Sample records for causing localised necrosis

  1. Electrolytic ablation of the rat pancreas: a feasibility trial

    PubMed Central

    Fosh, Beverley G; Finch, Jonathon Guy; Anthony, Adrian A; Texler, Michael; Maddern, Guy J

    2001-01-01

    Background Pancreatic cancer is a biologically aggressive disease with less than 20% of patients suitable for a "curative" surgical resection. This, combined with the poor 5-year survival indicates that effective palliative methods for symptom relief are required. Currently there are no ablative techniques to treat pancreatic cancer in clinical use. Tissue electrolysis is the delivery of a direct current between an anode and cathode to induce localised necrosis. Electrolysis has been shown to be safe and reliable in producing hepatic tissue and tumour ablation in animal models and in a limited number of patients. This study investigates the feasibility of using electrolysis to produce localised pancreatic necrosis in a healthy rat model. Method Ten rats were studied in total. Eight rats were treated with variable "doses" of coulombs, and the systemic and local effects were assessed; 2 rats were used as controls. Results Seven rats tolerated the procedure well without morbidity or mortality, and one died immediately post procedure. One control rat died on induction of anaesthesia. Serum amylase and glucose were not significantly affected. Conclusion Electrolysis in the rat pancreas produced localised necrosis and appears both safe, and reproducible. This novel technique could offer significant advantages for patients with unresectable pancreatic tumours. The next stage of the study is to assess pancreatic electrolysis in a pig model, prior to human pilot studies. PMID:11570977

  2. TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer.

    PubMed

    Azzouzi, Abdel-Rahmène; Barret, Eric; Moore, Caroline M; Villers, Arnaud; Allen, Clare; Scherz, Avigdor; Muir, Gordon; de Wildt, Michel; Barber, Neil J; Lebdai, Souhil; Emberton, Mark

    2013-10-01

    To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer. Men (aged >18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size <60 mL would receive 4 mg/kg TOOKAD(®) Soluble and patients with prostate size ≥60 mL would receive 6 mg/kg TOOKAD(®) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD(®) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD(®) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected. In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P < 0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P < 0.001) in patients treated with a therapeutic light density index (LDI) of ≥1 than those treated with a LDI of <1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of ≥1 than those treated with a LDI of <1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study. Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in >80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer. © 2013 The Authors. BJU International © 2013 BJU International.

  3. Acute Inactivation of Primary Auditory Cortex Causes a Sound Localisation Deficit in Ferrets

    PubMed Central

    Wood, Katherine C.; Town, Stephen M.; Atilgan, Huriye; Jones, Gareth P.

    2017-01-01

    The objective of this study was to demonstrate the efficacy of acute inactivation of brain areas by cooling in the behaving ferret and to demonstrate that cooling auditory cortex produced a localisation deficit that was specific to auditory stimuli. The effect of cooling on neural activity was measured in anesthetized ferret cortex. The behavioural effect of cooling was determined in a benchmark sound localisation task in which inactivation of primary auditory cortex (A1) is known to impair performance. Cooling strongly suppressed the spontaneous and stimulus-evoked firing rates of cortical neurons when the cooling loop was held at temperatures below 10°C, and this suppression was reversed when the cortical temperature recovered. Cooling of ferret auditory cortex during behavioural testing impaired sound localisation performance, with unilateral cooling producing selective deficits in the hemifield contralateral to cooling, and bilateral cooling producing deficits on both sides of space. The deficit in sound localisation induced by inactivation of A1 was not caused by motivational or locomotor changes since inactivation of A1 did not affect localisation of visual stimuli in the same context. PMID:28099489

  4. Counterintuitive electron localisation from density-functional theory with polarisable solvent models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dale, Stephen G., E-mail: sdale@ucmerced.edu; Johnson, Erin R., E-mail: erin.johnson@dal.ca

    2015-11-14

    Exploration of the solvated electron phenomena using density-functional theory (DFT) generally results in prediction of a localised electron within an induced solvent cavity. However, it is well known that DFT favours highly delocalised charges, rendering the localisation of a solvated electron unexpected. We explore the origins of this counterintuitive behaviour using a model Kevan-structure system. When a polarisable-continuum solvent model is included, it forces electron localisation by introducing a strong energetic bias that favours integer charges. This results in the formation of a large energetic barrier for charge-hopping and can cause the self-consistent field to become trapped in local minimamore » thus converging to stable solutions that are higher in energy than the ground electronic state. Finally, since the bias towards integer charges is caused by the polarisable continuum, these findings will also apply to other classical polarisation corrections, as in combined quantum mechanics and molecular mechanics (QM/MM) methods. The implications for systems beyond the solvated electron, including cationic DNA bases, are discussed.« less

  5. CGP 55398, a liposomal Ge(IV) phthalocyanine bearing two axially ligated cholesterol moieties: a new potential agent for photodynamic therapy of tumours.

    PubMed Central

    Segalla, A.; Milanesi, C.; Jori, G.; Capraro, H. G.; Isele, U.; Schieweck, K.

    1994-01-01

    Ge(IV) phthalocyanine (GePc) with two axially ligated cholesterol moieties was prepared by chemical synthesis and incorporated in a monomeric state into small unilamellar liposomes (CGP 55398). Upon photoexcitation with light wavelengths around its intense absorption peak at 680 nm, GePc shows an efficient photosensitising activity towards biological substrates through a mechanism which largely involves the intermediacy of singlet oxygen. GePc injected systemically into mice bearing an intramuscularly implanted MS-2 fibrosarcoma is quantitatively transferred to serum lipoproteins and localises in the tumour tissue with good efficiency: at 24 h post injection the GePc content in the tumour is 0.74 and 1.87 micrograms per g of tissue with a tumour/peritumoral ratio of 4.35 and 5.67 for injected doses of 0.76 and 1.52 mg kg-1 respectively. At this time the red-light irradiation of the GePc-loaded fibrosarcoma causes a fast and massive tumour necrosis involving both malignant cells and blood vessels. Images Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:8180009

  6. [High voltage accidents, characteristics and treatment].

    PubMed

    Hülsbergen-Krüger, S; Pitzler, D; Partecke, B D

    1995-04-01

    High-voltage injuries cause localised entrance and exit burns, extensive arc, flame and flash burns and, even more dangerous, necrosis of the underlying muscles on the pathway of the current through the body. Therefore it should be recognized that the ensuing disease is more like a crush injury than a thermal burn. The extent of injury cannot be judged by the percentage and depth of the skin burn. Diagnostic fasciotomies, radical debridement, and in many cases early amputation are necessary to prevent life-threatening complications. Over a period of 10 years, 43 patients with high-voltage injuries have been treated at the Hamburg Burn Center, 36 of them in primary care. Common causes of injury were accidents in railway areas (28%), using portable aluminium ladders near overhead power lines (9.3%), and working on electrical equipment (30.2%). Six of the primary care patients died (16.6%), and 34.9% had an amputation of one or more extremities. Nearly all patients underwent several debridement and split-skin graft procedures. In 30% of cases additional free and pedicled flaps were needed to cover soft tissue defects. Ten patients (23.3%) sustained fractures and other injuries from falls, seven (16.3%) of them severe polytrauma. Initial cardiac arrhythmics were diagnosed in 16.6% of the primarily treated patients. Thirty per cent of our patients had neurological complications such as peripheral paresis, tetraplegia and paraplegia, 20.7% of these caused solely by the electric current.

  7. Clozapine-induced acute gastrointestinal necrosis: a case report.

    PubMed

    Osterman, Mark T; Foley, Caitlin; Matthias, Isaac

    2017-09-23

    Clozapine is known to cause fecal impaction and ileus with resultant colonic necrosis due to compression of colonic mucosa. There are rare reports of clozapine causing necrosis of other portions of the gastrointestinal tract unrelated to constipation. We describe a case of acute necrosis of the upper gastrointestinal tract and small bowel to due to clozapine and quetiapine. A 66-year-old white man with a past medical history of schizophrenia, maintained on clozapine and quetiapine, presented with hypoxic respiratory failure caused by aspiration of feculent emesis due to impacted stool throughout his colon. His constipation resolved with discontinuation of clozapine and quetiapine, and his clinical condition improved. These medicines were restarted after 2 weeks, resulting in acute gastrointestinal necrosis from the mid esophagus through his entire small bowel. He died due to septic shock with Gram-negative rod bacteremia. Clozapine may cause acute gastrointestinal necrosis.

  8. Auditory Models for Speech Analysis

    DTIC Science & Technology

    1988-01-01

    to encode stimulus frequency by firing in period with the clicks, up to a critical value. (Godfrey ct al., 1975). Some binaural processing appears to...masking experiments avoid sinosoiVs since a sinusoidal signal combined with a sinusoidal masker can cause " beats " due to regular fluctuations in the...such as sound localisation (Lyon, 1983). Jeffress (1956) proposed a binaural localisation model where the "mechanism receives impulses from corresponding

  9. Model assessing thermal changes during high temperature root canal irrigation

    PubMed Central

    Bartolo, Analise; Koyess, Edmond; Micallef, Christopher

    2016-01-01

    The main aim of root canal irrigation is to eliminate micro-organisms. Sodium hypochlorite (NaOCl) is considered to be the ideal material and raising its temperature potentiates the antimicrobial activity. NaOCl may lead to localised tissue necrosis when extruded past the root apex. This study analyses the use of high temperature root canal irrigation as an alternative process for the elimination of microorganisms from the root canal system. An experimental set-up was designed where a constant supply of heat was passed from a heat source through a copper wire inside the root canal. The data acquired together with known constants pertaining to enamel and dentine was used to numerically model the thermal changes in a tooth using a finite element method. Results obtained from the finite element thermal model of the tooth were repeatable and were validated with the experimental results. The thermo-physical properties of the tooth were varied and convergence criteria met. The temperatures reached were below what has been reported to cause irreversible damage to the bone. This was further confirmed from a series of simulations that were undertaken. The temperatures achieved were suitable for the elimination of microorganisms during root canal therapy. PMID:27733934

  10. The lung in amyloidosis.

    PubMed

    Milani, Paolo; Basset, Marco; Russo, Francesca; Foli, Andrea; Palladini, Giovanni; Merlini, Giampaolo

    2017-09-30

    Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually death. Pulmonary amyloidosis may be localised or part of systemic amyloidosis.Pulmonary interstitial amyloidosis is symptomatic only if the amyloid deposits severely affect gas exchange alveolar structure, thus resulting in serious respiratory impairment. Localised parenchymal involvement may be present as nodular amyloidosis or as amyloid deposits associated with localised lymphomas. Finally, tracheobronchial amyloidosis, which is usually not associated with evident clonal proliferation, may result in airway stenosis.Because the treatment options for amyloidosis are dependent on the fibril protein type, the workup of all new cases should include accurate determination of the amyloid protein. Most cases are asymptomatic and need only a careful follow-up. Diffuse alveolar-septal amyloidosis is treated according to the underlying systemic amyloidosis. Nodular pulmonary amyloidosis is usually localised, conservative excision is usually curative and the long-term prognosis is excellent. Tracheobronchial amyloidosis is usually treated with bronchoscopic interventions or external beam radiation therapy. Copyright ©ERS 2017.

  11. Infected Peri-Pancreatic Necrosis Causing Gallbladder Necrosis by Direct Extension

    PubMed Central

    Assalia, Ahmad; Schmulevski, Pavel; Meislin, Vladimir; Hashmonai, Moshe

    1993-01-01

    Acute acalculous cholecystitis may develop in patients suffering from necrotizing pancreatitis. Conversely, acute pancreatitis may complicate acute gallbladder disease. We present a case that lends support to the existence of another possibility: gallbladder necrosis caused by direct extension of the necrotizing pancreatitic process. PMID:8260438

  12. Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

    PubMed

    Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

    Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

  13. Visceral brown fat necrosis in postperinatal mortality.

    PubMed Central

    Stephenson, T J; Variend, S

    1987-01-01

    Fat necrosis was present in 22 of 400 cases of consecutive postperinatal mortalities investigated to assess the presence and pattern of deep fat necrosis. In just over 50% of the cases of fat necrosis the cause of death was categorised as sudden infant death syndrome, which also showed more severe degrees of necrosis. The mechanism of necrosis may be vascular hypoperfusion, possibly related to shock, and brown adipose tissue, on account of its high metabolic activity and rich capillary plexus, may be particularly vulnerable to infarction. The occurrence of fat necrosis in association with other causes of death did not provide any definite clue as to the nature of the alleged shock. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 PMID:3654989

  14. Biological and genetic characterization of new and known necroviruses causing an emerging systemic necrosis disease of corn salad (Valerianella locusta L.) in France.

    PubMed

    Verdin, Eric; Marais, Armelle; Wipf-Scheibel, Catherine; Faure, Chantal; Pelletier, Brigitte; David, Perrine; Svanella-Dumas, Laurence; Poisblaud, Clement; Lecoq, Herve'; Candresse, Thierry

    2018-02-28

    An emerging systemic necrosis disease of corn salad was first observed in the Nantes region of France in the late 2000's. Classical virology and high-throughput sequencing approaches demonstrated that the disease is associated with four different necroviruses, tobacco necrosis virus A (TNVA), tobacco necrosis virus D (TNVD), olive mild mosaic virus (OMMV) and a novel recombinant Alphanecrovirus for which the name corn salad necrosis virus (CSNV) is proposed. Satellite tobacco necrosis virus (STNV) was also frequently observed. Koch's postulates were completed for all four agents, each one alone being able to cause systemic necrosis of varying severity in corn salad. OMMV was the most frequently observed virus and causes the most severe symptoms. TNVA was the second, both in terms of prevalence and symptom severity while TNVD and CSNV were only rarely observed and cause the less severe symptoms. The emergence of this systemic disease may have been favoured by the short and repeated cropping cycles used for corn salad, possibly allowing the selection of necrovirus isolates with an improved ability to systemically invade this specialty crop.

  15. Evidence of phase nucleation during olivine diffusion creep: a new perspective for mantle strain localisation

    NASA Astrophysics Data System (ADS)

    Précigout, Jacques; Stünitz, Holger

    2017-04-01

    Mantle strain localisation is of great importance for lithosphere dynamics, but the cause for this phenomenon remains very elusive, particularly in conditions of the strong and ductile uppermost mantle. In these latter, grain size reduction leading to diffusion creep in olivine is believed to be one of the best candidates to account for strain localisation. However, the mechanisms of grain size reduction in this regime are still poorly understood. Here we show the results of Griggs-type experiments that document grain size reduction and material weakening during wet olivine diffusion creep at 900 °C and 1.2 GPa. While occurring for both, mono-phase and two-phase aggregates, grain size reduction is coeval with strain localisation and local phase mixing in olivine-pyroxene aggregates. Based on evidence of fluid inclusions and cracks filled with a fine-grained phase mixture, we conclude that grain size reduces as a result of fluid-assisted nucleation. Cavitation induced by grain boundary sliding (creep cavitation) can be inferred, and may play a critical role for olivine grain size reduction. Amongst their implications for rock rheology in general, our findings highlight a key process for strain localisation in the ductile uppermost mantle. This study has been published under the reference: "Précigout, J., and Stünitz, H. (2016) Evidence of phase nucleation during olivine diffusion creep: a new perspective for mantle strain localisation. Earth and Planetary Science Letters 455: 94-105, doi:101016/j.epsl.2016.09.029".

  16. Infectious haematopoietic necrosis virus: Chapter 2

    USGS Publications Warehouse

    Leong, Jo-Ann; Kurath, Gael

    2017-01-01

    Infectious haematopoietic necrosis virus (IHNV) is a Rhabdovirus that causes significant disease in Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), and rainbow and steelhead trout (O. mykiss). IHNV causes necrosis of the haematopoietic tissues, and consequently it was named infectious haematopoietic necrosis. This virus is waterborne and may transmit horizontally and vertically through virus associated with seminal and ovarian fluids. The clinical signs of disease and diagnosis; pathology; pathophysiology; and control strategies against IHNV are discussed.

  17. A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia.

    PubMed

    Marriott, Helen M; Daigneault, Marc; Thompson, Alfred A R; Walmsley, Sarah R; Gill, Sharonjit K; Witcher, Derrick R; Wroblewski, Victor J; Hellewell, Paul G; Whyte, Moira K B; Dockrell, David H

    2012-11-01

    Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection.

  18. First description of necrosis in leaves and pseudo-bulbs of Oncidium orchids caused by Burkholderia gladioli in São Paulo State, Brazil

    USDA-ARS?s Scientific Manuscript database

    A necrosis of orchid leaves and pseudobulbs was observed in a commercial orchid nursery in Mogi das Cruzes, Sao Paulo, Brazil. The symptoms were water-soaked, brown lesions that can develop into large areas of necrosis that extend throughout the entire plant, ultimately causing death. Bacteria were...

  19. Numerical modelling of bifurcation and localisation in cohesive-frictional materials

    NASA Astrophysics Data System (ADS)

    de Borst, René

    1991-12-01

    Methods are reviewed for analysing highly localised failure and bifurcation modes in discretised mechanical systems as typically arise in numerical simulations of failure in soils, rocks, metals and concrete. By the example of a plane-strain biaxial test it is shown that strain softening and lack of normality in elasto-plastic constitutive equations and the ensuing loss of ellipticity of the governing field equations cause a pathological mesh dependence of numerical solutions for such problems, thus rendering the results effectively meaningless. The need for introduction of higher-order continuum models is emphasised to remedy this shortcoming of the conventional approach. For one such a continuum model, namely the unconstrained Cosserat continuum, it is demonstrated that meaningful and convergent solutions (in the sense that a finite width of the localisation zone is computed upon mesh refinement) can be obtained.

  20. Histopathological changes associated with high intensity focused ultrasound (HIFU) treatment for localised adenocarcinoma of the prostate

    PubMed Central

    Van Leenders, G J L H; Beerlage, H; Ruijter, E; de la Rosette, J J M C H; van de Kaa, C A

    2000-01-01

    Aims—Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment. Methods—Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes. Results—All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated. Conclusions—HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate. Key Words: prostate cancer • high intensity focused ultrasound treatment PMID:10889823

  1. Trigger wrist caused by avascular necrosis of the capitate: a case report.

    PubMed

    Matsui, Yuichiro; Kawamura, Daisuke; Kida, Hiroaki; Hatanaka, Kanako C; Iwasaki, Norimasa

    2018-03-27

    Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.

  2. Osteomyelitis: A rare complication of pancreatitis and PPP-syndrome.

    PubMed

    Langenhan, Ronny; Reimers, Niklas; Probst, Axel

    2016-03-01

    Pancreatic diseases can be accompanied by periarthritis with bone necrosis and panniculitis (PPP-syndrome). It is postulated that this is caused by systemic activity of pancreatic enzymes leading to microcirculatory disturbances and fat necrosis. The morbidity and mortality of the PPP-syndrome is high. Successful treatment of pancreatitis can lead to resolution of accompanying panniculitis and periarthritis without adverse sequelae, but weeks or months after pancreatitis, asymptomatic necrosis of the bone may become symptomatic by fracturing spontaneously. In this report, we also describe osteomyelitis as a severe septic complication of bone necrosis caused by pancreatitis, in one case as acute tissue necrosis and in another case months after pancreatitis spread haematogenously. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  3. Acute esophageal necrosis caused by alcohol abuse

    PubMed Central

    Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

    2005-01-01

    Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

  4. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn; National Institute of Biological Sciences, Beijing 102206; Jin, Wei

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

  5. Co-localisation of advanced glycation end products and D-β-aspartic acid-containing proteins in gelatinous drop-like corneal dystrophy.

    PubMed

    Kaji, Yuichi; Oshika, Tetsuro; Takazawa, Yutaka; Fukayama, Masashi; Fujii, Noriko

    2012-08-01

    Gelatinous drop-like corneal dystrophy (GDLD), also known as familial subepithelial corneal amyloidosis, is an autosomal recessive disorder that causes progressive corneal opacity due to accumulation of amyloid fibrils in the corneal stroma. Genetic analyses have revealed that a mutation in membrane component chromosome 1 surface marker 1 gene is responsible for GDLD. However, the mechanism of amyloid formation in the corneal stroma remains unclear. The present study attempted to reveal the role of advanced glycation end products (AGE) and d-amino acids in amyloid formation in GDLD. Informed consent was obtained from five patients with GDLD, three patients with bullous keratopathy and three patients with interstitial keratitis and all the specimens were analysed. Localisation of amyloid fibrils was analysed using Congo-red and thioflavin T staining. In addition, the localisation of AGE (N(ε)-carboxy(methyl)-L-lysine, pyrraline and pentosidine) and D-β-aspartic acid-containing proteins, a major form of d-amino acid-containing proteins, was analysed immunohistochemically. In all GDLD specimens, strong immunoreactivity to AGE and D-β-aspartic acid-containing proteins was detected in the subepithelial amyloid-rich region. In contrast, amyloid fibrils, AGE, or D-amino acid-containing proteins were slightly detected in the corneal stroma of patients with bullous keratopathy and interstitial keratitis. Abnormally accumulated proteins rich in AGE and D-β-aspartic acid co-localise in the amyloid lesions in GDLD. These results indicate that non-enzymatic post-translational modifications of proteins, including AGE formation and isomerisation of aspartyl residues, will be the cause as well as the result of amyloid fibril formations in GDLD.

  6. Co-localisation of advanced glycation end products and d-β-aspartic acid-containing proteins in gelatinous drop-like corneal dystrophy

    PubMed Central

    Oshika, Tetsuro; Takazawa, Yutaka; Fukayama, Masashi; Fujii, Noriko

    2012-01-01

    Purpose Gelatinous drop-like corneal dystrophy (GDLD), also known as familial subepithelial corneal amyloidosis, is an autosomal recessive disorder that causes progressive corneal opacity due to accumulation of amyloid fibrils in the corneal stroma. Genetic analyses have revealed that a mutation in membrane component chromosome 1 surface marker 1 gene is responsible for GDLD. However, the mechanism of amyloid formation in the corneal stroma remains unclear. The present study attempted to reveal the role of advanced glycation end products (AGE) and d-amino acids in amyloid formation in GDLD. Methods Informed consent was obtained from five patients with GDLD, three patients with bullous keratopathy and three patients with interstitial keratitis and all the specimens were analysed. Localisation of amyloid fibrils was analysed using Congo-red and thioflavin T staining. In addition, the localisation of AGE (Nɛ-carboxy(methyl)-l-lysine, pyrraline and pentosidine) and d-β-aspartic acid-containing proteins, a major form of d-amino acid-containing proteins, was analysed immunohistochemically. Results In all GDLD specimens, strong immunoreactivity to AGE and d-β-aspartic acid-containing proteins was detected in the subepithelial amyloid-rich region. In contrast, amyloid fibrils, AGE, or d-amino acid-containing proteins were slightly detected in the corneal stroma of patients with bullous keratopathy and interstitial keratitis. Conclusions Abnormally accumulated proteins rich in AGE and d-β-aspartic acid co-localise in the amyloid lesions in GDLD. These results indicate that non-enzymatic post-translational modifications of proteins, including AGE formation and isomerisation of aspartyl residues, will be the cause as well as the result of amyloid fibril formations in GDLD. PMID:22694960

  7. Novel allelic variants in ACD6 cause hybrid necrosis in local collection of Arabidopsis thaliana.

    PubMed

    Świadek, Magdalena; Proost, Sebastian; Sieh, Daniela; Yu, Jing; Todesco, Marco; Jorzig, Christian; Rodriguez Cubillos, Andrés Eduardo; Plötner, Björn; Nikoloski, Zoran; Chae, Eunyoung; Giavalisco, Patrick; Fischer, Axel; Schröder, Florian; Kim, Sang-Tae; Weigel, Detlef; Laitinen, Roosa A E

    2017-01-01

    Hybrid necrosis is a common type of hybrid incompatibility in plants. This phenomenon is caused by deleterious epistatic interactions, resulting in spontaneous activation of plant defenses associated with leaf necrosis, stunted growth and reduced fertility in hybrids. Specific combinations of alleles of ACCELERATED CELL DEATH 6 (ACD6) have been shown to be a common cause of hybrid necrosis in Arabidopsis thaliana. Increased ACD6 activity confers broad-spectrum resistance against biotrophic pathogens but reduces biomass production. We generated 996 crosses among individuals derived from a single collection area around Tübingen (Germany) and screened them for hybrid necrosis. Necrotic hybrids were further investigated by genetic linkage, amiRNA silencing, genomic complementation and metabolic profiling. Restriction site associated DNA (RAD)-sequencing was used to understand genetic diversity in the collection sites containing necrosis-inducing alleles. Novel combinations of ACD6 alleles found in neighbouring stands were found to activate the A. thaliana immune system. In contrast to what we observed in controlled conditions, necrotic hybrids did not show reduced fitness in the field. Metabolic profiling revealed changes associated with the activation of the immune system in ACD6-dependent hybrid necrosis. This study expands our current understanding of the active role of ACD6 in mediating trade-offs between defense responses and growth in A.  thaliana. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  8. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2016-06-01

    leaks extravascularly • Necrosis and inflammation involving the ear tip is considered to be a more severe manifestation of vascular damage associated...similar lesions to the 2M test solution, it appears that 2M test solution is more likely to cause vascular necrosis and inflammation (noted at 24 hours...injections • Although DMSO induced similar lesions to the 4M test solution, it appears that 4M test solution is more likely to cause vascular necrosis and

  9. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2016-06-01

    leaks extravascularly • Necrosis and inflammation involving the ear tip is considered to be a more severe manifestation of vascular damage associated...similar lesions to the 2M test solution, it appears that 2M test solution is more likely to cause vascular necrosis and inflammation (noted at 24 hours...injections • Although DMSO induced similar lesions to the 4M test solution, it appears that 4M test solution is more likely to cause vascular necrosis and

  10. [A serious complication after bladder embolisation due to massive tissue necrosis in the gluteal region].

    PubMed

    Osmonov, D K; Aksenov, A V; Naumann, C M; Jünemann, K-P

    2014-01-01

    Adequate and successful treatment of Hb-relevant macrohaematuria in bladder cancer patients is a frequent problem in clinical routine. It is often not easy to identify a good treatment option for inoperable older patients. A possible option is transcatheter-based arterial embolisation of the vesical artery. Unfortunately there are only few publications about this procedure; a detailed analysis of bladder embolisation is difficult to find in the literature. Our report illustrates the embolisation of the vesical artery in an 84-year-old patient with bladder cancer with an Hb-relevant, transurethral non-curable macrohaematuria. Massive necrosis of the M. gluteus maximus developed after embolisation of the vesical artery. During the ensuing surgery, the entire musculature of the gluteal region was removed, and the N. ischiadicus was cut. The patient was supervised first in the intensive care and then in the palliative care ward. The patient's prognosis is unfavourable due to the localisation and size of the wound and consecutive life-long immobility. Embolisation of the vesical artery is a viable procedure, but only if alternative therapeutic strategies are impossible. It should only be performed by an experienced radiologist and it is strongly recommended not to apply liquid embolisation agents. Inadequate embolisation of the vesical artery can lead to extensive necrosis. Radiological diagnostics help to identify the margins of the necrotic region. During the intervention, maximum attention should be paid to saving the entirety of N. ischiadicus, especially in patients with large necrotic areas. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Fibroblast growth factor receptor inhibition induces loss of matrix MCL1 and necrosis in cholangiocarcinoma.

    PubMed

    Kabashima, Ayano; Hirsova, Petra; Bronk, Steven F; Hernandez, Matthew C; Truty, Mark J; Rizvi, Sumera; Kaufmann, Scott H; Gores, Gregory J

    2018-03-08

    Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays. Mitochondrial oxidative metabolism was examined using a XF24 extracellular flux analyser. The efficiency of FGFR inhibition in patient-derived xenografts (PDX) was also assessed. CCA cells expressed two species of MCL1, a full-length form localised to the outer mitochondrial membrane, and an N terminus-truncated species compartmentalised within the mitochondrial matrix. The pan-FGFR inhibitor LY2874455 induced non-apoptotic cell death in the CCA cell lines associated with cellular depletion of both MCL1 species. The cell death was accompanied by failure of mitochondrial oxidative metabolism and was most consistent with necrosis. Enforced expression of N terminus-truncated MCL1 targeted to the mitochondrial matrix, but not full-length MCL1 targeted to the outer mitochondrial membrane, rescued cell death and mitochondrial function. LY2874455 treatment of PDX-bearing mice was associated with tumour cell loss of MCL1 and cell necrosis. FGFR inhibition induces loss of matrix MCL1, resulting in cell necrosis. These observations support a heretofore unidentified, alternative MCL1 survival function, namely prevention of cell necrosis, and have implications for treatment of human CCA. Herein, we report that therapeutic inhibition of a cell receptor expressed by bile duct cancer cells resulted in the loss of a critical survival protein termed MCL1. Cellular depletion of MCL1 resulted in the death of the cancer cells by a process characterised by cell rupture. Cell death by this process can stimulate the immune system and has implications for combination therapy using receptor inhibition with immunotherapy. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. A case of systemic lupus erythematosus presenting as bilateral avascular necrosis of femur.

    PubMed

    Adikari, Madura; Gunawardane, Aloka; Illangantilaka, Sachithra; Atukorale, Himantha; Rubasinghe, Jeevanie

    2016-08-05

    Avascular necrosis occur as a result of diverse etiology. Chronic inflammatory conditions such as systemic lupus erythematosus considered as a recognize cause. Many cases were reported in systemic lupus erythematosus after treating with corticosteroids. We report a case of a corticosteroid naïve patient presented as bilateral avascular necrosis of femoral head and later progressed to a case of systemic lupus erythematosus. A 26 year old lady presented with right sided hip pain and diagnosed as avascular necrosis of the femoral head. After 6 months she presented a similar pain in left hip, which revealed avascular necrosis of left femoral head as well. A probable cause for her clinical presentation could not be found after extensive clinical and laboratory evaluation. Patient reported high erythrocyte sedimentation rate persistently, and over the next few years progressed as a case of systemic lupus erythematosus. Above case illustrated avascular necrosis could be an early musculoskeletal manifestation of systemic lupus erythematosus even in the absence of corticosteroid administration.

  13. Indomethacin induced avascular necrosis of head of femur

    PubMed Central

    Prathapkumar, K; Smith, I; Attara, G

    2000-01-01

    Chemically induced avascular necrosis of bone is a well documented entity. Indomethacin is one of the causes of this condition but is often difficult to recognise. Review of the literature shows that only one case of indomethacin induced avascular necrosis has been reported in the English language between 1966 and the present.
The case of a young healthy man, who developed avascular necrosis of head of femur after prolonged administration of indomethacin, is reported here.


Keywords: indomethacin; avascular necrosis PMID:10964124

  14. [Morphea or juvenile localised scleroderma: Case report].

    PubMed

    Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

    2016-01-01

    Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Clinical Management of Heat-Related Illnesses

    DTIC Science & Technology

    2012-01-01

    rhabdomyolysis and multiorgan dysfunction syndrome, and it may result in death from overwhelming cell necrosis caused by a lethal heat-shock exposure...complications such as rhabdomyolysis and multiorgan dysfunction syndrome, and it may result in death from overwhelming cell necrosis caused by a...acetaminophen lower Tco by normalizing the elevated hypothalamic set point that is caused by pyrogens; in heatstroke, the set point is normal, with

  16. Phencyclidine-induced malignant hyperthermia causing submassive liver necrosis.

    PubMed

    Armen, R; Kanel, G; Reynolds, T

    1984-07-01

    This report describes three male patients arrested for aggressive and combative behavior, characteristic of phencyclidine intoxication, in whom severe hyperthermia, respiratory failure, and coma developed. Two days after the malignant hyperthermic event, serum transaminase levels rose acutely to extremely high levels with concomitant elevations in bilirubin levels and a fall in prothrombin activity. Liver biopsy specimens in two patients showed marked perivenular necrosis and collapse. No specific treatment was directed at the phencyclidine intoxication. Two of the three patients survived. Submassive liver necrosis caused by malignant hyperthermia is an unusual complication of phencyclidine abuse.

  17. Determinants of GPI-PLC Localisation to the Flagellum and Access to GPI-Anchored Substrates in Trypanosomes

    PubMed Central

    Sunter, Jack; Webb, Helena; Carrington, Mark

    2013-01-01

    In Trypanosoma brucei, glycosylphosphatidylinositol phospholipase C (GPI-PLC) is a virulence factor that releases variant surface glycoprotein (VSG) from dying cells. In live cells, GPI-PLC is localised to the plasma membrane where it is concentrated on the flagellar membrane, so activity or access must be tightly regulated as very little VSG is shed. Little is known about regulation except that acylation within a short internal motif containing three cysteines is necessary for GPI-PLC to access VSG in dying cells. Here, GPI-PLC mutants have been analysed both for subcellular localisation and for the ability to release VSG from dying cells. Two sequence determinants necessary for concentration on the flagellar membrane were identified. First, all three cysteines are required for full concentration on the flagellar membrane. Mutants with two cysteines localise predominantly to the plasma membrane but lose some of their flagellar concentration, while mutants with one cysteine are mainly localised to membranes between the nucleus and flagellar pocket. Second, a proline residue close to the C-terminus, and distant from the acylated cysteines, is necessary for concentration on the flagellar membrane. The localisation of GPI-PLC to the plasma but not flagellar membrane is necessary for access to the VSG in dying cells. Cellular structures necessary for concentration on the flagellar membrane were identified by depletion of components. Disruption of the flagellar pocket collar caused loss of concentration whereas detachment of the flagellum from the cell body after disruption of the flagellar attachment zone did not. Thus, targeting to the flagellar membrane requires: a titratable level of acylation, a motif including a proline, and a functional flagellar pocket. These results provide an insight into how the segregation of flagellar membrane proteins from those present in the flagellar pocket and cell body membranes is achieved. PMID:23990786

  18. Dual infection by streptococcus and atypical mycobacteria following Ahmed glaucoma valve surgery.

    PubMed

    Rao, Aparna; Wallang, Batriti; Padhy, Tapas Ranjan; Mittal, Ruchi; Sharma, Savitri

    2013-07-01

    To report a case of late postoperative endophthalmitis caused by Streptococcus pneumoniae and conjunctival necrosis by Streptococcus pneumoniae and Mycobacterium fortuitum following Ahmed glaucoma valve (AGV) surgery in a young patient. Case report of a 13-year-old boy with purulent exudates and extensive conjunctival necrosis two months following amniotic membrane graft and conjunctival closure (for conjunctival retraction post AGV for secondary glaucoma). The conjunctiva showed extensive necrosis causing exposure of the tube and plate associated with frank exudates in the area adjoining the plate and anterior chamber mandating explantation of the plate along with intravitreal antibiotics. The vitreous aspirate grew Streptococcus pneumoniae while Streptococcus pneumoniae with Mycobacterium fortuitum was isolated from the explanted plate. Despite adequate control of infection following surgery, the final visual outcome was poor owing to disc pallor. Conjunctival necrosis and retraction post-AGV can cause late postoperative co-infections by fulminant and slow-growing organisms. A close follow-up is therefore essential in these cases to prevent sight-threatening complications.

  19. Radiation necrosis causing failure of automatic ventilation during sleep with central sleep apnea

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Udwadia, Z.F.; Athale, S.; Misra, V.P.

    A patient operated upon for a midline cerebellar hemangioblastoma developed failure of automatic respiration during sleep, together with central sleep apnea syndrome, approximately two years after receiving radiation therapy to the brain. Clinical and CT scan findings were compatible with a diagnosis of radiation necrosis as the cause of his abnormal respiratory control.

  20. Hearing aid fitting for visual and hearing impaired patients with Usher syndrome type IIa.

    PubMed

    Hartel, B P; Agterberg, M J H; Snik, A F; Kunst, H P M; van Opstal, A J; Bosman, A J; Pennings, R J E

    2017-08-01

    Usher syndrome is the leading cause of hereditary deaf-blindness. Most patients with Usher syndrome type IIa start using hearing aids from a young age. A serious complaint refers to interference between sound localisation abilities and adaptive sound processing (compression), as present in today's hearing aids. The aim of this study was to investigate the effect of advanced signal processing on binaural hearing, including sound localisation. In this prospective study, patients were fitted with hearing aids with a nonlinear (compression) and linear amplification programs. Data logging was used to objectively evaluate the use of either program. Performance was evaluated with a speech-in-noise test, a sound localisation test and two questionnaires focussing on self-reported benefit. Data logging confirmed that the reported use of hearing aids was high. The linear program was used significantly more often (average use: 77%) than the nonlinear program (average use: 17%). The results for speech intelligibility in noise and sound localisation did not show a significant difference between type of amplification. However, the self-reported outcomes showed higher scores on 'ease of communication' and overall benefit, and significant lower scores on disability for the new hearing aids when compared to their previous hearing aids with compression amplification. Patients with Usher syndrome type IIa prefer a linear amplification over nonlinear amplification when fitted with novel hearing aids. Apart from a significantly higher logged use, no difference in speech in noise and sound localisation was observed between linear and nonlinear amplification with the currently used tests. Further research is needed to evaluate the reasons behind the preference for the linear settings. © 2016 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

  1. 7 CFR 51.1584 - Internal discoloration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Internal discoloration. Internal discoloration means discoloration such as is caused by net necrosis or any other type of necrosis, stem-end browning, internal brown spot, or other similar types of discoloration...

  2. 7 CFR 51.1584 - Internal discoloration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Internal discoloration. Internal discoloration means discoloration such as is caused by net necrosis or any other type of necrosis, stem-end browning, internal brown spot, or other similar types of discoloration...

  3. Purtscher's retinopathy and renal cortical necrosis: two rare vaso-occlusive complications in a patient with acute pancreatitis: a case report.

    PubMed

    Haque, Wasim Md Mohosin Ul; Ananna, Mehruba Alam; Haque, Hasna Fahmima; Rahim, Muhammad Abdur; Samad, Tabassum; Iqbal, Sarwar

    2016-11-15

    Purtscher's retinopathy and renal cortical necrosis are two rare vaso-occlusive complications of acute pancreatitis. Purtscher's retinopathy causes sudden impairment of vision, which was first reported in a patient with head trauma. Subsequently, it was also reported as a complication of acute pancreatitis and few other clinical conditions. Acute pancreatitis also rarely causes renal cortical necrosis leading to acute kidney injury. However, the simultaneous presence of both complications is rarely reported. A 20-year-old Bengali man presented to our hospital with a history of acute upper abdominal pain, vomiting, anuria, and disorientation. He was ultimately found to have bilateral complete blindness due to Purtscher's retinopathy and acute kidney injury due to renal cortical necrosis, as sequelae of acute pancreatitis. He became dialysis-dependent, his vision did not recover, and he died 16 months after diagnosis. This case highlights Purtscher's retinopathy and renal cortical necrosis might be considered as a recognized pair complication of acute pancreatitis.

  4. [Programmed necrosis mediated by receptor-interacting protein 3: a new target for liver disease research].

    PubMed

    Zhang, J; Jing, Y; Li, Y N; Zhou, L; Wang, B M

    2016-09-20

    Hepatocyte death mainly includes apoptosis and necrosis and is a critical process in the pathophysiological mechanism of liver injury caused by various reasons. Recent studies have shown that key regulatory molecules in the inhibition of apoptosis such as caspase cannot be used as targets for inhibiting disease progression in clinical practice. In recent years, programmed necrosis mediated by receptor-interacting protein 3(RIP3)becomes a new hot research topic. It not only plays an important role in inducing inflammatory response, but also is closely regulated by intracellular signal factors, and it is a type of active cell death which can be interfered with. Compared with apoptosis, programmed necrosis is accompanied by the release of various inflammatory factors, which significantly affects local immune microenvironment. RIP3-mediated programmed necrosis has been taken seriously in many diseases. Although its mechanism of action in liver disease remains unclear, the results of recent studies confirmed its important role in the development of liver disease. This article reviews the research advances in the role of RIP3-mediated programmed necrosis signaling pathway in liver disease of various causes and investigates the possibility of RIP3-mediated programmed necrosis as a new target in the treatment of liver disease.

  5. Diagnostic et traitement de la Maladie du charbon à localisation palpébrale: à propos d'un cas et revue de littérature

    PubMed Central

    Hafidi, Zouheir; Handor, Hanan; Laghmari, Mina; Handor, Najat; Cherkaoui, Lalla Ouafae; Tachfouti, Samira; Seffar, Myriame; Daoudi, Rajae

    2013-01-01

    L′anthrax est une zoonose causée par le Bacillus anthracis. les humains contractent généralement cette maladie dans des régions endémiques, par contact direct avec des animaux infectés ou avec leurs produits contaminés. Les localisations palpébrales sont rares dans la pratique clinique et posent des problèmes de diagnostic différentiel. Les auteurs rapportent l'observation d'un patient admis dans un tableau de cellulite préseptale, avec escarre noirâtre étendue de la paupière supérieure et œdème extensif de l′hémiface, faisant suspecter une localisation palpébrale de la maladie du charbon. L'examen bactériologique a permis de confirmer le diagnostic. Le patient a bénéficié d′une antibiothérapie à base de pénicilline G avec une bonne évolution. PMID:24171070

  6. Dual pathology—An unreported case

    PubMed Central

    Yap, Darren; Rasheed, Ashraf; Rashid, Majid

    2015-01-01

    Introduction Symptomatic biliary disease in children and young adults requiring surgical intervention are uncommon. However even rarer is the occurrence of a spontaneous gallbladder necrosis in a child. We report a case of spontaneous necrosis in a child with no apparent causative factors. Case Fit and well 16 year-old boy presented with acute generalized lower abdominal pain. Examination revealed mild epigastric pain with rebound tenderness and guarding of the right iliac fossa. Diagnostic laparoscopy showed a necrotic gallbladder and incidental finding of a Meckel’s diverticulum. He had a cholecystectomy and Meckel’s diverticulum resection. Patient recovered uneventfully and was discharged home. He was reviewed 2 months later and recovered well with no evidence of any post-operative complication. He was discharged without any further follow up. Discussion Gall bladder necrosis is a rare cause of an acute abdomen. We present the first reported case of a spontaneous gallbladder necrosis with no apparent cause. Literature review showed various causes of gall bladder necrosis including trauma, acalculous cholecystitis, gallbladder torsion, gangrenous cholecystitis and etc. Conclusion We report a case of spontaneous gallbladder necrosis in a young healthy male with no family history of thrombotic disorders or any history of sepsis, intervention, trauma and no obvious underlying anatomical or histological abnormalities. This is an exceedingly rare pathology and one would be forgiven for not including it on the list of a differential diagnosis in such circumstance. However it is important to send tissue sample to exclude any underlying histological aetiological factors. PMID:26657530

  7. Dual pathology-An unreported case.

    PubMed

    Yap, Darren; Rasheed, Ashraf; Rashid, Majid

    2015-01-01

    Symptomatic biliary disease in children and young adults requiring surgical intervention are uncommon. However even rarer is the occurrence of a spontaneous gallbladder necrosis in a child. We report a case of spontaneous necrosis in a child with no apparent causative factors. Fit and well 16 year-old boy presented with acute generalized lower abdominal pain. Examination revealed mild epigastric pain with rebound tenderness and guarding of the right iliac fossa. Diagnostic laparoscopy showed a necrotic gallbladder and incidental finding of a Meckel's diverticulum. He had a cholecystectomy and Meckel's diverticulum resection. Patient recovered uneventfully and was discharged home. He was reviewed 2 months later and recovered well with no evidence of any post-operative complication. He was discharged without any further follow up. Gall bladder necrosis is a rare cause of an acute abdomen. We present the first reported case of a spontaneous gallbladder necrosis with no apparent cause. Literature review showed various causes of gall bladder necrosis including trauma, acalculous cholecystitis, gallbladder torsion, gangrenous cholecystitis and etc. We report a case of spontaneous gallbladder necrosis in a young healthy male with no family history of thrombotic disorders or any history of sepsis, intervention, trauma and no obvious underlying anatomical or histological abnormalities. This is an exceedingly rare pathology and one would be forgiven for not including it on the list of a differential diagnosis in such circumstance. However it is important to send tissue sample to exclude any underlying histological aetiological factors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Sulfide toxicity: Mechanical ventilation and hypotension determine survival rate and brain necrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baldelli, R.J.; Green, F.H.Y.; Auer, R.N.

    1993-09-01

    Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause [open quotes]knockdown[close quotes] (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, the authors sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilatedmore » rats given high-dose sulfide (a dose that was lethal in [ge]50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to [le]35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. The authors conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect. 32 refs., 5 figs.« less

  9. Subcutaneous injection of liquid and foamed polidocanol: extravasation is not responsible for skin necrosis during reticular and spider vein sclerotherapy.

    PubMed

    Schuller-Petrović, S; Pavlović, M D; Neuhold, N; Brunner, F; Wölkart, G

    2011-08-01

    Cutaneous necrosis is one of the most annoying complications of reticular and spider vein sclerotherapy. The precise incidence of the complication is not known, although various sources reported incidence between 0.2% and 1.2%. Among a few mechanisms proposed to explain it, extravasation of the sclerosant into the perivascular tissue has been cited as the major cause. The aim of the experimental study in rats was to examine the potential of various concentrations and volumes of polidocanol in both liquid and foam forms to cause cutaneous necrosis after superficial subcutaneous injection. Twenty-four female Sprague Dawley rats were injected subcutaneously different concentrations (0.5%, 1%, 2% and 3%) of polidocanol as well as different preparations of polidocanol (liquid vs. foam) and volumes (0.1-0.5 mL). The animals were sacrificed 10 days after injections and biopsy specimens were obtained. Cutaneous necrosis was not seen at volumes <0.5 mL regardless of the concentration or form of polidocanol injected. Foam preparation was shown to be less potent in inducing necrosis with a minimal strength being 2% in comparison with the liquid form where 1% was sufficient to produce overt cutaneous necrosis. This experimental study shows that extravasation of polidocal in usual circumstances of sclerotherapy of spider and reticular veins cannot be a significant cause of cutaneous necrosis rarely observed in this setting. It is particularly true for the foamed polidocanol where 1% strength seems safe if injected extravascularly in volumes up to 0.5 mL. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  10. Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model

    PubMed Central

    2012-01-01

    Background Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. Methods 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. Results At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Conclusions Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels. PMID:22361346

  11. Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model.

    PubMed

    Homayounfar, Kia; Meis, Johanna; Jung, Klaus; Klosterhalfen, Bernd; Sprenger, Thilo; Conradi, Lena-Christin; Langer, Claus; Becker, Heinz

    2012-02-23

    Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels.

  12. Impact source localisation in aerospace composite structures

    NASA Astrophysics Data System (ADS)

    De Simone, Mario Emanuele; Ciampa, Francesco; Boccardi, Salvatore; Meo, Michele

    2017-12-01

    The most commonly encountered type of damage in aircraft composite structures is caused by low-velocity impacts due to foreign objects such as hail stones, tool drops and bird strikes. Often these events can cause severe internal material damage that is difficult to detect and may lead to a significant reduction of the structure’s strength and fatigue life. For this reason there is an urgent need to develop structural health monitoring systems able to localise low-velocity impacts in both metallic and composite components as they occur. This article proposes a novel monitoring system for impact localisation in aluminium and composite structures, which is able to determine the impact location in real-time without a-priori knowledge of the mechanical properties of the material. This method relies on an optimal configuration of receiving sensors, which allows linearization of well-known nonlinear systems of equations for the estimation of the impact location. The proposed algorithm is based on the time of arrival identification of the elastic waves generated by the impact source using the Akaike Information Criterion. The proposed approach was demonstrated successfully on both isotropic and orthotropic materials by using a network of closely spaced surface-bonded piezoelectric transducers. The results obtained show the validity of the proposed algorithm, since the impact sources were detected with a high level of accuracy. The proposed impact detection system overcomes current limitations of other methods and can be retrofitted easily on existing aerospace structures allowing timely detection of an impact event.

  13. Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation.

    PubMed

    Zhuang, Hongqing; Yuan, Xiangkun; Chang, Joe Y; Song, Yongchun; Wang, Junjie; Yuan, Zhiyong; Wang, Xiaoguang; Wang, Ping

    2016-07-26

    The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible.

  14. Genome sequencing and transposon mutagenesis of Burkholderia seminalis TC3.4.2R3 identify genes contributing to suppression of orchid necrosis caused by B. gladioli

    USDA-ARS?s Scientific Manuscript database

    Thirty six strains of Burkholderia spp. isolated from sugarcane were evaluated for biological control of leaf and pseudobulb necrosis of orchid caused by B. gladioli. Twenty nine of the sugarcane strains suppressed the disease in greenhouse assays. We generated a draft genomic sequence of one suppr...

  15. Understanding Breast Changes: A Health Guide for Women

    MedlinePlus

    ... for nipple discharge; and/or take antibiotics . Fat necrosis : A breast condition that may cause round, firm, ... be used to both diagnose and remove fat necrosis. Fibroadenoma : A benign tumor that feels like a ...

  16. Mathematical modelling of blood-brain barrier failure and edema

    NASA Astrophysics Data System (ADS)

    Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

    2015-11-01

    Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

  17. Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells.

    PubMed

    English, William R; Ireland-Zecchini, Heather; Baker, Andrew H; Littlewood, Trevor D; Bennett, Martin R; Murphy, Gillian

    2018-01-01

    Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis in VSMCs is highly dependent on FAS and is associated with changes in FAS and c-FLIP localisation, but is not solely dependent on shedding of the FAS ectodomain.

  18. Tissue Inhibitor of Metalloproteinase–3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells

    PubMed Central

    Ireland-Zecchini, Heather; Baker, Andrew H.; Littlewood, Trevor D.; Bennett, Martin R.; Murphy, Gillian

    2018-01-01

    Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis in VSMCs is highly dependent on FAS and is associated with changes in FAS and c-FLIP localisation, but is not solely dependent on shedding of the FAS ectodomain. PMID:29617412

  19. Anesthetic propofol overdose causes endothelial cytotoxicity in vitro and endothelial barrier dysfunction in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Ming-Chung; Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan, Taiwan; Chen, Chia-Ling

    An overdose and a prolonged treatment of propofol may cause cellular cytotoxicity in multiple organs and tissues such as brain, heart, kidney, skeletal muscle, and immune cells; however, the underlying mechanism remains undocumented, particularly in vascular endothelial cells. Our previous studies showed that the activation of glycogen synthase kinase (GSK)-3 is pro-apoptotic in phagocytes during overdose of propofol treatment. Regarding the intravascular administration of propofol, we therefore hypothesized that propofol overdose also induces endothelial cytotoxicity via GSK-3. Propofol overdose (100 μg/ml) inhibited growth in human arterial and microvascular endothelial cells. After treatment, most of the endothelial cells experienced caspase-independent necrosis-likemore » cell death. The activation of cathepsin D following lysosomal membrane permeabilization (LMP) determined necrosis-like cell death. Furthermore, propofol overdose also induced caspase-dependent apoptosis, at least in part. Caspase-3 was activated and acted downstream of mitochondrial transmembrane potential (MTP) loss; however, lysosomal cathepsins were not required for endothelial cell apoptosis. Notably, activation of GSK-3 was essential for propofol overdose-induced mitochondrial damage and apoptosis, but not necrosis-like cell death. Intraperitoneal administration of a propofol overdose in BALB/c mice caused an increase in peritoneal vascular permeability. These results demonstrate the cytotoxic effects of propofol overdose, including cathepsin D-regulated necrosis-like cell death and GSK-3-regulated mitochondrial apoptosis, on endothelial cells in vitro and the endothelial barrier dysfunction by propofol in vivo. Highlights: ► Propofol overdose causes apoptosis and necrosis in endothelial cells. ► Propofol overdose triggers lysosomal dysfunction independent of autophagy. ► Glycogen synthase kinase-3 facilitates propofol overdose-induced apoptosis. ► Propofol overdose causes an increase in peritoneal vascular permeability.« less

  20. Elkton: A new potato variety with resistance to internal heat necrosis and suitable for chipping directly from the field in the southern United States

    USDA-ARS?s Scientific Manuscript database

    Potato varieties grown in the southern U.S. are susceptible to a disorder called internal heat necrosis which causes death of flesh inside the potato tuber. We bred a new potato variety, Elkton, which is resistant to internal heat necrosis. Elkton was released by The Agricultural Research Service,...

  1. Orbital compressed air and petroleum injury mimicking necrotizing fasciitis.

    PubMed

    Mellington, Faye E; Bacon, Annette S; Abu-Bakra, Mohammed A J; Martinez-Devesa, Pablo; Norris, Jonathan H

    2014-09-01

    Orbital injury secondary to petroleum-based products is rare. We report the first case, to our knowledge, of a combined compressed air and chemical orbital injury, which mimicked necrotizing fasciitis. A 58-year-old man was repairing his motorcycle engine when a piston inadvertently fired, discharging compressed air and petroleum-based carburetor cleaner into his left eye. He developed surgical emphysema, skin necrosis, and a chemical cellulitis, causing an orbital compartment syndrome. He was treated initially with antibiotics and subsequently with intravenous steroid and orbital decompression surgery. There was almost complete recovery by 4 weeks postsurgery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Petroleum-based products can cause severe skin irritation and necrosis. Compressed air injury can cause surgical emphysema. When these two mechanisms of injury are combined, the resulting orbitopathy and skin necrosis can mimic necrotizing fasciitis and cause diagnostic confusion. A favorable outcome is achievable with aggressive timely management. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The ORF1 Products of Tombusviruses Play a Crucial Role in Lethal Necrosis of Virus-Infected Plants

    PubMed Central

    Burgyán, József; Hornyik, Csaba; Szittya, György; Silhavy, Dániel; Bisztray, György

    2000-01-01

    Hybrids of cymbidium ringspot (CymRSV) and carnation Italian ringspot (CIRV) tombusviruses were used to identify viral symptom determinants responsible for the generalized necrosis in tombusvirus-infected plants. Surprisingly, symptoms of Nicotiana benthamiana infected with CymRSV/CIRV hybrids were distinctly different. It was demonstrated that not all chimeras expressing wild-type (wt) levels of p19 protein caused systemic necrosis as both parents CymRSV and CIRV did. We showed here that hybrids containing chimeric ORF1 were not able to induce lethal necrosis even if the viral replication of these constructs was not altered significantly. However, if a wt p33 (product of ORF1) of CymRSV was provided in trans in transgenic plants expressing p33 and its readthrough product p92, the lethal necrosis characteristic to tombusvirus infection was restored. In addition, the expression of p33 by a potato virus X viral vector in N. benthamiana caused severe chlorosis and occasionally necrosis, indicating the importance of p33 in wt symptoms of tombusviruses. Thus, our results provide evidence that elicitation of the necrotic phenotype requires the presence of the wt p33 in addition to the p19 protein of tombusviruses. PMID:11069981

  3. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

    PubMed

    Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

    2010-07-16

    Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

  4. Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation

    PubMed Central

    Zhuang, Hongqing; Yuan, Xiangkun; Chang, Joe Y.; Song, Yongchun; Wang, Junjie; Yuan, Zhiyong; Wang, Xiaoguang; Wang, Ping

    2016-01-01

    Objective: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. Methods: This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. Results: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. Conclusion: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible. PMID:26934327

  5. Acute Esophageal Necrosis: A Case of Black Esophagus Associated with Bismuth Subsalicylate Ingestion

    PubMed Central

    Mankal, Pavan; Judeh, Hani; Kim, Sang

    2014-01-01

    We present a case of acute esophageal necrosis (AEN) likely caused by chronic use of bismuth subsalicylate, an active ingredient in over-the-counter Pepto-Bismol®, which contains 220 g of salicylic acid in each 30 mL quantity. While aspirin is known to cause gastritis and gastric ulcers, this is the first case, to our knowledge, reporting AEN after chronic bismuth subsalicylate use. PMID:26157851

  6. Avascular Necrosis of the Femoral Head.

    PubMed

    Seijas, Roberto; Sallent, Andrea; Rivera, Eila; Ares, Oscar

    2017-12-29

    About 250000 patients are operated on annually for hip arthroplasty in the USA alone. Of this number, about 10% the cause of their osteoarthritis is the avascular necrosis of the femoral head. But the causes of necrosis are multiple and many of them are still unknown. That is why small advances in etiopathogenesis, diagnosis and treatment of different causes are very important in order to reduce the number of affected patients. It may seem that small changes, studies focused on the details of different diseases do not bring great changes to science, but it is these small changes that end up adding great evolutions in our knowledge. In addition, the changes of recent years, are not focused on our specialty in technical or anatomical evolutions exclusively, but are often based on biological bases, which is the branch that evolves more within trauma and orthopedics. That is why open and constant minds are what help us move forward.

  7. [Asymptomatic Renal Stones: Do they really Exist?].

    PubMed

    Seseke, S; Rudolph, R; Rebmann, U

    2011-11-01

    Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. In a prospective study we evaluated 104  patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48  months (median: 25  months). During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8  mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39  cases (37.5 %). Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection. © Georg Thieme Verlag KG Stuttgart ˙ New York.

  8. Underwater Acoustic Source Localisation Among Blind and Sighted Scuba Divers: Comparative study.

    PubMed

    Cambi, Jacopo; Livi, Ludovica; Livi, Walter

    2017-05-01

    Many blind individuals demonstrate enhanced auditory spatial discrimination or localisation of sound sources in comparison to sighted subjects. However, this hypothesis has not yet been confirmed with regards to underwater spatial localisation. This study therefore aimed to investigate underwater acoustic source localisation among blind and sighted scuba divers. This study took place between February and June 2015 in Elba, Italy, and involved two experimental groups of divers with either acquired (n = 20) or congenital (n = 10) blindness and a control group of 30 sighted divers. Each subject took part in five attempts at an under-water acoustic source localisation task, in which the divers were requested to swim to the source of a sound originating from one of 24 potential locations. The control group had their sight obscured during the task. The congenitally blind divers demonstrated significantly better underwater sound localisation compared to the control group or those with acquired blindness ( P = 0.0007). In addition, there was a significant correlation between years of blindness and underwater sound localisation ( P <0.0001). Congenital blindness was found to positively affect the ability of a diver to recognise the source of a sound in an underwater environment. As the correct localisation of sounds underwater may help individuals to avoid imminent danger, divers should perform sound localisation tests during training sessions.

  9. Fault kinematics and localised inversion within the Troms-Finnmark Fault Complex, SW Barents Sea

    NASA Astrophysics Data System (ADS)

    Zervas, I.; Omosanya, K. O.; Lippard, S. J.; Johansen, S. E.

    2018-04-01

    The areas bounding the Troms-Finnmark Fault Complex are affected by complex tectonic evolution. In this work, the history of fault growth, reactivation, and inversion of major faults in the Troms-Finnmark Fault Complex and the Ringvassøy Loppa Fault Complex is interpreted from three-dimensional seismic data, structural maps and fault displacement plots. Our results reveal eight normal faults bounding rotated fault blocks in the Troms-Finnmark Fault Complex. Both the throw-depth and displacement-distance plots show that the faults exhibit complex configurations of lateral and vertical segmentation with varied profiles. Some of the faults were reactivated by dip-linkages during the Late Jurassic and exhibit polycyclic fault growth, including radial, syn-sedimentary, and hybrid propagation. Localised positive inversion is the main mechanism of fault reactivation occurring at the Troms-Finnmark Fault Complex. The observed structural styles include folds associated with extensional faults, folded growth wedges and inverted depocentres. Localised inversion was intermittent with rifting during the Middle Jurassic-Early Cretaceous at the boundaries of the Troms-Finnmark Fault Complex to the Finnmark Platform. Additionally, tectonic inversion was more intense at the boundaries of the two fault complexes, affecting Middle Triassic to Early Cretaceous strata. Our study shows that localised folding is either a product of compressional forces or of lateral movements in the Troms-Finnmark Fault Complex. Regional stresses due to the uplift in the Loppa High and halokinesis in the Tromsø Basin are likely additional causes of inversion in the Troms-Finnmark Fault Complex.

