use in cryostat. The scope of this project was to modify an off-the-shelf manually operated Cavendish Balance to allow for automated operation for periods of hours or days in cryostat. The purpose of this modification was to allow the balance to be used in the study of effects of superconducting materials on the local gravitational field strength to determine if the strength of gravitational fields can be reduced. A Cavendish Balance was chosen because it is a fairly simple piece of equipment for measuring gravity, one the least accurately known and least understood physical constants. The principle activities that occurred under this purchase order were: (1) All the components necessary to hold and automate the Cavendish Balance in a cryostat were designed. Engineering drawings were made of custom parts to be fabricated, other off-the-shelf parts were procured; (2) Software was written in LabView to control the automation process via a stepper motor controller and stepper motor, and to collect data from the balance during testing; (3)Software was written to take the data collected from the Cavendish Balance and reduce it to give a value for the gravitational constant; (4) The components of the system were assembled and fitted to a cryostat. Also the LabView hardware including the control computer, stepper motor driver, data collection boards, and necessary cabling were assembled; and (5) The system was operated for a number of periods, data collected, and reduced to give an average value for the gravitational constant.

  20. Balanced ultrafiltration: inflammatory mediator removal capacity.

    PubMed

    Guan, Yulong; Wan, Caihong; Wang, Shigang; Sun, Peng; Long, Cun

    2012-10-01

    Ultrafiltration with a hemoconcentrator may remove excess fluid load and alleviate tissue edema and has been universally adopted in extracorporeal circulation protocols during pediatric cardiac surgery. Balanced ultrafiltration is advocated to remove inflammatory mediators generated during surgery. However, whether balanced ultrafiltration can remove all or a portion of the inflammatory mediator load remains unclear. The inflammatory mediator removal capacity of zero-balanced ultrafiltration was measured during pediatric extracorporeal circulation in vitro. Extracorporeal circulation was composed of cardiotomy reservoir, D902 Lilliput 2 membrane oxygenator, and Capiox AF02 pediatric arterial line filter. The Hemoconcentrator BC 20 plus was placed between arterial purge line and oxygenator venous reservoir. Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24-28%. After 2 h of extracorporeal circulation, zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mmHg with Hoffman clamp. The rate of ultrafiltration (12 mL/min) was controlled by ultrafiltrate outlet pressure. Identical volume of plasmaslyte A was dripped into the circuit to maintain stable hematocrit during the 45 min of the experiment. Plasma and ultrafiltrate samples were drawn every 5 min, and concentrations of inflammatory mediators including interleukin-1β (IL-1β), IL-6, IL-10, neutrophil elastase (NE), and tumor necrosis factor-α (TNF-α) were measured. All assayed inflammatory mediators were detected in the ultrafiltrate, demonstrating that the ultrafiltrator may remove inflammatory mediators. However, dynamic observations suggested that the concentration of NE was highest among the five inflammatory mediators in both plasma and ultrafiltrate (P < 0.001). IL-1β had the lowest concentration in plasma, whereas the concentration of TNF-α was the lowest in ultrafiltrate (P

  1. Automatic force balance calibration system

    NASA Technical Reports Server (NTRS)

    Ferris, Alice T. (Inventor)

    1996-01-01

    A system for automatically calibrating force balances is provided. The invention uses a reference balance aligned with the balance being calibrated to provide superior accuracy while minimizing the time required to complete the calibration. The reference balance and the test balance are rigidly attached together with closely aligned moment centers. Loads placed on the system equally effect each balance, and the differences in the readings of the two balances can be used to generate the calibration matrix for the test balance. Since the accuracy of the test calibration is determined by the accuracy of the reference balance and current technology allows for reference balances to be calibrated to within .+-.0.05%, the entire system has an accuracy of a .+-.0.2%. The entire apparatus is relatively small and can be mounted on a movable base for easy transport between test locations. The system can also accept a wide variety of reference balances, thus allowing calibration under diverse load and size requirements.

  2. Flap Necrosis after Palatoplasty in Patients with Cleft Palate

    PubMed Central

    Rossell-Perry, Percy

    2015-01-01

    Palatal necrosis after palatoplasty in patients with cleft palate is a rare but significant problem encountered by any cleft surgeon. Few studies have addressed this disastrous complication and the prevalence of this problem remains unknown. Failure of a palatal flap may be attributed to different factors like kinking or section of the pedicle, anatomical variations, tension, vascular thrombosis, type of cleft, used surgical technique, surgeon's experience, infection, and malnutrition. Palatal flap necrosis can be prevented through identification of the risk factors and a careful surgical planning should be done before any palatoplasty. Management of severe fistulas observed as a consequence of palatal flap necrosis is a big challenge for any cleft surgeon. Different techniques as facial artery flaps, tongue flaps, and microvascular flaps have been described with this purpose. This review article discusses the current status of this serious complication in patients with cleft palate. PMID:26273624

  3. Synovial fat necrosis associated with ischemic pancreatic disease.

    PubMed

    Smukler, N M; Schumacher, H R; Pascual, E; Brown, S; Ryan, W E; Sadeghian, M R

    1979-05-01

    A 59-year-old man with ischemic pancreatic disease, polyarthritis, and cutaneous nodules has shown histopathologic findings indicative of disseminated fat necrosis in a percutaneous biopsy specimen from the right knee. The histopathologic findings in the synovium included necrotic fat cells, distorted fat cells and adjacent lymphocytes, lipid laden histiocytes, and giant cells. In prior histopathologic studies of the joint involvement associated with this disorder, fat cell necrosis has been found only in the periarticular tissues, and the synovium has appeared normal or showed nonspecific inflammation. However, the present study shows that the synovial membrane may also be the site of fat necrosis and an associated inflammatory reaction; thus patients with this disorder may manifest arthritis in addition to periarthritis.

  4. Tongue necrosis as first symptom of giant cell arteritis (GCA).

    PubMed

    Brodmann, M; Dorr, A; Hafner, F; Gary, T; Pilger, E

    2009-06-01

    Giant cell arteritis (GCA) is the most common systemic vasculitis affecting people over the age of 50 years, especially in the western world. Nevertheless, the initial diagnosis can be tricky, as some of the patients present at first time with a real unusual initial manifestation. One of these can be tongue necrosis, which is according to the literature in accordance with scalp necrosis, the rarest initial manifestation form of GCA. We describe two patients who presented with tongue necrosis as initial symptom of GCA. The diagnosis was made by the American College of Rheumatology criteria, biopsy and duplex sonography of their temporal arteries. A typical halo was seen as a sign of intimal edema. The patients were put on corticosteroids immediately after diagnosis was proven and their symptoms improved quickly.

  5. Cannabinoids act as necrosis-inducing factors in Cannabis sativa.

    PubMed

    Shoyama, Yoshinari; Sugawa, Chitomi; Tanaka, Hiroyuki; Morimoto, Satoshi

    2008-12-01

    Cannabis sativa is well known to produce unique secondary metabolites called cannabinoids. We recently discovered that Cannabis leaves induce cell death by secreting tetrahydrocannabinolic acid (THCA) into leaf tissues. Examinations using isolated Cannabis mitochondria demonstrated that THCA causes mitochondrial permeability transition (MPT) though opening of MPT pores, resulting in mitochondrial dysfunction (the important feature of necrosis). Although Ca(2+) is known to cause opening of animal MPT pores, THCA directly opened Cannabis MPT pores in the absence of Ca(2+). Based on these results, we conclude that THCA has the ability to induce necrosis though MPT in Cannabis leaves, independently of Ca(2+). We confirmed that other cannabinoids (cannabidiolic acid and cannabigerolic acid) also have MPT-inducing activity similar to that of THCA. Moreover, mitochondria of plants which do not produce cannabinoids were shown to induce MPT by THCA treatment, thus suggesting that many higher plants may have systems to cause THCA-dependent necrosis.

  6. Imaging of cavitary necrosis in complicated childhood pneumonia.

    PubMed

    Hodina, M; Hanquinet, S; Cotting, J; Schnyder, P; Gudinchet, F

    2002-02-01

    The aim of this study was to illustrate the chest radiographs (CR) and CT imaging features and sequential findings of cavitary necrosis in complicated childhood pneumonia. Among 30 children admitted in the Pediatric Intensive Care Unit for persistent or progressive pneumonia, respiratory distress or sepsis despite adequate antibiotic therapy, a study group of 9 children (5 girls and 4 boys; mean age 4 years) who had the radiographic features and CT criteria for cavitary necrosis complicated pneumonia was identified. The pathogens identified were Streptococcus pneumoniae( n=4), Aspergillus( n=2), Legionella( n=1), and Staphylococcus aureus( n=1). Sequential CR and CT scans were retrospectively reviewed. Follow-up CR and CT were evaluated for persistent abnormalities. Chest radiographs showed consolidations in 8 of the 9 patients. On CT examination, cavitary necrosis was localized to 1 lobe in 2 patients and 7 patients showed multilobar or bilateral areas of cavitary necrosis. In 3 patients of 9, the cavitary necrosis was initially shown on CT and visualization by CR was delayed by a time span varying from 5 to 9 days. In all patients with cavities, a mean number of five cavities were seen on antero-posterior CR, contrasting with the multiple cavities seen on CT. Parapneumonic effusions were shown by CR in 3 patients and in 5 patients by CT. Bronchopleural fistulae were demonstrated by CT alone ( n=3). No purulent pericarditis was demonstrated. The CT scan displayed persistent residual pneumatoceles of the left lower lobe in 2 patients. Computed tomography is able to define a more specific pattern of abnormalities than conventional CR in children with necrotizing pneumonia and allows an earlier diagnosis of this rapidly progressing condition. Lung necrosis and cavitation may also be associated with Aspergillus or Legionella pneumonia in the pediatric population.

  7. A new geographic and host record for infectious pancreatic necrosis

    USGS Publications Warehouse

    Parisot, T.J.; Yasutake, W.T.; Bressler, V.

    1963-01-01

    The occurrence of infectious pancreatic necrosis in rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), and cutthroat trout (Salmo clarki) has been experimentally authenticated for the first time in the western United States. The cutthroat trout represents a new host. Brook trout fin tissue culture inoculated with bacteria-free filtrate from the diseased fish tissue showed marked degenerative changes after 24 hours. Chinook salmon (Oncorhynchus tshawytscha), kokanee (O. nerka), and silver salmon (O. kisutch) were not susceptible to the virus when inoculated. Histologically, extensive pancreatic necrosis was observed in the original and experimental materials, but striated muscle hyalinization was detected only in the original material.

  8. Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

    PubMed Central

    Brodie, Bernard B.; Reid, Watson D.; Cho, Arthur K.; Sipes, Glenn; Krishna, Gopal; Gillette, James R.

    1971-01-01

    Treatment of rats with phenobarbital, which stimulates the activity of the drug-metabolizing enzymes in the liver, potentiates hepatic necrosis elicited by bromobenzene and a number of other chemically inert halogenated aromatic hydrocarbons. Radioautographic studies indicate that [14C]bromobenzene is covalently bound at the sites of necrosis. From these results, it is inferred that the hepatotoxic effects of the halogenated aromatic hydrocarbons are mediated by chemically active metabolites formed in hepatocytes. In accord with this view, a number of aromatic halogenated hydrocarbons are converted by microsomes in vitro to active intermediates which form covalent complexes with glutathione (GSH). Images PMID:4395686

  9. Sport-specific balance.

    PubMed

    Zemková, Erika

    2014-05-01

    This review includes the latest findings based on experimental studies addressing sport-specific balance, an area of research that has grown dramatically in recent years. The main objectives of this work were to investigate the postural sway response to different forms of exercise under laboratory and sport-specific conditions, to examine how this effect can vary with expertise, and to provide examples of the association of impaired balance with sport performance and/or increasing risk of injury. In doing so, sports where body balance is one of the limiting factors of performance were analyzed. While there are no significant differences in postural stability between athletes of different specializations and physically active individuals during standing in a standard upright position (e.g., bipedal stance), they have a better ability to maintain balance in specific conditions (e.g., while standing on a narrow area of support). Differences in magnitude of balance impairment after specific exercises (rebound jumps, repeated rotations, etc.) and mainly in speed of its readjustment to baseline are also observed. Besides some evidence on an association of greater postural sway with the increasing risk of injuries, there are many myths related to the negative influence of impaired balance on sport performance. Though this may be true for shooting or archery, findings have shown that in many other sports, highly skilled athletes are able to perform successfully in spite of increased postural sway. These findings may contribute to better understanding of the postural control system under various performance requirements. It may provide useful knowledge for designing training programs for specific sports.

  10. Multidimensional spectral load balancing

    SciTech Connect

    Hendrickson, B.; Leland, R.

    1993-01-01

    We describe an algorithm for the static load balancing of scientific computations that generalizes and improves upon spectral bisection. Through a novel use of multiple eigenvectors, our new spectral algorithm can divide a computation into 4 or 8 pieces at once. These multidimensional spectral partitioning algorithms generate balanced partitions that have lower communication overhead and are less expensive to compute than those produced by spectral bisection. In addition, they automatically work to minimize message contention on a hypercube or mesh architecture. These spectral partitions are further improved by a multidimensional generalization of the Kernighan-Lin graph partitioning algorithm. Results on several computational grids are given and compared with other popular methods.

  11. Rotary and Magnus balances

    NASA Technical Reports Server (NTRS)

    Malcolm, G. N.

    1981-01-01

    Two wind tunnel techniques for determining part of the aerodynamic information required to describe the dynamic bahavior of various types of vehicles in flight are described. Force and moment measurements are determined with a rotary-balance apparatus in a coning motion and with a Magnus balance in a high-speed spinning motion. Coning motion is pertinent to both aircraft and missiles, and spinning is important for spin stabilized missiles. Basic principles of both techniques are described, and specific examples of each type of apparatus are presented. Typical experimental results are also discussed.

  12. A Balancing Act

    ERIC Educational Resources Information Center

    Lewis, Tamika; Mobley, Mary; Huttenlock, Daniel

    2013-01-01

    It's the season for the job hunt, whether one is looking for their first job or taking the next step along their career path. This article presents first-person accounts to see how teachers balance the rewards and challenges of working in different types of schools. Tamica Lewis, a third-grade teacher, states that faculty at her school is…

  13. Multidimensional spectral load balancing

    DOEpatents

    Hendrickson, Bruce A.; Leland, Robert W.

    1996-12-24

    A method of and apparatus for graph partitioning involving the use of a plurality of eigenvectors of the Laplacian matrix of the graph of the problem for which load balancing is desired. The invention is particularly useful for optimizing parallel computer processing of a problem and for minimizing total pathway lengths of integrated circuits in the design stage.

  14. Balancing Family and Work.

    ERIC Educational Resources Information Center

    Yahnke, Sally; And Others

    The purpose of this monograph is to present a series of activities designed to teach strategies needed for effectively managing the multiple responsibilities of family and work. The guide contains 11 lesson plans dealing with balancing family and work that can be used in any home economics class, from middle school through college. The lesson…

  15. Balancing Your Evaluation Act.

    ERIC Educational Resources Information Center

    Willyerd, Karie A.

    1997-01-01

    Looks at different performance-measurement tools than can ensure that a training or performance solution is strategically aligned, objectively evaluated, and quantitatively measured for results. Suggests aiming for a balance among the financial, customer, and internal perspectives and the innovation and learning that can result. (Author/JOW)

  16. Balance functions reexamined

    SciTech Connect

    Bialas, A.

    2011-02-15

    The idea of glue clusters, i.e., short-range correlations in the quark-gluon plasma close to freeze-out, is used to estimate the width of balance functions in momentum space. A good agreement is found with the recent measurements of the STAR Collaboration for central Au-Au collisions.

  17. Regulation of Energy Balance.

    ERIC Educational Resources Information Center

    Bray, George A.

    1985-01-01

    Explains relationships between energy intake and expenditure focusing on the cellular, chemical and neural mechanisms involved in regulation of energy balance. Information is referenced specifically to conditions of obesity. (Physicians may earn continuing education credit by completing an appended test). (ML)

  18. Finding a Balance.

    ERIC Educational Resources Information Center

    Gordon, Milton A.; Gordon, Margaret F.

    1996-01-01

    New college presidents are inundated with requests for their time, and their private life is often sacrificed. Each administrator must decide what is the appropriate balance among various aspects of his/her position. Physical separation of public and private lives is essential, and the role of the spouse, who may have other professional…

  19. Lives in the Balance.

    ERIC Educational Resources Information Center

    Our Children, 1997

    1997-01-01

    Changes in the workplace that would provide flexibility for working parents are slowly developing and receiving government, business, and societal attention. A sidebar, "Mother, Professional, Volunteer: One Woman's Balancing Act," presents an account of how one woman rearranged her professional life to enable her to do full-time…

  20. Dynamic localized load balancing

    NASA Astrophysics Data System (ADS)

    Balandin, Sergey I.; Heiner, Andreas P.

    2003-08-01

    Traditionally dynamic load balancing is applied in resource-reserved connection-oriented networks with a large degree of managed control. Load balancing in connectionless networks is rather rudimentary and is either static or requires network-wide load information. This paper presents a fully automated, traffic driven dynamic load balancing mechanism that uses local load information. The proposed mechanism is easily deployed in a multi-vendor environment in which only a subset of routers supports the function. The Dynamic Localized Load Balancing (DLLB) mechanism distributes traffic based on two sets of weights. The first set is fixed and is inverse proportional to the path cost, typically the sum of reciprocal bandwidths along the path. The second weight reflects the utilization of the link to the first next hop along the path, and is therefore variable. The ratio of static weights defines the ideal load distribution, the ratio of variable weights the node-local load distribution estimate. By minimizing the difference between variable and fixed ratios the traffic distribution, with the available node-local knowledge, is optimal. The above mechanism significantly increases throughput and decreases delay from a network-wide perspective. Optionally the variable weight can include load information of nodes downstream to prevent congestion on those nodes. The latter function further improves network performance, and is easily implemented on top of the standard OSPF signaling. The mechanism does not require many node resources and can be implemented on existing router platforms.

  1. Maintaining an Environmental Balance

    ERIC Educational Resources Information Center

    Environmental Science and Technology, 1976

    1976-01-01

    A recent conference of the National Environmental Development Association focused on the concepts of environment, energy and economy and underscored the necessity for balancing the critical needs embodied in these issues. Topics discussed included: nuclear energy and wastes, water pollution control, federal regulations, environmental technology…

  2. Comparison of Types of Cell Death: Apoptosis and Necrosis.

    ERIC Educational Resources Information Center

    Manning, Francis; Zuzel, Katherine

    2003-01-01

    Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

  3. Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

    PubMed Central

    Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

    2009-01-01

    Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

  4. Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV).

    PubMed

    Alonso, Marta; Leong, Jo-Ann C

    2013-04-01

    This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns.

  5. Lunar Balance and Locomotion

    NASA Technical Reports Server (NTRS)

    Paloski, William H.

    2008-01-01

    Balance control and locomotor patterns were altered in Apollo crewmembers on the lunar surface, owing, presumably, to a combination of sensory-motor adaptation during transit and lunar surface operations, decreased environmental affordances associated with the reduced gravity, and restricted joint mobility as well as altered center-of-gravity caused by the EVA pressure suits. Dr. Paloski will discuss these factors, as well as the potential human and mission impacts of falls and malcoordination during planned lunar sortie and outpost missions. Learning objectives: What are the potential impacts of postural instabilities on the lunar surface? CME question: What factors affect balance control and gait stability on the moon? Answer: Sensory-motor adaptation to the lunar environment, reduced mechanical and visual affordances, and altered biomechanics caused by the EVA suit.

  6. Wind tunnel balance

    NASA Technical Reports Server (NTRS)

    Horne, Warren L. (Inventor); Kunz, Nans (Inventor); Luna, Phillip M. (Inventor); Roberts, Andrew C. (Inventor); Smith, Kenneth M. (Inventor); Smith, Ronald C. (Inventor)

    1989-01-01

    A flow-through balance is provided which includes a non-metric portion and a metric portion which form a fluid-conducting passage in fluid communication with an internal bore in the sting. The non-metric and metric portions of the balance are integrally connected together by a plurality of flexure beams such that the non-metric portion, the metric portion and the flexure beams form a one-piece construction which eliminates mechanical hysteresis between the non-metric and the metric portion. The system includes structures for preventing the effects of temperature, pressure and pressurized fluid from producing asymmetric loads on the flexure beams. A temperature sensor and a pressure sensor are located within the fluid-conducting passage of the balance. The system includes a longitudinal bellows member connected at two ends to one of the non-metric portion and the metric portion and at an intermediate portion thereof to the other of (1) and (2). A plurality of strain gages are mounted on the flexure beams to measure strain forces on the flexure beams. The flexure beams are disposed so as to enable symmetric forces on the flexure beams to cancel out so that only asymmetric forces are measured as deviations by the strain gages.

  7. Seismic offset balancing

    SciTech Connect

    Ross, C.P.; Beale, P.L.

    1994-01-01

    The ability to successfully predict lithology and fluid content from reflection seismic records using AVO techniques is contingent upon accurate pre-analysis conditioning of the seismic data. However, all too often, residual amplitude effects remain after the many offset-dependent processing steps are completed. Residual amplitude effects often represent a significant error when compared to the amplitude variation with offset (AVO) response that the authors are attempting to quantify. They propose a model-based, offset-dependent amplitude balancing method that attempts to correct for these residuals and other errors due to sub-optimal processing. Seismic offset balancing attempts to quantify the relationship between the offset response of back-ground seismic reflections and corresponding theoretical predictions for average lithologic interfaces thought to cause these background reflections. It is assumed that any deviation from the theoretical response is a result of residual processing phenomenon and/or suboptimal processing, and a simple offset-dependent scaling function is designed to correct for these differences. This function can then be applied to seismic data over both prospective and nonprospective zones within an area where the theoretical values are appropriate and the seismic characteristics are consistent. A conservative application of the above procedure results in an AVO response over both gas sands and wet sands that is much closer to theoretically expected values. A case history from the Gulf of Mexico Flexure Trend is presented as an example to demonstrate the offset balancing technique.

  8. Gait and balance disorders.

    PubMed

    Masdeu, Joseph C

    2016-01-01

    This chapter focuses on one of the most common types of neurologic disorders: altered walking. Walking impairment often reflects disease of the neurologic structures mediating gait, balance or, most often, both. These structures are distributed along the neuraxis. For this reason, this chapter is introduced by a brief description of the neurobiologic underpinning of walking, stressing information that is critical for imaging, namely, the anatomic representation of gait and balance mechanisms. This background is essential not only in order to direct the relevant imaging tools to the regions more likely to be affected but also to interpret correctly imaging findings that may not be related to the walking deficit object of clinical study. The chapter closes with a discussion on how to image some of the most frequent etiologies causing gait or balance impairment. However, it focuses on syndromes not already discussed in other chapters of this volume, such as Parkinson's disease and other movement disorders, already discussed in Chapter 48, or cerebellar ataxia, in Chapter 23, in the previous volume. As regards vascular disease, the spastic hemiplegia most characteristic of brain disease needs little discussion, while the less well-understood effects of microvascular disease are extensively reviewed here, together with the imaging approach.

  9. Simple Cell Balance Circuit

    NASA Technical Reports Server (NTRS)

    Johnson, Steven D.; Byers, Jerry W.; Martin, James A.

    2012-01-01

    A method has been developed for continuous cell voltage balancing for rechargeable batteries (e.g. lithium ion batteries). A resistor divider chain is provided that generates a set of voltages representing the ideal cell voltage (the voltage of each cell should be as if the cells were perfectly balanced). An operational amplifier circuit with an added current buffer stage generates the ideal voltage with a very high degree of accuracy, using the concept of negative feedback. The ideal voltages are each connected to the corresponding cell through a current- limiting resistance. Over time, having the cell connected to the ideal voltage provides a balancing current that moves the cell voltage very close to that ideal level. In effect, it adjusts the current of each cell during charging, discharging, and standby periods to force the cell voltages to be equal to the ideal voltages generated by the resistor divider. The device also includes solid-state switches that disconnect the circuit from the battery so that it will not discharge the battery during storage. This solution requires relatively few parts and is, therefore, of lower cost and of increased reliability due to the fewer failure modes. Additionally, this design uses very little power. A preliminary model predicts a power usage of 0.18 W for an 8-cell battery. This approach is applicable to a wide range of battery capacities and voltages.

  10. A glucose carbonate apatite complex exhibits in vitro and in vivo anti-tumour effects.

    PubMed

    Yamamoto, Hirofumi; Wu, Xin; Nakanishi, Hiroyuki; Yamamoto, Yuki; Uemura, Mamoru; Hata, Taishi; Nishimura, Junichi; Takemasa, Ichiro; Mizushima, Tsunekazu; Sasaki, Jun-Ichi; Imazato, Satoshi; Matsuura, Nariaki; Doki, Yuichiro; Mori, Masaki

    2015-01-13

    Tumour targeting nanotechnology has recently made therapeutic progress and several therapeutic nanoparticles have been approved for clinical application. However, an ideal nanotechnology based therapeutic for solid tumours, particularly for systemic administration, still remains a challenge in clinical cancer therapy. We previously reported a pH sensitive in vivo delivery system of doxorubicin, or microRNA, using carbonate apatite (CA) nanoparticles. To further explore utility of CA in cancer therapy, we attempted to transport excess glucose into tumour cells by conjugating glucose (Glc) to the nanoparticle. Despite the non-toxicity of CA and Glc, the complex (CA-[Glc]) exhibited an unexpected anti-cancer effect in vitro and in vivo. CA-[Glc] significantly reduced the growth of colon cancer cell lines. Intravenous injections successfully suppressed solid tumour growth. In mice and monkeys, intravenously injected CA-[Glc] complex resulted in no serious abnormalities in body weight or blood chemistry. Because cancer cells intensively metabolise glucose than normal cells, treatment of cancer using glucose seems paradoxical. However, with the aid of CA, this safe and 'sweet' complex may be a novel anti-cancer reagent.

  11. Cell uptake, distribution and response to aluminium chloro sulphonated phthalocyanine, a potential anti-tumour photosensitizer.

    PubMed Central

    Chan, W. S.; Svensen, R.; Phillips, D.; Hart, I. R.

    1986-01-01

    The uptake, retention and effects of aluminium chloro sulphonated phthalocyanine (AlSPc) were measured in two cell lines, UV-2237 a murine fibrosarcoma and the non-tumorigenic NIH/3T3 fibroblast line. The behaviour of cells treated with AlSPc was compared with that of those treated with haematoporphyrin derivative (HpD), a photosensitizer often used in photodynamic therapy (PDT) of cancer. AlSPc absorbs light strongly in the red region, is taken up by cells in a dose dependent fashion and is retained in vitro over a period of days (5 days after exposure greater than 40% remains cell-associated versus less than 25% of HpD). Additionally AlSPc was less cytotoxic to cells, maintained in darkness or exposed to room light, compared to HpD (100% viability versus 0% viability 3 days after 60 min exposure to room light). However red light (approximately 600-700 nm) caused greater toxicity in AlSPc-treated cells (100%) than in similarly exposed HpD-treated cells (less than 60%). No significant differences were detected between the responses of the fibrosarcoma and the fibroblast cell lines. These characteristics of AlSPc suggest that it may prove to be a useful photosensitizer for PDT of cancer and this possibility is discussed. Images Figure 4 PMID:2937437

  12. Mode of action of thiocoraline, a natural marine compound with anti-tumour activity

    PubMed Central

    Erba, E; Bergamaschi, D; Ronzoni, S; Faretta, M; Taverna, S; Bonfanti, M; Catapano, C V; Faircloth, G; Jimeno, J; D'Incalci, M

    1999-01-01

    Thiocoraline, a new anticancer agent derived from the marine actinomycete Micromonospora marina, was found to induce profound perturbations of the cell cycle. On both LoVo and SW620 human colon cancer cell lines, thiocoraline caused an arrest in G1 phase of the cell cycle and a decrease in the rate of S phase progression towards G2/M phases, as assessed by using bromodeoxyuridine/DNA biparametric flow cytometric analysis. Thiocoraline does not inhibit DNA-topoisomerase II enzymes in vitro, nor does it induce DNA breakage in cells exposed to effective drug concentrations. The cell cycle effects observed after exposure to thiocoraline appear related to the inhibition of DNA replication. By using a primer extension assay it was found that thiocoraline inhibited DNA elongation by DNA polymerase α at concentrations that inhibited cell cycle progression and clonogenicity. These studies indicate that the new anticancer drug thiocoraline probably acts by inhibiting DNA polymerase α activity. © 1999 Cancer Research Campaign PMID:10362104

  13. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses.

    PubMed

    Boks, Martine A; Ambrosini, Martino; Bruijns, Sven C; Kalay, Hakan; van Bloois, Louis; Storm, Gert; Garcia-Vallejo, Juan J; van Kooyk, Yvette

    2015-10-28

    Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with strong adjuvants such as TLR ligands. However, often these adjuvants have off-target effects, and would benefit from a DC-specific targeting strategy, similar to the tumour antigen. The goal of this study was to develop a strategy for specifically targeting DC with tumour antigen and adjuvant by using glycoliposomes. We have generated liposomes containing the glycan Lewis(Le)(X) which is highly specific for the C-type lectin receptor DC-SIGN expressed by DC. Le(X)-modified liposomes were taken up by human monocyte-derived DC in a DC-SIGN-specific manner. As adjuvants we incorporated the TLR ligands Pam3CySK4, Poly I:C, MPLA and R848 into liposomes and compared their adjuvant capacity on DC. Incorporation of the TLR4 ligand MPLA into glycoliposomes induced DC maturation and production of pro-inflammatory cytokines, in a DC-SIGN-specific manner, and DC activation was comparable to administration of soluble MPLA. Incorporation of MPLA into glycoliposomes significantly enhanced antigen cross-presentation of the melanoma tumour antigen gp100280-288 peptide to CD8(+) T cells compared to non-glycosylated MPLA liposomes. Importantly, antigen cross-presentation of the gp100280-288 peptide was significantly higher using MPLA glycoliposomes compared to the co-administration of soluble MPLA with glycoliposomes. Taken together, our data demonstrates that specific targeting of a gp100 tumour antigen and the adjuvant MPLA to DC-SIGN-expressing DC enhances the uptake of peptide-containing liposomes, the activation of DC, and induces tumour antigen-specific CD8(+) T cell responses. These data demonstrate that adjuvant-containing glycoliposome-based vaccines targeting DC-SIGN(+) DC represent a powerful new approach for CD8(+) T cell activation.

  14. Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies

    PubMed Central

    Ehrhardt, H; Pannert, L; Pfeiffer, S; Wachter, F; Amtmann, E; Jeremias, I

    2013-01-01

    Background and Purpose In polychemotherapy protocols, that is for treatment of neuroblastoma and Ewing sarcoma, Vinca alkaloids and cell cycle-arresting drugs are usually administered on the same day. Here we studied whether this combination enables the optimal antitumour effects of Vinca alkaloids to be manifested. Experimental Approach Vinca alkaloids were tested in a preclinical mouse model in vivo and in vitro in combination with cell cycle-arresting drugs. Signalling pathways were characterized using RNA interference. Key Results In vitro, knockdown of cyclins significantly inhibited vincristine-induced cell death indicating, in accordance with previous findings, Vinca alkaloids require active cell cycling and M-phase transition for induction of cell death. In contrast, anthracyclines, irradiation and dexamethasone arrested the cell cycle and acted like cytostatic drugs. The combination of Vinca alkaloids with cytostatic therapeutics resulted in diminished cell death in 31 of 36 (86%) tumour cell lines. In a preclinical tumour model, anthracyclines significantly inhibited the antitumour effect of Vinca alkaloids in vivo. Antitumour effects of Vinca alkaloids in the presence of cytostatic drugs were restored by caffeine, which maintained active cell cycling, or by knockdown of p53, which prevented drug-induced cell cycle arrest. Therapeutically most important, optimal antitumour effects were obtained in vivo upon separating the application of Vinca alkaloids from cytostatic therapeutics. Conclusion and Implications Clinical trials are required to prove whether Vinca alkaloids act more efficiently in cancer patients if they are applied uncoupled from cytostatic therapies. On a conceptual level, our data suggest the implementation of polychemotherapy protocols based on molecular mechanisms of drug–drug interactions. Linked Article This article is commented on by Solary, pp 1555–1557 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12101 PMID:23186127

  15. Breast necrosis induced by the use of coumadin: case report and review of literature

    PubMed Central

    Ejzenberg, Dani; Neusquen, Lucienne Pereira Del Grossi; Rolnik, Daniel Lorber; Lozinsky, Adriana Chebar; Piato, José Roberto Morales

    2015-01-01

    The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient. PMID:26018146

  16. Improving Balance with Tai Chi

    MedlinePlus

    ... 8428 · INFO @ VESTIBULAR . ORG · WWW . VESTIBULAR . ORG Improving Balance with Tai Chi By the Vestibular Disorders Association ... symptoms commonly experi- enced with vestibular (inner ear balance) disorders can cause overwhelming fatigue and anxiety. Many ...

  17. Bilateral putaminal necrosis in a comatose patient with metabolic acidosis

    PubMed Central

    Kumar, Sudhir; Reddy, Chenna Rajesh; Prabhakar, Subhashini

    2016-01-01

    We present a case of acute-onset coma in a young woman, associated with metabolic acidosis, respiratory distress, and hypotension. Magnetic resonance imaging of the brain done on day 2 of admission showed features of bilateral putaminal necrosis. History of methanol ingestion, though not forthcoming at admission, was confirmed later after the patient regained consciousness. A final diagnosis of methyl alcohol toxicity resulting in severe metabolic acidosis, coma, and bilateral blindness was made. This case is reported to emphasize the point that the finding of bilateral putaminal necrosis in a patient with coma and metabolic acidosis is virtually diagnostic of methyl alcohol toxicity even in the absence of any positive history. PMID:28149036

  18. Lovenox Induced Tissue Necrosis, a Case Report and Literature Review.

    PubMed

    Issa, Abdelfatah Abou; Simman, Richard

    2013-12-01

    Lovenox is a trade name for Enoxaparin. It is a low molecular weight heparin (LMWH) and has other trade names like Clexane and Xaparin. It is an anticoagulant used to prevent and treat venous thromboembolism events (VTE) like deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. General speaking, the most common skin reactions as a result of enoxaparin use are: urticarial, ecchymosis, and even skin necrosis due to vasculitis. These side effects are usually located at the injection site. New studies have pointed out the side effect that could occur a distance from the site of Lovenox injection. In our case extensive skin and subcutaneous tissue necrosis developed at the abdominal wall injection site.

  19. Diagnostic ultrasonography in cattle with abdominal fat necrosis.

    PubMed

    Tharwat, Mohamed; Buczinski, Sébastien

    2012-01-01

    This study describes the ultrasonographic findings in 14 cows with abdominal fat necrosis. Ultrasonography of the abdomen revealed the presence of heterogeneous hyperechoic masses and hyperechoic omentum with localized masses floating in a hypoechoic peritoneal fluid. A hyperechogenic rim was imaged around both kidneys. The intestines were coated with hyperechoic capsules and the intestinal lumens were constricted. Ultrasonographic examination of the pancreatic parenchyma showed an overall increased echogenicity which was homogenously distributed in 3 cases. A diagnosis of abdominal fat necrosis was made with ultrasound-guided biopsy of the echogenic masses, and thereafter at postmortem examination. Results from this study demonstrate the efficacy of ultrasonography as an imaging modality for antemortem diagnosis of abdominal lipomatosis in cattle. To the authors' knowledge, this study is the first that illustrates ultrasonographic findings in cattle affected with abdominal lipomatosis.

  20. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    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.

  1. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-08-10

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids.

  2. Necrosis Avidity of Organic Compounds: a Natural Phenomenon with Exploitable Theragnostic Potentials.

    PubMed

    Cona, Marlein Miranda; Oyen, Raymond; Ni, Yicheng

    2015-02-27

    Necrosis is an in vivo chaotic event distinguished by uncontrolled disintegration of the cell membrane leading to cytolysis, inflammation and tissue destruction followed by a healing or regenerating process. Targeting necrosis may offer potential diagnostic, therapeutic and/or theragnostic applications in translational medicine. This article reviews the current concept of necrosis including definition, etiology and pathophysiology. The evolution and development of a wide diversity of necrosis targeting agents and their potential applications in preclinical and clinical settings are also elaborated and discussed.

  3. More on Chemical Reaction Balancing.

    ERIC Educational Resources Information Center

    Swinehart, D. F.

    1985-01-01

    A previous article stated that only the matrix method was powerful enough to balance a particular chemical equation. Shows how this equation can be balanced without using the matrix method. The approach taken involves writing partial mathematical reactions and redox half-reactions, and combining them to yield the final balanced reaction. (JN)

  4. Tissue Necrosis due to Chloroform: A Case Report

    PubMed Central

    Mohammadzadeh Akhlaghi, Nahid; Baradaran Mohajeri, Ladan; Fazlyab, Mahta

    2013-01-01

    For many years, gutta-percha has been the root canal filling material of choice. Chloroform is one of the most efficient solvents widely used for gutta-percha removal in retreatment cases, despite being toxic and carcinogenic. The present case report discusses a chloroform extrusion through an existing perforation to the surrounding periodontal ligament space and subsequent necrosis in supporting bone and tissues, during an endodontic retreatment visit for an addicted patient. Subsequently, the management and preventive options are reviewed. PMID:24790633

  5. Pseudolaminar necrosis in cyanide intoxication: a neuropathology case report.

    PubMed

    Riudavets, Miguel Angel; Aronica-Pollak, Patricia; Troncoso, Juan C

    2005-06-01

    We describe the gross and microscopic neuropathological changes in the brain of a 17-year-old male who died 4 days after being poisoned with cyanide. Previous reports indicate that following cyanide intoxication, the brain develops diffuse hypoxic/ischemic changes, predominantly of the basal ganglia. The case we describe here had similar features but in addition showed striking laminar necrosis of the cerebral cortex. This finding in cyanide poisoning has been previously demonstrated by neuroimaging, but not pathologically.

  6. Carrot yellow leaf virus Is Associated with Carrot Internal Necrosis

    PubMed Central

    Adams, Ian P.; Skelton, Anna; Macarthur, Roy; Hodges, Tobias; Hinds, Howard; Flint, Laura; Nath, Palash Deb; Boonham, Neil; Fox, Adrian

    2014-01-01

    Internal necrosis of carrot has been observed in UK carrots for at least 10 years, and has been anecdotally linked to virus infection. In the 2009 growing season some growers had up to 10% of yield with these symptoms. Traditional diagnostic methods are targeted towards specific pathogens. By using a metagenomic approach with high throughput sequencing technology, other, as yet unidentified causes of root necrosis were investigated. Additionally a statistical analysis has shown which viruses are most closely associated with disease symptoms. Carrot samples were collected from a crop exhibiting root necrosis (102 Affected: 99 Unaffected) and tested for the presence of the established carrot viruses: Carrot red leaf virus (CtRLV), Carrot mottle virus (CMoV), Carrot red leaf associated viral RNA (CtRLVaRNA) and Parsnip yellow fleck virus (PYFV). The presence of these viruses was not associated with symptomatic carrot roots either as single viruses or in combinations. A sub-sample of carrots of mixed symptom status was subjected to MiSeq sequencing. The results from these tests suggested Carrot yellow leaf virus (CYLV) was associated with symptomatic roots. Additionally a novel Torradovirus, a novel Closterovirus and two novel Betaflexiviradae related plant viruses were detected. A specific diagnostic test was designed for CYLV. Of the 102 affected carrots, 98% were positive for CYLV compared to 22% of the unaffected carrots. From these data we conclude that although we have yet to practically demonstrate a causal link, CYLV appears to be strongly associated with the presence of necrosis of carrots. PMID:25365290

  7. Radiation necrosis after treatment of solitary intracranial metastases

    SciTech Connect

    Sundaresan, N.; Galicich, J.H.; Deck, M.D.; Tomita, T.

    1981-03-01

    During the period from July 1977 to June 1980, 75 patients underwent the surgical excision of solitary brain metastases, and 61 of these patients received whole brain radiation. Three patients developed chronic radiation necrosis. In the 3 patients with necrosis, computed tomography suggested recurrent tumor; the histological diagnosis of necrosis only was obtained at operation in 2 of these patients and by autopsy in the third. Radiation damage resulted in the death of 1 patient, a chronic vegetative state in another, and severe neurological deficit in the third. An additional 4 patients had neurological complications probably related to radiation therapy. As the survival of such patients is prolonged by aggressive treatment, the incidence of radiation-induced complications is likely to increase. The optimal dose of radiation necessary to destroy microscopic foci of tumor after the surgical resection of a single brain metastasis is unknown. Because of the significant incidence of damage after radiation as currently delivered, studies using graded, lower doses are indicated.

  8. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

    PubMed Central

    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

  9. Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

    PubMed Central

    Gandhi, Malay S.; Kamalov, German; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan C.

    2010-01-01

    Fibrosis is a fundamental component of the adverse structural remodeling of myocardium present in the failing heart. Replacement fibrosis appears at sites of previous cardiomyocyte necrosis to preserve the structural integrity of the myocardium, but not without adverse functional consequences. The extensive nature of this microscopic scarring suggests cardiomyocyte necrosis is widespread and the loss of these contractile elements, combined with fibrous tissue deposition in the form of a stiff in-series and in-parallel elastic elements, contributes to the progressive failure of this normally efficient muscular pump. Cellular and molecular studies into the signal-transducer-effector pathway involved in cardiomyocyte necrosis have identified the crucial pathogenic role of intracellular Ca2+ overloading and subsequent induction of oxidative stress, predominantly confined within its mitochondria, to be followed by the opening of the mitochondrial permeability transition pore that leads to the destruction of these organelles and cells. It is now further recognized that Ca2+ overloading of cardiac myocytes and mitochondria serves as a prooxidant and which is counterbalanced by an intrinsically coupled Zn2+ entry serving as antioxidant. The prospect of raising antioxidant defenses by increasing intracellular Zn2+ with adjuvant nutriceuticals can, therefore, be preferentially exploited to uncouple this intrinsically coupled Ca2+–Zn2+ dyshomeostasis. Hence, novel yet simple cardioprotective strategies may be at hand that deserve to be further explored. PMID:20405318

  10. Reconstruction of soft plate necrosis after endotracheal intubation.

    PubMed

    Lee, Hyuck Jae; Lim, So Young; Pyon, Jai-Kyong; Mun, Goo Hyun; Bang, Sa Ik; Oh, Kap Sung

    2014-01-01

    Uvular necrosis after long-term endotracheal intubation has been previously reported, but there have been no reports regarding soft palate necrosis after endotracheal intubation. Recently, we encountered 2 patients who had a high degree of soft palate necrosis following endotracheal intubation during long-term care in the intensive care unit. This study reports noncongenital soft palate cleft caused by endotracheal intubation. Two patients, aged 30 and 38 years, with noncongenital cleft palate were treated with pharyngeal flap and/or palatoplasty at our institution from March 2011 to May 2013. Initially, the patients complained of acquired speech disorder and severe oronasal regurgitation caused by a palatal defect. Speech ability was evaluated preoperatively and postoperatively by a perceptual language test and nasopharyngoscopy. The cleft soft palates of both patients were completely repaired, and the aforementioned symptoms improved after surgery. Postoperative courses were uneventful in both of the cases, and neither patient experienced a recurrence. Although rare, long-term intensive care unit care with endotracheal intubation can cause noncongenital soft palate cleft. In cases with iatrogenic cleft palate that does not heal with conservative treatment, surgical procedures such as pharyngeal flap and palatoplasty can be helpful.

  11. Mouse thymic necrosis virus: a novel murine lymphotropic agent.

    PubMed

    Morse, S S

    1987-12-01

    Mouse thymic necrosis virus (TA), one of two naturally occurring herpesviruses in laboratory mice, was first described in 1961. TA has received relatively little attention even though the virus has been isolated independently from various mouse colonies. This neglect is probably due, at least in part, to the lack of suitable cell culture systems. This review summarizes current knowledge concerning thymic necrosis virus, including new results from the author's laboratory. In vivo, TA causes massive thymic necrosis in newborn mice, with temporary ablation of thymocyte precursors for most T lymphocyte classes except T suppressor cells. All strains of laboratory mice appear susceptible. Severe immunosuppression has been demonstrated in acutely infected mice. Most infected animals survive and shed TA chronically from salivary glands and possibly other glandular tissues. In adult mice, primary infection results in persistent salivary gland infection without overt thymic lesions. Infection appears lifelong, with few clinical signs, but possible effects of chronic TA infection on immune function have been studied little. Recent evidence from the author's laboratory suggests that chronic infection may involve T lymphocytes. The name mouse T lymphotropic virus (abbreviation MTLV) is proposed.

  12. Intraductal membranous fat necrosis in a fibroadenoma of breast: a case report.

    PubMed

    Coyne, John D

    2014-09-01

    Membranous fat necrosis is an unusual type of fat necrosis occurring in the breast and normally involves the parenchyma. This report describes an apparently unique intraductal focus in a fibroadenoma following prior needling. Displacement of fatty tissue in the form of membranous fat necrosis within ducts could be added to the list of histological features following core biopsy.

  13. Lesson "Balance in Nature

    NASA Astrophysics Data System (ADS)

    Chapanova, V.

    2012-04-01

    Lesson "Balance in Nature" This simulation game-lesson (Balance in Nature) gives an opportunity for the students to show creativity, work independently, and to create models and ideas. It creates future-oriented thought connected to their experience, allowing them to propose solutions for global problems and personal responsibility for their activities. The class is divided in two teams. Each team chooses questions. 1. Question: Pollution in the environment. 2. Question: Care for nature and climate. The teams work on the chosen tasks. They make drafts, notes and formulate their solutions on small pieces of paper, explaining the impact on nature and society. They express their points of view using many different opinions. This generates alternative thoughts and results in creative solutions. With the new knowledge and positive behaviour defined, everybody realizes that they can do something positive towards nature and climate problems and the importance of individuals for solving global problems is evident. Our main goal is to recover the ecological balance, and everybody explains his or her own well-grounded opinions. In this work process the students obtain knowledge, skills and more responsible behaviour. This process, based on his or her own experience, dialogue and teamwork, helps the participant's self-development. Making the model "human↔ nature" expresses how human activities impact the natural Earth and how these impacts in turn affect society. Taking personal responsibility, we can reduce global warming and help the Earth. By helping nature we help ourselves. Teacher: Veselina Boycheva-Chapanova " Saint Patriarch Evtimii" Scholl Str. "Ivan Vazov"-19 Plovdiv Bulgaria

  14. Micromechanical Oscillating Mass Balance

    NASA Technical Reports Server (NTRS)

    Altemir, David A. (Inventor)

    1997-01-01

    A micromechanical oscillating mass balance and method adapted for measuring minute quantities of material deposited at a selected location, such as during a vapor deposition process. The invention comprises a vibratory composite beam which includes a dielectric layer sandwiched between two conductive layers. The beam is positioned in a magnetic field. An alternating current passes through one conductive layers, the beam oscillates, inducing an output current in the second conductive layer, which is analyzed to determine the resonant frequency of the beam. As material is deposited on the beam, the mass of the beam increases and the resonant frequency of the beam shifts, and the mass added is determined.

  15. Exploring Theranostic Potentials of Radioiodinated Hypericin in Rodent Necrosis Models

    PubMed Central

    Li, Junjie; Cona, Marlein Miranda; Chen, Feng; Feng, Yuanbo; Zhou, Lin; Yu, Jie; Nuyts, Johan; de Witte, Peter; Zhang, Jian; Himmelreich, Uwe; Verbruggen, Alfons; Ni, Yicheng

    2012-01-01

    Objectives: The present animal experiments were conducted to evaluate radioiodinated Hypericin (Hyp) for its regional distribution as well as theranostic potentials. Materials and Methods: Rat models of reperfused liver infarction (RLI) and hepatic rhabdomyosarcoma (R1) were surgically induced. R1 models received Combretastatin A4 phosphate (CA4P) intravenously at 10 mg/kg 24 h prior to radioiodinated Hyp. Three groups of 6 rats each containing 3 RLI and 3 R1 models received iv injections of 123I-Hyp at 37, 74, and 185 MBq/kg respectively and followed by 0.1 ml of 1% Evans blue solution were sacrificed at 4, 24 and 48 hour post injection immediately after in vivo examination of MRI and planar gamma scintigraphy. Besides, two groups of 6 R1 models that received either 300 MBq/kg of 131I-Hyp or vehicle intravenously were examined using MRI to compare tumor growth for 12 days. Autoradiography, gamma counting, and histopathology were performed for postmortem verifications and quantification. Results: Necrosis as seen in vivo on contrast-enhanced MRI corresponded well with the hot spots on planar scintigraphy. Autoradiography and gamma counting revealed intense accumulation of 123I-Hyp in necrotic liver (3.94 ± 1.60, 5.38 ± 1.04, and 6.03 ± 2.09 %ID/g ± SD) and necrotic tumor (4.27 ± 0.76, 5.57 ± 0.76, and 5.68 ± 1.33 %ID/g ± SD) relative to normal liver (1.76 ± 0.54, 0.41 ± 0.18, and 0.16 ± 0.07 %ID/g ± SD), with a high necrosis-to-liver ratio of 2.3, 14.0, and 37.0 at 4, 24 and 48 h respectively. Tumor volumes in R1 models that received 131I-Hyp and vehicle changed from 0.45 ± 0.09, and 0.47 ± 0.12 cm3 (p > 0.05) on day 0 to1.32 ± 0.76 and 3.63 ± 0.72 cm3 (p < 0.001) on day 12, with the corresponding necrosis ratios from 73 ± 12 %, and 76 ± 17 % to 47 ± 18% and 17 ± 13 % (p < 0.01), and with the tumor DT of 7.3 ± 1.0 and 4.2 ± 0.7 days, respectively. Conclusions: Radioiodinated Hyp as a necrosis avid tracer appears promising for non

  16. Resource Balancing Control Allocation

    NASA Technical Reports Server (NTRS)

    Frost, Susan A.; Bodson, Marc

    2010-01-01

    Next generation aircraft with a large number of actuators will require advanced control allocation methods to compute the actuator commands needed to follow desired trajectories while respecting system constraints. Previously, algorithms were proposed to minimize the l1 or l2 norms of the tracking error and of the control effort. The paper discusses the alternative choice of using the l1 norm for minimization of the tracking error and a normalized l(infinity) norm, or sup norm, for minimization of the control effort. The algorithm computes the norm of the actuator deflections scaled by the actuator limits. Minimization of the control effort then translates into the minimization of the maximum actuator deflection as a percentage of its range of motion. The paper shows how the problem can be solved effectively by converting it into a linear program and solving it using a simplex algorithm. Properties of the algorithm are investigated through examples. In particular, the min-max criterion results in a type of resource balancing, where the resources are the control surfaces and the algorithm balances these resources to achieve the desired command. A study of the sensitivity of the algorithms to the data is presented, which shows that the normalized l(infinity) algorithm has the lowest sensitivity, although high sensitivities are observed whenever the limits of performance are reached.

  17. Balance ability and athletic performance.

    PubMed

    Hrysomallis, Con

    2011-03-01

    The relationship between balance ability and sport injury risk has been established in many cases, but the relationship between balance ability and athletic performance is less clear. This review compares the balance ability of athletes from different sports, determines if there is a difference in balance ability of athletes at different levels of competition within the same sport, determines the relationship of balance ability with performance measures and examines the influence of balance training on sport performance or motor skills. Based on the available data from cross-sectional studies, gymnasts tended to have the best balance ability, followed by soccer players, swimmers, active control subjects and then basketball players. Surprisingly, no studies were found that compared the balance ability of rifle shooters with other athletes. There were some sports, such as rifle shooting, soccer and golf, where elite athletes were found to have superior balance ability compared with their less proficient counterparts, but this was not found to be the case for alpine skiing, surfing and judo. Balance ability was shown to be significantly related to rifle shooting accuracy, archery shooting accuracy, ice hockey maximum skating speed and simulated luge start speed, but not for baseball pitching accuracy or snowboarding ranking points. Prospective studies have shown that the addition of a balance training component to the activities of recreationally active subjects or physical education students has resulted in improvements in vertical jump, agility, shuttle run and downhill slalom skiing. A proposed mechanism for the enhancement in motor skills from balance training is an increase in the rate of force development. There are limited data on the influence of balance training on motor skills of elite athletes. When the effectiveness of balance training was compared with resistance training, it was found that resistance training produced superior performance results for

  18. Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Li, Lianhuang; Jiang, Weizhong; Yang, Yinghong; Chen, Zhifen; Feng, Changyin; Li, Hongsheng; Guan, Guoxian; Chen, Jianxin

    2014-06-01

    Dirty necrosis within glandular lumina is often considered as a characteristic of colorectal carcinomas (CRCs) that is a diagnostically useful feature of CRCs with DNA microsatellite instability (MSI). Multiphoton microscopy (MPM), which is based on the second-harmonic generation and two-photon excited fluorescence signals, was used to identify dirty necrosis. Our results demonstrated that MPM has the ability to exhibit the microstructure of dirty necrosis and the signal intensity as well as an emission spectrum that can help to differentiate dirty necrosis from cancer cells. These findings indicate that MPM may be helpful in distinguishing MSI colorectal carcinoma via the identification of dirty necrosis.

  19. Balancing Family and Career

    NASA Astrophysics Data System (ADS)

    Andam, Aba Bentil; Dawson, Silvina Ponce; Horton, K. Renee; Sandow, Barbara

    2005-10-01

    In essentially all countries, responsibilities for child care, cooking, cleaning, and other homemaking tasks fall predominantly on the wife and mother. In addition, the childbearing years come during the period when a physicist must study hard, work long hours on research, and take temporary positions, often abroad. Thus, balancing family and career has long been one of the major barriers to women's participation in science and engineering fields, including physics. While many young women believe that they must choose between having children and having a science career, the fact is that the majority of women physicists in both developing and developed countries have successfully done both. This paper summarizes some ideas and recommendations raised in discussions, especially focused on easing the challenges of having children while in temporary jobs, returning to physics after a career break, the need for "family-friendly" working conditions, and the dual-career problem facing couples where both are scientists.

  20. Energy balance climate models

    NASA Technical Reports Server (NTRS)

    North, G. R.; Cahalan, R. F.; Coakley, J. A., Jr.

    1981-01-01

    An introductory survey of the global energy balance climate models is presented with an emphasis on analytical results. A sequence of increasingly complicated models involving ice cap and radiative feedback processes are solved, and the solutions and parameter sensitivities are studied. The model parameterizations are examined critically in light of many current uncertainties. A simple seasonal model is used to study the effects of changes in orbital elements on the temperature field. A linear stability theorem and a complete nonlinear stability analysis for the models are developed. Analytical solutions are also obtained for the linearized models driven by stochastic forcing elements. In this context the relation between natural fluctuation statistics and climate sensitivity is stressed.

  1. Skin friction balance

    NASA Technical Reports Server (NTRS)

    Ping, Tcheng (Inventor); Supplee, Frank H., Jr. (Inventor)

    1989-01-01

    A skin friction balance uses a parallel linkage mechanism to avoid inaccuracies in skin friction measurement attributable to off-center normal forces. The parallel linkage mechanism includes a stationary plate mounted in a cage, and an upper and lower movable plate which are linked to each other and to the stationary plate throught three vertical links. Flexure pivots are provided for pivotally connecting the links and the plates. A sensing element connected to the upper plate moves in response to skin friction, and the lower plate moves in the opposite direction of the upper plate. A force motor maintains a null position of the sensing element by exerting a restoring force in response to a signal generated by a linear variable differential transformer (LVDT).

  2. Energy balance in peridynamics.

    SciTech Connect

    Lehoucq, Richard B.; Silling, Stewart Andrew

    2010-09-01

    The peridynamic model of solid mechanics treats internal forces within a continuum through interactions across finite distances. These forces are determined through a constitutive model that, in the case of an elastic material, permits the strain energy density at a point to depend on the collective deformation of all the material within some finite distance of it. The forces between points are evaluated from the Frechet derivative of this strain energy density with respect to the deformation map. The resulting equation of motion is an integro-differential equation written in terms of these interparticle forces, rather than the traditional stress tensor field. Recent work on peridynamics has elucidated the energy balance in the presence of these long-range forces. We have derived the appropriate analogue of stress power, called absorbed power, that leads to a satisfactory definition of internal energy. This internal energy is additive, allowing us to meaningfully define an internal energy density field in the body. An expression for the local first law of thermodynamics within peridynamics combines this mechanical component, the absorbed power, with heat transport. The global statement of the energy balance over a subregion can be expressed in a form in which the mechanical and thermal terms contain only interactions between the interior of the subregion and the exterior, in a form anticipated by Noll in 1955. The local form of this first law within peridynamics, coupled with the second law as expressed in the Clausius-Duhem inequality, is amenable to the Coleman-Noll procedure for deriving restrictions on the constitutive model for thermomechanical response. Using an idea suggested by Fried in the context of systems of discrete particles, this procedure leads to a dissipation inequality for peridynamics that has a surprising form. It also leads to a thermodynamically consistent way to treat damage within the theory, shedding light on how damage, including the

  3. Interleukin 10 and Tumor Necrosis Factor-Alpha in Pregnancy: Aspects of Interest in Clinical Obstetrics

    PubMed Central

    Brogin Moreli, Jusciele; Cirino Ruocco, Ana Maria; Vernini, Joice Monaliza; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

    2012-01-01

    The purpose of this study was to review the literature regarding the action of the cytokines interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in pregnancy and to emphasize the factors that are of interest to clinical obstetrics. The literature highlights several actions of IL-10 and TNF-α during pregnancy. The actions of these cytokines seem to be antagonistic and dependent on the balance between them, which is orchestrated by the specific immunosuppressive action of IL-10. TNF-α has a characteristic inflammatory action, and it is an additional diabetogenic factor in pregnancy. The loss of the control of the production of these cytokines, with increase of TNF-α, is related to the risk for developing obstetric complications, particularly recurrent fetal loss, gestational diabetes mellitus, hypertensive syndromes, and fetal growth restriction. However, study results are controversial and are not clearly defined. These issues are attributed to the heterogeneity of the studies, particularly regarding their sample sizes and sources, the evaluation methods, and the multiplicity of factors and conditions that influence cytokine production. These questions are fundamental and should be addressed in future investigations to obtain more consistent results that can be applied to obstetric practice. PMID:22462002

  4. Human Tumour Necrosis Factor: Physiological and Pathological Roles in Placenta and Endometrium

    PubMed Central

    Haider, S.; Knöfler, M.

    2010-01-01

    The cytokine tumour necrosis factor α (TNF) is a well known member of the TNF superfamily consisting of at least 18 ligands and 29 different receptors involved in numerous cellular processes. TNF signals through two distinct receptors TNFR1 and TNFR2 thereby controlling expression of cytokines, immune receptors, proteases, growth factors and cell cycle genes which in turn regulate inflammation, survival, apoptosis, cell migration, proliferation and differentiation. Since expression of TNF was discovered in amnion and placenta many studies demonstrated the presence of the cytokine and its receptors in the diverse human reproductive tissues. Whereas TNF has been implicated in ovulation, corpus luteum formation and luteolysis, this review focuses on the functions of TNF in human placental, endometrial and decidual cell types of normal tissues and also discusses its role in endometrial and gestational diseases. Physiological levels of the cytokine could be important for balancing cell fusion and apoptotic shedding of villous trophoblasts and to limit trophoblast invasion into maternal decidua. Regulation of the TNF/TNFR system by steroid hormones also suggests a role in uterine function including menstrual cycle-dependent destruction and regeneration of endometrial tissue. Aberrant levels of TNF, however, are associated with diverse reproductive diseases such as amniotic infections, recurrent spontaneous abortions, preeclampsia, preterm labour or endometriosis. Hence, concentrations, receptor distribution and length of stimulation determine whether TNF has beneficial or adverse effects on female reproduction and pregnancy. PMID:19027157

  5. Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration

    PubMed Central

    Dong, Yun; Fischer, Roman; Naudé, Petrus J. W.; Maier, Olaf; Nyakas, Csaba; Duffey, Maëlle; Van der Zee, Eddy A.; Dekens, Doortje; Douwenga, Wanda; Herrmann, Andreas; Guenzi, Eric; Kontermann, Roland E.; Pfizenmaier, Klaus; Eisel, Ulrich L. M.

    2016-01-01

    Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNFR2, an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration. Coadministration of either ATROSAB or EHD2-scTNFR2 into the magnocellular nucleus basalis significantly protected cholinergic neurons and their cortical projections against cell death, and reverted the neurodegeneration-associated memory impairment in a passive avoidance paradigm. Simultaneous blocking of TNFR1 and TNFR2 signaling, however, abrogated the therapeutic effect. Our results uncover an essential role of TNFR2 in neuroprotection. Accordingly, the therapeutic activity of ATROSAB is mediated by shifting the balance of the antithetic activity of endogenous TNF toward TNFR2, which appears essential for neuroprotection. Our data also explain earlier results showing that complete blocking of TNF activity by anti-TNF drugs was detrimental rather than protective and argue for the use of next-generation TNFR-selective TNF therapeutics as an effective approach in treating neurodegenerative diseases. PMID:27791020

  6. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

    Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

    2014-01-01

    Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to

  7. Phosphorus Necrosis of the Jaw: A Present-day Study

    PubMed Central

    Hughes, J. P. W.; Baron, R.; Buckland, D. H.; Cooke, M. A.; Craig, J. D.; Duffield, D. P.; Grosart, A. W.; Parkes, P. W. J.; Porter, A.

    1962-01-01

    A historical note on the aetiology of phossy jaw shows that present-day knowledge is little greater than it was a century ago. The varied clinical course of the disease is described together with a report of 10 classical cases not previously reported. Six cases, not amounting to true necrosis but in which healing after dental extraction was delayed, and described, and mention is made of the noticeable differences in the oral state and appearances of tartar of healthy workmen exposed to phosphorus compared with healthy workmen not exposed. But no systematic differences of any kind were found in the incidence of general infections, fractures of bones, haematological findings, and biochemical studies of blood and urine in two groups of healthy men most exposed and least exposed to phosphorous in the same factory. An intensive study in hospital of a case of classical necrosis showed no departure from normal, except delayed healing following bone biopsy from the iliac crest, and a reversed polymorphonuclear/lymphocyte ratio. In the discussion the time of onset of necrosis after first exposure to phosphorus, clinical and radiological diagnosis, the organisms present, personal susceptibility, the appearance of the sequestra, and regeneration of bone are considered. An up-to-date note on prevention of the disease is given, although this has met with only partial success. Some persons are highly susceptible and, whilst complete protection is impossible in the light of our present knowledge, early diagnosis and modern treatment have robbed the disease of its terrible manifestations of Victorian times and turned it into a minor, although often uncomfortable complaint, with little or no resulting disability. Images PMID:14449812

  8. Prognostic markers in acute pancreatitis: can pancreatic necrosis be predicted?

    PubMed Central

    Leese, T.; Shaw, D.; Holliday, M.

    1988-01-01

    The value of six prognostic markers was assessed prospectively in 198 attacks of acute pancreatitis with specific attention to their ability to predict pancreatic necrosis. The Imrie Prognostic Score (IPS) was recorded within 48 h of diagnosis. The serum C-reactive protein (CRP) alpha 1 antiprotease (A1AP), alpha 2 macroglobulin (A2M), amylase and white cell count (WCC) were measured on days 1, 3 and 7. When comparing all severe clinical outcomes to mile outcomes, serum CRP concentrations were higher on all three days (P less than 0.02, less than 0.001, less than 0.001), A1AP concentrations were higher on day 3 (P less than 0.05), A2M concentrations were lower on day 7 (P less than 0.01) and WCC was higher on all three days (P less than 0.001, less than 0.001, less than 0.001). Serum amylase concentrations showed no significant differences. None of the measured parameters were helpful in distinguishing patients who subsequently developed pancreatic necrosis from patients who had other severe outcomes. Multivariate analysis revealed that the initial IPS showed greatest independent significance in predicting severe outcome followed by the WCC (days 1 and 7) and CRP (day 3). CRP and WCC may be clinically useful predictors of severe outcome to supplement the initial IPS. These methods are unlikely to distinguish pancreatic necrosis from other severe outcomes, but they may supplement clinical judgment in selecting a high risk group of patients for contrast enhanced computed tomography. PMID:2458063

  9. FTY720 impairs necrosis development after ischemia-reperfusion injury.

    PubMed

    Oliveira, C M S; Borra, R C; Franco, M; Schor, N; Silva, H T; Pestana, J O M; Bueno, V

    2004-05-01

    Ischemia-reperfusion (IR) injury is a common early feature that contributes to graft damage by impairing resident cell function. Our previous results showed that IR injury impaired renal function, by causing extensive tubular necrosis and increasing MHC class II and ICAM-1 molecule expression by mesangial cells (MC). MCs are likely candidates to come into close contact with immune cells such as monocytes or lymphocytes. It has been suggested that under inflammatory circumstances, there is increased MC expression of MHC class II, of adhesion molecules (such as ICAM-1), of cytokines receptors, and of molecules associated with cellular death (apoptosis). The immunosuppressive properties of FTY720 have been shown in clinical and experimental situations. It has also been shown to be protective against IR injury in rats. We sought to evaluate the role of FTY720 in a murine IR model by measuring renal function, tubular necrosis, and surface molecule expression by cultured mesangial cells. Intravenous administration of FTY720 (1 mg/kg) immediately before IR induction did not improve the short-term (24 hours) outcome of renal function or reduced MHC class II and ICAM-1 surface molecule expression. However, there was a decreased percentage of tubular necrosis in mice treated with FTY720 (51.3% +/- 1.6%) compared with vehicle-treated mice (66% +/- 5.5%). These results suggest a protective role of FTY720 in an IR injury model. More studies are required to identify the mechanisms involved in the protective activity of FTY720 in the IR injury model.