  10. Carbohydrate and ethane release with Erwinia carotovora subspecies betavasculorum--induced necrosis.

    PubMed

    Kuykendall, L David; Hunter, William J

    2008-02-01

    Erwinia carotovora subspecies betavasculorum, also known as E. betavasculorum and Pectobacterium betavasculorum, is a soil bacterium that has the capacity to cause root rot necrosis of sugarbeets. The qualitatively different pathogenicity exhibited by the virulent E. carotovora strain and two avirulent strains, a Citrobacter sp. and an Enterobacter cloacae, was examined using digital analysis of photographic evidence of necrosis as well as for carbohydrate, ethane, and ethylene release compared with uninoculated potato tuber slices. Visual scoring of necrosis was superior to digital analysis of photographs. The release of carbohydrates and ethane from potato tuber slices inoculated with the soft rot necrosis-causing Erwinia was significantly greater than that of potato tuber slices that had not been inoculated or that had been inoculated with the nonpathogenic E. cloacae and Citrobacter sp. strains. Interestingly, ethylene production from potato slices left uninoculated or inoculated with the nonpathogenic Citrobacter strain was 5- to 10-fold higher than with potato slices inoculated with the pathogenic Erwinia strain. These findings suggest that (1) carbohydrate release might be a useful measure of the degree of pathogenesis, or relative virulence; and that (2) bacterial suppression of ethylene formation may be a critical step in root rot disease formation.

  11. Two types of bone necrosis in the Middle Triassic Pistosaurus longaevus bones: the results of integrated studies

    NASA Astrophysics Data System (ADS)

    Surmik, Dawid; Rothschild, Bruce M.; Dulski, Mateusz; Janiszewska, Katarzyna

    2017-07-01

    Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany.

  12. 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. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Underwater Acoustic Source Localisation Among Blind and Sighted Scuba Divers

    PubMed Central

    Cambi, Jacopo; Livi, Ludovica; Livi, Walter

    2017-01-01

    Objectives Many blind individuals demonstrate enhanced auditory spatial discrimination or localisation of sound sources in comparison to sighted subjects. However, this hypothesis has not yet been confirmed with regards to underwater spatial localisation. This study therefore aimed to investigate underwater acoustic source localisation among blind and sighted scuba divers. Methods This study took place between February and June 2015 in Elba, Italy, and involved two experimental groups of divers with either acquired (n = 20) or congenital (n = 10) blindness and a control group of 30 sighted divers. Each subject took part in five attempts at an under-water acoustic source localisation task, in which the divers were requested to swim to the source of a sound originating from one of 24 potential locations. The control group had their sight obscured during the task. Results The congenitally blind divers demonstrated significantly better underwater sound localisation compared to the control group or those with acquired blindness (P = 0.0007). In addition, there was a significant correlation between years of blindness and underwater sound localisation (P <0.0001). Conclusion Congenital blindness was found to positively affect the ability of a diver to recognise the source of a sound in an underwater environment. As the correct localisation of sounds underwater may help individuals to avoid imminent danger, divers should perform sound localisation tests during training sessions. PMID:28690888

  14. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dawson, P., E-mail: philip.dawson@manchester.ac.uk; Schulz, S.; Oliver, R. A.

    In this paper, we compare and contrast the experimental data and the theoretical predictions of the low temperature optical properties of polar and nonpolar InGaN/GaN quantum well structures. In both types of structure, the optical properties at low temperatures are governed by the effects of carrier localisation. In polar structures, the effect of the in-built electric field leads to electrons being mainly localised at well width fluctuations, whereas holes are localised at regions within the quantum wells, where the random In distribution leads to local minima in potential energy. This leads to a system of independently localised electrons and holes.more » In nonpolar quantum wells, the nature of the hole localisation is essentially the same as the polar case but the electrons are now coulombically bound to the holes forming localised excitons. These localisation mechanisms are compatible with the large photoluminescence linewidths of the polar and nonpolar quantum wells as well as the different time scales and form of the radiative recombination decay curves.« less

  15. Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

    PubMed Central

    del Hierro, Piedad Magdalena

    2011-01-01

    Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

  16. Proteomics profiling of interactome dynamics by colocalisation analysis (COLA).

    PubMed

    Mardakheh, Faraz K; Sailem, Heba Z; Kümper, Sandra; Tape, Christopher J; McCully, Ryan R; Paul, Angela; Anjomani-Virmouni, Sara; Jørgensen, Claus; Poulogiannis, George; Marshall, Christopher J; Bakal, Chris

    2016-12-20

    Localisation and protein function are intimately linked in eukaryotes, as proteins are localised to specific compartments where they come into proximity of other functionally relevant proteins. Significant co-localisation of two proteins can therefore be indicative of their functional association. We here present COLA, a proteomics based strategy coupled with a bioinformatics framework to detect protein-protein co-localisations on a global scale. COLA reveals functional interactions by matching proteins with significant similarity in their subcellular localisation signatures. The rapid nature of COLA allows mapping of interactome dynamics across different conditions or treatments with high precision.

  17. Localised boundary air layer and clothing evaporative resistances for individual body segments.

    PubMed

    Wang, Faming; del Ferraro, Simona; Lin, Li-Yen; Sotto Mayor, Tiago; Molinaro, Vincenzo; Ribeiro, Miguel; Gao, Chuansi; Kuklane, Kalev; Holmér, Ingvar

    2012-01-01

    Evaporative resistance is an important parameter to characterise clothing thermal comfort. However, previous work has focused mainly on either total static or dynamic evaporative resistance. There is a lack of investigation of localised clothing evaporative resistance. The objective of this study was to study localised evaporative resistance using sweating thermal manikins. The individual and interaction effects of air and body movements on localised resultant evaporative resistance were examined in a strict protocol. The boundary air layer's localised evaporative resistance was investigated on nude sweating manikins at three different air velocity levels (0.18, 0.48 and 0.78 m/s) and three different walking speeds (0, 0.96 and 1.17 m/s). Similarly, localised clothing evaporative resistance was measured on sweating manikins at three different air velocities (0.13, 0.48 and 0.70 m/s) and three walking speeds (0, 0.96 and 1.17 m/s). Results showed that the wind speed has distinct effects on local body segments. In contrast, walking speed brought much more effect on the limbs, such as thigh and forearm, than on body torso, such as back and waist. In addition, the combined effect of body and air movement on localised evaporative resistance demonstrated that the walking effect has more influence on the extremities than on the torso. Therefore, localised evaporative resistance values should be provided when reporting test results in order to clearly describe clothing local moisture transfer characteristics. Localised boundary air layer and clothing evaporative resistances are essential data for clothing design and assessment of thermal comfort. A comprehensive understanding of the effects of air and body movement on localised evaporative resistance is also necessary by both textile and apparel researchers and industry.

  18. Toxic myopathy and acute hepatic necrosis in cattle caused by ingestion of Senna obtusifolia (sicklepod; coffee senna) in Brazil.

    PubMed

    Furlan, Fernando Henrique; Zanata, Carina; Damasceno, Everson Dos Santos; de Oliveira, Leonardo Pintar; da Silva, Leilane Aparecida; Colodel, Edson Moleta; Riet-Correa, Franklin

    2014-12-15

    The epidemiological, clinical and pathological findings of field and experimental Senna obtusifolia (sicklepod; coffee senna) poisoning in cattle are described. The low availability of good quality forage and high rate of infestation of pastures by S. obtusifolia were the factors that led to poisonous plant ingestion. In this study, the morbidity ranged between 2% and 27.9%, and the lethality was 100%. For the experimental study, six cattle were fed with the aerial parts of S. obtusifolia collected in three different seasons at 9%-38% of the animal's body weight. The experimental and field diseases were similar. The main clinical signs were diarrhea, reluctance to move, muscular weakness and recumbency. The gross findings included pale discoloration of the skeletal muscle. Microscopically, the affected cattle showed degeneration and necrosis of the skeletal muscles and occasionally of the cardiac muscles. Additionally, two cattle showed centrilobular hepatic necrosis. In this study, S. obtusifolia collected from the same farm showed seasonal variation in toxicity. Poisoning by S. obtusifolia is an important cause of death of cattle in the Central Western region of Brazil. The toxicosis caused by this plant is similar to S. occidentalis poisoning; however, in S. obtusifolia poisoning, acute hepatic necrosis is sometimes present. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The accuracy of colonoscopic localisation of colorectal tumours: a prospective, multi-centred observational study.

    PubMed

    Johnstone, M S; Moug, S J

    2014-05-01

    Colonoscopy is essential for accurate pre-operative colorectal tumour localisation, but its accuracy for localisation remains undetermined due to limitations of previous work. This study aimed to establish the accuracy of colonoscopic localisation and to determine how frequently inaccuracy results in altered surgical management. A prospective, multi-centred, powered observational study recruited 79 patients with colorectal tumours that underwent curative surgical resection. Patient and colonoscopic factors were recorded. Pre-operative colonoscopic and radiological lesion localisations were compared to intra-operative localisation using pre-defined anatomical bowel segments to determine accuracy, with changes in planned surgical management documented. Colonoscopy accurately located the colorectal tumour in 64/79 patients (81%). Five out of 15 inaccurately located patients required on-table alteration in planned surgical management. Pre-operative imaging was unable to visualise the primary tumour in 23.1% of cases, a finding that was more prevalent amongst bowel screener patients compared to symptomatic patients (45.8% vs. 13%; p = 0.003). Colonoscopic lesion localisation is inaccurate in 19.0% of cases and occurred throughout the colon with a change in on-table surgical management in 6.3%. With CT unable to visualise lesions in just under a quarter of cases, particularly in the screening population, preoperative localisation is heavily reliant on colonoscopy.

  20. Regions of the Cf-9B disease resistance protein able to cause spontaneous necrosis in Nicotiana benthamiana lie within the region controlling pathogen recognition in tomato.

    PubMed

    Chakrabarti, Apratim; Panter, Stephen N; Harrison, Kate; Jones, Jonathan D G; Jones, David A

    2009-10-01

    The tomato Cf-9 and Cf-9B genes both confer resistance to the leaf mold fungus Cladosporium fulvum but only Cf-9 confers seedling resistance and recognizes the avirulence (Avr) protein Avr9 produced by C. fulvum. Using domain swaps, leucine-rich repeats (LRR) 5 to 15 of Cf-9 were shown to be required for Cf-9-specific resistance to C. fulvum in tomato, and the entire N-terminus up to LRR15 of Cf-9B was shown to be required for Cf-9B-specific resistance. Finer domain swaps showed that nine amino-acid differences in LRR 13 to 15 provided sufficient Cf-9-specific residues in a Cf-9B context for recognition of Avr9 in Nicotiana tabacum or sufficient Cf-9B residues in a Cf-9 context for a novel necrotic response caused by the expression of Cf-9B in N. benthamiana. The responses conferred by LRR 13 to 15 were enhanced by addition of LRR 10 to 12, and either region of Cf-9B was found to cause necrosis in N. benthamiana when the other was replaced by Cf-9 sequence in a Cf-9B context. As a consequence, the domain swap with LRR 13 to 15 of Cf-9 in a Cf-9B context gained the dual ability to recognize Avr9 and cause necrosis in N. benthamiana. Intriguingly, two Cf-9B-specific domain swaps gave differing results for necrosis assays in N. benthamiana compared with disease resistance assays in transgenic tomato. The different domain requirements in these two cases suggest that the two assays detect unrelated ligands or detect related ligands in slightly different ways. A heat-sensitive necrosis-inducing factor present in N. benthamiana intercellular washing fluids was found to cause a necrotic response in N. tabacum plants carrying Hcr9-9A, Cf-9B, and Cf-9 but not in plants carrying only Cf-9. We postulate that this necrosis-inducing factor is recognized by Cf-9B either directly as a ligand or indirectly as a regulator of Cf-9B autoactivity.

  1. Evaluation of porphyrin C analogues for photodynamic therapy of cerebral glioma.

    PubMed

    Karagianis, G; Hill, J S; Stylli, S S; Kaye, A H; Varadaxis, N J; Reiss, J A; Phillips, D R

    1996-02-01

    A series of monomeric porphyrins (2-8) based on porphyrin C (1) have been tested as sensitisers for photodynamic therapy (PDT) of cerebral glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vivo screening, consisting of cytotoxicity, phototoxicity (red light) and subcellular localisation studies, revealed two sensitisers (porphyrin 7, molecular weight 863 Da and porphyrin 8, molecular weight 889 Da), which had greater photoactivity than porphyrin C and similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellular localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of porphyrins 7 and 8 was studied in the mouse C6 glioma model as well as in biopsy samples from normal brain, liver, spleen and blood. Maximal drug uptake levels in tumour occurred 9 and 6 h after intraperitoneal injection for 7 and 8 respectively, at which time the tumour to normal brain ratios were 15:1 and 13:1 respectively. The effect of PDT using porphyrin 7 activated by the gold metal vapour laser tuned to 627.8 nm was studied in Wistar rats bearing intracerebral C6 glioma. At a drug dose of 10 mg porphyrin 7 kg-1 body weight and laser doses of up to 400 J cm-2 light, selective tumour kill with sparing of normal brain was achieved, with a maximal depth of tumour kill of 1.77+/-0.40. mm. Irradiation following a higher drug dose of 75 mg porphyrin 7 kg-1 body weight resulted in a greater depth of tumour kill, but also significantly increased the likelihood and extent of necrosis in normal brain.

  2. The nuclear proteome of Trypanosoma brucei

    PubMed Central

    Goos, Carina; Dejung, Mario; Janzen, Christian J.; Butter, Falk

    2017-01-01

    Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host. Here, we provide the nuclear proteome of procyclic Trypanosoma brucei, the stage that resides within the tsetse fly midgut. We have performed quantitative label-free mass spectrometry to score 764 significantly nuclear enriched proteins in comparison to whole cell lysates. A comparison with proteomes of several experimentally characterised nuclear and non-nuclear structures and pathways confirmed the high quality of the dataset: the proteome contains about 80% of all nuclear proteins and less than 2% false positives. Using motif enrichment, we found the amino acid sequence KRxR present in a large number of nuclear proteins. KRxR is a sub-motif of a classical eukaryotic monopartite nuclear localisation signal and could be responsible for nuclear localization of proteins in Kinetoplastida species. As a proof of principle, we have confirmed the nuclear localisation of six proteins with previously unknown localisation by expressing eYFP fusion proteins. While proteome data of several T. brucei organelles have been published, our nuclear proteome closes an important gap in knowledge to study trypanosome biology, in particular nuclear-related processes. PMID:28727848

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

    PubMed Central

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

    2014-01-01

    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. PMID:24440909

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

    PubMed

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

    2015-12-01

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

  5. Penile necrosis secondary to purpura fulminans: a case report and review of literature.

    PubMed

    Hogarth, David B; Cheon, Paul M; Kassam, Javeed; Seal, Alexander E; Kavanagh, Alexander G

    2017-02-01

    We report the case of a 60-year-old Hispanic male with widespread necrotic purpuric lesions involving the penile, suprapubic, inguinal and hip dermis due to purpura fulminans. Purpura fulminans describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin; this rapidly progressing syndrome features vascular collapse and disseminated intravascular coagulation. This patient's penile necrosis involved the majority of the penile shaft and glans penis, and ultimately required partial glansectomy and repeated debridement for treatment. Subsequently, full thickness skin grafting was completed for reconstruction with good effect. While reports of penile necrosis secondary to various causes are documented in the literature, no prior reports describe penile necrosis secondary to purpura fulminans.

  6. Concurrent Acute Retinal Necrosis in a Patient With Iridocorneal Endothelial Syndrome.

    PubMed

    Vignesh, A P; Srinivasan, Renuka

    2016-11-01

    To report a rare case of concurrent acute retinal necrosis in a patient with iridocorneal endothelial syndrome (ICE). Case report. A 42-year-old woman showed acute diminution of vision in the right eye. Her fundus examination revealed features of acute retinal necrosis. She had also experienced gradual diminution of vision in her left eye for 5 years. The examination of her left eye revealed corneal edema with mild corectopia and increased intraocular pressure with abnormal endothelium on specular microscopy pointing to a diagnosis of ICE. This is a rare case where concurrent acute retinal necrosis and ICE syndrome are present in the same patient, possibly pointing to a common viral etiology causing both entities.

  7. TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation.

    PubMed

    Morioka, Sho; Broglie, Peter; Omori, Emily; Ikeda, Yuka; Takaesu, Giichi; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun

    2014-02-17

    TNF activates three distinct intracellular signaling cascades leading to cell survival, caspase-8-mediated apoptosis, or receptor interacting protein kinase 3 (RIPK3)-dependent necrosis, also called necroptosis. Depending on the cellular context, one of these pathways is activated upon TNF challenge. When caspase-8 is activated, it drives the apoptosis cascade and blocks RIPK3-dependent necrosis. Here we report the biological event switching to activate necrosis over apoptosis. TAK1 kinase is normally transiently activated upon TNF stimulation. We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. In addition, we also demonstrated that activation of RIPK1 and RIPK3 promoted TAK1 activation, suggesting a positive feedforward loop of RIPK1, RIPK3, and TAK1. Conversely, ablation of TAK1 caused caspase-dependent apoptosis, in which Ripk3 deletion did not block cell death either in vivo or in vitro. Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis.

  8. Investigation of the Fusarium virguliforme Transcriptomes Induced during Infection of Soybean Roots Suggests that Enzymes with Hydrolytic Activities Could Play a Major Role in Root Necrosis

    PubMed Central

    Sahu, Binod B.; Baumbach, Jordan L.; Singh, Prashant; Srivastava, Subodh K.; Yi, Xiaoping

    2017-01-01

    Sudden death syndrome (SDS) is caused by the fungal pathogen, Fusarium virguliforme, and is a major threat to soybean production in North America. There are two major components of this disease: (i) root necrosis and (ii) foliar SDS. Root symptoms consist of root necrosis with vascular discoloration. Foliar SDS is characterized by interveinal chlorosis and leaf necrosis, and in severe cases by flower and pod abscission. A major toxin involved in initiating foliar SDS has been identified. Nothing is known about how root necrosis develops. In order to unravel the mechanisms used by the pathogen to cause root necrosis, the transcriptome of the pathogen in infected soybean root tissues of a susceptible cultivar, ‘Essex’, was investigated. The transcriptomes of the germinating conidia and mycelia were also examined. Of the 14,845 predicted F. virguliforme genes, we observed that 12,017 (81%) were expressed in germinating conidia and 12,208 (82%) in mycelia and 10,626 (72%) in infected soybean roots. Of the 10,626 genes induced in infected roots, 224 were transcribed only following infection. Expression of several infection-induced genes encoding enzymes with oxidation-reduction properties suggests that degradation of antimicrobial compounds such as the phytoalexin, glyceollin, could be important in early stages of the root tissue infection. Enzymes with hydrolytic and catalytic activities could play an important role in establishing the necrotrophic phase. The expression of a large number of genes encoding enzymes with catalytic and hydrolytic activities during the late infection stages suggests that cell wall degradation could be involved in root necrosis and the establishment of the necrotrophic phase in this pathogen. PMID:28095498

  9. Investigation of the Fusarium virguliforme Transcriptomes Induced during Infection of Soybean Roots Suggests that Enzymes with Hydrolytic Activities Could Play a Major Role in Root Necrosis.

    PubMed

    Sahu, Binod B; Baumbach, Jordan L; Singh, Prashant; Srivastava, Subodh K; Yi, Xiaoping; Bhattacharyya, Madan K

    2017-01-01

    Sudden death syndrome (SDS) is caused by the fungal pathogen, Fusarium virguliforme, and is a major threat to soybean production in North America. There are two major components of this disease: (i) root necrosis and (ii) foliar SDS. Root symptoms consist of root necrosis with vascular discoloration. Foliar SDS is characterized by interveinal chlorosis and leaf necrosis, and in severe cases by flower and pod abscission. A major toxin involved in initiating foliar SDS has been identified. Nothing is known about how root necrosis develops. In order to unravel the mechanisms used by the pathogen to cause root necrosis, the transcriptome of the pathogen in infected soybean root tissues of a susceptible cultivar, 'Essex', was investigated. The transcriptomes of the germinating conidia and mycelia were also examined. Of the 14,845 predicted F. virguliforme genes, we observed that 12,017 (81%) were expressed in germinating conidia and 12,208 (82%) in mycelia and 10,626 (72%) in infected soybean roots. Of the 10,626 genes induced in infected roots, 224 were transcribed only following infection. Expression of several infection-induced genes encoding enzymes with oxidation-reduction properties suggests that degradation of antimicrobial compounds such as the phytoalexin, glyceollin, could be important in early stages of the root tissue infection. Enzymes with hydrolytic and catalytic activities could play an important role in establishing the necrotrophic phase. The expression of a large number of genes encoding enzymes with catalytic and hydrolytic activities during the late infection stages suggests that cell wall degradation could be involved in root necrosis and the establishment of the necrotrophic phase in this pathogen.

  10. Dose-dependent effects of alpha-naphthylisothiocyanate disconnect biliary fibrosis from hepatocellular necrosis.

    PubMed

    Joshi, Nikita; Ray, Jessica L; Kopec, Anna K; Luyendyk, James P

    2017-01-01

    Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. © 2016 Wiley Periodicals, Inc.

  11. Dose-Dependent Effects of Alpha-Naphthylisothiocyanate Disconnect Biliary Fibrosis from Hepatocellular Necrosis

    PubMed Central

    Joshi, Nikita; Ray, Jessica L.; Kopec, Anna K.; Luyendyk, James P.

    2017-01-01

    Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well-characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. PMID:27605088

  12. Investigation of the distribution of localised and extended states in amorphous MoOx

    NASA Astrophysics Data System (ADS)

    Dizayee, Wala; Ying, Minju; Griffin, Jonathan; Alqahtani, Mohammed S.; Buckley, Alastair; Fox, A. Mark; Gehring, Gillian A.

    2018-05-01

    Amorphous films of MoOx have both structural disorder and also chemical disorder for x<3. We have shown that this disorder can introduce localised states in thin films and have shown that the existence of localised states can be deduced from the XPS data that identifies the relevant occupations of different ionisation states of the Mo ions. This effect, which depends on both the oxygen concentration and the method of fabrication, is more important than electron-electron interactions in producing the observed localisation. We have also shown that magneto-optical dichroism is also a powerful technique to determine the energy distribution of localised and delocalised states.

  13. Papillary Necrosis in Rats Caused by Aspirin and Aspirin-containing Mixtures

    PubMed Central

    Nanra, Ranjit S.; Kincaid-Smith, Priscilla

    1970-01-01

    Nearly half the rats gavage-fed with aspirin and aspirin-containing mixtures developed papillary necrosis in 20 weeks. This incidence is similar to that found in rats on A.P.C. mixtures with high and low concentrations of p-chloracetanilide, an impurity of phenacetin. Aspirin alone produced necrosis in 7 out of 19 rats (36·8%) whereas phenacetin in the same dose had failed to cause any renal damage over six to nine months. If these results also apply to man they suggest that aspirin and not phenacetin may be the major factor in analgesic nephropathy in patients taking A.P.C. mixtures. An augmented clearance of aspirin appeared to afford some protection to the medulla, and it is suggested that this observation may have important clinical and epidemiological applications. Imagesp560-a PMID:5454357

  14. Visual detail about the body modulates tactile localisation biases.

    PubMed

    Margolis, Aaron N; Longo, Matthew R

    2015-02-01

    The localisation of tactile stimuli requires the integration of visual and somatosensory inputs within an internal representation of the body surface and is prone to consistent bias. Joints may play a role in segmenting such internal body representations, and may therefore influence tactile localisation biases, although the nature of this influence remains unclear. Here, we investigate the relationship between conceptual knowledge of joint locations and tactile localisation biases on the hand. In one task, participants localised tactile stimuli applied to the dorsum of their hand. A distal localisation bias was observed in all participants, consistent with previous results. We also manipulated the availability of visual information during this task, to determine whether the absence of this information could account for the distal bias observed here and by Mancini et al. (Neuropsychologia 49:1194-1201, 2011). The observed distal bias increased in magnitude when visual information was restricted, without a corresponding decrease in precision. In a separate task, the same participants indicated, from memory, knuckle locations on a silhouette image of their hand. Analogous distal biases were also seen in the knuckle localisation task. The accuracy of conceptual joint knowledge was not correlated with tactile localisation bias magnitude, although a similarity in observed bias direction suggests that both tasks may rely on a common, higher-order body representation. These results also suggest that distortions of conceptual body representation may be more common in healthy individuals than previously thought.

  15. Effects of Tributyltin Chloride on Cybrids with or without an ATP Synthase Pathologic Mutation

    PubMed Central

    López-Gallardo, Ester; Llobet, Laura; Emperador, Sonia; Montoya, Julio; Ruiz-Pesini, Eduardo

    2016-01-01

    Background: The oxidative phosphorylation system (OXPHOS) includes nuclear chromosome (nDNA)– and mitochondrial DNA (mtDNA)–encoded polypeptides. Many rare OXPHOS disorders, such as striatal necrosis syndromes, are caused by genetic mutations. Despite important advances in sequencing procedures, causative mutations remain undetected in some patients. It is possible that etiologic factors, such as environmental toxins, are the cause of these cases. Indeed, the inhibition of a particular enzyme by a poison could imitate the biochemical effects of pathological mutations in that enzyme. Moreover, environmental factors can modify the penetrance or expressivity of pathological mutations. Objectives: We studied the interaction between mitochondrially encoded ATP synthase 6 (p.MT-ATP6) subunit and an environmental exposure that may contribute phenotypic differences between healthy individuals and patients suffering from striatal necrosis syndromes or other mitochondriopathies. Methods: We analyzed the effects of the ATP synthase inhibitor tributyltin chloride (TBTC), a widely distributed environmental factor that contaminates human food and water, on transmitochondrial cell lines with or without an ATP synthase mutation that causes striatal necrosis syndrome. Doses were selected based on TBTC concentrations previously reported in human whole blood samples. Results: TBTC modified the phenotypic effects caused by a pathological mtDNA mutation. Interestingly, wild-type cells treated with this xenobiotic showed similar bioenergetics when compared with the untreated mutated cells. Conclusions: In addition to the known genetic causes, our findings suggest that environmental exposure to TBTC might contribute to the etiology of striatal necrosis syndromes. Citation: López-Gallardo E, Llobet L, Emperador S, Montoya J, Ruiz-Pesini E. 2016. Effects of tributyltin chloride on cybrids with or without an ATP synthase pathologic mutation. Environ Health Perspect 124:1399–1405; http://dx.doi.org/10.1289/EHP182 PMID:27129022

  16. Effects of Tributyltin Chloride on Cybrids with or without an ATP Synthase Pathologic Mutation.

    PubMed

    López-Gallardo, Ester; Llobet, Laura; Emperador, Sonia; Montoya, Julio; Ruiz-Pesini, Eduardo

    2016-09-01

    The oxidative phosphorylation system (OXPHOS) includes nuclear chromosome (nDNA)- and mitochondrial DNA (mtDNA)-encoded polypeptides. Many rare OXPHOS disorders, such as striatal necrosis syndromes, are caused by genetic mutations. Despite important advances in sequencing procedures, causative mutations remain undetected in some patients. It is possible that etiologic factors, such as environmental toxins, are the cause of these cases. Indeed, the inhibition of a particular enzyme by a poison could imitate the biochemical effects of pathological mutations in that enzyme. Moreover, environmental factors can modify the penetrance or expressivity of pathological mutations. We studied the interaction between mitochondrially encoded ATP synthase 6 (p.MT-ATP6) subunit and an environmental exposure that may contribute phenotypic differences between healthy individuals and patients suffering from striatal necrosis syndromes or other mitochondriopathies. We analyzed the effects of the ATP synthase inhibitor tributyltin chloride (TBTC), a widely distributed environmental factor that contaminates human food and water, on transmitochondrial cell lines with or without an ATP synthase mutation that causes striatal necrosis syndrome. Doses were selected based on TBTC concentrations previously reported in human whole blood samples. TBTC modified the phenotypic effects caused by a pathological mtDNA mutation. Interestingly, wild-type cells treated with this xenobiotic showed similar bioenergetics when compared with the untreated mutated cells. In addition to the known genetic causes, our findings suggest that environmental exposure to TBTC might contribute to the etiology of striatal necrosis syndromes. López-Gallardo E, Llobet L, Emperador S, Montoya J, Ruiz-Pesini E. 2016. Effects of tributyltin chloride on cybrids with or without an ATP synthase pathologic mutation. Environ Health Perspect 124:1399-1405; http://dx.doi.org/10.1289/EHP182.

  17. Harmonious functional and aesthetic correction of severe localised pregnancy-induced gingival enlargement associated with capillary haemangioma

    PubMed Central

    Kaushal, Shalini; Kumar, Avadhesh; Azmatullah, Mohammed; Gupta, Sanjay; Singh, Rajeev Kumar

    2013-01-01

    Gingival enlargement is a clinical condition that has been widely studied and is directly associated with specific local or systemic conditions. Pregnancy has been presented to increase susceptibility to gingival inflammation. Sex hormones are believed to be a risk factor for periodontitis because of their ability to proliferate specific periodontal microorganisms and affect host immunological response, but it is unclear whether pregnancy gingivitis exposes or proceeds to periodontitis. In this case report, the patient reported with severe localised enlarged gingival mass which initiated when she was pregnant. After parturition, gingival enlargement was persisting and causing functional and aesthetic problem. Enlargement did not resolve even after non-surgical therapy; therefore, surgical excision of the entire enlarged gingival mass was preformed. Histopathological examination revealed capillary haemangioma. No evidence of malignancy was seen. No recurrence was seen even after 2 years of follow-up. PMID:23774710

  18. Alfred Walter Campbell's return to Australia.

    PubMed

    Macmillan, Malcolm

    2018-01-01

    Alfred Walter Campbell (1868-1937) established the basic cytoarchitectonic structure of the human brain while he was working as a pathologist at the Rainhill Lunatic Asylum near Liverpool in the United Kingdom. He returned to Australia in 1905 and continued doing research while establishing a neurological practice. His research over the next 17 years focused on four topics: (a) localisation in the cerebellum, (b) the neuroses and psychoses in war, (c) localisation in the cerebral cortex of the gorilla, and (d) the causes and pathology of the mysterious Australian "X" Disease (later known as Murray Valley encephalitis). In this article, I elaborate on his research in these areas, which provided evidence (a) against Louis Bolk's thesis that variation in the size of the cerebellar cortex reflected variation in the amount of cortex controlling various groups of muscle, (b) against the view that the neuroses and psychoses in war were different from those in civilian life, (c) for a parcelation of the cortex of the gorilla brain that supported his earlier findings in the higher apes, and (d) on the cause and pathophysiology of Australian "X" disease. Much of this research was overlooked, but it remains of considerable value and historical significance.

  19. Anderson localisation and optical-event horizons in rogue-soliton generation.

    PubMed

    Saleh, Mohammed F; Conti, Claudio; Biancalana, Fabio

    2017-03-06

    We unveil the relation between the linear Anderson localisation process and nonlinear modulation instability. Anderson localised modes are formed in certain temporal intervals due to the random background noise. Such localised modes seed the formation of solitary waves that will appear during the modulation instability process at those preferred intervals. Afterwards, optical-event horizon effects between dispersive waves and solitons produce an artificial collective acceleration that favours the collision of solitons, which could eventually lead to a rogue-soliton generation.

  20. Epidemiological Differences Between Localised and Non-Localised Low Back Pain

    PubMed Central

    Coggon, David; Ntani, Georgia; Walker-Bone, Karen; Palmer, Keith T; Felli, Vanda E; Harari, Raul; Barrero, Lope H; Felknor, Sarah A.; Gimeno, David; Cattrell, Anna; Vargas-Prada, Sergio; Bonzini, Matteo; Solidaki, Eleni; Merisalu, Eda; Habib, Rima R.; Sadeghian, Farideh; Kadir, M Masood; Warnakulasuriya, Sudath SP; Matsudaira, Ko; Nyantumbu, Busisiwe; Sim, Malcolm R; Harcombe, Helen; Cox, Ken; Sarquis, Leila M M; Marziale, Maria H; Harari, Florencia; Freire, Rocio; Harari, Natalia; Monroy, Magda V; Quintana, Leonardo A; Rojas, Marianela; Harris, E Clare; Serra, Consol; Martinez, J Miguel; Delclos, George; Benavides, Fernando G; Carugno, Michele; Ferrario, Marco M; Pesatori, Angela C; Chatzi, Leda; Bitsios, Panos; Kogevinas, Manolis; Oha, Kristel; Freimann, Tiina; Sadeghian, Ali; Peiris-John, Roshini J; Sathiakumar, Nalini; Wickremasinghe, A Rajitha; Yoshimura, Noriko; Kelsall, Helen L; Hoe, Victor C W; Urquhart, Donna M; Derrett, Sarah; McBride, David; Herbison, Peter; Gray, Andrew; Salazar Vega, Eduardo J.

    2017-01-01

    Study design Cross-sectional survey with longitudinal follow-up Objectives To test the hypothesis that pain which is localised to the low back differs epidemiologically from that which occurs simultaneously or close in time to pain at other anatomical sites Summary of background data Low back pain (LBP) often occurs in combination with other regional pain, with which it shares similar psychological and psychosocial risk factors. However, few previous epidemiological studies of LBP have distinguished pain that is confined to the low back from that which occurs as part of a wider distribution of pain. Methods We analysed data from a cohort study of musculoskeletal pain and associated disability in 47 occupational groups from 18 countries. Results Among 12,197 subjects at baseline, 609 (4.9%) reported localised LBP in the past month, and 3,820 (31.3%) non-localised LBP. Non-localised LBP was more frequently associated with sciatica in the past month (48.1% vs. 30.0% of cases), occurred on more days in the past month and past year, was more often disabling for everyday activities (64.1% vs. 47.3% of cases), and had more frequently led to medical consultation and sickness absence from work. It was also more often persistent when participants were followed up after a mean of 14 months (65.6% vs. 54.1% of cases). In adjusted Poisson regression analyses, non-localised LBP was differentially associated with female sex, older age, somatising tendency, poor mental health and report of time pressure at work,. There were also marked differences in the relative prevalence of localised and non-localised LBP by occupational group. Conclusions Future epidemiological studies should distinguish where possible between pain that is limited to the low back and LBP which occurs in association with pain at other anatomical locations. PMID:27820794

  1. Development of a prototype of the tele-localisation system in radiotherapy using personal digital assistant via wireless communication.

    PubMed

    Wu, Vincent Wing-Cheung; Tang, Fuk-hay; Cheung, Wai-kwan; Chan, Kit-chi

    2013-02-01

    In localisation of radiotherapy treatment field, the oncologist is present at the simulator to approve treatment details produced by the therapist. Problems may arise if the oncologist is not available and the patient requires urgent treatment. The development of a tele-localisation system is a potential solution, where the oncologist uses a personal digital assistant (PDA) to localise the treatment field on the image sent from the simulator through wireless communication and returns the information to the therapist after his or her approval. Our team developed the first tele-localisation prototype, which consisted of a server workstation (simulator) for the administration of digital imaging and communication in medicine localisation images including viewing and communication with the PDA via a Wi-Fi network; a PDA (oncologist's site) installed with the custom-built programme that synchronises with the server workstation and performs treatment field editing. Trial tests on accuracy and speed of the prototype system were conducted on 30 subjects with the treatment regions covering the neck, skull, chest and pelvis. The average time required in performing the localisation using the PDA was less than 1.5 min, with the blocked field longer than the open field. The transmission speed of the four treatment regions was similar. The average physical distortion of the images was within 4.4% and the accuracy of field size indication was within 5.3%. Compared with the manual method, the tele-localisation system presented with an average deviation of 5.5%. The prototype system fulfilled the planned objectives of tele-localisation procedure with reasonable speed and accuracy. © 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.

  2. Proteomics profiling of interactome dynamics by colocalisation analysis (COLA)† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6mb00701e Click here for additional data file. Click here for additional data file.

    PubMed Central

    Sailem, Heba Z.; Kümper, Sandra; Tape, Christopher J.; McCully, Ryan R.; Paul, Angela; Anjomani-Virmouni, Sara; Jørgensen, Claus; Poulogiannis, George; Marshall, Christopher J.

    2017-01-01

    Localisation and protein function are intimately linked in eukaryotes, as proteins are localised to specific compartments where they come into proximity of other functionally relevant proteins. Significant co-localisation of two proteins can therefore be indicative of their functional association. We here present COLA, a proteomics based strategy coupled with a bioinformatics framework to detect protein–protein co-localisations on a global scale. COLA reveals functional interactions by matching proteins with significant similarity in their subcellular localisation signatures. The rapid nature of COLA allows mapping of interactome dynamics across different conditions or treatments with high precision. PMID:27824369

  3. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production

    PubMed Central

    Fortes, Guilherme B.; Alves, Leticia S.; de Oliveira, Rosane; Dutra, Fabianno F.; Rodrigues, Danielle; Fernandez, Patricia L.; Souto-Padron, Thais; De Rosa, María José; Kelliher, Michelle; Golenbock, Douglas; Chan, Francis K. M.

    2012-01-01

    Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS. PMID:22262768

  4. Oxylipin Biosynthesis Genes Positively Regulate Programmed Cell Death during Compatible Infections with the Synergistic Pair Potato Virus X-Potato Virus Y and Tomato Spotted Wilt Virus

    PubMed Central

    García-Marcos, Alberto; Pacheco, Remedios; Manzano, Aranzazu; Aguilar, Emmanuel

    2013-01-01

    One of the most severe symptoms caused by compatible plant-virus interactions is systemic necrosis, which shares common attributes with the hypersensitive response to incompatible pathogens. Although several studies have identified viral symptom determinants responsible for systemic necrosis, mechanistic models of how they contribute to necrosis in infected plants remain scarce. Here, we examined the involvement of different branches of the oxylipin biosynthesis pathway in the systemic necrosis response caused either by the synergistic interaction of Potato virus X with Potato virus Y (PVX-PVY) or by Tomato spotted wilt virus (TSWV) in Nicotiana benthamiana. Silencing either 9-lipoxygenase (LOX), 13-LOX, or α-dioxygenase-1 (α-DOX-1) attenuated the programmed cell death (PCD)-associated symptoms caused by infection with either PVX-PVY or TSWV. In contrast, silencing of the jasmonic acid perception gene, COI1 (Coronatine insensitive 1), expedited cell death during infection with compatible viruses. This correlated with an enhanced expression of oxylipin biosynthesis genes and dioxygenase activity in PVX-PVY-infected plants. Moreover, the Arabidopsis thaliana double lox1 α-dox-1 mutant became less susceptible to TSWV infection. We conclude that oxylipin metabolism is a critical component that positively regulates the process of PCD during compatible plant-virus interactions but does not play a role in restraining virus accumulation in planta. PMID:23487466

  5. Penile necrosis secondary to purpura fulminans: a case report and review of literature

    PubMed Central

    Cheon, Paul M.; Kassam, Javeed; Seal, Alexander E.; Kavanagh, Alexander G.

    2017-01-01

    Abstract We report the case of a 60-year-old Hispanic male with widespread necrotic purpuric lesions involving the penile, suprapubic, inguinal and hip dermis due to purpura fulminans. Purpura fulminans describes a rare syndrome involving intravascular thrombosis and hemorrhagic infarction of the skin; this rapidly progressing syndrome features vascular collapse and disseminated intravascular coagulation. This patient’s penile necrosis involved the majority of the penile shaft and glans penis, and ultimately required partial glansectomy and repeated debridement for treatment. Subsequently, full thickness skin grafting was completed for reconstruction with good effect. While reports of penile necrosis secondary to various causes are documented in the literature, no prior reports describe penile necrosis secondary to purpura fulminans. PMID:28479975

  6. Management of diseases caused by thrips-transmitted tospoviruses in subsistence agriculture: the case of Peanut bud necrosis virus in India

    USDA-ARS?s Scientific Manuscript database

    Among the tospoviruses (genus Tospovirus, family Bunyaviridae) reported in India, Peanut bud necrosis virus is by far the most economically significant for tomato production in subsistence agriculture. Management of PBNV has been a challenge for farmers due to the broad host-range of PBNV and its ve...

  7. Evaluation of the tepary bean (Phaseolus acutifolius) CIAT germplasm collection for response to common bacterial blight and bean common mosaic necrosis virus

    USDA-ARS?s Scientific Manuscript database

    Aphid-transmitted Bean Common Mosaic Necrosis Virus (BCMNV) and Bean Common Mosaic Virus (BCMV) are potyvirus that cause production losses in common and tepary beans. Developing resistance to viruses, specifically BCMV, BCMNV and BGYMV, will be critical for expanding tepary bean production. This stu...

  8. Subcellular mRNA localisation at a glance

    PubMed Central

    Parton, Richard M.; Davidson, Alexander; Davis, Ilan; Weil, Timothy T.

    2014-01-01

    ABSTRACT mRNA localisation coupled to translational regulation provides an important means of dictating when and where proteins function in a variety of model systems. This mechanism is particularly relevant in polarised or migrating cells. Although many of the models for how this is achieved were first proposed over 20 years ago, some of the molecular details are still poorly understood. Nevertheless, advanced imaging, biochemical and computational approaches have started to shed light on the cis-acting localisation signals and trans-acting factors that dictate the final destination of localised transcripts. In this Cell Science at a Glance article and accompanying poster, we provide an overview of mRNA localisation, from transcription to degradation, focusing on the microtubule-dependent active transport and anchoring mechanism, which we will use to explain the general paradigm. However, it is clear that there are diverse ways in which mRNAs become localised and target protein expression, and we highlight some of the similarities and differences between these mechanisms. PMID:24833669

  9. Resonant photoluminescence studies of carrier localisation in c-plane InGaN/GaN quantum well structures

    NASA Astrophysics Data System (ADS)

    Blenkhorn, W. E.; Schulz, S.; Tanner, D. S. P.; Oliver, R. A.; Kappers, M. J.; Humphreys, C. J.; Dawson, P.

    2018-05-01

    In this paper we report on changes in the form of the low temperature (12 K) photoluminescence spectra of an InGaN/GaN quantum well structure as a function of excitation photon energy. As the photon energy is progressively reduced we observe at a critical energy a change in the form of the spectra from one which is determined by the occupation of the complete distribution of hole localisation centres to one which is determined by the resonant excitation of specific localisation sites. This change is governed by an effective mobility edge whereby the photo-excited holes remain localised at their initial energy and are prevented from scattering to other localisation sites. This assignment is confirmed by the results of atomistic tight binding calculations which show that the wave function overlap of the lowest lying localised holes with other hole states is low compared with the overlap of higher lying hole states with other higher lying hole states.

  10. A necrosis-inducing elicitor domain encoded by both symptomatic and asymptomatic Plantago asiatica mosaic virus isolates, whose expression is modulated by virus replication.

    PubMed

    Komatsu, Ken; Hashimoto, Masayoshi; Maejima, Kensaku; Shiraishi, Takuya; Neriya, Yutaro; Miura, Chihiro; Minato, Nami; Okano, Yukari; Sugawara, Kyoko; Yamaji, Yasuyuki; Namba, Shigetou

    2011-04-01

    Systemic necrosis is the most destructive symptom induced by plant pathogens. We previously identified amino acid 1154, in the polymerase domain (POL) of RNA-dependent RNA polymerase (RdRp) of Plantago asiatica mosaic virus (PlAMV), which affects PlAMV-induced systemic necrosis in Nicotiana benthamiana. By point-mutation analysis, we show that amino acid 1,154 alone is not sufficient for induction of necrotic symptoms. However, PlAMV replicons that can express only RdRp, derived from a necrosis-inducing PlAMV isolate, retain their ability to induce necrosis, and transient expression of PlAMV-encoded proteins indicated that the necrosis-eliciting activity resides in RdRp. Moreover, inducible-overexpression analysis demonstrated that the necrosis was induced in an RdRp dose-dependent manner. In addition, during PlAMV infection, necrotic symptoms are associated with high levels of RdRp accumulation. Surprisingly, necrosis-eliciting activity resides in the helicase domain (HEL), not in the amino acid 1,154-containing POL, of RdRp, and this activity was observed even in HELs of PlAMV isolates of which infection does not cause necrosis. Moreover, HEL-induced necrosis had characteristics similar to those induced by PlAMV infection. Overall, our data suggest that necrotic symptoms induced by PlAMV infection depend on the accumulation of a non-isolate specific elicitor HEL (even from nonnecrosis isolates), whose expression is indirectly regulated by amino acid 1,154 that controls replication.

  11. The in vitro secretome of Mycosphaerella fijiensis induces cell death in banana leaves.

    PubMed

    Chuc-Uc, José; Brito-Argáez, Ligia; Canto-Canché, Blondy; Tzec-Simá, Miguel; Rodríguez-García, Cecilia; Peraza-Echeverría, Leticia; Peraza-Echeverría, Santy; James-Kay, Andrew; Cruz-Cruz, Carlos Alberto; Peña-Rodríguez, Luis Manuel; Islas-Flores, Ignacio

    2011-06-01

    The hemibiotrophic filamentous fungus Mycosphaerella fijiensis causes the banana foliar disease known as black Sigatoka, responsible for major worldwide losses in the banana fruit industry. In this work the in vitro secretome of M. fijiensis was characterized. Native and denaturant polyacrylamide gel protease assays showed the M. fijiensis secretome contains protease activity capable of degrading gelatin. Necrotic lesions on leaves were produced by application of the in vitro secretome to the surface of one black Sigatoka-resistant banana wild species, one susceptible cultivar and the non-host plant Carica papaya. To distinguish if necrosis by the secretome is produced by phytotoxins or proteins, the latter ones were precipitated with ammonium sulfate and applied in native or denatured forms onto leaves of the same three plant species. Proteins applied in both preparations were able to produce necrotic lesions. Application of Pronase, a commercial bacterial protease suggested that the necrosis was, at least in part, caused by protease activity from the M. fijiensis secretome. The ability to cause necrotic lesions between M. fijiensis secreted- and ammonium sulfate-precipitated proteins, and purified lipophilic or hydrophilic phytotoxins, was compared. The results suggested that leaf necrosis arises from the combined action of non-host specific hydrolytic activities from the secreted proteins and the action of phytotoxins. This is the first characterization of the M. fijiensis protein secretome produced in vitro but, more importantly, it is also the first time the M. fijiensis secretome has been shown to contain virulence factors capable of causing necrosis to its natural host. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  12. Etoposide Induces Nuclear Re-Localisation of AID

    PubMed Central

    Lambert, Laurens J.; Walker, Simon; Feltham, Jack; Lee, Heather J.; Reik, Wolf; Houseley, Jonathan

    2013-01-01

    During B cell activation, the DNA lesions that initiate somatic hypermutation and class switch recombination are introduced by activation-induced cytidine deaminase (AID). AID is a highly mutagenic protein that is maintained in the cytoplasm at steady state, however AID is shuttled across the nuclear membrane and the protein transiently present in the nucleus appears sufficient for targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic reprogramming in primordial germ cells and cell fusions and in induced pluripotent stem cells (iPS cells), however AID expression in non-B cells is very low. We hypothesised that epigenetic reprogramming would require a pathway that instigates prolonged nuclear residence of AID. Here we show that AID is completely re-localised to the nucleus during drug withdrawal following etoposide treatment, in the period in which double strand breaks (DSBs) are repaired. Re-localisation occurs 2-6 hours after etoposide treatment, and AID remains in the nucleus for 10 or more hours, during which time cells remain live and motile. Re-localisation is cell-cycle dependent and is only observed in G2. Analysis of DSB dynamics shows that AID is re-localised in response to etoposide treatment, however re-localisation occurs substantially after DSB formation and the levels of re-localisation do not correlate with γH2AX levels. We conclude that DSB formation initiates a slow-acting pathway which allows stable long-term nuclear localisation of AID, and that such a pathway may enable AID-induced DNA demethylation during epigenetic reprogramming. PMID:24324754

  13. SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis.

    PubMed

    Choi, Seon-Guk; Kim, Hyunjoo; Jeong, Eun Il; Lee, Ho-June; Park, Sungwoo; Lee, Song-Yi; Lee, Hyeon-Jeong; Lee, Seong Won; Chung, Chin Ha; Jung, Yong-Keun

    2017-01-15

    Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. Copyright © 2017 American Society for Microbiology.

  14. SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis

    PubMed Central

    Choi, Seon-Guk; Kim, Hyunjoo; Jeong, Eun Il; Lee, Ho-June; Park, Sungwoo; Lee, Song-Yi; Lee, Hyeon-Jeong; Lee, Seong Won; Chung, Chin Ha

    2016-01-01

    ABSTRACT Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. PMID:27799292

  15. Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in partial-thickness scald burns in mice.

    PubMed

    Bayliss, Jill; Delarosa, Sara; Wu, Jianfeng; Peterson, Jonathan R; Eboda, Oluwatobi N; Su, Grace L; Hemmila, Mark; Krebsbach, Paul H; Cederna, Paul S; Wang, Stewart C; Xi, Chuanwu; Levi, Benjamin

    2014-01-01

    Extracellular adenosine triphosphate (ATP), present in thermally injured tissue, modulates the inflammatory response and causes significant tissue damage. The authors hypothesize that neutrophil infiltration and ensuing tissue necrosis would be mitigated by removing ATP-dependent signaling at the burn site. Mice were subjected to 30% TBSA partial-thickness scald burn by dorsal skin immersion in a water bath at 60 or 20°C (nonburn controls). In the treatment arm, an ATP hydrolyzing enzyme, apyrase, was applied directly to the site immediately after injury. Skin was harvested after 24 hours and 5 days for hematoxylin and eosin stain, elastase, and Ki-67 staining. Tumor necrosis factor (TNF)-α and interferon (IFN)-β expression were measured through quantitative real-time polymerase chain reaction. At 24 hours, the amount of neutrophil infiltration was different between the burn and burn + apyrase groups (P < .001). Necrosis was less extensive in the apyrase group when compared with the burn group at 24 hours and 5 days. TNF-α and IFN-β expression at 24 hours in the apyrase group was lower than in the burn group (P < .05). However, Ki-67 signaling was not significantly different among the groups. The results of this study support the role of extracellular ATP in neutrophil activity. The authors demonstrate that ATP hydrolysis at the burn site allays the neutrophil response to thermal injury and reduces tissue necrosis. This decrease in inflammation and tissue necrosis is at least partially because of TNF-α and IFN-β signaling. Apyrase could be used as topical inflammatory regulators to quell the injury caused by inflammation.

  16. Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

    PubMed

    Piekutowska-Abramczuk, Dorota; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Ciara, Elżbieta; Trubicka, Joanna; Pronicki, Maciej; Rokicki, Dariusz; Rydzanicz, Małgorzata; Płoski, Rafał; Pronicka, Ewa

    2016-01-01

    Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

  17. Electron localisation in static and time-dependent one-dimensional model systems

    NASA Astrophysics Data System (ADS)

    Durrant, T. R.; Hodgson, M. J. P.; Ramsden, J. D.; Godby, R. W.

    2018-02-01

    The most direct signature of electron localisation is the tendency of an electron in a many-body system to exclude other same-spin electrons from its vicinity. By applying this concept directly to the exact many-body wavefunction, we find that localisation can vary considerably between different ground-state systems, and can also be strongly disrupted, as a function of time, when a system is driven by an applied electric field. We use this measure to assess the well-known electron localisation function (ELF), both in its approximate single-particle form (often applied within density-functional theory) and its full many-particle form. The full ELF always gives an excellent description of localisation, but the approximate ELF fails in time-dependent situations, even when the exact Kohn-Sham orbitals are employed.

  18. Treatment of combined endodontic: periodontic lesion by sealing of palato-radicular groove using biodentine.

    PubMed

    Naik, Mayuri; de Ataide, Ida de Noronha; Fernandes, Marina; Lambor, Rajan

    2014-11-01

    Palatoradicular groove is a developmental anomaly which is predominantly found in maxillary lateral incisors. It provides a susceptible alcove for the progression of localised periodontal inflammation which can further cause pulpal involvement. This case report describes the successful treatment of a large periodontic - endodontic lesion usingnon surgical endodontic therapy and biodentine for the sealing of the palatoradicular groove.

  19. Turpentine oil inhalation leading to lung necrosis and empyema in a toddler.

    PubMed

    Khan, Awais J; Akhtar, Raja P; Faruqui, Zia S

    2006-05-01

    Household poisons can cause serious damage to the health of children. Turpentine oil, used chiefly as a solvent in paints, varnishes, and waxes; is often placed within easy reach of children during polishing or painting work. It is capable of causing serious toxicity, whether ingested or inhaled. Pulmonary aspiration can lead to lung parenchymal damage and turpentine-associated pneumonia. We report a case of exploratory ingestion and inhalation of turpentine oil in an 18-month-old boy, leading to extensive lung parenchymal damage, formation of multiple abscess cavities, and necrosis treated with decortication and segmental resection.

  20. Arsenic trioxide-induced osteo-necrosis treatment in a child: mini-review and case report.

    PubMed

    Marty, M; Noirrit-Esclassan, E; Diemer, F

    2016-10-01

    Arsenic oxide compounds were traditionally used as devitalizing agents. Due to its toxicity, leakage of such compounds into the periodontium can cause gingival and osteo-necrosis. Their use is forbidden in Europe and the USA for decades, however, some dentists seem to still use it. We report the case of a 14-year-old girl referred to the paediatric dentistry department of Toulouse University hospital, France, presenting a bone necrosis following the use of an arsenic trioxide product to accelerate pulp necrosis. The treatment included surgical removal of necrosis bone sequestrum, complete pulpectomy and an intermediate restoration of the tooth 27. After 1 week, the clinical conditions greatly improved. A restoration using a ceramic crown was performed after 2 months, and complete healing was observed after 1 year follow-up. Although arsenic trioxide is neither appropriate nor permitted for use in modern dentistry, especially in paediatric dentistry, some rare cases of arsenic-induced osteo-necrosis can still be encountered. A clearer message must be given to all dental practitioners against the use of arsenic trioxide in modern endodontic treatment.

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

    PubMed

    Plichta, Piotr; Pawelec, Katarzyna

    2011-01-01

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

  2. Phloem Necrosis of American Elm in the Mississippi Delta

    Treesearch

    T. H. Filer

    1966-01-01

    Phloem necrosis in elms, caused by the virus Morsus ulmi Holmes, has been found at Rolling Fork, Mississippi, 60 miles northwest of Jackson and 47 miles north of Vicksburg, in the Delta hardwoods area. It was first reported in Mississippi in 1941, when it was found at Jackson, and it appeared in the northeastern part of the State in 1945.

  3. Pectobacterium carotovorum. subsp. brasiliense is a causal agent of bacterial leaf rot of tobacco in China

    USDA-ARS?s Scientific Manuscript database

    A new leaf rot disease of tobacco was found in fields of the Shaowu region, Fujian Province of China in 2015. A typical symptom was necrosis along the main or lateral veins of tobacco leaves, eventually causing wilting and death of the leaves, while the necrosis spread no further than the epidermis ...

  4. Serratia marcescens Necrotizing Fasciitis Presenting as Bilateral Breast Necrosis

    PubMed Central

    Rehman, Tayyab; Moore, Thomas A.

    2012-01-01

    Serratia marcescens is an extremely rare cause of necrotizing fasciitis. We report the first case of necrotizing fasciitis of the chest wall due to infection with S. marcescens that initially manifested as bilateral breast necrosis. The patient had a fulminant course leading to death within 72 h of presentation. Literature pertinent to S. marcescens-mediated necrotizing fasciitis is also reviewed. PMID:22837315

  5. Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy

    NASA Astrophysics Data System (ADS)

    Maspero, Matteo; van den Berg, Cornelis A. T.; Zijlstra, Frank; Sikkes, Gonda G.; de Boer, Hans C. J.; Meijer, Gert J.; Kerkmeijer, Linda G. W.; Viergever, Max A.; Lagendijk, Jan J. W.; Seevinck, Peter R.

    2017-10-01

    An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of 1.1 × 1.1 × 1.2 mm3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a semi-automatic workflow facilitating the introduction of an MR-only workflow.

  6. Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake.

    PubMed

    Ferdek, Pawel E; Jakubowska, Monika A; Gerasimenko, Julia V; Gerasimenko, Oleg V; Petersen, Ole H

    2016-11-01

    Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca 2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca 2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3-sulfate primarily affects acinar cells. Ca 2+ signals and necrosis are strongly dependent on extracellular Ca 2+ as well as Na + ; and Na + -dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells. Bile acid-mediated pancreatic damage can be further escalated by bradykinin-induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca 2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca 2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca 2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca 2+ signals on extracellular Na + and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na + -dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca 2+ and significantly reduced in the absence of Na + , showing that bile-dependent cell death was a downstream event of Ca 2+ signals. Finally, combined application of TLC-S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC-S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells. © 2016 The Authors The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  7. Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

    PubMed Central

    Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

    2016-01-01

    Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na+‐dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca2+ and significantly reduced in the absence of Na+, showing that bile‐dependent cell death was a downstream event of Ca2+ signals. Finally, combined application of TLC‐S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC‐S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells. PMID:27406326

  8. Probabilistic self-localisation on a qualitative map based on occlusions

    NASA Astrophysics Data System (ADS)

    Santos, Paulo E.; Martins, Murilo F.; Fenelon, Valquiria; Cozman, Fabio G.; Dee, Hannah M.

    2016-09-01

    Spatial knowledge plays an essential role in human reasoning, permitting tasks such as locating objects in the world (including oneself), reasoning about everyday actions and describing perceptual information. This is also the case in the field of mobile robotics, where one of the most basic (and essential) tasks is the autonomous determination of the pose of a robot with respect to a map, given its perception of the environment. This is the problem of robot self-localisation (or simply the localisation problem). This paper presents a probabilistic algorithm for robot self-localisation that is based on a topological map constructed from the observation of spatial occlusion. Distinct locations on the map are defined by means of a classical formalism for qualitative spatial reasoning, whose base definitions are closer to the human categorisation of space than traditional, numerical, localisation procedures. The approach herein proposed was systematically evaluated through experiments using a mobile robot equipped with a RGB-D sensor. The results obtained show that the localisation algorithm is successful in locating the robot in qualitatively distinct regions.

  9. A new range-free localisation in wireless sensor networks using support vector machine

    NASA Astrophysics Data System (ADS)

    Wang, Zengfeng; Zhang, Hao; Lu, Tingting; Sun, Yujuan; Liu, Xing

    2018-02-01

    Location information of sensor nodes is of vital importance for most applications in wireless sensor networks (WSNs). This paper proposes a new range-free localisation algorithm using support vector machine (SVM) and polar coordinate system (PCS), LSVM-PCS. In LSVM-PCS, two sets of classes are first constructed based on sensor nodes' polar coordinates. Using the boundaries of the defined classes, the operation region of WSN field is partitioned into a finite number of polar grids. Each sensor node can be localised into one of the polar grids by executing two localisation algorithms that are developed on the basis of SVM classification. The centre of the resident polar grid is then estimated as the location of the sensor node. In addition, a two-hop mass-spring optimisation (THMSO) is also proposed to further improve the localisation accuracy of LSVM-PCS. In THMSO, both neighbourhood information and non-neighbourhood information are used to refine the sensor node location. The results obtained verify that the proposed algorithm provides a significant improvement over existing localisation methods.

  10. Virulence of Three Cylindrocladium Species to Yellow-Poplar Seedlings

    Treesearch

    T. H. Filer

    1970-01-01

    Cylindrocladium crotalariae and C. scoparium caused severe root rot on potted yellow-poplar seedlings. They appeared to be equally virulent. C. floridanum caused necrosis only on feeder roots of the seedlings.

  11. Strain localisation in mechanically layered rocks beneath detachment zones: insights from numerical modelling

    NASA Astrophysics Data System (ADS)

    Le Pourhiet, L.; Huet, B.; Labrousse, L.; Yao, K.; Agard, P.; Jolivet, L.

    2013-04-01

    We have designed a series of fully dynamic numerical simulations aimed at assessing how the orientation of mechanical layering in rocks controls the orientation of shear bands and the depth of penetration of strain in the footwall of detachment zones. Two parametric studies are presented. In the first one, the influence of stratification orientation on the occurrence and mode of strain localisation is tested by varying initial dip of inherited layering in the footwall with regard to the orientation of simple shear applied at the rigid boundary simulating a rigid hanging wall, all scaling and rheological parameter kept constant. It appears that when Mohr-Coulomb plasticity is being used, shear bands are found to localise only when the layering is being stretched. This corresponds to early deformational stages for inital layering dipping in the same direction as the shear is applied, and to later stages for intial layering dipping towards the opposite direction of shear. In all the cases, localisation of the strain after only γ=1 requires plastic yielding to be activated in the strong layer. The second parametric study shows that results are length-scale independent and that orientation of shear bands is not sensitive to the viscosity contrast or the strain rate. However, decreasing or increasing strain rate is shown to reduce the capacity of the shear zone to localise strain. In the later case, the strain pattern resembles a mylonitic band but the rheology is shown to be effectively linear. Based on the results, a conceptual model for strain localisation under detachment faults is presented. In the early stages, strain localisation occurs at slow rates by viscous shear instabilities but as the layered media is exhumed, the temperature drops and the strong layers start yielding plastically, forming shear bands and localising strain at the top of the shear zone. Once strain localisation has occured, the deformation in the shear band becomes extremely penetrative but the strength cannot drop since the shear zone has a finite thickness.

  12. Overexpression of HO-1 assisted PM2.5-induced apoptosis failure and autophagy-related cell necrosis.

    PubMed

    Zhou, Wei; Yuan, Xiaoyan; Zhang, Li; Su, Baoting; Tian, Dongdong; Li, Yang; Zhao, Jun; Wang, Yimei; Peng, Shuangqing

    2017-11-01

    Severe smog/haze events accompanied by extremely high concentrations of airborne fine particulate matter (PM2.5) have emerged frequently in China and the potential health risks have attracted ever-growing attention. During these episodes, a surge in hospital visits for acute respiratory symptoms and respiratory diseases exacerbation has been reported to be associated with acute exposure to high-levels of particulate matters. To investigate cell fate determination and the underlying pathogenic mechanisms during severe haze episodes or smog events, we exposed human lung epithelial cells (BEAS-2B) to PM2.5 (0-400μg/mL) for 24h and found that high doses of PM2.5 caused cell necrosis and autophagy dysfunction, while co-treatment with the autophagy inhibitor 3-MA could partially reduce PM2.5-induced cell necrosis. Exposure to PM2.5 also increased the expression and mitochondrial transposition of heme oxygenase 1 (HO-1), which consequently reduced the release of cytochrome C from mitochondria to cytosol. Knockdown of HO-1 by siRNA attenuated the mitochondrial accumulation of HO-1, reversed HO-1-induced the reduction of cytochrome C release and promoted PM2.5-induced cell apoptosis. In contrast to necrosis, PM2.5-induced autophagy was independent of HO-1. In conclusion, our results demonstrate that acute exposure to high PM2.5 concentrations causes autophagy-related cell necrosis. The decrease in cytochrome C release and apoptosis by upregulation of HO-1 maybe assist PM2.5-induced autophagy-related cell necrosis. Further, this study reveals dual roles for HO-1 in PM2.5-induced cytotoxicity and presents a possible explanation for the onset of acute respiratory symptoms under extreme particulate air pollution. Copyright © 2017. Published by Elsevier Inc.

  13. Thermal isotherms in PMMA and cell necrosis during total hip arthroplasty.

    PubMed

    Gundapaneni, Dinesh; Goswami, Tarun

    2014-12-30

    Polymethylmethacrylate (PMMA), also known as bone cement, is a commonly used adhesive material to fix implants in Total Hip Arthroplasty (THA). During implantation, bone cement undergoes a polymerization reaction which is an exothermic reaction and results in the release of heat to the surrounding bone tissue, which ultimately leads to thermal necrosis. Necrosis in the bony tissue results in early loosening of the implant, which causes pain and reduces the life of the implant. The main objective of the present study was to understand the thermal isotherms in PMMA and to determine the optimal cement mantle thickness to prevent cell necrosis during THA. In this study, the environment in the bony tissue during implantation was simulated by constructing 3D solid models to observe the temperature distribution in the bony tissue at different cement mantle thicknesses (1 mm, 3 mm and 5 mm), by applying the temperature conditions that exist during the surgery. Stems made with Co-Cr-Mo, 316L stainless steel and Ti6Al4V were used, which acted as heat sinks, and a thermal damage equation was used to measure the bone damage. FEA was conducted based on temperature conditions and thermal isotherms at different cement mantle thicknesses were obtained. Thermal isotherms derived with respect to distance in the bony tissue from the center of the cement mantle, and cell necrosis was determined at different mantle thicknesses. Based on the deduced results, cement mantle thickness of 1-5 mm does not cause thermal damage in the bony tissue. Considering the long term stability of the implant, cement mantle thickness range from 3 mm-5 mm was found to be optimal in THA to prevent cell necrosis.

  14. Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur mustard exposed HaCaT cell cultures.

    PubMed

    Heinrich, A; Balszuweit, F; Thiermann, H; Kehe, K

    2009-12-15

    Sulfur mustard (SM; bis(2-chloroethyl)sulphide; HD) is a blister inducing agent causing DNA damage and subsequently, cell death, mostly by apoptosis in basal keratinocytes. Despite intensive investigations on the cellular mechanism, there are, as of now, no causal therapeutics to prevent or antagonize SM-related damage to cells and tissues. In order to develop treatment strategies against vesication, it is important to distinguish apoptosis from necrosis in SM treated human keratinocytes. DNA fragmentation is a hallmark of apoptosis and regulated by a cascade of enzymes (endonucleases, DNase I, NUC 18), which finally cut the chromatin into specific formations of 180-200 base pairs, the nucleosomes. A feasible way to monitor apoptosis is the detection of nucleosomes by means of the Cell Death Detection ELISA(plus) (CDDE). In contrast, during necrosis DNA fragmentation is at random and delivers larger fragments, which therefore are significantly less in number and predominantly occur in cell culture supernatant. To monitor necrosis, we measured the release of intracellular adenylate kinase (AK) into cell culture supernatant by means of the ToxiLight Bioluminescence Assay (TL). With combination of the Cell Death Detection ELISA(plus) and the ToxiLight Bioluminescence Assay, we acquired more comprehensive information on cell survival and mechanisms of cell death, following an SM exposure. To validate the assay we tested common apoptosis- and necrosis-inducing agents like SM 300 microM for 30 min, Lewisite (L) 60 microM for 5 min and Triton X-100 0.1%. The results show that it is possible to differentiate between the two modes of cell death and to quantify their extent. This assay is highly effective in quantifying apoptosis and necrosis caused by cytotoxic agents and in estimating protective effects of potential active pharmaceutical ingredients.

  15. First report of Fusarium decemcellulare causing inflorescence wilt, vascular and flower necrosis of rambutan (Nephelium lappaceum), longan (Dimocarpus longan) and mango (Mangifera indica)

    USDA-ARS?s Scientific Manuscript database

    Longan, mango and rambutan are very important fruit crops in Puerto Rico. During a disease survey in Puerto Rico conducted from 2008 to 2010, 50% of the inflorescences were affected with inflorescence wilt, flower and vascular necrosis at 70% of the fields of rambutan and longan at the USDA-ARS Rese...

  16. Insights into Alternanthera mosaic virus TGB3 functions: Interactions with Nicotiana benthamiana PsbO correlate with chloroplast vesiculation and veinal necrosis caused by TGB3 overexpression

    USDA-ARS?s Scientific Manuscript database

    Alternanthera mosaic virus (AltMV) triple gene block 3 (TGB3) protein is involved in viral movement. AltMV TGB3 subcellular localization was previously shown to be distinct from that of Potato virus X (PVX) TGB3, and a chloroplast binding domain identified; veinal necrosis and chloroplast vesiculati...

  17. Nuclear localisation of 53BP1 is regulated by phosphorylation of the nuclear localisation signal.

    PubMed

    von Morgen, Patrick; Lidak, Tomas; Horejsi, Zuzana; Macurek, Libor

    2018-06-01

    Repair of damaged DNA is essential for maintaining genomic stability. TP53-binding protein 1 (53BP1) plays an important role in repair of the DNA double-strand breaks. Nuclear localisation of 53BP1 depends on importin β and nucleoporin 153, but the type and location of 53BP1 nuclear localisation signal (NLS) have yet to be determined. Here, we show that nuclear import of 53BP1 depends on two basic regions, namely 1667-KRK-1669 and 1681-KRGRK-1685, which are both needed for importin binding. Lysine 1667 is essential for interaction with importin and its substitution to arginine reduced nuclear localisation of 53BP1. Furthermore, we have found that CDK1-dependent phosphorylation of 53BP1 at S1678 impairs importin binding during mitosis. Phosphorylation-mimicking mutant S1678D showed reduced nuclear localisation, suggesting that phosphorylation of the NLS interferes with nuclear import of the 53BP1 CONCLUSIONS: We show that 53BP1 contains a classical bipartite NLS 1666-GKRKLITSEEERSPAKRGRKS-1686, which enables the importin-mediated nuclear transport of 53BP1. Additionally, we found that posttranslational modification within the NLS region can regulate 53BP1 nuclear import. Our results indicate that integrity of the NLS is important for 53BP1 nuclear localisation. Precise mapping of the NLS will facilitate further studies on the effect of posttranslational modifications and somatic mutations on the nuclear localisation 53BP1 and DNA repair. © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  18. Injury due to extravasation of thiopental and propofol: Risks/effects of local cooling/warming in rats.

    PubMed

    Shibata, Yuuka; Yokooji, Tomoharu; Itamura, Ryo; Sagara, Yumeka; Taogoshi, Takanori; Ogawa, Katsunari; Tanaka, Maiko; Hide, Michihiro; Kihira, Kenji; Matsuo, Hiroaki

    2016-12-01

    Inadvertent leakage of medications with vesicant properties can cause severe necrosis in tissue, which can have devastating long-term consequences. The aim of this study was to evaluate the extent of extravasation injury induced by thiopental and propofol, and the effects of cooling or warming of local tissue on extravasation injury at macroscopic and histopathologic levels. Rats were administered intradermally thiopental (2.5 mg/100 µL) or propofol (1.0 mg/100 µL). Rats were assigned randomly to three groups: control (no treatment), cooling and warming. Local cooling (18-20 °C) or warming (40-42 °C) was applied for 3 h immediately after agent injection. Lesion sizes (erythema, induration, ulceration, necrosis) were monitored after agent injection. Histopathology was evaluated in skin biopsies taken 24 h after agent injection. Thiopental injection induced severe skin injury with necrosis. Peak lesions developed within 24 h and healed gradually 18-27 days after extravasation. Propofol induced inflammation but no ulceration, and lesions healed within 1-2 days. Local cooling reduced thiopental- and propofol-induced extravasation injuries but warming strongly exacerbated the skin lesions (e.g., degeneration, necrosis) induced by extravasation of thiopental and propofol. Thiopental can be classified as a "vesicant" that causes tissue necrosis and propofol can be classified as an "irritant". Local cooling protects (at least in part) against skin disorders induced by thiopental and propofol, whereas warming is harmful.

  19. Is the Pauli exclusion principle the origin of electron localisation?

    NASA Astrophysics Data System (ADS)

    Rincón, Luis; Torres, F. Javier; Almeida, Rafael

    2018-03-01

    In this work, we inquire into the origins of the electron localisation as obtained from the information content of the same-spin pair density, γσ, σ(r2∣r1). To this end, we consider systems of non-interacting and interacting identical Fermions contained in two simple 1D potential models: (1) an infinite potential well and (2) the Kronig-Penney periodic potential. The interparticle interaction is considered through the Hartree-Fock approximation as well as the configuration interaction expansion. Morover, the electron localisation is described through the Kullback-Leibler divergence between γσ, σ(r2∣r1) and its associated marginal probability. The results show that, as long as the adopted method properly includes the Pauli principle, the electronic localisation depends only modestly on the interparticle interaction. In view of the latter, one may conclude that the Pauli principle is the main responsible for the electron localisation.

  20. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.

    PubMed

    Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

    2016-06-07

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons.

  1. Treatment of combined endodontic: periodontic lesion by sealing of palato-radicular groove using biodentine

    PubMed Central

    Naik, Mayuri; de Ataide, Ida de Noronha; Fernandes, Marina; Lambor, Rajan

    2014-01-01

    Introduction: Palatoradicular groove is a developmental anomaly which is predominantly found in maxillary lateral incisors. It provides a susceptible alcove for the progression of localised periodontal inflammation which can further cause pulpal involvement. This case report describes the successful treatment of a large periodontic – endodontic lesion usingnon surgical endodontic therapy and biodentine for the sealing of the palatoradicular groove. PMID:25506153

  2. AAV9 intracerebroventricular gene therapy improves lifespan, locomotor function and pathology in a mouse model of Niemann-Pick type C1 disease.

    PubMed

    Hughes, Michael P; Smith, Dave A; Morris, Lauren; Fletcher, Claire; Colaco, Alexandria; Huebecker, Mylene; Tordo, Julie; Palomar, Nuria; Massaro, Giulia; Henckaerts, Els; Waddington, Simon N; Platt, Frances M; Rahim, Ahad A

    2018-06-05

    Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative lysosomal storage disorder. It is caused in 95% of cases by a mutation in the NPC1 gene that encodes NPC1, an integral transmembrane protein localised to the limiting membrane of the lysosome. There is no cure for NP-C but there is a disease-modifying drug (miglustat) that slows disease progression but with associated side effects. Here, we demonstrate in a well-characterised mouse model of NP-C that a single administration of AAV-mediated gene therapy to the brain can significantly extend lifespan, improve quality of life, prevent or ameliorate neurodegeneration, reduce biochemical pathology and normalize or improve various indices of motor function. Over-expression of human NPC1 does not cause adverse effects in the brain and correctly localises to late endosomal/lysosomal compartments. Furthermore, we directly compare gene therapy to licensed miglustat. Even at a low dose, gene therapy has all the benefits of miglustat but without adverse effects. On the basis of these findings and on-going ascendency of the field, we propose intracerebroventricular gene therapy as a potential therapeutic option for clinical use in NP-C.

  3. Development of three-dimensional radiotherapy techniques in breast cancer

    NASA Astrophysics Data System (ADS)

    Coles, Charlotte E.

    Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research facilitated protocol development of a proposed national breast radiotherapy trial investigating IMRT and partial breast irradiation.

  4. Distinguishing cause from correlation in tokamak experiments to trigger edge-localised plasma instabilities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Webster, Anthony J.; CCFE, Culham Science Centre, Abingdon OX14 3DB

    2014-11-15

    The generic question is considered: How can we determine the probability of an otherwise quasi-random event, having been triggered by an external influence? A specific problem is the quantification of the success of techniques to trigger, and hence control, edge-localised plasma instabilities (ELMs) in magnetically confined fusion (MCF) experiments. The development of such techniques is essential to ensure tolerable heat loads on components in large MCF fusion devices, and is necessary for their development into economically successful power plants. Bayesian probability theory is used to rigorously formulate the problem and to provide a formal solution. Accurate but pragmatic methods aremore » developed to estimate triggering probabilities, and are illustrated with experimental data. These allow results from experiments to be quantitatively assessed, and rigorously quantified conclusions to be formed. Example applications include assessing whether triggering of ELMs is a statistical or deterministic process, and the establishment of thresholds to ensure that ELMs are reliably triggered.« less

  5. Acute Compartment Syndrome Which Causes Rhabdomyolysis by Carbon Monoxide Poisoning and Sciatic Nerve Injury Associated with It: A Case Report.

    PubMed

    Ji, Jung-Woo

    2017-09-01

    Rhabdomyolysis is most frequently caused by soft tissue injury with trauma to the extremities. Non-traumatic rhabdomyolysis may be caused by alcohol or drug abuse, infection, collagen disease, or intensive exercise, but incidence is low. In particular, rhabdomyolysis resulting from carbon monoxide poisoning is especially rare. If caught before death, carbon monoxide poisoning has been shown to cause severe muscle necrosis and severe muscle damage leading to acute renal failure. In cases of carbon-monoxide-induced rhabdomyolsis leading to acute compartment syndrome in the buttocks and sciatic nerve injury are rare. We have experience treating patients with acute compartment syndrome due to rhabdomyolysis following carbon monoxide poisoning. We report the characteristic features of muscle necrosis observed during a decompression operation and magnetic resonance imaging findings with a one-year follow-up in addition to a review of the literature.

  6. Effect of loading density of sockeye salmon, Oncorhynchus nerka (Walbaum), eggs in incubation boxes on mortality caused by infectious haematopoietic necrosis

    USGS Publications Warehouse

    Mulcahy, D.; Bauersfeld, K.

    1983-01-01

    Infectious haematopoietic necrosis (IHN) can cause massive mortalities of sockeye salmon, Oncorhynchus nerka (Walbaum), cultured in hatcheries. One method of enhancing sockeye salmon populations is to use a streamside egg incubation box from which the fry are automatically released into the stream as they emerge from the gravel. In this system, however, IHN epizootics occur as the fry emerge and continue for up to two months after the fry leave the box (Mulcahy, unpublished data). In as much as the high density of eggs and alevins in incubation boxes might be conducive to the fulmination of an IHN epizootic, we varied the egg density in incubation boxes and studied the cffect on mortality caused by IHN.

  7. Surgical treatment of ulcers caused by extravasation of cytotoxic drugs.

    PubMed

    D'Andrea, Francesco; Onesti, Maria Giuseppina; Nicoletti, Giovanni Francesco; Grella, Elisa; Renzi, Luca Francesco; Spalvieri, Cristina; Scuderi, Nicolò

    2004-01-01

    Despite preventive measures, the extravasation of cytotoxic drugs still occurs in 0.6% to 6% of cases. The aetiology is thought to be that tissue necrosis develops into a chronic ulcer, which causes problems if the harmful action of the drug is not blocked. From 1988-2002 at the Department of Plastic Surgery of Rome University "La Sapienza", 240 patients presented with extravasation of cytotoxic drugs; all had been treated with an original conservative protocol first described in 1994, based on the repeated local infiltration of a large quantity of saline solution (90-540 ml) into the area of extravasation. We considered only cases with actively necrotic lesions. Eleven of the 240 patients (5%) had ulcers ranging from small ulcers to extensive areas of tissue necrosis. Of the 11 patients, eight had already had ulcers, while the remaining three were those in whom our conservative protocol had not prevented necrosis. They were all operated on and given grafts, local flaps, reverse radial flaps, and free flaps.

  8. An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis

    PubMed Central

    Tokala, Madhusudhan R.; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R.

    2016-01-01

    Acute esophageal necrosis (AEN), also called “black esophagus,” is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN. PMID:27642529

  9. The antileishmanial drug miltefosine (Impavido(®)) causes oxidation of DNA bases, apoptosis, and necrosis in mammalian cells.

    PubMed

    Castelo Branco, Patrícia Valéria; Soares, Rossy-Eric Pereira; de Jesus, Luís Cláudio Lima; Moreira, Vanessa Ribeiro; Alves, Hugo José; de Castro Belfort, Marta Regina; Silva, Vera Lucia Maciel; Ferreira Pereira, Silma Regina

    2016-08-01

    Miltefosine was developed to treat skin cancer; further studies showed that the drug also has activity against Leishmania. Miltefosine is the first oral agent for treating leishmaniasis. However, its mechanism of action is not completely understood. We have evaluated the induction of DNA damage by miltefosine. Cytotoxicity and genotoxicity (comet assay) tests were performed on human leukocytes exposed to the drug in vitro. Apoptosis and necrosis were also evaluated. In vivo tests were conducted in Swiss male mice (Mus musculus) treated orally with miltefosine. Oxidation of DNA bases in peripheral blood cells was measured using the comet assay followed by digestion with formamidopyrimidine glycosylase (FPG), which removes oxidized guanine bases. The micronucleus test was performed on bone marrow erythrocytes. Miltefosine caused DNA damage, apoptosis, and necrosis in vitro. Mice treated with miltefosine showed an increase in the DNA damage score, which was further increased following FPG digestion. The micronucleus test was also positive. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. TOXICOLOGIC STUDIES ON POLYPHENYL COMPOUNDS USED AS ATOMIC REACTOR MODERATOR-COOLANTS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haley, T.J.; Detrick, L.E.; Komesu, N.

    1959-09-01

    A study has been made of certain aspects of the toxicology of organic polyphenyl compounds proposed for use as moderator-coolants in atomic reactors. Only monoisopropylbiphenyl, irradiated monoisopropylbiphenyl, and terphenyl mixtures (OMRE) were irritating to the conjunctiva in rabbits and oniy the unirradiated moderator-coolants caused skin irritation in rabbits. Both the moderators and their components were highly damaging to guinea pig skin following intracutaneous injection. All the polyphenyl compounds except irradiated monoisopropylbiphenyl produced sensitization and chemical necrosis. The latter produced only necrosis. Monoisopropylbiphenyl and o- and m-terphenyl were the only polyphenyls that caused death after inhalation, although all of the compoundsmore » produced some of the following symptoms: nasal congestion with rhinitis, lachrymation, labored respiration, and erythema of the ears and paws. The following histopathologic changes were also observed: acute tracheal necrosis, acute tracheobronchitis, pulmonary edema, bronchopneumonia, atelectasis, and petechial hemorrhages. All such toxic effects can be prevented by protective clothing and respirators. (auth)« less

  11. Necroptosis contributes to methamphetamine-induced cytotoxicity in rat cortical neurons.

    PubMed

    Xiong, Kun; Liao, Huidan; Long, Lingling; Ding, Yanjun; Huang, Jufang; Yan, Jie

    2016-09-01

    Necroptosis, a programmed necrosis, is involved in various types of neurodegenerative diseases. In this study, we investigated whether necroptosis contributed to neuronal damage in a methamphetamine injury model. Primary cultures of embryonic cortical neurons from Sprague-Dawley rats were subjected to different doses of methamphetamine with/without pre-treatment with a specific necroptosis inhibitor, Necrostatin-1. Necrosis was assessed by determining lactate dehydrogenase release and by Annexin V/propidium iodide double staining, while the neuronal ultra-structure was examined by electron microscopy. Tumor necrosis factor-α protein levels were determined by enzyme-linked immunosorbent assay. At early stages (12h) of post-treatment with methamphetamine, significant necrosis occurred and the viability of neurons decreased in a dose- and time-dependent manner in this model of acute neuronal injury. Pretreatment with Necrostatin-1 led to significant neuronal preservation compared with the methamphetamine-treated groups. Furthermore, tumor necrosis factor-α expression increased in a dose-dependent manner following methamphetamine exposure. Methamphetamine induced necrosis in rat cortical neurons in vitro, both time and dose dependently, and necroptosis may be an important newly identified mode of cortical neuronal death caused by single high-dose methamphetamine administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. HOW to Differentiate Dutch Elm Disease from Elm Phloem Necrosis

    Treesearch

    Lester Paul Gibson; Arthur R. Hastings; Leon A. LeMadeliene

    1981-01-01

    Dutch elm disease (DED) and elm phloem necrosis are the two most serious diseases of elm in the United States (Figs. 1 and 2). Most native species of elm are susceptible to both diseases. Dutch elm disease is caused by a fungus, Ceratocystis u1mi (Buisman) C. Moreau, and is transmitted by two species of elm bark beetles-the smaller European elm bark beetle, Scolytus...

  13. Attenuation of cadmium-induced necrotic cell death by necrostatin-1: Potential necrostatin-1 acting sites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hsu, T.-S.; Yang, P.-M.; Tsai, J.-S.

    2009-03-01

    Cadmium (Cd) induces necrotic death in Chinese hamster ovary (CHO) K1 cells and we have established the responsible signaling pathway. Reportedly, necrostatin-1 (Nec-1) rescues cells from necrotic death by mediating through the death domain receptor (DR) signaling pathway. We show here that Nec-1 also effectively attenuates necrotic death triggered by Cd. Two other treatments that cause necrotic cell death, one can (z-VAD-fmk/TNF-{alpha} on U937 cells) and the other cannot (etherynic acid (EA) on DLD-1 cells) be rescued by Nec-1, were also studied in parallel for comparison. Results show that Nec-1 is ineffectual in modulating intracellular calcium contents, calpain activity (amore » downstream protease), or reactive oxygen species production. It can counteract the reduction in mitochondrial membrane potential (MMP) caused by treating CHO K1 or U937 cells with necrosis-inducing agent. However, this effect was not found in EA-treated DLD-1 cells. Notably, Nec-1 elevates NF-{kappa}B activity in the presence or absence of necrosis-inducing agents. Our study shows that, in addition to DR-mediated necrosis, Nec-1 is effective in attenuating Cd-induced necrosis. It rescues cells with reduced MMP implying that mitochondrion is its major acting site.« less

  14. Diagnostic accuracy of 3T magnetic resonance imaging in the preoperative localisation of parathyroid adenomas: comparison with ultrasound and 99mTc-sestamibi scans.

    PubMed

    Argirò, Renato; Diacinti, Daniele; Sacconi, Beatrice; Iannarelli, Angelo; Diacinti, Davide; Cipriani, Cristiana; Pisani, Daniela; Romagnoli, Elisabetta; Biffoni, Marco; Di Gioia, Cira; Pepe, Jessica; Bezzi, Mario; Letizia, Claudio; Minisola, Salvatore; Catalano, Carlo

    2018-05-07

    To evaluate the diagnostic performance of 3TMRI in comparison with ultrasound (US) and 99mTc-sestamibi scan for presurgical localisation of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT). Fifty-seven patients affected by PHPT were prospectively enrolled and underwent US, 99mTc-sestamibi and 3TMRI. T2-weighted and post-contrast T1-weighted Iterative decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) sequences were acquired. Diagnostic performance of US, 99mTc-sestamibi and MRI in localising PTAs to correct quadrant were compared according to surgical and pathological findings. According to surgical findings, US correctly localised 41/46 PTAs (sensitivity of 89.1%; specificity 97.5%; PPV 93.1% and NPV 95.6%); 99mTc-sestamibi correctly localised 38/46 PTAs (sensitivity 83.6%, specificity 98.3%, PPV 95% and NPV 93.7%). US and 99mTc-sestamibi combined had a sensitivity of 93.4% (43/46 PTAs), specificity of 98.3%, PPV 95% and NPV 98.3%. MRI correctly localised 45/46 PTAs (sensitivity 97.8%; specificity 97.5%; PPV 93.7% and NPV 99.2%). MRI was able to detect six adenomas missed by 99mTc-sestamibi and two adenomas missed by US. MRI and US were able to detect all enlarged parathyroid glands in patients with multiglandular disease. MRI identified six of seven ectopic adenomas. Our study demonstrated high diagnostic performance of 3T MRI in the preoperative PTAs quadrant localisation, as well as in patients with multiglandular disease and ectopic PTAs. MRI may be preferred to adequately select patient candidates for minimally invasive parathyroidectomy (MIP). • PTA(s) quadrant localisation by 3TMRI was more accurate than US+99mTc-sestamibi. • MRI identified all enlarged glands in multiglandular disease similarly to US. • MRI identified 6/7 ectopic PTAs similarly to 99mTc-sestamibi. • Presurgical PTA(s) localisation by 3TMRI select the optimal candidates for MIP.

  15. Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS.

    PubMed

    Atkinson, L; Batten, T F C; Moores, T S; Varoqui, H; Erickson, J D; Deuchars, J

    2004-01-01

    Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR depended on the CNS region examined. In the spinal cord, P2X(7)R-IR co-localised with VGLUT2-IR. In the brainstem, co-localisation of P2X(7)R-IR with VGLUT2-IR was widespread, but co-localisation with VGLUT1-IR was seen only in the external cuneate nucleus and spinocerebellar tract region of the ventral medulla. In the cerebellum, P2X(7)R-IR co-localised with both VGLUT1 and VGLUT2-IR in the granular layer. In the hippocampus it was co-localised only with VGLUT1-IR, including in the polymorphic layer of the dentate gyrus and the substantia radiatum of the CA3 region. In other forebrain areas, P2X(7)R-IR co-localised with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate nucleus, amygdala and hypothalamus. Dual labelling studies performed using markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals. These data support our previous hypothesis that the P2X(7)R may play a role in modulating glutamate release in functionally different systems throughout the CNS but further suggest a role in modulating release of inhibitory transmitters in some regions.

  16. Elevated progranulin contributes to synaptic and learning deficit due to loss of fragile X mental retardation protein.

    PubMed

    Zhang, Kun; Li, Yu-Jiao; Guo, Yanyan; Zheng, Kai-Yin; Yang, Qi; Yang, Le; Wang, Xin-Shang; Song, Qian; Chen, Tao; Zhuo, Min; Zhao, Ming-Gao

    2017-12-01

    Fragile X syndrome is an inheritable form of intellectual disability caused by loss of fragile X mental retardation protein (FMRP, encoded by the FMR1 gene). Absence of FMRP caused overexpression of progranulin (PGRN, encoded by GRN), a putative tumour necrosis factor receptor ligand. In the present study, we found that progranulin mRNA and protein were upregulated in the medial prefrontal cortex of Fmr1 knock-out mice. In Fmr1 knock-out mice, elevated progranulin caused insufficient dendritic spine pruning and late-phase long-term potentiation in the medial prefrontal cortex of Fmr1 knock-out mice. Partial progranulin knock-down restored spine morphology and reversed behavioural deficits, including impaired fear memory, hyperactivity, and motor inflexibility in Fmr1 knock-out mice. Progranulin increased levels of phosphorylated glutamate ionotropic receptor GluA1 and nuclear factor kappa B in cultured wild-type neurons. Tumour necrosis factor receptor 2 antibody perfusion blocked the effects of progranulin on GluA1 phosphorylation; this result indicates that tumour necrosis factor receptor 2 is required for progranulin-mediated GluA1 phosphorylation and late-phase long-term potentiation expression. However, high basal level of progranulin in Fmr1 knock-out mice prevented further facilitation of synaptic plasticity by exogenous progranulin. Partial downregulation of progranulin or tumour necrosis factor receptor 2/nuclear factor kappa B signalling restored synaptic plasticity and memory deficits in Fmr1 knock-out mice. These findings suggest that elevated PGRN is linked to cognitive deficits of fragile X syndrome, and the progranulin/tumour necrosis factor receptor 2 signalling pathway may be a putative therapeutic target for improving cognitive deficits in fragile X syndrome. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

    PubMed Central

    2012-01-01

    Background Nephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins. PMID:22899815

  18. [Homicide, suicide or fatal accident?].

    PubMed

    Straka, L; Novomeský, F; Stuller, F; Krajovic, J; Macko, V; Malachovský, I; Hamzík, J

    2011-04-01

    A forensic explanation of womandrinker's death is presented in the article. Exsanguination from multiple cut wounds was cause of death. Origin of wounds was unable to explain due to its atypical character and localisation on body surface. Only a subsequent exact allocation of wounding object made clear biomechanical aspects of wounds. A hard ethanol alteration of psychical, senzorical et motorical functions with strong posttraumatic et toxometabolic changes of the body took share on mechanism of death.

  19. (18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.

    PubMed

    Toyonaga, Takuya; Hirata, Kenji; Yamaguchi, Shigeru; Hatanaka, Kanako C; Yuzawa, Sayaka; Manabe, Osamu; Kobayashi, Kentaro; Watanabe, Shiro; Shiga, Tohru; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Kuge, Yuji; Tamaki, Nagara

    2016-07-01

    Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.

  20. Neuronal NOS localises to human airway cilia.

    PubMed

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    PubMed Central

    Ruane, Peter T.; Gumy, Laura F.; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J.; Hoogenraad, Casper C.; Allan, Victoria J.

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons. PMID:27272132

  2. Acoustic emission source localization based on distance domain signal representation

    NASA Astrophysics Data System (ADS)

    Gawronski, M.; Grabowski, K.; Russek, P.; Staszewski, W. J.; Uhl, T.; Packo, P.

    2016-04-01

    Acoustic emission is a vital non-destructive testing technique and is widely used in industry for damage detection, localisation and characterization. The latter two aspects are particularly challenging, as AE data are typically noisy. What is more, elastic waves generated by an AE event, propagate through a structural path and are significantly distorted. This effect is particularly prominent for thin elastic plates. In these media the dispersion phenomenon results in severe localisation and characterization issues. Traditional Time Difference of Arrival methods for localisation techniques typically fail when signals are highly dispersive. Hence, algorithms capable of dispersion compensation are sought. This paper presents a method based on the Time - Distance Domain Transform for an accurate AE event localisation. The source localisation is found through a minimization problem. The proposed technique focuses on transforming the time signal to the distance domain response, which would be recorded at the source. Only, basic elastic material properties and plate thickness are used in the approach, avoiding arbitrary parameters tuning.

  3. [Pathological changes of the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis].

    PubMed

    Hu, Zhi-ming; Wang, Hai-bin; Zhou, Ming-qian; Yao, Xin-sheng; Ma, Li; Wang, Xiao-ning

    2006-06-01

    To observe the pathological changes in the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis and investigate the pathogenesis of glucocorticoid-induced osteonecrosis. Twenty New Zealand white rabbits were randomly divided into two groups, namely group A. which was injected with horse serum and prednisone and group B as the control group. Chinese ink was injected into the femoral cavity of the rabbits to observe the blood vessels in the femoral head under optical microscope and the femoral head was examined histopathologically. Compared with the normal control group, the rabbits in group A had significantly decreased number of perfused vessels, which was featured by defective perfusion, osteocytie pyknosis or necrosis, increase of empty ostoocyte lacunae and fat cells, decrease of hematopoietic tissue, and blood vessel occlusion. Vascular occlusion and vasculitis due to glucocorticoid treatment may cause avascular necrosis of the femoral head.

  4. [Localised bronchi amyloidosis: a case report].

    PubMed

    Ayadi, Lobna; Khabir, Abdelmajid; Boudawara, Tahya; Makni, Saloua; Rekik, Wajdi Karim; Ayoub, Abdelkader; Jlidi, Rachid

    2004-02-01

    Localised pulmonary amyloïdosis is exceptional. Tracheobronchial symptoms are the most frequent. We report a case of a 68 year-old man complaining of cough and breathlessness. Bronchoscopy showed a submucosal infiltration with stenosis of left upper and lower bronchi. Multiples biopsy were performed and concluded to amyloïdosis of AL type. Our objective is to describe the anatomopathologic aspects of localised pulmonary amyloïdosis and to discuss its pathogeny.

  5. Sensory Perception in the Human Research and Engineering Directorate: Thrust Areas and Recent Research 2011-2014

    DTIC Science & Technology

    2014-09-01

    estimation in an open space. In: Glotin, editor. Soundscape semiotics: localisation and categorisation. Rijeka (Croatia): InTech; 2014. Available at...Glotin H, editor. Soundscape semiotics – localisation and categorisation. Rijeka (Croatia): InTech; 2014. Available at: http://www.intechopen.com...books/ soundscape -semiotics-localisation -and-categorisation/auditory-distance-estimation-in-an-open-space. The purpose of the study was to expand our

  6. Bilateral avascular necrosis of the femoral head due to the use of heroin: A case report.

    PubMed

    Ozkunt, Okan; Sarıyılmaz, Kerim; Sungur, Mustafa; Ilen, Ferhat; Dikici, Fatih

    2015-01-01

    Femoral head avascular necrosis is caused by disruption of the blood supply of the femoral head, which finally results in hip dysfunction. Non traumatic osteonecrosis may related with corticosteroid use, alcohol abuse, SLE, hemoglobinopathies or exposure to cytotoxic agents. But avascular necrosis of the femoral head (ANFH) due to heroin use is a rare condition. We report a patient with bilateral ANFH due to heroin use treated by simultaneous bilateral hip arthroplasty. 37 year-old male patient presented with bilateral hip pain that had been occurring for four years. The patient had no history of smoking, excessive drinking, using corticosteroid and the other drugs or trauma but used heroin for 10 years. In clinic and radiologic examination indicated advanced degenerative changes on both hip due to femoral head avascular necrosis. The patient was treated with simultaneous bilateral total hip arthroplasty. After 6 months postoperatively the active hip range of motion was painless. Avascular femoral head necrosis caused by the using of heroin is rare. Ultimately, osteonecrosis of the femoral head occurs through one final common pathway, which is decreased blood flow to the femoral head that leads bone ischemia and death. But it is still unknown that heroin's systemic effects. Intravenous drug use more as a serious problem for today. There is a need for comprehensive studies to demonstrate effects of heroin on bone and vascularity metabolism. Heroin use will be important problem for population. That's why is crucial to understand the effect of heroin. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Radioguided localisation of impalpable breast lesions using 99m-Technetium macroaggregated albumin: Lessons learnt during introduction of a new technique to guide preoperative localisation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Landman, Joanne; Kulawansa, Sagarika; McCarthy, Michael

    2015-03-15

    Preoperative wire-guided localisation (WGL) of impalpable breast lesions is widely used but can be technically difficult. Risks include wire migration, inaccurate placement, and inadequate surgical margins. Research shows that radioguided occult lesion localisation (ROLL) is quicker, easier, and can improve surgical and cosmetic outcomes. An audited introduction of ROLL was conducted to validate the technique as a feasible alternative to WGL. Fifty patients with single impalpable lesions and biopsy proven malignancy or indeterminate histology underwent WGL followed by intralesional radiopharmaceutical injection of 99m-Technetium macroaggregated albumin. Postprocedural mammography was performed to demonstrate wire position, and scintigraphy to evaluate radiopharmaceutical migration. Lymphoscintigraphymore » and intraoperative sentinel node biopsy were performed if indicated, followed by lesion localisation and excision using a gamma probe. Specimen imaging was performed, with immediate reexcision for visibly inadequate margins. Accurate localisation was achieved in 86% of patients with ROLL compared to 72% with WGL. All lesions were successfully removed, with clear margins in 71.8% of malignant lesions. Reexcision and intraoperative sentinel node localisation rates were equivalent to preaudit figures for WGL. ROLL was easy to perform and problems were infrequent. Inaccurate radiopharmaceutical placement necessitating WGL occurred in four patients. Minor radiopharmaceutical migration was common, but precluded using ROLL in only two cases. ROLL is effective, simple, inexpensive, and easily learnt; however, preoperative confirmation of correct radiopharmaceutical placement using mammography and the gamma probe is important to help ensure successful lesion removal. Insertion of a backup hookwire is recommended during the initial introduction of ROLL.« less

  8. Fukunaga-Koontz feature transformation for statistical structural damage detection and hierarchical neuro-fuzzy damage localisation

    NASA Astrophysics Data System (ADS)

    Hoell, Simon; Omenzetter, Piotr

    2017-07-01

    Considering jointly damage sensitive features (DSFs) of signals recorded by multiple sensors, applying advanced transformations to these DSFs and assessing systematically their contribution to damage detectability and localisation can significantly enhance the performance of structural health monitoring systems. This philosophy is explored here for partial autocorrelation coefficients (PACCs) of acceleration responses. They are interrogated with the help of the linear discriminant analysis based on the Fukunaga-Koontz transformation using datasets of the healthy and selected reference damage states. Then, a simple but efficient fast forward selection procedure is applied to rank the DSF components with respect to statistical distance measures specialised for either damage detection or localisation. For the damage detection task, the optimal feature subsets are identified based on the statistical hypothesis testing. For damage localisation, a hierarchical neuro-fuzzy tool is developed that uses the DSF ranking to establish its own optimal architecture. The proposed approaches are evaluated experimentally on data from non-destructively simulated damage in a laboratory scale wind turbine blade. The results support our claim of being able to enhance damage detectability and localisation performance by transforming and optimally selecting DSFs. It is demonstrated that the optimally selected PACCs from multiple sensors or their Fukunaga-Koontz transformed versions can not only improve the detectability of damage via statistical hypothesis testing but also increase the accuracy of damage localisation when used as inputs into a hierarchical neuro-fuzzy network. Furthermore, the computational effort of employing these advanced soft computing models for damage localisation can be significantly reduced by using transformed DSFs.

  9. bicoid RNA localization requires specific binding of an endosomal sorting complex

    PubMed Central

    Irion, Uwe; St Johnston, Daniel

    2007-01-01

    Summary paragraph: bicoid mRNA localises to the anterior of the Drosophila egg, where it is translated to form a morphogen gradient of Bicoid protein that patterns the head and thorax of the embryo. Although bicoid was the first identified localised cytoplasmic determinant1-4, little is known about how the mRNA is coupled to the microtubule-dependent transport pathway that targets it to the anterior, and it has been proposed that it is recognised by a complex of many redundant proteins, each of which binds to the localisation element in its 3'UTR with little or no specificity5. Indeed, the only known RNA-binding protein that co-localises with bicoid mRNA is Staufen, which binds non-specifically to dsRNA in vitro6, 7. Here we show that mutants in all subunits of the ESCRT-II complex (Vps22, Vps25 and Vps36) abolish the final Staufen-dependent step in bcd RNA localisation. ESCRT-II is a highly conserved component of the pathway that sorts ubiquitinated endosomal proteins into internal vesicles8, 9, and functions as a tumour-suppressor by removing activated receptors from the cytoplasm10, 11. However, the role of ESCRT-II in bicoid localisation appears to be independent of endosomal sorting, because mutations in ESCRT-I and III components have no effect of the targeting of bicoid mRNA. Instead, Vps36 functions by binding directly and specifically to stem-loop V of the bicoid 3'UTR through its N-terminal GLUE domain12, making it the first example of a sequence specific RNA-binding protein that recognises the bicoid localisation signal. Furthermore, Vps36 localises to the anterior of the oocyte in a bicoid mRNA-dependent manner, and is required for the subsequent recruitment of Staufen to the bicoid complex. This novel function of ESCRT-II as an RNA-binding complex is conserved in vertebrates, and may explain some of its roles that are independent of endosomal sorting. PMID:17268469

  10. Gastric necrosis and perforation in a patient with Asperger's syndrome.

    PubMed

    Hicks, Georgina; D'Souza, Nigel; Thomas, Rhys; Brar, Ranjeet

    2017-09-27

    Acute gastric necrosis is a very rare but potentially fatal condition which has been reported in patients with abnormal eating behaviours.We describe the case of a 24-year-old female with a background of Asperger's syndrome, who presented with abdominal pain and gross distension. She underwent an emergency exploratory laparotomy and was found to have a massively distended, necrotic stomach. A total gastrectomy was performed with interval reconstruction planned. This case reports the surgical management of a rarely seen condition and highlights the importance of recognising gastric necrosis and its causes, which include patients with abnormal eating behaviours, the majority of whom are young females. This is the first report highlighting gastric necrosis in a patient with Asperger's syndrome and coincides with a growing recognition of the association between eating disorders and the autistic spectrum. It is also a rare example of patient survival following total gastric necrosis with perforation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis.

    PubMed

    Fu, Qiang; Chang, Yuan; An, Huimin; Fu, Hangcheng; Zhu, Yu; Xu, Le; Zhang, Weijuan; Xu, Jiejie

    2015-12-01

    Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time. We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models. The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years. Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.

  12. Preoperative imaging and prediction of oesophageal conduit necrosis after oesophagectomy for cancer.

    PubMed

    Lainas, P; Fuks, D; Gaujoux, S; Machroub, Z; Fregeville, A; Perniceni, T; Mal, F; Dousset, B; Gayet, B

    2017-09-01

    Oesophageal conduit necrosis following oesophagectomy is a rare but life-threatening complication. The present study aimed to assess the impact of coeliac axis stenosis on outcomes after oesophagectomy for cancer. The study included consecutive patients who had an Ivor Lewis procedure with curative intent for middle- and lower-third oesophageal cancer at two tertiary referral centres. All patients underwent preoperative multidetector CT with arterial phase to detect coeliac axis stenosis. The coeliac artery was classified as normal, with extrinsic stenosis due to a median arcuate ligament or with intrinsic stenosis caused by atherosclerosis. Some 481 patients underwent an Ivor Lewis procedure. Of these, ten (2·1 per cent) developed oesophageal conduit necrosis after surgery. Coeliac artery evaluation revealed a completely normal artery in 431 patients (91·5 per cent) in the group without conduit necrosis and in one (10 per cent) with necrosis (P < 0·001). Extrinsic stenosis of the coeliac artery due to a median arcuate ligament was found in two patients (0·4 per cent) without conduit necrosis and five (50 per cent) with necrosis (P < 0·001). Intrinsic stenosis of the coeliac artery was found in 11 (2·3 per cent) and eight (80 per cent) patients respectively (P < 0·001). Eight patients without (1·7 per cent) and five (50 per cent) with conduit necrosis had a single and thin left gastric artery (P < 0·001). This study suggests that oesophageal conduit necrosis after oesophagectomy for cancer may be due to pre-existing coeliac axis stenosis. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  13. Cell Toxicity in Fibroblasts, Tenocytes, and Human Mesenchymal Stem Cells-A Comparison of Necrosis and Apoptosis-Inducing Ability in Ropivacaine, Bupivacaine, and Triamcinolone.

    PubMed

    Zhang, Anja Z; Ficklscherer, Andreas; Gülecyüz, Mehmet F; Paulus, Alexander C; Niethammer, Thomas R; Jansson, Volkmar; Müller, Peter E

    2017-04-01

    To analyze the ability of ropivacaine, bupivacaine, and triamcinolone to induce apoptosis and necrosis in fibroblasts, tenocytes, and human mesenchymal stem cells. Human dermal fibroblasts, adipose-derived human mesenchymal stem cells (hMSCs), and tenocytes gained from the rotator cuff tendon were seeded with a cell density of 0.5 × 10 4 /cm 2 . One specimen of ropivacaine, bupivacaine, and triamcinolone was tested separately on the cells with separate concentrations of 0.5%, 0.25%, and 0.125% for each specimen. The negative control received no agent, only a change of medium. The incubation period for each agent was 30 minutes. After a change of medium and 1 hour, 24 hours, and 7 days of incubation, 10 4  cells were harvested and analyzed via fluorescence-activated cell sorting with double-staining with annexin V and propidium iodide. Statistical analysis to determine significant difference (P < .05) between the groups with SPSS statistics 23 through one-way analysis of variance with a univariate general linear model was performed. Bupivacaine showed necrosis-inducing effects on fibroblasts and tenocytes, with the necrotic effect peaking at 0.5% and 0.25%. Ropivacaine and triamcinolone caused no significant necrosis. Compared with fibroblasts and tenocytes, hMSCs did not show significant necrotic or apoptotic effects after exposure to bupivacaine. Overall, no significant differences in apoptosis were detected between different cell lines, varying concentrations, or time measurements. Bupivacaine 0.5% and 0.25% have the most necrosis-inducing effects on fibroblasts and tenocytes. Ropivacaine caused less necrosis than bupivaine. Compared with fibroblasts and tenocytes, hMSCs were not affected by necrosis using any of the tested agents. A significant apoptosis-inducing effect could not be detected for the different cell lines. Possible cell toxicity raises questions of concern for intra-articular injections using local anesthetics and corticosteroids. The present study demonstrates the necrotic and apoptotic effects of ropivacaine, bupivacaine, and triamcinolone and may give recommendations for intra-articular use of local anesthetics and corticosteroids. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  14. Vergence Neural Pathways: A Systematic Narrative Literature Review

    PubMed Central

    Searle, Annabelle; Rowe, Fiona J.

    2016-01-01

    ABSTRACT Research in the neural pathway for vergence is less understood in comparison to the other four visual eye movements. The aim of this study was to review the literature on vergence neural pathways and associated disorders. A review of previous published literature though to March 2016 was conducted. Intracranial pathologies that affect entire neural functioning were found to cause convergence insufficiencies. In contrast, pathologies with a more localised intracranial lesion cause more specific vergence disorders. There is debate as to the potential presence of a “divergence centre.” Detailed information on the divergence pathway is lacking and warrants further research. PMID:27928407

  15. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy.

    PubMed

    Rosas-Vargas, H; Bahi-Buisson, N; Philippe, C; Nectoux, J; Girard, B; N'Guyen Morel, M A; Gitiaux, C; Lazaro, L; Odent, S; Jonveaux, P; Chelly, J; Bienvenu, T

    2008-03-01

    Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.

  16. Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.

    PubMed

    Schaletzki, Yvonne; Kromrey, Marie-Luise; Bröderdorf, Susanne; Hammer, Elke; Grube, Markus; Hagen, Paul; Sucic, Sonja; Freissmuth, Michael; Völker, Uwe; Greinacher, Andreas; Rauch, Bernhard H; Kroemer, Heyo K; Jedlitschky, Gabriele

    2017-01-05

    The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit β3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.

  17. Exploring anti-bacterial compounds against intracellular Legionella.

    PubMed

    Harrison, Christopher F; Kicka, Sébastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

    2013-01-01

    Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an 'accidental' human pathogen and cause a severe pneumonia known as Legionnaires' disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target.

  18. Can glacial shearing of sediment reset the signal used for luminescence dating?

    NASA Astrophysics Data System (ADS)

    Bateman, Mark D.; Swift, Darrel A.; Piotrowski, Jan A.; Rhodes, Edward J.; Damsgaard, Anders

    2018-04-01

    Understanding the geomorphology left by waxing and waning of former glaciers and ice sheets during the late Quaternary has been the focus of much research. This has been hampered by the difficulty in dating such features. Luminescence has the potential to be applied to glacial sediments but requires signal resetting prior to burial in order to provide accurate ages. This paper explores the possibility that, rather than relying on light to reset the luminescence signal, glacial processes underneath ice might cause resetting. Experiments were conducted on a ring-shear machine set up to replicate subglacial conditions and simulate the shearing that can occur within subglacial sediments. Luminescence measurement at the single grain level indicates that a number (albeit small) of zero-dosed grains were produced and that these increased in abundance with distance travelled within the shearing zone. Observed changes in grain shape characteristics with increasing shear distance indicate the presence of localised high pressure grain-to-grain stresses caused by grain bridges. This appears to explain why some grains became zeroed whilst others retained their palaeodose. Based on the observed experimental trend, it is thought that localised grain stress is a viable luminescence resetting mechanism. As such relatively short shearing distances might be sufficient to reset a small proportion of the luminescence signal within subglacial sediments. Dating of previously avoided subglacial sediments may therefore be possible.

  19. [Avascular necrosis of the femoral head].

    PubMed

    Porubský, Peter; Trč, Tomáš; Havlas, Vojtěch; Smetana, Pavel

    Avascular necrosis of the femoral head in adults is not common, but not too rare diseases. In orthopedic practice, it is one of the diseases that are causing implantation of hip replacement at a relatively early age. In the early detection and initiation of therapy can delay the implantation of prosthesis for several years, which is certainly more convenient for the patient and beneficial. This article is intended to acquaint the reader with the basic diagnostic procedures and therapy.

  20. Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

    NASA Astrophysics Data System (ADS)

    Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der

    2015-09-01

    Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

  1. Assessing the Nature of the Distribution of Localised States in Bulk GaAsBi.

    PubMed

    Wilson, Tom; Hylton, Nicholas P; Harada, Yukihiro; Pearce, Phoebe; Alonso-Álvarez, Diego; Mellor, Alex; Richards, Robert D; David, John P R; Ekins-Daukes, Nicholas J

    2018-04-24

    A comprehensive assessment of the nature of the distribution of sub band-gap energy states in bulk GaAsBi is presented using power and temperature dependent photoluminescence spectroscopy. The observation of a characteristic red-blue-red shift in the peak luminescence energy indicates the presence of short-range alloy disorder in the material. A decrease in the carrier localisation energy demonstrates the strong excitation power dependence of localised state behaviour and is attributed to the filling of energy states furthest from the valence band edge. Analysis of the photoluminescence lineshape at low temperature presents strong evidence for a Gaussian distribution of localised states that extends from the valence band edge. Furthermore, a rate model is employed to understand the non-uniform thermal quenching of the photoluminescence and indicates the presence of two Gaussian-like distributions making up the density of localised states. These components are attributed to the presence of microscopic fluctuations in Bi content, due to short-range alloy disorder across the GaAsBi layer, and the formation of Bi related point defects, resulting from low temperature growth.

  2. Assessment of localisation to auditory stimulation in post-comatose states: use the patient’s own name

    PubMed Central

    2013-01-01

    Background At present, there is no consensus on how to clinically assess localisation to sound in patients recovering from coma. We here studied auditory localisation using the patient’s own name as compared to a meaningless sound (i.e., ringing bell). Methods Eighty-six post-comatose patients diagnosed with a vegetative state/unresponsive wakefulness syndrome or a minimally conscious state were prospectively included. Localisation of auditory stimulation (i.e., head or eyes orientation toward the sound) was assessed using the patient’s own name as compared to a ringing bell. Statistical analyses used binomial testing with bonferroni correction for multiple comparisons. Results 37 (43%) out of the 86 studied patients showed localisation to auditory stimulation. More patients (n=34, 40%) oriented the head or eyes to their own name as compared to sound (n=20, 23%; p<0.001). Conclusions When assessing auditory function in disorders of consciousness, using the patient’s own name is here shown to be more suitable to elicit a response as compared to neutral sound. PMID:23506054

  3. Physical analysis on laser-induced cerebral damage

    NASA Astrophysics Data System (ADS)

    Luo, Xiaosen; Liu, Jiangang; Tao, Chunkan; Lan, Xiufeng; Cao, Lingyan; Pan, Weimin; Shen, Zhonghua; Lu, Jian; Ni, Xiaowu

    2005-01-01

    Experimental investigation on cerebral damage of adult SD rats induced by 532nm CW laser was performed. Tissue heat conductive equation was set up based on two-layered structure model. Finite difference algorithm was utilized to numerically simulate the temperature distribution in the brain tissue. Allowing for tissue response to temperature variation, free boundary model was used to discuss tissue thermal coagulation formation in brain. Experimental observations show that thermal coagulation and necrosis can be caused due to laser light absorption. The result of the calculation shows that the process of the thermal coagulation of the given mode comprises two stages: fast and slow. At the first stage, necrosis domain grows fast. Then necrosis domain growth becomes slower because of the competition between the heat diffusion into the surrounding undamaged tissue and the heat dissipation caused by blood perfusion. At the center of coagulation area no neuron was observed and at the transitional zone few nervous cells were seen by microscope. The research can provide reference data for developing clinical therapy of some kind of encephalic diseases by using 532nm laser, and for making cerebral infarction models in animal experiment.

  4. Identification of a second family of genes in Moniliophthora perniciosa, the causal agent of witches' broom disease in cacao, encoding necrosis-inducing proteins similar to cerato-platanins.

    PubMed

    Zaparoli, Gustavo; Cabrera, Odalys García; Medrano, Francisco Javier; Tiburcio, Ricardo; Lacerda, Gustavo; Pereira, Gonçalo Guimarães

    2009-01-01

    The hemibiotrophic basidiomycete Moniliophthora perniciosa is the causal agent of witches' broom disease in cacao. This is a dimorphic species, with monokaryotic hyphae during the biotrophic phase, which is converted to dikaryotic mycelia during the saprophytic phase. The infection in pod is characterized by the formation of hypertrophic and hyperplasic tissues in the biotrophic phase, which is followed by necrosis and complete degradation of the organ. We found at least five sequences in the fungal genome encoding putative proteins similar to cerato-platanin (CP)-like proteins, a novel class of proteins initially found in the phytopathogen Ceratocystis fimbriata. One M. perniciosa CP gene (MpCP1) was expressed in vitro and proved to have necrosis-inducing ability in tobacco and cacao leaves. The protein is present in solution as dimers and is able to recover necrosis activity after heat treatment. Transcription analysis ex planta showed that MpCP1 is more expressed in biotrophic-like mycelia than saprotrophic mycelia. The necrosis profile presented is different from that caused by M. perniciosa necrosis and ethylene-inducing proteins (MpNEPs), another family of elicitors expressed by M. perniciosa. Remarkably, a mixture of MpCP1 with MpNEP2 led to a synergistic necrosis effect very similar to that found in naturally infected plants. This is the first report of a basidiomycete presenting both NEP1-like proteins (NLPs) and CPs in its genome.

  5. An experimental study of the pathogenicity of a duck hepatitis A virus genotype C isolate in specific pathogen free ducklings.

    PubMed

    Zhang, Huanrong; Pi, JinKui; Tang, Cheng; Yue, Hua; Yang, Falong

    2012-12-01

    Duck hepatitis A virus genotype C (DHAV-C), recognized recently, is one of the pathogens causing fatal duck viral hepatitis in ducklings, especially in Asia. To demonstrate the pathogenesis of the DHAV-C isolate, 3-day-old specific pathogen free ducklings were inoculated subcutaneously with a DHAV-C isolate and the clinical signs were observed. Virus distribution, histological and apoptotic morphological changes of various tissues were examined at different times post inoculation. The serial, characteristic changes included haemorrhage and swelling of the liver. Apoptotic cells and virus antigen staining were found in all of the tissues examined. Where more virus antigen staining was detected, there were more severe histopathological and apoptotic changes. The amount of virus antigen and the histological and apoptotic morphological changes agreed with each other and became increasingly severe with length of time after infection. Apoptotic cells were ubiquitously distributed, especially among lymphocytes, macrophages and monocytes in immune organs such as the bursa of Fabricius, thymus and spleen, and in liver, kidney and cerebral cells. Necrosis was also observed within 72 h post inoculation in all organs examined, except the cerebrum, and was characterized by cell swelling and collapsed plasma membrane. These results suggest that the recent outbreak of disease caused by DHAV-C virus is pantropic, causing apoptosis and necrosis of different organs. The apoptosis and necrosis caused by the DHAV-C field strain in this study is associated with pathogenesis and DHAV-C-induced lesions.

  6. Changing picture of renal cortical necrosis in acute kidney injury in developing country

    PubMed Central

    Prakash, Jai; Singh, Vijay Pratap

    2015-01-01

    Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients. PMID:26558184

  7. Enantioselective cellular localisation of europium(iii) coordination complexes† †Electronic supplementary information (ESI) available: Complex synthesis and characterisation, selected cell images showing correspondence with commercial lysosomal or mitochondrial stains and spectral imaging profiles. See DOI: 10.1039/c7sc04422d

    PubMed Central

    Frawley, Andrew T.; Linford, Holly V.; Starck, Matthieu; Pal, Robert

    2017-01-01

    The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis. PMID:29675151

  8. Surgical hazards posed by marine and freshwater animals in Florida.

    PubMed

    Howard, R J; Burgess, G H

    1993-11-01

    Marine and freshwater animals can cause injury to humans by biting, stinging, being poisonous to eat, and causing infections. Biting aquatic animals in Florida include sharks, barracudas, alligators, and moray eels. Devitalized tissue should be débrided, and vascular, neurologic, and tendinous injuries should be repaired. Radiographs should be obtained to examine the injury sit for fractures and retained foreign bodies (teeth). The spines of stingrays and marine catfish can cause soft tissue injury and infection. The spine has a recurved, serrated shape that may cause further injury and break if it is pulled out. The venom may cause local tissue necrosis requiring débridement. Soft tissue infections with marine Vibrio bacteria can occur after eating raw oysters or receiving even minor injuries from marine animals. Thirty-one individuals developed soft tissue infections, 49 developed sepsis, and 23 developed both sepsis and soft tissue infection with marine Vibrio species during a 12-year period. Sixteen patients developed necrotizing soft tissue infections. Treatment is with antibiotics and débridement when necrosis occurs.