  10. [Protocol for the treatment of severe acute pancreatitis with necrosis].

    PubMed

    Barreda, Luis; Targarona, Javier; Rodriguez, César

    2005-01-01

    The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

  11. Brain necrosis after radiotherapy for primary intracerebral tumor.

    PubMed

    Hohwieler, M L; Lo, T C; Silverman, M L; Freidberg, S R

    1986-01-01

    Radiotherapy is a standard postoperative treatment for cerebral glioma. We have observed the onset of symptoms related to brain necrosis, as opposed to recurrent tumor, in surviving patients. This has been manifest as dementia with a computed tomographic pattern of low density in the frontal lobe uninvolved with tumor, but within the field of radiotherapy. Two patients presented with mass lesions also unrelated to recurrent tumor. We question the necessity of full brain irradiation and suggest that radiotherapy techniques be altered to target the tumor and not encompass the entire brain.

  12. Acute hepatic encephalopathy presenting as cortical laminar necrosis: case report.

    PubMed

    Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young

    2013-01-01

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

  13. Tumor necrosis factor inhibitors – state of knowledge

    PubMed Central

    Lis, Krzysztof; Kuzawińska, Olga

    2014-01-01

    Tumor necrosis factor (TNF) is considered a major proinflammatory cytokine, affecting various aspects of the immune reaction. All five TNF inhibitors currently available on the market (i.e., etanercept, infliximab, adalimumab, certolizumab and golimumab) are top sellers, although indicated only in autoimmune diseases, including rheumatoid arthritis, Crohn's disease and psoriasis. This article briefly discusses the background and place for TNF inhibitors in modern therapy. The main safety aspects of TNF inhibitor administration are described in particular, with special consideration of the available meta-analyses. Finally, perspectives on the next-generation TNF inhibitors and their use in the clinic are given. PMID:25624856

  14. Dynamic load balancing of applications

    DOEpatents

    Wheat, S.R.

    1997-05-13

    An application-level method for dynamically maintaining global load balance on a parallel computer, particularly on massively parallel MIMD computers is disclosed. Global load balancing is achieved by overlapping neighborhoods of processors, where each neighborhood performs local load balancing. The method supports a large class of finite element and finite difference based applications and provides an automatic element management system to which applications are easily integrated. 13 figs.

  15. Dynamic load balancing of applications

    DOEpatents

    Wheat, Stephen R.

    1997-01-01

    An application-level method for dynamically maintaining global load balance on a parallel computer, particularly on massively parallel MIMD computers. Global load balancing is achieved by overlapping neighborhoods of processors, where each neighborhood performs local load balancing. The method supports a large class of finite element and finite difference based applications and provides an automatic element management system to which applications are easily integrated.

  16. Radar channel balancing with commutation

    SciTech Connect

    Doerry, Armin Walter

    2014-02-01

    When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

  17. Rotor balancing apparatus and system

    NASA Technical Reports Server (NTRS)

    Lyman, Frank (Inventor); Lyman, Joseph (Inventor)

    1976-01-01

    Rotor balancing apparatus and a system comprising balance probes for measuring unbalance at the ends of a magnetically suspended rotor are disclosed. Each balance probe comprises a photocell which is located in relationship to the magnetically suspended rotor such that unbalance of the rotor changes the amount of light recorded by each photocell. The signal from each photocell is electrically amplified and displayed by a suitable device, such as an oscilloscope.

  18. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  19. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  20. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  1. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  2. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  3. The role of tumour necrosis factor alpha and soluble tumour necrosis factor alpha receptors in the symptomatology of schizophrenia.

    PubMed

    Turhan, Levent; Batmaz, Sedat; Kocbiyik, Sibel; Soygur, Arif Haldun

    2016-07-01

    Background Immunological mechanisms may be responsible for the development and maintenance of schizophrenia symptoms. Aim The aim of this study is to measure tumour necrosis factor-alpha (TNF-α), soluble tumour necrosis factor-alpha receptor I (sTNF-αRI), and soluble tumour necrosis factor-alpha receptor II (sTNF-αRII) levels in patients with schizophrenia and healthy individuals, and to determine their relationship with the symptoms of schizophrenia. Methods Serum TNF-α, sTNF-αRI and sTNF-αRII levels were measured. The Positive and Negative Syndrome Scale (PANSS) was administered for patients with schizophrenia (n = 35), and the results were compared with healthy controls (n = 30). Hierarchical regression analyses were undertaken to predict the levels of TNF-α, sTNF-αRI and sTNF-αRII. Results No significant difference was observed in TNF-α levels, but sTNF-αRI and sTNF-αRII levels were lower in patients with schizophrenia. Serum sTNF-αRI and sTNF-αRII levels were found to be negatively correlated with the negative subscale score of the PANSS, and sTNF-αRI levels were also negatively correlated with the total score of the PANSS. Smoking, gender, body mass index were not correlated with TNF-α and sTNF-α receptor levels. Conclusions These results suggest that there may be a change in anti-inflammatory response in patients with schizophrenia due to sTNF-αRI and sTNF-αRII levels. The study also supports low levels of TNF activity in schizophrenia patients with negative symptoms.

  4. Mastectomy Weight and Tissue Expander Volume Predict Necrosis and Increased Costs Associated with Breast Reconstruction

    PubMed Central

    Yalanis, Georgia C.; Nag, Shayoni; Georgek, Jakob R.; Cooney, Carisa M.; Manahan, Michele A.; Rosson, Gedge D.

    2015-01-01

    Introduction: Impaired vascular perfusion in tissue expander (TE) breast reconstruction leads to mastectomy skin necrosis. We investigated factors and costs associated with skin necrosis in postmastectomy breast reconstruction. Methods: Retrospective review of 169 women with immediate TE placement following mastectomy between May 1, 2009 and May 31, 2013 was performed. Patient demographics, comorbidities, intraoperative, and postoperative outcomes were collected. Logistic regression analysis on individual variables was performed to determine the effects of tissue expander fill volume and mastectomy specimen weight on skin necrosis. Billing data was obtained to determine the financial burden associated with necrosis. Results: This study included 253 breast reconstructions with immediate TE placement from 169 women. Skin necrosis occurred in 20 flaps for 15 patients (8.9%). Patients with hypertension had 8 times higher odds of skin necrosis [odd ratio (OR), 8.10, P < 0.001]. Patients with TE intraoperative fill volumes >300 cm3 had 10 times higher odds of skin necrosis (OR, 10.66, P =0.010). Volumes >400 cm3 had 15 times higher odds of skin necrosis (OR, 15.56, P = 0.002). Mastectomy specimen weight was correlated with skin necrosis. Specimens >500 g had 10 times higher odds of necrosis and specimens >1000 g had 18 times higher odds of necrosis (OR, 10.03 and OR, 18.43; P =0.003 and P <0.001, respectively). Mastectomy skin necrosis was associated with a 50% increased inpatient charge. Conclusion: Mastectomy flap necrosis is associated with HTN, larger TE volumes and mastectomy specimen weights, resulting in increased inpatient charges. Conservative TE volumes should be considered for patients with hypertension and larger mastectomy specimens. PMID:26301139

  5. Subchondral avascular necrosis: a common cause of arthritis.

    PubMed Central

    Bullough, P G; DiCarlo, E F

    1990-01-01

    (1) Subchondral avascular necrosis is an important cause of joint pain and disability and accounts for upwards of 20% of total hip replacements done in our hospital. (2) Early diagnosis may be made with the aid of magnetic resonance imaging and radioactive isotope studies. (3) Although the signs and symptoms are similar to those of osteoarthritis, there are significant differences--namely, (a) a history of sudden onset of pain, present in more than half the patients; (b) a younger age group; (c) a shorter duration of symptoms at time of surgery; (d) clinically the limiting factor is pain rather than actual joint deformity to account for restriction of movement; (e) a high incidence of multiple sites of involvement. (4) The disease is commonly associated with steroid treatment or alcohol abuse. Although many other causes are recognised, they are rare in Western urban practice. (5) Patients with stage I-II subchondral avascular necrosis, especially of the knee, are better treated conservatively. (6) Surgical treatment gives less satisfactory results than the treatment of osteoarthritis by similar modalities. Images PMID:2200357

  6. Aloe emodin inhibits the cytotoxic action of tumor necrosis factor.

    PubMed

    Harhaji, Ljubica; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Popadic, Dusan; Isakovic, Aleksandra; Todorovic-Markovic, Biljana; Trajkovic, Vladimir

    2007-07-30

    We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.

  7. Porphyrin-laser photodynamic induction of focal brain necrosis

    SciTech Connect

    Stroop, W.G.; Battles, E.J.; Townsend, J.J.; Schaefer, D.C.; Baringer, J.R.; Straight, R.C. )

    1989-09-01

    A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and by edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.

  8. Gastric necrosis: A late complication of nissen fundoplication

    PubMed Central

    Salinas, Javier; Georgiev, Tihomir; González-Sánchez, Juan Antonio; López-Ruiz, Elena; Rodríguez-Montes, José Antonio

    2014-01-01

    Gastric necrosis is a rare condition because of the rich blood supply and the extensive submucosal vascular network of the stomach. “Gas-bloat” syndrome is a well known Nissen fundoplication postoperative complication. It may cause severe gastric dilatation, but very rarely an ischemic compromise of the organ. Other factors, such as gastric outlet obstruction, may concur to cause an intraluminal pressure enough to blockade venous return and ultimately arterial blood supply and oxygen deliver, leading to ischaemia. We report a case of a 63-year-old women, who presented a total gastric necrosis following laparoscopic Nissen fundoplication and a pyloric phytobezoar which was the trigger event. No preexisting gastric motility disorders were present by the time of surgery, as demonstrated in the preoperative barium swallow, thus a poor mastication (patient needed no dentures) of a high fiber meal (cabbage) may have been predisposing factors for the development of a bezoar in an otherwise healthy women at the onset of old age. A total gastrectomy with esophagojejunostomy was performed and patient was discharged home after a 7-d hospital stay with no immediate complications. We also discuss some technical aspects of the procedure that might be important to reduce the incidence of this complication. PMID:25276288

  9. Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

    PubMed

    Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

    2016-06-10

    Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted.

  10. X-ray-induced cell death: Apoptosis and necrosis

    SciTech Connect

    Nakano, Hisako; Shinohara, Kunio

    1994-10-01

    X-ray-induced cell death in MOLT-4N1, a subclone of MOLT-4 cells, and M10 cells was studied with respect to their modes of cell death, apoptosis and necrosis. MOLT-4N1 cells showed radiosensitivity similar to that of M10 cells, a radiosensitive mutant of L5178Y, as determined by the colony formation assay. Analysis of cell size demonstrated that MOLT-4N1 cells increased in size at an early stage after irradiation and then decreased to a size smaller than that of control cells, whereas the size of irradiated M10 cells increased continuously. Apoptosis detected by morphological changes and DNA ladder formation (the cleavage of DNA into oligonucleosomal fragments) occurred in X-irradiated MOLT-4N1 cells but not in M10 cells. Pulsed-field gel electrophoresis showed that the ladder formation involved an intermediate-sized DNA (about 20 kbp). Most of the DNA was detected at the origin in both methods of electrophoresis in the case of M10 cells, though a trace amount of ladder formation was observed. Heat treatment of M10 cells induced apoptosis within 30 min after treatment, in contrast to MOLT-4N1 cells. The results suggest that apoptosis and necrosis are induced by X rays in a manner which is dependent on the cell line irrespective of the capability of the cells to develop apoptosis. DNA fragmentation was the earliest change observed in the development of apoptosis. 27 refs., 8 figs., 1 tab.

  11. A novel quantitative immunomagnetic reduction assay for Nervous necrosis virus.

    PubMed

    Yang, Shieh Yueh; Wu, Jen Leih; Tso, Chun Hsi; Ngou, Fang Huar; Chou, Hsin Yiu; Nan, Fan Hua; Horng, Herng Er; Lu, Ming Wei

    2012-09-01

    Rapid, sensitive, and automatic detection platforms are among the major approaches of controlling viral diseases in aquaculture. An efficient detection platform permits the monitoring of pathogen spread and helps to enhance the economic benefits of commercial aquaculture. Nervous necrosis virus (NNV), the cause of viral encephalopathy and retinopathy, is among the most devastating aquaculture viruses that infect marine fish species worldwide. In the present study, a highly sensitive magnetoreduction assay was developed for detecting target biomolecules with a primary focus on NNV antigens. A standard curve of the different NNV concentrations that were isolated from infected Malabar grouper (Epinephelus malabaricus) was established before experiments were conducted. The test solution was prepared by homogeneous dispersion of magnetic nanoparticles coated with rabbit anti-NNV antibody. The magnetic nanoparticles in the solution were oscillated by magnetic interaction with multiple externally applied, alternating current magnetic fields. The assay's limit of detection was approximately 2 × 10(1) TCID(50)/ml for NNV. Moreover, the immunomagnetic reduction readings for other aquatic viruses (i.e., 1 × 10(7) TCID(50)/ml for Infectious pancreatic necrosis virus and 1 × 10(6.5) TCID(50)/ml for grouper iridovirus) were below the background noise in the NNV solution, demonstrating the specificity of the new detection platform.

  12. Haemostatic balance in cirrhosis.

    PubMed

    Baccouche, Héla; Labidi, Asma; Fekih, Monia; Mahjoub, Sonia; Kaabi, Houda; Hmida, Slama; Filali, Azza; Romdhane, Neila B

    2017-03-01

    Despite the prolongation of coagulation tests, recent studies reported an increased frequency of thromboembolic events in patients with cirrhosis. The aim of this study was to evaluate the haemostatic balance in cirrhotic patients through assessing the variation of pro- and anticoagulant factors and evaluating the in-vitro thrombin generation in patients with cirrhosis and in healthy patients. Fifty-one cirrhotic patients with or without thromboembolic events and 50 controls matched by age and sex were enrolled. Procoagulant (factors VII, II, V, VIII, and XII) and inhibitor (protein C, protein S and antithrombin) factor activities were determined. Thrombin generation was measured as endogenous thrombin potential (ETP). Haemostatic balance was assessed by means of both procoagulant to inhibitor coagulation factor ratios and ETP with to without protein C activation ratios. There were 24 males and 27 females. The mean age was 57.8 years [16-91 years]. Pro and anticoagulant factors were significantly lower in patients than in controls (P < 0.001) except for factor VIII and protein S. In fact factor VIII level was significantly higher in patients than in controls and protein S levels were not significantly different between patients and controls. Almost all the pro to anticoagulant factor ratios were higher in cirrhotics than in controls, especially the factor VIII to protein C ratios which increased significantly from Child Pugh A to C (P < 0.001), the ratio of ETP with to without protein C activator was higher in patients than in controls, but did not reach a significant level (0.8 vs. 0.52) There was no statistically significant difference between Child classes. When comparing patients with history of thrombosis (n = 7) to those matched by age and sex and without history of thrombosis (n = 14), the ratios were not statistically different between the two groups. Haemostatic changes in cirrhosis tend to rebalance the haemostatic system. This state often

  13. Dynamic Balancing Of Turbomachinery Shafts And Rotors

    NASA Technical Reports Server (NTRS)

    Verhoff, Vincent G.

    1993-01-01

    Method for dynamic balancing of turbomachinery shafts and rotors developed with view toward reducing time spent in balancing process. Improved method based on existing dynamic-balancing techniques and equipment, incorporating use of balancing arbor, which is mandrel duplicating mounting geometry and dynamic-balance properties of shaft balanced. Once shaft balanced, not necessary to disassemble machinery and/or shaft completely and rebalance shaft when replacing rotor on shaft. Instead, one balances replacement rotor on balancing arbor, then installs balanced rotor on shaft.

  14. In the Balance:

    PubMed Central

    Weaver, Lawrence T.

    2010-01-01

    Summary The nineteenth century saw the incorporation of technology, such as the stethoscope, microscope, and thermometer, into clinical medicine. An instrument that has received less attention in the history of the role of technology in medicine is the weighing balance, or scale. Although not new to nineteenth-century medicine, it played an important part in the rise of the numerical method and its application to the development and shaping of pediatrics. This article explores the origin and development of the weighing of babies. During its clinical and scientific adoption, this simple procedure was refined and applied in a number of increasingly sophisticated and far-reaching ways: as a measure of the dimensions of the fetus and newborn, as an index of the viability of the newborn, as a means of estimating milk intake, as a way of distinguishing normality from abnormality, as a summary measure of infant health, and as an instrument of mass surveillance. In so doing it changed the way in which medical care was delivered to infants. PMID:20632732

  15. A Balanced Memory Network

    PubMed Central

    Roudi, Yasser; Latham, Peter E

    2007-01-01

    A fundamental problem in neuroscience is understanding how working memory—the ability to store information at intermediate timescales, like tens of seconds—is implemented in realistic neuronal networks. The most likely candidate mechanism is the attractor network, and a great deal of effort has gone toward investigating it theoretically. Yet, despite almost a quarter century of intense work, attractor networks are not fully understood. In particular, there are still two unanswered questions. First, how is it that attractor networks exhibit irregular firing, as is observed experimentally during working memory tasks? And second, how many memories can be stored under biologically realistic conditions? Here we answer both questions by studying an attractor neural network in which inhibition and excitation balance each other. Using mean-field analysis, we derive a three-variable description of attractor networks. From this description it follows that irregular firing can exist only if the number of neurons involved in a memory is large. The same mean-field analysis also shows that the number of memories that can be stored in a network scales with the number of excitatory connections, a result that has been suggested for simple models but never shown for realistic ones. Both of these predictions are verified using simulations with large networks of spiking neurons. PMID:17845070

  16. Balancing "we" and "me".

    PubMed

    Congdon, Christine; Flynn, Donna; Redman, Melanie

    2014-10-01

    The open office is the dominant form of workspace design for good reason: It fosters collaboration, promotes learning, and nurtures strong culture. But what most companies fail to realize is that collaboration has a natural rhythm that requires both interaction and private contemplation. Companies have been trying for decades to find the balance between public and private workspace that best supports collaboration. In 1980 52% of U.S. employees lacked workspaces where they could concentrate without distraction. In response, high-walled cubicles took over the corporate landscape. By the late 1990s, the tide had turned, and only 23% of employees wanted more privacy, and 50% wanted more access to other people. Ever since, firms have been beefing up spaces that support collaboration and shrinking areas for individual work. But the pendulum seems to have swung too far: Once again, people feel a pressing need for privacy, not only to do heads-down work but to cope with the intensity of work today. To address these needs, according to the authors, we have to rethink our assumptions about privacy. Traditionally defined in physical terms, privacy is now about the individual's ability to control information and stimulation. In this article, the authors examine workspace design through the new lens of privacy and offer insights on how to foster teamwork and solitude.

  17. Heat balance of the Earth

    NASA Technical Reports Server (NTRS)

    Budyko, M. I.; Berlyand, T. G.; Yefimova, N. A.; Zubenok, L. I.; Strokina, L. A.

    1980-01-01

    Results of improved calculations of the heat balance components of Earth's surface are reported for yearly average conditions. The technique used to determine the heat-balance components from land- and sea-based actinometric observations as well as from satellite data on the radiation balance of the Earth-atmosphere system is described, with special attention given to short-wavelength solar radiation on the continents, effective radiation from the land surface, the radiation balance of the ocean surface, heat expended by both evaporation from the ocean surface, and turbulent heat transfer between the ocean surface and the atmosphere. World maps of heat-balance components show yearly average values of total radiation, radiation balance, heat expended by evaporation, the turbulent heat flow between Earth's surface and atmosphere, and heat transfer between the ocean surface and underlying waters. The global surface heat balance is estimated along with global values of the various components and the heat-balance components for different latitude zones.

  18. Balancing Safety and Free Speech

    ERIC Educational Resources Information Center

    Hudson, David L., Jr.

    2004-01-01

    According to Jay Worona, general counsel for the New York State School Board Association, "Balancing safety and student constitutional rights is not easy. It has to be a careful balance. School officials must be prudent and not overreact. But one part of the equation has to be paramount. And safety should be the primary concern"…

  19. Characterization of necrosis-inducing NLP proteins in Phytophthora capsici

    PubMed Central

    2014-01-01

    Background Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. Results We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Conclusions Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and Pc

  20. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    PubMed

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

  1. Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

    PubMed

    Bahia, Malkeet S; Silakari, Om

    2010-05-01

    Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

  2. Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature.

    PubMed

    Ching, Jessica A; Smith, David J

    2012-01-01

    This represents the largest case of skin necrosis related to levamisole, a common cocaine contaminant, requiring closure with skin grafts, and is the only case resulting in nasal amputation, central upper lip excision, extremity bone necrosis, and above knee amputation. The case report is followed by a review of the literature. Unique considerations for the full-thickness necrosis induced by levamisole vasculitis are highlighted, including antibody level monitoring, need for multiple excisions, timing of skin grafting, and potential for soft tissue and bone necrosis as well. A 54-year-old man presented to an outside facility with fever, generalized weakness, and agranulocytosis, with a history of cocaine use 3 weeks before. After admission, he developed generalized violaceous lesions and an elevated p-antineutrophilic cytoplasmic antibody and was diagnosed with disseminated vasculitis and agranulocytosis secondary to levamisole-contaminated cocaine exposure. On transfer to the authors' facility, 52% TBSA was involved with violaceous, nonblanching lesions, which progressed to full-thickness necrosis. Local wound care continued until necrotic areas fully demarcated and progressive necrosis stabilized, and skin grafting for closure was not performed until antibody levels normalized. Current treatment of levamisole-induced skin rash or necrosis focuses on discontinuation of levamisole. As demonstrated by this case, extensive necrosis secondary to levamisole-induced vasculitis can be successfully treated with multiple excisions until necrosis stabilizes, and then, split-thickness autografts may be applied. In areas with poor vascular supply or areas with poor functional prognosis, amputation may ultimately be required.

  3. Nodular cystic fat necrosis with calcification in a patient with juvenile dermatomyositis.

    PubMed

    Ferenczi, Katalin; Berke, Adrienne; Makkar, Hanspaul S

    2014-01-01

    Nodular cystic fat necrosis is a rare, benign form of encapsulated fat necrosis with distinct histology, characterized by cystic fat necrosis with lipomembranous changes and, in later stages, calcification. We report the case of a 7-year-old child with juvenile dermatomyositis who presented with three asymptomatic, firm, mobile nodules on the arms and neck. Histology was consistent with nodular cystic fat necrosis with prominent calcification. This is an unusual presentation of this entity because it has never been previously reported in association with juvenile dermatomyositis.

  4. Ischaemic necrosis of the tongue as a rare complication of cardiogenic shock.

    PubMed

    Hulstaert, E; Roggeman, E; Beeckman, A-S; Moerman, M; Vanderstraeten, E; Rasquin, K; Monsaert, E; Baert, D; Dewint, P; Burvenich, P; Van Steenkiste, C

    2015-12-01

    Ischaemic necrosis of the tongue is an unusual clinical finding. In most cases it is associated with vasculitis, particularly giant cell arteritis (GCA). Other causes include profound cardiogenic shock. We report a case of tongue necrosis in an 81-year-old Caucasian woman. The patient was admitted to the intensive care unit (ICU) for cardiogenic shock. Swelling of the tongue was reported before intubation and evolved into tongue ischaemia and necrosis of the tip of the tongue. After surgical debridement the patient recovered. To our knowledge, this is the second report of a patient surviving tongue necrosis resulting from cardiogenic shock.

  5. Phylogeography of infectious haematopoietic necrosis virus in North America

    USGS Publications Warehouse

    Kurath, Gael; Garver, Kyle A.; Troyer, Ryan M.; Emmenegger, Eveline J.; Einer-Jensen, Katja; Anderson, Eric D.

    2003-01-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323 IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8.6 %, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which varied in topography and geographical range. Intragenogroup genetic diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors influencing IHNV evolution may have included ocean migration ranges of their salmonid host populations and anthropogenic effects associated with fish culture.

  6. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

    Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan

    2010-01-01

    There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044

  7. Therapeutic inhibitors of tumor necrosis factor in Crohn's disease.

    PubMed

    Ganesan, Srinivasan; Travis, Simon P L; Ahmad, Tariq; Jazrawi, Riadh

    2002-09-01

    Therapeutic options for patients with refractory ulcerative colitis or Crohn's disease have recently been augmented by the introduction of biological therapies. The pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha is present in elevated concentrations in patients with inflammatory bowel disease and inhibitors of TNF alpha have proved effective as treatment. Strategies aimed at reducing TNF in patients with Crohn's disease, include the mouse/human chimeric monoclonal antibody, infliximab (Centocor Inc), the humanized monoclonal antibody, CDP-571 (Celltech Group plc), the human recombinant TNF receptor fusion protein, etanercept (Immunex Corp), and thalidomide. New approaches, including the use of soluble TNF receptors, appear promising. This article reviews the evidence of therapeutic inhibition of TNF.

  8. Role of Tumor Necrosis Factor Superfamily in Neuroinflammation and Autoimmunity.

    PubMed

    Sonar, Sandip; Lal, Girdhari

    2015-01-01

    Tumor necrosis factor superfamily (TNFSF) molecules play an important role in the activation, proliferation, differentiation, and migration of immune cells into the central nervous system (CNS). Several TNF superfamily molecules are known to control alloimmunity, autoimmunity, and immunity. Development of transgenic and gene knockout animals, and monoclonal antibodies against TNFSF molecules have increased our understanding of individual receptor-ligand interactions, and their intracellular signaling during homeostasis and neuroinflammation. A strong clinical association has been observed between TNFSF members and CNS autoimmunity such as multiple sclerosis and also in its animal model experimental autoimmune encephalomyelitis. Therefore, they are promising targets for alternative therapeutic options to control autoimmunity. Although, TNFSF ligands are widely distributed and have diverse functions, we have restricted the discussions in this review to TNFSF receptor-ligand interactions and their role in the pathogenesis of neuroinflammation and CNS autoimmunity.

  9. Early onset acute tubular necrosis following single infusion of zoledronate

    PubMed Central

    Yachoui, Ralph

    2016-01-01

    Summary Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent. PMID:27920815

  10. Some aspects of pathogenesis of infectious hematopoietic necrosis (IHN)

    USGS Publications Warehouse

    Yasutake, William T.; Amend, Donald F.

    1972-01-01

    The histopathogenesis of infectious haematopoietic necrosis (IHN) virus infection was studied by exposing juvenile sockeye salmon (Oncorhynchus nerka) to the IHN virus. Fish samples were taken every 24 h for histological examination and for determination of virus concentration. A close correlation was found between histopathological changes and virus concentration. The most significant changes occurred 4 days after exposure. The haematopocitic tissue of the kidney was the most extensively involved but minor degenerative changes were seen in the liver, pancreas, and in the granular cells of the digestive tract. On the 4th day, maximum tissue concentration of virus was reached and the mortality increased. By the 5th day, 90% of the samples showed extensive pathological changes in the kidney, together with variable changes in spleen, liver, pancreas, and gut. Similarities in the histopathogenesis of IHN, Oregon sockeye disease (OSD), Sacramento River chinook disease (SRCD) and viral haemorrhagic septicaemia (VHS), are discussed.

  11. Magnetic resonance imaging of avascular necrosis of the lunate.

    PubMed

    Jackson, M D; Barry, D T; Geiringer, S R

    1990-06-01

    Avascular necrosis (AVN) of carpal bones, particularly the lunate, is often an elusive cause of wrist pain. Physical examination can be indistinguishable from that of a simple wrist sprain, and standard radiographic evaluations are frequently normal. Early diagnosis is critical, since late treatment is often simple observation of the natural history of the disease, which includes progressive collapse of the lunate and derangement of the carpal architecture. Magnetic resonance imaging (MRI) produces images of high contrast, demarcating necrotic from normal bone. We present a case of lunate AVN ("Kienböck's disease") to illustrate the ability of MRI to identify necrotic bone in the wrist. We suggest that MRI is useful in diagnosing AVN in the wrist and that it may allow an earlier diagnosis of lunate AVN than is possible with standard radiographs.

  12. [Graner's intercarpal arthrodesis as therapy of aseptic lunate bone necrosis].

    PubMed

    Ehall, R; Neubauer, W; Stampfel, O; Peicha, G

    1990-07-01

    From 1978 till 1989 at the Department of Orthopaedics (University of Graz, Faculty of Medicine, Division of Surgery) 25 patients were operated for the reason of an avascular necrosis of the lunate bone when the bone structures were already destroyed. The form of therapy was the intercarpal-arthrodesis, developed by Orlando Graner 1966, in a slightly modified way. On the one hand through creating an intercarpal block it is possible to create more or less plain sides of the radiocarpal joint and on the other hand one can stop the carpal collapse what explains long-term-results rather acceptable. The most important disadvantage of this form of therapy is the often found loss of range of movement in the operated radiocarpal joint.

  13. Mediation of mouse natural cytotoxic activity by tumour necrosis factor

    NASA Astrophysics Data System (ADS)

    Ortaldo, John R.; Mason, Llewellyn H.; Mathieson, Bonnie J.; Liang, Shu-Mei; Flick, David A.; Herberman, Ronald B.

    1986-06-01

    Natural cell-mediated cytotoxic activity in the mouse has been associated with two types of effector cells, the natural killer (NK) cell and the natural cytotoxic (NC) cell, which seem to differ with regard to their patterns of target selectivity, cell surface characteristics and susceptibility to regulatory factors1. During studies on the mechanism of action of cytotoxic molecules, it became evident that WEHI-164, the prototype NC target cell, was highly susceptible to direct lysis by both human and mouse recombinant tumour necrosis factor (TNF). Here we show that NC, but not NK activity mediated by normal splenocytes, is abrogated by rabbit antibodies to recombinant and natural TNF, respectively. Thus, the cell-mediated activity defined as NC is due to release of TNF by normal spleen cells and does not represent a unique natural effector mechanism.

  14. Tumour necrosis factor-α in nasal allergy

    PubMed Central

    Ganbo, T.; Nakazawa, T.; Nakajima, T.; Ko, J.; Goto, R.; Murakami, Y.; Misui, K.

    1995-01-01

    Tumour necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay and eosinophil cationic protein (ECP) by radio-immunoassay to evaluate TNF-α in nasal allergy. There was no significant difference either between the mean concentrations of TNF-α in nasal secretions from the patients with perennial nasal allergy and those of normal subjects, or between the TNF-α and ECP concentrations. However, reverse transcription polymerase chain reaction showed a specific increase of TNF-α mRNA and IFN-γ mRNA in allergic nasal mucosa after allergen challenge in vitro. These findings suggest a possibility that T cell-derived IFN-γ up-regulates macrophages to elaborate TNF-α, which may play a role in amplifying allergic inflammation in the nose through the cytokine network. PMID:18475667

  15. [A case of nasal tip necrosis after hyaluronic acid injection].

    PubMed

    Honart, J-F; Duron, J-B; Mazouz Dorval, S; Rausky, J; Revol, M

    2013-12-01

    Hyaluronic acid (HA) is the most used dermal filler. Some complications associated with its use have been described, but most of them are rare and benign. We report an exceptional case of skin necrosis of the tip of the nose, in a 22-year-old patient, after HA injection. The initial appearance may occurred subsequent aesthetic sequels. After necrotic tissue excision, patient was followed in rapid succession. Daily local care has led to wound healing, without any important sequel. This rare complication reminds us that HA injections are not without risk, despite their apparent simplicity of use. Moreover, the case presented confirms the potential healing of the nasal tip, allowing treatment with wound healing, rather than other early invasive procedure.