  9. Chlorinated lime poisoning

    MedlinePlus

    ... AND AIRWAYS Breathing difficulty (from breathing in the chlorinated lime) Throat swelling (which may also cause breathing difficulty) SKIN Burns Holes (necrosis) in the skin or tissues underneath Irritation

  10. Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl polyamine derivatives.

    PubMed

    Pavlov, V; Kong Thoo Lin, P; Rodilla, V

    2001-07-31

    Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.

  11. Reflecting on the mirror neuron system in autism: a systematic review of current theories.

    PubMed

    Hamilton, Antonia F de C

    2013-01-01

    There is much interest in the claim that dysfunction of the mirror neuron system in individuals with autism spectrum condition causes difficulties in social interaction and communication. This paper systematically reviews all published studies using neuroscience methods (EEG/MEG/TMS/eyetracking/EMG/fMRI) to examine the integrity of the mirror system in autism. 25 suitable papers are reviewed. The review shows that current data are very mixed and that studies using weakly localised measures of the integrity of the mirror system are hard to interpret. The only well localised measure of mirror system function is fMRI. In fMRI studies, those using emotional stimuli have reported group differences, but studies using non-emotional hand action stimuli do not. Overall, there is little evidence for a global dysfunction of the mirror system in autism. Current data can be better understood under an alternative model in which social top-down response modulation is abnormal in autism. The implications of this model and future research directions are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Lionfish envenomation of the hand.

    PubMed

    Patel, M R; Wells, S

    1993-05-01

    Lionfish (Pterois volitans) envenomation of the hand causes excruciating pain and occurs in three grades: (1) erythematous reaction, (2) blister formation, and (3) dermal necrosis. The initial treatment in all cases is to soak the hand in nonscalding water (45 degrees C) until the pain subsides by denaturing the thermolabile venom proteins. The blisters should be immediately excised to prevent dermal necrosis, inasmuch as the blister fluid contains residual active venom. To prevent a hypersensitivity reaction, any further contact with the fish should be avoided.

  13. Hallux amputation after a freshwater stingray injury in the Brazilian Amazon.

    PubMed

    Monteiro, Wuelton Marcelo; Oliveira, Sâmella Silva de; Sachett, Jacqueline de Almeida Gonçalves; Silva, Iran Mendonça da; Ferreira, Luiz Carlos de Lima; Lacerda, Marcus Vinícius Guimarães

    2016-01-01

    Freshwater stingray injuries are a common problem in the Brazilian Amazon, affecting mostly riverine and indigenous populations. These injuries cause severe local and regional pain, swelling and erythema, as well as complications, such as local necrosis and bacterial infection. Herein, we report a case of bacterial infection and hallux necrosis, after a freshwater stingray injury in the Brazilian Amazon, which eventually required amputation. Different antimicrobial regimens were administered at different stages of the disease; however, avoiding amputation through effective treatment was not achieved.

  14. Rin4 Causes Hybrid Necrosis and Race-Specific Resistance in an Interspecific Lettuce Hybrid[W

    PubMed Central

    Jeuken, Marieke J.W.; Zhang, Ningwen W.; McHale, Leah K.; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W.; Visser, Richard G.F.; Niks, Rients E.

    2009-01-01

    Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis. PMID:19855048

  15. Rin4 causes hybrid necrosis and race-specific resistance in an interspecific lettuce hybrid.

    PubMed

    Jeuken, Marieke J W; Zhang, Ningwen W; McHale, Leah K; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W; Visser, Richard G F; Niks, Rients E

    2009-10-01

    Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis.

  16. Comparison of the time taken for localised breast surgery pre- and post-introduction of intra-operative digital specimen mammography.

    PubMed

    Carraro do Nascimento, Vinicius; Bourke, Anita G

    2018-02-01

    More than half of the patients with an impalpable malignant breast lesion have a mammographically detected and imaged-guided localisation, which can be technically challenging for the breast surgeon. Specimen imaging is used to confirm successful excision of the localised index lesion and has improved the operating list efficiency resulting in a higher number of excisions per surgical list. The aim of this study was to evaluate whether introducing IDSM (intra-operative digital specimen mammography) saved operation time for localised breast surgery. A single-centre retrospective review was undertaken to compare the operation time (from incision to wound closure) taken for excision of 114 consecutive image-guided localised impalpable breast lesions, performed using departmental specimen radiography (DSR), 6 months prior to the introduction of IDSM (Hologic, Trident ® ) in March 2013, with the theatre time taken for excision of 121 consecutive image-guided localised impalpable breast lesions in the 6 months following introduction of IDSM. There was no significant difference in mean surgical time, which were 47.8 (±27.3) minutes in the CSR group and 48.8 (±25.7) minutes in the IDSM group. We were expecting to confirm a reduction in theatre time with the introduction of IDSM. Surprisingly, no difference in operating times was demonstrated. Factors that influenced the impact of IDSM included the proximity of the imaging department to the operating theatre. © 2017 The Royal Australian and New Zealand College of Radiologists.

  17. KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

    PubMed

    Alshareeda, A T; Negm, O H; Green, A R; Nolan, C C; Tighe, P; Albarakati, N; Sultana, R; Madhusudan, S; Ellis, I O; Rakha, E A

    2015-06-09

    It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) proteins in breast cancer (BC) is associated with loss-of-function phenotype. This study aims to investigate the biological and clinical significance of the nucleocytoplasmic transport protein karyopherin α-2 (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC. A large (n=1494) and well-characterised series of early-stage invasive BC with a long-term follow-up was assessed for KPNA2 protein by using immunohistochemistry. KPNA2 expression was associated with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, γH2AX, BARD1, UBC9, PIAS1 and CHK1. High level of KPNA2 was associated not only with cytoplasmic localisation of these proteins but also with their low/negative nuclear expression. Positive KPNA2 expression was associated with negative oestrogen receptor and triple-negative phenotype. Survival analysis showed that KPNA2 was associated with poor outcome (P<0.0001), but this effect was not independent of other prognostic variables. This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function.

  18. Subcellular localisations of the CPTI collection of YFP-tagged proteins in Drosophila embryos

    PubMed Central

    Lye, Claire M.; Naylor, Huw W.; Sanson, Bénédicte

    2014-01-01

    A key challenge in the post-genomic area is to identify the function of the genes discovered, with many still uncharacterised in all metazoans. A first step is transcription pattern characterisation, for which we now have near whole-genome coverage in Drosophila. However, we have much more limited information about the expression and subcellular localisation of the corresponding proteins. The Cambridge Protein Trap Consortium generated, via piggyBac transposition, over 600 novel YFP-trap proteins tagging just under 400 Drosophila loci. Here, we characterise the subcellular localisations and expression patterns of these insertions, called the CPTI lines, in Drosophila embryos. We have systematically analysed subcellular localisations at cellularisation (stage 5) and recorded expression patterns at stage 5, at mid-embryogenesis (stage 11) and at late embryogenesis (stages 15-17). At stage 5, 31% of the nuclear lines (41) and 26% of the cytoplasmic lines (67) show discrete localisations that provide clues on the function of the protein and markers for organelles or regions, including nucleoli, the nuclear envelope, nuclear speckles, centrosomes, mitochondria, the endoplasmic reticulum, Golgi, lysosomes and peroxisomes. We characterised the membranous/cortical lines (102) throughout stage 5 to 10 during epithelial morphogenesis, documenting their apico-basal position and identifying those secreted in the extracellular space. We identified the tricellular vertices as a specialized membrane domain marked by the integral membrane protein Sidekick. Finally, we categorised the localisation of the membranous/cortical proteins during cytokinesis. PMID:25294944

  19. Conservative management of distal leg necrosis in lung transplant recipients.

    PubMed

    Aigner, F; Husmann, M; Huber, L C; Benden, C; Schuurmans, M M

    2017-05-01

    Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  20. Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin.

    PubMed

    Yang, Fan; Li, Yuan; Yan, Gege; Liu, Tianyi; Feng, Chao; Gong, Rui; Yuan, Ye; Ding, Fengzhi; Zhang, Lai; Idiiatullina, Elina; Pavlov, Valentin; Han, Zhenbo; Ma, Wenya; Huang, Qi; Yu, Ying; Bao, Zhengyi; Wang, Xiuxiu; Hua, Bingjie; Du, Zhimin; Cai, Benzhi; Yang, Lei

    2017-05-09

    Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls' Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways.

  1. Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin

    PubMed Central

    Yan, Gege; Liu, Tianyi; Feng, Chao; Gong, Rui; Yuan, Ye; Ding, Fengzhi; Zhang, Lai; Idiiatullina, Elina; Pavlov, Valentin; Han, Zhenbo; Ma, Wenya; Huang, Qi; Yu, Ying; Bao, Zhengyi; Wang, Xiuxiu; Hua, Bingjie; Du, Zhimin; Cai, Benzhi; Yang, Lei

    2017-01-01

    Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls’ Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways. PMID:28415572

  2. Cancer and necroptosis: friend or foe?

    PubMed

    Philipp, Stephan; Sosna, Justyna; Adam, Dieter

    2016-06-01

    Regulated cell death is one major factor to ensure homoeostasis in multicellular organisms. For decades, apoptosis was considered as the sole form of regulated cell death, whereas necrosis was believed to be accidental and unregulated. Due to this view, research on necrosis was somewhat neglected, especially in the field of anti-cancer treatment. However, new interest in necrosis has been sparked by the recent discovery of different forms of necrosis that show indeed regulated pathways. More and more studies now address the molecular pathways of regulated necrosis and its connections within the cellular signaling networks. Necroptosis, a subform of regulated necrosis, has so far hardly been focused on with regard to a future treatment of cancer patients and may emerge as a novel and effective approach to eliminate tumor cells. However, and similar to apoptosis, tumor cells can develop resistances against necroptosis to ensure their own survival. In this context, new molecules that enhance necroptosis are currently being identified to overcome such resistances. This review discusses cancer and necroptosis as friends or foes, i.e. the options to exploit necroptosis in anti-cancer therapies ("foes"), but also potential limitations that may block or actually cause necroptosis to act in a protumoral manner ("friends"). The balance between these two possible roles will determine whether necroptosis can indeed be used as a promising tool for early diagnosis of tumors, prevention of metastasis and anti-cancer treatment.

  3. [Necrosis in fingers and toes following local anaesthesia with adrenaline--an urban legend?].

    PubMed

    Finsen, Vilhjalmur

    2013-09-17

    It is often maintained that a local anaesthetic (usually lidocaine) with adrenaline must not be used in fingers and toes because it may cause necrosis due to vascular spasm in end arteries. This review article is an attempt to find evidence to support this warning. Relevant literature was found by means of searches in PubMed limited downwards to 1946 and in EMBASE from 1980 to 2012, and in reference lists. Five review articles on finger necrosis following local anaesthesia concluded that lidocaine with adrenaline does not entail a risk of ischaemic injury. One article found 48 reported cases of finger necrosis in the period 1880 to 2000. Most were from the first half of the 1900s, and none involved lidocaine. Gangrene of part of the finger tip has subsequently been described in one patient with Raynaud's syndrome. No cases of necrosis have been described in a large number of reported accidents in which EpiPen injections contained the same quantity of adrenaline as is found in 60 ml lidocaine with adrenaline. Over a quarter of a million reports have been made of operations on feet, hands, fingers and toes anaesthetised with lidocaine with adrenaline without resulting necrosis. There are no grounds for the warning against using lidocaine with adrenaline in fingers and toes. This anaesthetic offers considerable practical advantages. Care should be taken with infected fingers or fingers with poor circulation.

  4. [The role of core decompression for the treatment of femoral head avascular necrosis in renal transplant recipients].

    PubMed

    Zivcić-Cosić, Stela; Stalekar, Hrvoje; Mamula, Mihaela; Miletić, Damir; Orlić, Lidija; Racki, Sanjin; Cicvarić, Tedi

    2012-10-01

    Avascular bone necrosis is a relatively rare but significant complication in renal transplant recipients because it causes progressive pain and invalidity. It can be the consequence of the action of numerous causative factors, but it is mostly connected to corticosteroid treatment.The underlying pathophysiologic mechanism is a diminished blood flow to the bone leading to necrosis and bone destruction. During the past 25-years period, 570 renal transplantations and five combined kidney and pancreas transplantations were performed in our centre. A part of the patients was lost to follow-up due to the separation of Croatia from the former Republic of Yugoslavia. After transplantation, we revealed aseptic necrosis of the femoral head in five female patients. All patients had a history of treatment with pulse doses of corticosteroids. At transplantation the average age of the patients was 52.2 yrs (range 46 to 62 yrs), and dialytic treatment before transplantation lasted in average 9.2 yrs (range 2.5 to 21.2 yrs). The period between renal transplantation and the development of clinical signs of avascular bone necrosis lasted in average 1.2 yrs (range 0.3 to 2.3 yrs). We will demonstrate our 62-year old female patient with terminal renal failure caused by post-streptococcal glomerulonephritis, who was treated with peritoneal dialysis 2.5 years before renal transplantation. Twenty months before renal transplantation the patient received pulse doses of corticosteroids, together with immunoglobulins and plasmapheresis, for the treatment of an acute polyradiculoneuritis Guillaine Barré. After transplantation a standard immunosuppressive protocol was applied which included tacrolimus, mycophenolate mofetil, corticosteroids and induction with basiliximab. Four months after transplantation the patient started to feel pain in the right hip after longer standing, in addition to the earlier long-lasting problems caused by bilateral coxarthrosis. The pelvic radiograph showed subchondral radiolucencies in the lateral part of the head circumference spreading into the proximal part of the neck of the right femur, which indicated the presence of aseptic necrosis, but these changes could have also been caused by coxarthrosis. Unexpectedly, magnetic resonance imaging (MRI) did not reveal changes characteristic for avascular bone necrosis. Due to the progressively worsening of pain and the radiographic finding, the patient was submitted to decompression surgery of the femoral head. The surgical procedure was performed under diascopic guidance (C-arm) which allowed the correct positioning of a Kuerschner wire. A cannulated drill (diameter 4.0 mm) was placed over the wire and we performed two drillings of the spongiosis of the femoral head through to the subchondral area. Postoperatively, the patient was soon verticalized and advised to walk with crooks during a period of six weeks. This time is necessary to allow the mineralisation and strengthening of the bone which is now better vascularised. The patient recovered well and had no more pain. In renal transplant recipients it is most important to raise suspicion and verify the presence of avascular bone necrosis early, because timely bone decompression surgery can eliminate pain and cure the patient or it can prevent or delay bone destruction. When clinical signs of avascular bone necrosis arise and radiographic or standard MRI findings are negative, additional investigations (i.e. SPECT or MRI with contrast) should be performed to confirm or exclude the diagnosis. In latter phases of the disease, surgical decompression of the femoral head cannot lead to permanent amelioration, and it is inevitable to perform more invasive surgical procedures like "resurfacing" or bone grafting in younger patients, or the implantation of total hip endoprotheses.

  5. Passive RFID Rotation Dimension Reduction via Aggregation

    NASA Astrophysics Data System (ADS)

    Matthews, Eric

    Radio Frequency IDentification (RFID) has applications in object identification, position, and orientation tracking. RFID technology can be applied in hospitals for patient and equipment tracking, stores and warehouses for product tracking, robots for self-localisation, tracking hazardous materials, or locating any other desired object. Efficient and accurate algorithms that perform localisation are required to extract meaningful data beyond simple identification. A Received Signal Strength Indicator (RSSI) is the strength of a received radio frequency signal used to localise passive and active RFID tags. Many factors affect RSSI such as reflections, tag rotation in 3D space, and obstacles blocking line-of-sight. LANDMARC is a statistical method for estimating tag location based on a target tag's similarity to surrounding reference tags. LANDMARC does not take into account the rotation of the target tag. By either aggregating multiple reference tag positions at various rotations, or by determining a rotation value for a newly read tag, we can perform an expected value calculation based on a comparison to the k-most similar training samples via an algorithm called K-Nearest Neighbours (KNN) more accurately. By choosing the average as the aggregation function, we improve the relative accuracy of single-rotation LANDMARC localisation by 10%, and any-rotation localisation by 20%.

  6. Immunogold staining procedure for the localisation of regulatory peptides.

    PubMed

    Varndell, I M; Tapia, F J; Probert, L; Buchan, A M; Gu, J; De Mey, J; Bloom, S R; Polak, J M

    1982-01-01

    The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.

  7. Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif.

    PubMed

    Jespersen, Thomas; Rasmussen, Hanne B; Grunnet, Morten; Jensen, Henrik S; Angelo, Kamilla; Dupuis, Delphine S; Vogel, Lotte K; Jorgensen, Nanna K; Klaerke, Dan A; Olesen, Søren-Peter

    2004-09-01

    KCNQ1 potassium channels are expressed in many epithelial tissues as well as in the heart. In epithelia KCNQ1 channels play an important role in salt and water transport and the channel has been reported to be located apically in some cell types and basolaterally in others. Here we show that KCNQ1 channels are located basolaterally when expressed in polarised MDCK cells. The basolateral localisation of KCNQ1 is not affected by co-expression of any of the five KCNE beta-subunits. We characterise two independent basolateral sorting signals present in the N-terminal tail of KCNQ1. Mutation of the tyrosine residue at position 51 resulted in a non-polarized steady-state distribution of the channel. The importance of tyrosine 51 in basolateral localisation was emphasized by the fact that a short peptide comprising this tyrosine was able to redirect the p75 neurotrophin receptor, an otherwise apically located protein, to the basolateral plasma membrane. Furthermore, a di-leucine-like motif at residues 38-40 (LEL) was found to affect the basolateral localisation of KCNQ1. Mutation of these two leucines resulted in a primarily intracellular localisation of the channel.

  8. Non-Gaussian probabilistic MEG source localisation based on kernel density estimation☆

    PubMed Central

    Mohseni, Hamid R.; Kringelbach, Morten L.; Woolrich, Mark W.; Baker, Adam; Aziz, Tipu Z.; Probert-Smith, Penny

    2014-01-01

    There is strong evidence to suggest that data recorded from magnetoencephalography (MEG) follows a non-Gaussian distribution. However, existing standard methods for source localisation model the data using only second order statistics, and therefore use the inherent assumption of a Gaussian distribution. In this paper, we present a new general method for non-Gaussian source estimation of stationary signals for localising brain activity from MEG data. By providing a Bayesian formulation for MEG source localisation, we show that the source probability density function (pdf), which is not necessarily Gaussian, can be estimated using multivariate kernel density estimators. In the case of Gaussian data, the solution of the method is equivalent to that of widely used linearly constrained minimum variance (LCMV) beamformer. The method is also extended to handle data with highly correlated sources using the marginal distribution of the estimated joint distribution, which, in the case of Gaussian measurements, corresponds to the null-beamformer. The proposed non-Gaussian source localisation approach is shown to give better spatial estimates than the LCMV beamformer, both in simulations incorporating non-Gaussian signals, and in real MEG measurements of auditory and visual evoked responses, where the highly correlated sources are known to be difficult to estimate. PMID:24055702

  9. Domains involved in calcineurin phosphatase inhibition and nuclear localisation in the African swine fever virus A238L protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abrams, Charles C.; Chapman, Dave A.G.; Silk, Rhiannon

    2008-05-10

    The African swine fever virus A238L protein inhibits calcineurin phosphatase activity and activation of NF-{kappa}B and p300 co-activator. An 82 amino acid domain containing residues 157 to 238 at the C-terminus of A238L was expressed in E. coli and purified. This purified A238L fragment acted as a potent inhibitor of calcineurin phosphatase in vitro with an IC{sub 50} of approximately 70 nM. Two putative nuclear localisation signals were identified between residues 80 to 86 (NLS-1) and between residues 203 to 207 overlapping with the N-terminus of the calcineurin docking motif (NLS-2). Mutation of these motifs independently did not reduce nuclearmore » localisation compared to the wild type A238L protein, whereas mutation of both motifs significantly reduced nuclear localisation of A238L. Mutation of the calcineurin docking motif resulted in a dramatic increase in the nuclear localisation of A238L provided an intact NLS was present. We propose that binding of calcineurin to A238L masks NLS-2 contributing to the cytoplasmic retention of A238L.« less

  10. Control of E-cadherin apical localisation and morphogenesis by a SOAP-1/AP-1/clathrin pathway in C. elegans epidermal cells.

    PubMed

    Gillard, Ghislain; Shafaq-Zadah, Massiullah; Nicolle, Ophélie; Damaj, Raghida; Pécréaux, Jacques; Michaux, Grégoire

    2015-05-01

    E-cadherin (E-cad) is the main component of epithelial junctions in multicellular organisms, where it is essential for cell-cell adhesion. The localisation of E-cad is often strongly polarised in the apico-basal axis. However, the mechanisms required for its polarised distribution are still largely unknown. We performed a systematic RNAi screen in vivo to identify genes required for the strict E-cad apical localisation in C. elegans epithelial epidermal cells. We found that the loss of clathrin, its adaptor AP-1 and the AP-1 interactor SOAP-1 induced a basolateral localisation of E-cad without affecting the apico-basal diffusion barrier. We further found that SOAP-1 controls AP-1 localisation, and that AP-1 is required for clathrin recruitment. Finally, we also show that AP-1 controls E-cad apical delivery and actin organisation during embryonic elongation, the final morphogenetic step of embryogenesis. We therefore propose that a molecular pathway, containing SOAP-1, AP-1 and clathrin, controls the apical delivery of E-cad and morphogenesis. © 2015. Published by The Company of Biologists Ltd.

  11. [Novel Anticancer Strategy Targeting Switch Mechanisms in Two Types of Cell Death: Necrosis and Apoptosis].

    PubMed

    Sato, Akira

    2017-01-01

     Two types of cell death, necrosis and apoptosis, are defined in terms of cell death morphological features. We have been studying the mechanisms by which cell death processes are switched during the treatment of mouse tumor FM3A with anticancer, 5-fluoro-2'-deoxyuridine (FUdR): it induces original clone F28-7 to necrosis, but its sub-clone F28-7-A to apoptosis. We identified several such switch regulators of cell death: heat shock protein 90 (HSP90), lamin-B1, cytokeratin-19, and activating transcription factor 3 (ATF3), by using transcriptomic, proteomic analyses and siRNA screening. For example, the inhibition of HSP90 by its inhibitor geldanamycin in F28-7 caused a shift from necrosis to apoptosis. We also observed that the knockdown of lamin-B1, cytokeratin-19, or ATF3 expression in F28-7 resulted in a shift from necrosis to apoptosis. Recently, we used microRNA (miRNA, miR) microarray analyses to investigate the miRNA expression profiles in these sister cells. The miR-351 and miR-743a were expressed at higher levels in F28-7-A than in F28-7. Higher expression of miR-351 or miR-743a in F28-7, induced by transfecting the miR mimics, resulted in a switch of cell death mode: necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in morphological changes, and mode of cell death from apoptosis to necrosis. These findings suggest that the identified cell death regulators may have key roles in switching cell death mode. Possible mechanisms involving cell death regulators in the switch of necrosis or apoptosis are discussed. We propose a novel anticancer strategy targeting the switch regulators of necrosis or apoptosis.

  12. Viral-induced systemic necrosis in plants involves both programmed cell death and the inhibition of viral multiplication, which are regulated by independent pathways.

    PubMed

    Komatsu, Ken; Hashimoto, Masayoshi; Ozeki, Johji; Yamaji, Yasuyuki; Maejima, Kensaku; Senshu, Hiroko; Himeno, Misako; Okano, Yukari; Kagiwada, Satoshi; Namba, Shigetou

    2010-03-01

    Resistant plants respond rapidly to invading avirulent plant viruses by triggering a hypersensitive response (HR). An HR is accompanied by a restraint of virus multiplication and programmed cell death (PCD), both of which have been observed in systemic necrosis triggered by a successful viral infection. Here, we analyzed signaling pathways underlying the HR in resistance genotype plants and those leading to systemic necrosis. We show that systemic necrosis in Nicotiana benthamiana, induced by Plantago asiatica mosaic virus (PlAMV) infection, was associated with PCD, biochemical features, and gene expression patterns that are characteristic of HR. The induction of necrosis caused by PlAMV infection was dependent on SGT1, RAR1, and the downstream mitogen-activated protein kinase (MAPK) cascade involving MAPKKKalpha and MEK2. However, although SGT1 and RAR1 silencing led to an increased accumulation of PlAMV, silencing of the MAPKKKalpha-MEK2 cascade did not. This observation indicates that viral multiplication is partly restrained even in systemic necrosis induced by viral infection, and that this restraint requires SGT1 and RAR1 but not the MAPKKKalpha-MEK2 cascade. Similarly, although both SGT1 and MAPKKKalpha were essential for the Rx-mediated HR to Potato virus X (PVX), SGT1 but not MAPKKKalpha was involved in the restraint of PVX multiplication. These results suggest that systemic necrosis and HR consist of PCD and a restraint of virus multiplication, and that the latter is induced through unknown pathways independent from the former.

  13. Postradiation atrophy of mature bone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ergun, H.; Howland, W.J.

    1980-01-01

    The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiationmore » of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.« less

  14. Giant Cell Arteritis Presenting as Scalp Necrosis

    PubMed Central

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

    2011-01-01

    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. PMID:21789466

  15. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

    PubMed Central

    Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

    2016-01-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

  16. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

    PubMed

    Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

    2016-08-05

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Authors.

  17. 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

  18. Novel findings in the management of acute pancreatitis.

    PubMed

    Bolado, Federico; de-Madaria, Enrique

    2016-09-01

    Acute pancreatitis (AP) is a potentially serious disease whose incidence is on the increase. Pancreas divisum does not meet the required criteria to be considered an aetiological factor. Sphincter of Oddi dysfunction may be another cause of idiopathic AP. Less invasive methods cannot replace Sphincter of Oddi manometry in diagnosis. Almost half of patients with systemic inflammatory response syndrome develop organ failure, but the mechanisms involved are not completely understood. Obesity is a risk factor for severity in AP; the cause could be the presence of free unsaturated fatty acids, which have pro-inflammatory activity. Prognosis is better in patients with isolated extra-pancreatic necrosis than in those with parenchymal necrosis or with both. The mortality rate among those with infected pancreatic necrosis is 15-20%. The "moderately severe" group is widely heterogeneous and this category may require redefinition. Laparoscopic treatment of pseudocysts is an alternative to endoscopic drainage and could be the first-line option in patients requiring cholecystectomy. The use of lumen-apposing metal stents to treat pancreatic necrosis is cost-effective. Quality of life in some patients following an attack of AP is significantly impaired even at 1 year. Aggressive fluid therapy is not superior to standard fluid therapy in preventing post-ERCP AP. The role of statins in AP prevention is still unclear. Aggressive fluid resuscitation and the use of lactated Ringer solution seem to be beneficial in the treatment of AP. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  19. Medication-induced acute esophageal necrosis: a case report.

    PubMed

    Pautola, Lauri; Hakala, Tapio

    2016-09-29

    Acute esophageal necrosis or Gurvits syndrome is a rare clinical condition characterized by necrotic esophageal mucosa with an abrupt end at the gastroesophageal junction. Its etiology is multifactorial, but mainly related to low-flow states. We describe a case in which a patient accidentally took the wrong medication, with clozapine and olanzapine most probably being the cause of his subsequent acute esophageal necrosis. This situation is, to the best of our knowledge, unprecedented in the medical literature. A 65-year-old Finnish male patient with schizoaffective disorder accidentally took another patient's medication, including clozapine 300 mg, olanzapine 30 mg, teofyllamine 200 mg, warfarin 5 mg, and potassium chloride 1 g. He arrived at our hospital for a routine examination 6 h after the incident. At hospital he started to vomit brownish liquid and had tachycardia and fever. Gastroparesis was found. An endoscopy revealed necrotic esophageal mucosa that was typical for Gurvits syndrome. A computed tomography scan showed an edematous esophagus and raised suspicion of a proximal jejunal obstruction. A laparotomy was performed but only healthy paralytic bowel was found. Our patient healed uneventfully within a week. There are analogous case reports describing ischemic colitis associated with the use of clozapine and olanzapine, but none describing the same for the other medications our patient took. We believe that in this case clozapine and olanzapine caused acute esophageal necrosis and this possibility should be taken into account when treating patients with acute ischemic enteropathy.

  20. Divergent RNA Localisation Patterns of Maternal Genes Regulating Embryonic Patterning in the Butterfly Pararge aegeria

    PubMed Central

    Carter, Jean-Michel; Gibbs, Melanie; Breuker, Casper J.

    2015-01-01

    The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP) axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i.e. germ band) and extra-embryonic tissue (i.e. serosa) is already specified in the oocyte during oogenesis in the ovariole, long before blastoderm cellularisation. To examine the extent by which a female butterfly specifies and patterns the AP axis within the region fated to be the germ band, and whether she specifies a germ plasm, we performed in situ hybridisation experiments on oocytes in P. aegeria ovarioles and on early embryos. RNA localisation of the following key maternal effect genes were investigated: caudal (cad), orthodenticle (otd), hunchback (hb) and four nanos (nos) paralogs, as well as TDRD7 a gene containing a key functional domain (OST-HTH/LOTUS) shared with oskar. TDRD7 was mainly confined to the follicle cells, whilst hb was exclusively zygotically transcribed. RNA of some of the nos paralogs, otd and cad revealed complex localisation patterns within the cortical region prefiguring the germ band (i.e. germ cortex). Rather interestingly, otd was localised within and outside the anterior of the germ cortex. Transcripts of nos-O formed a distinct granular ring in the middle of the germ cortex possibly prefiguring the region where germline stem cells form. These butterfly RNA localisation patterns are highly divergent with respect to other insects, highlighting the diverse ways in which different insect orders maternally regulate early embryogenesis of their offspring. PMID:26633019

  1. Improvement of localised corrosion resistance of AISI 2205 Duplex Stainless Steel joints made by gas metal arc welding under electromagnetic interaction of low intensity

    NASA Astrophysics Data System (ADS)

    García-Rentería, M. A.; López-Morelos, V. H.; García-Hernández, R.; Dzib-Pérez, L.; García-Ochoa, E. M.; González-Sánchez, J.

    2014-12-01

    The resistance to localised corrosion of AISI 2205 duplex stainless steel plates joined by Gas Metal Arc Welding (GMAW) under the effect of electromagnetic interaction of low intensity (EMILI) was evaluated with sensitive electrochemical methods. Welds were made using two shielding gas mixtures: 98% Ar + 2% O2 (M1) and 97% Ar + 3% N2 (M2). Plates were welded under EMILI using the M1 gas with constant welding parameters. The modified microstructural evolution in the high temperature heat affected zone and at the fusion zone induced by application of EMILI during welding is associated with the increase of resistance to localised corrosion of the welded joints. Joints made by GMAW using the shielding gas M2 without the application of magnetic field presented high resistance to general corrosion but high susceptibility to undergo localised attack.

  2. Differences in finger localisation performance of patients with finger agnosia.

    PubMed

    Anema, Helen A; Kessels, Roy P C; de Haan, Edward H F; Kappelle, L Jaap; Leijten, Frans S; van Zandvoort, Martine J E; Dijkerman, H Chris

    2008-09-17

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe patients with impaired detection, but intact sensorimotor localisation. This study examined three patients with a lesion of the angular gyrus with intact somatosensory processing, but with selectively disturbed finger identification (finger agnosia). These patients performed normally when pointing towards the touched finger on their own hand but failed to indicate this finger on a drawing of a hand or to name it. Similar defects in the perception of other body parts were not observed. The findings provide converging evidence for the dissociation between body image and body schema and, more importantly, reveal for the first time that this distinction is also present in higher-order cognitive processes selectively for the fingers.

  3. Flows and Stratification of an Enclosure Containing Both Localised and Vertically Distributed Sources of Buoyancy

    NASA Astrophysics Data System (ADS)

    Partridge, Jamie; Linden, Paul

    2013-11-01

    We examine the flows and stratification established in a naturally ventilated enclosure containing both a localised and vertically distributed source of buoyancy. The enclosure is ventilated through upper and lower openings which connect the space to an external ambient. Small scale laboratory experiments were carried out with water as the working medium and buoyancy being driven directly by temperature differences. A point source plume gave localised heating while the distributed source was driven by a controllable heater mat located in the side wall of the enclosure. The transient temperatures, as well as steady state temperature profiles, were recorded and are reported here. The temperature profiles inside the enclosure were found to be dependent on the effective opening area A*, a combination of the upper and lower openings, and the ratio of buoyancy fluxes from the distributed and localised source Ψ =Bw/Bp . Industrial CASE award with ARUP.

  4. Scientific Benefit of Enlarging Gravitational Wave Detector Networks

    NASA Astrophysics Data System (ADS)

    Chu, Qi; Wen, Linqing; Blair, David

    2012-06-01

    Localising the sources of gravitational waves (GWs) in the sky is crucial to observing the electromagnetic counterparts of GW sources. The localisation capability is poor by a single GW detector yet can be improved by adding more detectors to the detector network. In this paper we review recent studies on scientific benefits of global detector networks and focus on their localisation capability. We employ Wen-Chen's formula to compare this merit of current and future detector networks for localising gravitational wave bursts. We find that the addition of a new detector located in Japan, or India, or Australia will increase angular resolution 3~5 fold with respect to current LIGO-Virgo network, and that the angular resolution improvement by adding a single detector in Australia is comparable to that achieved by adding detectors in both India and Japan. A six-site network achieves a 11-fold improvement in angular resolution compared with the existing three-site network.

  5. Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

    PubMed

    Maple, Jodi; Møller, Simon G

    2007-10-01

    Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

  6. Kyste hydatique à localisation costo vertébrale

    PubMed Central

    Marouf, Rachid

    2014-01-01

    L'hydatidose est une affection parasitaire due à la contamination de l'homme par la forme larvaire de ténia échinococcus granulosus, la forme costo vertébrale est une localisation très rare qui représente 0,18 à 1,21% de l'ensemble des localisations hydatiques. Nous rapportons le cas d'une femme de 32 ans qui présente un kyste hydatique multi vésiculaire à localisation costovertébrale, traité par chirurgie radicale associée à un traitement médical anti parasitaire pour une durée de 6 mois, avec bonne évolution. L'atteinte costo-vertébrale par la maladie hydatique est rare et l’évolution est insidieuse. Malgré un traitement chirurgical radical, la fréquence des récidives rend le pronostic sombre. PMID:25922632

  7. Absolute High-Precision Localisation of an Unmanned Ground Vehicle by Using Real-Time Aerial Video Imagery for Geo-referenced Orthophoto Registration

    NASA Astrophysics Data System (ADS)

    Kuhnert, Lars; Ax, Markus; Langer, Matthias; Nguyen van, Duong; Kuhnert, Klaus-Dieter

    This paper describes an absolute localisation method for an unmanned ground vehicle (UGV) if GPS is unavailable for the vehicle. The basic idea is to combine an unmanned aerial vehicle (UAV) to the ground vehicle and use it as an external sensor platform to achieve an absolute localisation of the robotic team. Beside the discussion of the rather naive method directly using the GPS position of the aerial robot to deduce the ground robot's position the main focus of this paper lies on the indirect usage of the telemetry data of the aerial robot combined with live video images of an onboard camera to realise a registration of local video images with apriori registered orthophotos. This yields to a precise driftless absolute localisation of the unmanned ground vehicle. Experiments with our robotic team (AMOR and PSYCHE) successfully verify this approach.

  8. bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring

    PubMed Central

    Trovisco, Vítor; Belaya, Katsiaryna; Nashchekin, Dmitry; Irion, Uwe; Sirinakis, George; Butler, Richard; Lee, Jack J; Gavis, Elizabeth R; St Johnston, Daniel

    2016-01-01

    bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning. Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior, but with no directional bias. Furthermore, bicoid mRNA localises normally in shot2A2, which abolishes the polarised microtubule organisation. FRAP and photo-conversion experiments demonstrate that the RNA is stably anchored at the anterior, independently of microtubules. Thus, bicoid mRNA is localised by random active transport and anterior anchoring. Super-resolution imaging reveals that bicoid mRNA forms 110–120 nm particles with variable RNA content, but constant size. These particles appear to be well-defined structures that package the RNA for transport and anchoring. DOI: http://dx.doi.org/10.7554/eLife.17537.001 PMID:27791980

  9. Warfarin

    MedlinePlus

    ... forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types ... symptoms You should know that warfarin may cause necrosis or gangrene (death of skin or other body ...

  10. Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice.

    PubMed

    Li, Jingjing; Chen, Kan; Wang, Fan; Dai, Weiqi; Li, Sainan; Feng, Jiao; Wu, Liwei; Liu, Tong; Xu, Shizan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Xu, Ling; Guo, Chuanyong

    2017-07-11

    Methyl jasmonate has recently been found to have anti-cancer activity. Methyl jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. The results were applied to the in vivo treatment of nude mice with a satisfactory effect. Collectively, our results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors due to its mechanism in cancer cells compared to that in normal cells: The major function is to inhibit glycolysis instead of changing aerobic metabolism.

  11. Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice

    PubMed Central

    Li, Jingjing; Chen, Kan; Wang, Fan; Dai, Weiqi; Li, Sainan; Feng, Jiao; Wu, Liwei; Liu, Tong; Xu, Shizan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Xu, Ling; Guo, Chuanyong

    2017-01-01

    Methyl jasmonate has recently been found to have anti-cancer activity. Methyl jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. The results were applied to the in vivo treatment of nude mice with a satisfactory effect. Collectively, our results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors due to its mechanism in cancer cells compared to that in normal cells: The major function is to inhibit glycolysis instead of changing aerobic metabolism. PMID:28498814

  12. Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

    PubMed

    Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

    2017-12-18

    Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

  13. Baccharis megapotamica var. weirii poisoning in water buffalo (Bubalus bubalis).

    PubMed

    Oliveira-Filho, José C; Carmo, Priscila M S; Lucena, Ricardo B; Pierezan, Felipe; Barros, Claudio S L

    2011-05-01

    An outbreak of an acute disease in buffalo (Bubalus bubalis) caused by the ingestion of Baccharis megapotamica var. weirii occurred in the southern region of Brazil. Ten out of 50 buffalo died 24-48 hr after being introduced into a pasture containing abundant amounts of the plant. Factors influencing the ingestion of the plant and consequent toxicosis included hunger, stress caused by shipment, and unfamiliarity with the plant. Clinical signs included serous ocular discharge, incoordination, mild bloat, and muscle trembling. One buffalo was necropsied. Gross findings included dehydration, abundant liquid in the rumen, reddening of the mucosa of forestomachs, abomasum, and intestine, and edema of the wall of the rumen. The main histologic lesions were superficial to full thickness degeneration and necrosis of the stratified epithelium lining the forestomachs, necrosis of the intestinal mucosa, and widespread lymphoid necrosis. A calf (Bos taurus) was fed a single dose of 5 g/kg/body weight of B. megapotamica var. weirii harvested from the same site where the buffalo died. Twenty hours after the administration of the plant this calf died with clinical signs and lesions similar to those observed in the naturally poisoned buffalo. © 2011 The Author(s)

  14. Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells.

    PubMed

    Xu, Ming-Long; Hu, Jin; Guo, Bao-Ping; Niu, Ya-Ru; Xiao, Cheng; Xu, Yin-Xue

    2016-12-01

    Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016. © 2015 Wiley Periodicals, Inc.

  15. Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

    PubMed Central

    Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

    2012-01-01

    Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

  16. [A right sided colon volvulus with necrosis in a young patient. A case reported].

    PubMed

    Márquez-Díaz, Adrián; Ramírez-Ortega, Miguel Angel

    2010-01-01

    Colon volvulus (CV) is the twisting or rotation of an intestinal segment over the mesenterium, which causes occlusion and vascular compromise. It is a frequent disease in individuals over 65 years-old. We report a young patient with right CV and necrosis. A 17 year-old male with clinical findings of acute abdomen presented in the emergency room. During the surgical procedure, a right sided was found, CV with ileocecal valve and caecum ischemia and right colon necrosis with mesenteric vessels thrombosis. The case presented begun with sudden abdominal pain, with intestinal occlusion data, and widespread peritoneal rebound tenderles which suggested an intestinal occlusion. A simple abdomen Rx showed prominent right side colon distention with air levels in small bowel and a "coffee bean" image, suggestive of CVA hemicolectomy with termino-lateral ileocolic anastomosis was performed. Right-sided CV is considered as congenital in origin. They corresponded to 21% of cases in Mexico, with an average age of presentation at 62 years. The CV represents 10% of the causes of large bowel obstruction in Mexico. This is the first case in young people reported in Mexican literature.

  17. Mechanical compression insults induce nanoscale changes of membrane-skeleton arrangement which could cause apoptosis and necrosis in dorsal root ganglion neurons.

    PubMed

    Quan, Xin; Guo, Kai; Wang, Yuqing; Huang, Liangliang; Chen, Beiyu; Ye, Zhengxu; Luo, Zhuojing

    2014-01-01

    In a primary spinal cord injury, the amount of mechanical compression insult that the neurons experience is one of the most critical factors in determining the extent of the injury. The ultrastructural changes that neurons undergo when subjected to mechanical compression are largely unknown. In the present study, using a compression-driven instrument that can simulate mechanical compression insult, we applied mechanical compression stimulation at 0.3, 0.5, and 0.7 MPa to dorsal root ganglion (DRG) neurons for 10 min. Combined with atomic force microscopy, we investigated nanoscale changes in the membrane-skeleton, cytoskeleton alterations, and apoptosis induced by mechanical compression injury. The results indicated that mechanical compression injury leads to rearrangement of the membrane-skeleton compared with the control group. In addition, mechanical compression stimulation induced apoptosis and necrosis and also changed the distribution of the cytoskeleton in DRG neurons. Thus, the membrane-skeleton may play an important role in the response to mechanical insults in DRG neurons. Moreover, sudden insults caused by high mechanical compression, which is most likely conducted by the membrane-skeleton, may induce necrosis, apoptosis, and cytoskeletal alterations.

  18. Quantum State Diffusion

    NASA Astrophysics Data System (ADS)

    Percival, Ian

    2005-10-01

    1. Introduction; 2. Brownian motion and Itô calculus; 3. Open quantum systems; 4. Quantum state diffusion; 5. Localisation; 6. Numerical methods and examples; 7. Quantum foundations; 8. Primary state diffusion; 9. Classical dynamics of quantum localisation; 10. Semiclassical theory and linear dynamics.

  19. Exploring Anti-Bacterial Compounds against Intracellular Legionella

    PubMed Central

    Harrison, Christopher F.; Kicka, Sébastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

    2013-01-01

    Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoeba castellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

  20. Kawasaki disease

    MedlinePlus

    ... signs of heart disease, adding steroids or tumor necrosis factor (TNF) inhibitors such as infliximab (Remicade) or ... Possible Complications Kawasaki disease can cause inflammation of blood vessels in the arteries, especially the coronary arteries. This ...

  1. Abdominal sounds

    MedlinePlus

    ... intestines, or strangulation of the bowel and death ( necrosis ) of the bowel tissue. Very high-pitched bowel ... missing bowel sounds may be caused by: Blocked blood vessels prevent the intestines from getting proper blood flow. ...

  2. Autoinflammatory Diseases

    MedlinePlus

    ... damage. Vision loss. Hearing loss. Mental retardation. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is associated ... red spots on the skin caused by burst blood vessels (purpura). Joint pain. Permanent shortening of a muscle ...

  3. Contralateral routing of signals disrupts monaural level and spectral cues to sound localisation on the horizontal plane.

    PubMed

    Pedley, Adam J; Kitterick, Pádraig T

    2017-09-01

    Contra-lateral routing of signals (CROS) devices re-route sound between the deaf and hearing ears of unilaterally-deaf individuals. This rerouting would be expected to disrupt access to monaural level cues that can support monaural localisation in the horizontal plane. However, such a detrimental effect has not been confirmed by clinical studies of CROS use. The present study aimed to exercise strict experimental control over the availability of monaural cues to localisation in the horizontal plane and the fitting of the CROS device to assess whether signal routing can impair the ability to locate sources of sound and, if so, whether CROS selectively disrupts monaural level or spectral cues to horizontal location, or both. Unilateral deafness and CROS device use were simulated in twelve normal hearing participants. Monaural recordings of broadband white noise presented from three spatial locations (-60°, 0°, and +60°) were made in the ear canal of a model listener using a probe microphone with and without a CROS device. The recordings were presented to participants via an insert earphone placed in their right ear. The recordings were processed to disrupt either monaural level or spectral cues to horizontal sound location by roving presentation level or the energy across adjacent frequency bands, respectively. Localisation ability was assessed using a three-alternative forced-choice spatial discrimination task. Participants localised above chance levels in all conditions. Spatial discrimination accuracy was poorer when participants only had access to monaural spectral cues compared to when monaural level cues were available. CROS use impaired localisation significantly regardless of whether level or spectral cues were available. For both cues, signal re-routing had a detrimental effect on the ability to localise sounds originating from the side of the deaf ear (-60°). CROS use also impaired the ability to use level cues to localise sounds originating from straight ahead (0°). The re-routing of sounds can restrict access to the monaural cues that provide a basis for determining sound location in the horizontal plane. Perhaps encouragingly, the results suggest that both monaural level and spectral cues may not be disrupted entirely by signal re-routing and that it may still be possible to reliably identify sounds originating on the hearing side. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. An overview of translational (radio)pharmaceutical research related to certain oncological and non-oncological applications

    PubMed Central

    Cona, Marlein Miranda; de Witte, Peter; Verbruggen, Alfons; Ni, Yicheng

    2013-01-01

    Translational medicine pursues the conversion of scientific discovery into human health improvement. It aims to establish strategies for diagnosis and treatment of diseases. Cancer treatment is difficult. Radio-pharmaceutical research has played an important role in multiple disciplines, particularly in translational oncology. Based on the natural phenomenon of necrosis avidity, OncoCiDia has emerged as a novel generic approach for treating solid malignancies. Under this systemic dual targeting strategy, a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin (123I-Hyp), a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation. In this review, by emphasizing the potential clinical applicability of OncoCiDia, we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution, dosimetry, pharmacokinetic and, chemical and radiochemical toxicities of the preparations. Myocardial infarction is a global health problem. Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability, searching for diagnostic imaging agents with authentic necrosis avidity is pursued. Therefore, a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated. Cholelithiasis or gallstone disease may cause gallbladder inflammation, infection and other severe complications. While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives, their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones. The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented. Multiple uses of automatic contrast injectors may reduce costs and save resources. However, cross-contaminations with blood-borne pathogens of infectious diseases may occur. We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system. By mimicking pathogens with a radiotracer, we assessed the feasibility of using the system repeatedly without septic risks. This overview is deemed to be interesting to those involved in the related fields for translational research. PMID:25237623

  5. A Tomato necrotic dwarf virus isolate from Datura with poor transmissibility by the whitefly, Bemisia tabaci

    USDA-ARS?s Scientific Manuscript database

    Tomato necrotic dwarf virus (ToNDV); genus Torradovirus, is a whitefly-transmitted virus that caused significant losses for tomato production in the Imperial Valley of California during the 1980s. The virus causes severe stunting, dwarfing of leaves, foliar and fruit necrosis, and greatly reduced f...

  6. Phomalactone from a phytopathogenic fungus infecting Zinnia elegans (Asteraceae) leaves

    USDA-ARS?s Scientific Manuscript database

    Zinnia elegans plants are infected by a fungus that causes necrosis with dark red spots particularly in late spring to the middle of summer in the Mid-South part of the United States. This fungal disease when untreated causes the leaves to wilt and eventually kills the plant. The fungus was isolated...

  7. Corrosion of Nickel-Titanium Orthodontic Archwires in Saliva and Oral Probiotic Supplements

    PubMed Central

    Turco, Gianluca; Contardo, Luca; Serdarević, Nikolina Leona; Otmačić, Helena; Ćurković; Špalj, Stjepan

    2017-01-01

    Objectives The aim of the study was to examine how probiotic supplements affect the corrosion stability of orthodontic archwires made of nickel-titanium alloy (NiTi). Materials and Methods NiTi archwires (0.508x0.508 and having the length of 2.5 cm) were tested. The archwires (composition Ni=50.4%, Ti=49.6%) were uncoated, nitrified and rhodium coated. Surface microgeometry was observed by using scanning electron microscope and surface roughness was measured by profilometer through these variables: roughness average, maximum height and maximum roughness depth. Corrosion was examined by electrochemical method of cyclic polarisation. Results Rhodium coated alloy in saliva has significantly higher general corrosion in saliva than nitrified alloy and uncoated alloy, with large effect size (p=0.027; η2=0.700). In the presence of probiotics, the result was even more pronounced (p<0.001; η2=0.936). Probiotic supplement increases general and localised corrosion of rhodium coated archwire and slightly decreases general corrosion and increases localised corrosion in uncoated archwire, while in the case of nitrified archwire the probability of corrosion is very low. The differences in surface roughness between NiTi wires before corrosion are not significant. Exposure to saliva decreases roughness average in rhodium coated wire (p=0.015; η2=0.501). Media do not significantly influence surface microgeometry in nitrified and uncoated wires. Conclusion Probiotic supplement affects corrosion depending on the type of coating of the NiTi archwire. It increases general corrosion of rhodium coated wire and causes localised corrosion of uncoated and rhodium coated archwire. Probiotic supplement does not have greater influence on surface roughness compared to that of saliva. PMID:29872237

  8. Spotted black snake (Pseudechis guttatus) envenomation in a maned wolf (Chrysocyon brachyurus).

    PubMed

    Portas, Timothy J; Montali, Richard J

    2007-09-01

    Envenomation by a spotted black snake (Pseudechis guttatus), following multiple bites on the buccal mucosa of a captive maned wolf (Chrysocyon brachyurus), caused the animal's collapse, hemolysis, rhabdomyolysis, local tissue necrosis, hepatic and renal failure, and subsequent death. The wolf died despite intensive supportive care including antivenom administration, fluid support, and a blood transfusion. Gross necropsy findings included myocardial and intestinal hemorrhage, pulmonary congestion, hepatomegaly, and splenomegaly. Microscopic examination of formalin-fixed tissues demonstrated pulmonary and abdominal visceral hemorrhage, acute nephrosis with casts, multifocal hepatic necrosis, and splenic congestion.

  9. Sickle cell crisis leading to extensive necrosis in a low-grade glioma and masquerading high-grade lesion.

    PubMed

    Agrawal, Amit; Balpande, D N; Khan, A; Vagh, S J; Shukla, Samarth; Chopra, Sumit

    2008-01-01

    A 9-year-old female child presented with rapid neurological deterioration. Clinical features and imaging findings were suggestive of high-grade malignancy, and hematological investigations were suggestive of sickle cell trait. Histopathology showed features of low-grade malignancy and extensive intratumoral sickling. We hypothesize that the vicious cycle of hypoxia, sickling, thrombosis, ischemia and infarction resulted in the extensive tumor necrosis in the present case causing the initial symptoms and rapid deterioration in the condition of the patient. Copyright 2008 S. Karger AG, Basel.

  10. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura

    PubMed Central

    Bernstein, Gregory R.; Malik, Zubair; Schey, Ron

    2015-01-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  11. [Calcificated necrotic inflammatory granuloma after intradiscal injection of triamcinolone hexacetonide].

    PubMed

    Menei, P; Fournier, D; Alhayek, G; Mercier, P; François, H; Audran, M; Guy, G

    1991-10-01

    Recently, it has been demonstrated that symptomatic epidural calcifications represent a complication of intradiscal injection of triamcinolone hexacetonide (Hexatrione). Out of our three cases, pathological examination showed lesions of necrosis with granulomatous inflammatory reaction and bone metaplasia. Necrosis seems to be the primary cause of calcifications so we propose to call the lesion inflammatory and necrotic granuloma. The incidence of these granulomas is unknown. They are unpredictable and appear with a mean range of a year following the intradiscal injection. The treatment is surgery if they become symptomatic.

  12. The multifunctional Staufen proteins: conserved roles from neurogenesis to synaptic plasticity

    PubMed Central

    Heraud-Farlow, Jacki E.; Kiebler, Michael A.

    2014-01-01

    Staufen (Stau) proteins belong to a family of RNA-binding proteins (RBPs) that are important for RNA localisation in many organisms. In this review we discuss recent findings on the conserved role played by Stau during both the early differentiation of neurons and in the synaptic plasticity of mature neurons. Recent molecular data suggest mechanisms for how Stau2 regulates mRNA localisation, mRNA stability, translation, and ribonucleoprotein (RNP) assembly. We offer a perspective on how this multifunctional RBP has been adopted to regulate mRNA localisation under several different cellular and developmental conditions. PMID:25012293

  13. Game of life on phyllosilicates: Gliders, oscillators and still life

    NASA Astrophysics Data System (ADS)

    Adamatzky, Andrew

    2013-10-01

    A phyllosilicate is a sheet of silicate tetrahedra bound by basal oxygens. A phyllosilicate automaton is a regular network of finite state machines - silicon nodes and oxygen nodes - which mimics structure of the phyllosilicate. A node takes states 0 and 1. Each node updates its state in discrete time depending on a sum of states of its three (silicon) or six (oxygen) neighbours. Phyllosilicate automata exhibit localisations attributed to Conway's Game of Life: gliders, oscillators, still lifes, and a glider gun. Configurations and behaviour of typical localisations, and interactions between the localisations are illustrated.

  14. Distributed estimation of sensors position in underwater wireless sensor network

    NASA Astrophysics Data System (ADS)

    Zandi, Rahman; Kamarei, Mahmoud; Amiri, Hadi

    2016-05-01

    In this paper, a localisation method for determining the position of fixed sensor nodes in an underwater wireless sensor network (UWSN) is introduced. In this simple and range-free scheme, the node localisation is achieved by utilising an autonomous underwater vehicle (AUV) that transverses through the network deployment area, and that periodically emits a message block via four directional acoustic beams. A message block contains the actual known AUV position as well as a directional dependent marker that allows a node to identify the respective transmit beam. The beams form a fixed angle with the AUV body. If a node passively receives message blocks, it could calculate the arithmetic mean of the coordinates existing in each messages sequence, to find coordinates at two different time instants via two different successive beams. The node position can be derived from the two computed positions of the AUV. The major advantage of the proposed localisation algorithm is that it is silent, which leads to energy efficiency for sensor nodes. The proposed method does not require any synchronisation among the nodes owing to being silent. Simulation results, using MATLAB, demonstrated that the proposed method had better performance than other similar AUV-based localisation methods in terms of the rates of well-localised sensor nodes and positional root mean square error.

  15. [Legg-Calvé-Perthes disease].

    PubMed

    Wiig, Ola; Svenningsen, Svein; Terjesen, Terje

    2011-05-20

    Legg-Calvé-Perthes disease is characterized by avascular necrosis of the head of the femur. This article deals with the epidemiology, possible causes, treatment and prognostic factors connected with the disease. The article is based on a non-systematic literature search and own clinical practice, with special emphasis on a Norwegian countrywide study of children with Legg-Calvé-Perthes disease. The incidence of Legg-Calvé-Perthes disease varies in different countries and regions. Those who are older than six years at the time of diagnosis and have over 50% femoral head necrosis have a worse prognosis than younger children where the necrosis is less extensive. Treatment has been discussed extensively over the past 100 years, and still varies considerably. The Norwegian countrywide investigation showed that the results in children who were over six years at the time of diagnosis and had more than 50% femoral head necrosis were significantly better after varus femoral osteotomy than after physiotherapy or orthosis. This agrees with the only other prospective study that has been published. Operative treatment should be considered in children who are six years old or older and have over 50% femoral head necrosis when the diagnosis Legg-Calvé-Perthes disease is made. Those who are younger than six years at the time of diagnosis or who have less than 50% femoral head necrosis should be treated symptomatically. Abduction orthosis has no place in the treatment of Legg-Calvé-Perthes disease.

  16. Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

    NASA Astrophysics Data System (ADS)

    Sulmartiwi, Laksmi; Triastuti, Juni; Andriyono, Sapto; Umami, Mardiah Rahma

    2017-02-01

    Many procedures continuously in aquaculture and scientific research like tagging and vaccinating cause pain, involving damaging tissue and also cause stress responses in fish. Stress responses in fish influence liver because liver have vital role to supply energy and metabolism. Histology alteration in liver is caused by stress response like changes of vacuolation hepatocyte and characteristic colour. Triterpenoid was known had hepatoprotective activity. One of marine organism contained triterpenoid was sea cucumber. Result of research showed that liver tissue in fish with injected acetic acid 5 % (in upper lip) as pain stimulus have histopathology damages such as pyknosis (medium damage level) and oedema (heavy damage level) after 8 hour injection. Injected Lidocaine 1mg/fish as analgesic drug have histopathology damages such as oedema (heavy damages level), necrosis and pyknosis (low damages level). Injected acetic acid 5 % (in upper lip) and ethanolic extract of sea cucumber Phyllophorus sp. dose 5 mg/50 gr body weight shown histopathology damages such as necrosis, edema (medium damage level) and pyknosis (low damage level).

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

    PubMed

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

    2018-02-01

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

  18. Contraction Bands Are Induced by Cardiac Massage Itself.

    PubMed

    Morita, Satomu; Furukawa, Satoshi; Nishi, Katsuji; Hitosugi, Masahito

    2016-09-01

    Pathological contraction bands (CB) are recognized as a type of necrosis pattern found in the myocardium. It is well known that CB are induced by cardiopulmonary resuscitation (CPR) with cardiac massage. However, it is not known whether the reperfusion or massage itself causes the formation of CB. We studied 10 cardiac tissues taken from forensic autopsy cases that had not received CPR. We excluded the cases where the cause of death was a cardiac event. After making sections for forensic research, we massaged the left ventricles for 10 minutes. We found CB in all cases with massage performed within 12 hours after death, which is the time frame for supravital reactions. We did not find CB in any cases where more than 24 hours had elapsed since the time of death. Contraction bands were not observed in any sections that were taken before massage. We suggested here that CB induced by CPR were caused by the cardiac massage itself, and that most CPR-induced CB are not contraction band necrosis but rather artifactual CB.

  19. Aeromonas hydrophila exotoxin induces cytoplasmic vacuolation and cell death in VERO cells.

    PubMed

    Di Pietro, Angela; Picerno, Isa; Visalli, Giuseppa; Chirico, Cristina; Spataro, Pasquale; Cannavò, Giuseppe; Scoglio, Maria E

    2005-07-01

    Many organisms are able to cause cell vacuolation, but it is unclear if this can be considered a step of apoptosis or necrosis, or a distinct form of cell death. In this study VERO cells were used to evaluate the relationship between vacuolation and cell death pattern caused by exotoxins produced by environmental strains of A. hydrophila. Cell damage has been evaluated morphologically as well as biochemically. Cytotoxic and vacuolating titres were strictly correlated and the vacuolation has to be considered an early indicator of cytotoxicity that causes cell apoptosis or necrosis in relation to the dose. Signs of apoptosis (chromatin condensation and blebbing) were observed at low concentration and TGase activity, referable to apoptosis induction, confirms morphological observations. In fact, putrescine incorporation was related both to cytotoxin concentration and time of incubation. Moreover, the observed doubling cells with necrotic features permit us to suppose that cell sensitivity and death pattern could change during the different phases of cellular cycle.

  20. Giant Fecalith Causing Near Intestinal Obstruction and Rectal Ischemia

    PubMed Central

    Nigar, Sofia; Sunkara, Tagore; Culliford, Andrea; Gaduputi, Vinaya

    2017-01-01

    Fecal impaction if left untreated can lead to the hardening of stools and the formation of fecalith. Fecaliths rarely cause serious complications and are usually managed conservatively. We present this rare case of a giant fecalith causing near obstruction in an institutionalized paraplegic patient at high risk for chronic constipation and fecal impaction. This case was also unusual for causing ischemic pressure necrosis in the rectum, thereby highlighting the possible serious complications of fecalith. PMID:28611554

  1. Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model.