  16. Extensive bone marrow necrosis associated with antiphospholipid antibodies.

    PubMed

    Bulvik, S; Aronson, I; Ress, S; Jacobs, P

    1995-06-01

    Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis.

  17. Laser-induced fluorescence spectroscopy in tissue local necrosis detection

    NASA Astrophysics Data System (ADS)

    Cip, Ondrej; Buchta, Zdenek; Lesundak, Adam; Randula, Antonin; Mikel, Bretislav; Lazar, Josef; Veverkova, Lenka

    2014-03-01

    The recent effort leads to reliable imaging techniques which can help to a surgeon during operations. The fluorescence spectroscopy was selected as very useful online in vivo imaging method to organics and biological materials analysis. The presented work scopes to a laser induced fluorescence spectroscopy technique to detect tissue local necrosis in small intestine surgery. In first experiments, we tested tissue auto-fluorescence technique but a signal-to-noise ratio didn't express significant results. Then we applied a contrast dye - IndoCyanine Green (ICG) which absorbs and emits wavelengths in the near IR. We arranged the pilot experimental setup based on highly coherent extended cavity diode laser (ECDL) used for stimulating of some critical areas of the small intestine tissue with injected ICG dye. We demonstrated the distribution of the ICG exciter with the first file of shots of small intestine tissue of a rabbit that was captured by high sensitivity fluorescent cam.

  18. Role of Tumor Necrosis Factor Superfamily in Neuroinflammation and Autoimmunity

    PubMed Central

    Sonar, Sandip; Lal, Girdhari

    2015-01-01

    Tumor necrosis factor superfamily (TNFSF) molecules play an important role in the activation, proliferation, differentiation, and migration of immune cells into the central nervous system (CNS). Several TNF superfamily molecules are known to control alloimmunity, autoimmunity, and immunity. Development of transgenic and gene knockout animals, and monoclonal antibodies against TNFSF molecules have increased our understanding of individual receptor–ligand interactions, and their intracellular signaling during homeostasis and neuroinflammation. A strong clinical association has been observed between TNFSF members and CNS autoimmunity such as multiple sclerosis and also in its animal model experimental autoimmune encephalomyelitis. Therefore, they are promising targets for alternative therapeutic options to control autoimmunity. Although, TNFSF ligands are widely distributed and have diverse functions, we have restricted the discussions in this review to TNFSF receptor–ligand interactions and their role in the pathogenesis of neuroinflammation and CNS autoimmunity. PMID:26257732

  19. Phylogeography of infectious haematopoietic necrosis virus in North America.

    PubMed

    Kurath, Gael; Garver, Kyle A; Troyer, Ryan M; Emmenegger, Eveline J; Einer-Jensen, Katja; Anderson, Eric D

    2003-04-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323 IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8.6 %, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which varied in topography and geographical range. Intragenogroup genetic diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors influencing IHNV evolution may have included ocean migration ranges of their salmonid host populations and anthropogenic effects associated with fish culture.

  20. Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.

    PubMed

    Turno-Kręcicka, A; Boratyńska, M; Tomczyk-Socha, M; Mazanowska, O

    2015-06-01

    Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications.

  1. Pediatric Scaphoid Proximal Pole Nonunion With Avascular Necrosis.

    PubMed

    Jernigan, Edward W; Smetana, Brandon S; Patterson, J Megan M

    2016-12-24

    A 13-year-old, right hand-dominant, otherwise healthy boy presented with left wrist pain 19 months after a nonmotorized scooter injury. Radiographs and magnetic resonance imaging at presentation demonstrated proximal pole scaphoid nonunion with avascular necrosis of the proximal fragment. Operative and nonsurgical treatment options were discussed and the family elected for an attempt at nonsurgical management. The patient was placed in a short-arm thumb spica cast, with a window for a bone stimulator, for 14 weeks. At the conclusion of the treatment, the pain had resolved and x-ray and computed tomography scan demonstrated bony union. The authors recommend considering an initial trial of nonsurgical management for treatment of all pediatric scaphoid nonunions.

  2. Mechanisms balancing skeletal matrix synthesis and degradation.

    PubMed Central

    Blair, Harry C; Zaidi, Mone; Schlesinger, Paul H

    2002-01-01

    Bone is regulated by evolutionarily conserved signals that balance continuous differentiation of bone matrix-producing cells against apoptosis and matrix removal. This is continued from embryogenesis, where the skeleton differentiates as a solid mass and is shaped into separate bones by cell death and proteolysis. The two major tissues of the skeleton are avascular cartilage, with an extracellular matrix based on type II collagen and hydrophilic proteoglycans, and bone, a stronger and lighter material based on oriented type I collagen and hydroxyapatite. Both differentiate from the same mesenchymal stem cells. This differentiation is regulated by a family of related signals centred on bone morphogenic proteins. Fibroblast growth factors, Indian hedgehog and parathyroid hormone-related protein are important in determining the type of matrix and the relation of skeletal and non-skeletal structures. Removal of mineralized matrix involves apoptosis of matrix cells and differentiation of acid-secreting cells (osteoclasts) from macrophage precursors. Key regulators of matrix removal are signals in the tumour-necrosis-factor family. Osteoclasts dissolve bone by isolating a region of the matrix and secreting HCl and proteinases at that site. Successive cycles of removal and replacement allow growth, repair and remodelling. The signals for bone turnover are predominantly cell-membrane-associated, allowing very specific spatial regulation. In addition to its support function, bone is a reservoir of Ca2+, PO3-(4) and OH-. Secondary modulation of mineral secretion and bone degradation are mediated by humoral signals, including parathyroid hormone and vitamin D, as well as the cytokines that also regulate the underlying cell differentiation. PMID:12023876

  3. Tumor necrosis factor alpha and lymphotoxin production in Hodgkin's disease.

    PubMed

    Kretschmer, C; Jones, D B; Morrison, K; Schlüter, C; Feist, W; Ulmer, A J; Arnoldi, J; Matthes, J; Diamantstein, T; Flad, H D

    1990-08-01

    It is likely that the characteristic histologic features of Hodgkin's disease reflect cytokine production by the tumor cell population. Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin (tumor necrosis factor beta [TNF-beta]) are important inflammatory mediators with wide-ranging effects within the lymphoreticular system. The aim of the present study was to investigate TNF-alpha and lymphotoxin production in the Hodgkin's disease-derived cell lines L428 and L540. At the product level, both cytokines could be demonstrated by immunostaining with specific monoclonal antibodies. TNF-alpha could be demonstrated by means of an enzyme-linked immunosorbent assay in culture supernatants from both cell lines as well as in cell lysates of L428 and L540 cells. Cytotoxic activity could be achieved only in L428 supernatants. This cytotoxic activity could not be blocked by the addition of a polyclonal antibody against TNF-alpha, but was partially inhibited with the monoclonal antibody against lymphotoxin. Synthesis of TNF-alpha and lymphotoxin in both L428 and L540 was confirmed by demonstrating the intracellular-specific messenger RNA (mRNA) using specific cDNA clones in Northern blot analysis. In situ hybridization studies with the TNF-alpha cDNA probe gave positive hybridization signals in L428 and in L540. These results demonstrate the transcription, translation, and export of TNF-alpha and lymphotoxin in cultured Hodgkin's disease-derived cell lines. In addition, results of preliminary experiments are presented in which we demonstrate Reed-Sternberg cells positive for TNF-alpha protein and mRNA in different Hodgkin's disease tissue biopsies, indicating that, at least for TNF-alpha, our cell line data are relevant to the neoplastic population present in Hodgkin's disease tissue.

  4. A world in balance.

    PubMed

    Westing, A H

    1981-01-01

    The objectives of this paper are to define the scope of global population growth within the uncompromising everyday realities of technology, economies, and politics and to demonstrate the intimate between the human population problem and the increasing problem of Nature's destruction. It is hoped that the human species will come to its sense in time to create an adequate standard of living of all of its members in peace and environmental balance. The number of people the world can support is considered in terms of 1) the provision for a standard of living adequate for everyone's health and wellbeing, 2) consideration for wildlife and nature, and 3) reliance on existing levels of technology and politics. Standards of living are suggested for the affluent and the austere. The focus on the discussion is on standards of living, global carrying capacity, the imperatives of population control and respect for nature, humans versus wildlife, and the need for a universal declaration of respect for nature. Carrying capacity is determined by total land area, cultivated land area, forest land area, cereals (grain), and wood. Use per capita of each of the 5 essentials is determined for the affluent or austere standard of living. An affluent standard means that world population would be limited to 2 billion, which is 50% of the current population. An austere standard of living means a limit of 3 billion, or 33% less than the existing population. The unfortunate reality is that today's total population of 4.5 billion is increasing at an annual rate of 1.9% and is not expected to level off until it has increased 3 times. This population growth occurs at the expense of wildlife. Of the total terrestrial animal biomass, humans constitute 4% and domestic livestock 15%, which, in 40 years, will reach a combined 40% and lead to more species extinction. One species of bird or mammal will become extinct for each increase of 220 million people, which happens every 3 years. The solution is

  5. Laboratory Workhorse: The Analytical Balance.

    ERIC Educational Resources Information Center

    Clark, Douglas W.

    1979-01-01

    This report explains the importance of various analytical balances in the water or wastewater laboratory. Stressed is the proper procedure for utilizing the equipment as well as the mechanics involved in its operation. (CS)

  6. Aging: Balancing regeneration and cancer

    SciTech Connect

    Beausejour, Christian M.; Campisi, Judith

    2006-08-24

    The proliferation of cells must balance the longevity assured by tissue renewal against the risk of developing cancer. The tumor-suppressor protein p16{sup INK4a} seems to act at the pivot of this delicate equilibrium.

  7. Skylab water balance error analysis

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1977-01-01

    Estimates of the precision of the net water balance were obtained for the entire Skylab preflight and inflight phases as well as for the first two weeks of flight. Quantitative estimates of both total sampling errors and instrumentation errors were obtained. It was shown that measurement error is minimal in comparison to biological variability and little can be gained from improvement in analytical accuracy. In addition, a propagation of error analysis demonstrated that total water balance error could be accounted for almost entirely by the errors associated with body mass changes. Errors due to interaction between terms in the water balance equation (covariances) represented less than 10% of the total error. Overall, the analysis provides evidence that daily measurements of body water changes obtained from the indirect balance technique are reasonable, precise, and relaible. The method is not biased toward net retention or loss.

  8. Cautions Concerning Electronic Analytical Balances.

    ERIC Educational Resources Information Center

    Johnson, Bruce B.; Wells, John D.

    1986-01-01

    Cautions chemists to be wary of ferromagnetic samples (especially magnetized samples), stray electromagnetic radiation, dusty environments, and changing weather conditions. These and other conditions may alter readings obtained from electronic analytical balances. (JN)

  9. Study on correlation between bone marrow edema, stage of necrosis and area ratio of necrosis with the hip pain grading in nontraumatic osteonecrosis of the femoral head

    PubMed Central

    Jianchuan, Wang; Lei, Yang; Benjie, Wang; Dewei, Zhao

    2015-01-01

    The objective of this study was to explore the correlation between bone marrow edema, stage of necrosis, and area ratio of necrosis with the hip pain grading in non-traumatic osteonecrosis of the femoral head. Bone marrow edema grading at all levels and the hip pain grade differences were statistically significant (P < 0.001). Bone marrow edema grading increased by levels of 0, 1, and 2, whereas average pain rating increased as well to 40.73, 104.66 and 143.49. I ~ III period stage of necrosis and the hip pain grade difference was statistically significant (P < 0.001), with the average grade progress pain stage by the death of a rank gradually increased, I period, II period, III period was 57.00, 88.58 and 120.62, respectively. Area ratio of necrosis between 0 ~ 3 were positively correlated with pain, compared the two was statistically significant (P < 0.001), and with the degree of pathological changes is aggravating, increase the average rank of levels of pain. 0, 1, 2 and 3 are 36.88, 98.03, 123.87 and 151.93 respectively. We can choose the treatment method and evaluate treatment effect by considering a patients’ degree of bone marrow edema, stage of necrosis and area ratio of necrosis.

  10. Seeking Balance in Cyber Education

    DTIC Science & Technology

    2015-02-01

    14 CrossTalk—January/February 2015 SOFTWARE EDUCATION TODAY Commander Michael Bilzor, USN, PhD, U.S. Naval Academy Abstract. The future cyber...course. In the paragraphs that follow, we advocate for a balanced approach that maximizes educational value, in order to prepare those future cyber...warriors for the battles that lay ahead of them. Seeking Balance in Cyber Education Theory vs. Application • The Biba model, published in 1975, did

  11. Classroom Racial Balance and Students' Interracial Attitudes

    ERIC Educational Resources Information Center

    Koslin, Sandra; And Others

    1972-01-01

    Relationships between classroom racial balance and third graders' interracial attitudes were analyzed. Interracial attitudes were more favorable in balanced than in unbalanced classes. Results suggest that classroom racial balance is strongly related to students' interracial attitudes. (Author)

  12. Form 6 - gas balancing agreement

    SciTech Connect

    Not Available

    1990-01-01

    In 1988, a special Committee of the Rocky Mountain Mineral Law Foundation undertook a project to draft a model from gas balancing agreement. This project was initiated at the request of a number of Foundation members who felt that a model form gas balancing agreement would facilitate the negotiation of operating agreement, since gas balancing issues had become sticking points in the process. The Committee was composed of attorneys representing a wide cross-section of the oil and gas industry including both major and independent oil companies, production companies with interstate pipeline affiliates, and private practitioners. The Committee attempted to address the more controversial issues in gas balancing with optional provisions in the Form. To facilitate the negotiation process, the number of optional provisions was minimized. This form may be used as an Appendix to the new A.A.P.L. Form 610-1989 Model Form Operating Agreement. This book includes provision of this Form which are: Ownership of gas production; Balancing of production accounts; Cash balancing upon depletion; Deliverability tests; Nominations; Statements; Payment of taxes; Operating expenses; Overproducing allowable; Payment of leasehold burdens; Operator's liability; Successors and assigns; Audits; Arbitration; and Operator's fees.

  13. Nasal Skin Necrosis: An Unexpected New Finding in Severe Chikungunya Fever.

    PubMed

    Torres, Jaime R; Córdova, Leopoldo G; Saravia, Víctor; Arvelaez, Joanne; Castro, Julio S

    2016-01-01

    Three adult Venezuelan patients with virologically confirmed Chikungunya fever, who developed extensive acute nasal skin necrosis early in the course of a life-threatening illness characterized by shock and multiple organ dysfunction syndrome, are discussed. One patient survived and fully recovered. Nasal necrosis has not previously been associated with the disease.

  14. Bone necrosis and tumor induction following experimental intraoperative irradiation.

    PubMed

    Powers, B E; Gillette, E L; McChesney, S L; LeCouteur, R A; Withrow, S J

    1989-09-01

    The bone of the lumbar vertebrae of 153 dogs was examined 2 and 5 years after intraoperative irradiation (IORT), fractionated external beam irradiation (EBRT), or the combination. Groups of dogs received 15 to 55 Gy IORT only, 10 to 47.5 Gy IORT combined with 50 Gy EBRT in 2 Gy fractions or 60 to 80 Gy EBRT in 30 fractions. Six MeV electrons were used for IORT, and EBRT was done using photons from a 6 MV linear accelerator. The paraaortic region was irradiated and the ventral part of the lumbar vertebrae was in the 90% isodose level. Two years after irradiation, the dose causing significant bone necrosis as determined by at least 50% empty lacunae in the vertebral cortex was 38.2 Gy IORT alone and 32.5 Gy IORT combined with EBRT. Five years after irradiation, the dose causing 50% empty lacunae was 28.5 Gy IORT only and 14.4 Gy IORT combined with EBRT. The ED50 for lesions of the ventral vertebral artery was 21.7 Gy IORT only and 20.1 Gy IORT combined with 50 Gy EBRT 2 years after irradiation and 27.0 Gy IORT only and 20.0 Gy IORT combined with 50 Gy EBRT 5 years after irradiation. All lesions after EBRT only were mild. Eight dogs developed osteosarcomas 4 to 5 years after irradiation, one at 47.5 Gy IORT only and the remainder at 25.0 Gy IORT and above combined with 50 Gy EBRT. In conclusion, the extent of empty lacunae, indicating bone necrosis, was more severe 5 years after irradiation than after 2 years. The effect of 50 Gy EBRT in 2 Gy fractions was equivalent to about 6 Gy IORT 2 years after irradiation and to about 14 Gy 5 years after irradiation. Based on these estimates, IORT doses of 10 to 15 Gy have an effect 5 times or greater than the amount given in 2 Gy fractions. Osteosarcomas occurred in 21% of dogs which received doses greater than 25 Gy IORT. Doses of 15 to 20 Gy IORT in combination with 50 Gy EBRT in 2 Gy fractions may be near the tolerance level for late developing bone injury.

  15. [Progress on tantalum rod implanting for the treatment of femur head necrosis].

    PubMed

    Tang, Xiao-kang; Ye, Fu-sheng; Tong, Pei-jian; Fan, Yan-hua; Li, Min; Ying, Hang; Xiao, Lu-wei

    2013-07-01

    Incorrect treatment for femur head necrosis can cause collapse of femoral head and tresult in severe harm for the patients (especially for the patient with middle-aged and young). The structure and mechanics characteristics of tantalum rod is similar to bone tissue, it higher strength and can adapt the internal environment of organism, so it has a large potency in treating femur head necrosis. Treatment of early femur head necrosis with tantalum rod implanting had alreadly widey applied at home and abroad, the method has the advantages of simple operation, little risk, less complication and beseems the patient with stage I - II of ARCO. But reasons that the difficult diagnosis of early femur head necrosis, localized effect of tantalum rod, different experience of medical worker,caused the contentions about effect of tantalum rod implanting. With development of science, tantalum rod implanting combined with correlative biotechnology should raise the effect in treating femur head necrosis.

  16. [Brachial plexus compression from supraclavicular encapsulated fat necrosis. A case report].

    PubMed

    Domínguez-Páez, Miguel; de Miguel-Pueyo, Luis; Marín-Salido, Esteban José; Carrasco-Brenes, Antonio; Martín-Gallego, Alvaro; Arráez-Sánchez, Miguel Ángel

    2014-01-01

    We report the case of a 44-year-old male, lacking clinical history of previous illness, who had surgery at our hospital to treat a mass in the supraclavicular space. The patient presented with a 1-month progressive distal paresis of the left arm. The histo-pathological examination of the mass revealed an encapsulated fat necrosis. Fat necrosis is characterised by cystic architecture, encapsulation with fat necrosis within, and inflammatory infiltration of its walls. Neural structure compression secondary to this tumour mass is very rare. Fat necrosis is more frequent in the lower limbs, in areas exposed to trauma. This article is the first report of brachial plexus compression due to supraclavicular fat necrosis.

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

    PubMed

    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.

  18. Quantitative tumour necrosis is an independent predictor of overall survival in clear cell renal cell carcinoma.

    PubMed

    Renshaw, Andrew A; Cheville, John C

    2015-01-01

    Previous studies have reached conflicting results regarding whether tumour necrosis is a predictor of survival in clear cell renal cell carcinoma. In addition, studies quantifying the extent of necrosis are limited.The aim of this study was to determine if quantifying tumour necrosis could improve its predictive value for survival in clear cell renal cell carcinoma.We reviewed the clinical pathological information contained in The Cancer Genome Atlas for clear cell renal cell carcinoma and correlated it with overall survival using a Cox proportional hazard model. Necrosis was quantified on a single frozen section slide taken at the time of tissue harvesting for molecular studies.For all tumours, the presence of tumour necrosis was a significant predictor of overall survival (p < 0.001) on univariate analysis. When quantitated, >10% necrosis was associated with survival, but ≤10% necrosis was not. On multivariate analysis, age (p = 0.004), T3b stage (p = 0.02), M1 stage (p < 0.001), necrosis >30% (p < 0.001), and elevated serum calcium (p = 0.003) remained significant. For clinical stage 1-2 (T1-T2N0M0) tumours, necrosis >20% was significant on univariate analysis (p ≤ 0.005), and remained so on multivariate analysis (p < 0.001).We conclude that quantitating the extent of tumour necrosis adds prognostic information in clear cell renal cell carcinomas, including organ confined tumours.

  19. The genetic diversity and epizootiology of infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Oshima, Kevin H.; Arakawa, Cindy K.; Higman, Keith H.; Landolt, Marsha L.; Nichol, Stuart T.; Winton, James R.

    1994-01-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which causes a serious disease in salmondd fish. The T1 ribonuclease fingerprinttin method was used to compare the RNA genomes of 26 isolates of IHNV recovered from sockeye salmon (Oncorhynchus nerka), chinook salmon (O. tshawytscha), and steelhead trout (O. mykiss) throughout the enzootic portion of western North America. Most of the isolates as a source of genetic variation. In from a single year (1987) to limit time of isolation as a source of genetic variation. In addition, isolates from different years collected at three sites were analyzed to investigate genetic drift or evolution of IHNV within specific locations. All of the isolates examined by T1 fingerprint analysis contained less than a 50% variation in spot location and were represented by a single fingerprint group. The observed variation was estimated to correspond to less than 5% variation in the nucleic acid sequence. However, sufficient variation was detected to separate the isolates into four subgroups which appeared to correlate to different geographic regions. Host species appeared not to be a significant source of variation. The evolutionary and epizootiologic significance of these findings and their relationship to other evidence of genetic variation in IHNV isolates are discussed.

  20. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    PubMed Central

    Cai, Weibo; Kerner, Zachary J.; Hong, Hao; Sun, Jiangtao

    2013-01-01

    Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation. PMID:24115841

  1. The complete nucleotide sequence of chrysanthemum stem necrosis virus.

    PubMed

    Dullemans, A M; Verhoeven, J Th J; Kormelink, R; van der Vlugt, R A A

    2015-02-01

    The complete genome sequence of chrysanthemum stem necrosis virus (CSNV) was determined using Roche 454 next-generation sequencing. CSNV is a tentative member of the genus Tospovirus within the family Bunyaviridae, whose members are arthropod-borne. This is the first report of the entire RNA genome sequence of a CSNV isolate. The large RNA of CSNV is 8955 nucleotides (nt) in size and contains a single open reading frame of 8625 nt in the antisense arrangement, coding for the putative RNA-dependent RNA polymerase (L protein) of 2874 aa with a predicted Mr of 331 kDa. Two untranslated regions of 397 and 33 nt are present at the 5' and 3' termini, respectively. The medium (M) and small (S) RNAs are 4830 and 2947 nt in size, respectively, and show 99 % identity to the corresponding genomic segments of previously partially characterized CSNV genomes. Protein sequences for the precursor of the Gn/Gc proteins, N and NSs, are identical in length in all of the analysed CSNV isolates.

  2. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis

    PubMed Central

    Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko; Takehara, Masaya; Nagahama, Masahiro

    2016-01-01

    Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis. PMID:26807591

  3. Immunomagnetic reduction assay for nervous necrosis virus extracted from groupers.

    PubMed

    Lu, M W; Yang, S Y; Horng, H E; Yang, C C; Chieh, J J; Hong, Y W; Hong, C Y; Yang, H C; Wu, J L

    2012-04-01

    Nervous necrosis virus (NNV) is the cause of viral nervous disease, which is a serious constraint on production for grouper aquaculture. Real-time PCR is commonly used to detect and quantify NNV, has the disadvantages of being expensive and technically demanding. In this study, an immunomagnetic reduction (IMR) assay was developed as a rapid and cost-effective alternative to real-time PCR. This method used magnetic nanoparticles conjugated with antibodies specific for viral surface antigens to detect NNV in grouper tissue samples. The association of NNV with the antibody-conjugated magnetic particles resulted in a reduction in magnetic signal, which was strongly correlated with the concentration of NNV, as determined by real-time PCR. Grouper larvae were prepared for testing using a viral extraction buffer which provided a rapid, 15-min method of extracting viral antigens and had an extraction efficiency of higher than 80%. In addition, this study proposes using magnetic nanoparticles as labeling markers and as an assaying reagent for NNV. The magnetic nanoparticles are functionalized with antibodies against the viral surface of NNV and are able to associate specifically with NNV. The reduction of the magnetic signals comes from the association between magnetic particles and NNV, and relates to the concentration of NNV. The results show that the detected concentrations of NNV are highly correlated to those detected by real-time PCR.

  4. Detection of acute hepatopancreatic necrosis disease (AHPND) in Mexico.

    PubMed

    Nunan, Linda; Lightner, Donald; Pantoja, Carlos; Gomez-Jimenez, Silvia

    2014-08-21

    Acute hepatopancreatic necrosis disease (AHPND), which has also been referred to as early mortality syndrome (EMS), initially emerged as a destructive disease of cultured shrimp species in Asia in 2009. The pathogen associated with the disease, Vibrio parahaemolyticus, subsequently spread to the Western Hemisphere and emerged in Mexico in early 2013. The spread to the Western Hemisphere is a major concern to shrimp producers in the region. To date, the only peer-reviewed published method for determining whether mortalities are due to AHPND is through histological examination. A novel PCR detection method was employed to assess samples from Mexico in order to confirm the presence of the pathogen in this country. This manuscript details the detection methods used to confirm the presence of AHPND in Mexico. Both immersion and per os challenge studies were used to expose the Penaeus vannamei to the bacteria in order to induce the disease. Histological analysis confirmed AHPND status following the challenge studies. Also provided are the details of the molecular test by PCR that was used for screening candidate V. parahaemolyticus isolates. A rapid PCR assay for detection of AHPND may help with early detection and help prevent the spread of AHPND to other countries.

  5. The genome organization of the broad bean necrosis virus (BBNV).

    PubMed

    Lu, X; Yamamoto, S; Tanaka, M; Hibi, T; Namba, S

    1998-01-01

    The genome of the broad bean necrosis virus Oita-isolate (BBNV-O) [RNA1 (6.0 kb), RNA2 (2.8 kb) and RNA3 (2.4 kb)] was cloned and sequenced. Computer analysis indicates that methyltransferase, helicase and RNA-dependent RNA polymerase (RdRp) motifs are present in RNA1. The viral capsid protein (CP) cistron is located at the 5' terminal end of RNA2 and the Mr of CP (20 K) is close to that determined by SDS-PAGE analysis. An ochre codon (UAA) in the CP cistron is thought to be partially suppressed to produce a large readthrough protein. RNA3 possesses typical motifs of triple gene block proteins, which are also reported in several other plant viruses. The furovirus genome organization and phylogenetic analysis using RdRp and CP amino acid sequences suggest that BBNV is closely related to potato mop-top virus (PMTV), but is relatively distantly related to other furoviruses. The data also suggest that the genus Furovirus should be separated into several genera: the prototypical genus Furovirus, which excludes the following viruses: the PMTV group including BBNV; the beet necrotic yellow vein virus (BNYVV) group; and the peanut clump virus (PCV) group.

  6. [Skin-sparing mastectomies: how to avoid skin necrosis?].

    PubMed

    Delbaere, M; Delaporte, T; Toussoun, G; Delay, E

    2008-04-01

    Skin-sparing mastectomy (SSM) has emerged as the surgical technique best adapted to the treatment of early breast cancers or breast cancer recurrences after conservative treatment; the technique is particularly appreciated by the patients who had been expecting the development of immediate, high-quality breast reconstruction for over 15 years. SSM preserves anatomical landmarks on the skin surface (notably the under-breast fold and the conical shape of the breast). The procedure must be performed by a skilled surgical team in order to maximize the quality of breast resection and reconstruction, particularly to avoid postoperative complications, notably damage to blood vessels within the skin flap and prosthesis infection. These complications generally affect the cosmetic outcome of the reconstruction, with serious short-term and long-term consequences for the acceptability of the surgical procedure, and may sometimes compromise the delivery of adjuvant treatments (either chemo- or radiotherapy). Based on our previous experience (1000 new cases since 1992), we will compare the advantages and drawbacks of the procedure, discuss its indications, describe the clinical situations encountered and the various specific interventions available, as well as the methods to reduce the risks of tissue damage and skin necrosis.

  7. Necrosis prediction of photodynamic therapy applied to skin disorders

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Romanov, O. G.; López-Escobar, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2009-02-01

    The great selectivity and the lack of side effects of Photodynamic Therapy make it more advantageous than radiotherapy or chemotherapy. The application of PDT to skin diseases is particularly appropriate, due to the accessibility of this tissue. Common disorders like nonmelanoma skin cancer, that includes basocelullar or squamous cell carcinomas, can be treated with PDT. Conventional procedures, like surgery or radiotherapy, are not so efficient and do not, in general, obtain the same favourable results. PDT in dermatology medical praxis uses fixed protocols depending on the photosensitizer and the optical source used. These protocols are usually provided by the photosensitizer laboratory, and every lesion is treated with the same parameters. In this work we present a photo-chemical model of PDT applied to skin disorders treated with topical photosensitizers. Optical propagation inside the tissue is calculated by means of a 3D diffusion equation, solved via a finite difference numerical method. The photosensitizer degradation or photobleaching is taken into account, as the drug looses efficiency with the irradiation time. With these data the necrosis area is estimated, so this model could be used as a predictive tool to adjust the optical power and exposition time for the particular disease under treatment.

  8. Endothelial cell activation induced by tumor necrosis factor and lymphotoxin.

    PubMed Central

    Cavender, D. E.; Edelbaum, D.; Ziff, M.

    1989-01-01

    Alterations in the morphology and histochemistry of vascular endothelial cells (EC) have been repeatedly observed at sites of chronic inflammation and immune reactions. These changes, which are most prominent in the EC postcapillary venules present in areas with large lymphocytic infiltrates, include the acquisition of a columnar or cuboidal morphology, the development of ribonuclease-sensitive metachromasia, and an increase in intracellular organelles. Thus, EC at sites of inflammation appear to be activated and to demonstrate increased metabolic activity. This study reports that both tumor necrosis factor-alpha (TNF) and lymphotoxin (LT) can activate cultured human umbilical vein EC, as measured by: 1) increased adhesiveness for lymphocytes, 2) increased cell metabolism, as measured by RNA and protein synthesis, and 3) increased cell volume. Although gamma interferon (IFN-gamma) and interleukin-1 (IL-1) have been shown previously to stimulate EC adhesiveness for lymphocytes, these two cytokines had only marginal effects on EC RNA and protein synthesis, and both caused a decrease in EC volume. These findings suggest that TNF and LT play a role in the type of activation of EC in vivo that leads to the development of tall endothelium and increased lymphocyte emigration. PMID:2466402

  9. Production of polyclonal antibodies to feline tumor necrosis factor.

    PubMed Central

    Otto, C M; Niagro, F; McGraw, R A; Rawlings, C A

    1997-01-01

    Two 13-amino-acid peptides were synthesized based on the putative feline tumor necrosis factor (FeTNF) sequence. The synthesized peptides were conjugated to keyhole limpet hemocyanin, emulsified in complete Freund's adjuvant, and injected into rabbits. The gene for FeTNF was cloned into the FLAG (International Biotechnologies Inc. [IBI], Kodak, New Haven, Conn.) fusion protein expression vector. The expressed fusion protein was purified by using the M-1 anti-FLAG octapeptide monoclonal antibody (IBI, Kodak). The fusion protein was emulsified in complete Freund's adjuvant and injected into chickens. The immune sera generated to the synthetic peptides and the fusion protein recognized the recombinant FeTNF fusion protein on Western or dot blot assay. The preimmune and immune sera were incubated with naturally occurring FeTNF (supernatants from lipopolysaccharide-stimulated cultured feline peritoneal exudate or peripheral mononuclear cells). The antibody raised to the recombinant FeTNF fusion protein and N-terminal synthetic peptide neutralized bioactivity of native FeTNF and recombinant human TNF. Preimmune sera did not have any neutralizing activity. The polyclonal antibodies were not specific for FeTNF, since both porcine and human recombinant TNF were neutralized by the fusion protein antibodies. The synthetic peptide antibodies recognized recombinant feline and equine TNF on a Western blot. PMID:9220170

  10. Molecular diagnosis of infectious hematopoietic necrosis and viral hemorrhagic septicemia

    USGS Publications Warehouse

    Winton, James R.; Einer-Jensen, Katja

    2002-01-01

    The fish rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), cause extensive losses among salmon and trout in several areas of the world (Bootland and Leong, 1999; Smail, 1999; Wolf, 1988). Historically, IHNV was endemic among wild anadromous salmonids in the western portion of North America, but the virus has spread to stocks of cultured rainbow trout (Oncorhynchus mykiss) in the United States, Asia and Western Europe, probably as a result of the movement of infected fish or eggs (Winton, 1991). Prior to 1989, VHSV was thought to be largely restricted to freshwater fishes in Western Europe (Wolf, 1988); however, in the last decade, VHSV has been isolated from an increasing number of free-living marine fish species in the North Pacific and North Atlantic Oceans (Dixon et al., 1997; Dixon, 1999; Kent et al., 1998; Meyers and Winton, 1995; Meyers et al., 1999; Mortensen et al., 1999; Smail; 2000, Takano et al., 2000). These findings have lead to the conclusion that both viruses are principally endemic among marine or anadromous fish species, but have established themselves in freshwater among cultured salmonids where their effects are most frequently observed.