    PubMed

    Fukunaga, Yutaka; Izawa-Ishizawa, Yuki; Horinouchi, Yuya; Sairyo, Eriko; Ikeda, Yasumasa; Ishizawa, Keisuke; Tsuchiya, Koichiro; Abe, Yoshiro; Hashimoto, Ichiro; Tamaki, Toshiaki

    2017-04-01

    Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis. © 2017 by the Wound Healing Society.

  2. Lack of the Transcription Factor Hypoxia-Inducible Factor 1α (HIF-1α) in Macrophages Accelerates the Necrosis of Mycobacterium avium-Induced Granulomas.

    PubMed

    Cardoso, Marcos S; Silva, Tânia M; Resende, Mariana; Appelberg, Rui; Borges, Margarida

    2015-09-01

    The establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1α (HIF-1α) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1α in the caseation of granulomas. The genetic ablation of HIF-1α in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1α in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1α inactivation, accelerates granuloma necrosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis.

    PubMed

    Tóth, F; Nissi, M J; Wang, L; Ellermann, J M; Carlson, C S

    2015-02-01

    Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  4. Cytoprotection by fructose and other ketohexoses during bile salt-induced apoptosis of hepatocytes.

    PubMed

    Zeid, I M; Bronk, S F; Fesmier, P J; Gores, G J

    1997-01-01

    Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis at lower concentrations. Although fructose prevents bile salt-induced necrosis, the effect of fructose on bile salt-induced apoptosis is unclear. Our aim was to determine if fructose also protects against bile salt-induced apoptosis. Fructose inhibited glycochenodeoxycholate (GCDC)-induced apoptosis in a concentration-dependent manner with a maximum inhibition of 72% +/- 10% at 10 mmol/L. First, we determined if fructose inhibited apoptosis by decreasing adenosine triphosphate (ATP) and intracellular pH (pHi). Although fructose decreased ATP to <25% of basal values, oligomycin (an ATP synthase inhibitor) did not inhibit apoptosis despite decreasing ATP to similar values. Fructose (10 mmol/L) decreased intracellular pH (pHi) by 0.2 U. However, extracellular acidification (pH 6.8), which decreased hepatocyte pHi 0.35 U and is known to inhibit necrosis, actually potentiated apoptosis 1.6-fold. Fructose cytoprotection also could not be explained by induction of bcl-2 transcription or metal chelation. Because we could not attribute fructose cytoprotection to metabolic effects, alterations in the expression of bcl-2, or metal chelation, we next determined if the poorly metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis; unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt-induced apoptosis and necrosis are inhibited by fructose, these data suggest that similar processes initiate bile salt-induced hepatocyte necrosis and apoptosis. In contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus, ketohexose-sensitive pathways appear to initiate both bile salt-induced cell apoptosis and necrosis, whereas dissimilar, pH-sensitive, effector mechanisms execute these two different cell death processes.

  5. Treatment of Implant Exposure due to Skin Necroses after Skin Sparing Mastectomy: Initial Experiences Using a Not Selective Random Epigastric Flap.

    PubMed

    Echazarreta-Gallego, Estíbaliz; Pola-Bandrés, Guillermo; Arribas-Del Amo, María Dolores; Gil-Romea, Ismael; Sousa-Domínguez, Ramón; Güemes-Sánchez, Antonio

    2017-10-01

    Breast prostheses exposure is probably the most devastating complication after a skin sparing mastectomy (SSM) and implant-based, one-stage, breast reconstruction. This complication may occur in the immediate post-operative period or in the weeks and even months after the procedure. In most cases, the cause is poor skin coverage of the implant due to skin necrosis. Eight consecutive cases of implant exposure (or risk of exposure) due to skin necrosis in SSM patients over a period of 5 years, all patients were treated using a random epigastric rotation flap, executed by the same medical team. A random epigastric flap (island or conventional rotation flap) was used to cover the skin defect. All the patients completed the procedure and all prostheses were saved; there were no cases of flap necrosis or infection. Cases of skin necrosis after SSM and immediate implant reconstruction, in which the implant is at risk of exposure, can be successfully treated with a random epigastric rotation flap.

  6. Congenital tuberculosis localised to the ear.

    PubMed Central

    Naranbhai, R C; Mathiassen, W; Malan, A F

    1989-01-01

    We report two infants who had localised congenital tuberculous otitis. In both cases the infants presented with an ear discharge and both mothers had been diagnosed as having miliary tuberculosis. Infection is thought to have occurred in utero or during birth. Images Figure PMID:2786383

  7. Acute Hepatopancreatic Necrosis Disease-Causing Vibrio parahaemolyticus Strains Maintain an Antibacterial Type VI Secretion System with Versatile Effector Repertoires.

    PubMed

    Li, Peng; Kinch, Lisa N; Ray, Ann; Dalia, Ankur B; Cong, Qian; Nunan, Linda M; Camilli, Andrew; Grishin, Nick V; Salomon, Dor; Orth, Kim

    2017-07-01

    Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp disease that has severely damaged the global shrimp industry. AHPND is caused by toxic strains of Vibrio parahaemolyticus that have acquired a "selfish plasmid" encoding the deadly binary toxins PirA vp /PirB vp To better understand the repertoire of virulence factors in AHPND-causing V. parahaemolyticus , we conducted a comparative analysis using the genome sequences of the clinical strain RIMD2210633 and of environmental non-AHPND and toxic AHPND isolates of V. parahaemolyticus Interestingly, we found that all of the AHPND strains, but none of the non-AHPND strains, harbor the antibacterial type VI secretion system 1 (T6SS1), which we previously identified and characterized in the clinical isolate RIMD2210633. This finding suggests that the acquisition of this T6SS might confer to AHPND-causing V. parahaemolyticus a fitness advantage over competing bacteria and facilitate shrimp infection. Additionally, we found highly dynamic effector loci in the T6SS1 of AHPND-causing strains, leading to diverse effector repertoires. Our discovery provides novel insights into AHPND-causing pathogens and reveals a potential target for disease control. IMPORTANCE Acute hepatopancreatic necrosis disease (AHPND) is a serious disease that has caused severe damage and significant financial losses to the global shrimp industry. To better understand and prevent this shrimp disease, it is essential to thoroughly characterize its causative agent, Vibrio parahaemolyticus Although the plasmid-encoded binary toxins PirA vp /PirB vp have been shown to be the primary cause of AHPND, it remains unknown whether other virulent factors are commonly present in V. parahaemolyticus and might play important roles during shrimp infection. Here, we analyzed the genome sequences of clinical, non-AHPND, and AHPND strains to characterize their repertoires of key virulence determinants. Our studies reveal that an antibacterial type VI secretion system is associated with the AHPND strains and differentiates them from non-AHPND strains, similar to what was seen with the PirA/PirB toxins. We propose that T6SS1 provides a selective advantage during shrimp infections. Copyright © 2017 American Society for Microbiology.

  8. Acute Hepatopancreatic Necrosis Disease-Causing Vibrio parahaemolyticus Strains Maintain an Antibacterial Type VI Secretion System with Versatile Effector Repertoires

    PubMed Central

    Li, Peng; Kinch, Lisa N.; Ray, Ann; Dalia, Ankur B.; Nunan, Linda M.; Camilli, Andrew; Grishin, Nick V.

    2017-01-01

    ABSTRACT Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp disease that has severely damaged the global shrimp industry. AHPND is caused by toxic strains of Vibrio parahaemolyticus that have acquired a “selfish plasmid” encoding the deadly binary toxins PirAvp/PirBvp. To better understand the repertoire of virulence factors in AHPND-causing V. parahaemolyticus, we conducted a comparative analysis using the genome sequences of the clinical strain RIMD2210633 and of environmental non-AHPND and toxic AHPND isolates of V. parahaemolyticus. Interestingly, we found that all of the AHPND strains, but none of the non-AHPND strains, harbor the antibacterial type VI secretion system 1 (T6SS1), which we previously identified and characterized in the clinical isolate RIMD2210633. This finding suggests that the acquisition of this T6SS might confer to AHPND-causing V. parahaemolyticus a fitness advantage over competing bacteria and facilitate shrimp infection. Additionally, we found highly dynamic effector loci in the T6SS1 of AHPND-causing strains, leading to diverse effector repertoires. Our discovery provides novel insights into AHPND-causing pathogens and reveals a potential target for disease control. IMPORTANCE Acute hepatopancreatic necrosis disease (AHPND) is a serious disease that has caused severe damage and significant financial losses to the global shrimp industry. To better understand and prevent this shrimp disease, it is essential to thoroughly characterize its causative agent, Vibrio parahaemolyticus. Although the plasmid-encoded binary toxins PirAvp/PirBvp have been shown to be the primary cause of AHPND, it remains unknown whether other virulent factors are commonly present in V. parahaemolyticus and might play important roles during shrimp infection. Here, we analyzed the genome sequences of clinical, non-AHPND, and AHPND strains to characterize their repertoires of key virulence determinants. Our studies reveal that an antibacterial type VI secretion system is associated with the AHPND strains and differentiates them from non-AHPND strains, similar to what was seen with the PirA/PirB toxins. We propose that T6SS1 provides a selective advantage during shrimp infections. PMID:28432099

  9. Microvascular complications associated with injection of cosmetic facelift dermal fillers

    NASA Astrophysics Data System (ADS)

    Yousefi, Siavash; Prendes, Mark; Chang, Shu-Hong; Wang, Ruikang K.

    2015-02-01

    Minimally-invasive cosmetic surgeries such as injection of subdermal fillers have become very popular in the past decade. Although rare, some complications may follow injections such as tissue necrosis and even blindness. There exist two hypothesis regarding source of these complications both of which include microvasculature. The first hypothesis is that fillers in between the tissue structures and compress microvasculature that causes blockage of tissue neutrition and oxygen exchange in the tissue. In another theory, it is hypothesized that fillers move inside major arteries and block the arteries/veins. In this paper, we study these hypotheses using optical coherence tomography and optical microangiography technologies with different hyaluronic-acid fillers in a mouse ear model. Based on our observations, the fillers eventually block arteries/veins if injected directly into them that eventually causes tissue necrosis.

  10. Femoral Head Avascular Necrosis Is Not Caused by Arthroscopic Posterolateral Femoroplasty.

    PubMed

    Rupp, Robert E; Rupp, Sasha N

    2016-05-01

    This study was conducted to identify the risk of avascular necrosis of the femoral head after arthroscopic femoroplasty extending to the posterolateral femoral neck, the source of the primary blood supply to the femoral head. Cam lesions of femoroacetabular impingement are typically anterior along the junction of the femoral head and neck. However, anatomic variations can involve the posterolateral vascular region of the femoral head and neck. Femoroplasty involving this vascular region can lead to injury to the blood supply to the femoral head, with subsequent avascular necrosis. If the posterolateral portion of the cam lesion is preserved, persistent femoroacetabular impingement may occur. A retrospective review identified 112 patients who underwent arthroscopic femoroplasty for femoroacetabular impingement over a 2-year period. Of these patients, 14 had femoroplasty that extended to the posterolateral femoral head. Of this group, 5 had undergone magnetic resonance imaging (MRI) after femoroplasty and the other 9 were contacted to undergo MRI of the hip to evaluate for avascular necrosis. A radiologist and the senior author evaluated all MRI scans specifically for avascular necrosis of the femoral head. All procedures were performed by the senior author. Mean age of the 14 patients (8 women and 6 men) with femoroplasty that extended into the posterolateral vascular region of the femoral head was 44 years (range, 23-69 years). All 14 patients underwent MRI evaluation of the affected hip a mean of 25 months (range, 7-44 months) after femoroplasty. No MRI scans showed evidence of avascular necrosis of the femoral head. Femoroplasty of the posterolateral vascular region of the femoral head is not associated with avascular necrosis. Patients with femoroacetabular impingement and a cam lesion extending to the posterolateral femoral head can undergo femoroplasty of this region without the development of avascular necrosis. [Orthopedics. 2016; 39(3):177-180.]. Copyright 2016, SLACK Incorporated.

  11. Inflammatory Pathways Regulated by Tumor Necrosis Receptor-Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced Obesity.

    PubMed

    Anto Michel, Nathaly; Colberg, Christian; Buscher, Konrad; Sommer, Björn; Pramod, Akula Bala; Ehinger, Erik; Dufner, Bianca; Hoppe, Natalie; Pfeiffer, Katharina; Marchini, Timoteo; Willecke, Florian; Stachon, Peter; Hilgendorf, Ingo; Heidt, Timo; von Zur Muhlen, Constantin; von Elverfeldt, Dominik; Pfeifer, Dietmar; Schüle, Roland; Kintscher, Ulrich; Brachs, Sebastian; Ley, Klaus; Bode, Christoph; Zirlik, Andreas; Wolf, Dennis

    2018-03-02

    The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-α, IL (interleukin)-1β, and TLRs (toll-like receptors). Mice deficient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1 -/- mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by β3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-deficient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism. © 2018 American Heart Association, Inc.

  12. Colic caused by Panicum maximum toxicosis in equidae in northern Brazil.

    PubMed

    Cerqueira, Valíria D; Riet-Correa, Gabriela; Barbosa, José D; Duarte, Marcos D; Oliveira, Carlos M C; de Oliveira, Carlos A; Tokarnia, Carlos; Lee, Stephen T; Riet-Correa, Franklin

    2009-11-01

    In the Amazon region of northern Brazil, Panicum maximum cultivars Mombaça, Tanzânia, and Massai cause severe colic and death in horses and mules. The disease occurs in the rainy season, when sprouting pastures are grazed by equidae. In the 8 separate disease outbreaks studied, a total of 52 out of 153 equidae were affected, including 19 that died (10 mules and 9 horses). Clinical signs were colic and abdominal dilatation, with a clinical manifestation period of 12 hr to 4 days. Serum activities of gamma-glutamyl transferase and aspartate aminotransferase were within reference intervals; however, serum urea nitrogen and creatinine concentrations were occasionally elevated. The primary gross and histologic lesions were observed in the digestive system. The stomach, small intestine, and large intestine had severe hemorrhages and occasional mucosal erosions and ulcerations. Ulceration and hemorrhage of the urinary bladder were rarely observed. Histologic examination revealed diffuse lymphoplasmacytic gastritis and enteritis with severe congestion, hemorrhage, and occasional epithelial necrosis and ulceration. Lymphocellular necrosis was occasionally observed within gut-associated lymphoid tissue. Tubular nephrosis occurred in some animals. Degeneration and occasional necrosis of bile duct epithelial cells and degeneration of hepatocytes were observed in the liver. Toxic pastures were negative for diosgenin- and yamogenin-based saponins, and oxalate concentrations were within reference intervals for the species. The toxin or toxins causing disease and the reason for the toxicity of the plant in the northern region are unknown.

  13. Human bronchial epithelial cells injury and cytokine production induced by Tityus serrulatus scorpion venom: An in vitro study.

    PubMed

    Rigoni, Vera Lucia Silva; Kwasniewski, Fabio H; Vieira, Rodolfo Paula; Linhares, Ingrid Sestrem; da Silva, Joelmir Lucena Veiga; Nogueira-Pedro, Amanda; Zamuner, Stella Regina

    2016-09-15

    Tityus serrulatus is the scorpion specie responsible for the majority of scorpion sting accidents in Brazil. Symptoms of envenomation by Tityus serrulatus range from local pain to severe systemic reactions such as cardiac dysfunction and pulmonary edema. Thus, this study has evaluated the participation of bronchial epithelial cells in the pulmonary effects of Tityus serrulatus scorpion venom (Tsv). Human bronchial epithelial cell line BEAS-2B were utilized as a model target and were incubated with Tsv (10 or 50 μg/mL) for 1, 3, 6 and 24 h. Effects on cellular response of venom-induce cytotoxicity were examined including cell viability, cell integrity, cell morphology, apoptosis/necrosis as well as cell activation through the release of pro-inflammatory cytokines IL-1β, IL-6 and IL-8. Tsv caused a decrease in cell viability at 10 and 50 μg/mL, which was confirmed by lactate dehydrogenase (LDH) measurement. Flow cytometry analyses revealed necrosis as the main cell death pathway caused by Tsv. Furthermore, Tsv induced the release of IL-1β, IL-6 and IL-8. Altogether, these results demonstrate that Tsv induces cytotoxic effects on bronchial epithelial cells, involving necrosis and release of pro-inflammatory cytokines, suggesting that bronchial epithelial cells may play a role in the pulmonary injury caused by Tsv. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Wisdom tooth extraction causing lingual nerve and styloglossus muscle damage: a mimic of multiple cranial nerve palsies.

    PubMed

    Carr, Aisling S; Evans, Matthew; Shah, Sachit; Catania, Santi; Warren, Jason D; Gleeson, Michael J; Reilly, Mary M

    2017-06-01

    The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and highlight the clinical features that allowed localisation of the lesion to a focal, iatrogenic injury of the lingual nerve and adjacent styloglossus muscle. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Disseminated sporotrichosis

    PubMed Central

    Romero-Cabello, Raúl; Bonifaz, Alexandro; Romero-Feregrino, Raúl; Sánchez, Carlos Javier; Linares, Yancy; Zavala, Jorge Tay; Romero, Leticia Calderón; Romero-Feregrino, Rodrigo; Vega, José T Sánchez

    2011-01-01

    Sporotrichosis is a subacute or chronic infection caused by Sporothrix schenckii. It is a primary cutaneous infection and it has different clinical forms: disseminated by lymphatic vessels (75%), localised cutaneous form (20%), disseminated cutaneous and extracuteus rarely. The systemic disseminated sporotrichosis is considered a severe opportunistic infection. The best diagnostic test is the culture. The authors report a case of a 36-year-old man, originally from Puebla, Mexico, with a diagnosis of disseminated sporotrichosis. Differential diagnosis with other pathologies includes leishmaniasis, chromoblastomycosis, tuberculosis verrucose and lymphangitis. The development of unusual presentations in immunocompromised patients has been reported. PMID:22700076

  16. Diverse chromosomal locations of quantitative trait loci for tolerance to maize chlorotic mottle in five maize populations

    USDA-ARS?s Scientific Manuscript database

    The recent rapid emergence of maize lethal necrosis (MLN), caused by coinfection of maize with maize chlorotic mottle virus (MCMV) and a second virus usually from the family Potyviridae, is causing extensive losses for farmers in East Africa, Southeast Asia and South America. Although the genetic ba...

  17. Extravasation of antineoplastic agents: prevention and treatments.

    PubMed

    Boschi, Rita; Rostagno, Elena

    2012-07-31

    The extravasation of antineoplastic agents is an unwanted and distressing situation that can easily occur. It may cause severe and irreversible local injuries. Left untreated, vesicant chemotherapy extravasation can potentially cause tissue necrosis, functional impairment and permanent disfigurement. This article provides a review of current literature regarding recommendations on the prevention and treatment of extravasation of antineoplastic agents.

  18. A genome-wide resource for the analysis of protein localisation in Drosophila

    PubMed Central

    Sarov, Mihail; Barz, Christiane; Jambor, Helena; Hein, Marco Y; Schmied, Christopher; Suchold, Dana; Stender, Bettina; Janosch, Stephan; KJ, Vinay Vikas; Krishnan, RT; Krishnamoorthy, Aishwarya; Ferreira, Irene RS; Ejsmont, Radoslaw K; Finkl, Katja; Hasse, Susanne; Kämpfer, Philipp; Plewka, Nicole; Vinis, Elisabeth; Schloissnig, Siegfried; Knust, Elisabeth; Hartenstein, Volker; Mann, Matthias; Ramaswami, Mani; VijayRaghavan, K; Tomancak, Pavel; Schnorrer, Frank

    2016-01-01

    The Drosophila genome contains >13000 protein-coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here, we present a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins, we created transgenic lines, and for a total of 207 lines, we assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we visualised many proteins at endogenous expression levels and found a large fraction of them localising to subcellular compartments. By applying genetic complementation tests, we estimate that about two-thirds of the tagged proteins are functional. Moreover, these tagged proteins enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will boost systematic analysis of protein expression and localisation in various cellular and developmental contexts. DOI: http://dx.doi.org/10.7554/eLife.12068.001 PMID:26896675

  19. La tuberculose extra-ganglionnaire primitive de la sphère ORL: à propos de 15 cas

    PubMed Central

    Touati, Mohamed Mliha; Darouassi, Youssef; Chihani, Mehdi; Lakouichmi, Mohammed; Tourabi, Khalid; Ammar, Haddou; Bouaity, Brahim

    2014-01-01

    Les localisations ORL extra ganglionnaires de la tuberculose sont rares. La symptomatologie clinique ainsi que les examens paracliniques sont souvent trompeurs,posant ainsi le problème de diagnostic différentiel avec la pathologie tumorale. Nous rapportons 15 cas de localisations extra ganglionnaires de tuberculose, colligés au service ORL et CCF de l'Hopital Militaire Avicenne de Marrakech colligés entre 2009 et 2013. L’âge moyen de nos patients est de 33 ans. L’étude topographique a montré 6 cas au niveau du cavum, un cas de miliaire tuberculeuse pharyngée, 4 cas laryngés; 2 localisations auriculaires; 1 parotidienne et 1 localisation sous maxillaire. Le diagnostic était anatomopathologiquedans tous les cas. Tous nos patients ont reçu un traitement antituberculeux avec une bonne évolution. Mots-clés: Tuberculose, amygdale, rhinopharynx, larynx, glandes salivaires,Oreille moyenne. PMID:25815100

  20. Correlative and integrated light and electron microscopy of in-resin GFP fluorescence, used to localise diacylglycerol in mammalian cells

    PubMed Central

    Peddie, Christopher J.; Blight, Ken; Wilson, Emma; Melia, Charlotte; Marrison, Jo; Carzaniga, Raffaella; Domart, Marie-Charlotte; O׳Toole, Peter; Larijani, Banafshe; Collinson, Lucy M.

    2014-01-01

    Fluorescence microscopy of GFP-tagged proteins is a fundamental tool in cell biology, but without seeing the structure of the surrounding cellular space, functional information can be lost. Here we present a protocol that preserves GFP and mCherry fluorescence in mammalian cells embedded in resin with electron contrast to reveal cellular ultrastructure. Ultrathin in-resin fluorescence (IRF) sections were imaged simultaneously for fluorescence and electron signals in an integrated light and scanning electron microscope. We show, for the first time, that GFP is stable and active in resin sections in vacuo. We applied our protocol to study the subcellular localisation of diacylglycerol (DAG), a modulator of membrane morphology and membrane dynamics in nuclear envelope assembly. We show that DAG is localised to the nuclear envelope, nucleoplasmic reticulum and curved tips of the Golgi apparatus. With these developments, we demonstrate that integrated imaging is maturing into a powerful tool for accurate molecular localisation to structure. PMID:24637200

  1. Null stream analysis of Pulsar Timing Array data: localisation of resolvable gravitational wave sources

    NASA Astrophysics Data System (ADS)

    Goldstein, Janna; Veitch, John; Sesana, Alberto; Vecchio, Alberto

    2018-04-01

    Super-massive black hole binaries are expected to produce a gravitational wave (GW) signal in the nano-Hertz frequency band which may be detected by pulsar timing arrays (PTAs) in the coming years. The signal is composed of both stochastic and individually resolvable components. Here we develop a generic Bayesian method for the analysis of resolvable sources based on the construction of `null-streams' which cancel the part of the signal held in common for each pulsar (the Earth-term). For an array of N pulsars there are N - 2 independent null-streams that cancel the GW signal from a particular sky location. This method is applied to the localisation of quasi-circular binaries undergoing adiabatic inspiral. We carry out a systematic investigation of the scaling of the localisation accuracy with signal strength and number of pulsars in the PTA. Additionally, we find that source sky localisation with the International PTA data release one is vastly superior than what is achieved by its constituent regional PTAs.

  2. Localised burst reconstruction from space-time PODs in a turbulent channel

    NASA Astrophysics Data System (ADS)

    Garcia-Gutierrez, Adrian; Jimenez, Javier

    2017-11-01

    The traditional proper orthogonal decomposition of the turbulent velocity fluctuations in a channel is extended to time under the assumption that the attractor is statistically stationary and can be treated as periodic for long-enough times. The objective is to extract space- and time-localised eddies that optimally represent the kinetic energy (and two-event correlation) of the flow. Using time-resolved data of a small-box simulation at Reτ = 1880 , minimal for y / h 0.25 , PODs are computed from the two-point spectral-density tensor Φ(kx ,kz , y ,y' , ω) . They are Fourier components in x, z and time, and depend on y and on the temporal frequency ω, or, equivalently, on the convection velocity c = ω /kx . Although the latter depends on y, a spatially and temporally localised `burst' can be synthesised by adding a range of PODs with specific phases. The results are localised bursts that are amplified and tilted, in a time-periodic version of Orr-like behaviour. Funded by the ERC COTURB project.

  3. Scedosporium apiospermum: An unreported cause of fungal sporotrichoid-like lymphocutaneous infection in Australia and review of the literature.

    PubMed

    Boyce, Zachary; Collins, Neville

    2015-05-01

    Scedosporium apiospermum is a fungus emerging as a rare but important cause of both localised and disseminated infections in immunocompromised patients. Most cutaneous lesions present as mycetoma, however a review of the literature revealed an increasing number of cases worldwide presenting with lymphocutaneous spread resembling sporotrichosis. An 85-year-old man with an extensive medical history including type II diabetes mellitus and meningioma presented with crusted haemorrhagic areas on the dorsum of his left foot and multiple crusted nodules extending proximally along his leg in a sporotrichoid-like lymphocutaneous pattern. A mycological examination and culture of the cutaneous tissue found the fungus, Scedosporium apiospermum. © 2013 The Australasian College of Dermatologists.

  4. Fine-needle aspirate cytology suggesting hepatic lipidosis in four cats with infiltrative hepatic disease.

    PubMed

    Willard, M D; Weeks, B R; Johnson, M

    1999-12-01

    Four cats are reported in which cytology smears obtained by ultrasound-guided fine needle aspiration of the liver were interpreted as indicative of hepatic lipidosis. However, histopathology of hepatic tissue samples obtained with Tru-Cut-like needles or wedge biopsy revealed that the cats had inflammatory or neoplastic hepatic disease causing their clinical signs. Fine needle aspiration and cytology may not detect infiltrative lesions, particularly those that are nodular, multifocal, or localised around the portal regions. Fine needle aspirate cytology is a useful diagnostic procedure with many advantages, but care must be taken to avoid diagnosing hepatic lipidosis as the cause of illness when an infiltrative lesion is responsible. Copyright 1999 European Society of Feline Medicine.

  5. Fault architecture and deformation processes within poorly lithified rift sediments, Central Greece

    NASA Astrophysics Data System (ADS)

    Loveless, Sian; Bense, Victor; Turner, Jenni

    2011-11-01

    Deformation mechanisms and resultant fault architecture are primary controls on the permeability of faults in poorly lithified sediments. We characterise fault architecture using outcrop studies, hand samples, thin sections and grain-size data from a minor (1-10 m displacement) normal-fault array exposed within Gulf of Corinth rift sediments, Central Greece. These faults are dominated by mixed zones with poorly developed fault cores and damage zones. In poorly lithified sediment deformation is distributed across the mixed zone as beds are entrained and smeared. We find particulate flow aided by limited distributed cataclasis to be the primary deformation mechanism. Deformation may be localised in more competent sediments. Stratigraphic variations in sediment competency, and the subsequent alternating distributed and localised strain causes complexities within the mixed zone such as undeformed blocks or lenses of cohesive sediment, or asperities at the mixed zone/protolith boundary. Fault tip bifurcation and asperity removal are important processes in the evolution of these fault zones. Our results indicate that fault zone architecture and thus permeability is controlled by a range of factors including lithology, stratigraphy, cementation history and fault evolution, and that minor faults in poorly lithified sediment may significantly impact subsurface fluid flow.

  6. Cell-wall structural changes in wheat straw pretreated for bioethanol production

    PubMed Central

    Kristensen, Jan B; Thygesen, Lisbeth G; Felby, Claus; Jørgensen, Henning; Elder, Thomas

    2008-01-01

    Background Pretreatment is an essential step in the enzymatic hydrolysis of biomass and subsequent production of bioethanol. Recent results indicate that only a mild pretreatment is necessary in an industrial, economically feasible system. The Integrated Biomass Utilisation System hydrothermal pretreatment process has previously been shown to be effective in preparing wheat straw for these processes without the application of additional chemicals. In the current work, the effect of the pretreatment on the straw cell-wall matrix and its components are characterised microscopically (atomic force microscopy and scanning electron microscopy) and spectroscopically (attenuated total reflectance Fourier transform infrared spectroscopy) in order to understand this increase in digestibility. Results The hydrothermal pretreatment does not degrade the fibrillar structure of cellulose but causes profound lignin re-localisation. Results from the current work indicate that wax has been removed and hemicellulose has been partially removed. Similar changes were found in wheat straw pretreated by steam explosion. Conclusion Results indicate that hydrothermal pretreatment increases the digestibility by increasing the accessibility of the cellulose through a re-localisation of lignin and a partial removal of hemicellulose, rather than by disruption of the cell wall. PMID:18471316

  7. Modulation of flagellum attachment zone protein FLAM3 and regulation of the cell shape in Trypanosoma brucei life cycle transitions

    PubMed Central

    Sunter, Jack D.; Benz, Corinna; Andre, Jane; Whipple, Sarah; McKean, Paul G.; Gull, Keith; Ginger, Michael L.; Lukeš, Julius

    2015-01-01

    ABSTRACT The cell shape of Trypanosoma brucei is influenced by flagellum-to-cell-body attachment through a specialised structure – the flagellum attachment zone (FAZ). T. brucei exhibits numerous morphological forms during its life cycle and, at each stage, the FAZ length varies. We have analysed FLAM3, a large protein that localises to the FAZ region within the old and new flagellum. Ablation of FLAM3 expression causes a reduction in FAZ length; however, this has remarkably different consequences in the tsetse procyclic form versus the mammalian bloodstream form. In procyclic form cells FLAM3 RNAi results in the transition to an epimastigote-like shape, whereas in bloodstream form cells a severe cytokinesis defect associated with flagellum detachment is observed. Moreover, we demonstrate that the amount of FLAM3 and its localisation is dependent on ClpGM6 expression and vice versa. This evidence demonstrates that FAZ is a key regulator of trypanosome shape, with experimental perturbations being life cycle form dependent. An evolutionary cell biology explanation suggests that these differences are a reflection of the division process, the cytoskeleton and intrinsic structural plasticity of particular life cycle forms. PMID:26148511

  8. Characterisation of FAP-1 expression and CD95 mediated apoptosis in the A818-6 pancreatic adenocarcinoma differentiation system.

    PubMed

    Winterhoff, Boris J N; Arlt, Alexander; Duttmann, Angelika; Ungefroren, Hendrik; Schäfer, Heiner; Kalthoff, Holger; Kruse, Marie-Luise

    2012-03-01

    The present study investigated the expression and localisation of FAP-1 (Fas associated phosphatase-1) and CD95 in a 3D differentiation model in comparison to 2D monolayers of the pancreatic adenocarcinoma cell line A818-6. Under non-adherent growth conditions, A818-6 cells differentiate into 3D highly organised polarised epithelial hollow spheres, resembling duct-like structures. A818-6 cells showed a differentiation-dependent FAP-1 localisation. Cells grown as 2D monolayers revealed FAP-1 staining in a juxtanuclear cisternal position, as well as localisation in the nucleus. After differentiation into hollow spheres, FAP-1 was relocated towards the actin cytoskeleton beneath the outer plasma membrane of polarised cells and no further nuclear localisation was observed. CD95 surface staining was found only in a subset of A818-6 monolayer cells, while differentiated hollow spheres appeared to express CD95 in all cells of a given sphere. We rarely observed co-localisation of CD95 and FAP-1 in A818-6 monolayer cells, but strong co-localisation beneath the outer plasma membrane in polarised cells. Analysis of surface expression by flow cytometry revealed that only a subset (36%) of monolayer cells showed CD95 surface expression, and after induction of hollow spheres, CD95 presentation at the outer plasma membrane was reduced to 13% of hollow spheres. Induction of apoptosis by stimulation with agonistic anti-CD95 antibodies, resulted in increased caspase activity in both, monolayer cells and hollow spheres. Knock down of FAP-1 mRNA in A818-6 monolayer cells did not alter resposiveness to CD95 agonistic antibodies. These data suggested that CD95 signal transduction was not affected by FAP-1 expression in A818-6 monolayer cells. In differentiated 3D hollow spheres, we found a polarisation-induced co-localisation of CD95 and FAP-1. A tight control of receptor surface representation and signalling induced apoptosis ensures controlled removal of individual cells instead of a "snowball effect" of apoptotic events. Copyright © 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  9. The multifunctional Staufen proteins: conserved roles from neurogenesis to synaptic plasticity.

    PubMed

    Heraud-Farlow, Jacki E; Kiebler, Michael A

    2014-09-01

    Staufen (Stau) proteins belong to a family of RNA-binding proteins (RBPs) that are important for RNA localisation in many organisms. In this review we discuss recent findings on the conserved role played by Stau during both the early differentiation of neurons and in the synaptic plasticity of mature neurons. Recent molecular data suggest mechanisms for how Stau2 regulates mRNA localisation, mRNA stability, translation, and ribonucleoprotein (RNP) assembly. We offer a perspective on how this multifunctional RBP has been adopted to regulate mRNA localisation under several different cellular and developmental conditions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. DOE Office of Scientific and Technical Information (OSTI.GOV)

    You, Jae-Hwan; Reed, Mark L.; Hiscox, Julian A.

    The severe acute respiratory syndrome-coronavirus nucleocapsid (N) protein is involved in virus replication and modulation of cell processes. In this latter respect control may in part be achieved through the sub-cellular localisation of the protein. N protein predominately localises in the cytoplasm (the site of virus replication and assembly) but also in the nucleus/nucleolus. Using a combination of live-cell and confocal microscopy coupled to mutagenesis we identified a cryptic nucleolar localisation signal in the central part of the N protein. In addition, based on structural comparison to the avian coronavirus N protein, a nuclear export signal was identified in themore » C-terminal region of the protein.« less

  11. Localised sarcoptic mange in dogs: a retrospective study of 10 cases.

    PubMed

    Pin, D; Bensignor, E; Carlotti, D-N; Cadiergues, M C

    2006-10-01

    The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.

  12. [The embolisation of venous malformations].

    PubMed

    Barbera, L; Fiedler, H-W; Krauss, M

    2012-10-01

    The treatment of congenital, vascular malformations is a challenge for physicians and patients. Although different therapeutic options have been described to date, their individual relevance has still to be defined. Â METHODS: We performed a retrospective study of 61 patients with a venous malformation (VM, mean age 22  years), who were referred to our depart-ment during the last 5 years. The size of the VM was larger than 5  cm in 41 patients (66 %). The lower extremities were involved in 45  cases (73 %). The most frequent clinical manifestations were recurrent swelling (80 %), pain (63 %), varicosis (60 %) and thrombophlebitis (39 %). MR angiography with venous sequences was always performed before treatment. Depending on the localisation and the extension of the VM, different techniques of embolisation were selected: foam sclerotherapy or application of synthetic glue by direct punction, coiling of pelvic veins or arterial embolisation with glue. 42  patients (69 %) underwent a procedure because of the complaints or the extension of the VM. An embolisation was performed in 25  patients with 65  interventional sessions. The most frequent technique was foam sclerotherapy (45 ×), followed by glue injection (13 ×), pelvic -venous coiling (6 ×) and arterial embolisation with glue (1 ×). Fifteen patients (60 %) reported a very good and 8  patients a marked improvement (32 %). In two cases there was no change of the complaints. The postinterventional complications were severe pain (n = 3) and skin/fat necrosis at the toe of one patient. The embolisation of venous malformations is an effective therapeutic tool. Different techniques can be used to address specific localisations and morphological patterns. The com-plication rate is very low when a step-by-step -approach is used, so that a repeat intervention is feasible. However, a more specific documentation of the post-interventional changes of the VM is needed before a general recommendation can be given. © Georg Thieme Verlag KG Stuttgart ˙ New York.

  13. The Future of Digital Working: Knowledge Migration and Learning

    ERIC Educational Resources Information Center

    Malcolm, Irene

    2014-01-01

    Against the backdrop of intensified migration linked to globalisation, this article considers the implications of knowledge migration for future digital workers. It draws empirically on a socio-material analysis of the international software localisation industry. Localisers' work requires linguistic, cultural and software engineering skills to…

  14. IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena.

    PubMed

    Nakagawa, Hiroyuki; Miki, Hiroaki; Nozumi, Motohiro; Takenawa, Tadaomi; Miyamoto, Shigeaki; Wehland, Jürgen; Small, J Victor

    2003-06-15

    The insulin receptor tyrosine kinase substrate p53 (IRSp53) links Rac and WAVE2 and has been implicated in lamellipodia protrusion. Recently, however, IRSp53 has been reported to bind to both Cdc42 and Mena to induce filopodia. To shed independent light on IRSp53 function we determined the localisations and dynamics of IRSp53 and WAVE2 in B16 melanoma cells. In cells spread well on a laminin substrate, IRSp53 was localised by antibody labelling at the tips of both lamellipodia and filopodia. The same localisation was observed in living cells with IRSp53 tagged with enhanced green florescence protein (EGFP-IRSp53), but only during protrusion. From the transfection of deletion mutants the N-terminal region of IRSp53, which binds active Rac, was shown to be responsible for its localisation. Although IRSp53 has been reported to regulate filopodia formation with Mena, EGFP-IRSp53 showed the same localisation in MVD7 Ena/VASP (vasodilator stimulated phosphoprotein) family deficient cells. WAVE2 tagged with DsRed1 colocalised with EGFP-IRSp53 at the tips of protruding lamellipodia and filopodia and, in double-transfected cells, the IRSp53 signal in filopodia decreased before that of WAVE2 during retraction. These results suggest an alternative modulatory role for IRSp53 in the extension of both filopodia and lamellipodia, through WAVE2.

  15. Bacteroides fragilis induce necrosis on mice peritoneal macrophages: In vitro and in vivo assays

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vieira, J.M.B.D., E-mail: jmanya@terra.com.br; Laboratorio de Biologia de Anaerobios, IMPPG, UFRJ, Rio de Janeiro; Seabra, S.H.

    Bacteroides fragilis is an anaerobic bacteria component of human intestinal microbiota and agent of infections. In the host B. fragilis interacts with macrophages, which produces toxic radicals like NO. The interaction of activated mice peritoneal macrophages with four strains of B. fragilis was evaluated on this study. Previously was shown that such strains could cause metabolic and morphologic alterations related to macrophage death. In this work propidium iodide staining showed the strains inducing macrophage necrosis in that the labeling was evident. Besides nitroblue tetrazolium test showed that B. fragilis stimulates macrophage to produce oxygen radicals. In vivo assays performed inmore » BalbC mice have results similar to those for in vitro tests as well as scanning electron microscopy, which showed the same surface pore-like structures observed in vitro before. The results revealed that B. fragilis strains studied lead to macrophage death by a process similar to necrosis.« less

  16. Recent advances in detection and control of infectious hematopoietic necrosis virus in aquaculture

    USGS Publications Warehouse

    Winton, James R.

    1991-01-01

    Infectious hematopoietic necrosis (IHN) is one of the most important viral diseases of salmon and trout reared in culture. The disease remains untreatable with avoidance being the only control measure. Much has been learned about the chemical, physical, and serological characteristics of the rhabdovirus causing IHN, but critical gaps exist in our understanding of the biology of the virus in nature. The tools of molecular biology have provided improved methods for detection of pathogens and new strategies for control of viral diseases. This paper reviews several recent improvements in methods for detecting infectious hematopoietic necrosis virus including the application of enzyme-linked immunosorbent assays, development of monoclonal antibodies and DNA probes, and use of the polymerase chain reaction. New strategies for control of IHN through the use of better water treatment, more resistant fish, antiviral drugs or chemicals, and new generation vaccines are discussed.

  17. Tissue necrosis following extravasation of acyclovir in an adolescent: A case report.

    PubMed

    Neocleous, Charalambos; Andonopoulou, Eleni; Adramerina, Alkistis; Pegkou, Antigoni; Savelieva, Olga; Georgiadou, Petroula; Drikos, Ioannis

    2017-05-01

    Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  18. Time-lapse imaging points towards a non-toxic, mainly immune-driven mode of action of ingenol mebutate in the treatment of anogenital warts.

    PubMed

    Braun, Stephan Alexander; Bünemann, Erich; Baran, Julia; Homey, Bernhard; Gerber, Peter Arne

    2018-02-20

    Recently, it has been reported that ingenol mebutate (IM) is an effective treatment option for anogenital warts (AGW), inducing fast wart necrosis within 24 hours in vivo. With regard to its mode of action, IM is thought to act both as an inducer of direct cytotoxic effects and immunologic mechanisms. To distinguish whether the wart necrosis is mainly caused by cytotoxic effects, or whether immune mechanisms are leading, we used time-lapse imaging to analyse IM-treated warts ex vivo over 24 hours. Ex vivo IM-treated warts, which have been detached from the immune system, did not show destructive necrosis, pointing towards a primarily immune-driven mode of action of IM in the treatment of AGW. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

    NASA Astrophysics Data System (ADS)

    Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

    2011-02-01

    A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

  20. Avascular necrosis of the hips with increased activity on 68Ga-DOTATATE PET/CT

    PubMed Central

    Papadakis, Georgios Z.; Millo, Corina; Karantanas, Apostolos H.; Bagci, Ulas; Patronas, Nicholas J.

    2016-01-01

    Prolonged exposure to cortisol is one of the major causes of avascular bone necrosis (AVN). We report on a case of a woman with Cushing’s syndrome attributed to ectopic ACTH secreting tumor who was evaluated with whole body PET/CT study using 68Ga-DOTATATE. The scan showed increased activity by both femoral heads, corresponding to the margins of bilateral AVN seen on MRI. The presented data suggests AVN-induced reactive inflammatory alterations adjacent to the necrotic segment of the bone which can be effectively targeted using radiolabeled somatostatin (SST) analogues. PMID:28033218

  1. Pouching a draining duodenal cutaneous fistula: a case study.

    PubMed

    Zwanziger, P J

    1999-01-01

    Blockage of the mesenteric artery typically causes necrosis to the colon, requiring extensive surgical resection. In severe cases, the necrosis requires removal of the entire colon, creating numerous problems for the WOC nurse when pouching the opening created for effluent. This article describes the management of a draining duodenal fistula in a middle-aged woman, who survived surgery for a blocked mesenteric artery that necessitated the removal of the majority of the small and large intestine. Nutrition, skin management, and pouch options are described over a number of months as the fistula evolved and a stoma was created.

  2. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  3. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

    PubMed

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-04-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  4. Moving with Modernisation and Civilisation: Taiwanese Nativist Education in the Early 1930s

    ERIC Educational Resources Information Center

    Huang, Hsuan-Yi

    2017-01-01

    This study examines localisation endeavours in contemporary Taiwan to explore the history of the Taiwanese localisation movement as a way of reimagining meanings of "Taiwaneseness" constructed under different historical circumstances. It focuses on the "xiangtu" (nativist) literature movement in colonial Taiwan in the early…

  5. Chinese Localisation of Evergreen: An Open Source Integrated Library System

    ERIC Educational Resources Information Center

    Zou, Qing; Liu, Guoying

    2009-01-01

    Purpose: The purpose of this paper is to investigate various issues related to Chinese language localisation in Evergreen, an open source integrated library system (ILS). Design/methodology/approach: A Simplified Chinese version of Evergreen was implemented and tested and various issues such as encoding, indexing, searching, and sorting…

  6. Characterizing lesions in corals from American Samoa

    NASA Astrophysics Data System (ADS)

    Work, T. M.; Rameyer, R. A.

    2005-11-01

    The study of coral disease has suffered from an absence of systematic approaches that are commonly used to determine causes of diseases in animals. There is a critical need to develop a standardized and portable nomenclature for coral lesions in the field and to incorporate more commonly available biomedical tools in coral disease surveys to determine the potential causes of lesions in corals. We characterized lesions in corals from American Samoa based on gross and microscopic morphology and classified them as discoloration, growth anomalies, or tissue loss. The most common microscopic finding in corals manifesting discoloration was the depletion of zooxanthellae, followed by necrosis, sometimes associated with invasive algae or fungi. The most common microscopic lesion in corals manifesting tissue loss was cell necrosis often associated with algae, fungi, or protozoa. Corals with growth anomaly had microscopic evidence of hyperplasia of gastrovascular canals, followed by necrosis associated with algae or metazoa (polychaete worms). Several species of apparently normal corals also had microscopic changes, including the presence of bacterial aggregates or crustacea in tissues. A single type of gross lesion (e.g., discoloration) could have different microscopic manifestations. This phenomenon underlines the importance of using microscopy to provide a more systematic description of coral lesions and to detect potential pathogens associated with these lesions.

  7. Acute massive gastric dilatation causing ischaemic necrosis and perforation of the stomach.

    PubMed

    Moslim, Maitham A; Mittal, Jay; Falk, Gavin A; Ustin, Jeffrey S; Morris-Stiff, Gareth

    2017-06-15

    Acute massive gastric dilatation (AMGD) is a rare distinctive condition but associates with high morbidity and mortality. Though usually seen in patients with eating disorders, many aetiologies of AMGD have been described. The distension has been reported to cause gastric necrosis with or without perforation, usually within 1-2 days of an inciting event of AMGD.We report the case of a 58-year-old male who presented with gastric perforation associated with AMGD 11 days after surgical relief of a proximal small bowel obstruction. The AMGD arose from a closed loop obstruction between a tumour at the gastro-oesophageal junction and a small bowel obstruction as a result of volvulus around a jejunal feeding tube.To our knowledge, this is the first case of a closed loop obstruction of this aetiology reported in the literature, and the presentation of this patient's AMGD was notable for the delayed onset of gastric necrosis. The patient underwent an exploratory laparotomy and a partial gastrectomy to excise a portion of his perforated stomach. Surgeons should be aware of the possibility of delayed ischaemic gastric perforation in cases of AMGD. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Characterizing lesions in corals from American Samoa

    USGS Publications Warehouse

    Work, Thierry M.; Rameyer, Robert A.

    2005-01-01

    The study of coral disease has suffered from an absence of systematic approaches that are commonly used to determine causes of diseases in animals. There is a critical need to develop a standardized and portable nomenclature for coral lesions in the field and to incorporate more commonly available biomedical tools in coral disease surveys to determine the potential causes of lesions in corals. We characterized lesions in corals from American Samoa based on gross and microscopic morphology and classified them as discoloration, growth anomalies, or tissue loss. The most common microscopic finding in corals manifesting discoloration was the depletion of zooxanthellae, followed by necrosis, sometimes associated with invasive algae or fungi. The most common microscopic lesion in corals manifesting tissue loss was cell necrosis often associated with algae, fungi, or protozoa. Corals with growth anomaly had microscopic evidence of hyperplasia of gastrovascular canals, followed by necrosis associated with algae or metazoa (polychaete worms). Several species of apparently normal corals also had microscopic changes, including the presence of bacterial aggregates or crustacea in tissues. A single type of gross lesion (e.g., discoloration) could have different microscopic manifestations. This phenomenon underlines the importance of using microscopy to provide a more systematic description of coral lesions and to detect potential pathogens associated with these lesions.

  9. Evaluating coral reef health in American Samoa

    USGS Publications Warehouse

    Work, Thierry M.; Rameyer, Robert A.

    2005-01-01

    The study of coral disease has suffered from an absence of systematic approaches that are commonly used to determine causes of diseases in animals. There is a critical need to develop a standardized and portable nomenclature for coral lesions in the field and to incorporate more commonly available biomedical tools in coral disease surveys to determine the potential causes of lesions in corals. We characterized lesions in corals from American Samoa based on gross and microscopic morphology and classified them as discoloration, growth anomalies, or tissue loss. The most common microscopic finding in corals manifesting discoloration was the depletion of zooxanthellae, followed by necrosis, sometimes associated with invasive algae or fungi. The most common microscopic lesion in corals manifesting tissue loss was cell necrosis often associated with algae, fungi, or protozoa. Corals with growth anomaly had microscopic evidence of hyperplasia of gastrovascular canals, followed by necrosis associated with algae or metazoa (polychaete worms). Several species of apparently normal corals also had microscopic changes, including the presence of bacterial aggregates or crustacea in tissues. A single type of gross lesion (e.g., discoloration) could have different microscopic manifestations. This phenomenon underlines the importance of using microscopy to provide a more systematic description of coral lesions and to detect potential pathogens associated with these lesions.

  10. Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis.

    PubMed

    Shahi, Sanjeet K

    2017-05-01

    Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno-compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis. © 2016 Optometry Australia.

  11. Triaxial testing of Lopez Fault gouge at 150 MPa mean effective stress

    USGS Publications Warehouse

    Scott, D.R.; Lockner, D.A.; Byerlee, J.D.; Sammis, C.G.

    1994-01-01

    Triaxial compression experiments were performed on samples of natural granular fault gouge from the Lopez Fault in Southern California. This material consists primarily of quartz and has a self-similar grain size distribution thought to result from natural cataclasis. The experiments were performed at a constant mean effective stress of 150 MPa, to expose the volumetric strains associated with shear failure. The failure strength is parameterized by the coefficient of internal friction ??, based on the Mohr-Coulomb failure criterion. Samples of remoulded Lopez gouge have internal friction ??=0.6??0.02. In experiments where the ends of the sample are constrained to remain axially aligned, suppressing strain localisation, the sample compacts before failure and dilates persistently after failure. In experiments where one end of the sample is free to move laterally, the strain localises to a single oblique fault at around the point of failure; some dilation occurs but does not persist. A comparison of these experiments suggests that dilation is confined to the region of shear localisation in a sample. Overconsolidated samples have slightly larger failure strengths than normally consolidated samples, and smaller axial strains are required to cause failure. A large amount of dilation occurs after failure in heavily overconsolidated samples, suggesting that dilation is occurring throughout the sample. Undisturbed samples of Lopez gouge, cored from the outcrop, have internal friction in the range ??=0.4-0.6; the upper end of this range corresponds to the value established for remoulded Lopez gouge. Some kind of natural heterogeneity within the undisturbed samples is probably responsible for their low, variable strength. In samples of simulated gouge, with a more uniform grain size, active cataclasis during axial loading leads to large amounts of compaction. Larger axial strains are required to cause failure in simulated gouge, but the failure strength is similar to that of natural Lopez gouge. Use of the Mohr-Coulomb failure criterion to interpret the results from this study, and other recent studies on intact rock and granular gouge, leads to values of ?? that depend on the loading configuration and the intact or granular state of the sample. Conceptual models are advanced to account for these descrepancies. The consequences for strain-weakening of natural faults are also discussed. ?? 1994 Birkha??user Verlag.

  12. Oral Steroids (Steroid Pills and Syrups)

    MedlinePlus

    ... compressions, especially of the backbone and the hip Loss of blood supply to bones (aseptic necrosis) may cause severe bone pain and may require surgical correction Bones To prevent osteoporosis (loss of calcium in the bones), it is important ...

  13. Mortality Caused by Bath Exposure of Zebrafish (Danio rerio) Larvae to Nervous Necrosis Virus Is Limited to the Fourth Day Postfertilization

    PubMed Central

    Morick, Danny; Faigenbaum, Or; Smirnov, Margarita; Fellig, Yakov; Inbal, Adi

    2015-01-01

    Nervous necrosis virus (NNV) is a member of the Betanodavirus genus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively. PMID:25746990

  14. Mortality Caused by Bath Exposure of Zebrafish (Danio rerio) Larvae to Nervous Necrosis Virus Is Limited to the Fourth Day Postfertilization.

    PubMed

    Morick, Danny; Faigenbaum, Or; Smirnov, Margarita; Fellig, Yakov; Inbal, Adi; Kotler, Moshe

    2015-05-15

    Nervous necrosis virus (NNV) is a member of the Betanodavirus genus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Inclusion body disease of cranes: comparison of pathologic findings in cranes with acquired vs. experimentally induced disease

    USGS Publications Warehouse

    Schuh, J.C.; Sileo, L.; Siegfried, Lynne M.; Yuill, Thomas M.

    1986-01-01

    Inclusion body disease of cranes was the cause of death in 17 immature and mature cranes of 5 different species in Wisconsin. A herpesvirus of unknown origin was the apparent cause. An isolate of this herpesvirus was used to experimentally infect 3 species of cranes. Macroscopic and microscopic lesions associated with naturally acquired and experimentally induced disease were essentially identical. Multifocal hepatic and splenic necrosis was found in all cranes evaluated. Necrosis of the gastrointestinal tract, thymus, and bursa of Fabricius also was seen in some of the cranes. Eosinophilic intranuclear inclusion bodies often were commonly associated with hepatic lesions, sometimes with the splenic lesions, and rarely with the thymic or gastrointestinal tract lesions. The lesions of this inclusion body disease were similar to those reported for cranes in Austria from which a crane herpesvirus was isolated.

  16. [Skin burns, necrosis and ulcers caused by wet cement, ready-mixed concrete and lime. 8 cases].

    PubMed

    Koch, P

    1996-01-01

    Skin burns and caustic ulcers caused by wet cement, due to calcium hydroxyde, are rarely reported in the literature. They occur mostly among amateur cement users. We report seven cases of skin burns, necrosis and ulcerations after use of wet cement and ready-mixed concrete, and one case of caustic ulcers induced by wet lime. Even short skin contacts to wet cement or concrete may induce extensive lesions in some cases. However, we were not able to incriminate with certainty any special concrete additives which could increase skin penetration of calcium hydroxyde. Warning notices about the danger of skin contact should be prominent on sacked cement. When ready-mixed concrete is delivered, the purchaser should be handed a note explaining the risk of kneeling in wet concrete and the importance of protective measures. This may probably contribute to reduce the frequency of those accidents.

  17. 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.

  18. Minimal hardware Bluetooth tracking for long-term at-home elder supervision.

    PubMed

    Kelly, Damian; McLoone, Sean; Farrell, Ronan

    2010-01-01

    The ability to automatically detect the location of an elder within their own home is a significant enabler of remote elder supervision and interaction applications. This location information is typically generated via a myriad of sensors throughout the home environment. Even with high sensor redundancy, there are still situations where traditional elder monitoring systems are unable to resolve the location of the elder. This work develops a minimal infrastructure radio-frequency localisation system for long-term elder location tracking. An RFID room-labelling technique is employed and with it, the localisation system developed in this work is shown to exhibit superior performance to more traditional localisation systems in realistic long-term deployments.

  19. [Extragenital endometriosis: Parietal, thoracic, diaphragmatic and nervous lesions. CNGOF-HAS Endometriosis Guidelines].

    PubMed

    Merlot, B; Ploteau, S; Abergel, A; Rubob, C; Hocke, C; Canis, M; Fritel, X; Roman, H; Collinet, P

    2018-03-01

    According to some studies, extragenital endometriosis represents 5% of the localisations. Its prevalence seems to be underestimated. The extra pelvic localisation can make the diagnosis more difficult. Nevertheless, the recurrent and catamenial symptomatology can evoke this pathology. Surgery seems to be the unique efficient treatment for parietal lesions. Pain linked to nervous lesions (peripheric and sacral roots) seems to be underestimated and difficult to diagnose because of various localisations. Neurolysis seems to have encouraging results. Diaphragmatic lesions are often discovered either incidentally during laparoscopy, or by pulmonary symptomatology as recurrent catamenial pneumothorax or cyclic thoracic pain. Surgical treatment seems as well to be efficient. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Nationalisation, Localisation and Globalisation in Finnish Higher Education

    ERIC Educational Resources Information Center

    Valimaa, Jussi

    2004-01-01

    This article analyses and discusses the interplay between the social processes of nationalisation, localisation and globalisation in a single European nation state. The view of nationalisation put forward draws on a national case study based on historical and sociological research findings. The second part of the article presents a case study of…

  1. Collaborations between Foreign-Invested Enterprises and China's VET Schools: Making the System Work amid Localised Skill Shortages

    ERIC Educational Resources Information Center

    Li, Yiqiong; Sheldon, Peter

    2014-01-01

    This article examines collaborative initiatives individual foreign-invested enterprises (FIEs) develop with China's vocational education and training (VET) schools amid localised shortages of skilled workers. It thus focuses on employer initiatives in responding to VET system weaknesses rather than, as is common, those weaknesses. Using Suzhou…

  2. Nuclear localisation of calreticulin in vivo is enhanced by its interaction with glucocorticoid receptors.

    PubMed

    Roderick, H L; Campbell, A K; Llewellyn, D H

    1997-03-24

    The multi-functional protein calreticulin (CRT) is normally found within the lumen of the endoplasmic reticulum (ER). However, some of its proposed functions require it to be located within the nucleus, where its presence is contentious. We have investigated this in live COS7, HeLa and LM(TK-) cells using green fluorescent protein (GFP)-fusion proteins. GFP-CRT, and GFP, with an ER signal peptide and a KDEL sequence (ER-GFP), were localised to the ER. In addition, GFP-CRT was located in the nucleus of all the cell types at low levels. The higher levels of nuclear fluorescence in LM(TK-) and HeLa cells suggested that glucocorticoid receptors might enhance nuclear localisation of calreticulin. Dexamethasone treatment of LM(TK-) cells doubled the amount of nuclear GFP-CRT, but did not affect the localisation of a GFP-CRT fusion in which the glucocorticoid receptor-binding N-domain of calreticulin had been deleted. Thus, despite ER targeting and retention signals, calreticulin is also located within the nucleus where its presence increases due to its interaction with glucocorticoid receptors.

  3. Connexin Communication Compartments and Wound Repair in Epithelial Tissue.

    PubMed

    Chanson, Marc; Watanabe, Masakatsu; O'Shaughnessy, Erin M; Zoso, Alice; Martin, Patricia E

    2018-05-03

    Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems.

  4. Phosphorylation of Tat-interactive protein 60 kDa by protein kinase C epsilon is important for its subcellular localisation.

    PubMed

    Sapountzi, Vasileia; Logan, Ian R; Nelson, Glyn; Cook, Susan; Robson, Craig N

    2008-01-01

    Tat-interactive protein 60 kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60 kDa is phosphorylated by protein kinase C epsilon. In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60 kDa and the interaction of Tat-interactive protein 60 kDa with protein kinase C epsilon. A phosphomimetic mutant Tat-interactive protein 60 kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase C epsilon phosphorylation sites on Tat-interactive protein 60 kDa are important for its subcellular localisation. Regulation of the subcellular localisation of Tat-interactive protein 60 kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60 kDa function.

  5. The geometry of propagating rifts

    NASA Astrophysics Data System (ADS)

    McKenzie, Dan

    1986-03-01

    The kinematics of two different processes are investigated, both of which have been described as rift propagation. Courtillot uses this term to describe the change from distributed to localised extension which occurs during the early development of an ocean basin. The term localisation is instead used here to describe this process, to distinguish it from Hey's type of propagation. Localisation generally leads to rotation of the direction of magnetisation. To Hey propagation means the extension of a rift into the undeformed plate beyond a transform fault. Detail surveys of the Galapagos rift have shown that the propagating and failing rifts are not connected by a single transform fault, but by a zone which is undergoing shear. The principal deformation is simple shear, and the kinematics of this deformation are investigated in some detail. The strike of most of the lineations observed in the area can be produced by such deformation. The mode of extension on the propagating rift appears to be localised for some periods but to be distributed for others. Neither simple kinematic arguments nor stretching of the lithosphere with conservation of crust can account for the observed variations in water depth.

  6. Reliability of horizontal and vertical tube shift techniques in the localisation of supernumerary teeth.

    PubMed

    Mallineni, S K; Anthonappa, R P; King, N M

    2016-12-01

    To assess the reliability of the vertical tube shift technique (VTST) and horizontal tube shift technique (HTST) for the localisation of unerupted supernumerary teeth (ST) in the anterior region of the maxilla. A convenience sample of 83 patients who attended a major teaching hospital because of unerupted ST was selected. Only non-syndromic patients with ST and who had complete clinical and radiographic and surgical records were included in the study. Ten examiners independently rated the paired set of radiographs for each technique. Chi-square test, paired t test and kappa statistics were employed to assess the intra- and inter-examiner reliability. Paired sets of 1660 radiographs (830 pairs for each technique) were available for the analysis. The overall sensitivity for VTST and HTST was 80.6 and 72.1% respectively, with slight inter-examiner and good intra-examiner reliability. Statistically significant differences were evident between the two localisation techniques (p < 0.05). Localisation of unerupted ST using VTST was more successful than HTST in the anterior region of the maxilla.

  7. Intracellular localisation of proteins to specific cellular areas by nanocapsule mediated delivery.

    PubMed

    Wang, Huabin; Chen, Ligang; Sun, Xianchao; Fu, Ailing

    2017-09-01

    Nanocapsules are promising carriers with great potential for intracellular protein transport. Although many studies have intended to improve cell uptake efficacy, there is an increasing interest in understanding of subcellular distribution of cargoes inside cells, which is essential for purposeful delivery of biomolecules into specific sites within cells. Herein, we interrogate the intracellular localisation of exogenous proteins, including fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) and green fluorescent protein (GFP), mediated by specially designed nanocapsules. The results show that the designed nanocapsules can deliver the two types of fluorescent proteins into different cellular destinations (cytosol, nucleus or the whole cell), depending on the composition of nanocapsules. Meanwhile, several impact factors that influence the distribution of proteins in cells have also been investigated, and the results suggest that the localisation of capsule-mediated proteins in cells is strongly affected by the surface properties of nanocapsules, the types of stabilisers and proteins, and environmental temperatures. The rational control of intracellular localised delivery of exogenous proteins as we demonstrated in this study might open new avenues to obtain desired magnitude of drug effects for modulating cell activity.

  8. Mechanisms for localising calcineurin and CaMKII in dendritic spines.

    PubMed

    Penny, Christopher J; Gold, Matthew G

    2018-05-27

    Calcineurin and calmodulin-dependent protein kinase II (CaMKII) are both highly abundant in neurons, and both are activated by calmodulin at similar Ca 2+ concentrations in the test tube. However, they fulfill opposite functions in dendritic spines, with CaMKII activity driving long-term synaptic potentiation following large influxes of Ca 2+ through NMDA-type glutamate receptors (NMDARs), and calcineurin responding to smaller influxes of Ca 2+ through the same receptors to induce long-term depression. In this review, we explore the notion that precise dynamic localisation of the two enzymes at different sites within dendritic spines is fundamental to this behavior. We describe the structural basis of calcineurin and CaMKII localisation by their interaction with proteins including AKAP79, densin-180, α-actinin, and NMDARs. We then consider how interactions with these proteins likely position calcineurin and CaMKII at different distances from Ca 2+ microdomains emanating from the mouths of NMDARs in order to drive the divergent responses. We also highlight shortcomings in our current understanding of synaptic localisation of these two important signalling enzymes. Copyright © 2017. Published by Elsevier Inc.

  9. Oxygen environment and islet size are the primary limiting factors of isolated pancreatic islet survival

    PubMed Central

    Komatsu, Hirotake; Cook, Colin; Wang, Chia-Hao; Medrano, Leonard; Lin, Henry; Kandeel, Fouad; Tai, Yu-Chong; Mullen, Yoko

    2017-01-01

    Background Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency. Methodology The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model. In vitro human islet viability was also assessed after culturing in different oxygen conditions. Correlation between simulation data and experimentally measured islet viability was examined. Using these in vitro viability data of human islets, the effect of islet diameter and oxygen tension of the culture environment on islet viability was also analyzed using a logistic regression model. Principal findings Computational simulation clearly revealed the oxygen gradient inside the islet structure. We found that oxygen tension in the islet core was greatly lower (hypoxic) than that on the islet surface due to the oxygen consumption by the cells. The hypoxic core was expanded in the larger islets or in lower oxygen cultures. These findings were consistent with results from in vitro islet viability assays that measured central necrosis in the islet core, indicating that hypoxia is one of the major causes of central necrosis. The logistic regression analysis revealed a negative effect of large islet and low oxygen culture on islet survival. Conclusions/Significance Hypoxic core conditions, induced by the oxygen gradient inside islets, contribute to the development of central necrosis of human isolated islets. Supplying sufficient oxygen during culture could be an effective and reasonable method to maintain isolated islets viable. PMID:28832685

  10. Experimental investigation of temperature rise in bone drilling with cooling: A comparison between modes of without cooling, internal gas cooling, and external liquid cooling.

    PubMed

    Shakouri, Ehsan; Haghighi Hassanalideh, Hossein; Gholampour, Seifollah

    2018-01-01

    Bone fracture occurs due to accident, aging, and disease. For the treatment of bone fractures, it is essential that the bones are kept fixed in the right place. In complex fractures, internal fixation or external methods are used to fix the fracture position. In order to immobilize the fracture position and connect the holder equipment to it, bone drilling is required. During the drilling of the bone, the required forces to chip formation could cause an increase in the temperature. If the resulting temperature increases to 47 °C, it causes thermal necrosis of the bone. Thermal necrosis decreases bone strength in the hole and, subsequently, due to incomplete immobilization of bone, fracture repair is not performed correctly. In this study, attempts have been made to compare local temperature increases in different processes of bone drilling. This comparison has been done between drilling without cooling, drilling with gas cooling, and liquid cooling on bovine femur. Drilling tests with gas coolant using direct injection of CO 2 and N 2 gases were carried out by internal coolant drill bit. The results showed that with the use of gas coolant, the elevation of temperature has limited to 6 °C and the thermal necrosis is prevented. Maximum temperature rise reached in drilling without cooling was 56 °C, using gas and liquid coolant, a maximum temperature elevation of 43 °C and 42 °C have been obtained, respectively. This resulted in decreased possibility of thermal necrosis of bone in drilling with gas and liquid cooling. However, the results showed that the values obtained with the drilling method with direct gas cooling are independent of the rotational speed of drill.

  11. Distribution of lesions and antigen of highly pathogenic avian influenza virus A/Swan/Germany/R65/06 (H5N1) in domestic cats after presumptive infection by wild birds.

    PubMed

    Klopfleisch, R; Wolf, P U; Uhl, W; Gerst, S; Harder, T; Starick, E; Vahlenkamp, T W; Mettenleiter, T C; Teifke, J P

    2007-05-01

    In early 2006, the highly pathogenic avian influenza virus (HPAIV) H5N1 of the Asian lineage caused the death of wild aquatic birds in Northern Germany. In the mainly affected areas, a trans-species transmission of HPAIV H5N1 to mammals occurred between birds and domestic cats and 1 Stone Marten (Martes foina), respectively. Here, we report lesions and distribution of influenza virus antigen in 3 cats infected naturally with HPAIV H5N1 A/swan/Germany/R65/06. The hemagglutinin partial nucleotide sequences of the viruses were genetically closely related to a H5N1 HPAIV obtained from a dead Whooper Swan (Cygnus cygnus) of the same area. At necropsy, within the patchy dark-red and consolidated lungs, there was granulomatous pneumonia caused by Aelurostrongylus sp. Histologically, the main findings associated with influenza in all cats were bronchointerstitial pneumonia and marked random hepatic necrosis. In addition, all animals displayed lymphoid necrosis in the spleen and Peyer's patches and necrosis of the adrenal cortex. Immunohistochemically, nucleoprotein of HPAIV was present intralesionally in the lungs, liver, adrenal glands, and lymphoid tissues. Oropharyngeal swabs were shown to be suited to detect HPAIV by quantitative real-time polymerase chain reaction (RT-PCR) in these cats, despite the paucity of influenza virus antigen in the upper respiratory tract by means of immunohistochemistry. The results show that outdoor cats in areas affected by HPAIV in wild birds are at risk for lethal infection. In conclusion, hepatic necrosis was, besides bronchointerstitial pneumonia, the primary lesion, suggesting that in naturally infected cats, damage to the liver plays an important role in the pathogenesis of H5N1 influenza.

  12. Continuous thermographic observation may predict extravasation in chemotherapy-treated patients.

    PubMed

    Oya, Maiko; Murayama, Ryoko; Oe, Makoto; Yabunaka, Koichi; Tanabe, Hidenori; Takahashi, Toshiaki; Matsui, Yuko; Otomo, Eiko; Komiyama, Chieko; Sanada, Hiromi

    2017-06-01

    Extravasation, or leakage of vesicant drugs into subcutaneous tissues, causes serious complications such as induration and necrosis in chemotherapy-treated patients. As macroscopic observation may overlook symptoms during infusion, we focused on skin temperature changes at puncture sites and studied thermographic patterns related to induration or necrosis caused by extravasation. Outpatients undergoing chemotherapy using peripheral intravenous catheters were enrolled in this prospective observational study. We filmed and classified infrared thermography movies of puncture sites during infusion; ultrasonography was also utilized at puncture sites to observe the subcutaneous condition. Multiple logistic regression analysis was performed to examine the association of thermographic patterns with induration or necrosis observed on the next chemotherapy day. Differences in patient characteristics, puncture sites, and infusions were analyzed by Mann-Whitney's U test and Fisher's exact test according to thermographic patterns. Eight patients developed induration among 74 observations in 62 patients. Among six thermographic patterns, a fan-shaped lower temperature area gradually spreading from the puncture site (fan at puncture site) was significantly associated with induration. Ultrasonography revealed that catheters of patients with fan at puncture site remained in the vein at the end of infusion, indicating that the infusion probably leaked from the puncture site. Patients with fan at puncture site had no significant differences in characteristics and infusion conditions compared with those with the other five thermographic patterns. We determined that fan at puncture site was related to induration caused by extravasation. Continuous thermographic observation may enable us to predict adverse events of chemotherapy. Copyright © 2017. Published by Elsevier Ltd.

  13. Late effects of whole brain irradiation within the therapeutic range

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage x irradiation was carried out in three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures, respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvement at and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation.more » Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20 to 26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys.« less

  14. Current Understanding of Acute Bovine Liver Disease in Australia.

    PubMed

    Read, Elizabeth; Edwards, Jacqueline; Deseo, Myrna; Rawlin, Grant; Rochfort, Simone

    2016-12-26

    Acute bovine liver disease (ABLD) is a hepatotoxicity principally of cattle which occurs in southern regions of Australia. Severely affected animals undergo rapid clinical progression with mortalities often occurring prior to the recognition of clinical signs. Less severely affected animals develop photosensitization and a proportion can develop liver failure. The characteristic histopathological lesion in acute fatal cases is severe, with acute necrosis of periportal hepatocytes with hemorrhage into the necrotic areas. Currently there are a small number of toxins that are known to cause periportal necrosis in cattle, although none of these have so far been linked to ABLD. Furthermore, ABLD has frequently been associated with the presence of rough dog's tail grass ( Cynosurus echinatus ) and Drechslera spp. fungi in the pasture system, but it is currently unknown if these are etiological factors. Much of the knowledge about ABLD is contained within case reports, with very little experimental research investigating the specific cause(s). This review provides an overview of the current and most recently published knowledge of ABLD. It also draws on wider research and unpublished reports to suggest possible fungi and mycotoxins that may give rise to ABLD.

  15. Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

    PubMed Central

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

    2012-01-01

    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats. PMID:22666115

  16. Membrane glucocorticoid receptors are localised in the extracellular matrix and signal through the MAPK pathway in mammalian skeletal muscle fibres

    PubMed Central

    Boncompagni, Simona; Arthurton, Lewis; Akujuru, Eugene; Pearson, Timothy; Steverding, Dietmar; Protasi, Feliciano; Mutungi, Gabriel

    2015-01-01

    A number of studies have previously proposed the existence of glucocorticoid receptors on the plasma membrane of many cell types, including skeletal muscle fibres. However, their exact localisation and the cellular signalling pathway(s) they utilise to communicate with the rest of the cell are still poorly understood. In this study, we investigated the localisation and the mechanism(s) underlying the non-genomic physiological functions of these receptors in mouse skeletal muscle cells. The results show that the receptors were localised in the cytoplasm in myoblasts, in the nucleus in myotubes, in the extracellular matrix, in satellite cells and in the proximity of mitochondria in adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent manner. Treating small skeletal muscle fibre bundles with the synthetic glucocorticoid beclomethasone dipropionate increased the phosphorylation (= activation) of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. This occurred within 5 min and depended on the fibre type and the duration of the treatment. It was also abolished by the glucocorticoid receptor inhibitor, mifepristone, and a monoclonal antibody against the receptor. From these results we conclude that the non-genomic/non-canonical physiological functions of glucocorticoids, in adult skeletal muscle fibres, are mediated by a glucocorticoid receptor localised in the extracellular matrix, in satellite cells and close to mitochondria, and involve activation of the mitogen-activated protein kinase pathway. PMID:25846902

  17. Novel technology of molecular radio-guidance for lymph node dissection in recurrent prostate cancer by PSMA-ligands.

    PubMed

    Rauscher, Isabel; Horn, Thomas; Eiber, Matthias; Gschwend, Jürgen E; Maurer, Tobias

    2018-04-01

    Recently, prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) has been introduced as a promising new and individual treatment concept in patients with localised recurrent prostate cancer (PC). In the following, we want to review our experience with PSMA-RGS in patients with localised biochemical recurrent PC. A non-systematic review of the literature was carried out with focus on technical and logistical aspects of PSMA-RGS. Furthermore, published data on intraoperative detection of metastatic lesions compared to preoperative PSMA-PET and postoperative histopathology, postoperative complications as well as oncological follow-up data are summarized. Finally, relevant aspects on prerequisites for PSMA-RGS, patient selection, and the potential benefit of additional salvage radiotherapy or potential future applications of robotic PSMA-RGS with drop-in γ-probes are discussed. First results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for patient selection and localisation of tumour recurrence is a positive Ga-HBED-CC PSMA positron-emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence after primary treatment. Furthermore, PSMA-RGS has the potential to positively influence oncological outcome. PSMA-RGS seems to be of high value in patients with localised PC recurrence for exact localisation and resection of oftentimes small metastatic lesions using intraoperative and ex vivo γ-probe measurements. However, patient identification on the basis of Ga-HBED-CC-PSMA PET imaging as well as clinical parameters is crucial to obtain satisfactory results.

  18. Modelling of deformation around magmatic intrusions with application to gold-related structures in the Yilgarn Craton, Western Australia

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Karrech, A.; Schaubs, P. M.; Regenauer-Lieb, K.; Poulet, T.; Cleverley, J. S.

    2012-03-01

    This study simulates rock deformation around high temperature granite intrusions and explores how gold bearing shear zones near intrusions were developed in the Yilgarn, using a new continuum damage mechanics algorithm that considers the temperature and time dependent elastic-visco-plastic constitutive behaviour of crustal materials. The results demonstrate that strain rates have the most significant effects on structural patterns for both extensional and compressional cases. Smaller strain rates promote the formation of narrow high-strain shear zones and strong strain localisation along the flank or shoulder areas of the intrusion and cold granite dome. Wider diffuse shear zones are developed under higher strain rates due to strain hardening. The cooling of the intrusion to background temperatures occurred over a much shorter time interval when compared to the duration of deformation and shear zones development. Strong strain localisation near the intrusion and shear zone development in the crust occurred under both extensional and compressional conditions. There is always clear strain localisation around the shoulders of the intrusion and the flanks of the "cold" granitic dome in early deformation stages. In the models containing a pre-existing fault, strain localisation near the intrusion became asymmetric with much stronger localisation and the development of a damage zone at the shoulder adjacent to the reactivated fault. At higher deformation stages, the models produced a range of structural patterns including graben and half graben basin (extension), "pop-up" wedge structures (compression), tilted fault blocks and switch of shear movement from reverse to normal on shear zones. The model explains in part why a number of gold deposits (e.g. Wallaby and Paddington deposits) in the Yilgarn were formed near the flank of granite-cored domes and deep "tapping" faults, and shows that the new modelling approach is capable of realistically simulating high strain localisation and shear zone development.

  19. Feasibility of imaging epileptic seizure onset with EIT and depth electrodes.

    PubMed

    Witkowska-Wrobel, Anna; Aristovich, Kirill; Faulkner, Mayo; Avery, James; Holder, David

    2018-06-01

    Imaging ictal and interictal activity with Electrical Impedance Tomography (EIT) using intracranial electrode mats has been demonstrated in animal models of epilepsy. In human epilepsy subjects undergoing presurgical evaluation, depth electrodes are often preferred. The purpose of this work was to evaluate the feasibility of using EIT to localise epileptogenic areas with intracranial electrodes in humans. The accuracy of localisation of the ictal onset zone was evaluated in computer simulations using 9M element FEM models derived from three subjects. 5 mm radius perturbations imitating a single seizure onset event were placed in several locations forming two groups: under depth electrode coverage and in the contralateral hemisphere. Simulations were made for impedance changes of 1% expected for neuronal depolarisation over milliseconds and 10% for cell swelling over seconds. Reconstructions were compared with EEG source modelling for a radially orientated dipole with respect to the closest EEG recording contact. The best accuracy of EIT was obtained using all depth and 32 scalp electrodes, greater than the equivalent accuracy with EEG inverse source modelling. The localisation error was 5.2 ± 1.8, 4.3 ± 0 and 46.2 ± 25.8 mm for perturbations within the volume enclosed by depth electrodes and 29.6 ± 38.7, 26.1 ± 36.2, 54.0 ± 26.2 mm for those without (EIT 1%, 10% change, EEG source modelling, n = 15 in 3 subjects, p < 0.01). As EIT was insensitive to source dipole orientation, all 15 perturbations within the volume enclosed by depth electrodes were localised, whereas the standard clinical method of visual inspection of EEG voltages, only localised 8 out of 15 cases. This suggests that adding EIT to SEEG measurements could be beneficial in localising the onset of seizures. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. The surgical manegement of metastases to humerus-clinical evaluation.

    PubMed

    Chrobok, Adam; Spindel, Jerzy; Miszczyk, Leszek; Koczy, Bogdan; Pilecki, Bogdan; Jarosz, Adam; Mrozek, Tomasz

    2003-06-30

    Background. The humerus is a common localisation of cancer metastases. The restoration of anatomical order and tumor resection within humerus is important for patients quality of everyday life and for their pain relief. The surgical treatment is one of the most important part of the whole oncological ways of tratment.
    The study objective was a clinical assesment of tumor resection and reconstruction within humerus according to matastasis localisation and the choice of surgical technique.
    Material and methods. In the years 1999-2002 19 patients underwent surgery due to pathological fracture or/and cancer metastasis within humerus. The shaft localisation of the tumor was found in 8 cases and in 11 patients the metastatic foci were found in proximnal diaphysis. In patients with proximal diaphysis localisation of the tumor the partial resection with subsequent joint exchange procedure was made. The humeral shaft metastatic cancer changes were treated by the segmental resection with subsequent surgical cement filling or auto/allogenical bone grafting combined with intramedullary nail or AO/ASIF plate stabilisation. The average follow-up period was 8,5 months.
    Results. In patients after resection with shoulder joint alloplasty according to the Enneking test a very good result was found in 7 and very good in 4 cases.
    In patients with femoral shaft metastatic tumor locaslisation, 6 good and 2 fair results were found. In 1 patient after 2 months rehabilitation a reoperation was needed due to the mechanical destabilisation. The best results were found in patients after intramedullary nailing.An acute soft tissue inflamation requiering surgical treatment was found in 1 patient after shoulder joint replacement.
    Conclusions. After clinical analysis of the material we highly recomend the partial humeral bone resection with subsequent shoulder alloplasty in patients with proximal humeral diaphysis metastatic localisation. In cases with shaft localisation a better results were found after intramedullary nailing compared to common plate technique.

  1. Physiological Disorders of Pear Shoot Cultures

    USDA-ARS?s Scientific Manuscript database

    Physiological disorders are some of the most difficult challenges in micropropagation. Little is known of the causes of plant growth disorders which include callus formation, hyperhydricity, shoot tip necrosis, leaf lesions, epinasty, fasciation and hypertrophy. During our study of mineral nutritio...

  2. The relationship of leaf rust resistance gene Lr13 and hybrid necrosis gene Ne2m on wheat chromosome 2BS.

    PubMed

    Zhang, Peng; Hiebert, Colin W; McIntosh, Robert A; McCallum, Brent D; Thomas, Julian B; Hoxha, Sami; Singh, Davinder; Bansal, Urmil

    2016-03-01

    Genetic and mutational analyses of wheat leaf rust resistance gene Lr13 and hybrid necrosis gene Ne2 m indicated that they are the same gene. Hybrid necrosis in wheat characterized by chlorosis and eventual necrosis of plant tissues in certain wheat hybrids is controlled by the interaction of complementary dominant genes Ne1 and Ne2 located on chromosome arms 5BL and 2BS, respectively. Multiple alleles at each locus can be identified by differences in necrotic phenotypes when varieties are crossed with a fixed accession of the other genotype. Some of at least five Ne2 alleles were described as s (strong), m (medium) and w (weak); alleles of Ne1 were similarly described. Ne2m causes moderate necrosis in hybrids with genotypes having Ne1s. Ne2 is located on chromosome arm 2BS in close proximity to Lr13. Most wheat lines with Ne2m carry Lr13, and all wheat lines with Lr13 appear to carry Ne2m. To further dissect the relationship between Lr13 and Ne2m, more than 350 crosses were made between cv. Spica (Triticum aestivum) or Kubanka (T. durum) carrying Ne1s and recombinant inbred lines or doubled haploid lines from three crosses segregating for Lr13. F1 plants from lines carrying Lr13 crossed with Spica (Ne1s) always showed progressive necrosis; those lacking Lr13 did not. Four wheat cultivars/lines carrying Lr13 were treated with the mutagen EMS. Thirty-five susceptible mutants were identified; eight were distinctly less glaucous and late maturing indicative of chromosome 2B or sub-chromosome loss. Hybrids of phenotypically normal Lr13 mutant plants crossed with Spica did not produce symptoms of hybrid necrosis. Thus, Lr13 and one particular Ne2m allele may be the same gene.

  3. Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice.

    PubMed

    Sendler, Matthias; Dummer, Annegret; Weiss, Frank U; Krüger, Burkhard; Wartmann, Thomas; Scharffetter-Kochanek, Karin; van Rooijen, Nico; Malla, Sudarshan Ravi; Aghdassi, Ali; Halangk, Walter; Lerch, Markus M; Mayerle, Julia

    2013-03-01

    Acute pancreatitis has long been considered a disorder of pancreatic self-digestion, in which intracellular activation of digestive proteases induces tissue injury. Chemokines, released from damaged pancreatic cells then attract inflammatory cells, whose systemic action ultimately determines the disease severity. In the present work the opposite mechanism is investigated; that is, whether and how inflammatory cells can activate intracellular proteases. Using mice either deficient for the CD18-α subunit of the membrane attack complex-1 (MAC-1) complex or tumour necrosis factor (TNF)α, as well as after depletion of leucocyte subpopulations, pancreatitis was induced by 7-hourly caerulein injections (50 μg/kg, intraperitoneally). Pancreatic acini were coincubated in vitro from wild-type and cathepsin-B-deficient animals with phorbol-12-myristate-13-acetate (PMA)-activated neutrophils and macrophages, caerulein or TNFα, and activities of trypsin, cathepsin-B and caspase-3 were measured, as well as necrosis using fluorogenic substrates. TNFα was inhibited with monospecific antibodies. Deletion of CD18 prevented transmigration of leucocytes into the pancreas during pancreatitis, greatly reduced disease severity and abolished digestive protease activation. Depletion of neutrophils and macrophages equally reduced premature trypsinogen activation and disease severity. In vitro activated neutrophils and macrophages directly induced premature protease activation and cell death in pancreatic acini and stimulation of acini with TNFα induced caspase-3 activation and necrosis via a cathepsin-B and calcium-dependent mechanism. Neutralising antibodies against TNFα and genetic deletion of TNFα prevented leucocyte-induced trypsin activity and necrosis in isolated acini. The soluble inflammatory cell mediator TNFα directly induces premature protease activation and necrosis in pancreatic acinar cells. This activation depends on calcium and cathepsin-B activity. The findings from the present work further suggest that targeting TNFα, for which pharmaceutical agents are readily available, could be an effective treatment strategy that directly addresses the cellular causes of pancreatitis.

  4. Human Bone Matrix Changes During Deep Saturation Dives

    DTIC Science & Technology

    2008-08-08

    of theories have been investigated to elucidate this 2 separate factor. They include fat embolism , decompression triggered intravascular...arterial gas embolism . In bone, bubbles can also cause a mechanical blockage of blood flow that result in tissue damage and necrosis. Blood flow is...exposures, but the longest follow-up to date is only 10 years.11 If lesions progress and cause femoral fractures or osteoarthritis, the typical

  5. Necrosis After Craniospinal Irradiation: Results From a Prospective Series of Children With Central Nervous System Embryonal Tumors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Murphy, Erin S.; Merchant, Thomas E., E-mail: thomas.merchant@stjude.org; Wu Shengjie

    Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy tomore » the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% {+-} 1.3% (n = 236) for the entire cohort and 4.4% {+-} 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: {>=}50 Gy (92.12% {+-} 4.58% vs 72.89% {+-} 1.96%; P=.0337), {>=}52 Gy (88.95% {+-} 5.50% vs 69.16% {+-} 1.97%; P=.0275), and {>=}54 Gy (82.28% {+-} 7.06% vs 63.37% {+-} 1.96%; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.« less

  6. Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lash, Lawrence H.; Putt, David A.; Hueni, Sarah E.

    Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg{sup 2+}) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg{sup 2+} increased expression of glutathione S-transferase-{alpha}1 (GST{alpha}1) but decreased expression of GST{alpha}2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI.more » Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg{sup 2+}. Pretreatment of human proximal tubular (hPT) cells with Hg{sup 2+} caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg{sup 2+} by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg{sup 2+} exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg{sup 2+}-induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg{sup 2+}, TRI, or DCVC are markedly altered by prior exposures.« less

  7. Effects of nitroglycerin ointment on mastectomy flap necrosis in immediate breast reconstruction: a randomized controlled trial.

    PubMed

    Gdalevitch, Perry; Van Laeken, Nancy; Bahng, Seokjae; Ho, Adelyn; Bovill, Esta; Lennox, Peter; Brasher, Penelope; Macadam, Sheina

    2015-06-01

    Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo. This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing. The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)]. In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis. Therapeutic, I.

  8. [Visceral diseases as cause of lumbar syndromes].

    PubMed

    Tilscher, H; Bogner, G; Landsiedl, F

    1977-01-01

    30 patients with hepatitis, 50 patients with gynecological diseases, and 100 with urological diseases were investigated with regards to lumbago to find out whether there is a correlation between the internal disease and the signs of low back pain. The patients were compared with a control group of 33 healthy people. The vertebral localisation of the pain and its radiation were investigated and discussed in certain diseases as well as any correlation between lumbago and average age. The various possibilities of pain radiation are described and the importance of the vertebral column as secondary seat of low back pain is pointed out.

  9. Globalisation and Localisation in Music Education in Hong Kong and Taiwan

    ERIC Educational Resources Information Center

    Ho, Wai-Chung

    2013-01-01

    The purpose of the study is to analyse and discuss the influences of globalisation and localisation on music education in Hong Kong and Taiwan. It argues that the reform of music education concerns changes to the contents of the curriculum that envisage the cultural and political developments that arise from processes of globalisation and…

  10. The management of anterior tooth wear using gold palatal veneers in canine guidance.

    PubMed

    Eliyas, S; Martin, N

    2013-03-01

    Localised anterior tooth wear can be managed using minimally invasive techniques with conservation of tooth structure and preservation of pulp vitality. This article describes and illustrates with two clinical cases, the management of localised tooth wear, with the restoration of canine guidance by a combination of gold palatal veneers and direct composite restorations.

  11. Application of the Localisation Platform Crowdin in Translator Education

    ERIC Educational Resources Information Center

    Kudla, Dominik

    2017-01-01

    This article is an attempt to briefly describe the potential of the online localisation platform Crowdin for the education of the future translators at universities and in private courses or workshops. This description is provided on the basis of the information gathered through the user experience of the author and uses the example of the Khan…

  12. Robust weak anti-localisation effect in strongly textured nanocrystalline Bi2Se3 samples

    NASA Astrophysics Data System (ADS)

    Pereira, V. M. M.; Henriques, M. S. C.; Paixão, J. A.

    2018-05-01

    Topological insulators are a quantum state of matter that has recently created a great interest among the scientific community, with Bi2Se3 being one of the most extensively studied materials. Here, we demonstrate that polycrystalline nanostructured samples of Bi2Se3 preserve the existence of topological surface states, where electrons cannot be localised. The nanosheet crystals were synthesised by a microwave-assisted method and their structure, composition and morphology thoroughly characterised. The transport properties of a textured polycrystalline sample with strong preferred orientation along the c-axis were measured, showing the presence of the weak anti-localisation effect and Shubnikov-de Haas oscillations. These features are robust against the presence of non-magnetic impurities and structural defects.

  13. Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Klein, Seth J., E-mail: kleins@mir.wustl.edu; Saad, Nael; Korenblat, Kevin

    A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

  14. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

    PubMed Central

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-01-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN. PMID:29582832

  15. [Rhytidectomy and Raynaud's phenomenon: about two cases].

    PubMed

    Nicolas, J; Labbé, D

    2004-12-01

    Raynaud's phenomenon is a currently vascular syndrome (8 to 10% of women and 3 to 5% of men). It was defined as episodic ischaemia of the fingers, toes, nose, ears and nipples, which presents clinically as pallor, cyanosis, and often rubor of the skins, in response to cold, emotional stimuli and vasoconstriction agents. The phenomenon is caused by a vasoconstriction of arterials skin. In severe forms of the phenomenon, we can see ulcerations and necrosis. We report here two cases of rhytidectomy flap necrosis in Raynaud's Phenomenon. After review of literature, we explain the elements of physiopathology whose can explain these complications and we try to establish recommendations to these complications.

  16. QTL mapping of sulfur tolerance in melon

    USDA-ARS?s Scientific Manuscript database

    Elemental sulfur is a cheap, effective fungicide with multi-site action, which inhibits the evolution of pathogen resistance. Fungal pathogens cause significant yield losses in melon production. Many melon genotypes, however, suffer leaf necrosis in response to elemental sulfur application preventin...

  17. Lettuce dieback

    USDA-ARS?s Scientific Manuscript database

    Two related viruses, Tomato bushy stunt virus (TBSV) and Moroccan pepper virus (MPV) cause a disease known as lettuce dieback in California and Arizona. Lettuce dieback is characterized by yellowing, necrosis, stunting and death of lettuce plants, and often occurs in low lying areas with poor drain...

  18. Superomedial pedicle reduction mammaplasty: increased resection weight does not increase nipple necrosis.

    PubMed

    Brownlee, Pamela; Chesire, David; Crandall, Marie; Murray, John

    2017-11-01

    The superomedial pedicle (SMP) reduction mammaplasty offers several advantages over more traditional operative techniques, such as retained sensation to the nipple areola complex (NAC) and improved preservation of long-term breast shape. However, many surgeons believe that using the SMP can cause an increase in NAC necrosis rates up to 13.1%, especially in large volume reductions. The aims of this paper are to determine the rate of nipple necrosis when performing an SMP reduction mammaplasty at our institution and establish if there is a difference in those rates based on the weight of tissue removed. We then compared our overall rate of nipple necrosis to those found using a systematic review of literature involving other pedicles to determine if this technique is equivalent to more commonly used methods. We performed a retrospective chart review of patients who underwent breast reduction surgery using SMP at a single institution between May 1, 2013, and May 1, 2015. Each breast was counted separately, and the weight of the tissue removed was recorded. Six-mo follow-up data were analyzed using the chi-square analysis to compare rates of NAC necrosis among our patients and historical cohorts. One hundred thirty-five breasts (70 patients) met inclusion criteria. Patients had a mean resection weight per breast of 1016.7 g (±478.3). There was an NAC necrosis rate of 0% in the groups where 1200 g or less of tissue were removed and 2.3% (n = 1) in the group where greater than 1200 g of tissue were removed. We found no statistically significant difference in the rate of NAC necrosis with increased resection weights, (P = 0.32). The overall rate of NAC necrosis for this study was 0.7% per breast, which is equivalent to the rates found during the systematic review of literature. In this study, the SMP breast reduction technique shows a low rate of NAC. We found no statistically significant increase in NAC necrosis rates as the volume of tissue removed increases, and the SMP appears to have an overall rate of NAC necrosis similar to more commonly used pedicles. Although the results of this study may be related to patient selection or surgical technique, we believe that this pedicle preserves the breast's main blood supply so that less tissue ischemia occurs. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The role of electrical stimulation in the management of avascular necrosis of the femoral head in adults: a systematic review.

    PubMed

    Al-Jabri, Talal; Tan, Jessica Yan Qi; Tong, Gabriel Yihan; Shenoy, Ravikiran; Kayani, Babar; Parratt, Timothy; Khan, Tahir

    2017-07-28

    Avascular necrosis of the femoral head causes significant morbidity and occurs in up to 20,000 people per year. A variety of nonoperative and operative measures have been trialled however a definitive treatment algorithm is yet to be established. Young adults in many cases have undergone multiple surgical procedures in their lifetime with increasing risks of complications. Less invasive techniques may help reduce the number of operations required and positively influence the natural history of the disease process. Our aim was to navigate the literature and examine the results of electrical stimulation of the femoral head in avascular necrosis. The following defined search strategy was used to perform a systematic review using MEDLINE and Google Scholar databases: ((avascular necrosis) OR (osteonecrosis)) AND (femoral head) AND ((electrical stimulation) OR (capacitive coupling) OR (pulsed electromagnetic fields)). Articles were reviewed and data compiled into tables for analysis. Fourty six articles were identified with a total of 10 articles meeting the inclusion criteria. 8 articles were prospective studies and 2 were retrospective. Early Ficat stages showed the best responses to treatment via pulsed electromagnetic fields with improvements in both clinical and radiographic parameters. Direct current and capacitative coupling have had a more ambiguous outcome. Pulsed electromagnetic fields may have a role in the management of early avascular necrosis. The paucity of clinical studies into this technique indicates a need for further studies.

  20. CCL11-induced eosinophils inhibit the formation of blood vessels and cause tumor necrosis.

    PubMed

    Xing, Yanjiang; Tian, Yijun; Kurosawa, Takamasa; Matsui, Sayaka; Touma, Maki; Yanai, Takanori; Wu, Qiong; Sugimoto, Kenkichi

    2016-06-01

    We previously demonstrated that IL-18 and CCL11 were highly expressed in an NFSA tumor cell line that showed limited angiogenesis and severe necrosis. However, IL-18 was not responsible for the immune cell accumulation and necrosis. Here, we attempted to clarify the relevance of CCL11 in angiogenesis and tumor formation. We established CCL11-overexpressing MS-K cell clones (MS-K-CCL11) to assess the role of CCL11 in immune cell accumulation and angiogenesis. The MS-K-CCL11 cells did not form tumors in mice. MS-K-CCL11-conditioned medium (CM) and recombinant CCL11 induced macrophage and eosinophil differentiation from bone marrow cells. The MS-K-CCL11-CM effectively recruited the differentiated eosinophils. Furthermore, the eosinophils damaged the MS-K, NFSA and endothelial cells in a dose-dependent manner. Administration of an antagonist of CCR3, a CCL11 receptor, to NFSA tumor-bearing mice restored the blood vessel formation and blocked the eosinophil infiltration into the NFSA tumors. Furthermore, other CCL11-overexpressing LM8 clones were established, and their tumor formation ability was reduced compared to the parental LM8 cells, accompanied by increased eosinophil infiltration, blockade of angiogenesis and necrosis. These results indicate that CCL11 was responsible for the limited angiogenesis and necrosis by inducing and attracting eosinophils in the tumors. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  1. Carrot yellow leaf virus is associated with carrot internal necrosis.

    PubMed

    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.

  2. Heat stress induces different forms of cell death in sea anemones and their endosymbiotic algae depending on temperature and duration.

    PubMed

    Dunn, S R; Thomason, J C; Le Tissier, M D A; Bythell, J C

    2004-11-01

    Bleaching of reef building corals and other symbiotic cnidarians due to the loss of their dinoflagellate algal symbionts (=zooxanthellae), and/or their photosynthetic pigments, is a common sign of environmental stress. Mass bleaching events are becoming an increasingly important cause of mortality and reef degradation on a global scale, linked by many to global climate change. However, the cellular mechanisms of stress-induced bleaching remain largely unresolved. In this study, the frequency of apoptosis-like and necrosis-like cell death was determined in the symbiotic sea anemone Aiptasia sp. using criteria that had previously been validated for this symbiosis as indicators of programmed cell death (PCD) and necrosis. Results indicate that PCD and necrosis occur simultaneously in both host tissues and zooxanthellae subject to environmentally relevant doses of heat stress. Frequency of PCD in the anemone endoderm increased within minutes of treatment. Peak rates of apoptosis-like cell death in the host were coincident with the timing of loss of zooxanthellae during bleaching. The proportion of apoptosis-like host cells subsequently declined while cell necrosis increased. In the zooxanthellae, both apoptosis-like and necrosis-like activity increased throughout the duration of the experiment (6 days), dependent on temperature dose. A stress-mediated PCD pathway is an important part of the thermal stress response in the sea anemone symbiosis and this study suggests that PCD may play different roles in different components of the symbiosis during bleaching.

  3. Restoration of mutant bestrophin-1 expression, localisation and function in a polarised epithelial cell model

    PubMed Central

    Briant, Kit; Streit, Anne-Kathrin; Thomson, Steven; Koay, Yee Hui

    2016-01-01

    ABSTRACT Autosomal recessive bestrophinopathy (ARB) is a retinopathy caused by mutations in the bestrophin-1 protein, which is thought to function as a Ca2+-gated Cl− channel in the basolateral surface of the retinal pigment epithelium (RPE). Using a stably transfected polarised epithelial cell model, we show that four ARB mutant bestrophin-1 proteins were mislocalised and subjected to proteasomal degradation. In contrast to the wild-type bestrophin-1, each of the four mutant proteins also failed to conduct Cl− ions in transiently transfected cells as determined by whole-cell patch clamp. We demonstrate that a combination of two clinically approved drugs, bortezomib and 4-phenylbutyrate (4PBA), successfully restored the expression and localisation of all four ARB mutant bestrophin-1 proteins. Importantly, the Cl− conductance function of each of the mutant bestrophin-1 proteins was fully restored to that of wild-type bestrophin-1 by treatment of cells with 4PBA alone. The functional rescue achieved with 4PBA is significant because it suggests that this drug, which is already approved for long-term use in infants and adults, might represent a promising therapy for the treatment of ARB and other bestrophinopathies resulting from missense mutations in BEST1. PMID:27519691

  4. X-ray tomographic imaging of tensile deformation modes of electrospun biodegradable polyester fibres

    NASA Astrophysics Data System (ADS)

    Maksimcuka, Jekaterina; Obata, Akiko; Sampson, William W.; Blanc, Remi; Gao, Chunxia; Withers, Philip J.; Tsigkou, Olga; Kasuga, Toshihiro; Lee, Peter D.; Poologasundarampillai, Gowsihan

    2017-12-01

    Electrospinning allows the production of fibrous networks for tissue engineering, drug delivery and wound healing in healthcare. It enables the production of constructs with large surface area and a fibrous morphology that closely resembles the extracellular matrix of many tissues. A fibrous structure not only promotes cell attachment and tissue formation, but could also lead to very interesting mechanical properties. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) is a biodegradable polyester that exhibits large (>400%) elongation before failure. In this study, synchrotron X-ray phase contrast imaging was performed during tensile deformation to failure on a non-woven fibre mat of P(3HB-co-4HB) fibres. Significant reorientation of the fibres in straining direction was observed, followed by localised necking and eventual failure. From an original average fibre diameter of 4.3 μm a bimodal distribution of fibre diameter (modal diameters of 1.9 and 3.7 μm) formed after tensile deformation. Extensive localised necking (thinning) of fibres between (thicker) fibre-fibre contacts was found to be the cause for non-uniform thinning of the fibres, a phenomenon that is expected, but has not been observed in 3D previously. The data presented here has implications not only in tissue regeneration but for fibrous materials in general.

  5. Restoration of mutant bestrophin-1 expression, localisation and function in a polarised epithelial cell model.

    PubMed

    Uggenti, Carolina; Briant, Kit; Streit, Anne-Kathrin; Thomson, Steven; Koay, Yee Hui; Baines, Richard A; Swanton, Eileithyia; Manson, Forbes D

    2016-11-01

    Autosomal recessive bestrophinopathy (ARB) is a retinopathy caused by mutations in the bestrophin-1 protein, which is thought to function as a Ca 2+ -gated Cl - channel in the basolateral surface of the retinal pigment epithelium (RPE). Using a stably transfected polarised epithelial cell model, we show that four ARB mutant bestrophin-1 proteins were mislocalised and subjected to proteasomal degradation. In contrast to the wild-type bestrophin-1, each of the four mutant proteins also failed to conduct Cl - ions in transiently transfected cells as determined by whole-cell patch clamp. We demonstrate that a combination of two clinically approved drugs, bortezomib and 4-phenylbutyrate (4PBA), successfully restored the expression and localisation of all four ARB mutant bestrophin-1 proteins. Importantly, the Cl - conductance function of each of the mutant bestrophin-1 proteins was fully restored to that of wild-type bestrophin-1 by treatment of cells with 4PBA alone. The functional rescue achieved with 4PBA is significant because it suggests that this drug, which is already approved for long-term use in infants and adults, might represent a promising therapy for the treatment of ARB and other bestrophinopathies resulting from missense mutations in BEST1. © 2016. Published by The Company of Biologists Ltd.

  6. Methodological study of submarine groundwater discharge from a karstic aquifer in the Western Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Mejías, Miguel; Ballesteros, Bruno J.; Antón-Pacheco, Carmen; Domínguez, José A.; Garcia-Orellana, Jordi; Garcia-Solsona, Ester; Masqué, Pere

    2012-09-01

    SummaryA multiproxy approach of complementary techniques is applied to localise and quantify submarine groundwater discharge (SGD) from El Maestrazgo Jurassic aquifer, an example of widespread carbonate coastal aquifer of the Western Mediterranean Sea (Castellón, Spain). Unconventional water resources are critical in this area where highly populated resorts have been developed. The aquifer has two main features of particular interest: a karstic system with a deep saturated zone reaching 450 m and with no significant surface discharge occurring within the continental area. On the other hand, SGD can alter the condition of coastal marine environments, reducing salinities and providing nutrients that can cause eutrophication and algal blooms. The applied combined techniques make it possible to detect groundwater outflows using airborne thermal infrared (TIR) images to monitor physico-chemical anomalies in the sea and to quantify the submarine groundwater discharges by means of direct measurements and radium isotopic analyses. Three main coastal areas affected by SGD and a submarine spring located at 3 km from the coast, which seems to be associated with tectonic discontinuities, were localised. The calculated fresh SGD from Ra isotopes, 375 Mm3 y-1, is in agreement with the mean aquifer recharge obtained by hydrogeological methods, 394 Mm3 y-1.

  7. Localised anodic oxidation of aluminium material using a continuous electrolyte jet

    NASA Astrophysics Data System (ADS)

    Kuhn, D.; Martin, A.; Eckart, C.; Sieber, M.; Morgenstern, R.; Hackert-Oschätzchen, M.; Lampke, T.; Schubert, A.

    2017-03-01

    Anodic oxidation of aluminium and its alloys is often used as protection against material wearout and corrosion. Therefore, anodic oxidation of aluminium is applied to produce functional oxide layers. The structure and properties of the oxide layers can be influenced by various factors. These factors include for example the properties of the substrate material, like alloy elements and heat treatment or process parameters, like operating temperature, electric parameters or the type of the used electrolyte. In order to avoid damage to the work-piece surface caused by covering materials in masking applications, to minimize the use of resources and to modify the surface in a targeted manner, the anodic oxidation has to be localised to partial areas. Within this study a proper alternative without preparing the substrate by a mask is investigated for generating locally limited anodic oxidation by using a continuous electrolyte jet. Therefore aluminium material EN AW 7075 is machined by applying a continuous electrolyte jet of oxalic acid. Experiments were carried out by varying process parameters like voltage or processing time. The realised oxide spots on the aluminium surface were investigated by optical microscopy, SEM and EDX line scanning. Furthermore, the dependencies of the oxide layer properties from the process parameters are shown.

  8. Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria.

    PubMed

    Miwa, Satomi; Czapiewski, Rafal; Wan, Tengfei; Bell, Amy; Hill, Kirsten N; von Zglinicki, Thomas; Saretzki, Gabriele

    2016-10-22

    Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/- mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.

  9. Surface waves on a soft viscoelastic layer produced by an oscillating microbubble.

    PubMed

    Tinguely, Marc; Hennessy, Matthew G; Pommella, Angelo; Matar, Omar K; Garbin, Valeria

    2016-05-14

    Ultrasound-driven bubbles can cause significant deformation of soft viscoelastic layers, for instance in surface cleaning and biomedical applications. The effect of the viscoelastic properties of a boundary on the bubble-boundary interaction has been explored only qualitatively, and remains poorly understood. We investigate the dynamic deformation of a viscoelastic layer induced by the volumetric oscillations of an ultrasound-driven microbubble. High-speed video microscopy is used to observe the deformation produced by a bubble oscillating at 17-20 kHz in contact with the surface of a hydrogel. The localised oscillating pressure applied by the bubble generates surface elastic (Rayleigh) waves on the gel, characterised by elliptical particle trajectories. The tilt angle of the elliptical trajectories varies with increasing distance from the bubble. Unexpectedly, the direction of rotation of the surface elements on the elliptical trajectories shifts from prograde to retrograde at a distance from the bubble that depends on the viscoelastic properties of the gel. To explain these behaviours, we develop a simple three-dimensional model for the deformation of a viscoelastic solid by a localised oscillating force. By using as input for the model the values of the shear modulus obtained from the propagation velocity of the Rayleigh waves, we find good qualitative agreement with the experimental observations.

  10. Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

    PubMed Central

    Yeste, Marc; Jones, Celine; Amdani, Siti Nornadhirah; Yelumalai, Suseela; Mounce, Ginny; da Silva, Sarah J. Martins; Child, Tim; Coward, Kevin

    2016-01-01

    Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22–54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ–related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm’s fundamental ability to activate an oocyte. PMID:27270687

  11. Coeval emplacement and orogen-parallel transport of gold in oblique convergent orogens

    NASA Astrophysics Data System (ADS)

    Upton, Phaedra; Craw, Dave

    2016-12-01

    Varying amounts of gold mineralisation is occurring in all young and active collisional mountain belts. Concurrently, these syn-orogenic hydrothermal deposits are being eroded and transported to form placer deposits. Local extension occurs in convergent orogens, especially oblique orogens, and facilitates emplacement of syn-orogenic gold-bearing deposits with or without associated magmatism. Numerical modelling has shown that extension results from directional variations in movement rates along the rock transport trajectory during convergence, and is most pronounced for highly oblique convergence with strong crustal rheology. On-going uplift during orogenesis exposes gold deposits to erosion, transport, and localised placer concentration. Drainage patterns in variably oblique convergent orogenic belts typically have an orogen-parallel or sub-parallel component; the details of which varies with convergence obliquity and the vagaries of underlying geological controls. This leads to lateral transport of eroded syn-orogenic gold on a range of scales, up to > 100 km. The presence of inherited crustal blocks with contrasting rheology in oblique orogenic collision zones can cause perturbations in drainage patterns, but numerical modelling suggests that orogen-parallel drainage is still a persistent and robust feature. The presence of an inherited block of weak crust enhances the orogen-parallel drainage by imposition of localised subsidence zones elongated along a plate boundary. Evolution and reorientation of orogen-parallel drainage can sever links between gold placer deposits and their syn-orogenic sources. Many of these modelled features of syn-orogenic gold emplacement and varying amounts of orogen-parallel detrital gold transport can be recognised in the Miocene to Recent New Zealand oblique convergent orogen. These processes contribute little gold to major placer goldfields, which require more long-term recycling and placer gold concentration. Most eroded syn-orogenic gold becomes diluted by abundant lithic debris in rivers and sedimentary basins except where localised concentration occurs, especially on beaches.

  12. PROTEIN TARGETING TO STARCH Is Required for Localising GRANULE-BOUND STARCH SYNTHASE to Starch Granules and for Normal Amylose Synthesis in Arabidopsis

    PubMed Central

    Seung, David; Soyk, Sebastian; Coiro, Mario; Maier, Benjamin A.; Eicke, Simona; Zeeman, Samuel C.

    2015-01-01

    The domestication of starch crops underpinned the development of human civilisation, yet we still do not fully understand how plants make starch. Starch is composed of glucose polymers that are branched (amylopectin) or linear (amylose). The amount of amylose strongly influences the physico-chemical behaviour of starchy foods during cooking and of starch mixtures in non-food manufacturing processes. The GRANULE-BOUND STARCH SYNTHASE (GBSS) is the glucosyltransferase specifically responsible for elongating amylose polymers and was the only protein known to be required for its biosynthesis. Here, we demonstrate that PROTEIN TARGETING TO STARCH (PTST) is also specifically required for amylose synthesis in Arabidopsis. PTST is a plastidial protein possessing an N-terminal coiled coil domain and a C-terminal carbohydrate binding module (CBM). We discovered that Arabidopsis ptst mutants synthesise amylose-free starch and are phenotypically similar to mutants lacking GBSS. Analysis of granule-bound proteins showed a dramatic reduction of GBSS protein in ptst mutant starch granules. Pull-down assays with recombinant proteins in vitro, as well as immunoprecipitation assays in planta, revealed that GBSS physically interacts with PTST via a coiled coil. Furthermore, we show that the CBM domain of PTST, which mediates its interaction with starch granules, is also required for correct GBSS localisation. Fluorescently tagged Arabidopsis GBSS, expressed either in tobacco or Arabidopsis leaves, required the presence of Arabidopsis PTST to localise to starch granules. Mutation of the CBM of PTST caused GBSS to remain in the plastid stroma. PTST fulfils a previously unknown function in targeting GBSS to starch. This sheds new light on the importance of targeting biosynthetic enzymes to sub-cellular sites where their action is required. Importantly, PTST represents a promising new gene target for the biotechnological modification of starch composition, as it is exclusively involved in amylose synthesis. PMID:25710501

  13. The Lavrion Pb-Zn-Fe-Cu-Ag detachment-related district (Attica, Greece): Structural control on hydrothermal flow and element transfer-deposition

    NASA Astrophysics Data System (ADS)

    Scheffer, Christophe; Tarantola, Alexandre; Vanderhaeghe, Olivier; Voudouris, Panagiotis; Rigaudier, Thomas; Photiades, Adonis; Morin, Denis; Alloucherie, Alison

    2017-10-01

    The impact of lithological heterogeneities on deformation, fluid flow and ore deposition is discussed based on the example of the Lavrion low-angle detachment partly accommodating gravitational collapse of the Hellenides orogenic belt in Greece. The Lavrion peninsula is characterised by a multiphase Pb-Zn-Fe-Cu-Ag ore system with a probable pre-concentration before subduction followed by progressive remobilisation and deposition coeval with the development of a low-angle ductile to brittle shear zone. The mylonitic marble below the detachment shear zone is composed of white layers of pure marble alternating with blue layers containing impurities (SiO2, Al2O3, carbonaceous material). Ductile mylonitic deformation is more pervasive in the less competent impure blue marble. We propose that localised deformation in the impure marble is associated with fluid circulation and dolomitisation, which in turn causes an increase in competence of these layers. Mineralised cataclastic zones, crosscutting the mylonitic fabric, are preferentially localised in the more competent dolomitic layers. Oxygen and carbon isotopic signatures of marble invaded by carbonate replacement deposits during ductile to ductile-brittle deformation are consistent with decarbonation coeval with the invasion of magmatic fluids. Mineralised cataclastic zones reflecting brittle deformation evolve from low 13C to low 18O signatures, interpreted as local interaction with carbonaceous material that trends toward the contribution of a surface-derived fluid. These features indicate that the Lavrion area records a complex deposition history influenced by the evolution of fluid reservoirs induced by the thermal and mechanical evolution of the marble nappe stack. Ore remobilisation and deposition associated with the activity of the low-angle detachment is (i) firstly related to the intrusion of the Plaka granodiorite leading to porphyry-type and carbonate replacement mineralisation during ductile-brittle deformation and (ii) then marked by progressive penetration of surface-derived fluids guided by strain localisation in the more competent levels leading to epithermal mineralisation associated with brittle deformation.

  14. Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus).

    PubMed

    Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

    2014-05-01

    Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

  15. Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus)

    PubMed Central

    Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

    2014-01-01

    Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors. PMID:25183148

  16. BILATERAL RETINOCHOROIDITIS CAUSED BY AN ATYPICAL STRAIN OF TOXOPLASMA GONDII

    PubMed Central

    Bottós, Juliana; Miller, Robin H.; Belfort, Rubens N.; Macedo, Ana Carolina; Belfort, Rubens; Grigg, Michael E.

    2012-01-01

    Background A 53-year-old man presented with an acute bilateral posterior uveitis with extensive necrotizing retinochoroiditis but without chorioretinal scarring. A thorough workup did not reveal any underlying disease. The possibilities of atypical ocular toxoplasmosis as well as herpetic retinal necrosis were considered and specific therapy instituted, with little improvement. The patient died within two months as result of an undifferentiated squamous cell carcinoma. Methods Histopathological examination, immunohistochemistry and multi-locus polymerase chain reaction confirmed T. gondii infection of the retina Results Macroscopic examination of enucleated globe showed extensive retinal necrosis and vitreous detachment. Histological examination of retinal tissue identified numerous round–to-elliptical toxoplasmic cysts within the retina, with retinal necrosis and minimal choroidal inflammation. Immunohistochemical analyses confirmed the cysts were due to Toxoplasma gondii. DNA extracted from formalin-fixed, paraffin-embedded tissue sections was subjected to multi-locus PCR analysis at the following typing loci: SAG1, SAG2, SAG3, SAG4, B1, NTS2, GRA6, and GRA7. DNA sequencing of positive PCR products at the NTS2, SAG1, and GRA7 loci confirmed the presence of a non-archetypal strain of T. gondii infecting the eye of the patient experiencing a severe, atypical ocular toxoplasmosis Conclusion A highly divergent, non-archetypal strain of Toxoplasma gondii was responsible for causing a severe, atypical bilateral retinochoroiditis in a patient from Brazil. PMID:19666926

  17. The atomic structure of polar and non-polar InGaN quantum wells and the green gap problem.

    PubMed

    Humphreys, C J; Griffiths, J T; Tang, F; Oehler, F; Findlay, S D; Zheng, C; Etheridge, J; Martin, T L; Bagot, P A J; Moody, M P; Sutherland, D; Dawson, P; Schulz, S; Zhang, S; Fu, W Y; Zhu, T; Kappers, M J; Oliver, R A

    2017-05-01

    We have used high resolution transmission electron microscopy (HRTEM), aberration-corrected quantitative scanning transmission electron microscopy (Q-STEM), atom probe tomography (APT) and X-ray diffraction (XRD) to study the atomic structure of (0001) polar and (11-20) non-polar InGaN quantum wells (QWs). This paper provides an overview of the results. Polar (0001) InGaN in QWs is a random alloy, with In replacing Ga randomly. The InGaN QWs have atomic height interface steps, resulting in QW width fluctuations. The electrons are localised at the top QW interface by the built-in electric field and the well-width fluctuations, with a localisation energy of typically 20meV. The holes are localised near the bottom QW interface, by indium fluctuations in the random alloy, with a localisation energy of typically 60meV. On the other hand, the non-polar (11-20) InGaN QWs contain nanometre-scale indium-rich clusters which we suggest localise the carriers and produce longer wavelength (lower energy) emission than from random alloy non-polar InGaN QWs of the same average composition. The reason for the indium-rich clusters in non-polar (11-20) InGaN QWs is not yet clear, but may be connected to the lower QW growth temperature for the (11-20) InGaN QWs compared to the (0001) polar InGaN QWs. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Analysis of Mitochondrial haemoglobin in Parkinson's disease brain.

    PubMed

    Shephard, Freya; Greville-Heygate, Oliver; Liddell, Susan; Emes, Richard; Chakrabarti, Lisa

    2016-07-01

    Mitochondrial dysfunction is an early feature of neurodegeneration. We have shown there are mitochondrial haemoglobin changes with age and neurodegeneration. We hypothesised that altered physiological processes are associated with recruitment and localisation of haemoglobin to these organelles. To confirm a dynamic localisation of haemoglobin we exposed Drosophila melanogaster to cyclical hypoxia with recovery. With a single cycle of hypoxia and recovery we found a relative accumulation of haemoglobin in the mitochondria compared with the cytosol. An additional cycle of hypoxia and recovery led to a significant increase of mitochondrial haemoglobin (p<0.05). We quantified ratios of human mitochondrial haemoglobin in 30 Parkinson's and matched control human post-mortem brains. Relative mitochondrial/cytosolic quantities of haemoglobin were obtained for the cortical region, substantia nigra and cerebellum. In age matched post-mortem brain mitochondrial haemoglobin ratios change, decreasing with disease duration in female cerebellum samples (n=7). The change is less discernible in male cerebellum (n=18). In cerebellar mitochondria, haemoglobin localisation in males with long disease duration shifts from the intermembrane space to the outer membrane of the organelle. These new data illustrate dynamic localisation of mitochondrial haemoglobin within the cell. Mitochondrial haemoglobin should be considered in the context of gender differences characterised in Parkinson's disease. It has been postulated that cerebellar circuitry may be activated to play a protective role in individuals with Parkinson's. The changing localisation of intracellular haemoglobin in response to hypoxia presents a novel pathway to delineate the role of the cerebellum in Parkinson's disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. The cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer.

    PubMed

    Lao, Chunhuan; Edlin, Richard; Rouse, Paul; Brown, Charis; Holmes, Michael; Gilling, Peter; Lawrenson, Ross

    2017-08-08

    Radical prostatectomy is the most common treatment for localised prostate cancer in New Zealand. Active surveillance was introduced to prevent overtreatment and reduce costs while preserving the option of radical prostatectomy. This study aims to evaluate the cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy. Markov models were constructed to estimate the life-time cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer patients aged 45-70 years, using national datasets in New Zealand and published studies including the SPCG-4 study. This study was from the perspective of the Ministry of Health in New Zealand. Radical prostatectomy is less costly than active surveillance in men aged 45-55 years with low risk localised prostate cancer, but more costly for men aged 60-70 years. Scenario analyses demonstrated significant uncertainty as to the most cost-effective option in all age groups because of the unavailability of good quality of life data for men under active surveillance. Uncertainties around the likelihood of having radical prostatectomy when managed with active surveillance also affect the cost-effectiveness of active surveillance against radical prostatectomy. Active surveillance is less likely to be cost-effective compared to radical prostatectomy for younger men diagnosed with low risk localised prostate cancer. The cost-effectiveness of active surveillance compared to radical prostatectomy is critically dependent on the 'trigger' for radical prostatectomy and the quality of life in men on active surveillance. Research on the latter would be beneficial.