  11. Methods to Differentiate Radiation Necrosis and Recurrent Disease in Gliomas

    NASA Astrophysics Data System (ADS)

    Ewell, Lars

    2007-03-01

    Given the difficulty in differentiating Radiation Induced Necrosis (RIN) and recurrent disease in glioma patients using conventional techniques (CT scans, MRI scans), researchers have looked for different imaging modalities. Among these different modalities are Diffusion Weighted Magnetic Resonance Imaging (DWMRI) and Magnetic Resonance Spectroscopy (MRS). In DWMRI, an Apparent Diffusion Coefficient (ADC) is calculated for a Region Of Interest (ROI), and then monitored over time (longitudinally). In the brain, different anatomical features can complicate the interpretation of ADCs. In particular, the density and spatial variation of the cerebral spinal fluid filled fissures known as sulci can influence how a change in an ADC is explained. We have used the covariance of pixel intensity in T1 weighted MRI scans to study how intra-patient and inter-patient sulci density varies, and will present these results. MRS uses the shift in the MR signal due to the local chemical environment to determine the concentration of brain metabolites like choline and creatin. The ratio of metabolites such as these has been shown to have the power to discriminate between RIN and recurrent disease in glioma patients. At our institution, we have initiated a protocol whereby we will use DWMRI and MRS to study how best to utilize these complimentary forms of imaging.

  12. Tumor Necrosis Factor–α Overexpression in Lung Disease

    PubMed Central

    Lundblad, Lennart K. A.; Thompson-Figueroa, John; Leclair, Timothy; Sullivan, Michael J.; Poynter, Matthew E.; Irvin, Charles G.; Bates, Jason H. T.

    2005-01-01

    Rationale: Tumor necrosis factor α (TNF-α) has been implicated as a key cytokine in many inflammatory lung diseases. These effects are currently unclear, because a transgenic mouse overexpressing TNF-α in the lung has been shown in separate studies to produce elements of both emphysema and pulmonary fibrosis. Objectives: We sought to elucidate the phenotypic effects of TNF-α overexpression in a mouse model. Measurements: We established the phenotype by measuring lung impedance and thoracic gas volume, and using micro–computed tomography and histology. Main Results: We found that airways resistance in this mouse was not different to control mice, but that lung tissue dampening, elastance, and hysteresivity were significantly elevated. Major heterogeneous abnormalities of the parenchyma were also apparent in histologic sections and in micro–computed tomography images of the lung. These changes included airspace enlargement, loss of small airspaces, increased collagen, and thickened pleural septa. We also found significant increases in lung and chest cavity volumes in the TNF-α–overexpressing mice. Conclusions: We conclude that TNF-α overexpression causes pathologic changes consistent with both emphysema and pulmonary fibrosis combined with a general lung inflammation, and consequently does not model any single human disease. Our study thus confirms the pleiotropic effects of TNF-α, which has been implicated in multiple inflammatory disorders, and underscores the necessity of using a wide range of investigative techniques to link gene expression and phenotype in animal models of disease. PMID:15805183

  13. Leptin: at the crossroads of energy balance and systemic inflammation

    PubMed Central

    Steiner, Alexandre A.; Romanovsky, Andrej A.

    2007-01-01

    In addition to playing a central role in energy homeostasis, leptin is also an important player in the inflammatory response. Systemic inflammation is accompanied by fever (less severe cases) or hypothermia (more severe cases). In leptin-irresponsive mutants, the hypothermia of systemic inflammation is exaggerated, presumably due to the enhanced production and cryogenic action of tumor necrosis factor (TNF)-α. Mechanisms that exaggerate hypothermia can also attenuate fever, particularly in a cool environment. Another common manifestation of systemic inflammation is behavioral depression. Along with the production of interleukin (IL)-1β, this manifestation is exaggerated in leptin-irresponsive mutants. The enhanced production of TNF-α and IL-1β may be due, at least in part, to insufficient activation of the anti-inflammatory hypothalamo-pituitary-adrenal axis by immune stimuli in the absence of leptin signaling. In experimental animals and humans that are responsive to leptin, suppression of leptin production under conditions of negative energy balance (e.g., fasting) can exaggerate both hypothermia and behavioral depression. Since these manifestations aid energy conservation, exaggeration of these manifestations under conditions of negative energy balance is likely to be beneficial. PMID:17275915

  14. Survival of the salmonid viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV) in ozonated, chlorinated, and Untreated waters

    USGS Publications Warehouse

    Wedemeyer, Gary A.; Nelson, Nancy C.; Smith, Cathy A.

    1978-01-01

    Ozone and chlorine inactivation curves were determined in three water types at 10 °C for the fish pathogenic viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV). In phosphate-buffered, distilled water (PBDW) an ozone dose of 0.01 mg/L for 30 or 60 s inactivated IHNV or IPNV, respectively, suspended at a tissue culture 50% infective dose (TCID50) of 104–105/mL. In hard (120 mg/L as CaCO3) and soft water (30 mg/L) lake waters, an ozone application rate of 70 mg∙h−1∙L−1 for 10 min destroyed IHNV. IPNV inactivation in hard water required 90 mg∙O3∙h−1∙L−1 for 10 min but only a 30-s contact time in soft water. The IPNV was also somewhat more resistant to chlorine. In PBDW, a residual of 0.1 mg/L with contact times of 30 and 60 s, respectively, destroyed IHNV and IPNV. In soft lake water IHNV was destroyed within 5 min at 0.5 mg/L, while in hard water a 10-min contact time was required. For IPNV disinfection in soft water, 0.2 mg/L for 10 min was sufficient but this chlorine residual had essentially no effect on IPNV in hard water. Increasing this dose to 0.7 mg/L destroyed IPNV in hard water within 2 min. In untreated waters, IPNV was stable for at least 8 wk in either distilled, soft, or hard lake waters. However, IHNV survived only about 2 wk in distilled and 7 wk in the soft or hard lake waters. We suggest the serious consideration of ozone as a fish disease control agent. Key words: ozone, chlorine disinfection, fish pathogens, viruses

  15. Necrosis, and then stress induced necrosis-like cell death, but not apoptosis, should be the preferred cell death mode for chemotherapy: clearance of a few misconceptions

    PubMed Central

    Zhang, Ju; Lou, Xiaomin; Jin, Longyu; Zhou, Rongjia; Liu, Siqi; Xu, Ningzhi; Liao, D. Joshua

    2014-01-01

    Cell death overarches carcinogenesis and is a center of cancer researches, especially therapy studies. There have been many nomenclatures on cell death, but only three cell death modes are genuine, i.e. apoptosis, necrosis and stress-induced cell death (SICD). Like apoptosis, SICD is programmed. Like necrosis, SICD is a pathological event and may trigger regeneration and scar formation. Therefore, SICD has subtypes of stress-induced apoptosis-like cell death (SIaLCD) and stress-induced necrosis-like cell death (SInLCD). Whereas apoptosis removes redundant but healthy cells, SICD removes useful but ill or damaged cells. Many studies on cell death involve cancer tissues that resemble parasites in the host patients, which is a complicated system as it involves immune clearance of the alien cancer cells by the host. Cancer resembles an evolutionarily lower-level organism having a weaker apoptosis potential and poorer DNA repair mechanisms. Hence, targeting apoptosis for cancer therapy, i.e. killing via SIaLCD, will be less efficacious and more toxic. On the other hand, necrosis of cancer cells releases cellular debris and components to stimulate immune function, thus counteracting therapy-caused immune suppression and making necrosis better than SIaLCD for chemo drug development. PMID:25594039

  16. Thermal balance in convective therapies.

    PubMed

    Santoro, Antonio; Mancini, Elena; Canova, Cristina; Mambelli, Emanuele

    2003-08-01

    Among the factors causing intradialytic haemodynamic instability, dialysate temperature has been shown to play a relevant role. An improved cardiovascular response during isolated ultrafiltration or with cooled dialysate has been described in the past. Cold dialysate may increase the external heat loss compensating for the increase in core temperature, thus avoiding vasodilatation, but it also increases myocardial contractility. However, a better haemodynamic response to dialysis treatment has long been known in convective therapies as well, and the hypothesis of a leading role for thermal balance is under discussion. In conventional haemofiltration (HF), venous blood cooling is expected, on the basis of the infusate temperature and the filtration fraction. In on-line HF, the infusate temperature and its volume may have a different impact on thermal balance depending on the site of infusion (pre- or post-dialyser). In an in vitro study comparing haemodialysis (HD) (conventional HD, dialysate 37 degrees C; and cold HD, dialysate 35.5 degrees C) with HF (pre- and post-dilution, 37 degrees C), we observed a more negative thermal balance with cold HD (-130 kJ/h) and with post-dilution HF (-75 kJ/h). The beneficial pressor effects of HF have been confirmed even in on-line HF, which actually has very few differences in the thermal balance compared with conventional HD (dialysate 37 degrees C). In on-line HF, the amount of warm infusion, often exceeding the blood flow, makes the achievement of a negative thermal balance highly unlikely. Thus, there is not sufficient evidence that vascular stability in on-line HF is solely related to different thermal energy balances. Other factors playing a relevant role in the cardiocirculatory response to convective dialysis should thus be considered.

  17. Decisional balance: Alcohol decisional balance intervention for heavy drinking undergraduates

    PubMed Central

    2015-01-01

    Background This study evaluated a decisional balance intervention among heavy drinking undergraduates and compared a non-weighted decisional balance proportion (DBP; Collins, Carey, & Otto, 2009) to a participant-weighted DBP with weights based on relative importance of items. We expected: 1) the intervention to decrease drinking compared to control; 2) the weighted intervention to be more effective compared to the non-weighted or control in reducing drinking; and 3) intervention efficacy to be moderated by initial DBP. Method Participants (N =162, Mean age = 24.37, SD = 6.81, 27% male) were randomly assigned to an alcohol intervention wherein they were either asked to assign weights of importance to pros and cons (weighted intervention), or not (non-weighted intervention), or to control. Participants completed web-based questionnaires at baseline and again during a one month follow-up assessment. Results Consistent with expectations, the non-weighted intervention was associated with reduced follow-up weekly drinking, and the weighted intervention was associated with reductions in drinking frequency. Results further indicated that initial decisional balance did not moderate intervention efficacy. Discussion Findings suggest that the decisional balance procedure can reduce drinking but there was not compelling evidence for the addition of weights. This study lays the groundwork for enhancing future interventions by increasing empirical knowledge of the role motivation plays in heavy alcohol use. PMID:26555004

  18. BALANCER: A Computer Program for Balancing Chemical Equations.

    ERIC Educational Resources Information Center

    Jones, R. David; Schwab, A. Paul

    1989-01-01

    Describes the theory and operation of a computer program which was written to balance chemical equations. Software consists of a compiled file of 46K for use under MS-DOS 2.0 or later on IBM PC or compatible computers. Additional specifications of courseware and availability information are included. (Author/RT)

  19. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  20. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  1. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  2. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  3. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  4. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  5. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  6. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  7. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  8. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  9. A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis.

    PubMed

    Kung, G; Dai, P; Deng, L; Kitsis, R N

    2014-04-01

    TNFα signaling can promote apoptosis or a regulated form of necrosis. ARC (apoptosis repressor with CARD (caspase recruitment domain)) is an endogenous inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. We discovered that ARC blocks not only apoptosis but also necrosis. TNFα-induced necrosis was abrogated by overexpression of wild-type ARC but not by a CARD mutant that is also defective for inhibition of apoptosis. Conversely, knockdown of ARC exacerbated TNFα-induced necrosis, an effect that was rescued by reconstitution with wild-type, but not CARD-defective, ARC. Similarly, depletion of ARC in vivo exacerbated necrosis caused by infection with vaccinia virus, which elicits severe tissue damage through this pathway, and sensitized mice to TNFα-induced systemic inflammatory response syndrome. The mechanism underlying these effects is an interaction of ARC with TNF receptor 1 that interferes with recruitment of RIP1, a critical mediator of TNFα-induced regulated necrosis. These findings extend the role of ARC from an apoptosis inhibitor to a regulator of the TNFα pathway and an inhibitor of TNFα-mediated regulated necrosis.

  10. On the relation of necrosis and inflammation to denaturation of proteins.

    PubMed

    OPIE, E L

    1962-03-01

    Necrosis of the skin was produced by the injection of measured quantities of electrolytes and of amino compounds into the dermis, and the relative ability of these substances to produce it was determined. Inflammation characterized by edema and accumulation of leucocytes accompanied necrosis. The ability of electrolytes to produce necrosis was found to increase with the valence of their basic ion, and in this respect was in accord with their ability to denature proteins. The quantity of different electrolytes needed to produce necrosis varied in the same order as the molar concentration of these electrolytes, that is isotonic with liver or kidney cells. Necrosis caused by amino compounds occurred with similar relation to the isotonicity of liver cells. In this as in other relations the cells acted as osmometers. The foregoing relations indicate that denaturation of proteins, necrosis of living tissue, and osmotic activity of liver or kidney cells are determined by molecular weight, valence, and ion-dissociation of electrolytes, that is, by the factors that determine the colligative properties of electrolytes. Agents such as turpentine, mustard, or croton oil and some halogen substitution compounds of methyl that are insoluble in water and soluble in lipoids have produced skin necrosis and inflammation.

  11. A Disease Model of Muscle Necrosis Caused by Aeromonas dhakensis Infection in Caenorhabditis elegans

    PubMed Central

    Chen, Po-Lin; Chen, Yi-Wei; Ou, Chun-Chun; Lee, Tzer-Min; Wu, Chi-Jung; Ko, Wen-Chien; Chen, Chang-Shi

    2017-01-01

    A variety of bacterial infections cause muscle necrosis in humans. Caenorhabditis elegans has epidermis and bands of muscle that resemble soft-tissue structures in mammals and humans. Here, we developed a muscle necrosis model caused by Aeromonas dhakensis infection in C. elegans. Our data showed that A. dhakensis infected and killed C. elegans rapidly. Characteristic muscle damage in C. elegans induced by A. dhakensis was demonstrated in vivo. Relative expression levels of host necrosis-associated genes, asp-3, asp-4, and crt-1 increased significantly after A. dhakensis infection. The RNAi sensitive NL2099 rrf-3 (pk1426) worms with knockdown of necrosis genes of crt-1 and asp-4 by RNAi showed prolonged survival after A. dhakensis infection. Specifically knockdown of crt-1 and asp-4 by RNAi in WM118 worms, which restricted RNAi only to the muscle cells, conferred significant resistance to A. dhakensis infection. In contrast, the severity of muscle damage and toxicity produced by the A. dhakensis hemolysin-deletion mutant is attenuated. In another example, shiga-like toxin-producing enterohemorrhagic E. coli (EHEC) known to elicit toxicity to C. elegans with concomitant enteropathogenicty, did not cause muscle necrosis as A. dhakensis did. Taken together, these results show that Aeromonas infection induces muscle necrosis and rapid death of infected C. elegans, which are similar to muscle necrosis in humans, and then validate the value of the C. elegans model with A. dhakensis infection in studying Aeromonas pathogenicity. PMID:28101079

  12. Low temperature-induced necrosis shows phenotypic plasticity in wheat triploid hybrids.

    PubMed

    Takumi, Shigeo; Mizuno, Nobuyuki

    2011-10-01

    Hybrid necrosis sometimes appears in triploid hybrids between tetraploid wheat and Aegilops tauschii Coss. Two types of hybrid necrosis (type II and type III) were observed when cultivar Langdon was used as female parent for hybrid production. Type II necrosis symptoms occurred only under low temperature conditions, whereas bushy and dwarf phenotypes were observed under normal temperature conditions. The developmental plasticity might be related to a temperature-responsive alteration of meristematic activity at the crown tissue of triploid hybrids. Epistatic interaction between the AB and D genomes induced not only upregulation of a number of defense-related genes, but also extensive changes in plant architecture in the type II necrosis hybrids. Such phenotypic plasticity was also observed in other cross combinations between cultivated tetraploid wheat and type II necrosis-induced Ae. tauschii accessions. Wild tetraploid wheat, Triticum turgidum subspecies dicoccoides, did not induce type II necrosis in the triploid hybrids, indicating the possibility of identifying the chromosomal location of a causal gene for type II necrosis in the AB genome.

  13. Bevacizumab as Therapy for Radiation Necrosis in Four Children With Pontine Gliomas

    SciTech Connect

    Liu, Arthur K.; Macy, Margaret E.; Foreman, Nicholas K.

    2009-11-15

    Purpose: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in nearly all patients. Given the poor prognosis for patients with this tumor, their quality of life is very important. Radiation therapy provides some palliation, but can result in radiation necrosis and associated neurologic decline. The typical treatment for this necrosis is steroid therapy. Although the steroids are effective, they have numerous side effects that can often significantly compromise quality of life. Bevacizumab, an antibody against vascular endothelial growth factor, has been suggested as a treatment for radiation necrosis. We report on our initial experience with bevacizumab therapy for radiation necrosis in pediatric pontine gliomas. Materials and Methods: Four children with pontine gliomas treated at the Children's Hospital in Denver and the University of Colorado Denver developed evidence of radiation necrosis both clinically and on imaging. Those 4 children then received bevacizumab as a treatment for the radiation necrosis. We reviewed the clinical outcome and imaging findings. Results: After bevacizumab therapy, 3 children had significant clinical improvement and were able to discontinue steroid use. One child continued to decline, and, in retrospect, had disease progression, not radiation necrosis. In all cases, bevacizumab was well tolerated. Conclusions: In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.

  14. Stress-induced intestinal necrosis resulting from severe trauma of an earthquake

    PubMed Central

    Gong, Jia-Qing; Zhang, Guo-Hu; Tian, Fu-Zhou; Wang, Yong-Hua; Zhang, Lin; Cao, Yong-Kuan; Wang, Pei-Hong

    2012-01-01

    AIM: To investigate the possible reasons and suggest therapeutic plan of stress-induced intestinal necrosis resulting from the severe trauma. METHODS: Three patients in our study were trapped inside collapsed structures for 22, 21 and 37 h, respectively. The patients underwent 3-4 operations after sustaining their injuries. Mechanical ventilation, intermittent hemodialysis and other treatments were also provided. The patients showed signs of peritoneal irritation on postoperative days 10-38. Small intestinal necrosis was confirmed by emergency laparotomy, and for each patient, part of the small bowel was removed. RESULTS: Two patients who all performed 3 operations died of respiratory complications on the first and second postoperative days respectively. The third patient who performed 4 operations was discharged and made a full recovery. Three patients had the following common characteristics: (1) Multiple severe trauma events with no direct penetrating gastrointestinal injury; (2) Multiple surgeries with impaired renal function and intermittent hemodialysis treatment; (3) Progressive abdominal pain and tenderness, and peritoneal irritation was present on post-traumatic days 10-38; (4) Abdominal operations confirmed segment ulcer, necrosis of the small intestine, hyperplasia and stiffness of the intestinal wall; and (5) Pathological examinations suggested submucosal hemorrhage, necrosis, fibrosis and hyalinization of the vascular wall. Pathological examinations of all 3 patients suggested intestinal necrosis with fistulas. CONCLUSION: Intestinal necrosis is strongly asso-ciated with stress from trauma and post-traumatic complications; timely exploratory laparotomy maybe an effective method for preventing and treating stress-induced intestinal necrosis. PMID:22563202

  15. Increased concentrations of tumour necrosis factor in "cachectic" patients with severe chronic heart failure.

    PubMed Central

    McMurray, J; Abdullah, I; Dargie, H J; Shapiro, D

    1991-01-01

    OBJECTIVE--To ascertain whether patients with cardiac failure and reduced body weight ("cardiac cachexia") have increased circulating concentrations of tumour necrosis factor (cachectin). DESIGN--Patients with cardiac failure were prospectively identified as "cachectic" (body fat less than 27% in men and less than 29% in women measured by skinfold thickness callipers) or "non-cachectic". Tumour necrosis factor was assayed blind to patient group. SETTING--Cardiology unit in a tertiary referral centre. PATIENTS--26 consecutive patients (10 women) (mean age 61) admitted for investigation or treatment of chronic heart failure. All were in New York Heart Association class III or IV. RESULTS--In nine of the 16 cachectic patients the concentration of tumour necrosis factor was increased (mean (SEM) 74 (20) pg/ml) compared with one of the 10 "non-cachectic" patients (22 pg/ml, p less than 0.001). Patients with a raised circulating concentration of tumour necrosis factor weighed significantly less (55.6 (3.5) kg) than those in whom the concentration of tumour necrosis factor was normal (69.0 (4.1) kg) (p = 0.02). CONCLUSIONS--Circulating concentrations of tumour necrosis factor were increased in a significant proportion of patients with chronic heart failure and low body weight. Tumour necrosis factor stimulates catabolism experimentally and it may be a factor in the weight loss seen in patients with "cardiac cachexia". PMID:1747295

  16. Purification of human immunoglobulin G autoantibodies to tumor necrosis factor using affinity chromatography and magnetic separation.

    PubMed

    Sennikov, S V; Golikova, E A; Kireev, F D; Lopatnikova, J A

    2013-04-30

    Autoantibodies to cytokines are important biological effector molecules that can regulate cytokine activities. The aim of the study was to develop a protocol to purify autoantibodies to tumor necrosis factor from human serum, for use as a calibration material to determine the absolute content of autoantibodies to tumor necrosis factor by enzyme-linked immunosorbent assay. The proposed protocol includes a set of affinity chromatography methods, namely, Bio-Gel P6DG sorbent to remove albumin from serum, Protein G Sepharose 4 Fast Flow to obtain a total immunoglobulin G fraction of serum immunoglobulins, and Affi-Gel 15 to obtain specifically antibodies to tumor necrosis factor. The addition of a magnetic separation procedure to the protocol eliminated contaminant tumor necrosis factor from the fraction of autoantibodies to tumor necrosis factor. The protocol generated a pure fraction of autoantibodies to tumor necrosis factor, and enabled us to determine the absolute concentrations of different subclasses of immunoglobulin G autoantibodies to tumor necrosis factor in apparently healthy donors.

  17. Current balancing for battery strings

    DOEpatents

    Galloway, James H.

    1985-01-01

    A battery plant is described which features magnetic circuit means for balancing the electrical current flow through a pluraliircuitbattery strings which are connected electrically in parallel. The magnetic circuit means is associated with the battery strings such that the conductors carrying the electrical current flow through each of the battery strings pass through the magnetic circuit means in directions which cause the electromagnetic fields of at least one predetermined pair of the conductors to oppose each other. In an alternative embodiment, a low voltage converter is associated with each of the battery strings for balancing the electrical current flow through the battery strings.

  18. Balancer effects in opinion dynamics

    NASA Astrophysics Data System (ADS)

    Cheon, Taksu; Morimoto, Jun

    2016-01-01

    We introduce a novel type of contrarian agent, the balancer, to the Galam model of opinion dynamics, which features group-majority update, in order to account for the existence of social skepticism over one-sidedness. We find that, along with majoritarian floaters and single-sided inflexibles, the inclusion of balancers, who normally act as floaters but oppose inflexibles in their presence, brings about the emergence of a critical point on parametric plane of the dynamical system. Around the critical point, three distinct phases of opinion dynamics separated by discontinuous changes are found.

  19. A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis.

    PubMed

    Delahunt, Brett; McKenney, Jesse K; Lohse, Christine M; Leibovich, Bradley C; Thompson, Robert Houston; Boorjian, Stephen A; Cheville, John C

    2013-03-01

    Grading of renal cell carcinoma (RCC) has prognostic significance, and there is recent consensus by the International Society of Urological Pathology (ISUP) that for clear cell and papillary RCC, grading should primarily be based on nucleolar prominence. Microscopic tumor necrosis also predicts outcome independent of tumor grading. This study was undertaken to assess whether the incorporation of microscopic tumor necrosis into the ISUP grading system provides survival information superior to ISUP grading alone. Data on 3017 patients treated surgically for clear cell RCC, 556 for papillary RCC, and 180 for chromophobe RCC were retrieved from the Mayo Clinic Registry. Median follow-up periods were 8.9, 9.7, and 8.5 years, respectively. Four proposed grades were defined: grade 1: ISUP grade 1+ISUP grade 2 without necrosis; grade 2: ISUP grade 2 with necrosis+ISUP grade 3 without necrosis; grade 3: ISUP grade 3 with necrosis+ISUP grade 4 without necrosis; grade 4: ISUP grade 4 with necrosis or sarcomatoid/rhabdoid tumors. There was a significant difference in survival between each of the grades for clear cell RCC, and the concordance index was superior to that of ISUP grading. The proposed grading system also outperformed the ISUP grading system when cases were stratified according to the TNM stage. Similar results were not obtained for papillary RCC or chromophobe RCC. We conclude that grading for clear cell RCC should be based on nucleolar prominence and necrosis, that ISUP grading should be used for papillary RCC, and that chromophobe RCC should not be graded.

  20. Can balance training promote balance and strength in prepubertal children?

    PubMed

    Granacher, Urs; Muehlbauer, Thomas; Maestrini, Lea; Zahner, Lukas; Gollhofer, Albert

    2011-06-01

    The prevalence of sustaining a fall is particularly high in children. Deficits in postural control and muscle strength are important intrinsic fall risk factors. Thus, the purpose of this study was to investigate the impact of balance training (BT) followed by detraining on postural control, plantar flexor strength, and jumping height in prepubertal children. Thirty grade 1 school children participated in this study and were assigned to either an intervention class (INT, n = 15, age 6.7 ± 0.5 years) or a control class (n = 15, age 6.6 ± 0.5 years). The INT participated in 4 weeks of BT (3 per week) integrated in their physical education lessons. Pre, post, and follow-up tests included the measurements of postural sway on a balance platform, maximal torque and rate of force development of the plantar flexors on an isokinetic device, and jumping height on a force platform. The significance level was set at p < 0.05. Balance training resulted in tendencies in terms of small to medium interaction effects yet not statistically significant improvements in postural sway (f = 0.14; p > 0.05), force production of the plantar flexors (f = 0.18; p> 0.05), and jumping height (f = 0.25; p> 0.05). Immaturity of the postural control system and deficits in attentional focus during practice of balance exercises could be responsible for the nonsignificant findings in this study. Thus, other training regimen (e.g., resistance training) should be applied alone or in combination with BT, which may have the potential to promote balance and strength in children.

  1. Palliation of malignant dysphagia by ethanol induced tumour necrosis.

    PubMed Central

    Nwokolo, C U; Payne-James, J J; Silk, D B; Misiewicz, J J; Loft, D E

    1994-01-01

    Thirty two patients (74 (43-93) years; median, (range)) with dysphagia because of inoperable, unresectable or recurrent oesophagogastric carcinoma were treated by ethanol induced tumour necrosis (ETN). Endoscopic injection of absolute alcohol was performed using a variceal injector needle, with 0.5-1 ml aliquots injected retrogradely from distal to proximal tumour margin. Dilatation to 12 mm was used only if the endoscope would not traverse the stricture. In patients with total occlusion, injection into the proximal tumour was followed by a repeat endoscopy 3-7 days later. Dysphagia was graded from 0 = no dysphagia to 4 = total dysphagia. The significance of changes in the dysphagia grade after ETN were assessed using the Wilcoxon rank sum test. Results (median (range)) were as follows: stricture length = 5.0 cm (1-15). Dysphagia grade before treatment was 3 (2-4) improving after first treatment to 1 (0-3), p < 0.003. Best dysphagia grade achieved was 1 (0-3) and interval between treatments was 28.5 days (4-170). The volume of ethanol injected = 10 ml (1.5-29) and survival after first treatment was 93 days (6-660). The number of treatment sessions required to achieve best grade = 1 (1-3). There were no treatment complications. ETN significantly improves dysphagia. Results of palliation are similar to those of laser therapy, but can be achieved quickly and safely on a day case basis in most patients and at a small proportion of the cost. Images Figure 3 Figure 4 PMID:7512062

  2. Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.

    PubMed Central

    Delfino, D; Cianci, L; Migliardo, M; Mancuso, G; Cusumano, V; Corradini, C; Teti, G

    1996-01-01

    Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) [corrected] glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 microg of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 microg/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans. PMID:8945566

  3. Regulation of bitter taste responses by tumor necrosis factor.

    PubMed

    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.

  4. Regulation of bitter taste responses by tumor necrosis factor

    PubMed Central

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

    2015-01-01

    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. PMID:25911043

  5. Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors

    PubMed Central

    Mewar, Devesh; Wilson, Anthony G

    2011-01-01

    Advances in our understanding of the key mediators of chronic inflammation and tissue damage characteristic of rheumatoid arthritis (RA) have resulted in the development of novel therapies primarily targeting pro-inflammatory cytokines. Inhibitors of tumour necrosis factor (TNF) are the most widely used of the biological therapies at present with five different agents currently available; four are based on monoclonal anti-TNF antibodies and a soluble TNF receptor-Fc fusion protein. Long-term use of these molecules has proven to be highly effective in the majority of patients; however, around one-third have a suboptimal response potentially leading to further cartilage and bone damage, furthermore these agents are expensive compared with conventional therapies such as methotrexate. Many recent studies have attempted to identify therapeutic response biomarkers of TNF inhibitors which could be used to improve therapeutic targeting. The presence of rheumatoid factor and anti-cyclic citullinated protein antibodies, present in around 65% of RA patients, are associated with a poorer response to anti-TNF agents. Poorer response is also associated with levels of C-reactive protein and cartilage degradation product at initiation of treatment. Intriguingly, genetic studies of variants of TNF and of genes encoding members of the Toll-like receptors, nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling families have been associated with response to individual anti-TNF agents. Continued advances in technologies such as ultra high throughput sequencing and proteomics should facilitate the discovery of additional biomarkers of response to anti-TNF resulting in improved disease control and quality of life for RA patients and reduced costs for healthcare funders. PMID:21039421

  6. A third distinct tumor necrosis factor receptor of orthopoxviruses

    PubMed Central

    Loparev, Vladimir N.; Parsons, Joseph M.; Knight, Janice C.; Panus, Joanne Fanelli; Ray, Caroline A.; Buller, R. Mark L.; Pickup, David J.; Esposito, Joseph J.

    1998-01-01

    Cowpox virus Brighton red strain (CPV) contains a gene, crmD, which encodes a 320-aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively, to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC. The crmD gene was interrupted in three other cowpox strains examined and absent in various other orthopoxviruses; however, four strains of ectromelia virus (ECT) examined contained an intact crmD (97% identity to CPV crmD) and lacked cognates of crmB and crmC. The protein, CrmD, contains a transport signal; a 151-aa cysteine-rich region with 21 cysteines that align with human TNFRII ligand-binding region cysteines; and C-terminal region sequences that are highly diverged from cellular TNFR C-terminal region sequences involved in signal transduction. Bacterial maltose-binding proteins containing the CPV or ECT CrmD cysteine-rich region bound TNF and lymphotoxin-α (LTα) and blocked their in vitro cytolytic activity. Secreted viral CrmD bound TNF and LTα and was detectable after the early stage of replication, using nonreducing conditions, as 60- to 70-kDa predominant and 90- to 250-kDa minor disulfide-linked complexes that were able to be reduced to a 46-kDa form and deglycosylated to a 38-kDa protein. Cells infected with CPV produced extremely low amounts of CrmD compared with ECT. Possessing up to three TNFRs, including CrmD, which is secreted as disulfide-linked complexes in varied amounts by CPV and ECT, likely enhances the dynamics of the immune modulating mechanisms of orthopoxviruses. PMID:9520445

  7. Efficacy of certain disinfectants against infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Elliott, Diane G.; Amend, Donald F.

    1978-01-01

    The virucidal properties of iodophor, chlorine (sodium hypochlorite), formalin, thimerosal (organic mercurial compound), malachite green, and acriflavine were tested on infectious pancreatic necrosis virus (IPNV). Iodine and chlorine showed good activity, but efficacy depended on the concentration of virus, the presence of organic matter (calf serum), and water pH. Water hardness (0-300 mg 1−1 as CaCO3) did not affect virucidal activity. In a 5 min exposure, 4 mg 1−1available iodine inactivated 103.9 TCID50 m1−1 IPNV but 16 mg 1−1 iodine were needed for inactivation of 106.3TCID50m1−1. The addition of 0-5% calf serum significantly reduced the iodine concentration and the virucidal activity. In comparison, 4 mg 1−1 chlorine were needed to inactivate 1046 TCID50 m1−1 IPNV in 5 min. However, the addition of 0-07 % serum greatly reduced the chlorine concentration and extended the virucidal contact time to 30 min or more. IPNV at 106.3 TCID60 m1−1 was not inactivated by exposures for 60 min to 0-2% formalin, 10 min to 0-2% thimerosal, 60 min to 5 mg 1−1 malachite green, or 20 min to 500 mg 1−1 acriflavine. However, acriflavine at 0-5 mg 1−1 in cell culture media prevented the development of cytopathology caused by IPNV and may be useful in the treatment of the disease.

  8. Bone marrow necrosis in a cat infected with feline leukemia virus.

    PubMed

    Shimoda, T; Shiranaga, N; Mashita, T; Hasegawa, A

    2000-01-01

    A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection.

  9. Skin and soft tissue necrosis from calcium chloride in a deicer.

    PubMed

    Kim, Min P; Raho, Vittorio J; Mak, John; Kaynar, A Murat

    2007-01-01

    Calcium chloride salt is the principle ingredient of many commercially available deicers. Calcium chloride melts snow and ice by its osmotic action. We present a case of skin and soft tissue necrosis associated with the use of a calcium chloride-containing deicer. Although calcium chloride is known to produce soft tissue necrosis if it extravasates during intravenous administration, necrosis and skin sloughing has rarely been described after topical exposure to this salt. Calcium chloride likely produces tissue injury from the heat liberated by mixing calcium chloride with water (exothermic reaction) and from direct calcium deposits in the skin (calcinosis cutis) and soft tissue.

  10. Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks.

    PubMed

    Weber, Martha A; Terrell, Scott P; Neiffer, Donald L; Miller, Michele A; Mangold, Barbara J

    2002-08-01

    Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

  11. Structure/Function analysis of p55 tumor necrosis factor receptor and fas-associated death domain. Effect on necrosis in L929sA cells.

    PubMed

    Boone, E; Vanden Berghe, T; Van Loo, G; De Wilde, G; De Wael, N; Vercammen, D; Fiers, W; Haegeman, G; Vandenabeele, P

    2000-12-01

    Tumor necrosis factor (TNF) induces a typical apoptotic cell death program in various cell lines by interacting with the p55 tumor necrosis factor receptor (TNF-R55). In contrast, triggering of the fibrosarcoma cell line L929sA gives rise to characteristic cellular changes resulting in necrosis. The intracellular domain of TNF-R55 can be subdivided into two parts: a membrane-proximal domain (amino acids 202-325) and a C-terminal death domain (DD) (amino acids 326-413), which has been shown to be necessary and sufficient for apoptosis. Structure/function analysis of TNF-R55-mediated necrosis in L929sA cells demonstrated that initiation of necrotic cell death, as defined by swelling of the cells, rapid membrane permeabilization, absence of nuclear condensation, absence of DNA hypoploidy, and generation of mitochondrial reactive oxygen intermediates, is also confined to the DD. The striking synergistic effect of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone on TNF-induced necrosis was also observed with receptors solely containing the DD. TNF-R55-mediated necrosis is not affected by the dominant negative deletion mutant of the Fas-associated death domain (FADD-(80-205)) that lacks the N-terminal death effector domain. Moreover, overexpression of FADD-(80-205) in L929sA is cytotoxic and insensitive to CrmA, while the cytotoxicity due to overexpression of the deletion mutant FADD-(1-111) lacking the DD is prevented by CrmA. These results demonstrate that the death domain of FADD can elicit an active necrotic cell death pathway.

  12. Going International: The Balanced Scorecard.

    ERIC Educational Resources Information Center

    Rojas, Alicia M.

    2001-01-01

    Explains the balanced scorecard as a management system that provides a framework for strategic measurement which translates the vision and strategy of the organization in operational terms by four indicators: financial, process, employee and client satisfaction, and results. Also considers the importance of cultural differences in performance…

  13. Balanced Assessment. K-College.

    ERIC Educational Resources Information Center

    Fogarty, Robin

    To say that assessments must be authentic, dynamic, fluid, and formative is not to say that normative, standardized evaluations have no place in the overall assessment scheme. What is needed is a combination and balance of assessments. The tri-assessment model promotes using traditional assessments along with portfolio and performance assessments.…

  14. Up for Discussion: Balancing Act.

    ERIC Educational Resources Information Center

    Flannery, Susan

    1981-01-01

    Recommends that libraries include conservative 'Moral Majority' as well as liberal views of human sexuality in their acquisition of books for young adults to provide a balanced collection and blunt atttempts to limit academic freedom through censorship. Five 'New Right' choices are reviewed. (RAA)

  15. Learning from Balance Sheet Visualization

    ERIC Educational Resources Information Center

    Tanlamai, Uthai; Soongswang, Oranuj

    2011-01-01

    This exploratory study examines alternative visuals and their effect on the level of learning of balance sheet users. Executive and regular classes of graduate students majoring in information technology in business were asked to evaluate the extent of acceptance and enhanced capability of these alternative visuals toward their learning…

  16. Dual shell pressure balanced vessel

    DOEpatents

    Fassbender, Alexander G.

    1992-01-01

    A dual-wall pressure balanced vessel for processing high viscosity slurries at high temperatures and pressures having an outer pressure vessel and an inner vessel with an annular space between the vessels pressurized at a pressure slightly less than or equivalent to the pressure within the inner vessel.

  17. The Revenue vs. Service Balance

    ERIC Educational Resources Information Center

    Savarese, John

    2006-01-01

    Ten years ago, students at the University of Vermont (UVM) had to carry separate ID cards, meal cards, and athletic cards. Today, the single CATcard combines all of these functions, plus library privileges, an optional declining balance program called CAT$cratch, access to computer labs, use of vending machines without quarters, and even a ride on…

  18. Finding Balance in the Winds.

    ERIC Educational Resources Information Center

    Wilbur, Michael

    1999-01-01

    Describes the author's experience of and reflections concerning a group workshop facilitated by Michael Tlanusta Garrett of the Eastern Band of Cherokee. Provides information about the Native American teachings and traditions of the four winds, balance, and harmony, and discusses the use of self by group leaders as a powerful therapeutic and…

  19. Off-Balance Sheet Financing.

    ERIC Educational Resources Information Center

    Adams, Matthew C.

    1998-01-01

    Examines off-balance sheet financing, the facilities use of outsourcing for selected needs, as a means of saving operational costs and using facility assets efficiently. Examples of using outside sources for energy supply and food services, as well as partnering with business for facility expansion are provided. Concluding comments address tax…

  20. A Balanced Higher Education System

    ERIC Educational Resources Information Center

    Brown, Roger

    2011-01-01

    This article explores what is meant by "a balanced higher education system". It argues that the Clarkian "triangle of coordination" (Clark, 1983) and the more recent model of Martinez and Richardson (2003) should be replaced by one that distinguishes between "self" and "collective" interests in both the…

  1. Haematopoietic necrosis in a goldfish (Carassius auratus) associated with an agent morphologically similar to herpesvirus.

    PubMed

    Stephens, F J; Raidal, S R; Jones, B

    2004-03-01

    One of 14 goldfish (Carassius auratus) died 4 weeks after purchase and was investigated by necropsy and histological examination. Routine formalin fixation of the goldfish was followed by histopathology. Formalin fixed spleen and kidney from the fish was further processed by embedding in epoxy resin and examined by transmission electron microscopy (EM). Severe, diffuse necrosis of haematopoietic tissue in the spleen, thymus and kidney and severe, diffuse hyperplasia in the gill epithelial cells were seen. In the spleen there was severe, diffuse necrosis of lymphocytes and many nuclei with marginated chromatin and intranuclear inclusions were scattered throughout the necrotic tissue. EM of affected tissues demonstrated intranuclear particles morphologically similar to herpesvirus. The presence of an agent similar to a herpesvirus in a goldfish with severe haematopoietic necrosis suggests that the herpesvirus responsible for haematopoietic necrosis in cyprinid species throughout the world has entered the goldfish population in Australia.

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

    PubMed

    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.

  3. A case of spontaneous myocardial necrosis and cerebral ischemic lesions in a laboratory beagle dog.

    PubMed

    Matsushita, Kohei; Kohara, Yukari; Ito, Yuko; Yoshikawa, Tsuyoshi; Sato, Makoto; Kitaura, Keisuke; Matsumoto, Satoshi

    2015-10-01

    A beagle dog treated with saline as a control animal in a preclinical study was euthanized due to sudden systemic deterioration. On histopathological examination, contraction band necrosis of myocardial cells was observed widely in the left ventricular wall, including the papillary muscle and apex, and observed slightly in the ventricular septum and left atrium. In the brain, necrosis was observed in neurons and glia of the cerebral cortex, hippocampal pyramidal cells, glial cells of the rostral commissure and Purkinje cells of the cerebellar vermis. It is highly probable that the marked systemic deterioration was caused by cardiac dysfunction due to the spontaneous contraction band necrosis of the myocardial cells, although the pathogenesis of the myocardial lesions remains unclear. Given the distribution of neuronal necrosis in the brain, it is likely that these lesions resulted from the ischemia responsible for acute cardiac failure.

  4. Genetics Home Reference: tumor necrosis factor receptor-associated periodic syndrome

    MedlinePlus

    ... 1 link) University College London: National Amyloidosis Center (UK) General Information from MedlinePlus (5 links) Diagnostic Tests ... of Hereditary Periodic Fever Syndromes NHS Foundation Trust (UK) Orphanet: Tumor necrosis factor receptor 1 associated periodic ...

  5. Shedding of tumor necrosis factor receptors by activated human neutrophils

    PubMed Central

    1990-01-01

    The capacity of human neutrophils (PMN) to bind tumor necrosis factor (TNF) was rapidly lost when the cells were incubated in suspension with agents that can stimulate their migratory and secretory responses. Both physiological (poly)peptides (FMLP, C5a, CSF-GM) and pharmacologic agonists (PMN, calcium ionophore A23187) induced the loss of TNF receptors (TNF-R) from the cell surface. Half-maximal loss in TNF-R ensued after only approximately 2 min with 10(-7) M FMLP at 37 degrees C, and required only 10(-9) M FMLP during a 30-min exposure. However, there were no such changes even with prolonged exposure of PMN to FMLP at 4 degrees or 16 degrees C. Scatchard analysis revealed loss of TNF- binding sites without change in their affinity (Kd approximately 0.4 nM) as measured at incompletely modulating concentrations of FMLP, C5a, PMA, or A23187. The binding of anti-TNF-R mAbs to PMN decreased in parallel, providing independent evidence for the loss of TNF-R from the cell surface. At the same time, soluble TNF-R appeared in the medium of stimulated PMN. This inference was based on the PMN- and FMLP-dependent generation of a nonsedimentable activity that could inhibit the binding of TNF to fresh human PMN or to mouse macrophages, and the ability of mAbs specific for human TNF-R to abolish inhibition by PMN-conditioned medium of binding of TNF to mouse macrophages. Soluble TNF-R activity was associated with a protein of Mr approximately 28,000 by ligand blot analysis of cell-free supernatants of FMLP-treated PMN. Thus, some portion of the FMLP-induced loss of TNF-R from human PMN is due to shedding of TNF-R. Shedding was unaffected by inhibitors of serine and thiol proteases and could not be induced with phosphatidylinositol- specific phospholipase C. Loss of TNF-R from PMN first stimulated by other agents may decrease their responsiveness to TNF. TNF-R shed by PMN may be one source of the TNF-binding proteins found in body fluids, and may blunt the actions of the

  6. [Brain radiation necrosis after stereotactic radiotherapy of the resection cavity for intracranial metastases: analysis of the literature from four cases].

    PubMed

    Doré, M; Lefebvre, L; Delpon, G; Thillays, F

    2015-04-01

    Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts.

  7. Real-time magnetic resonance imaging texture characterization of necrosis during laser interstitital thermotherapy procedures

    NASA Astrophysics Data System (ADS)

    Betrouni, N.; Lopes, R.; Colin, P.; Mordon, S.

    2010-02-01

    This paper aims to describe the development of a method to monitor laser interstitial thermo therapy by MR images. The method is based on the texture analysis using fractal geometry features of the images to estimate the size of the induced necrosis. The method was validated by comparing the results to macroscopic measurements. It demonstrates the ability to achieve good estimation of the necrosis in ex-vivo experimentations involving pig liver and in vivo experimentations done on tumors grown on Copenhagen rats.

  8. [Intracardiac mass: Why not a liquefaction necrosis of a mitral annulus calcification?].

    PubMed

    Leddet, P; Couppié, P; De Poli, F; Uhry, S; Hanssen, M

    2015-11-01

    We report the case of an asymptomatic 70-year-old woman with a liquefaction necrosis of mitral annulus calcification. This mass was discovered incidentally during an echocardiographic examination. Additional treatment was not performed because liquefaction necrosis of mitral calcification usually has a benign prognosic. A scheduled clinical review with an echocardiographic examination and cardiac MRI was planified. The patient is actually healthy without any complication.

  9. The incidence of fat necrosis in balloon-based breast brachytherapy

    PubMed Central

    Vallow, Laura; Magalhaes, Wilza; Heckman, Michael G.; Kim, Siyong; Smith, Ashley; Diehl, Nancy N.; McLaughlin, Sarah

    2015-01-01

    Purpose To investigate the incidence of and potential risk factors for fat necrosis in high dose-rate (HDR) balloon-based breast brachytherapy (BBB). Material and methods Fifty-four patients were treated postoperatively with HDR-BBB between May 2007 and December 2010. Median age was 71 years (range: 50-88 years). Median tumor size was 1 cm (range: 0.1-2.7 cm). Forty-four had invasive histology; 43% were grade 1, 24% grade 2, and 15% grade 3. The median margin size was 0.7 cm (range: 0.1-1.5 cm). Results With a median follow-up of 2.9 years (range: 0.5-5.2 years), local control was 98% with one in-breast failure, and overall survival was 89%. Fifty percent of patients experienced fat necrosis. Seven patients were symptomatic, with the remainder detected by mammography alone. Two patients required surgical resection with pathology confirming fat necrosis; 1 required i.v. steroids. At 1, 3, and 5 years following treatment, estimated cumulative incidences of fat necrosis were 7.5%, 52.7%, and 60.6%. Breast laterality, location, tumor size, histology, margin size, balloon volume, skin distance, skin dose, and number of dwell positions were not significantly associated with fat necrosis on univariate analysis. Conclusions In this retrospective review of HDR-BBB, we found a 50% incidence of both asymptomatic and symptomatic fat necrosis. Only three patients, however, required intervention. None of the risk factors considered were significantly associated with fat necrosis. Further studies evaluating factors associated with fat necrosis for patients undergoing HDR-BBB are necessary to appropriately assess the risks associated with treatment. PMID:25829934

  10. The relevance of clinical balance assessment tools to differentiate balance deficits

    PubMed Central

    Mancini, Martina; Horak, Fay B

    2011-01-01

    Control of balance is complex and involves maintaining postures, facilitating movement, and recovering equilibrium. Balance control consists of controlling the body center of mass over its limits of stability. Clinical balance assessment can help assess fall risk and/or determine the underlying reasons for balance disorders. Most functional balance assessment scales assess fall risk and the need for balance rehabilitation but do not differentiate types of balance deficits. A system approach to clinical balance assessment can differentiate different kinds of balance disorders and a physiological approach can determine underlying sensorimotor mechanisms contributing to balance disorders. Objective measures of balance using computerized systems and wearable inertial sensors can bring more sensitive, specific and responsive balance testing to clinical practice. PMID:20485226

  11. A quantitative real-time approach for discriminating apoptosis and necrosis

    PubMed Central

    Lekshmi, Asha; Varadarajan, Shankara Narayanan; Lupitha, Santhik Subhasingh; Indira, Deepa; Mathew, Krupa Ann; Chandrasekharan Nair, Aneesh; Nair, Mydhily; Prasad, Tilak; Sekar, Hari; Gopalakrishnan, Anurup Kochucherukkan; Murali, Abitha; Santhoshkumar, Thankayyan Retnabai

    2017-01-01

    Apoptosis and necrosis are the two major forms of cell death mechanisms. Both forms of cell death are involved in several physiological and pathological conditions and also in the elimination of cancer cells following successful chemotherapy. Large number of cellular and biochemical assays have evolved to determine apoptosis or necrosis for qualitative and quantitative purposes. A closer analysis of the assays and their performance reveal the difficulty in using any of these methods as a confirmatory approach, owing to the secondary induction of necrosis in apoptotic cells. This highlights the essential requirement of an approach with a real-time analysis capability for discriminating the two forms of cell death. This paper describes a sensitive live cell-based method for distinguishing apoptosis and necrosis at single-cell level. The method uses cancer cells stably expressing genetically encoded FRET-based active caspase detection probe and DsRed fluorescent protein targeted to mitochondria. Caspase activation is visualized by loss of FRET upon cleavage of the FRET probe, while retention of mitochondrial fluorescence and loss of FRET probe before its cleavage confirms necrosis. The absence of cleavage as well as the retention of mitochondrial fluorescence indicates live cells. The method described here forms an extremely sensitive tool to visualize and quantify apoptosis and necrosis, which is adaptable for diverse microscopic, flow cytometric techniques and high-throughput imaging platforms with potential application in diverse areas of cell biology and oncology drug screening. PMID:28179996

  12. Response-driven Imaging Biomarkers for Predicting Radiation Necrosis of the Brain

    PubMed Central

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-01-01

    Purpose Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy. Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Methods and Materials Twenty-nine patients with glioblastoma received six weeks of intensity modulated radiation therapy (RT) and concurrent temozolamide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Results Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p=0.05 and p=0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Conclusions Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid in predicting delayed radiation necrosis, which could provide guidance in dose-escalation trials. PMID:24778364

  13. Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

    NASA Astrophysics Data System (ADS)

    Yasui, Linda; Gladden, Samantha; Andorf, Christine; Kroc, Thomas

    2011-06-01

    Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy γ rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy γ rays or 2 Gy fast neutrons. Very few γ irradiated cells had features of necrosis (U87 or U251 cell samples processed for TEM 1 day after 10 Gy γ irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to γ irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.

  14. Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

    PubMed

    Zhang, Dongjian; Jiang, Cuihua; Yang, Shengwei; Gao, Meng; Huang, Dejian; Wang, Xiaoning; Shao, Haibo; Feng, Yuanbo; Sun, Ziping; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-01-01

    Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.

  15. Rapid Detection of Necrosis in Breast Cancer with Desorption Electrospray Ionization Mass Spectrometry

    PubMed Central

    Tata, Alessandra; Woolman, Michael; Ventura, Manuela; Bernards, Nicholas; Ganguly, Milan; Gribble, Adam; Shrestha, Bindesh; Bluemke, Emma; Ginsberg, Howard J.; Vitkin, Alex; Zheng, Jinzi; Zarrine-Afsar, Arash

    2016-01-01

    Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl]− which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391.25 which is present in small abundance only in viable cancer subregions; and (3) a slight increase in the relative intensity of known breast cancer biomarker ions of m/z 281.25 [FA(18:1)-H]− and 303.23 [FA(20:4)-H]−. Necrosis is accompanied by alterations in the tissue optical depolarization rate, allowing tissue polarimetry to guide DESI-MS analysis for rapid MS profiling or targeted MS imaging. This workflow, in combination with the MS profile of necrosis, may permit rapid characterization of necrotic tumors from tissue slices. Further, necrosis-specific biomarker ions are detected in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the identification workflow by avoiding tissue sectioning and slide preparation. PMID:27734938

  16. Histopathological changes in the pancreas of cattle with abdominal fat necrosis

    PubMed Central

    TANI, Chikako; PRATAKPIRIYA, Watanyoo; TANI, Mineto; YAMAUCHI, Takenori; HIRAI, Takuya; YAMAGUCHI, Ryoji; ANO, Hitoshi; KATAMOTO, Hiromu

    2016-01-01

    The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process. PMID:27795463

  17. Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization

    SciTech Connect

    Sonomura, Tetsuo; Yamada, Ryusaku; Kishi, Kazushi; Nishida, Norifumi; Yang, Ren J.; Sato, Morio

    1997-01-15

    Purpose. To determine the optimal size of gelatin sponge particles (GSPs) to produce maximum tumor necrosis with minimum side effects after canine hepatic artery embolization (HAE). Methods. GSPs were separated into four size ranges: A, up to 200 {mu}m (mean 152) as Gelfoam powder; B, 200-500 {mu}m (mean 336) as Gelfoam powder; C, 500-1000 {mu}m (mean 649) as Spongel; and D, 1000-2000 {mu}m (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE with each particle size. On day 7 after HAE, the livers were removed and subjected to pathological examination. Results. The mean volume of liver necrosis was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1% with D. Coagulation necrosis was found in all livers with particles of sizes A and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis was found in one dog with size B and pancreas necrosis in one with size A. Conclusion. GSPs of 500 {mu}m are considered optimally effective for tissue necrosis according to this model.

  18. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure

    PubMed Central

    Nakayama, Hiroyuki; Chen, Xiongwen; Baines, Christopher P.; Klevitsky, Raisa; Zhang, Xiaoying; Zhang, Hongyu; Jaleel, Naser; Chua, Balvin H.L.; Hewett, Timothy E.; Robbins, Jeffrey; Houser, Steven R.; Molkentin, Jeffery D.

    2007-01-01

    Loss of cardiac myocytes in heart failure is thought to occur largely through an apoptotic process. Here we show that heart failure can also be precipitated through myocyte necrosis associated with Ca2+ overload. Inducible transgenic mice with enhanced sarcolemmal L-type Ca2+ channel (LTCC) activity showed progressive myocyte necrosis that led to pump dysfunction and premature death, effects that were dramatically enhanced by acute stimulation of β-adrenergic receptors. Enhanced Ca2+ influx–induced cellular necrosis and cardiomyopathy was prevented with either LTCC blockers or β-adrenergic receptor antagonists, demonstrating a proximal relationship among β-adrenergic receptor function, Ca2+ handling, and heart failure progression through necrotic cell loss. Mechanistically, loss of cyclophilin D, a regulator of the mitochondrial permeability transition pore that underpins necrosis, blocked Ca2+ influx–induced necrosis of myocytes, heart failure, and isoproterenol-induced premature death. In contrast, overexpression of the antiapoptotic factor Bcl-2 was ineffective in mitigating heart failure and death associated with excess Ca2+ influx and acute β-adrenergic receptor stimulation. This paradigm of mitochondrial- and necrosis-dependent heart failure was also observed in other mouse models of disease, which supports the concept that heart failure is a pleiotropic disorder that involves not only apoptosis, but also necrotic loss of myocytes in association with dysregulated Ca2+ handling and β-adrenergic receptor signaling. PMID:17694179

  19. Response-driven imaging biomarkers for predicting radiation necrosis of the brain

    NASA Astrophysics Data System (ADS)

    Nazem Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-05-01

    Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials.

  20. Comparative transcriptome analysis to reveal genes involved in wheat hybrid necrosis.

    PubMed

    Zhang, Yong; Cheng, Yan; Guo, Jiahui; Yang, Ennian; Liu, Cheng; Zheng, Xuelian; Deng, Kejun; Zhou, Jianping

    2014-12-16

    Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469) were investigated using digital gene expression (DGE). A total of 1300 differentially expressed genes were identified, indicating that the response to hybrid necrosis in wheat is complicated. The assignments of the annotated genes based on Gene Ontology (GO) revealed that most of the up-regulated genes belong to "universal stress related", "DNA/RNA binding", "protein degradation" functional groups, while the down-regulated genes belong to "carbohydrate metabolism" and "translation regulation" functional groups. These findings suggest that these pathways were affected by hybrid necrosis. Our results provide preliminarily new insight into the underlying molecular mechanisms of hybrid necrosis and will help to identify important candidate genes involved in wheat hybrid necrosis.

  1. Pancreatic Necrosis and Gas in the Retroperitoneum: Treatment with Antibiotics Alone

    PubMed Central

    Rasslan, Roberto; da Costa Ferreira Novo, Fernando; Rocha, Marcelo Cristiano; Bitran, Alberto; de Souza Rocha, Manoel; de Oliveira Bernini, Celso; Rasslan, Samir; Utiyama, Edivaldo Massazo

    2017-01-01

    OBJECTIVE: To present our experience in the management of patients with infected pancreatic necrosis without drainage. METHODS: The records of patients with pancreatic necrosis admitted to our facility from 2011 to 2015 were retrospectively reviewed. RESULTS: We identified 61 patients with pancreatic necrosis. Six patients with pancreatic necrosis and gas in the retroperitoneum were treated exclusively with clinical support without any type of drainage. Only 2 patients had an APACHE II score >8. The first computed tomography scan revealed the presence of gas in 5 patients. The Balthazar computed tomography severity index score was >9 in 5 of the 6 patients. All patients were treated with antibiotics for at least 3 weeks. Blood cultures were positive in only 2 patients. Parenteral nutrition was not used in these patients. The length of hospital stay exceeded three weeks for 5 patients; 3 patients had to be readmitted. A cholecystectomy was performed after necrosis was completely resolved; pancreatitis recurred in 2 patients before the operation. No patients died. CONCLUSIONS: In selected patients, infected pancreatic necrosis (gas in the retroperitoneum) can be treated without percutaneous drainage or any additional surgical intervention. Intervention procedures should be performed for patients who exhibit clinical and laboratory deterioration. PMID:28273241

  2. Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

    SciTech Connect

    Yasui, Linda; Gladden, Samantha; Andorf, Christine; Kroc, Thomas

    2011-06-01

    Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy {gamma} rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy {gamma} rays or 2 Gy fast neutrons. Very few {gamma} irradiated cells had features of necrosis (U87 or U251 cell samples processed for TEM 1 day after 10 Gy {gamma} irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to {gamma} irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.

  3. Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis.

    PubMed

    Borab, Zachary; Mirmanesh, Michael D; Gantz, Madeleine; Cusano, Alessandro; Pu, Lee L Q

    2017-04-01

    Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis.

  4. Balanced pressure gerotor fuel pump

    DOEpatents

    Raney, Michael Raymond; Maier, Eugen

    2004-08-03

    A gerotor pump for pressurizing gasoline fuel is capable of developing pressures up to 2.0 MPa with good mechanical and volumetric efficiency and satisfying the durability requirements for an automotive fuel pump. The pump has been designed with optimized clearances and by including features that promote the formation of lubricating films of pressurized fuel. Features of the improved pump include the use of a shadow port in the side plate opposite the outlet port to promote balancing of high fuel pressures on the opposite sides of the rotors. Inner and outer rotors have predetermined side clearances with the clearances of the outer rotor being greater than those of the inner rotor in order to promote fuel pressure balance on the sides of the outer rotor. Support of the inner rotor and a drive shaft on a single bushing with bearing sleeves maintains concentricity. Additional features are disclosed.

  5. BALANCED PRODUCTION OF RIBOSOMAL PROTEINS

    PubMed Central

    Perry, Robert P.

    2017-01-01

    Eukaryotic ribosomes contain one molecule each of 79 different proteins. The genes encoding these proteins are usually at widely scattered loci and have distinctive promoters with certain common features. This minireview discusses the means by which cells manage to balance the production of ribosomal proteins so as to end up with equimolar quantities in the ribosome. Regulation at all levels of gene expression, from transcription to protein turnover, is considered. PMID:17689889

  6. [Balance disorders in the elderly].

    PubMed

    Bracchi, E; Rizzo, S; Longari, F; Bernardini, M; Bizzotti, C; Frenguelli, A

    2002-10-01

    In the elderly patient, instability is a syndrome in which a loss of balance, during ambulation or while standing, can give rise to falls, with consequent disability and morbidity. Maintaining the correct static and dynamic balance is known to be the result of the synergetic functioning of different systems. In old age, however, the efficiency of these mechanisms is impaired because of the physiological process of aging, which affects all of the organs and systems of the human body. Besides that, different concomitant causes such as cardiovascular and dysmetabolic pathologies, chronic pharmacological therapies etc. contribute to the aging of our organism. The object of this study was to evaluate 40 subjects, 21 males and 19 females, aged between 70 and 86, who were referred to us with craniofacial trauma consequent to a fall. Upon hospitalization, all of the patients were asked to fill in a questionnaire evaluating the incidence of the vertigo symptom as a possible cause of the falls. All of the subjects underwent the following clinicoinstrumental examinations: standard audiometric evaluation, vestibular tests, neurological and ophthalmic examination. Careful appraisal of the results obtained enabled us to conclude that balance disorders in the elderly patient are due to the synergetic action of three factors: aging, concomitant diseases and environmental factors. In conclusion, we can affirm that balance disorders giving rise to a fall in the elderly are attributable to the concomitance of different factors that determine a clinical state of imbalance, defined by some Authors with the term "presbivertigo". It follows that a suitable diagnostic protocol must be employed, comprising a detailed medical, pharmacological and functional history, a study both of the environmental conditions in which the patient lives and the modalities according to which the traumatic event occurred. It is, last of all, indispensable that steps be taken to improve these environmental

  7. Constrained Allocation Flux Balance Analysis

    PubMed Central

    Mori, Matteo; Hwa, Terence; Martin, Olivier C.

    2016-01-01

    New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints to extend and complement Flux Balance Analysis. We introduce here Constrained Allocation Flux Balance Analysis, CAFBA, in which the biosynthetic costs associated to growth are accounted for in an effective way through a single additional genome-wide constraint. Its roots lie in the experimentally observed pattern of proteome allocation for metabolic functions, allowing to bridge regulation and metabolism in a transparent way under the principle of growth-rate maximization. We provide a simple method to solve CAFBA efficiently and propose an “ensemble averaging” procedure to account for unknown protein costs. Applying this approach to modeling E. coli metabolism, we find that, as the growth rate increases, CAFBA solutions cross over from respiratory, growth-yield maximizing states (preferred at slow growth) to fermentative states with carbon overflow (preferred at fast growth). In addition, CAFBA allows for quantitatively accurate predictions on the rate of acetate excretion and growth yield based on only 3 parameters determined by empirical growth laws. PMID:27355325

  8. Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout: hematological and blood chemical changes in moribund fish

    USGS Publications Warehouse

    Amend, D.F.; Smith, L.

    1975-01-01

    Infectious hematopoietic necrosis (IHN) is a rhabdoviral disease of rainbow trout (Salmo gairdneri). Trout were injected with IHNV, and various hematological and biochemical measurements of clinically ill fish were compared to uninfected controls. Infected fish had reduced corpuscular counts, hemoglobin, and packed cell volume, but normal mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The percentage of immature erythrocytes was increased, but the percentage of leukocytes was unchanged. Differential leukocyte counts showed a significant decrease in neutrophils, increase in lymphocytes, but no change in monocytes. Unidentifiable necrobiotic cells were prevelant in blood smears and hematopoietic tissue imprints. Plasma bicarbonate, chloride, calcium, phosphorus, bilirubin, and osmolality were significantly reduced, but plasma glucose and anterior kidney ascorbate were unchanged. Plasma pH increased and the alpha fractions of the serum proteins were altered. No change was found in plasma enzymes, except that a LDH isozyme was significantly increased. The alkali reserve was diminished and alterations in acid-base and fluid balance occurred. Death probably resulted from a severe electrolyte and fluid imbalance caused by renal failure.

  9. Tumor necrosis factor inhibits ligand-stimulated EGF receptor activation through a TNF receptor 1-dependent mechanism

    PubMed Central

    McElroy, Steven J.; Frey, Mark R.; Yan, Fang; Edelblum, Karen L.; Goettel, Jeremy A.; John, Sutha; Polk, D. Brent

    2008-01-01

    Tumor necrosis factor (TNF) and epidermal growth factor (EGF) are key regulators in the intricate balance maintaining intestinal homeostasis. Previous work from our laboratory shows that TNF attenuates ligand-driven EGF receptor (EGFR) phosphorylation in intestinal epithelial cells. To identify the mechanisms underlying this effect, we examined EGFR phosphorylation in cells lacking individual TNF receptors. TNF attenuated EGF-stimulated EGFR phosphorylation in wild-type and TNFR2−/−, but not TNFR1−/−, mouse colon epithelial (MCE) cells. Reexpression of wild-type TNFR1 in TNFR1−/− MCE cells rescued TNF-induced EGFR inhibition, but expression of TNFR1 deletion mutant constructs lacking the death domain (DD) of TNFR1 did not, implicating this domain in EGFR downregulation. Blockade of p38 MAPK, but not MEK, activation of ERK rescued EGF-stimulated phosphorylation in the presence of TNF, consistent with the ability of TNFR1 to stimulate p38 phosphorylation. TNF promoted p38-dependent EGFR internalization in MCE cells, suggesting that desensitization is achieved by reducing receptor accessible to ligand. Taken together, these data indicate that TNF activates TNFR1 by DD- and p38-dependent mechanisms to promote EGFR internalization, with potential impact on EGF-induced proliferation and migration key processes that promote healing in inflammatory intestinal diseases. PMID:18467504

  10. Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

    SciTech Connect

    McDonald, Mark W.; Linton, Okechukwu R.; Calley, Cynthia S.J.