  20. Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome caused by post-pancreatitis pseudocyst with mesenteric fistula. Diagnosis and successful surgical treatment. Case report and review of literature.

    PubMed

    Dieker, Wulf; Derer, Johannes; Henzler, Thomas; Schneider, Alexander; Rückert, Felix; Wilhelm, Torsten J; Krüger, Bernd

    2017-01-01

    Pancreatitis, panniculitis and polyarthritis syndrome is a very rare extra-pancreatic complication of pancreatic diseases. While in most cases this syndrome is caused by acute or chronic pancreatitis, we report a case of a 62-year-old man presenting with extensive intraosseous fat necrosis, polyarthritis and panniculitis caused by a post-pancreatitis pseudocyst with a fistula to the superior mesenteric vein and extremely high blood levels of lipase. This became symptomatic 2.5 years after an episode of acute pancreatitis and as in most cases abdominal symptoms were absent. Treatment by surgical resection of the pancreatic head with the pseudocyst and mesenteric fistula led to complete remission of all symptoms. A review of the literature revealed that all publications are limited to case reports. Most authors hypothesize that an unspecific damage can cause a secretion of pancreatic enzymes to the bloodstream leading to a systemic lipolysis and fat tissue necrosis, especially of subcutaneous tissue, bone marrow, inducing panniculitis, polyarthritis and osteonecrosis. Even if caused by an acute pancreatitis abdominal symptoms are often mild or absent in most cases leading to misdiagnosis and poor prognosis. While symptomatic treatment with NSAR and cortisone showed poor to moderate response, causal treatment can be successful depending on the underlying pancreatic disease. Copyright © 2017. Published by Elsevier Ltd.

  1. Histopathological changes in the liver and stomach of Didelphis virginiana (Didelphimorphia: Didelphidae) during natural infection with Gnathostoma turgidum (Nematoda: Gnathostomidae).

    PubMed

    Torres-Montoya, E H; Zazueta-Moreno, J M; Osuna-Martínez, L U; Castillo-Ureta, H; Silva-Hidalgo, G; López-Moreno, H S; Osuna-Ramírez, I; Noguera-Corona, E; Rendón-Maldonado, J G

    2017-11-06

    Gnathostoma turgidum is a nematode parasite that exploits the stomach of Virginian opossums, Didelphis virginiana, in Latin America. The opossum is the definitive host of G. turgidum in the wild. Intrahepatic growth and maturation of the parasite, subsequent migration to the stomach and spontaneous expulsion are common. However, the histopathological lesions caused by G. turgidum are poorly described. A better understanding of the life cycle of this parasite and the pathological changes in natural host-parasite interactions could help to clarify the progression of human infections caused by Gnathostoma binucleatum. The aim of this work was to study morphological changes in the liver and stomach of D. virginiana during natural infection and adult worm expulsion. Three opossums naturally infected with G. turgidum were captured from an endemic area of gnathostomosis. Three uninfected opossums captured from a non-endemic area were used as controls. The opossums were sacrificed at different stages of infection (March, May and December), and a histopathological study of their livers and stomachs was conducted. Injuries in livers were observed by histopathology - areas of necrosis and collagen septa were identified. Parasites caused nodules with necrosis on the periphery of lesions, and collagen fibres were also observed in stomachs. Collagen septa may be caused by antigenic remains of the parasite. Further immunological studies are necessary to verify that stimulation is caused by these factors.

  2. Exploring the Function of Online Narratives to Develop Critical Thinking and Localisation of Knowledge in an International Science Program

    ERIC Educational Resources Information Center

    Hicks, Marianne; Tham, Melissa; Brookes, Rowan

    2017-01-01

    e-learning practitioners have long recognised the benefits of using online training to achieve knowledge transfer, less is understood about facilitating the sharing of values, attitudes, critical thinking, and localisation using online platforms. In this article an online learning platform in the context of an international scientific program was…

  3. Nonlinear Light Dynamics in Multi-Core Structures

    DTIC Science & Technology

    2017-02-27

    be generated in continuous- discrete optical media such as multi-core optical fiber or waveguide arrays; localisation dynamics in a continuous... discrete nonlinear system. Detailed theoretical analysis is presented of the existence and stability of the discrete -continuous light bullets using a very...and pulse compression using wave collapse (self-focusing) energy localisation dynamics in a continuous- discrete nonlinear system, as implemented in a

  4. Gradual collapse of nuclear wave functions regulated by frequency tuned X-ray scattering.

    PubMed

    Ignatova, Nina; Cruz, Vinícius V; Couto, Rafael C; Ertan, Emelie; Zimin, Andrey; Guimarães, Freddy F; Polyutov, Sergey; Ågren, Hans; Kimberg, Victor; Odelius, Michael; Gel'mukhanov, Faris

    2017-03-07

    As is well established, the symmetry breaking by isotope substitution in the water molecule results in localisation of the vibrations along one of the two bonds in the ground state. In this study we find that this localisation may be broken in excited electronic states. Contrary to the ground state, the stretching vibrations of HDO are delocalised in the bound core-excited state in spite of the mass difference between hydrogen and deuterium. The reason for this effect can be traced to the narrow "canyon-like" shape of the potential of the state along the symmetric stretching mode, which dominates over the localisation mass-difference effect. In contrast, the localisation of nuclear motion to one of the HDO bonds is preserved in the dissociative core-excited state . The dynamics of the delocalisation of nuclear motion in these core-excited states is studied using resonant inelastic X-ray scattering of the vibrationally excited HDO molecule. The results shed light on the process of a wave function collapse. After core-excitation into the state of HDO the initial wave packet collapses gradually, rather than instantaneously, to a single vibrational eigenstate.

  5. Aquaporins 7 and 11 in boar spermatozoa: detection, localisation and relationship with sperm quality.

    PubMed

    Prieto-Martínez, Noelia; Vilagran, Ingrid; Morató, Roser; Rodríguez-Gil, Joan E; Yeste, Marc; Bonet, Sergi

    2016-04-01

    Aquaporins (AQPs) are integral membrane water channels that allow transport of water and small solutes across cell membranes. Although water permeability is known to play a critical role in mammalian cells, including spermatozoa, little is known about their localisation in boar spermatozoa. Two aquaporins, AQP7 and AQP11, in boar spermatozoa were identified by western blotting and localised through immunocytochemistry analyses. Western blot results showed that boar spermatozoa expressed AQP7 (25kDa) and AQP11 (50kDa). Immunocytochemistry analyses demonstrated that AQP7 was localised in the connecting piece of boar spermatozoa, while AQP11 was found in the head and mid-piece and diffuse labelling was also seen along the tail. Despite differences in AQP7 and AQP11 content between boar ejaculates, these differences were not found to be correlated with sperm quality in the case of AQP7. Conversely, AQP11 content showed a significant correlation (P<0.05) with sperm membrane integrity and fluidity and sperm motility. In conclusion, boar spermatozoa express AQP7 and AQP11, and the amounts of AQP11 but not those of AQP7 are correlated with sperm motility and membrane integrity.

  6. Fully localised nonlinear energy growth optimals in pipe flow

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pringle, Chris C. T.; Willis, Ashley P.; Kerswell, Rich R.

    A new, fully localised, energy growth optimal is found over large times and in long pipe domains at a given mass flow rate. This optimal emerges at a threshold disturbance energy below which a nonlinear version of the known (streamwise-independent) linear optimal [P. J. Schmid and D. S. Henningson, “Optimal energy density growth in Hagen-Poiseuille flow,” J. Fluid Mech. 277, 192–225 (1994)] is selected and appears to remain the optimal up until the critical energy at which transition is triggered. The form of this optimal is similar to that found in short pipes [Pringle et al., “Minimal seeds for shearmore » flow turbulence: Using nonlinear transient growth to touch the edge of chaos,” J. Fluid Mech. 702, 415–443 (2012)], but now with full localisation in the streamwise direction. This fully localised optimal perturbation represents the best approximation yet of the minimal seed (the smallest perturbation which is arbitrarily close to states capable of triggering a turbulent episode) for “real” (laboratory) pipe flows. Dependence of the optimal with respect to several parameters has been computed and establishes that the structure is robust.« less

  7. Muscarinic receptor M1 and M2 subtypes in the human eye: QNB, pirenzipine, oxotremorine, and AFDX-116 in vitro autoradiography.

    PubMed Central

    Gupta, N; McAllister, R; Drance, S M; Rootman, J; Cynader, M S

    1994-01-01

    Muscarinic cholinergic agents are used to lower intraocular pressure in the medical management of glaucoma and subtypes of muscarinic receptors have now been recognised in many tissues including the eye. To localise muscarinic receptors and their M1 and M2 subtypes in the human eye, in vitro ligand binding and autoradiographic techniques with densitometric quantitation on postmortem eye sections were used. As ligands, [3H] quinuclydinyl benzylate (QNB) (non-subtype specific muscarinic antagonist), [3H]pirenzipine (M1 antagonist), [3H]oxotremorine (M2 muscarinic agonist), [3H]AFDX-116(11[(2[diethylaminomethyl]1-piperidinyl)acetyl]5 , 11dihydro-6H-pyrido [2,3b][1,4]benzodiazepine-6-one) (M2 antagonist) were studied. Specific binding sites for QNB, pirenzipine, and AFDX-116 were localised in the entire ciliary muscle, the iris, and ciliary epithelium. [3H]oxotremorine localised only in the longitudinal portion of the ciliary muscle, and additionally, was not localised in the iris or ciliary epithelium. These results suggest that oxotremorine, by binding selectively to receptors on the longitudinal ciliary muscle and inducing its contraction, may modulate outflow facility independently from accommodation and miosis. Images PMID:7918268

  8. Localised task-dependent motor-unit recruitment in the masseter.

    PubMed

    Schindler, H J; Hellmann, D; Giannakopoulos, N N; Eiglsperger, U; van Dijk, J P; Lapatki, B G

    2014-07-01

    Localised motor-unit (MU) recruitment in the masseter was analysed in this study. We investigated whether differential activation behaviour, which has already been reported for distant masseter regions, can also be detected in small muscle subvolumes at the level of single MUs. Two bipolar fine-wire electrodes and an intra-oral 3D bite-force transmitter were used to record intra-muscular electromyograms (EMG) resulting from controlled bite-forces of 10 healthy human subjects (mean age 24.1 ± 1.2 years). Two-hundred and seventeen decomposed MUs were organised into localised MU task groups with different (P < 0.001) force-direction-specific behaviour. Proportions of MUs involved in one, two, three or four examined tasks were 46%, 31%, 18% and 5%, respectively. This study provides evidence of the ability of the neuromuscular system to modify the mechanical output of small masseter subvolumes by differential control of adjacent MUs belonging to distinct task groups. Localised differential activation behaviour of the masseter may be the crucial factor enabling highly flexible and efficient adjustment of the muscle activity in response to complex local biomechanical needs, for example, continually varying bite-forces during the demanding masticatory process. © 2014 John Wiley & Sons Ltd.

  9. Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu Xiaopeng; Huang Lichao; Weng Shaoping

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} andmore » tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.« less

  10. Histopathology of radiation necrosis with severe peritumoral edema after gamma knife radiosurgery for parasagittal meningioma. A report of two cases.

    PubMed

    Chen, Chien-hua; Shen, Chiung-chyi; Sun, Ming-hsi; Ho, William L; Huang, Chuan-fu; Kwan, Po-cheung

    2007-01-01

    Gamma knife radiosurgery (GKS) has been an effective treatment for meningiomas. Nevertheless, it still has certain risks. We present 2 cases of parasagittal meningioma after GKS complicated with radiation necrosis and peritumoral edema. The results of histologic examination are discussed. Two cases of parasagittal meningioma received GKS. Symptomatic peritumoral edema developed 3-4 months after GKS. Both of them underwent surgical resection of their tumor afterwards. Histologic examination showed necrotic change inside the tumor and infiltration of inflammatory cells in both cases. Hyalinization of blood vessels was seen in the 2nd case. The patients had improvement of neurologic function after surgical resection. Imaging performed 3 months after surgical resection showed alleviation of brain edema. After radiosurgery peritumoral edema tends to occur in meningiomas with a parasagittal position. Radiation necrosis, infiltration of inflammatory cells, and radiation injury to the vasculature causing hyalinization of blood vessels are suggested as the underlying histopathology. (c) 2007 S. Karger AG, Basel.

  11. Polyarteritis nodosa clinically mimicking nonocclusive mesenteric ischemia

    PubMed Central

    Shirai, Tsuyoshi; Fujii, Hiroshi; Saito, Shinichiro; Ishii, Tomonori; Yamaya, Hideyuki; Miyagi, Shigehito; Sekiguchi, Satoshi; Kawagishi, Naoki; Nose, Masato; Harigae, Hideo

    2013-01-01

    Here, we present the case of a 74-year-old Japanese man with segmental intestinal necrosis, which developed after treatment with pulsed methylprednisolone for mononeuritis multiplex. The patient was weakly positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA). Computed tomography and surgical findings were compatible with nonocclusive mesenteric ischemia (NOMI). He underwent small intestinal resection by emergency surgery and an intestinal fistula was made. Pathologically, necrotizing vasculitis with fibrinoid necrosis was present in medium to small-sized arteries, which was equivalent to Arkin’s classification II-IV. Most of the arteries had fibrous intimal thickening, which was considered to obstruct the arteries and thus cause segmental intestinal necrosis. A diagnosis of polyarteritis nodosa (PAN) was made, and intravenous cyclophosphamide pulse therapy was added to the therapeutic regimen. This patient was successfully treated with these multidisciplinary therapies and his stoma was finally closed. This is a very rare and indicative case of PAN weakly positive for MPO-ANCA and clinically mimicking NOMI, which occurred even after treatment with pulsed methylprednisolone. PMID:23801874

  12. An investigation of ear necrosis in pigs.

    PubMed

    Park, Jeonghwa; Friendship, Robert M; Poljak, Zvonimir; DeLay, Josepha; Slavic, Durda; Dewey, Catherine E

    2013-05-01

    Porcine ear necrosis was investigated in 23 conveniently chosen farms, consisting of 14 case farms and 9 control farms. Biopsies of lesions and oral swabs from pigs on 11 case farms were examined by histology and bacterial culture. All farms were visited for observations and a survey on management, housing, and the presence of other clinical signs or behavioral vices. Histological examination revealed that the lesions began on the surface and progressed to deeper layers, and that vascular damage did not appear to be the initiating cause. Spirochetes were only rarely observed in histological examination and were not cultured from biopsies and oral swabs. Staphylococcus aureus and Staphylococcus hyicus were cultured from 91% and 66% of samples, respectively. Ear biting and a humid environment were associated with ear necrosis. On some farms large numbers of pigs were affected and lesions were sometimes extensive. The condition appears to be an infectious disease beginning on the surface of the skin; contributing environmental and management factors are likely.

  13. An investigation of ear necrosis in pigs

    PubMed Central

    Park, Jeonghwa; Friendship, Robert M.; Poljak, Zvonimir; DeLay, Josepha; Slavic, Durda; Dewey, Catherine E.

    2013-01-01

    Porcine ear necrosis was investigated in 23 conveniently chosen farms, consisting of 14 case farms and 9 control farms. Biopsies of lesions and oral swabs from pigs on 11 case farms were examined by histology and bacterial culture. All farms were visited for observations and a survey on management, housing, and the presence of other clinical signs or behavioral vices. Histological examination revealed that the lesions began on the surface and progressed to deeper layers, and that vascular damage did not appear to be the initiating cause. Spirochetes were only rarely observed in histological examination and were not cultured from biopsies and oral swabs. Staphylococcus aureus and Staphylococcus hyicus were cultured from 91% and 66% of samples, respectively. Ear biting and a humid environment were associated with ear necrosis. On some farms large numbers of pigs were affected and lesions were sometimes extensive. The condition appears to be an infectious disease beginning on the surface of the skin; contributing environmental and management factors are likely. PMID:24155434

  14. A Migrated Aortic Stent Graft Causing Erosive Spondylopathy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gestrich, Christopher, E-mail: christopher.gestrich@ukb.uni-bonn.de; Probst, Chris, E-mail: chris.probst@ukb.uni-bonn.de; Wilhelm, Kai, E-mail: kai.wilhelm@ek-bonn.de

    We report about a patient presenting with back pain 4 months after an uneventful endovascular implantation of an aortic stent graft. Computed tomography scan revealed a migration of the stent with consecutive endoleakage, kink formation, and movement of the stent toward the spine, which caused destruction of the aortic wall as well as vertebral necrosis. Explantation of the stent and replacement of the native aorta relieved the patient of his symptoms.

  15. The resolution of rayless goldenrod (Isocoma pluriflora) poisoning in goats

    USDA-ARS?s Scientific Manuscript database

    Rayless goldenrod (Isocoma pluriflora) occasionally poisons livestock causing myocardial and skeletal muscle degeneration and necrosis. The objectives of this study were to describe the resolution of the clinical and pathologic changes of rayless goldenrod poisoning in goats. Eight goats were gava...

  16. Coherence-controlled holographic microscopy enabled recognition of necrosis as the mechanism of cancer cells death after exposure to cytopathic turbid emulsion

    NASA Astrophysics Data System (ADS)

    Collakova, Jana; Krizova, Aneta; Kollarova, Vera; Dostal, Zbynek; Slaba, Michala; Vesely, Pavel; Chmelik, Radim

    2015-11-01

    Coherence-controlled holographic microscopy (CCHM) in low-coherence mode possesses a pronounced coherence gate effect. This offers an option to investigate the details of cellular events leading to cell death caused by cytopathic turbid emulsions. CCHM capacity was first assessed in model situations that showed clear images obtained with low coherence of illumination but not with high coherence of illumination. Then, the form of death of human cancer cells induced by treatment with biologically active phospholipids (BAPs) preparation was investigated. The observed overall retraction of cell colony was apparently caused by the release of cell-to-substratum contacts. This was followed by the accumulation of granules decorating the nuclear membrane. Then, the occurrence of nuclear membrane indentations signaled the start of damage to the integrity of the cell nucleus. In the final stage, cells shrunk and disintegrated. This indicated that BAPs cause cell death by necrosis and not apoptosis. An intriguing option of checking the fate of cancer cells caused by the anticipated cooperative effect after adding another tested substance sodium dichloroacetate to turbid emulsion is discussed on grounds of pilot experiments. Such observations should reveal the impact and mechanism of action of the interacting drugs on cell behavior and fate that would otherwise remain hidden in turbid milieu.

  17. Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localisation.

    PubMed

    Csukai, M; Mochly-Rosen, D

    1999-04-01

    Protein kinase C (PKC) isozymes are highly homologous kinases and several different isozymes can be present in a cell. Each isozyme is likely to mediate unique functions, but pharmacological tools to explore their isozyme-specific roles have not been available until recently. In this review, we describe the development and application of isozyme-selective inhibitors of PKC. The identification of these inhibitors stems from the observation that PKC isozymes are each localised to unique subcellular locations following activation. Inhibitors of this isozyme-unique localisation have been shown to act as selective inhibitors of the functions of individual isozymes. The identification of isozyme-specific inhibitors should allow the exploration of individual PKC isozyme function in a wide range of cell systems. Copyright 1999 The Italian Pharmacological Society.

  18. Zebrafish as a useful model for zoonotic Vibrio parahaemolyticus pathogenicity in fish and human.

    PubMed

    Zhang, Qinghua; Dong, Xuehong; Chen, Biao; Zhang, Yonghua; Zu, Yao; Li, Weiming

    2016-02-01

    Vibrio parahaemolyticus is an important aquatic zoonotic pathogen worldwide that causes vibriosis in many marine fish, and sepsis, gastroenteritis and wound infection in humans. However, the pathogenesis of different sources of V. parahaemolyticus is not fully understood. Here, we examined the pathogenicity and histopathology of fish (V. parahaemolyticus 1.2164) and human (V. parahaemolyticus 17) strains in a zebrafish (Danio rerio). We found that different infection routes resulted in different mortality in zebrafish. Moreover, death due to V. parahaemolyticus 1.2164 infection occurred quicker than that caused by V. parahaemolyticus 17 infection. Hematoxylin-eosin staining of liver, kidney and intestine sections showed histological lesions in all three organs after infection with either strain. V. parahaemolyticus 1.2164 caused more severe damage than V. parahaemolyticus 17. In particular, V. parahaemolyticus 1.2164 treatment induced more serious hydropic degeneration and venous sinus necrosis in the liver than V. parahaemolyticus 17 treatment. The expression levels of three proinflammatory cytokines, interleukin 1β (il1β), interferon phi 1 (ifnϕ1) and tumor necrosis factor α (tnfα), as determined by quantitative real-time PCR, were upregulated in all examined tissues of infected fish. Notably, the peak levels of tnfα were significantly higher than those of il1β and ifnϕ1, suggesting, together with pathological results, that tnfα and il1β play an important role in acute sepsis. High amounts of tnfα may be related to acute liver necrosis, while ifnϕ1 may respond to V. parahaemolyticus and play an antibacterial role for chronically infected adult zebrafish. Taken together, our results suggest that the zebrafish model of V. parahaemolyticus infection is useful for studying strain differences in V. parahaemolyticus pathogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Recombinant infectious hematopoietic necrosis virus expressing infectious pancreatic necrosis virus VP2 protein induces immunity against both pathogens.

    PubMed

    Guo, Mengting; Shi, Wen; Wang, Yanxue; Wang, Yuting; Chen, Yaping; Li, Dechuan; Ren, Xuanyu; Hua, Xiaojing; Tang, Lijie; Li, Yijing; Liu, Min

    2018-04-21

    Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are typical pathogens of rainbow trout. Their co-infection is also common, which causes great economic loss in juvenile salmon species. Although vaccines against IHNV and IPNV have been commercialized in many countries, the prevalence of IHNV and IPNV is still widespread in modern aquaculture. In the present study, two IHNV recombinant viruses displaying IPNV VP2 protein (rIHNV-IPNV VP2 and rIHNV-IPNV VP2COE) were generated using the RNA polymerase Ⅱ system to explore the immunogenicity of IHNV and IPNV. The recombinant IHNV viruses were stable, which was confirmed by sequencing, indirect immunofluorescence assay, western blotting, transmission electron microscopy and viral growth curve assay. IHNV and IPNV challenge showed that the recombinant viruses had high protection rates against IHNV and IPNV with approximately 65% relative percent survival rates. Rainbow trout (mean weight 20 g) vaccinated with these two recombinant viruses showed a high level of antibodies against IHNV and IPNV infection. Taken together, our findings demonstrate that rIHNV-IPNV VP2 and rIHNV-IPNV VP2COE might be promising vaccine candidates against IHNV and IPNV. Copyright © 2018. Published by Elsevier Ltd.

  20. Fatal trematodiasis in research turtles.

    PubMed

    Johnson, C A; Griffith, J W; Tenorio, P; Hytrek, S; Lang, C M

    1998-08-01

    During a 5-year period, 16 freshwater turtles (Trachemys scripta elegans and Chrysemys picta) that were purchased for research purposes died spontaneously. Clinical signs of disease included lethargy, constant swimming, swimming sideways, hemiplegia, and ulcerative lesions on the carapace. At necropsy, subcutaneous edema, hepatic necrosis, pancreatic necrosis, splenic necrosis, and intestinal parasites were identified. Histologically, trematode eggs were seen within the liver, brain, spleen, kidney, myocardium, lung, pancreas, testes, and bladder, and were associated with granulomatous reactions. The size and distribution of the eggs were consistent with Spirorchis sp. infection, although adults could not be found to confirm the species. Spirorchid flukes are 1 to 2 mm long and inhabit the heart and blood vessels where they produce eggs. Spirorchis parvus are capable of invading various tissues, including pancreas and the central nervous system. The pathogenicity of the flukes seems to be related to widespread deposition of the eggs, which may block small blood vessels within the intestines, causing necrosis and bacteremia. Antemortem diagnosis is made by direct examination of fecal smears for eggs. Postmortem diagnosis is accomplished by examination of tissues for adult parasites and microgranulomas associated with the fluke eggs. The parasite requires a snail intermediate host to complete its life cycle. Intramuscular or oral administration of praziquantel is reported to be an effective treatment.

  1. Alternariol induce toxicity via cell death and mitochondrial damage on Caco-2 cells.

    PubMed

    Fernández-Blanco, Celia; Juan-García, Ana; Juan, Cristina; Font, Guillermina; Ruiz, Maria-Jose

    2016-02-01

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, appears as food contaminant in fruit, vegetables and cereal products. Its toxicity has been demonstrated, but the mechanisms involved have not been elucidated yet. In this study, the pathways triggered by AOH and degradation products generated on Caco-2 cells were evaluated. Cells were exposed to AOH sub-cytotoxic concentrations of 15, 30 and 60 μM. Cell cycle disruption, the induction of apoptosis/necrosis and changes in mitochondrial membrane potential (Δψm) after 24 and 48 h was asses by flow cytometry. Also, AOH and its degradation products were evaluated after 24 and 48 h by high-performance liquid chromatography with tandem mass spectrometric (LC-MS/MS) to detect and quantify its levels. Cell cycle was significantly decreased at G1 phase and increased at S and G2/M phase at the time of exposure. AOH induced necrosis, apoptosis/necrosis and loss of Δψm in a dose and time-dependent manner. The concentrations of AOH quantified in the culture media exposed to AOH decreased as the exposure time was increased. In conclusion, AOH caused cytotoxic effects supported by blocking cell cycle, decreasing cell proliferation and increasing apoptosis/necrosis cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Comparison of behavior in muscle fiber regeneration after bupivacaine hydrochloride- and acid anhydride-induced myonecrosis.

    PubMed

    Akiyama, C; Kobayashi, S; Nonaka, I

    1992-01-01

    We compared the morphologic characteristics of muscle fiber necrosis and subsequent regeneration after injury induced by intramuscular injections of bupivacaine hydrochloride (BPVC) and a variety of solutions at acid and alkaline pH (acetic anhydride, citric acid buffer, and sodium carbonate buffer). After BPVC injection the necrotic muscle fibers were rapidly invaded by phagocytic cells, followed by active regeneration and very little fibrous scar formation. The regenerating muscle fibers increased rapidly in size and attained complete fiber type differentiation and regained their initial fiber diameter within 1 month. Both alkaline and acid solutions induced muscle fiber necrosis followed by regeneration. Fiber necrosis induced by alkaline buffers and acetic anhydride solutions above pH 5.0 produced changes quite similar to that induced by BPVC. However, injection with 0.1 M acetic anhydride at pH below 4.0 resulted in coagulative necrosis of the injured muscle with very little phagocytic infiltration with poor regenerative activity and dense fibrous tissue scarring. Thus, pH 4.0 appears to be the critical pH determining the type of muscle injury and subsequent poor phagocytic and regenerative activities. This model of acidic acetic anhydride injury may lead to the identification of factors which interfere with regeneration and cause fibrous tissue scarring in human muscular dystrophy.

  3. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  4. Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

    PubMed

    Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

    2013-03-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6-10.5 for intermediate-risk patients and 7.8-9.3 for high-risk patients. There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease. RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer. © 2012 BJU International.

  5. To localise or to be localised with WiFi in the Hubei museum?

    NASA Astrophysics Data System (ADS)

    Verbree, E.; Zlatanova, S.; van Winden, K. B. A.; van der Laan, E. B.; Makri, A.; Taizhou, L.; Haojun, A.

    2013-11-01

    Indoor localisation is in demand for a variety of applications within the built environment. An overall solution based on a single technology has not yet been determined. The aim of this paper is to gain insight on Signal Strength monitoring by a special kind of WiFi Monitors in comparison to the commonly known fingerprinting method for the purpose of a 3D indoor navigation system. Ttwo different WiFi based localisation techniques are tested during the MSc Geomatics DaRen Syntheses Project in the Hubei Provincial Museum, China. The first method detects the beacon frames send by smartphones, laptops and other WiFi enabled devices in range using Libelium Meshlium Xtreme monitors. Their MAC addresses and the signal strength is measured by the Meshlium Xtreme and stored on an external database. We call this method WiFi monitoring. The second method a Wifi enabled device, like a smartphone, measures the signal strength of multiple Wifi Access Points in range to localise itself based on a previously created radio map. This method is known as WiFi fingerprinting. Both methods have some advantages and disadvantages. Advantages of the common way of WiFi fingerprinting are that the implementation costs are relatively low, because it is usually possible to use (a part of) the existing WiFi AP infrastructure. WiFi fingerprinting can reach a relatively high accuracy in the order of magnitude of meters. Finally, the location granularity can be adjusted to what is necessary for the purpose of the indoor localisation. This makes it employable for a wide range of purposes. The question remains how suitable these methods are for a 3D indoor navigation system for the Hubei provincial museum. One important aspect is the localisation-granularity necessary for the application. In a museum it is not necessary to know the exact X,Y position of a user (such high accuracy is unnecessary), more important is to know in which room the user is located so the information on exhibitions can be presented and the starting point of the navigation can be determined. Both methods can track the user and tell the room he or she is located at. Although WiFi smartphone monitoring may have a low update frequency it is still suitable for a navigation system for a museum since visitors usually spend more than a couple of minutes within a room.

  6. Developing lettuce with improved quality for processed salads.

    USDA-ARS?s Scientific Manuscript database

    Lettuce is increasingly consumed as minimally processed salads. Cultivars grown for this market may require breeding for improved shelf-life and resistance to physiological defects such as tipburn (TB). Tipburn is a calcium deficiency related defect causing necrosis on the leaf margins, typically on...

  7. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    DTIC Science & Technology

    2014-11-07

    portal hypertension , and liver failure [4]. Liver fibrosis typically starts with apoptosis or necrosis of hepatocytes, which causes reactive oxygen...Arroyo V, et al. (2007) Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats

  8. Cocklebur (Xanthium strumarium, L. var. strumarium) intoxication in swine: review and redefinition of the toxic principle.

    PubMed

    Stuart, B P; Cole, R J; Gosser, H S

    1981-05-01

    Cocklebur (Xanthium strumarium) fed to feeder pigs was associated with acute to subacute hepatotoxicosis. Cotyledonary seedings fed at 0.75% to 3% of body weight or ground bur fed at 20% to 30% of the ration caused acute depression, convulsions, and death. Principle gross lesions were marked serofibrinous ascites, edema of the gallbladder wall, and lobular accentuation of the liver. Acute to subacute centrilobular hepatic necrosis was present microscopically. The previously reported toxic principle, hydroquinone, was not recovered from the plant or bur of X. strumarium. Authentic hydroquinone administered orally failed to produce lesions typical of cocklebur intoxication but did produce marked hyperglycemia. Carboxyatractyloside recovered from the aqueous extract of X. strumarium and authentic carboxyatractyloside, when fed to pigs, caused signs and lesions typical of cocklebur intoxication. Marked hypoglycemia and elevated serum glutamic oxaloacetic transaminase and serum isocitric dehydrogenase concentrations occurred in pigs with acute hepatic necrosis that had received either cocklebur seedlings, ground bur or carboxyatractyloside.

  9. Occurrence of Internal Stipe Necrosis of Cultivated Mushrooms (Agaricus bisporus) Caused by Ewingella americana in Korea

    PubMed Central

    Jhune, Chang-Sung; Cheong, Jong-Chun; Yun, Hyung-Sik; Cho, Weon-Dae

    2009-01-01

    The internal stipe necrosis of cultivated mushrooms (Agaricus bisporus) is caused by the bacterium Ewingella americana, a species of the Enterobacteriaceae. Recently, Ewingella americana was isolated from cultivated white button mushrooms in Korea evidencing symptoms of internal stipe browning. Its symptoms are visible only at harvest, and appear as a variable browning reaction in the center of the stipes. From these lesions, we isolated one bacterial strain (designated CH4). Inoculation of the bacterial isolate into mushroom sporocarps yielded the characteristic browning symptoms that were distinguishable from those of the bacterial soft rot that is well known to mushroom growers. The results of Gram stain, flagellal staining, and biochemical tests identified these isolates as E. americana. This was verified by pathogenicity, physiological and biochemical characteristics, and the results of an analysis of the 16S rRNA gene sequences and the fatty acids profile. This is the first report of the isolation of E. americana from cultivated white button mushrooms in Korea. PMID:23983509

  10. Case reports - When bronchial obstruction in the young adult is not asthma and inhalers do not help.

    PubMed

    Sigvard, Anne; Bødtger, Uffe

    2016-08-01

    Localised bronchial obstruction is a rare differential diagnosis to asthma. We describe two younger patients treated unsuccessfully for asthma and eventually diagnosed with localised bronchoconstriction. Bronchoscopy revealed bronchoconstriction: Tracheobronchomalacia in case 1 and fixed obstruction in case 2. A systematic approach to the asthma patient with absent response to therapy facilitates rational use of therapeutic and diagnostic resources.

  11. Game Localisation as Software-Mediated Cultural Experience: Shedding Light on the Changing Role of Translation in Intercultural Communication in the Digital Age

    ERIC Educational Resources Information Center

    O'Hagan, Minako

    2015-01-01

    In this rapidly technologising age translation practice has been undergoing formidable changes with the implication that there is a need to expand the disciplinary scope of translation studies. Taking the case of game localisation this article problematises the role of translation as intercultural communication by focusing on cultural elements of…

  12. Challenges to Globalisation, Localisation and Sinophilia in Music Education: A Comparative Study of Hong Kong, Shanghai and Taipei

    ERIC Educational Resources Information Center

    Ho, Wai-Chung; Law, Wing-Wah

    2006-01-01

    In the past, the music curricula of Hong Kong (HK), Mainland China and Taiwan have focused on Western music, but with the advent of music technology and the new tripartite paradigm of globalisation, localisation and Sinophilia this has begun to change. Hong Kong, Shanghai and Taipei share a common historical culture and their populations are…

  13. High-Intensity Focused Ultrasound for the Treatment of Localized and Locally Advanced Hormone-Resistant Prostate Cancer: 2,5 Year Outcome

    NASA Astrophysics Data System (ADS)

    Solovov, V. A.; Dvoynikov, S. Y.; Vozdvizhenskiy, M. O.

    2011-09-01

    Introduction & Objectives: High-Intensity Focused Ultrasound (HIFU) has been shown to be a successful treatment for localised prostate cancer (PC). Here we have explored the effectiveness of the HIFU treatment for hormone-resistant prostate cancer (HRPC). Materials & Methods: 341 patients were treated in our center between September 2007 and December 2009; all of them showed treatment failure following hormone ablation. The median time before hormone-resistance was 20 (3-48) months. In the group with localised PC: number of patients 237, Gleason score ≤7, stage T1-2N0M0, age 69 (60-89) years, mean PSA before treatment 40,0 (5,8-92,9) ng/ml, mean prostate volume—39,3 (28-92) cc; in the group with locally advanced PC: number of patients 104, Gleason score ≤9, stage T2-3N0M0, age 72 (52-83) years, PSA before treatment 30,3 (20,1-60) ng/ml, mean prostate volume—41,2 (25-198) cc. HIFU was delivered under spinal anesthesia using the Ablatherm HIFU device (EDAP, France). Pre HIFU transurethral resection of the prostate (TURP) was performed for all patients. Mean follow-up time 18 months (3-30). Results: The median PSA level 12 months after HIFU treatment was 0,04 (0-2,24) ng/ml—localised PC, and for locally advanced disease—0,05 (0-48,4) ng/ml, at 18 months after HIFU treatment this was 0,2 (0,02-2,0) ng/ml for localised PC, and for locally advanced disease 0,18 (0,04-7,45) ng/ml. Patients with localised PC has 4,5% recurrence, those with locally advanced PC 20%. Kaplan-Meir analyses of the total group indicated that the risk of recurrence after 1 year follow-up was 10%, the risk of recurrence was 19% after 2 years of follow-up. Conclusions: Our initial experience shows that ultrasound ablation is safe, minimally invasive and effective as a treatment for localised and locally advanced hormone-resistant prostate cancer.

  14. Automaticity and localisation of concurrents predicts colour area activity in grapheme-colour synaesthesia.

    PubMed

    Gould van Praag, Cassandra D; Garfinkel, Sarah; Ward, Jamie; Bor, Daniel; Seth, Anil K

    2016-07-29

    In grapheme-colour synaesthesia (GCS), the presentation of letters or numbers induces an additional 'concurrent' experience of colour. Early functional MRI (fMRI) investigations of GCS reported activation in colour-selective area V4 during the concurrent experience. However, others have failed to replicate this key finding. We reasoned that individual differences in synaesthetic phenomenology might explain this inconsistency in the literature. To test this hypothesis, we examined fMRI BOLD responses in a group of grapheme-colour synaesthetes (n=20) and matched controls (n=20) while characterising the individual phenomenology of the synaesthetes along dimensions of 'automaticity' and 'localisation'. We used an independent functional localiser to identify colour-selective areas in both groups. Activations in these areas were then assessed during achromatic synaesthesia-inducing, and non-inducing conditions; we also explored whole brain activations, where we sought to replicate the existing literature regarding synaesthesia effects. Controls showed no significant activations in the contrast of inducing > non-inducing synaesthetic stimuli, in colour-selective ROIs or at the whole brain level. In the synaesthete group, we correlated activation within colour-selective ROIs with individual differences in phenomenology using the Coloured Letters and Numbers (CLaN) questionnaire which measures, amongst other attributes, the subjective automaticity/attention in synaesthetic concurrents, and their spatial localisation. Supporting our hypothesis, we found significant correlations between individual measures of synaesthetic phenomenology and BOLD responses in colour-selective areas, when contrasting inducing against non-inducing stimuli. Specifically, left-hemisphere colour area responses were stronger for synaesthetes scoring high on phenomenological localisation and automaticity/attention, while right-hemisphere colour area responses showed a relationship with localisation only. In exploratory whole brain analyses, the BOLD response within several other areas was also correlated with these phenomenological factors, including the intra-parietal sulcus, insula, precentral and supplementary motor areas. Our findings reveal a network of regions underlying synaesthetic phenomenology and they help reconcile the diversity of previous results regarding colour-selective BOLD responses during synaesthesia, by establishing a bridge between neural responses and individual synaesthetic phenomenology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral 99mTc-colloid Sentinel Node Lymphoscintigraphy.

    PubMed

    Hung, Te-Jui; Burrage, John; Bourke, Anita; Taylor, Donna

    2017-08-24

    Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Resistance and Protective Immunity in Redfish Lake Sockeye Salmon Exposed to M Type Infectious Hematopoietic Necrosis Virus (IHNV)

    USGS Publications Warehouse

    Kurath, Gael; Garver, Kyle; Purcell, Maureen K.; LaPatra, Scott E.

    2010-01-01

    Differential virulence of infectious hematopoietic necrosis virus (IHNV) isolates from the U and M phylogenetic subgroups is clearly evident in the Redfish Lake (RFL) strain of sockeye salmon Oncorhynchus nerka. In these fish, experimental immersion challenges with U isolates cause extremely high mortality and M isolates cause low or no mortality. When survivors of M virus immersion challenges were exposed to a secondary challenge with virulent U type virus they experienced high mortality, indicating that the primary M challenge did not elicit protective immunity. Delivery of a moderate dose (2 × 104 plaque-forming units [PFU]/fish) of virus by intraperitoneal injection challenge did not overcome RFL sockeye salmon resistance to M type IHNV. Injection challenge with a high dose (5 × 106 PFU/fish) of M type virus caused 10% mortality, and in this case survivors did develop protective immunity against a secondary U type virus challenge. Thus, although it is possible for M type IHNV to elicit cross-protective immunity in this disease model, it does not develop after immersion challenge despite entry, transient replication of M virus to low levels, stimulation of innate immune genes, and development of neutralizing antibodies in some fish.

  17. Current Understanding of Acute Bovine Liver Disease in Australia

    PubMed Central

    Read, Elizabeth; Edwards, Jacqueline; Deseo, Myrna; Rawlin, Grant; Rochfort, Simone

    2016-01-01

    Acute bovine liver disease (ABLD) is a hepatotoxicity principally of cattle which occurs in southern regions of Australia. Severely affected animals undergo rapid clinical progression with mortalities often occurring prior to the recognition of clinical signs. Less severely affected animals develop photosensitization and a proportion can develop liver failure. The characteristic histopathological lesion in acute fatal cases is severe, with acute necrosis of periportal hepatocytes with hemorrhage into the necrotic areas. Currently there are a small number of toxins that are known to cause periportal necrosis in cattle, although none of these have so far been linked to ABLD. Furthermore, ABLD has frequently been associated with the presence of rough dog’s tail grass (Cynosurus echinatus) and Drechslera spp. fungi in the pasture system, but it is currently unknown if these are etiological factors. Much of the knowledge about ABLD is contained within case reports, with very little experimental research investigating the specific cause(s). This review provides an overview of the current and most recently published knowledge of ABLD. It also draws on wider research and unpublished reports to suggest possible fungi and mycotoxins that may give rise to ABLD. PMID:28035972

  18. Burkholderia cenocepacia K56-2 trimeric autotransporter adhesin BcaA binds TNFR1 and contributes to induce airway inflammation.

    PubMed

    Mil-Homens, Dalila; Pinto, Sandra N; Matos, Rute G; Arraiano, Cecília; Fialho, Arsenio M

    2017-04-01

    Chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). CF pathogens acquire antibiotic resistance, overcome host defenses, and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. Among the multiple CF-associated pathogens, Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria have become prominent contributors of disease progression. Here, we demonstrate that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B. cenocepacia K56-2, is a tumor necrosis factor receptor 1-interacting protein able to regulate components of the tumor necrosis factor signaling pathway and ultimately leading to a significant production of the proinflammatory cytokine IL-8. Notably, this study is the first to demonstrate that a protein belonging to the TAA family is involved in the induction of the inflammatory response during B. cenocepacia infections, contributing to the success of the pathogen. Moreover, our results reinforce the relevance of the TAA BcaA as a multifunctional protein with a major role in B. cenocepacia virulence. © 2016 John Wiley & Sons Ltd.

  19. Imaging of Posttraumatic Arthritis, Avascular Necrosis, Septic Arthritis, Complex Regional Pain Syndrome, and Cancer Mimicking Arthritis.

    PubMed

    Rupasov, Andrey; Cain, Usa; Montoya, Simone; Blickman, Johan G

    2017-09-01

    This article focuses on the imaging of 5 discrete entities with a common end result of disability: posttraumatic arthritis, a common form of secondary osteoarthritis that results from a prior insult to the joint; avascular necrosis, a disease of impaired osseous blood flow, leading to cellular death and subsequent osseous collapse; septic arthritis, an infectious process leading to destructive changes within the joint; complex regional pain syndrome, a chronic limb-confined painful condition arising after injury; and cases of cancer mimicking arthritis, in which the initial findings seem to represent arthritis, despite a more insidious cause. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

    PubMed

    Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H

    2003-02-01

    Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

  1. 18F-FDG PET and PET/CT in the Localization and Characterization of Lesions in Patients with Ovarian Cancer.

    PubMed

    Caprio, M G; Capacchione, D; Mainolfi, C; Spera, A M; Salvatore, B; Cella, L; Salvatore, M; Pace, L

    2012-01-01

    The aim was to compare the imaging findings of (18)F-fluorodeoxyglucose ((18)F-FDG) PET and integrated PET/CT in patients with primary, recurrent or metastatic ovarian cancer. 21 women with ovarian cancer were evaluated. All patients had a integrated PET/CT scan. Localization, infiltration and uptake intensity of [(18)F]FDG were evaluated on PET and PET/CT. The certainty of localisation and characterisation was scored on a 3 point scale (L1 definite localisation; L2 probable localisation; L3 uncertain localisation; C1 benign; C2 equivocal; C3 malignant). PET scored as L1 54 lesions (44%), as L2 51 (42%), and as L3 17 (14%). On the other hand, PET/CT scored as L1 120 lesions (98%), as L2 2 (2%), and none as L3. Thus PET/CT allowed a better localization in 54% of lesions. Moreover, PET scored as C1 25 lesions (20%), as C2 62 (51%), and as C3 35 (29%). On the other hand, PET/CT scored as C1 57 lesions (47%), as C2 13 (11%), and as C3 52 (42%). Thus PET/CT allowed a sensible reduction in the number of equivocal lesions (40%). Even when patients were subgrouped on the basis of clinical stage of the disease, PET/CT was capable of better definition of the lesions either for localization and for characterization. In patients with ovarian cancer, PET/CT allows better anatomical localisation of pathologic uptake providing high accuracy for staging and restaging of ovarian cancer when compared with PET alone.

  2. Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

    PubMed Central

    Jadhav, Swati S; Lila, Anurag R; Kasaliwal, Rajeev; Khare, Shruti; Yerawar, Chaitanya G; Hira, Priya; Phadke, Uday; Shah, Hina; Lele, Vikram R; Malhotra, Gaurav; Bandgar, Tushar; Shah, Nalini S

    2016-01-01

    Background Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. Materials and methods Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared. Results Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). Conclusion CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID:27006371

  3. Localised hyperthermia in rodent models using an MRI-compatible high-intensity focused ultrasound system

    PubMed Central

    Bing, Chenchen; Nofiele, Joris; Staruch, Robert; Ladouceur-Wodzak, Michelle; Chatzinoff, Yonatan; Ranjan, Ashish; Chopra, Rajiv

    2015-01-01

    Purpose Localised hyperthermia in rodent studies is challenging due to the small target size. This study describes the development and characterisation of an MRI-compatible high-intensity focused ultrasound (HIFU) system to perform localised mild hyperthermia treatments in rodent models. Material and methods The hyperthermia platform consisted of an MRI-compatible small animal HIFU system, focused transducers with sector-vortex lenses, a custom-made receive coil, and means to maintain systemic temperatures of rodents. The system was integrated into a 3T MR imager. Control software was developed to acquire images, process temperature maps, and adjust output power using a proportional-integral-derivative feedback control algorithm. Hyperthermia exposures were performed in tissue-mimicking phantoms and in a rodent model (n = 9). During heating, an ROI was assigned in the heated region for temperature control and the target temperature was 42 °C; 30 min mild hyperthermia treatment followed by a 10-min cooling procedure was performed on each animal. Results 3D-printed sector-vortex lenses were successful at creating annular focal regions which enables customisation of the heating volume. Localised mild hyperthermia performed in rats produced a mean ROI temperature of 42.1 ± 0.3 °C. The T10 and T90 percentiles were 43.2 ± 0.4 °C and 41.0 ± 0.3 °C, respectively. For a 30-min treatment, the mean time duration between 41–45 °C was 31.1 min within the ROI. Conclusions The MRI-compatible HIFU system was successfully adapted to perform localised mild hyperthermia treatment in rodent models. A target temperature of 42 °C was well-maintained in a rat thigh model for 30 min. PMID:26540488

  4. A discussion on the merits and limitations of using drive-by monitoring to detect localised damage in a bridge

    NASA Astrophysics Data System (ADS)

    Hester, David; González, Arturo

    2017-06-01

    Given the large number of bridges that currently have no instrumentation, there are obvious advantages in monitoring the condition of a bridge by analysing the response of a vehicle crossing it. As a result, the last two decades have seen a rise in the research attempting to solve the problem of identifying damage in a bridge from vehicle measurements. This paper examines the theoretical feasibility and practical limitations of a drive-by system in identifying damage associated to localised stiffness losses. First, the nature of the damage feature that is sought within the vehicle response needs to be characterized. For this purpose, the total vehicle response is considered to be made of 'static' and 'dynamic' components, and where the bridge has experienced a localised loss in stiffness, an additional 'damage' component. Understanding the nature of this 'damage' component is crucial to have an informed discussion on how damage can be identified and localised. Leveraging this new understanding, the authors propose a wavelet-based drive-by algorithm. By comparing the effect of the 'damage' component to other key effects defining the measurements such as 'vehicle speed', the 'road profile' and 'noise' on a wavelet contour plot, it is possible to establish if there is a frequency range where drive-by can be successful. The algorithm uses then specific frequency bands to improve the sensitivity to damage with respect to limitations imposed by Vehicle-Bridge vibrations. Recommendations on the selection of the mother wavelet and frequency band are provided. Finally, the paper discusses the impact of noise and road profile on the ability of the approach to identify damage and how periodic measurements can be effective at monitoring localised stiffness changes.

  5. Non-orthogonal tool/flange and robot/world calibration.

    PubMed

    Ernst, Floris; Richter, Lars; Matthäus, Lars; Martens, Volker; Bruder, Ralf; Schlaefer, Alexander; Schweikard, Achim

    2012-12-01

    For many robot-assisted medical applications, it is necessary to accurately compute the relation between the robot's coordinate system and the coordinate system of a localisation or tracking device. Today, this is typically carried out using hand-eye calibration methods like those proposed by Tsai/Lenz or Daniilidis. We present a new method for simultaneous tool/flange and robot/world calibration by estimating a solution to the matrix equation AX = YB. It is computed using a least-squares approach. Because real robots and localisation are all afflicted by errors, our approach allows for non-orthogonal matrices, partially compensating for imperfect calibration of the robot or localisation device. We also introduce a new method where full robot/world and partial tool/flange calibration is possible by using localisation devices providing less than six degrees of freedom (DOFs). The methods are evaluated on simulation data and on real-world measurements from optical and magnetical tracking devices, volumetric ultrasound providing 3-DOF data, and a surface laser scanning device. We compare our methods with two classical approaches: the method by Tsai/Lenz and the method by Daniilidis. In all experiments, the new algorithms outperform the classical methods in terms of translational accuracy by up to 80% and perform similarly in terms of rotational accuracy. Additionally, the methods are shown to be stable: the number of calibration stations used has far less influence on calibration quality than for the classical methods. Our work shows that the new method can be used for estimating the relationship between the robot's and the localisation device's coordinate systems. The new method can also be used for deficient systems providing only 3-DOF data, and it can be employed in real-time scenarios because of its speed. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Evolution of the localisation and composition of phenolics in grape skin between veraison and maturity in relation to water availability and some climatic conditions.

    PubMed

    Cadot, Yves; Chevalier, Michel; Barbeau, Gerard

    2011-08-30

    Several studies have investigated the composition of phenolics in grape skin during grape maturation under various conditions of light exposure, water stress, nitrogen supply and mineral nutrition, but their localisation during berry development is not well known. In this study the composition and localisation of proanthocyanidins were monitored for three years on four plots known to induce a distinctive behaviour of the vine (Cabernet Franc). The composition of phenolics was determined by spectrophotometry; also, in one year, proanthocyanidins were determined by high-performance liquid chromatography. Further information was obtained histochemically by means of toluidine blue O staining and image analysis. The results indicated that clear differences in phenolic quantification existed between the biochemical and histochemical approaches; the proportion of cells without phenolics was not linked with the quantity determined by the analytical methods used. The histochemical method showed the evolution of the localisation and typology of cells with and without phenolics during ripening. The number of cells without any phenolic compounds appeared to be very dependent on the mesoclimatic conditions and only slightly dependent on the site water status. Clear differences in phenolic quantification existed between the biochemical and histochemical approaches; the proportion of cells with phenolics was not linked with the quantity determined by biochemistry. The histochemical method showed an evolution of the localisation and typology of cells with and without phenolics in which mesoclimatic conditions were the most influential factor. Finally, the study showed some advantages of the histochemical approach: it gives information about the anatomy of the tissue as well as the nature and distribution of some of the large macromolecules and allows reconstruction of the three-dimensional plant structure. Copyright © 2011 Society of Chemical Industry.

  7. Novel maximum likelihood approach for passive detection and localisation of multiple emitters

    NASA Astrophysics Data System (ADS)

    Hernandez, Marcel

    2017-12-01

    In this paper, a novel target acquisition and localisation algorithm (TALA) is introduced that offers a capability for detecting and localising multiple targets using the intermittent "signals-of-opportunity" (e.g. acoustic impulses or radio frequency transmissions) they generate. The TALA is a batch estimator that addresses the complex multi-sensor/multi-target data association problem in order to estimate the locations of an unknown number of targets. The TALA is unique in that it does not require measurements to be of a specific type, and can be implemented for systems composed of either homogeneous or heterogeneous sensors. The performance of the TALA is demonstrated in simulated scenarios with a network of 20 sensors and up to 10 targets. The sensors generate angle-of-arrival (AOA), time-of-arrival (TOA), or hybrid AOA/TOA measurements. It is shown that the TALA is able to successfully detect 83-99% of the targets, with a negligible number of false targets declared. Furthermore, the localisation errors of the TALA are typically within 10% of the errors generated by a "genie" algorithm that is given the correct measurement-to-target associations. The TALA also performs well in comparison with an optimistic Cramér-Rao lower bound, with typical differences in performance of 10-20%, and differences in performance of 40-50% in the most difficult scenarios considered. The computational expense of the TALA is also controllable, which allows the TALA to maintain computational feasibility even in the most challenging scenarios considered. This allows the approach to be implemented in time-critical scenarios, such as in the localisation of artillery firing events. It is concluded that the TALA provides a powerful situational awareness aid for passive surveillance operations.

  8. Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

    PubMed Central

    Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan

    2014-01-01

    The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792

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

    PubMed

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

    2015-02-01

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

  10. 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

  11. Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An Experimental Study in Rats.

    PubMed

    Ayoub, Isabelle; Oh, Man S; Gupta, Raavi; McFarlane, Michael; Babinska, Anna; Salifu, Moro O

    2015-01-01

    Based on a single rat study by Lillemoe et al, the consensus has been formed to implicate sorbitol rather than sodium polystyrene sulfonate (SPS) as the culprit for colon necrosis in humans treated with SPS and sorbitol. We tested the hypothesis that colon necrosis by sorbitol in the experiment was due to the high osmolality and volume of sorbitol rather than its chemical nature. 26 rats underwent 5/6 nephrectomy. They were divided into 6 groups and given enema solutions under anesthesia (normal saline, 33% sorbitol, 33% mannitol, SPS in 33% sorbitol, SPS in normal saline, and SPS in distilled water). They were sacrificed after 48 hours of enema administration or earlier if they were very sick. The gross appearance of the colon was visually inspected, and then sliced colon tissues were examined under light microscopy. 1 rat from the sorbitol and 1 from the mannitol group had foci of ischemic colonic changes. The rats receiving SPS enema, in sorbitol, normal saline, distilled water, had crystal deposition with colonic necrosis and mucosal erosion. All the rats not given SPS survived until sacrificed at 48 h whereas 11 of 13 rats that received SPS in sorbitol, normal saline or distilled water died or were clearly dying and sacrificed sooner. There was no difference between sorbitol and mannitol when given without SPS. In a surgical uremic rat model, SPS enema given alone or with sorbitol or mannitol seemed to cause colon necrosis and high mortality rate, whereas 33% sorbitol without SPS did not.

  12. Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An Experimental Study in Rats

    PubMed Central

    Ayoub, Isabelle; Oh, Man S.; Gupta, Raavi; McFarlane, Michael; Babinska, Anna; Salifu, Moro O.

    2015-01-01

    Introduction Based on a single rat study by Lillemoe et al, the consensus has been formed to implicate sorbitol rather than sodium polystyrene sulfonate (SPS) as the culprit for colon necrosis in humans treated with SPS and sorbitol. We tested the hypothesis that colon necrosis by sorbitol in the experiment was due to the high osmolality and volume of sorbitol rather than its chemical nature. Methods 26 rats underwent 5/6 nephrectomy. They were divided into 6 groups and given enema solutions under anesthesia (normal saline, 33% sorbitol, 33% mannitol, SPS in 33% sorbitol, SPS in normal saline, and SPS in distilled water). They were sacrificed after 48 hours of enema administration or earlier if they were very sick. The gross appearance of the colon was visually inspected, and then sliced colon tissues were examined under light microscopy. Results 1 rat from the sorbitol and 1 from the mannitol group had foci of ischemic colonic changes. The rats receiving SPS enema, in sorbitol, normal saline, distilled water, had crystal deposition with colonic necrosis and mucosal erosion. All the rats not given SPS survived until sacrificed at 48 h whereas 11 of 13 rats that received SPS in sorbitol, normal saline or distilled water died or were clearly dying and sacrificed sooner. There was no difference between sorbitol and mannitol when given without SPS. Conclusions In a surgical uremic rat model, SPS enema given alone or with sorbitol or mannitol seemed to cause colon necrosis and high mortality rate, whereas 33% sorbitol without SPS did not. PMID:26413782

  13. Dorsal thermal necrosis in dogs: a retrospective analysis of 16 cases in the southwestern USA (2009-2016).

    PubMed

    Schwartz, Stephanne L; Schick, Anthea E; Lewis, Thomas P; Loeffler, Diana

    2018-04-01

    Prolonged sun exposure in high ambient temperatures has been recognized as a cause of thermal burns on the dorsal skin of dogs, termed dorsal thermal necrosis (DTN). To characterize the clinical presentation, histopathology and outcomes of 16 dogs diagnosed with DTN and to identify associated risk factors. Sixteen dogs diagnosed with DTN. Medical records from 2009 to 2016 were reviewed retrospectively. Inclusion criteria included: (i) historical solar exposure; (ii) dorsal burn injuries and (iii) histopathological findings consistent with DTN. The majority of cases (15 of 16) occurred during warmer months (May-September) in the southwestern USA. Affected dogs had predominantly dark, short hair coats, whereas four of 16 dogs had lighter coat colours. Five dogs had naturally longer hair, but two hair coats had been recently clipped. Signs consistent with heat exhaustion or heatstroke were reported prior to the development of cutaneous lesions in four of 16 dogs. The most common skin lesions were alopecia, erythema, ulcerations, eschars/necrosis and crusts. Histological findings were consistent with other types of partial and full-thickness thermal burns, and included coagulation necrosis in the majority of cases. Most dogs were treated supportively with analgesics and antimicrobial therapies. The majority of DTN wounds healed via second intention, although surgery was performed on two dogs. Dorsal thermal necrosis should be considered as a differential diagnosis for dogs with dorsal cutaneous burns and a history of sun exposure in high external temperatures. Dogs with dark, short hair coats may be at an increased risk. © 2018 ESVD and ACVD.

  14. Diagnostic utility of endobronchial ultrasound features in differentiating malignant and benign lymph nodes.

    PubMed

    Agrawal, Sumita P; Ish, Pranav; Goel, Akhil D; Gupta, Nitesh; Chakrabarti, Shibdas; Bhattacharya, Dipak; Sen, Manas K; Suri, Jagdish C

    2018-06-25

    Endobronchial ultrasound (EBUS) features have been shown to be useful in predicting etiology of enlarged malignant lymph nodes. However, there is dearth of evidence especially from developing countries. We assessed the EBUS characteristics across various mediastinal and hilar lymphadenopathies. In this prospective study, all patients with mediastinal and hilar lymphadenopathy on CT Chest and who were planned for EBUS-FNA (Fine Needle Aspiration) were included. EBUS features of lymph nodes studied were shape, size, margins, echogenicity, central hilar structure (CHS), coagulation necrosis sign and colour power doppler index (CPDI). These were scored and compared between benign and malignant lymphadenopathies. A total of 86 lymph nodes in 46 patients were prospectively studied of which 23 (26.7%) were malignant, 27 (31.3%) tuberculosis and 36 (41.8%) sarcoidosis. There was significant difference between malignant and benign lymph nodes in terms of CHS [central hilar structutre] (p=0.011), margins (p=0.036) and coagulation necrosis sign (p<0.001). On comparison of features of malignancy and tuberculosis, there were significant differences in margins (p=0.016) and coagulation necrosis sign (p 0.001). However, when malignancy and sarcoidosis was compared, there were differences in echogenicity (p=0.002), CHS (p=0.009) and coagulation necrosis sign (p<0.001). Only coagulation necrosis sign was found to be highly consistent with malignant lymph nodes. The other features cannot be used to distinguish malignant from benign lymph nodes, especially in a developing country like India where tuberculosis is a common cause of mediastinal lymphadenopathy.