    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

  11. [Chronic inflammatory bowel disease--pathogenic concepts and therapeutic perspectives].

    PubMed

    Madsen, J R

    2000-03-06

    Chronic inflammatory bowel disease (IBD) is considered to be a consequence of inappropriate upregulation of immune reactions evoked by the colonic microflora. Abnormalities observed in IBD may be explained, at least in part, by an unfavourable balance between pro- and anti-inflammatory cytokines. Conventional drug treatment of IBD may soon be replaced by more selective inhibitors that act centrally in the inflammatory process. Immunoneutralisation with chimeric anti-tumour necrosis factor-alpha (TNF alpha) antibodies reduces treatment refractory IBD, including fistular Chrons' disease, but recombinant human TNF alpha-receptor fusion proteins may be equally effective with potentially fewer side effects. This view also applies to chimeric antibodies directed against cytokines or adhesion molecules. Potentially more promising are antisense oligonucleotides and matrix-metalloproteinase inhibitors. Whether sustained remission can be achieved probably depends on successful unravelling of the aetiology of IBD.

  12. Leadership and Work-Life Balance.

    PubMed

    Mattock, Sarah L

    2015-01-01

    Simply stated, work-life balance is something that is both difficult to define and difficult to achieve. Leaders, throughout the continuum of trauma care, need to have a sound understanding of what work-life balance means and set an example of a healthy work-life balance for those they lead. This article offers strategies for enhancing work-life balance and challenges individuals to use self-reflection as a means to furthering their personal and professional growth.

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

    SciTech Connect

    Joskin, Julien Baere, Thierry de; Auperin, Anne; Tselikas, Lambros Guiu, Boris Farouil, Geoffroy; Boige, Valérie Malka, David; Leboulleux, Sophie; Ducreux, Michel; Baudin, Eric; Deschamps, Frédéric

    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.

  14. 2 CFR 200.98 - Unobligated balance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Unobligated balance. 200.98 Section 200.98... REQUIREMENTS FOR FEDERAL AWARDS Acronyms and Definitions Acronyms § 200.98 Unobligated balance. Unobligated balance means the amount of funds under a Federal award that the non-Federal entity has not obligated....

  15. Hatha yoga on body balance

    PubMed Central

    Prado, Erick Tadeu; Raso, Vagner; Scharlach, Renata Coelho; Kasse, Cristiane Akemi

    2014-01-01

    Background: A good body balance requires a proper function of vestibular, visual, and somatosensory systems which can be reach with exercise practice and/or yoga. Aim: To determine the effects of a 5-month hatha yoga training program on body balance in young adults. Materials and Methods: This study used a controlled, nonrandomized design, where the experimental group underwent a 5-month training program and were then compared with the control group that had a sedentary lifestyle. A convenience sample of 34 out of 40 men aged 25-55 years old (34.0 ± 0.9) were deemed eligible for this study. They were randomly divided into two groups: Experimental and control groups. Subjects in the experimental group were engaged in 60 min sessions of hatha yoga three times a week for 5 months. We evaluated postural control by measuring the limit of stability and velocity of oscillation (VOS) in three conditions of the balance rehabilitation unit (BRU) and through field procedures (four position, plane, flamingo, hopscotch, and dynamic test). Results: We observed differences (P < 0.05) in postintervention scores between the groups regardless of BRU parameters and field procedures (except for flamingo) even after adjusting for preintervention scores, suggesting that these changes were induced by hatha yoga training. The partial eta squared on BRU parameters ranged from 0.78 (VOS1)-0.97 (COP2), and from 0.00 (flamingo)-0.94 (four position) for the field procedures. Conclusions: Our results provide substantial evidence that postural control in healthy young adults can be improved through practicing hatha yoga. PMID:25035623

  16. Possible anti-tumour-promoting activity of components in Japanese soybean fermented food, Natto: effect on gap junctional intercellular communication.

    PubMed

    Takahashi, C; Kikuchi, N; Katou, N; Miki, T; Yanagida, F; Umeda, M

    1995-03-01

    In order to detect any protective agent against tumor formation, we examined the anti-tumor-promoting effect of a Japanese traditional soybean fermented food, Natto. Dye transfer was employed as an assay method. When fluorescent dye was microinjected into cultured BALB/3T3 cells, the dye was transformed into the neighboring cells through the gap junction. This dye transfer was blocked by the treatment with the tumor promoters 12-O-tetra-decanoylphorbol-13-acetate (TPA), a high concentration of NaCl and lithocholic acid (LCA). This reduction of the dye transfer by TPA treatment was not observed when the cells were pretreated with retinoic acid, an anti-tumor promoter. Thus, the recovery of the dye transfer in TPA-treated BALB/3T3 cells was proven to ge a good indicator for detecting some possible anti-tumor promoters. After extraction and fractionation of Natto, we obtained an active fraction (H1) which showed recovery of the dye transfer in TPA-treated cells. The fraction contained straight-chain saturated hydrocarbons. A comparison of the fraction and the authentic samples by GC analysis suggests that the H1 fraction contained straight-chain saturated hydrocarbons from around C30 to C32. Among these hydrocarbons, hentriacontane (C31) was found at the highest concentrations, and was shown to have the highest activity. Hentriacontane at a very low concentration of 0.65 ng/ml was shown to recover the dye transfer inhibited by the treatment with TPA as well as with NaCl and LCA.

  17. Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice

    PubMed Central

    Lau, Janet; Cheung, Jeanne; Navarro, Armando; Lianoglou, Steve; Haley, Benjamin; Totpal, Klara; Sanders, Laura; Koeppen, Hartmut; Caplazi, Patrick; McBride, Jacqueline; Chiu, Henry; Hong, Rebecca; Grogan, Jane; Javinal, Vincent; Yauch, Robert; Irving, Bryan; Belvin, Marcia; Mellman, Ira; Kim, Jeong M.; Schmidt, Maike

    2017-01-01

    Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics. Using genetic deletion in preclinical mouse models, here we show that PD-L1 from disparate cellular sources, including tumour cells, myeloid or other immune cells can similarly modulate the degree of cytotoxic T-cell function and activity in the tumour microenvironment. PD-L1 expression in both the host and tumour compartment contribute to immune suppression in a non-redundant fashion, suggesting that both sources could be predictive of sensitivity to therapeutic agents targeting the PD-L1/PD-1 axis. PMID:28220772

  18. Preparation, characterisation and tumour targeting of cross-linked divalent and trivalent anti-tumour Fab' fragments.

    PubMed Central

    Casey, J. L.; King, D. J.; Chaplin, L. C.; Haines, A. M.; Pedley, R. B.; Mountain, A.; Yarranton, G. T.; Begent, R. H.

    1996-01-01

    The monoclonal anti-CEA antibody, A5B7, has previously been administered to patients for radioimmunotherapy (RIT). Long circulation time and the formation of an immune response have limited therapeutic success in the clinic. Antibody fragments can be used to reduce the in vivo circulation time, but the best combination of fragment and radioisotope to use for therapy is far from clear. In this study we have compared the biodistribution of A5B7 IgG and F(ab')2 with chemically cross-linked divalent (DFM) and trivalent (TFM) A5B7 Fab' fragments in nude mice bearing human colorectal tumour xenografts. The cross-linkers were designed to allow site-specific labelling using yttrium 90 (90Y), a high-energy beta-emitter. We have also compared the above antibody forms conjugated to both 131I and 90Y. Both DFM and TFM were fully immunoreactive and remained intact after radiolabelling and incubation in serum at 37 degrees C for 24 h. Biodistribution results showed similar tumour uptake levels and an identical blood clearance pattern for F(ab')2 and DFM with high tumour-blood ratios generated in each case. However, unacceptably high kidney accumulation for both F(ab')2 and DFM and elevated splenic uptake of DFM labelled with 90Y was observed. Kinetic analysis of antigen binding revealed that DFM had the fastest association rate (kass = 1.6 x 10(5) Ms-1) of the antibody forms, perhaps owing to increased flexibility of the cross-linker. This advantage implies that DFM may be more suitable than F(ab')2 radiolabelled with 131I for RIT. TFM cleared from the blood significantly faster than A5B7 IgG when labelled with both 131I and 90Y, producing an improved therapeutic tumour-blood ratio. Kidney accumulation was not observed for [90Y]TFM, but a slightly higher splenic uptake was observed that may indicate reticuloendothelial system (RES) uptake. Overall, tumour uptake was higher for 90Y-labelled antibodies than for 131I-labelled antibodies. Because of the faster clearance, it should be possible to administer a higher total dose of 90Y-labelled TFM than IgG, which is attractive for RIT. Both A5B7 DFM and TFM, therefore, show favourable properties compared with their parent antibody forms. Images Figure 1 PMID:8912535

  19. The genome-wide DNA sequence specificity of the anti-tumour drug bleomycin in human cells.

    PubMed

    Murray, Vincent; Chen, Jon K; Tanaka, Mark M

    2016-07-01

    The cancer chemotherapeutic agent, bleomycin, cleaves DNA at specific sites. For the first time, the genome-wide DNA sequence specificity of bleomycin breakage was determined in human cells. Utilising Illumina next-generation DNA sequencing techniques, over 200 million bleomycin cleavage sites were examined to elucidate the bleomycin genome-wide DNA selectivity. The genome-wide bleomycin cleavage data were analysed by four different methods to determine the cellular DNA sequence specificity of bleomycin strand breakage. For the most highly cleaved DNA sequences, the preferred site of bleomycin breakage was at 5'-GT* dinucleotide sequences (where the asterisk indicates the bleomycin cleavage site), with lesser cleavage at 5'-GC* dinucleotides. This investigation also determined longer bleomycin cleavage sequences, with preferred cleavage at 5'-GT*A and 5'- TGT* trinucleotide sequences, and 5'-TGT*A tetranucleotides. For cellular DNA, the hexanucleotide DNA sequence 5'-RTGT*AY (where R is a purine and Y is a pyrimidine) was the most highly cleaved DNA sequence. It was striking that alternating purine-pyrimidine sequences were highly cleaved by bleomycin. The highest intensity cleavage sites in cellular and purified DNA were very similar although there were some minor differences. Statistical nucleotide frequency analysis indicated a G nucleotide was present at the -3 position (relative to the cleavage site) in cellular DNA but was absent in purified DNA.

  20. Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans.

    PubMed

    Bigley, A B; Rezvani, K; Shah, N; Sekine, T; Balneger, N; Pistillo, M; Agha, N; Kunz, H; O'Connor, D P; Bollard, C M; Simpson, R J

    2016-08-01

    Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A- NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we determined the impact of latent CMV infection on NK cell cytotoxicity against four tumour target cell lines with varying levels of HLA-E expression. NK cell cytotoxicity against K562 (leukaemia origin) and U266 (multiple myeloma origin) target cells was strikingly greater in healthy CMV-seropositive donors than seronegative donors and was associated strongly with target cell HLA-E and NK cell NKG2C expression. NK cell cytotoxicity against HLA-E transfected lymphoma target cells (221.AEH) was ∼threefold higher with CMV, while NK cell cytotoxicity against non-transfected 721.221 cells was identical between the CMV groups. NK cell degranulation (CD107a(+) ) and interferon (IFN)-γ production to 221.AEH cells was localized almost exclusively to the NKG2C subset, and antibody blocking of NKG2C completely eliminated the effect of CMV on NK cell cytotoxicity against 221.AEH cells. Moreover, 221.AEH feeder cells and interleukin (IL)-15 were found to expand NKG2C(+) /NKG2A(-) NK cells preferentially from CMV-seronegative donors and increase NK cell cytotoxicity against HLA-E(+) tumour cell lines. We conclude that latent CMV infection enhances NK cell cytotoxicity through accumulation of NKG2C(+) NK cells, which may be beneficial in preventing the initiation and progression of haematological malignancies characterized by high HLA-E expression.

  1. Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties

    PubMed Central

    de Medina, Philippe; Paillasse, Michael R.; Segala, Gregory; Voisin, Maud; Mhamdi, Loubna; Dalenc, Florence; Lacroix-Triki, Magali; Filleron, Thomas; Pont, Frederic; Saati, Talal Al; Morisseau, Christophe; Hammock, Bruce D.; Silvente-Poirot, Sandrine; Poirot, Marc

    2013-01-01

    We previously synthesized dendrogenin A and hypothesized that it could be a natural metabolite occurring in mammals. Here we explore this hypothesis and report the discovery of dendrogenin A in mammalian tissues and normal cells as an enzymatic product of the conjugation of 5,6α-epoxy-cholesterol and histamine. Dendrogenin A was not detected in cancer cell lines and was fivefold lower in human breast tumours compared with normal tissues, suggesting a deregulation of dendrogenin A metabolism during carcinogenesis. We established that dendrogenin A is a selective inhibitor of cholesterol epoxide hydrolase and it triggered tumour re-differentiation and growth control in mice and improved animal survival. The properties of dendrogenin A and its decreased level in tumours suggest a physiological function in maintaining cell integrity and differentiation. The discovery of dendrogenin A reveals a new metabolic pathway at the crossroads of cholesterol and histamine metabolism and the existence of steroidal alkaloids in mammals. PMID:23673625

  2. Electronic Elections: A Balancing Act

    NASA Astrophysics Data System (ADS)

    Rezende, Pedro A. D.

    This article aims to share some major lessons learned from the pioneering experience in Brazil with the world's first full national implementation of universal electronic voting. Differing notions of security, and their "collateral entanglements", appear to play a key role and are contrasted in Brazil's pioneering electronic voting saga. After an introduction, we puzzle through what election security may mean. We elaborate on how technological innovations may affect the underlying risks, their nature, corrections and balance. Then we describe some ways in which innovations have been deployed and validated, and how the results are being perceived, before some closing remarks.

  3. Synchronization in random balanced networks

    NASA Astrophysics Data System (ADS)

    García del Molino, Luis Carlos; Pakdaman, Khashayar; Touboul, Jonathan; Wainrib, Gilles

    2013-10-01

    Characterizing the influence of network properties on the global emerging behavior of interacting elements constitutes a central question in many areas, from physical to social sciences. In this article we study a primary model of disordered neuronal networks with excitatory-inhibitory structure and balance constraints. We show how the interplay between structure and disorder in the connectivity leads to a universal transition from trivial to synchronized stationary or periodic states. This transition cannot be explained only through the analysis of the spectral density of the connectivity matrix. We provide a low-dimensional approximation that shows the role of both the structure and disorder in the dynamics.

  4. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  5. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... Effect of prefunding balance and funding standard carryover balance. (a) In general—(1) Overview....

  6. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.430(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  7. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.430(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  8. 26 CFR 1.430(f)-1 - Effect of prefunding balance and funding standard carryover balance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Effect of prefunding balance and funding standard carryover balance. 1.430(f)-1 Section 1.430(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.430(f)-1 Effect of prefunding balance and funding standard carryover balance. (a) In...

  9. Effect of Selected Balance Exercises on the Dynamic Balance of Children with Visual Impairments

    ERIC Educational Resources Information Center

    Jazi, Shirin Davarpanah; Purrajabi, Fatemeh; Movahedi, Ahmadreza; Jalali, Shahin

    2012-01-01

    Introduction: Maintaining balance while walking is of utmost importance for individuals with visual impairments because deficits in dynamic balance have been associated with a high risk of falling. Thus, the primary aim of the study presented here was to determine whether balance training effects the dynamic balance of children with visual…

  10. Rotary balances: A selected, annotated bibliography

    NASA Technical Reports Server (NTRS)

    Tuttle, Marie H.; Kilgore, Robert A.; Sych, Karen L.

    1989-01-01

    This bibliography on rotary balances contains 102 entries. It is part of NASA's support of the AGARD Fluid Dynamics Panel Working Group 11 on Rotary Balances. This bibliography includes works that might be useful to anyone interested in building or using rotor balances. Emphasis is on the rotary balance rigs and testing techniques rather than the aerodynamic data. Also included are some publications of historical interest which relate to key events in the development and use of rotary balances. The arrangement is chronological by date of publication in the case of reports and by presentation in the case of papers.

  11. Engine balance apparatus and accessory drive device

    NASA Technical Reports Server (NTRS)

    Brogdon, James William (Inventor); Gill, David Keith (Inventor)

    2000-01-01

    A balancing mechanism for an engine that has a rotating crankshaft and reciprocating pistons such as those engines used in automobiles, aircrafts, boats, piston-driven compressors, piston-driven slider crank mechanisms, etc. The present balancing mechanism may comprise a first balance mass non-rotatably affixed to the crankshaft and a second balance mass rotatably supported on the crankshaft. A driver assembly is affixed to crankshaft to cause the second balance mass to rotate in a direction that is opposite to the direction in which the crank shaft is rotating. The driver assembly may include auxiliary gears configured to transport rotary power to auxiliary components.

  12. AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX

    PubMed Central

    Artus, Cédric; Boujrad, Hanan; Bouharrour, Aïda; Brunelle, Marie-Noëlle; Hoos, Sylviane; Yuste, Victor J; Lenormand, Pascal; Rousselle, Jean-Claude; Namane, Abdelkader; England, Patrick; Lorenzo, Hans K; Susin, Santos A

    2010-01-01

    Programmed necrosis induced by DNA alkylating agents, such as MNNG, is a caspase-independent mode of cell death mediated by apoptosis-inducing factor (AIF). After poly(ADP-ribose) polymerase 1, calpain, and Bax activation, AIF moves from the mitochondria to the nucleus where it induces chromatinolysis and cell death. The mechanisms underlying the nuclear action of AIF are, however, largely unknown. We show here that, through its C-terminal proline-rich binding domain (PBD, residues 543–559), AIF associates in the nucleus with histone H2AX. This interaction regulates chromatinolysis and programmed necrosis by generating an active DNA-degrading complex with cyclophilin A (CypA). Deletion or directed mutagenesis in the AIF C-terminal PBD abolishes AIF/H2AX interaction and AIF-mediated chromatinolysis. H2AX genetic ablation or CypA downregulation confers resistance to programmed necrosis. AIF fails to induce chromatinolysis in H2AX or CypA-deficient nuclei. We also establish that H2AX is phosphorylated at Ser139 after MNNG treatment and that this phosphorylation is critical for caspase-independent programmed necrosis. Overall, our data shed new light in the mechanisms regulating programmed necrosis, elucidate a key nuclear partner of AIF, and uncover an AIF apoptogenic motif. PMID:20360685

  13. Endoscopic ultrasound criteria to predict the need for intervention in pancreatic necrosis

    PubMed Central

    2012-01-01

    Background The natural course and treatment strategies for asymptomatic or oligosymptomatic pancreatic necrosis are still poorly defined. The aim of this retrospective study was to establish criteria for the need of intervention in patients with pancreatic necrosis. Methods A total of 31 consecutive patients (18 male, median age 58 yrs.) diagnosed with pancreatic necrosis by endoscopic ultrasound, in whom a decision for initial conservative treatment was made, were followed for the need of interventions such as endoscopic or surgical intervention, or death. Results After a median follow-up of 243 days, 21 patients remained well without intervention and in 10 patients an endpoint event occurred. In a multivariate logistic regression analysis of the clinical and endosonographic parameters, liquid content was the single independent predictor for intervention (p = 0.0006). The presence of high liquid content in the pancreatic necrosis resulted in a 64% predicted endpoint risk as compared to 2% for solid necrosis. Conclusions Pancreatic necrotic cavities with high liquid content are associated with a high risk of complications. Therefore, close clinical monitoring is needed and early elective intervention might be considered in these patients. PMID:22584080

  14. Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence.

    PubMed

    Shah, Ritu; Vattoth, Surjith; Jacob, Rojymon; Manzil, Fathima Fijula Palot; O'Malley, Janis P; Borghei, Peyman; Patel, Bhavik N; Curé, Joel K

    2012-01-01

    Radiation necrosis in the brain commonly occurs in three distinct clinical scenarios, namely, radiation therapy for head and neck malignancy or intracranial extraaxial tumor, stereotactic radiation therapy (including radiosurgery) for brain metastasis, and radiation therapy for primary brain tumors. Knowledge of the radiation treatment plan, amount of brain tissue included in the radiation port, type of radiation, location of the primary malignancy, and amount of time elapsed since radiation therapy is extremely important in determining whether the imaging abnormality represents radiation necrosis or recurrent tumor. Conventional magnetic resonance (MR) imaging findings of these two entities overlap considerably, and even at histopathologic analysis, tumor mixed with radiation necrosis is a common finding. Advanced imaging modalities such as diffusion tensor imaging and perfusion MR imaging (with calculation of certain specific parameters such as apparent diffusion coefficient ratios, relative peak height, and percentage of signal recovery), MR spectroscopy, and positron emission tomography can be useful in differentiating between recurrent tumor and radiation necrosis. In everyday practice, the visual assessment of diffusion-weighted and perfusion images may also be helpful by favoring one diagnosis over the other, with restricted diffusion and an elevated relative cerebral blood volume being seen much more frequently in recurrent tumor than in radiation necrosis.

  15. Oxidative Burst-Dependent NETosis Is Implicated in the Resolution of Necrosis-Associated Sterile Inflammation.

    PubMed

    Biermann, Mona H C; Podolska, Malgorzata J; Knopf, Jasmin; Reinwald, Christiane; Weidner, Daniela; Maueröder, Christian; Hahn, Jonas; Kienhöfer, Deborah; Barras, Alexandre; Boukherroub, Rabah; Szunerits, Sabine; Bilyy, Rostyslav; Hoffmann, Markus; Zhao, Yi; Schett, Georg; Herrmann, Martin; Munoz, Luis E

    2016-01-01

    Necrosis is associated with a profound inflammatory response. The regulation of necrosis-associated inflammation, particularly the mechanisms responsible for resolution of inflammation is incompletely characterized. Nanoparticles are known to induce plasma membrane damage and necrosis followed by sterile inflammation. We observed that injection of metabolically inert nanodiamonds resulted in paw edema in WT and Ncf1** mice. However, while inflammation quickly resolved in WT mice, it persisted over several weeks in Ncf1** mice indicating failure of resolution of inflammation. Mechanistically, NOX2-dependent reactive oxygen species (ROS) production and formation of neutrophil extracellular traps were essential for the resolution of necrosis-induced inflammation: hence, by evaluating the fate of the particles at the site of inflammation, we observed that Ncf1** mice deficient in NADPH-dependent ROS failed to generate granulation tissue therefore being unable to trap the nanodiamonds. These data suggest that NOX2-dependent NETosis is crucial for preventing the chronification of the inflammatory response to tissue necrosis by forming NETosis-dependent barriers between the necrotic and healthy surrounding tissue.

  16. The Oncogenic MicroRNA miR-21 Promotes Regulated Necrosis in Mice

    PubMed Central

    Ma, Xiaodong; Conklin, Daniel J.; Li, Fenge; Dai, Zhongping; Hua, Xiang; Li, Yan; Xu-Monette, Zijun Y.; Young, Ken H.; Xiong, Wei; Wysoczynski, Marcin; Sithu, Srinivas D.; Srivastava, Sanjay; Bhatnagar, Aruni; Li, Yong

    2015-01-01

    MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumor necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis, and miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway and could be a therapeutic target for preventing pathologic necrosis. PMID:25990308

  17. Oxidative Burst-Dependent NETosis Is Implicated in the Resolution of Necrosis-Associated Sterile Inflammation

    PubMed Central

    Biermann, Mona H. C.; Podolska, Malgorzata J.; Knopf, Jasmin; Reinwald, Christiane; Weidner, Daniela; Maueröder, Christian; Hahn, Jonas; Kienhöfer, Deborah; Barras, Alexandre; Boukherroub, Rabah; Szunerits, Sabine; Bilyy, Rostyslav; Hoffmann, Markus; Zhao, Yi; Schett, Georg; Herrmann, Martin; Munoz, Luis E.

    2016-01-01

    Necrosis is associated with a profound inflammatory response. The regulation of necrosis-associated inflammation, particularly the mechanisms responsible for resolution of inflammation is incompletely characterized. Nanoparticles are known to induce plasma membrane damage and necrosis followed by sterile inflammation. We observed that injection of metabolically inert nanodiamonds resulted in paw edema in WT and Ncf1** mice. However, while inflammation quickly resolved in WT mice, it persisted over several weeks in Ncf1** mice indicating failure of resolution of inflammation. Mechanistically, NOX2-dependent reactive oxygen species (ROS) production and formation of neutrophil extracellular traps were essential for the resolution of necrosis-induced inflammation: hence, by evaluating the fate of the particles at the site of inflammation, we observed that Ncf1** mice deficient in NADPH-dependent ROS failed to generate granulation tissue therefore being unable to trap the nanodiamonds. These data suggest that NOX2-dependent NETosis is crucial for preventing the chronification of the inflammatory response to tissue necrosis by forming NETosis-dependent barriers between the necrotic and healthy surrounding tissue. PMID:27990145

  18. A Case of Periodontal Necrosis following Embolization of Maxillary Artery for Epistaxis

    PubMed Central

    Yoshida, Ryoji; Hirai, Toshinori; Yumoto, Eiji

    2016-01-01

    Embolization of the maxillary artery (MA) is a common treatment modality for refractory epistaxis. Tissue necrosis after embolization of the MA is a rare complication. Here, we reported the first case of the development of necrosis of soft tissue and alveolar bone in the periodontium after embolization. A 48-year-old man with poor oral hygiene and a heavy smoking habit was referred to our clinic due to intractable epistaxis. After treatment with anterior-posterior nasal packing (AP nasal packing), the epistaxis relapsed. Therefore, he underwent embolization of the MA. Although he did not experience epistaxis after embolization, periodontal necrosis developed gradually. The wound healed with necrotomy, administration of antibiotics and prostaglandin, and hyperbaric oxygen therapy. We speculated that the periodontal necrosis was provoked by reduction of blood supply due to embolization and AP nasal packing based on this preexisting morbid state in the periodontium. Poor condition of the oral cavity and smoking may increase the risk of periodontal necrosis after embolization. PMID:27990309

  19. Apoptosis and necrosis during the circadian cycle in the centipede midgut.

    PubMed

    Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K

    2016-07-01

    Three types of cells have been distinguished in the midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata: digestive, secretory, and regenerative cells. According to the results of our previous studies, we decided to analyze the relationship between apoptosis and necrosis in their midgut epithelium and circadian rhythms. Ultrastructural analysis showed that these processes proceed in a continuous manner that is independent of the circadian rhythm in L. forficatus, while in S. cingulata necrosis is activated at midnight. Additionally, the description of apoptosis and necrosis showed no differences between males and females of both species analyzed. At the beginning of apoptosis, the cell cytoplasm becomes electron-dense, apparently in response to shrinkage of the cell. Organelles such as the mitochondria, cisterns of endoplasmic reticulum transform and degenerate. Nuclei gradually assume lobular shapes before the apoptotic cell is discharged into the midgut lumen. During necrosis, however, the cytoplasm of the cell becomes electron-lucent, and the number of organelles decreases. While the digestive cells of about 10 % of L. forficatus contain rickettsia-like pathogens, the corresponding cells in S. cingulata are free of rickettsia. As a result, we can state that apoptosis in L. forficatus is presumably responsible for protecting the organism against infections, while in S. cingulata apoptosis is not associated with the elimination of pathogens. Necrosis is attributed to mechanical damage, and the activation of this process coincides with proliferation of the midgut regenerative cells at midnight in S. cingulata.

  20. Field balancing in the real world

    SciTech Connect

    Bracher, B.

    1997-09-05

    Field balancing can achieve significant results when other problems are present in the frequency spectrum and multiple vibrations are evident in the waveform. Many references suggest eliminating other problems before attempting to balance. That`s great - if you can do it. There are valid reasons for this approach, and it would be much easier to balance machinery when other problems have been corrected. It is the theoretical ideal in field balancing. However, in the real world of machinery maintained for years by reacting to immediate problems, the classic vibration signature for unbalance is rarely seen. Maintenance personnel make most of their decisions with limited information. The decision to balance or not to balance is usually made the same way. This paper will demonstrate significant results of field balancing in the presence of multiple problems. By examining the data available and analyzing the probabilities, a reasonable chance for success can be assured.

  1. Control Allocation with Load Balancing

    NASA Technical Reports Server (NTRS)

    Bodson, Marc; Frost, Susan A.

    2009-01-01

    Next generation aircraft with a large number of actuators will require advanced control allocation methods to compute the actuator commands needed to follow desired trajectories while respecting system constraints. Previously, algorithms were proposed to minimize the l1 or l2 norms of the tracking error and of the actuator deflections. The paper discusses the alternative choice of the l(infinity) norm, or sup norm. Minimization of the control effort translates into the minimization of the maximum actuator deflection (min-max optimization). The paper shows how the problem can be solved effectively by converting it into a linear program and solving it using a simplex algorithm. Properties of the algorithm are also investigated through examples. In particular, the min-max criterion results in a type of load balancing, where the load is th desired command and the algorithm balances this load among various actuators. The solution using the l(infinity) norm also results in better robustness to failures and to lower sensitivity to nonlinearities in illustrative examples.

  2. Balanced Branching in Transcription Termination

    NASA Technical Reports Server (NTRS)

    Harrington, K. J.; Laughlin, R. B.; Liang, S.

    2000-01-01

    The theory of stochastic transcription termination based on free-energy competition [von Hippel, P. H. & Yager, T. D. (1992) Science 255,809-812 and van Hippel, P. H. & Yager, T. D. (1991) Proc. Natl. Acad. Sci. USA 88, 2307-2311] requires two or more reaction rates to be delicately balanced over a wide range of physical conditions. A large body of work on glasses and large molecules suggests that this balancing should be impossible in such a large system in the absence of a new organizing principle of matter. We review the experimental literature of termination and find no evidence for such a principle, but do find many troubling Inconsistencies, most notably, anomalous memory effects. These effects suggest that termination has a deterministic component and may conceivably not be stochastic at all. We find that a key experiment by Wilson and von Hippel [Wilson, K. S. & von Hippel, P. H. (1994) J. Mol. Biol. 244,36-51] thought to demonstrate stochastic termination was an incorrectly analyzed regulatory effect of Mg(2+) binding.

  3. Mass balance assessment using GPS

    NASA Technical Reports Server (NTRS)

    Hulbe, Christina L.

    1993-01-01

    Mass balance is an integral part of any comprehensive glaciological investigation. Unfortunately, it is hard to determine at remote locations where there is no fixed reference. The Global Positioning System (GPS) offers a solution. Simultaneous GPS observations at a known location and the remote field site, processed differentially, will accurately position the camp site. From there, a monument planted in the firn atop the ice can also be accurately positioned. Change in the monument's vertical position is a direct indicator of ice thickness change. Because the monument is not connected to the ice, its motion is due to both mass balance change and to the settling of firn as it densifies into ice. Observations of relative position change between the monument and anchors at various depths within the firn are used to remove the settling effect. An experiment to test this method has begun at Byrd Station on the West Antarctic Ice Sheet and the first epoch of observations was made. Analysis indicates that positioning errors will be very small. It appears likely that the largest errors involved with this technique will arise from ancillary data needed to determine firn settling.

  4. The suspension balance model revisited

    NASA Astrophysics Data System (ADS)

    Nott, Prabhu R.; Guazzelli, Elisabeth; Pouliquen, Olivier

    2011-04-01

    This paper addresses a fundamental discrepancy between the suspension balance model and other two-phase flow formulations. The former was proposed to capture the shear-induced migration of particles in Stokesian suspensions, and hinges on the presence of a particle phase stress to drive particle migration. This stress is taken to be the "particle stress," defined as the particle contribution to the suspension stress. On the other hand, the two-phase flow equations derived in several studies show only a force acting on the particle phase, but no stress. We show that the identification of the particle phase stress with the particle contribution to the suspension stress in the suspension balance model is incorrect, but there exists a well-defined particle phase stress. Following the rigorous method of volume averaging, we show that the force on the particle phase may be written as the sum of an interphase drag and the divergence of the particle phase stress. We derive exact micromechanical relations for these quantities. We also comment on the interpretations and results of previous studies that are based on the identification of the particle phase stress with the particle contribution to the suspension stress.