  15. [Epidemiologic reasons for screening programs in the national health service].

    PubMed

    Ottó, Szabolcs

    2003-11-30

    The author describes the current health state of the Hungarian population in terms of cancer mortality and morbidity. Based on the comparative analysis of national and international, mainly European, data he describes the unfavourable Hungarian indices trying to identify their causes and the possible breaking free from them, as well. The greatest potential lies in the organised, continuous screenings within the frame of "Johan Béla National Programme of the Decade of Health". Since tumour diseases pose severe and alarming problems in national health care the reduction of extremely high mortality in three tumour localisation (cervix uteri, breast and colorectum) by regular screenings is absolutely justified.

  16. Significance of independent radon entry rate and air exchange rate assessment for the purpose of radon mitigation effectiveness proper evaluation: case studies.

    PubMed

    Froňka, A; Jílek, K; Moučka, L; Brabec, M

    2011-05-01

    Two new single-family houses identified as insufficient with regard to existing radon barrier efficiency, have been selected for further examination. A complex set of radon diagnosis procedures has been applied in order to localise and quantify radon entry pathways into the indoor environment. Independent assessment of radon entry rate and air exchange rate has been carried out using the continuous indoor radon measurement and a specific tracer gas application. Simultaneous assessment of these key determining factors has turned out to be absolutely crucial in the context of major cause identification of elevated indoor radon concentration.

  17. Detection and quantification of Bremia lactucae by spore trapping and quantitative PCR

    USDA-ARS?s Scientific Manuscript database

    Bremia lactucae causes the characteristic vein-delimited lesions, leaf chlorosis and necrosis and adversely affects marketability of lettuce. The disease has been managed with a combination of host resistance and fungicide applications with mixed success over the years. Fungicide applications are ro...

  18. Tomato necrotic streak virus, a novel subgroup 2 ilarvirus

    USDA-ARS?s Scientific Manuscript database

    A novel plant virus has been identified infecting fresh market tomato plants in south and southeast Florida. The virus causes necrosis of tomato leaves, petioles and stems, and necrotic rings or spots on tomato fruits. Symptomatic tomato plant tissue was used to mechanically inoculate tomato plant...

  19. Peripheral Vascular Disease

    MedlinePlus

    ... smokers aged 20 to 40. Smoking causes the blood vessels to tighten in everyone who smokes. But in people with Buerger’s disease, there is so much tightening in the vessels that a lack of oxygen to the cells (ischemia) or tissue death (necrosis) may result. The symptoms may be different for ...

  20. Hip fracture surgeries

    MedlinePlus

    ... risks. Risks Following are risks of surgery: Avascular necrosis. This is when the blood supply in part of the femur is cut off for a period of time. This can cause part of the bone to die. Injury to nerves or blood vessels. Parts of the hip bone may not join ...

  1. A Case of Lionfish Envenomation Presenting to an Inland Emergency Department.

    PubMed

    Schult, Rachel F; Acquisto, Nicole M; Stair, Crystal K; Wiegand, Timothy J

    2017-01-01

    Lionfish envenomation can cause erythema, edema, necrosis, and severe pain at the exposed site. Treatment often includes supportive wound care, pain management, and hot water immersion. We report a case of lionfish exposure presenting to an inland emergency department treated successfully with these measures.

  2. A new virus of soybean confirmed in Wisconsin

    USDA-ARS?s Scientific Manuscript database

    This week our laboratory confirmed the presence of Soybean vein necrosis-associated virus (SVNaV) in soybeans sampled in Wisconsin. Samples were taken at several times during September and processed in our laboratory. Symptoms of the disease caused by the virus include yellowing (chlorosis) of the ...

  3. A Recombinant of Bean common mosaic virus Induces Temperature-Insensitive Necrosis in an I Gene-Bearing Line of Common Bean.

    PubMed

    Feng, Xue; Poplawsky, Alan R; Karasev, Alexander V

    2014-11-01

    The I gene is a single, dominant gene conferring temperature-sensitive resistance to all known strains of Bean common mosaic virus (BCMV) in common bean (Phaseolus vulgaris). However, the closely related Bean common mosaic necrosis virus (BCMNV) induces whole plant necrosis in I-bearing genotypes of common bean, and the presence of additional, recessive genes is required to prevent this severe whole plant necrotic reaction caused by BCMNV. Almost all known BCMNV isolates have so far been classified as having pathotype VI based on their interactions with the five BCMV resistance genes, and all have a distinct serotype A. Here, we describe a new isolate of BCMV, RU1M, capable of inducing whole plant necrosis in the presence of the I gene, that appears to belong to pathotype VII and exhibits B-serotype. Unlike other isolates of BCMV, RU1M was able to induce severe whole plant necrosis below 30°C in bean cultivar Jubila that carries the I gene and a protective recessive gene bc-1. The whole genome of RU1M was cloned and sequenced and determined to be 9,953 nucleotides long excluding poly(A), coding for a single polyprotein of 3,186 amino acids. Most of the genome was found almost identical (>98%) to the BCMV isolate RU1-OR (also pathotype VII) that did not induce necrotic symptoms in 'Jubila'. Inspection of the nucleotide sequences for BCMV isolates RU1-OR, RU1M, and US10 (all pathotype VII) and three closely related sequences of BCMV isolates RU1P, RU1D, and RU1W (all pathotype VI) revealed that RU1M is a product of recombination between RU1-OR and a yet unknown potyvirus. A 0.8-kb fragment of an unknown origin in the RU1M genome may have led to its ability to induce necrosis regardless of temperature in beans carrying the I gene. This is the first report of a BCMV isolate inducing temperature-insensitive necrosis in an I gene containing bean genotype.

  4. Towards Unmanned Systems for Dismounted Operations in the Canadian Forces

    DTIC Science & Technology

    2011-01-01

    LIDAR , and RADAR) and lower power/mass, passive imaging techniques such as structure from motion and simultaneous localisation and mapping ( SLAM ...sensors and learning algorithms. 5.1.2 Simultaneous localisation and mapping SLAM algorithms concurrently estimate a robot pose and a map of unique...locations and vehicle pose are part of the SLAM state vector and are estimated in each update step. AISS developed a monocular camera-based SLAM

  5. Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat.

    PubMed

    Assier, E; Bouzinba-Segard, H; Stolzenberg, M C; Stephens, R; Bardos, J; Freemont, P; Charron, D; Trowsdale, J; Rich, T

    1999-04-16

    A novel human gene RED, and the murine homologue, MuRED, were cloned. These genes were named after the extensive stretch of alternating arginine (R) and glutamic acid (E) or aspartic acid (D) residues that they contain. We term this the 'RED' repeat. The genes of both species were expressed in a wide range of tissues and we have mapped the human gene to chromosome 5q22-24. MuRED and RED shared 98% sequence identity at the amino acid level. The open reading frame of both genes encodes a 557 amino acid protein. RED fused to a fluorescent tag was expressed in nuclei of transfected cells and localised to nuclear dots. Co-localisation studies showed that these nuclear dots did not contain either PML or Coilin, which are commonly found in the POD or coiled body nuclear compartments. Deletion of the amino terminal 265 amino acids resulted in a failure to sort efficiently to the nucleus, though nuclear dots were formed. Deletion of a further 50 amino acids from the amino terminus generates a protein that can sort to the nucleus but is unable to generate nuclear dots. Neither construct localised to the nucleolus. The characteristics of RED and its nuclear localisation implicate it as a regulatory protein, possibly involved in transcription.

  6. The plasma membrane recycling pathway and cell polarity in plants: studies on PIN proteins.

    PubMed

    Boutté, Yohann; Crosnier, Marie-Thérèse; Carraro, Nicola; Traas, Jan; Satiat-Jeunemaitre, Béatrice

    2006-04-01

    The PIN-FORMED (PIN) proteins are plasma-membrane-associated facilitators of auxin transport. They are often targeted to one side of the cell only through subcellular mechanisms that remain largely unknown. Here, we have studied the potential roles of the cytoskeleton and endomembrane system in the localisation of PIN proteins. Immunocytochemistry and image analysis on root cells from Arabidopsis thaliana and maize showed that 10-30% of the intracellular PIN proteins mapped to the Golgi network, but never to prevacuolar compartments. The remaining 70-90% were associated with yet to be identified structures. The maintenance of PIN proteins at the plasma membrane depends on a BFA-sensitive machinery, but not on microtubules and actin filaments. The polar localisation of PIN proteins at the plasmamembrane was not reflected by any asymmetric distribution of cytoplasmic organelles. In addition, PIN proteins were inserted in a symmetrical manner at both sides of the cell plate during cytokinesis. Together, the data indicate that the localisation of PIN proteins is a postmitotic event, which depends on local characteristics of the plasma membrane and its direct environment. In this context, we present evidence that microtubule arrays might define essential positional information for PIN localisation. This information seems to require the presence of an intact cell wall.

  7. Quantitative Evaluation of Stereo Visual Odometry for Autonomous Vessel Localisation in Inland Waterway Sensing Applications

    PubMed Central

    Kriechbaumer, Thomas; Blackburn, Kim; Breckon, Toby P.; Hamilton, Oliver; Rivas Casado, Monica

    2015-01-01

    Autonomous survey vessels can increase the efficiency and availability of wide-area river environment surveying as a tool for environment protection and conservation. A key challenge is the accurate localisation of the vessel, where bank-side vegetation or urban settlement preclude the conventional use of line-of-sight global navigation satellite systems (GNSS). In this paper, we evaluate unaided visual odometry, via an on-board stereo camera rig attached to the survey vessel, as a novel, low-cost localisation strategy. Feature-based and appearance-based visual odometry algorithms are implemented on a six degrees of freedom platform operating under guided motion, but stochastic variation in yaw, pitch and roll. Evaluation is based on a 663 m-long trajectory (>15,000 image frames) and statistical error analysis against ground truth position from a target tracking tachymeter integrating electronic distance and angular measurements. The position error of the feature-based technique (mean of ±0.067 m) is three times smaller than that of the appearance-based algorithm. From multi-variable statistical regression, we are able to attribute this error to the depth of tracked features from the camera in the scene and variations in platform yaw. Our findings inform effective strategies to enhance stereo visual localisation for the specific application of river monitoring. PMID:26694411

  8. A secondary wave of neutrophil infiltration causes necrosis and ulceration in lesions of experimental American cutaneous leishmaniasis.

    PubMed

    Peniche, Alex G; Bonilla, Diana L; Palma, Gloria I; Melby, Peter C; Travi, Bruno L; Osorio, E Yaneth

    2017-01-01

    We evaluated the importance of neutrophils in the development of chronic lesions caused by L. Viannia spp. using the hamster as experimental model of American Cutaneous Leishmaniasis (ACL). Neutrophils infiltrated the lesion within the first six hours post-infection. Inhibition of this early infiltration using a polyclonal antibody or cyclophosphamide was associated with transient parasite control but the protective effect vanished when lesions became clinically apparent. At lesion onset (approximately 10 days p.i.), there was an increased proportion of both uninfected and infected macrophages, and subsequently a second wave of neutrophils infiltrated the lesion (after 19 days p.i.) This second neutrophil infiltration was associated with lesion necrosis and ulceration (R2 = 0.75) and maximum parasite burden. Intradermal delivery of N-formylmethionyl-leucyl-phenylalanine (fMLP), aimed to increase neutrophil infiltration, resulted in larger lesions with marked necrosis and higher parasite burden than in mock treated groups (p<0.001 each). In contrast, reduced neutrophil infiltration via cyclophosphamide-mediated depletion led to more benign lesions and lower parasite loads compared to controls (p<0.001 each). Neutrophils of the second wave expressed significantly lower GM-CSF, reactive oxygen species and nitric oxide than those of the first wave, suggesting that they had less efficient anti-leishmania activity. However, there was increased inflammatory cytokines and expression of neutrophil proteases (myeloperoxidase, cathepsin G and elastase) in lesions during the second wave of neutrophil infiltration compared with the levels reached during the first wave (6h p.i.). This suggests that augmented neutrophil proteases and inflammatory cytokines during the secondary wave of neutrophils could contribute to skin inflammation, ulceration and necrosis in ACL. The overall results indicate that neutrophils were unable to clear the infection in this model, and that the second wave of neutrophils played an important role in the severity of ACL.

  9. A rare case of avascular necrosis in sickle cell trait: a case report.

    PubMed

    Sanders, William J

    2018-01-01

    Sickle cell trait is usually an asymptomatic presentation of a patient with slightly different hemoglobin molecule makeup than normal. It is similar to a more serious disease, sickle cell disease, in which a person's hemoglobin is mutated in such a way that causes their red blood cells to easily change shape in certain environmental and internal states; this causes red blood cells to adhere to the walls and occlude the lumen of the arteries in which they travel, leading to downstream effects secondary to ischemia. Sickle cell trait does not have these ischemic effects, usually. In this case, a young African American female patient presents to the clinic with severe right hip pain. Her past medical history includes sickle cell trait and asthma. She has not been symptomatic of her asthma for years and is not on therapy for it. The pain has lasted for several months and has not improved with anti-inflammatory medication. There is severe pain with internal and external rotation of the hip. The neurovascularity of the lower extremities is intact bilaterally. MRI of the femur shows stage 2 or 3 avascular necrosis of the femoral head, while X-rays of the femur are unremarkable. Non weight-bearing for several weeks was unsuccessful; shortly thereafter, the patient underwent core decompression of the right femoral head as well as starting bisphosphonates. The patient improved temporarily but regressed shortly thereafter. Her avascular necrosis worsened radiographically over the next several months. At this point, the only other option would be to do a total hip arthroplasty, but the patient may need several more throughout her lifetime due to the lifespan of the artificial replacement. There have only been scarce reports of avascular necrosis in patients with sickle cell trait. This manuscript presents such a case and includes the trials and tribulations associated with its management.

  10. p53-PGC-1α Pathway Mediates Oxidative Mitochondrial Damage and Cardiomyocyte Necrosis Induced by Monoamine Oxidase-A Upregulation: Role in Chronic Left Ventricular Dysfunction in Mice

    PubMed Central

    Villeneuve, Christelle; Guilbeau-Frugier, Céline; Sicard, Pierre; Lairez, Olivier; Ordener, Catherine; Duparc, Thibaut; De Paulis, Damien; Couderc, Bettina; Spreux-Varoquaux, Odile; Tortosa, Florence; Garnier, Anne; Knauf, Claude; Valet, Philippe; Borchi, Elisabetta; Nediani, Chiara; Gharib, Abdallah; Ovize, Michel; Delisle, Marie-Bernadette; Mialet-Perez, Jeanne

    2013-01-01

    Abstract Aims: Oxidative stress and mitochondrial dysfunction participate together in the development of heart failure (HF). mRNA levels of monoamine oxidase-A (MAO-A), a mitochondrial enzyme that produces hydrogen peroxide (H2O2), increase in several models of cardiomyopathies. Therefore, we hypothesized that an increase in cardiac MAO-A could cause oxidative stress and mitochondrial damage, leading to cardiac dysfunction. In the present study, we evaluated the consequences of cardiac MAO-A augmentation on chronic oxidative damage, cardiomyocyte survival, and heart function, and identified the intracellular pathways involved. Results: We generated transgenic (Tg) mice with cardiac-specific MAO-A overexpression. Tg mice displayed cardiac MAO-A activity levels similar to those found in HF and aging. As expected, Tg mice showed a significant decrease in the cardiac amounts of the MAO-A substrates serotonin and norepinephrine. This was associated with enhanced H2O2 generation in situ and mitochondrial DNA oxidation. As a consequence, MAO-A Tg mice demonstrated progressive loss of cardiomyocytes by necrosis and ventricular failure, which were prevented by chronic treatment with the MAO-A inhibitor clorgyline and the antioxidant N-acetyl-cystein. Interestingly, Tg hearts exhibited p53 accumulation and downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial function. This was concomitant with cardiac mitochondrial ultrastructural defects and ATP depletion. In vitro, MAO-A adenovirus transduction of neonatal cardiomyocytes mimicked the results in MAO-A Tg mice, triggering oxidative stress-dependent p53 activation, leading to PGC-1α downregulation, mitochondrial impairment, and cardiomyocyte necrosis. Innovation and Conclusion: We provide the first evidence that MAO-A upregulation in the heart causes oxidative mitochondrial damage, p53-dependent repression of PGC-1α, cardiomyocyte necrosis, and chronic ventricular dysfunction. Antioxid. Redox Signal. 18, 5–18. PMID:22738191

  11. Idiopathic avascular necrosis of the femoral heads in five members of a Moroccan family.

    PubMed

    Sekkat, Jihane; Rachidi, Ouafaa; Janani, Saadia; Mkinsi, Ouafaa

    2012-10-01

    Avascular necrosis (AVN) is idiopathic in about 40% of cases. The pathophysiology of avascular necrosis remains incompletely elucidated. Here, we report a case that underlines the role for inherited factors in AVN of the femoral heads. Idiopathic AVN of the femoral heads occurred in five members of the same family (a woman, her two paternal aunts, her male paternal cousin and her female paternal cousin) at a mean age of 42.4 years (range, 33-58 years). Standard pelvic radiographs showed Arlet and Ficat stage 4 AVN in three patients and stage 3 in two patients. None of the patients had a history of glucocorticoid therapy, alcohol abuse, or trauma. All five patients underwent investigations for a cause, including blood cell counts, a lipid profile, coagulation tests, testing for antinuclear antibodies, hemoglobin electrophoresis, ultrasonography of the abdomen, and standard radiographs of the long limb bones. The results were normal or negative, ruling out known hereditary causes of AVN such as sickle cell anemia and Gaucher disease. Many cases of familial AVN of the femoral head have been described in patients with sickle cell anemia or Gaucher disease. However, only five families with idiopathic familial AVN of the femoral heads have been reported (three in the US and two in Taiwan). All the patients in these families had isolated bilateral AVN of the femoral heads without AVN at other sites. Copyright © 2012. Published by Elsevier SAS.

  12. Morphology of certain viruses of Salmonid Fishes. I. in vitro studies of some viruses causing Hematopoietic Necrosis

    USGS Publications Warehouse

    Amend, Donald F.; Chambers, Velma C.

    1970-01-01

    An electron microscope study was performed on three virus isolates that caused hematopoietic necrosis in salmonid fishes: infectious hematopoietic necrosis (IHN), Oregon Sockeye Disease (OSD), and Sacramento River Chinook Salmon Disease (SRCD). All three isolates were examined by negative staining of fathead minnow (FHM) monolayer tissue culture concentrates and IHN virus was also examined in thin sections of FHM cells. Viruslike particles were observed in infected tissues, but similar structures were not found in uninfected cultures. All three isolates were bullet-shaped, but oval and truncated forms were also observed. Mean measurements of particles from IHN-virus-infected tissue were 158 × 90 mμ. They consisted of an outer coat 15 mμ thick, a core 60 mμ in diameter, subunits about 5 mμ, and an axial pore about 20 mμ in diameter. These particles also were seen budding from the cytoplasmic membrane. Similar particles from SRCD were 159 × 90 mμ and isolates from OSD were 181 × 91 mμ. The three isolates were morphologically indistinguishable from one another and the greater length of OSD was considered insignificant. IHN, SRCD, and OSD viruses were tentatively placed in the rhabdovirus group, but serological studies are needed to determine if they are antigenically identical or should be included as separate members. Biochemical and physical characteristics of these viruses and a comparison with other salmonid viruses is also discussed.

  13. [Micrococcus sp.--the pathogen of leaf necrosis of horse-chestnuts (Aesculus L.) in Kiev].

    PubMed

    Iakovleva, L M; Makhinia, L V; Shcherbina, T N; Ogorodnik, L E

    2013-01-01

    A group of phytopathogenic bacteria was isolated from patterns of drying horse-chestnuts (Aesculus L.), which grow in Kyiv. The properties of slowly growing, highly aggressive microorganisms have been described in the paper. They grow up on the 8-10th day after sowing. The investigated microorganisms form very small (0.5-1 mm in diameter) colonies on the potato agar. Bacteria are protuberant, shining, smooth with flat edges, they are pale yellow, yellow, or pink. The bacteria are Gram-positive, spherical, are disposed in smears singly, in pairs, as accumulations, or netting. They are aerobes, do not form spores, are not mobile. They are inert in respect of different sources of carbon. They reduce nitrates, do not dilute gelatin, do not hydrolyze starch, do not release hydrogen sulphide and indole. The bacteria are catalase-positive, oxidase-negative. They do not cause potato and carrot rot. They lose quickly their viability under the laboratory conditions. The saturated acids C 14:0; C 15:0; C16:0; C18:0 have been revealed in the composition of cellular fatty acids. Microorganisms are identified as Micrococcus sp. Under artificial inoculation this highly aggressive pathogen causes drying of the horse-chestnut buds and necrosis, which occupies 1/3-1/2 of the leaf plate. A wide zone of chlorosis, surrounding necrosis, may occupy the whole leaf surface. The infected leaves use to twist up from the top (apex) or along a midrib and to dry.

  14. Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease.

    PubMed

    Crowe, J Scott; Roberts, Kevin J; Carlton, Timothy M; Maggiore, Luana; Cubitt, Marion F; Clare, Simon; Harcourt, Katherine; Reckless, Jill; MacDonald, Thomas T; Ray, Keith P; Vossenkämper, Anna; West, Michael R

    2018-03-21

    TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.

  15. Mass envenomation of a mare and foal by bees.

    PubMed

    Lewis, N; Racklyeft, D J

    2014-05-01

    The clinical course of toxic envenomation of a mare and her foal after an attack by a swarm of bees in the Upper Hunter Valley of New South Wales is described. Early agitation and urticaria were followed by more severe systemic clinical signs within 18 h. There was severe, generalised angioedema, rhabdomyolysis, hypovolaemia, gastrointestinal stasis and renal injury. A particular feature in the mare was almost maniacal behaviour during the first 48 h. Clinical pathological examination showed evidence of haemoconcentration, intravascular haemolysis, thrombocytopenia, azotaemia, rhabdomyolysis and hypoproteinaemia. Symptomatic treatment was initiated using intravenous fluids, anti-inflammatory drugs, histamine antagonists, analgesia and antibiotics. The foal responded within 12 h, but management of the mare was complicated by severe pain, generalised oedema, intrauterine haemorrhage, renal injury and later, recurrent fever. The most severe, acute effects of mass envenomation lasted for 3-4 days. Neither mare nor foal suffered any known lasting systemic effects of envenomation, although localised dermal necrosis resulted in white hairs at some sting sites and deformed ear tips in the foal. Early recognition of clinical signs and treatment of toxic envenomation with an understanding of the physiological effects of hymenoptera venom can lead to a favourable outcome in horses receiving a non-lethal dose. Further case reports of the treatment of affected horses are needed to expand knowledge of how best to approach this rare, but serious intoxication. © 2014 Australian Veterinary Association.

  16. Contribution of Transjugular Liver Biopsy in Patients with the Clinical Presentation of Acute Liver Failure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Luca, Angelo; Gruttadauria, Salvatore

    2006-12-15

    Purpose. Acute liver failure (ALF) treated with conservative therapy has a poor prognosis, although individual survival varies greatly. In these patients, the eligibility for liver transplantation must be quickly decided. The aim of this study was to assess the role of transjugular liver biopsy (TJLB) in the management of patients with the clinical presentation of ALF. Methods. Seventeen patients with the clinical presentation of ALF were referred to our institution during a 52 month period. A TJLB was performed using the Cook Quick-Core needle biopsy. Clinical data, procedural complications, and histologic findings were evaluated. Results. Causes of ALF were virusmore » hepatitis B infection in 7 patients, drug toxicity in 4, mushroom in 1, Wilson's disease in 1, and unknown origin in 4. TJLB was technically successful in all patients without procedure-related complications. Tissue specimens were satisfactory for diagnosis in all cases. In 14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3 patients the initial diagnosis was altered by the presence of unknown cirrhosis. Seven patients with necrosis <60% were successfully treated with medical therapy; 6 patients with submassive or massive necrosis ({>=}85%) were treated with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had submassive necrosis. There was a strict statistical correlation (r = 0.972, p < 0.0001) between the amount of necrosis at the frozen section examination and the necrosis found at routine histologic examination. The average time for TJLB and frozen section examination was 80 min. Conclusion. In patients with the clinical presentation of ALF, submassive or massive liver necrosis and cirrhosis are predictors of poor prognosis. TLJB using an automated device and frozen section examination can be a quick and effective tool in clinical decision-making, especially in deciding patient selection and the best timing for liver transplantation.« less

  17. Effects of temperature on germination of sporangia, infection and protein secretion by Phytophthora kernoviae

    USDA-ARS?s Scientific Manuscript database

    Phytophthora kernoviae has been reported to cause bleeding stem lesions and foliar necrosis on a wide range of species, with little knowledge of the optimal conditions for infection. Detached Rhododendron ponticum leaves were inoculated with six different isolates of P. kernoviae sporangia and set ...

  18. Complete sequence and diversity of a maize-associated Polerovirus in East Africa

    USDA-ARS?s Scientific Manuscript database

    Since 2011-2012, Maize lethal necrosis (MLN) has emerged in East Africa, causing massive yield loss and propelling research to identify viruses and virus populations present in maize. As expected, next generation sequencing (NGS) has revealed diverse and abundant viruses from the family Potyviridae,...

  19. Lesion expansion of Sclerotinia minor and S. sclerotiorum on two peanut cultivars

    USDA-ARS?s Scientific Manuscript database

    Inoculation of peanut stems with Sclerotinia minor (SM) or S. sclerotiorum (SS) causes Sclerotinia blight, which is characterized by the formation of tan, water-soaked lesions on infected plant parts, leading to tissue collapse and necrosis of the affected tissue. Significant losses occur in Oklaho...

  20. Calcium Montmorillonite-based dietary supplement attenuates Necrotic Enteritis induced by Eimeria maxima and Clostridium perfringens in broilers

    USDA-ARS?s Scientific Manuscript database

    We provide the first description of Dietary Supplement of sorbent minerals attenuates Necrotic Enteritis Induced by Eimeria maxima and Clostridium perfringens in Broilers. Necrotic enteritis (NE) is a poultry disease caused by Clostridium perfringens and characterized by severe intestinal necrosis....

  1. A Case of Lionfish Envenomation Presenting to an Inland Emergency Department

    PubMed Central

    Stair, Crystal K.; Wiegand, Timothy J.

    2017-01-01

    Lionfish envenomation can cause erythema, edema, necrosis, and severe pain at the exposed site. Treatment often includes supportive wound care, pain management, and hot water immersion. We report a case of lionfish exposure presenting to an inland emergency department treated successfully with these measures. PMID:28884031

  2. Sporulation of Phytophthora ramorum and P. kernoviae on asymptomatic foliage and fruit

    Treesearch

    S. Denman; E. Moralejo; S.A. Kirk; E. Orton; A. Whybrow

    2008-01-01

    Phytophthora ramorum and P. kernoviae are newly discovered invasive Phytophthoras causing leaf necrosis, shoot tip dieback (mostly on ornamental and forest understorey host species) and bleeding cankers on tree trunks of a wide range of plant species. Both pathogens are now present in south-west England....

  3. Pyrrolizidine alkaloids: Potential role in the etiology of cancers, pulmonary hypertension, congenital anomalies, and liver disease

    USDA-ARS?s Scientific Manuscript database

    Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute...

  4. Inclusion body hepatitis in kestrels (Falco sparverius)

    USGS Publications Warehouse

    Sileo, L.; Franson, J.C.; Graham, D.L.; Domermuth, C.H.; Rattner, B.A.; Pattee, O.H.

    1982-01-01

    Inclusion body disease of suspected adenovirus etiology was the apparent cause of death of 9 captive kestrels (Falco sparverius). Cloacal hemorrhage was the only prominent gross lesion; disseminated hepatocellular necrosis and intranuclear inclusion bodies were evident microscopically. Attempts to reproduce the disease, and to propagate and serologically characterize the agent were unsuccessful.

  5. (-)-7(S)-hydroxymatairesinol protects against tumor necrosis factor-α-mediated inflammation response in endothelial cells by blocking the MAPK/NF-κB and activating Nrf2/HO-1.

    PubMed

    Yang, Di; Xiao, Chen-Xi; Su, Zheng-Hua; Huang, Meng-Wei; Qin, Ming; Wu, Wei-Jun; Jia, Wan-Wan; Zhu, Yi-Zhun; Hu, Jin-Feng; Liu, Xin-Hua

    2017-08-15

    Endothelial inflammation is an increasingly prevalent condition in the pathogenesis of many cardiovascular diseases. (-)-7(S)-hydroxymatairesinol (7-HMR), a naturally occurring plant lignan, possesses both antioxidant and anti-cancer properties and therefore would be a good strategy to suppress tumor necrosis factor-α (TNF-α)-mediated inflammation in vascular endothelial cells (VECs). The objective of this study is to evaluate for its anti-inflammatory effect on TNF-α-stimulated VECs and underling mechanisms. The effect of the 7-HMR on suppression of TNF-α-induced inflammation mediators in VECs were determined by qRT-PCR and Western blot. MAPKs and phosphorylation of Akt, HO-1 and NF-κB p65 were examined using Western blot. Nuclear localisation of NF-κB was also examined using Western blot and immunofluorescence. Here we found that 7-HMR could suppress TNF-α-induced inflammatory mediators, such as vascularcelladhesion molecule-1, interleukin-6 and inducible nitric oxide synthase expression both in mRNA and protein levels, and concentration-dependently attenuated reactive oxidase species generation. We further identified that 7-HMR remarkably induced superoxide dismutase and heme oxygenase-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (keap1) and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, 7-HMR time- and concentration-dependently attenuated TNF-α-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) and Akt, but not p38, or c-Jun N-terminal kinase 1/2. Moreover, 7-HMR significantly suppressed TNF-α-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. Our results demonstrated that 7-HMR inhibited TNF-α-stimulated endothelial inflammation, at least in part, through inhibition of NF-κB activation and upregulation of Nrf2-antioxidant response element signaling pathway, suggesting 7-HMR might be used as a promising vascular protective drug. Copyright © 2017. Published by Elsevier GmbH.

  6. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sueyoshi, Eijun, E-mail: EijunSueyoshi@aol.com; Sakamoto, Ichiro; Okimoto, Tomoaki

    Amyloidosis is a rare systemic disease. However, involvement of the heart is a common finding and is the most frequent cause of death in amyloidosis. We report the sonographic, scintigraphic, and MRI features of a pathologically proven case of cardiac amyloidosis. Delayed contrast-enhanced MR images, using an inversion recovery prepped gradient-echo sequence, revealed diffuse enhancement in the wall of both left and right ventricles. This enhancement suggested expansion of the extracellular space of the myocardium caused by diffuse myocardial necrosis secondary to deposition of amyloid.

  7. Carotid Artery Dissection and Ischemic Stroke Originating from Localized Aortic Arch Dissection.

    PubMed

    Kamimura, Teppei; Nomura, Eiichi; Hara, Naoyuki; Maetani, Yuta; Agari, Dai; Ichimura, Kouichi; Yoshida, Hideo; Yamawaki, Takemori

    2016-11-01

    Aortic dissection is an infrequent but important cause of acute ischemic stroke (AIS), and must not be overlooked because of a possible worse outcome, especially with the use of an intravenous recombinant tissue plasminogen activator. We report a case of left carotid artery dissection and AIS originating from localized aortic arch dissection, pathologically caused by cystic medial necrosis in the tunica media. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Photodynamic impact induces ischemic tolerance in models in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Demyanenko, Svetlana; Sharifulina, Svetlana; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Maria; Zhukovskaya, Ludmila

    2016-04-01

    Ischemic tolerance determines resistance to lethal ischemia gained by a prior sublethal stimulus (i.e., preconditioning). We reproduced this effect in two variants. In vitro the preliminary short (5 s) photodynamic treatment (PDT) (photosensitizer Photosens, 10 nM, 30 min preincubation; laser: 670 nm, 100 mW/cm2) significantly reduced the necrosis of neurons and glial cells in the isolated crayfish stretch receptor, which was caused by following 30-min PDT by 66% and 46%, respectively. In vivo PDT of the rat cerebral cortex with hydrophilic photosensitizer Rose Bengal (i.v. administration, laser irradiation: 532 nm, 60 mW/cm2, 3 mm beam diameter, 30 min) caused occlusion of small brain vessels and local photothrombotic infarct (PTI). It is a model of ischemic stroke. Cerebral tissue edema and global necrosis of neurons and glial cells occurred in the infarction core, which was surrounded by a 1.5 mm transition zone, penumbra. The maximal pericellular edema, hypo- and hyperchromia of neurons were observed in penumbra 24 h after PTI. The repeated laser irradiation of the contralateral cerebral cortex also caused PTI but lesser as compared with single PDT. Preliminary unilateral PTI provided ischemic tolerance: at 14 day after second exposure the PTI volume significantly decreased by 24% than in the case of a single exposure. Sensorimotor deficits in PDT-treated rats was registered using the behavioral tests. The preliminary PTI caused the preconditioning effect.

  9. Comparative study of cyanotoxins affecting cytoskeletal and chromatin structures in CHO-K1 cells.

    PubMed

    Gácsi, Mariann; Antal, Otilia; Vasas, Gábor; Máthé, Csaba; Borbély, György; Saker, Martin L; Gyori, János; Farkas, Anna; Vehovszky, Agnes; Bánfalvi, Gáspár

    2009-06-01

    In this study we compared the effects of the two frequently occuring and most dangerous cyanobacterial toxins on the cellular organization of microfilaments, microtubules and on the chromatin structure in Chinese hamster ovary (CHO-K1) cells. These compounds are the widely known microcystin-LR (MC-LR) and cylindrospermopsin (CYN) classified as the highest-priority cyanotoxin. Toxic effects were tested in a concentration and time dependent manner. The hepatotoxic MC-LR did not cause significant cytotoxicity on CHO-K1 cells under 20 microM, but caused apoptotic changes at higher concentrations. Apoptotic shrinkage was associated with the shortening and loss of actin filaments and with a concentration dependent depolymerization of microtubules. No necrosis was observed over the concentration range (1-50 microM MC-LR) tested. Cylindrospermopsin did cause apoptosis at low concentrations (1-2 microM) and over short exposure periods (12h). Necrosis was observed at higher concentrations (5-10 microM) and following longer exposure periods (24 or 48h). Cyanotoxins also affected the chromatin structure. The condensation process was inhibited by MC-LR at a later stage and manifested as broken elongated prechromosomes. CYN inhibited chromatin condensation at the early fibrillary stage leading to blurred fluorescent images of apoptotic bodies and preventing the formation of metaphase chromosomes. Cylindrospermopsin exhibited a more pronounced toxic effect causing cytoskeletal and nuclear changes as well as apoptotic and necrotic alterations.

  10. Inducible nuclear translocation of a STAT protein in Dictyostelium prespore cells: implications for morphogenesis and cell-type regulation.

    PubMed

    Dormann, D; Abe, T; Weijer, C J; Williams, J

    2001-04-01

    Dd-STATa, the Dictyostelium STAT (signal transducer and activator of transcription) protein, is selectively localised in the nuclei of a small subset of prestalk cells located in the slug tip. Injection of cAMP into the extracellular spaces in the rear of the slug induces rapid nuclear translocation of a Dd-GFP:STATa fusion protein in prespore cells surrounding the site of injection. This suggests that cAMP signals that emanate from the tip direct the localised nuclear accumulation of Dd-STATa. It also shows that prespore cells are competent to respond to cAMP, by Dd-STATa activation, and it implies that cAMP signalling is in some way limiting in the rear of the slug. Co-injection of a specific inhibitor of the cAR1 serpentine cAMP receptor almost completely prevents the cAMP-induced nuclear translocation, showing that most or all of the cAMP signal is transduced by cAR1. Dd-GFP:STATa also rapidly translocates into the nuclei of cells adjoining the front and back cut edges when a slug is bisected. Less severe mechanical disturbances, such as pricking the rear of a slug with an unfilled micropipette, also cause a more limited nuclear translocation of Dd-GFP:STATa. We propose that these signalling events form part of a repair mechanism that is activated when the migrating slug suffers mechanical damage.

  11. Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy.

    PubMed

    Carlsson, Emil; Thwaite, Joanne E; Jenner, Dominic C; Spear, Abigail M; Flick-Smith, Helen; Atkins, Helen S; Byrne, Bernadette; Ding, Jeak Ling

    2016-01-01

    Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence.

  12. Intestinal volvulus and perforation caused by multiple magnet ingestion: report of a case.

    PubMed

    Ilçe, Zekeriya; Samsum, Hakan; Mammadov, Emil; Celayir, Sinan

    2007-01-01

    Ingested magnets can cause intestinal fistulas, perforation, and obstruction. There have been reports of magnet ingestion causing intestinal volvulus, but multiple magnet ingestion causing perforation and intestinal volvulus in a child is very unusual. We report the case of a 4-year-old girl, who ingested four magnets she acquired as toys, which caused intestinal volvulus and perforation as a result of pressure necrosis, several days after ingestion. At surgery we repaired two perforations, but additional bowel resection was not required. The patient was discharged on postoperative day 10. If multiple magnet ingestion is suspected in a child, the child must be monitored carefully. If there are signs of obstruction, emergency surgery is mandatory.

  13. The Nuclear Protein Database (NPD): sub-nuclear localisation and functional annotation of the nuclear proteome

    PubMed Central

    Dellaire, G.; Farrall, R.; Bickmore, W.A.

    2003-01-01

    The Nuclear Protein Database (NPD) is a curated database that contains information on more than 1300 vertebrate proteins that are thought, or are known, to localise to the cell nucleus. Each entry is annotated with information on predicted protein size and isoelectric point, as well as any repeats, motifs or domains within the protein sequence. In addition, information on the sub-nuclear localisation of each protein is provided and the biological and molecular functions are described using Gene Ontology (GO) terms. The database is searchable by keyword, protein name, sub-nuclear compartment and protein domain/motif. Links to other databases are provided (e.g. Entrez, SWISS-PROT, OMIM, PubMed, PubMed Central). Thus, NPD provides a gateway through which the nuclear proteome may be explored. The database can be accessed at http://npd.hgu.mrc.ac.uk and is updated monthly. PMID:12520015

  14. A Variational Reduction and the Existence of a Fully Localised Solitary Wave for the Three-Dimensional Water-Wave Problem with Weak Surface Tension

    NASA Astrophysics Data System (ADS)

    Buffoni, Boris; Groves, Mark D.; Wahlén, Erik

    2017-12-01

    Fully localised solitary waves are travelling-wave solutions of the three- dimensional gravity-capillary water wave problem which decay to zero in every horizontal spatial direction. Their existence has been predicted on the basis of numerical simulations and model equations (in which context they are usually referred to as `lumps'), and a mathematically rigorous existence theory for strong surface tension (Bond number {β} greater than {1/3} ) has recently been given. In this article we present an existence theory for the physically more realistic case {0 < β < 1/3} . A classical variational principle for fully localised solitary waves is reduced to a locally equivalent variational principle featuring a perturbation of the functional associated with the Davey-Stewartson equation. A nontrivial critical point of the reduced functional is found by minimising it over its natural constraint set.

  15. A Variational Reduction and the Existence of a Fully Localised Solitary Wave for the Three-Dimensional Water-Wave Problem with Weak Surface Tension

    NASA Astrophysics Data System (ADS)

    Buffoni, Boris; Groves, Mark D.; Wahlén, Erik

    2018-06-01

    Fully localised solitary waves are travelling-wave solutions of the three- dimensional gravity-capillary water wave problem which decay to zero in every horizontal spatial direction. Their existence has been predicted on the basis of numerical simulations and model equations (in which context they are usually referred to as `lumps'), and a mathematically rigorous existence theory for strong surface tension (Bond number {β} greater than {1/3}) has recently been given. In this article we present an existence theory for the physically more realistic case {0 < β < 1/3}. A classical variational principle for fully localised solitary waves is reduced to a locally equivalent variational principle featuring a perturbation of the functional associated with the Davey-Stewartson equation. A nontrivial critical point of the reduced functional is found by minimising it over its natural constraint set.

  16. From dichoptic to dichotic: historical contrasts between binocular vision and binaural hearing.

    PubMed

    Wade, Nicholas J; Ono, Hiroshi

    2005-01-01

    Phenomena involving vision with two eyes have been commented upon for several thousand years whereas those concerned with hearing with two ears have a much more recent history. Studies of binocular vision and binaural hearing are contrasted with respect to the singleness of the percept, experimental manipulations of dichoptic and dichotic stimuli, eye and ear dominance, spatial localisation, and the instruments used to stimulate the paired organs. One of the principal phenomena that led to studies of dichotic hearing was dichoptic colour mixing. There was similar disagreement regarding whether colours or sounds could be combined when presented to different paired organs. Direction and distance in visual localisation were analysed before those for auditory localisation, partly due to difficulties in controlling the stimuli. Instruments for investigating binocular vision, like the stereoscope and pseudoscope, were invented before those for binaural hearing, like the stethophone and pseudophone.

  17. Recovery of infrastructure networks after localised attacks.

    PubMed

    Hu, Fuyu; Yeung, Chi Ho; Yang, Saini; Wang, Weiping; Zeng, An

    2016-04-14

    The stability of infrastructure network is always a critical issue studied by researchers in different fields. A lot of works have been devoted to reveal the robustness of the infrastructure networks against random and malicious attacks. However, real attack scenarios such as earthquakes and typhoons are instead localised attacks which are investigated only recently. Unlike previous studies, we examine in this paper the resilience of infrastructure networks by focusing on the recovery process from localised attacks. We introduce various preferential repair strategies and found that they facilitate and improve network recovery compared to that of random repairs, especially when population size is uneven at different locations. Moreover, our strategic repair methods show similar effectiveness as the greedy repair. The validations are conducted on simulated networks, and on real networks with real disasters. Our method is meaningful in practice as it can largely enhance network resilience and contribute to network risk reduction.

  18. The Rényi divergence enables accurate and precise cluster analysis for localisation microscopy.

    PubMed

    Staszowska, Adela D; Fox-Roberts, Patrick; Hirvonen, Liisa M; Peddie, Christopher J; Collinson, Lucy M; Jones, Gareth E; Cox, Susan

    2018-06-01

    Clustering analysis is a key technique for quantitatively characterising structures in localisation microscopy images. To build up accurate information about biological structures, it is critical that the quantification is both accurate (close to the ground truth) and precise (has small scatter and is reproducible). Here we describe how the Rényi divergence can be used for cluster radius measurements in localisation microscopy data. We demonstrate that the Rényi divergence can operate with high levels of background and provides results which are more accurate than Ripley's functions, Voronoi tesselation or DBSCAN. Data supporting this research will be made accessible via a web link. Software codes developed for this work can be accessed via http://coxphysics.com/Renyi_divergence_software.zip. Implemented in C ++. Correspondence and requests for materials can be also addressed to the corresponding author. adela.staszowska@gmail.com or susan.cox@kcl.ac.uk. Supplementary data are available at Bioinformatics online.

  19. Capsule-odometer: a concept to improve accurate lesion localisation.

    PubMed

    Karargyris, Alexandros; Koulaouzidis, Anastasios

    2013-09-21

    In order to improve lesion localisation in small-bowel capsule endoscopy, a modified capsule design has been proposed incorporating localisation and - in theory - stabilization capabilities. The proposed design consists of a capsule fitted with protruding wheels attached to a spring-mechanism. This would act as a miniature odometer, leading to more accurate lesion localization information in relation to the onset of the investigation (spring expansion e.g., pyloric opening). Furthermore, this capsule could allow stabilization of the recorded video as any erratic, non-forward movement through the gut is minimised. Three-dimensional (3-D) printing technology was used to build a capsule prototype. Thereafter, miniature wheels were also 3-D printed and mounted on a spring which was attached to conventional capsule endoscopes for the purpose of this proof-of-concept experiment. In vitro and ex vivo experiments with porcine small-bowel are presented herein. Further experiments have been scheduled.

  20. Clutter elimination for deep clinical optoacoustic imaging using localised vibration tagging (LOVIT)☆

    PubMed Central

    Jaeger, Michael; Bamber, Jeffrey C.; Frenz, Martin

    2013-01-01

    This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering. In this study we demonstrate that signals of interest can be distinguished from clutter by tagging them at the place of origin with localised tissue vibration induced by the acoustic radiation force in a focused ultrasonic beam. We show phantom results where this technique allowed almost full clutter elimination and thus strongly improved contrast for deep imaging. Localised vibration tagging by means of acoustic radiation force is especially promising for integration into ultrasound systems that already have implemented radiation force elastography. PMID:25302147

  1. Genomic and Histopathological Tissue Biomarkers That Predict Radiotherapy Response in Localised Prostate Cancer

    PubMed Central

    Wilkins, Anna; Dearnaley, David; Somaiah, Navita

    2015-01-01

    Localised prostate cancer, in particular, intermediate risk disease, has varied survival outcomes that cannot be predicted accurately using current clinical risk factors. External beam radiotherapy (EBRT) is one of the standard curative treatment options for localised disease and its efficacy is related to wide ranging aspects of tumour biology. Histopathological techniques including immunohistochemistry and a variety of genomic assays have been used to identify biomarkers of tumour proliferation, cell cycle checkpoints, hypoxia, DNA repair, apoptosis, and androgen synthesis, which predict response to radiotherapy. Global measures of genomic instability also show exciting capacity to predict survival outcomes following EBRT. There is also an urgent clinical need for biomarkers to predict the radiotherapy fraction sensitivity of different prostate tumours and preclinical studies point to possible candidates. Finally, the increased resolution of next generation sequencing (NGS) is likely to enable yet more precise molecular predictions of radiotherapy response and fraction sensitivity. PMID:26504789

  2. Model updating strategy for structures with localised nonlinearities using frequency response measurements

    NASA Astrophysics Data System (ADS)

    Wang, Xing; Hill, Thomas L.; Neild, Simon A.; Shaw, Alexander D.; Haddad Khodaparast, Hamed; Friswell, Michael I.

    2018-02-01

    This paper proposes a model updating strategy for localised nonlinear structures. It utilises an initial finite-element (FE) model of the structure and primary harmonic response data taken from low and high amplitude excitations. The underlying linear part of the FE model is first updated using low-amplitude test data with established techniques. Then, using this linear FE model, the nonlinear elements are localised, characterised, and quantified with primary harmonic response data measured under stepped-sine or swept-sine excitations. Finally, the resulting model is validated by comparing the analytical predictions with both the measured responses used in the updating and with additional test data. The proposed strategy is applied to a clamped beam with a nonlinear mechanism and good agreements between the analytical predictions and measured responses are achieved. Discussions on issues of damping estimation and dealing with data from amplitude-varying force input in the updating process are also provided.

  3. Une localisation exceptionnelle de la tuberculose vertébrale Mal de Pott sous-occipital

    PubMed Central

    Yahyaoui, Sana; Majdoub, Senda; Zaghouani, Houneida; Fradj, Hosni Ben; Bakir, Dejla; Bouajina, Elyes; Kraiem, Chakib

    2013-01-01

    Le mal de Pott est la forme la plus commune de la tuberculose osseuse touchant essentiellement le rachis dorso-lombaire. La localisation sous-occipitale reste exceptionnelle. Le diagnostic de cette entité est le plus souvent tardif ce qui expose à des complications graves. Les radiographies standard ne sont parlantes qu’à un stade tardif de la maladie, d'où l'intérêt de l'imagerie moderne notamment la tomodensitométrie (TDM) et l'imagerie par résonance magnétique (IRM) qui permettent un diagnostic précoce. Nous rapportons un nouveau cas de tuberculose sous-occipitale. Le diagnostic était posé sur l'imagerie en coupe et confirmé histologiquement à la biopsie transorale. Sont rappelés les aspects en imagerie de cette localisation particulière du mal de Pott. PMID:23819005

  4. Recovery of infrastructure networks after localised attacks

    PubMed Central

    Hu, Fuyu; Yeung, Chi Ho; Yang, Saini; Wang, Weiping; Zeng, An

    2016-01-01

    The stability of infrastructure network is always a critical issue studied by researchers in different fields. A lot of works have been devoted to reveal the robustness of the infrastructure networks against random and malicious attacks. However, real attack scenarios such as earthquakes and typhoons are instead localised attacks which are investigated only recently. Unlike previous studies, we examine in this paper the resilience of infrastructure networks by focusing on the recovery process from localised attacks. We introduce various preferential repair strategies and found that they facilitate and improve network recovery compared to that of random repairs, especially when population size is uneven at different locations. Moreover, our strategic repair methods show similar effectiveness as the greedy repair. The validations are conducted on simulated networks, and on real networks with real disasters. Our method is meaningful in practice as it can largely enhance network resilience and contribute to network risk reduction. PMID:27075559

  5. Change in nomenclature for the immunologic synapse from Troxis Necrosis to trogocytosis.

    PubMed

    French, Samuel W

    2017-10-01

    The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the CD4 lymphocyte. This process is performed by the immunologic synapse now called trogocytosis meaning "gnaw" (Martinez-Martin N et al., Immunity 2011, 35: 208-222 and Dustin ML, Cancer Immunol Res 2014, 2: 1023-1033). The repeated episodes of uptake of the hepatocyte bite by bite causes the hepatocyte to slowly disappear like the Cheshire cat. This immunological synapse process is also involved in drug hepatitis, Hashimoto's thyroiditis, type I diabetes, autoimmune adrenalitis, autoimmune gastritis and cancer therapy. Treatment of Alzheimer's disease is also now being studied with PD-L1 antibody as used in the treatment of cancer allowing recruitment of disease modifying leukocytes to the sites of brain pathology (Schwartz M. Science 2017, 357: 254-255). Acknowledgement: Supported by a Grant from NIAAAUO1-021898. Copyright © 2017. Published by Elsevier Inc.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2011-08-01

    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 Ca(2+) accumulation (EICA), and mitochondrial Ca(2+) 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.

  8. A study of tail tip necrosis in young fattening bulls on slatted floors.

    PubMed

    Madsen, E B; Nielsen, K

    1985-01-01

    A questionnaire sent to 78 producers revealed that tail tip necrosis was seen only in units with fattening bulls housed on slatted floors. Out of 43 such units, 20 (46.5 per cent) reported that tail tip necrosis was a herd problem. All 43 herds were visited, owners were interviewed and housing and management data recorded. It is concluded that tail tip necrosis is a multifactorial disease. The initial lesion is caused by tramping, but the following factors are essential in the development and severity of the disease, i) slatted concrete floors, ii) close confinement, iii) hot season and iv) body weight above 200 kg. The stocking density (expressed as kg bodyweight per square meter pen) was significantly higher in problem herds (210 kg/m2) than in control herds (165 kg/m2). There was a close relationship between high environmental temperature and tail tip necroses. The majority of incidents occurred during the warm season (May through September), very few cases were seen during the colder months. The general morbidity and mortality rates were significantly higher in problem herds than in control herds. Microbiology of affected tails revealed mixed infections in most cases, with Corynebacterium pyogenes and Bacteroides melaninogenicus as the most frequently isolated organisms. Principles of treatment and prevention are discussed. There is evidence to assume that a 10-20 per cent reduction in stocking density could be an efficient prophylactic measure.

  9. Immunity to Rice Blast Disease by Suppression of Effector-Triggered Necrosis.

    PubMed

    Wang, Ruyi; Ning, Yuese; Shi, Xuetao; He, Feng; Zhang, Chongyang; Fan, Jiangbo; Jiang, Nan; Zhang, Yu; Zhang, Ting; Hu, Yajun; Bellizzi, Maria; Wang, Guo-Liang

    2016-09-26

    Hemibiotrophic pathogens are some of the most destructive plant pathogens, causing huge economic losses and threatening global food security. Infection with these organisms often involves an initial biotrophic infection phase, during which the pathogen spreads in host tissue asymptomatically, followed by a necrotrophic phase, during which host-cell death is induced. How hemibiotrophic pathogens trigger host necrosis and how plants inhibit the transition from the biotrophic stage to the necrotrophic stage in disease symptom expression are mainly unknown. The rice blast fungus Magnaporthe oryzae spreads in rice biotrophically early during infection, but this biotrophic stage is followed by a pronounced switch to cell death and lesion formation. Here, we show that the M. oryzae effector AvrPiz-t interacts with the bZIP-type transcription factor APIP5 in the cytoplasm and suppresses its transcriptional activity and protein accumulation at the necrotrophic stage. Silencing of APIP5 in transgenic rice leads to cell death, and the phenotype is enhanced by the expression of AvrPiz-t. Conversely, Piz-t interacts with and stabilizes APIP5 to prevent necrosis at the necrotrophic stage. At the same time, APIP5 is essential for Piz-t stability. These results demonstrate a novel mechanism for the suppression of effector-triggered necrosis at the necrotrophic stage by an NLR receptor in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. 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

  11. Analysis of localised dose distribution in human body by Monte Carlo code system for photon irradiation.

    PubMed

    Ohnishi, S; Odano, N; Nariyama, N; Saito, K

    2004-01-01

    In usual personal dosimetry, whole body irradiation is assumed. However, the opportunity of partial irradiation is increasing and the tendencies of protection quantities caused under those irradiation conditions are different. The code system has been developed and effective dose and organ absorbed doses have been calculated in the case of horizontal narrow photon beam irradiated from various directions at three representative body sections, 40, 50 and 60 cm originating from the top of the head. This work covers 24 beam directions, each 15 degrees angle ranging from 0 degrees to 345 degrees, three energy levels, 45 keV, 90 keV and 1.25 MeV, and three beam diameters of 1, 2 and 4 cm. These results show that the beam injected from diagonally front or other specific direction causes peak dose in the case of partial irradiation.

  12. Spontaneous Intrahepatic Type II Gallbladder Perforation: A Rare Cause of Liver Abscess – Case Report

    PubMed Central

    Singh, Kumkum; Singh, Amit; Vidyarthi, Shivaji H; Jindal, Satyaprakash; Thounaojam, Chandra Kumar

    2013-01-01

    A liver abscess formation is a rare complication of a gallbladder perforation, with a cholecystohepatic communication. Niemeier, in 1934, classified free gallbladder perforations and generalised biliary peritonitis as an acute or a Type I gallbladder perforation, a pericholecystic abscess and localised peritonitis as a subacute or a Type II gallbladder perforation, and cholecystoenteric fistulas as chronic or Type III gallbladder perforations. We are describing a 50–year–old male patient who presented with right upper quadrant pain and was found to have an intrahepatic perforation of the gallbladder. Our patient had a Type II perforation. We have discussed the diagnostic work-up and the management of this rare entity. Due to the high mortality that can be caused by a delay in making the correct diagnosis, a gallbladder perforation represents a special diagnostic and surgical challenge. PMID:24179927

  13. Could anterior papillary muscle partial necrosis explain early mitral valve repair failure?

    PubMed

    Pozzi, Matteo; Generali, Tommaso; Henaine, Roland; Mitchell, Julia; Lemaire, Anais; Chiari, Pascal; Fran, Jean; Obadia, Jean François

    2014-09-01

    Standardized techniques of mitral valve repair (MVR) have recently witnessed the introduction of a 'respect rather than resect' concept, the strategy of which involves the use of artificial chordae. MVR displays several advantages over mitral valve replacement in degenerative mitral regurgitation (MR), but the risk of reoperation for MVR failure must be taken into account. Different mechanisms could be advocated as the leading cause of MVR failure; procedure-related mechanisms are usually involved in early MVR failure, while valve-related mechanisms are common in late failure. Here, the case is reported of an early failure of MVR using artificial chordae that could be explained by an unusual procedure-related mechanism, namely anterior papillary muscle necrosis. MVR failure is a well-known complication after surgical repair of degenerative MR, but anterior papillary muscle partial necrosis might also be considered a possible mechanism of procedure-related MVR failure, especially when considering the increasing use of artificial chordae. Owing to the encouraging results obtained, mitral valve re-repair might be considered a viable solution, but must be selected after only a meticulous evaluation of the underlying mechanism of MVR failure.

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

    PubMed

    Xu, Menglin; Wang, Xiangdong

    2017-08-01

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

  15. Postradiation atrophy of mature bone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Erguen, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographicmore » evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecting demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.« less

  16. Postradiation atrophy of mature bone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ergun, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographicmore » evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecing demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.« less

  17. Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection.

    PubMed

    Flieger, Miroslav; Bandouchova, Hana; Cerny, Jan; Chudíčková, Milada; Kolarik, Miroslav; Kovacova, Veronika; Martínková, Natália; Novák, Petr; Šebesta, Ondřej; Stodůlková, Eva; Pikula, Jiri

    2016-09-13

    Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml(-1), indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats' primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay.

  18. Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection

    PubMed Central

    Flieger, Miroslav; Bandouchova, Hana; Cerny, Jan; Chudíčková, Milada; Kolarik, Miroslav; Kovacova, Veronika; Martínková, Natália; Novák, Petr; Šebesta, Ondřej; Stodůlková, Eva; Pikula, Jiri

    2016-01-01

    Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml−1, indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats’ primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay. PMID:27620349

  19. [Acute traumatic and especially neglected traumatic hip dislocations are very rare in children].

    PubMed

    Fernandez, F F; Wirth, T; Eberhardt, O

    2012-09-01

    We report about the first hip arthroscopies of extracapsular neglected hip dislocations with concomitant injuries in two children (2 and 4 years old). The major problem of traumatic hip dislocation is avascular necrosis. Further problems are possible concomitant injuries. It is important not to cause further damage by therapeutic procedures. In a 4-year-old child the hip could be reduced under visualization and in a 2-year-old child with epiphyseal fracture the extent of the operation could be reduced. In both children large avulsion injuries of the ligamentum capitis femoris could be resected via hip arthroscopy. Hip arthroscopy can reduce surgical morbidity considerably and can possibly contribute to prevention of the feared avascular necrosis of the femoral head.

  20. Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response

    PubMed Central

    Wei, Xiawei; Shao, Bin; He, Zhiyao; Ye, Tinghong; Luo, Min; Sang, Yaxiong; Liang, Xiao; Wang, Wei; Luo, Shuntao; Yang, Shengyong; Zhang, Shuang; Gong, Changyang; Gou, Maling; Deng, Hongxing; Zhao, Yinglan; Yang, Hanshuo; Deng, Senyi; Zhao, Chengjian; Yang, Li; Qian, Zhiyong; Li, Jiong; Sun, Xun; Han, Jiahuai; Jiang, Chengyu; Wu, Min; Zhang, Zhirong

    2015-01-01

    Nanocarriers with positive surface charges are known for their toxicity which has limited their clinical applications. The mechanism underlying their toxicity, such as the induction of inflammatory response, remains largely unknown. In the present study we found that injection of cationic nanocarriers, including cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic cells. Cell necrosis induced by cationic nanocarriers is dependent on their positive surface charges, but does not require RIP1 and Mlkl. Instead, intracellular Na+ overload was found to accompany the cell death. Depletion of Na+ in culture medium or pretreatment of cells with the Na+/K+-ATPase cation-binding site inhibitor ouabain, protected cells from cell necrosis. Moreover, treatment with cationic nanocarriers inhibited Na+/K+-ATPase activity both in vitro and in vivo. The computational simulation showed that cationic carriers could interact with cation-binding site of Na+/K+-ATPase. Mice pretreated with a small dose of ouabain showed improved survival after injection of a lethal dose of cationic nanocarriers. Further analyses suggest that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal a novel mechanism whereby cationic nanocarriers induce acute cell necrosis through the interaction with Na+/K+-ATPase, with the subsequent exposure of mitochondrial damage-associated molecular patterns as a key event that mediates the inflammatory responses. Our study has important implications for evaluating the biocompatibility of nanocarriers and designing better and safer ones for drug delivery. PMID:25613571

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