  5. Vital staining for cell death identifies Atg9a-dependent necrosis in developmental bone formation in mouse

    PubMed Central

    Imagawa, Yusuke; Saitoh, Tatsuya; Tsujimoto, Yoshihide

    2016-01-01

    Programmed cell death has a crucial role in various biological events, including developmental morphogenesis. Recent evidence indicates that necrosis contributes to programmed cell death in addition to apoptosis, but it is unclear whether necrosis acts as a compensatory mechanism for failure of apoptosis or has an intrinsic role during development. In contrast to apoptosis, there have been no techniques for imaging physiological necrosis in vivo. Here we employ vital staining using propidium iodide to identify cells with plasma membrane disruption (necrotic cells) in mouse embryos. We discover a form of necrosis at the bone surface, which does not occur in embryos with deficiency of the autophagy-related gene Atg9a, although it is unaffected by Atg5 knockout. We also find abnormalities of the bone surface in Atg9a knockout mice, suggesting an important role of Atg9a-dependent necrosis in bone surface formation. These findings suggest that necrosis has an active role in developmental morphogenesis. PMID:27811852

  6. Post-operative avascular necrosis of the maxilla: a rare complication following orthognathic surgery

    PubMed Central

    Teemul, Trevor A.; Perfettini, Jean; Morris, David O.; Russell, John L.

    2017-01-01

    We present a patient with sickle cell trait who suffered avascular necrosis of the maxilla as a complication of maxillary osteotomy. Understanding the blood supply of the maxilla and how possible patient related, anaesthetic and operative factors affect it, is important in understanding how the vascularity of the maxilla can become compromised in a surgical procedure. The perioperative parameters were analysed to identify any prognostic elements. Avascular necrosis of the maxilla is a rare complication of orthognathic surgery with few cases reported in the literature. There are identifiable risk factors that can influence the blood supply of the maxilla. Careful preoperative assessment is required to exclude patient factors that have the potential to affect tissue vascularity. This in conjunction with sound anaesthetic and surgical technique should all minimize the risk of avascular necrosis. Even so it is still possible for this rare complication to occur. PMID:28122898

  7. HYBRID ANKLE PROSTHESIS IN A CASE OF POST-TRAUMATIC AVASCULAR NECROSIS OF THE TALUS

    PubMed Central

    de Sousa, Ricardo Jorge Gomes; Pinto, Ricardo Pedro Ferreira Rodrigues; de Oliveira Massada, Marta Maria Teixeira; Pereira, Manuel Alexandre Negrais Pinho Gonçalves; Geada, José Muras; Costa, Isabel Maria Gonçalves

    2015-01-01

    Talus fractures often lead to late post-traumatic arthrosis. In such cases, the use of latest generation, cementless prostheses has been hindered by the presence of avascular necrosis. We report the case of a 65-year-old patient who presented four years after a talus neck fracture. He had painful ankle arthrosis (AOFAS ankle-hindfoot score 19) and avascular necrosis, with collapse of the entire talar dome. Given the extent of the necrosis, it was decided to cement the talus prosthetic component. One year after the surgery, the patient shows good clinical and radiological results (AOFAS ankle-hindfoot score 87) and is satisfied with the procedure. We are not aware of any similar reports in the literature. PMID:27026994

  8. Mobile encapsulated bodies comprising fat necrosis and fibrous tissue in the abdominal cavity of cows.

    PubMed

    Herzog, K; Burgdorf, W; Hewicker-Trautwein, M

    2010-11-01

    The microscopical features of 18 samples of fat necrosis and/or fibrous tissue removed from the abdominal cavity during laparotomy from 15 cows were studied. The nodular, ivory-coloured mobile structures were free-floating in the abdominal cavity, were not attached to any abdominal tissues or organs, and were completely surrounded by a fibrous capsule. Abdominal fat necrosis (bovine lipomatosis) was not observed in any animal. The structures comprised either necrotic fat, fibrous tissue or varying proportions of both. Focal calcification and mild inflammatory cell infiltration and accumulations of haemosiderin were also present. Microscopically, the lesions resembled encapsulated fat necrosis occurring in human subcutaneous tissue. The mechanisms of development of these mobile encapsulated bodies in cows is unknown and it is not clear how, in the absence of a blood supply, there can be inflammatory cell infiltration, calcification and proliferation of fibroblasts.

  9. Binge Eating Leading to Acute Gastric Dilatation, Ischemic Necrosis and Rupture –A Case Report

    PubMed Central

    Khare, Manish Kumar; Mishra, Sumanta; Marhual, Jogesh Chandra

    2016-01-01

    Acute gastric dilatation is a rarely encountered clinical scenario in our day to day practice. This is very rapidly progressing condition and can lead to ischemic necrosis and perforation/rupture of the stomach. It could be fatal if not timely intervened. We report such a case of a 17-year-old, otherwise healthy boy, who presented with pain and distension of abdomen following binge eating episode after 24 hours of prolonged fasting. On exploration, stomach was dilated with necrosis and perforation at fundus near greater curvature. He was managed with excision of all the devitalized area and primary repair with feeding jejunostomy. The case is presented due to its rarity. Acute gastric dilatation (AGD) leading to ischemic necrosis and perforation because of binge eating episode in an otherwise healthy person is an exceptional occurrence with only few cases reported in literature. The clinician should be aware of this condition for prompt and appropriate management. PMID:27134932

  10. An unusual cause of necrosis and nasal septum perforation after septoplasty: Enterobacter cloacae.

    PubMed

    Binar, M; Arslan, F; Tasli, H; Karakoc, O; Kilic, A; Aydin, U

    2015-11-01

    A 20-year-old man with nasal obstruction underwent septoplasty due to nasal septal deviation. Nasal packs were inserted at the end of surgery and removed 48 hours after surgery. Twenty-four hours after removal of nasal packs, there was necrosis in both sides of septal mucosa and in bilateral inferior turbinates. Nasal swab culture was performed from both nasal cavities. Enterobacter cloacae was isolated from samples. Two weeks after surgery, nasal septum perforation was unavoidable. To our knowledge, this is the first case in literature describing septal mucosal necrosis caused by this pathogen after septoplasty. Mucosal necrosis and perforation as septoplasty complications should be kept in mind, the result of causes both common and, as in the present case, unusual.

  11. Segmental myofiber necrosis in myotonic dystrophy - An immunoperoxidase study of immunoglobulins in skeletal muscle.

    PubMed Central

    Silver, M. M.; Banerjee, D.; Hudson, A. J.

    1983-01-01

    Because serum immunoglobulin G levels are low in patients with myotonic dystrophy, it was hypothesized that it might be catabolized within abnormal muscle fibers. Accordingly, immunohistochemical stains for immunoglobulins were performed on muscle sections derived at biopsy or autopsy from patients with myotonic dystrophy, other forms of muscular dystrophy, nondystrophic muscle disease, or normal muscle. Positive staining for immunoglobulins was found only in necrotic segments of myofibers (in 7 of 19 dystrophic and 6 of 27 nondystrophic subjects), and it is believed that the staining was due to nonspecific diffusion. However, staining reactions distinguished between incipient necrosis and artifactual contraction bands and allowed us to study segmental myofiber necrosis, comparing its frequency in the various muscle diseases. Segmental myofiber necrosis was present in 4 of 16 cases of myotonic dystrophy. The relevance of this finding to the clinical and morphologic features of myotonic dystrophy is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6351629

  12. Caffeine protects human skin fibroblasts from acute reactive oxygen species-induced necrosis.

    PubMed

    Silverberg, Jonathan I; Patel, Mital; Brody, Neil; Jagdeo, Jared

    2012-11-01

    Oxidative damage by reactive oxygen species (ROS) plays a major role in aging and carcinogenesis. Little is known about either the effects of acute ROS in necrosis and inflammation of skin or the therapeutic agents for prevention and treatment. Previously, our laboratory identified caffeine as an inhibitor of hydrogen peroxide (H2O2)-generated lipid peroxidation products in human skin fibroblasts. Here, we study effects of caffeine on acute ROS-mediated necrosis. Human skin fibroblasts were incubated with caffeine, followed by H2O2 challenge. Flow cytometry was used to analyze cell morphology, counts, apoptosis and necrosis, and ROS. We found that caffeine protects from H2O2 cell damage at lower (0.01 mM) and intermediate (0.1 mM) doses. The beneficial effects of caffeine appear to be mediated by a mechanism other than antioxidant function.

  13. G-CSF-Associated Bone Marrow Necrosis in AML after Induction Chemotherapy.

    PubMed

    Osuorji, Ikenna; Goldman, Lyle

    2012-01-01

    Bone marrow necrosis (BMN) is defined as necrosis of the myeloid tissues and stroma without involvement of the cortical bone. We report a case of 66-year-old male with AML-M4 (FAB classification) who was given induction chemotherapy with cytarabine and daunorubicin. Filgrastim at 480 micrograms was administered on days 15-19 to shorten the duration of neutropenia. Consequently patient developed severe pelvic bone pain, leukoerythroblastosis, and severe leukocytosis. Repeat bone marrow aspiration and biopsy on day 21 confirmed bone marrow necrosis. These manifestations responded quickly to discontinuation of filgrastim. Subsequently, he recovered full myelopoiesis. We suggest that there may be more cases of BMN associated with G-CSF that are undiagnosed.

  14. Hybrid necrosis: autoimmunity as a potential gene-flow barrier in plant species.

    PubMed

    Bomblies, Kirsten; Weigel, Detlef

    2007-05-01

    Ecological factors, hybrid sterility and differences in ploidy levels are well known for contributing to gene-flow barriers in plants. Another common postzygotic incompatibility, hybrid necrosis, has received comparatively little attention in the evolutionary genetics literature. Hybrid necrosis is associated with a suite of phenotypic characteristics that are similar to those elicited in response to various environmental stresses, including pathogen attack. The genetic architecture is generally simple, and complies with the Bateson-Dobzhansky-Muller model for hybrid incompatibility between species. We survey the extensive literature on this topic and present the hypothesis that hybrid necrosis can result from autoimmunity, perhaps as a pleiotropic effect of evolution of genes that are involved in pathogen response.

  15. Differential modulation of apoptosis and necrosis by antioxidants in immunosuppressed human lymphocytes.

    PubMed

    Rojas, Mauricio; Rugeles, María Teresa; Gil, Diana Patricia; Patiño, Pablo

    2002-04-15

    In the present study, we explored whether mitogenic stimulation of dexamethasone (DXM)- and cyclosporine A (CsA)-immunosuppressed peripheral blood lymphocytes (PBML) induced apoptosis or necrosis and their relation with the production of reactive oxygen intermediates. Our results indicate that both phenomena can occur in these cells and that antioxidants such as N-acetyl cysteine (NAC) and ascorbic acid (AA) can modulate them. However, DXM-induced apoptosis was only partially inhibited by NAC and AA, suggesting that DXM-treated PBMC had an additional apoptotic pathway independent of ROIs. Furthermore, we observed that the inhibition of apoptosis by antioxidants correlated with an increased cell proliferation, suggesting that the immunomodulation of both DXM and CsA may be related to induction of apoptosis. The ability to differentially modulate apoptosis and necrosis by antioxidants opens new possibilities in the management of immunosuppressive therapy, since the inhibition of necrosis may avoid inflammation and the tissue damage associated with immunosuppressors.

  16. Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

    SciTech Connect

    Timmons, J.H.; Hartshorne, M.F.; Peters, V.J.; Cawthon, M.A.; Bauman, J.M.

    1988-04-01

    A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.

  17. Adrenocortical hemorrhagic necrosis: the role of catecholamines and retrograde medullary-cell embolism

    SciTech Connect

    Szabo, S.; McComb, D.J.; Kovacs, K.; Huettner, I.

    1981-10-01

    We investigated the pathogenesis of adrenal necrosis using animal models of the disease (induced by administration of acrylonitrile, cysteamine, or pyrazole) and human cases. Results of electron-microscopic and histochemical time-response studies with rat models revealed an early, retrograde embolization of medullary cells and cell fragments in the cortical capillaries that showed prominent endothelial injury. The experimental adrenal lesions were prevented by surgical removal of the medulla one month before administration of adrenocorticolytic chemicals, or by the administration of the alpha-adrenergic antagonist phenoxybenzamine hydrochloride. Histochemical staining for medullary (argyrophil) granules in human cases of adrenal necrosis demonstrated tissue fragments that stained positively for silver in vascular cortical spaces in nine of ten autopsy specimens and in all four surgical cases we reviewed. Thus, catecholamines released from the adrenal medulla and from the retrograde medullary emboli in the cortex may have a role in the pathogenesis of adrenocortical necrosis.

  18. A GSK-3β Inhibitor Protects Against Radiation Necrosis in Mouse Brain

    SciTech Connect

    Jiang, Xiaoyu; Perez-Torres, Carlos J.; Thotala, Dinesh; Engelbach, John A.; Yuan, Liya; Cates, Jeremy; Gao, Feng; Drzymala, Robert E.; Rich, Keith M.; Schmidt, Robert E.; Ackerman, Joseph J.H.; Hallahan, Dennis E.; Garbow, Joel R.

    2014-07-15

    Purpose: To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3β, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model. Methods and Materials: Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. Results: Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3β inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. Conclusions: The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3β inhibitors.

  19. Thioacetamide-induced Hepatocellular Necrosis Is Attenuated in Diet-induced Obese Mice

    PubMed Central

    Shirai, Makoto; Arakawa, Shingo; Miida, Hiroaki; Matsuyama, Takuya; Kinoshita, Junzo; Makino, Toshihiko; Kai, Kiyonori; Teranishi, Munehiro

    2013-01-01

    To assess modification of thioacetamide-induced hepatotoxicity in mice fed a high-fat diet, male C57BL/6J mice were fed a normal rodent diet or a high-fat diet for 8 weeks and then treated once intraperitoneally with thioacetamide at 50 mg/kg body weight. At 24 and 48 hours after administration, massive centrilobular hepatocellular necrosis was observed in mice fed the normal rodent diet, while the necrosis was less severe in mice fed the high-fat diet. In contrast, severe swelling of hepatocytes was observed in mice fed the high-fat diet. In addition, mice fed the high-fat diet displayed more than a 4-fold higher number of BrdU-positive hepatocytes compared with mice fed the normal rodent diet at 48 hours after thioacetamide treatment. To clarify the mechanisms by which the hepatic necrosis was attenuated, we investigated exposure to thioacetamide and one of its metabolites, the expression of CYP2E1, which converts thioacetamide to reactive metabolites, and the content of glutathione S-transferases in the liver. However, the reduced hepatocellular necrosis noted in mice fed the high-fat diet could not be explained by the differences in exposure to thioacetamide or thioacetamide sulfoxide or by differences in the expression of drug-metabolizing enzymes. On the other hand, at 8 hours after thioacetamide administration, hepatic total glutathione in mice fed the high-fat diet was significantly lower than that in mice fed the normal diet. Hence, decreased hepatic glutathione amount is a candidate for the mechanism of the attenuated necrosis. In conclusion, this study revealed that thioacetamide-induced hepatic necrosis was attenuated in mice fed the high-fat diet. PMID:23914059

  20. Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

    PubMed Central

    Patel, Krutika; Trivedi, Ram N.; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A.; DeLany, James P.; Navina, Sarah; Singh, Vijay P.

    2016-01-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  1. Warfarin-induced skin necrosis diagnosed on clinical grounds and treated with maggot debridement therapy

    PubMed Central

    Biscoe, Anna Louise; Bedlow, Alison

    2013-01-01

    A patient with a history of deep vein thrombosis presented with painful bruising and blistering on his left leg 7–10 days after warfarin treatment. A complicated 2-month treatment followed, where vasculitis was originally diagnosed from histological findings before the final diagnosis of warfarin-induced skin necrosis (WISN) was made on clinical grounds. Warfarin was stopped, reversed and low molecular weight heparin started but, the lesions had progressed to full thickness necrosis. This was originally treated with conventional surgical debridement before introducing maggot debridement therapy (MDT) in an effort to try to salvage the limb. PMID:23362073

  2. Colonic necrosis and perforation due to calcium polystyrene sulfonate in a uraemic patient: a case report

    PubMed Central

    Yazici, Halil; Gulluoglu, Mine G.; Yegen, Gulcin; Turkmen, Aydin

    2011-01-01

    Sodium or calcium polystyrene sulfonate (Kayexalate or analog) is an ion-exchange resin commonly used to treat hyperkalaemia in patients with chronic kidney disease. It is known to cause digestive complications, such as nausea, vomiting and constipation. Although rare, colonic necrosis and perforation are very severe complications associated with the medication. In this case report, we present a case of calcium polystyrene sulfonate-induced colonic necrosis and perforation to remind clinicians of this rare, but dangerous, toxicity associated with this commonly used medication. PMID:25984206

  3. Colonic necrosis and perforation due to calcium polystyrene sulfonate in a uraemic patient: a case report.

    PubMed

    Akagun, Tulin; Yazici, Halil; Gulluoglu, Mine G; Yegen, Gulcin; Turkmen, Aydin

    2011-12-01

    Sodium or calcium polystyrene sulfonate (Kayexalate or analog) is an ion-exchange resin commonly used to treat hyperkalaemia in patients with chronic kidney disease. It is known to cause digestive complications, such as nausea, vomiting and constipation. Although rare, colonic necrosis and perforation are very severe complications associated with the medication. In this case report, we present a case of calcium polystyrene sulfonate-induced colonic necrosis and perforation to remind clinicians of this rare, but dangerous, toxicity associated with this commonly used medication.

  4. Ischemic Necrosis of Upper Lip, and All Fingers and Toes After Norepinephrine Use.

    PubMed

    Shin, Jin Yong; Roh, Si-Gyun; Lee, Nae-Ho; Yang, Kyung-Moo

    2016-03-01

    A 68-year-old woman with necrosis of total finger, toe, and upper lip was requested by department of internal medicine. She was diagnosed with septic shock and treated with norepinephrine 10 days ago. Norepinephrine is an often-used medicine for normalizing blood pressure in septic shock patients. Norepinephrine stimulates adrenergic receptors, causing vasoconstriction and the rise of blood pressure. These peripheral vasoconstrictions sometimes lead to ischemic changes in end organs. In this case report, the authors describe ischemic necrosis of the upper lip and all fingers and toes after norepinephrine use in a patient in the intensive care unit.

  5. Partial necrosis of the lunate after a translunate palmar perilunate fracture dislocation.

    PubMed

    Akane, Mao; Tatebe, Masahiro; Iyoda, Kazuhito; Ota, Kyotaro; Iwatsuki, Katsuyuki; Yamamoto, Michiro; Hirata, Hitoshi

    2014-02-01

    We present an extreme rare case of traumatic partial avascular necrosis of the lunate after palmar perilunate dislocation with lunate fracture. A 32-year-old female was injured by motorcycle accident with palmar perilunate fracture dislocation and lunate fracture. Scapholunate and lunotriquetrum dislocations were reduced and fixed temporarily. The torn dorsal ligament was repaired. Considering close observation with both arthroscopy and fluoroscopy, we decided not to conduct open reduction and internal fixation for the lunate. Partial avascular necrosis of the lunate appeared gradually in follow-up.

  6. PARTIAL NECROSIS OF THE LUNATE AFTER A TRANSLUNATE PALMAR PERILUNATE FRACTURE DISLOCATION

    PubMed Central

    AKANE, MAO; TATEBE, MASAHIRO; IYODA, KAZUHITO; OTA, KYOTARO; IWATSUKI, KATSUYUKI; YAMAMOTO, MICHIRO; HIRATA, HITOSHI

    2014-01-01

    ABSTRACT We present an extreme rare case of traumatic partial avascular necrosis of the lunate after palmar perilunate dislocation with lunate fracture. A 32-year-old female was injured by motorcycle accident with palmar perilunate fracture dislocation and lunate fracture. Scapholunate and lunotriquetrum dislocations were reduced and fixed temporarily. The torn dorsal ligament was repaired. Considering close observation with both arthroscopy and fluoroscopy, we decided not to conduct open reduction and internal fixation for the lunate. Partial avascular necrosis of the lunate appeared gradually in follow-up. PMID:25130008

  7. Classical syndromes in occupational medicine: phosphorus necrosis--a classical occupational disease

    SciTech Connect

    Felton, J.S.

    1982-01-01

    A disease nearly extinct in occupational health history is phosphorus necrosis, previously seen in near-epidemic proportions among workers making phosphorus-containing matches. Similar destructive lesions were encountered early in the 20th century among personnel fabricating fireworks. Through the diligent efforts of an economist and a supportive congressman, legislation was passed in 1912 placing a tax on phosphorus matches, and because of the fiscal burden resulting, a nontoxic substitute for elemental phosphorus was adopted by all manufacturers. Today phosphorus necrosis is extremely rare, but the former presence of the disease points up both apathy and courage in the identification and eradication of a remarkably disfiguring work-caused disease.

  8. Posttraumatic fat necrosis presenting as prepatellar loose bodies in an adolescent football player.

    PubMed

    Sole, Joshua S; Wisniewski, Steve J; Dahm, Diane L; Bond, Jeffrey; Smith, Jay

    2014-08-01

    A 16-year-old high school football player presented with 4 months of anterior knee pain and small, mobile, prepatellar "lumps" after falling onto an opponent's cleat. He reported knee pain primarily during knee flexion and direct pressure during squatting and kneeling. Knee radiographs were unremarkable. Ultrasonography revealed multiple, freely mobile, subcutaneous nodules of variable size and echogenicity in the prepatellar region. Analysis of magnetic resonance imaging suggested possible fat necrosis but was nondiagnostic. The patient opted for surgical exploration, at which time multiple, opalescent subcutaneous nodules were removed. Pathology was consistent with encapsulated fat necrosis. After surgery, his symptoms resolved, and he returned to sports without restrictions.

  9. Subcutaneous thigh fat necrosis as a result of tourniquet control during total knee arthroplasty.

    PubMed

    Tamvakopoulos, George S; Toms, Andoni P; Glasgow, Malcolm

    2005-09-01

    The use of a pneumatic tourniquet in total knee arthroplasty has been linked to complications caused by local tissue hypoxia. Fat necrosis is a rare condition that presents as an ill-defined subcutaneous lesion. The clinical features resemble that of a lipoma but histological appearance is characteristic. Ultrasound imaging is helpful in establishing the diagnosis both by sonographic appearance as well as in directing a biopsy if necessary. We present a case of encapsulated fat necrosis caused by the use of a pneumatic tourniquet during total knee arthroplasty.

  10. Avascular necrosis of stapes crura in one case of operated otosclerosis.

    PubMed

    Erdoglija, Milan; Sotirovic, Jelena; Jacimovic, Violeta; Vukomanovic, Biserka

    2012-01-01

    Unilateral otosclerosis combined with avascular necrosis of stapes crura is a rare entity. It should be considered in a case of high grade otosclerosis. Symptoms are the same as in patients who suffer from common otosclerosis. Patients complain on progressive hearing loss and tinnitus. The diagnosis is made clinically by conventional audiologic evaluation and radiologically by x-ray mastoid Schuller's view and CT scan. HRCT scan makes visible all parts of ossicular chain and gives surgeon some information about ossicular chain damage. Surgery with stapedotomy and stapes prosthesis implantation in a case of otosclerosis with avascular necrosis of stapes crura can be success therapy to improve patient's hearing

  11. Low Molecular Weight Heparin Induced Skin Necrosis without Platelet Fall Revealing Immunoallergic Heparin Induced Thrombocytopenia

    PubMed Central

    Godet, Thomas; Perbet, Sébastien; Lebreton, Aurélien; Gayraud, Guillaume; Cayot, Sophie; Tremblay, Aymeric; Ravinet, Aurélie; Christophe, Sébastien; Guérin, Renaud; Pascal, Julien; Jabaudon, Matthieu; Hassan, Amr; Sapin, Anne-Françoise; Bazin, Jean-Etienne; Constantin, Jean-Michel

    2013-01-01

    Low molecular weight heparins (LMWH) are commonly used in the ICU setting for thromboprophylaxis as well as curative decoagulation as required during renal replacement therapy (RRT). A rare adverse event revealing immunoallergic LMWH induced thrombopenia (HIT) is skin necrosis at injection sites. We report the case of a patient presenting with skin necrosis witnessing an HIT after RRT, without thrombocytopenia. The mechanism remains unclear. Anti-PF4/heparin antibodies, functional tests (HIPA and/or SRA), and skin biopsy are of great help to evaluate differential diagnosis with a low pretest probability 4T's score. PMID:24307958

  12. Viral erythrocytic necrosis: Some physiological consequences of infection in chum salmon (Oncorhynchus keta)

    USGS Publications Warehouse

    MacMillan, John R.; Mulcahy, Daniel M.; Landolt, Marsha L.

    1980-01-01

    Erythroid cells in chum salmon (Oncorhynchus keta) susceptible to infection with erythrocytic necrosis virus (ENV) were examined by light and electron microscopy. Cells of stages II, III, IV, V, and VI contained complete eyrthrocytic necrosis virions in the cytoplasm. Viruses closely resembling ENV were also detected in the nuclei of some erythroblasts. Some secondary consequences of ENV infection were a threefold greater mortality rate from vibriosis, a significantly decreased tolerance to oxygen depletion, and a decreased ability to regulate serum sodium and potassium in saltwater.

  13. TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

    PubMed Central

    2014-01-01

    Background The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin. Methods Cell death/viability was measured by flow cytometry/determination of intracellular ATP levels/crystal violet staining. Cell surface expression of TRAIL receptors was detected by flow cytometry, expression of proteins by Western blot. Ceramide levels were quantified by high-performance thin layer chromatography and densitometric analysis, clonogenic survival of cells was determined by crystal violet staining or by soft agarose cloning. Results TRAIL-induced programmed necrosis killed eight out of 14 tumor cell lines. Clonogenic survival was reduced in all sensitive and even one resistant cell lines tested. TRAIL synergized with chemotherapeutics in killing tumor cell lines by programmed necrosis, enhancing their effect in eight out of 10 tested tumor cell lines and in 41 out of 80 chemotherapeutic/TRAIL combinations. Susceptibility/resistance of the investigated tumor cell lines to programmed necrosis seems to primarily depend on expression of the pro-necrotic kinase RIPK3 rather than the related kinase RIPK1 or cell surface expression of TRAIL receptors. Furthermore, interference with production of the lipid ceramide protected all tested tumor cell lines. Conclusions Our study provides evidence that TRAIL-induced programmed necrosis represents a feasible approach for the elimination of

  14. Necrosis of the tail of pancreas following proximal splenic artery embolization.

    PubMed

    Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

    2016-05-13

    The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication.

  15. Alcohol-Dependent Liver Cell Necrosis in vitro: A New Model

    NASA Astrophysics Data System (ADS)

    Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel

    1981-04-01

    In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

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

    PubMed

    Brock, C; Brock, B; Aziz, Q; Møller, H J; Pfeiffer Jensen, M; Drewes, A M; Farmer, A D

    2016-12-12

    The vagus nerve is a central component of cholinergic anti-inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t-VNS) on validated parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t-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 warrants further evaluation in larger controlled studies.

  17. Dabigatran in the Treatment of Warfarin-Induced Skin Necrosis: A New Hope

    PubMed Central

    Bakoyiannis, Christos; Karaolanis, Georgios; Patelis, Nikolaos; Maskanakis, Anastasios; Tsaples, Georgios; Klonaris, Christos; Georgopoulos, Sotirios; Liakakos, Theodoros

    2016-01-01

    Warfarin-induced skin necrosis is an infrequent and well-recognized complication of warfarin treatment. The incidence was estimated between 0.01% and 0.1% whereas a paradoxal prothrombotic state that arises from warfarin therapy seems to be responsible for this life-threatening disease. To the best of our knowledge we present the first case of an old woman diagnosed with warfarin-induced skin necrosis, in whom novel oral anticoagulants and extensive surgical debridement were combined safely with excellent results. PMID:27110410

  18. [Disorders in sodium-water balance].

    PubMed

    Petitclerc, Thierry

    2013-02-01

    Water balance control is aimed at normalizing cellular hydration, and sodium balance control at normalizing extracellular volume. Water balance control is based on the regulation of body fluid tonicity, while the control of sodium balance is based on the regulation of effective arterial volume. Disorders of water balance act on cellular hydration: primary disorders induce a proportional change in tonicity; secondary disorders are induced by a change in tonicity or effective arterial volume. Disorders of sodium balance act on extracellular volume: primary disorders of sodium balance induce a change in effective arterial volume; secondary disorders are induced by a change in effective arterial volume. Physical examination of the patient allows assessing the extracellular volume and the severity of the sodium balance disorder. Natremia - that generally reflects tonicity - allows to assess cellular hydration and to determine the type of water balance disorder. In the case of natremia disturbance, the assessment of both the tonicity and the extracellular volume allows the determination of the type of water and/or sodium balance disorder that is necessary for prescribing the adequate therapy.

  19. Artificial balancer - supporting device for postural reflex.

    PubMed

    Wojtara, Tytus; Sasaki, Makoto; Konosu, Hitoshi; Yamashita, Masashi; Shimoda, Shingo; Alnajjar, Fady; Kimura, Hidenori

    2012-02-01

    The evolutionarily novel ability to keep ones body upright while standing or walking, the human balance, deteriorates in old age or can be compromised after accidents or brain surgeries. With the aged society, age related balance problems are on the rise. Persons with balance problems are more likely to fall during their everyday life routines. Especially in elderly, falls can lead to bone fractures making the patient bedridden, weakening the body and making it more prone to other diseases. Health care expenses for a fall patient are often very high. There is a great deal of research being done on exoskeletons and power assists. However, these technologies concentrate mainly on the amplifications of human muscle power while balance has to be provided by the human themself. Our research has been focused on supporting human balance in harmony with the human's own posture control mechanisms such as postural reflexes. This paper proposes an artificial balancer that supports human balance through acceleration of a flywheel attached to the body. Appropriate correcting torques are generated through our device based on the measurements of body deflections. We have carried out experiments with test persons standing on a platform subject to lateral perturbations and ambulatory experiments while walking on a balance beam. These experiments have demonstrated the effectiveness of our device in supporting balance and the possibility of enhancing balance-keeping capability in human beings through the application of external torque.

  20. Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating levels of soluble tumour necrosis factor receptors in rheumatoid arthritis

    PubMed Central

    Glossop, John R; Dawes, Peter T; Nixon, Nicola B; Mattey, Derek L

    2005-01-01

    Levels of soluble tumour necrosis factor receptors (sTNFRs) are elevated in the circulation of patients with rheumatoid arthritis (RA). Although these receptors can act as natural inhibitors of tumour necrosis factor-α, levels of sTNFRs in RA appear to be insufficient to prevent tumour necrosis factor-α induced inflammation. The factors that regulate circulating levels of sTNFRs are unclear, but polymorphisms in the tumour necrosis factor receptor genes may play a role. We investigated the relationship between polymorphisms in the tumour necrosis factor receptor I (TNF-RI) and II (TNF-RII) genes and levels of sTNFRs in two groups of Caucasian RA patients: one with early (disease duration ≤2 years; n = 103) and one with established disease (disease duration ≥5 years; n = 151). PCR restriction fragment length polymorphism analysis was used to genotype patients for the A36G polymorphism in the TNF-RI gene and the T676G polymorphism in TNF-RII. Levels of sTNFRs were measured using ELISA. We also isolated T cells from peripheral blood of 58 patients with established RA with known TNF-R genotypes, and release of sTNFRs into the culture medium was measured in cells incubated with or without phytohaemagglutinin. Serum levels of the two sTNFRs (sTNF-RI and sTNF-RII) were positively correlated in both populations, and the level of each sTNFR was significantly higher in the patients with established disease (P < 0.0001). Multiple regression analyses corrected for age, sex and disease duration revealed a significant trend toward decreasing sTNF-RI and sTNF-RII levels across the TNF-RII genotypes (TT > TG > GG) of patients with established disease (P for trend = 0.01 and P for trend = 0.03, respectively). A similar nonsignificant trend was seen for early disease. No relationship with the TNF-RI A36G polymorphism was observed. sTNFRs released by isolated T cells exhibited a similar trend toward decreasing levels according to TNF-RII genotype, although only the association